Asian Pacific Journal of Cancer Prevention

Sahmani, Mehdi;Vatanmakanian, Mousa;Goudarzi, Mehdi;Mobarra, Naser;Azad, Mehdi 879

https://doi.org/10.7314/APJCP.2016.17.3.879 PDF KSCI

In micro-fluid systems, fluids are injected into extremely narrow polymer channels in small amounts such as micro-, nano-, or pico-liter scales. These channels themselves are embedded on tiny chips. Various specialized structures in the chips including pumps, valves, and channels allow the chips to accept different types of fluids to be entered the channel and along with flowing through the channels, exert their effects in the framework of different reactions. The chips are generally crystal, silicon, or elastomer in texture. These highly organized structures are equipped with discharging channels through which products as well as wastes of the reactions are secreted out. A particular advantage regarding the use of fluids in micro-scales over macro-scales lies in the fact that these fluids are much better processed in the chips when they applied as micro-scales. When the laboratory is miniaturized as a microchip and solutions are injected on a micro-scale, this combination makes a specialized construction referred to as "lab-on-chip". Taken together, micro-fluids are among the novel technologies which further than declining the costs; enhancing the test repeatability, sensitivity, accuracy, and speed; are emerged as widespread technology in laboratory diagnosis. They can be utilized for monitoring a wide spectrum of biological disorders including different types of cancers. When these microchips are used for cancer monitoring, circulatory tumor cells play a fundamental role.

Krishnamurthy, Arvind;Soundara, Viveka;Ramshankar, Vijayalakshmi 895

https://doi.org/10.7314/APJCP.2016.17.3.895 PDF KSCI

Breast cancer is the most commonly diagnosed invasive cancer among women. Many factors, both genetic and non-genetic, determine a woman's risk of developing breast cancer and several breast cancer risk prediction models have been proposed. It is vitally important to risk stratify patients as there are now effective preventive strategies available. All women need to be counseled regarding healthy lifestyle recommendations to decrease breast cancer risk. As such, management of these women requires healthcare professionals to be familiar with additional risk factors so that timely recommendations can be made on surveillance/risk-reducing strategies. Breast cancer risk reduction strategies can be better understood by encouraging the women at risk to participate in clinical trials to test new strategies for decreasing the risk. This article reviews the advances in the identification of women at high risk of developing breast cancer and also reviews the strategies available for breast cancer prevention.

Su, Min;Huang, Chun-Xia;Dai, Ai-Ping 905

https://doi.org/10.7314/APJCP.2016.17.3.905 PDF KSCI

Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

Francisconi, Carolina Favaro;Caldas, Rogerio Jardim;Martins, Lazara Joyce Oliveira;Rubira, Cassia Maria Fischer;da Silva Santos, Paulo Sergio 911

https://doi.org/10.7314/APJCP.2016.17.3.911 PDF KSCI

Leukemia is the most common neoplastic disease of the white blood cells which is important as a pediatric malignancy. Oral manifestations occur frequently in leukemic patients and may present as initial evidence of the disease or its relapse. The symptoms include gingival enlargement and bleeding, oral ulceration, petechia, mucosal pallor, noma, trismus and oral infections. Oral lesions arise in both acute and chronic forms of all types of leukemia. These oral manifestations either may be the result of direct infiltration of leukemic cells (primary) or secondary to underlying thrombocytopenia, neutropenia, or impaired granulocyte function. Despite the fact that leukemia has long been known to be associated with oral lesions, the available literature on this topic consists mostly of case reports, without data summarizing the main oral changes for each type of leukemia. Therefore, the present review aimed at describing oral manifestations of all leukemia types and their dental management. This might be useful in early diagnosis, improving patient outcomes.

Raei, Negin;Behrouz, Bahador;Zahri, Saber;Latifi-Navid, Saeid 917

https://doi.org/10.7314/APJCP.2016.17.3.917 PDF KSCI

However, the incidence of gastric cancer (GC) has been decreased in past decades; GC is the second cause of cancer related death in the world. Evidence has illustrated that several factors including Helicobacter pylori (H. pylori) infection, host genetics, and environmental factors (smoking and particularly diet) may play a crucial role in gastric carcinogenesis. It has been demonstrated that high consumption of fresh fruits, vegetables, high level of selenium and zinc in drinking water, sufficient iron, and cholesterol protect against GC, while; smoked, pickled, and preserved foods in salt, and nitrites increase the risk of GC. Epidemiological studies have also proved that H. pylori infection and a high salt diet could independently induce atrophic gastritis and intestinal metaplasia. Recently, studies have been demonstrated that dietary factors directly influence H. pylori virulence. The use of appropriate diet could reduce levels of H. pylori colonization or virulence and prevent or delay development of peptic ulcers or gastric carcinoma. This is attractive from a number of perspectives including those of cost, treatment tolerability, and cultural acceptability. This review will describe new insights into the pathogenesis of H. pylori in relation to environmental factors, especially dietary, not only to find the developed means for preventing and treating GC, but also for understanding the role of chronic inflammation in the development of other malignancies.

Ahmed, Rifat Zubair;Rashid, Munazza;Ahmed, Nuzhat;Nadeem, Muhammad;Shamsi, Tahir Sultan 923

https://doi.org/10.7314/APJCP.2016.17.3.923 PDF KSCI

The classic BCR-ABL1-negative myeloproliferative neoplasm is an operational sub-category of MPNs that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation is found in ~ 95% of PV and 50-60% of ET or PMF. In most of the remaining JAK2V617F-negative PV cases, JAK2 exon 12 mutations are present. Amongst the JAK2V617F-negative ET or PMF 5-10% of patients carry mutations in the MPL gene. Prior to 2013, there was no specific molecular marker described in the remaining 30-40% ET and PMF. In December 2013, two research groups independently reported mutations in the gene CALR found specifically in ET (67-71%) and PMF (56-88%) but not in PV. Initially CALR mutations were reported mutually exclusive with JAK2 or MPL. However, co-occurrence of CALR mutations with JAK2V617F has been reported recently in a few MPN cases. Many studies have reported important diagnostic and prognostic significance of CALR mutations in ET and PMF patients and CALR mutation screening has been proposed to be incorporated into WHO diagnostic criteria for MPN. It is suggestive in diagnostic workup of MPN that CALR mutations should not be studied in MPN patients who carry JAK2 or MPL mutations. However JAK2V617F and CALR positive patients might have a different phenotype and clinical course, distinct from the JAK2-positive or CALR-positive subgroups and identification of the true frequency of these patients may be an important factor for defining the prognosis, risk factors and outcomes for MPN patients.

Zaid, Khaled Waleed;Chantiri, Mansour;Bassit, Ghassan 927

https://doi.org/10.7314/APJCP.2016.17.3.927 PDF KSCI

Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-${\beta}$ superfamily, regulate many cellular activities including cell migration, differentiation, adhesion, proliferation and apoptosis. Use of recombinant human bone morphogenic protein-2 (rhBMP-2) in oral and maxillofacial surgery has seen a tremendous increase. Due to its role in many cellular pathways, the influence of this protein on carcinogenesis in different organs has been intensively studied over the past decade. BMPs also have been detected to have a role in the development and progression of many tumors, particularly disease-specific bone metastasis. In oral squamous cell carcinoma - the tumor type accounting for more than 90% of head and neck malignancies- aberrations of both BMP expression and associated signaling pathways have a certain relation with the development and progression of the disease by regulating a range of biological functions in the altered cells. In the current review, we discuss the influence of BMPs -especially rhBMP-2- in the development and progression of oral squamous cell carcinoma.

Mohammadzadeh, Zeinab;Davoodi, Somayeh;Ghazisaeidi, Marjan 933

https://doi.org/10.7314/APJCP.2016.17.3.933 PDF KSCI

Online social network technologies have become important to health and apply in most health care areas. Particularly in cancer care, because it is a disease which involves many social aspects, online social networks can be very useful. Use of online social networks provides a suitable platform for cancer patients and families to present and share information about their medical conditions, address their educational needs, support decision making, and help to coping with their disease and improve their own outcomes. Like any other new technologies, online social networks, along with many benefits, have some negative effects such as violation of privacy and publication of incorrect information. However, if these effects are managed properly, they can empower patients to manage cancer through changing behavioral patterns and enhancing the quality of cancer patients lives This paper explains some application of online social networks in the cancer patient care process. It also covers advantages and disadvantages of related technologies.

Cihan, Yasemin Benderli 937

https://doi.org/10.7314/APJCP.2016.17.3.937 PDF KSCI

Stereotactic body radiation therapy (SBRT) appears an effective and safe treatment modality for spinal bone metastasis, which can enhance local control and improve quality of life. Life expectation, predicted fracture risk, localization, quality, size and number of metastasis and presence or absence of nerve compression seem to be important factors in decision-making for treatment. Further studies are needed to identify subsets of patient which will most benefit from treatment.

El-Gayar, Dina;El-Abd, Nevine;Hassan, Noha;Ali, Reem 939

https://doi.org/10.7314/APJCP.2016.17.3.939 PDF KSCI

Background: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. Objectives: To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Materials and Methods: Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ALU 115bp. Results: Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (p<0.001). ROC curves for differentiating CRC patients from normal controls and benign groups had areas under curves of 0.90 and 0.85 respectively. Conclusions: The DNA integrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.

Chaowawanit, Woraphot;Tangjitgamol, Siriwan;Kantathavorn, Nuttavut;Phoolcharoen, Natacha;Kittisiam, Thannaporn;Khunnarong, Jakkapan;Supawattanabodee, Busaba;Srijaipracharoen, Sunamchok;Thavaramara, Thaovalai;Pataradool, Kamol 945

https://doi.org/10.7314/APJCP.2016.17.3.945 PDF KSCI

Purpose: To assess knowledge, attitudes and cervical cancer screening behavior of Bangkok Metropolitan women. Materials and Methods: Thai women, aged 25-to-65 years old, having lived in Bangkok for 5 years or more were invited to participate in the study. After signing informed consent, all women were asked to complete a self-questionnaire (Thai language) with literate assistance if needed. The questionnaire was divided into 3 parts: (I) demographic data; (II) knowledge about cervical cancer screening; and (III) behavior and attitudes, towards cervical cancer screening. Adequate screening was defined as women who had ${\geq}$two cervical cancer screening tests except women aged 25-30 years who may have only one screening, and the last screen was within 5 year or had had regular screening. Results: Of 4,339 women, there were 1,857 (42.8%) with adequate screening and 2,482 (57.2%) with inadequate screening. Significant factors associated with inadequate screening included age < 45 years, pre-menopausal status, family monthly income <625 USD, no reported sexual intercourse, nulliparous, no knowledge, lack of awareness and poor attitudes. Three major reasons provided by women for inadequate screening were no symptoms (54.4%), fear of pain (33.2%), and embarrassment (34.6%). Conclusions: Personal features, knowledge, and attitudes influence screening behavior of Bangkok Metropolitan women. The three most common reasons of women for not undergoinging screening are no symptoms, fear of pain, and embarrassment. These factors should be the focus of attention to improve coverage of cervical cancer screening in Bangkok.

Chinchai, Teeraporn;Homchan, Krittaphak;Sopipong, Watanyoo;Chansaenroj, Jira;Swangvaree, Sukumarn;Junyangdikul, Pairoj;Vongpunsawad, Sompong;Poovorawan, Yong 953

https://doi.org/10.7314/APJCP.2016.17.3.953 PDF KSCI

The risk of developing cervical cancer in women infected with human papillomavirus (HPV) may be influenced by an individual's genetic susceptibility. Published data linking single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-${\alpha}$) promoter region at positions -308G>A (rs1800629) and -238G>A (rs361525) to cervical cancer risk have been inconclusive. In this study, we examined 251 cervical specimens and classified them into two groups according to their cytological findings: 121 cancer cases and 130 controls (low-grade squamous intraepithelial lesion and normal cytology). All specimens were typed by PCR and sequencing for TNF-${\alpha}$ promoter -308G>A (rs1800629) and -238G>A (rs361525). The genotype distribution of SNPs in either rs1800629 or rs361525 did not significantly demonstrate higher frequency in the cancer group (p=0.621 and p=0.68, respectively). Based on these results, neither the TNF-${\alpha}$ promoter -308G>A (rs1800629) nor the -238G>A (rs361525) polymorphism presents a major risk factor for cervical cancer among Thai women. Larger studies are necessary to elucidate possible genetic mechanisms influencing cervical cancer development.

Moolmuang, Benchamart;Singhirunnusorn, Pattama;Ruchirawat, Mathuros 957

https://doi.org/10.7314/APJCP.2016.17.3.957 PDF KSCI

Cellular senescence, a barrier to tumorigenesis, controls aberrant proliferation of cells. We here aimed to investigate cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines using five different inducing agents: 5-aza-2'deoxycytidine, bromodeoxyuridine, interferons ($IFN{\beta}$ and $IFN{\gamma}$), and hydrogen peroxide. We analyzed senescence characteristics, colony formation ability, expression of genes involved in cell cycling and interferon signaling pathways, and protein levels. Treatment with all five agents decreased cell proliferation and induced cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines with different degrees of growth-inhibitory effects depending on cell type and origin. Bromodeoxyuridine gave the strongest stimulus to inhibit growth and induce senescence in most cell lines tested. Expression of p21 and interferon related genes was upregulated in most conditions. The fact that bromodeoxyuridine had the strongest effects on growth inhibition and senescence induction implies that senescence in cholangiocarcinoma cells is likely controlled by DNA damage response pathways relating to the p53/p21 signaling. In addition, interferon signaling pathways may partly regulate this mechanism in cholangiocarcinoma cells.

Zhou, Juan;Song, Xing-Bo;He, He;Zhou, Yi;Lu, Xiao-Jun;Ying, Bin-Wu 965

https://doi.org/10.7314/APJCP.2016.17.3.965 PDF KSCI

Aims: To investigate the distribution of epidermal growth factor receptor (EGFR) mutations, and explore any relationships with clinical characteristics in non-small-cell lung carcinoma (NSCLC) patients. Materials and Methods: EGFR mutations were assessed by ADx-ARMS in 261 NSCLC patients from West China Hospital of Sichuan University. Relationships between EGFR mutation and clinical characteristics were analyzed by SPSS. Results: The EGFR mutation rate was 48.7% (127/261), 19-del and L858R mutations occurred predominantly, accounting for 33.1% and 40.9%, respectively, in mutated cases. Moreover, 10.2% patients were found to carry double mutations. EGFR mutations occurred more frequently in women (57.5%) than in men (41.8%) (P=0.01), and were more frequent in non-smokers (61.2%) than in former or current smokers (31.2%) (P<0.00). In addition, they were more common in adenocarcinomas (52.8%) and adenosquamous carcinomas (42.8%) than in squamous cell carcinomas (14.8%) (p<0.00). However, only smoking history and pathological types, rather than gender, proved to be associated with EGFR mutations on multivariate logistic regression analysis. No significant differences in pathological stage and metastasis status were found between EGFR wild-type and mutated cases, although EGFR mutation type was related to pathological type (p=0.00) - 19-del, L858R and other mutation types respectively occurred in 34.2%, 42.5% and 23.3% of adenocarcinomas, but in 14.3%, 0% and 85.7% of non-adenocarcinomas. Conclusions: The EGFR mutation rate was 48.7% in NSCLCs in Southwest China, so that nearly 40% patients might benefit from targeted therapies. Smoking status and pathological types were independent predictors of EGFR mutation, while EGFR mutation type was related to only pathological type, rather than smoking status.

Yusof, Mastura Md;Abdullah, Nik MA;Sharial, MSN Mohd;Zaatar, Adel 973

https://doi.org/10.7314/APJCP.2016.17.3.973 PDF KSCI

Background: Between October 2012 and February 2015, 25 patients with metastatic colorectal cancer (mCRC) (mean age, $57.0{\pm}12.1years$) were granted access to aflibercept via the Aflibercept Named Patient Program at four centers. Materials and Methods: Here we reported the initial experience of aflibercept / FOLFIRI in combination. We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Results: The majority of the patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%), mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events. Aflibercept-related toxicity was managed as per practice guidelines. No grade 5 event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12 months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6-43.3), and 37.5% (95% CI: 22.5-52.5), respectively. Conclusions: Aflibercept/FOLFIRI can be administered safely in a second line setting to Malaysian patients with mCRC, as the AEs experienced were generally reversible and manageable. The safety and efficacy outcomes were consistent with those observed in Western populations.

Tanaka, Tsutomu;Mulyadi, I Ketut;Moestikaningsih, Moestikaningsih;Oka, Tjok Gede;Soeripto, Soeripto;Triningsih, FX Ediati;Triyono, Teguh;Heriyanto, Didik Setyo;Hosono, Akihiro;Suzuki, Sadao;Tokudome, Shinkan 979

https://doi.org/10.7314/APJCP.2016.17.3.979 PDF KSCI

The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be strikingly lower than that in Japan. We conducted an on-site ecological study to investigate the association between the stomach cancer incidence and Helicobacter pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155 women) from the general population in Bali, Indonesia, we conducted a urea breath test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect chronic atrophic gastritis and urine analysis to estimate sodium and potassium excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and 7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0-3) for men and 3% (0-5) for women, significantly lower than the respective values in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4) for women, also significantly lower than the Japanese figures. Computed values for daily salt excretion were $13.3{\pm}4.1g$ (mean${\pm}$SD) for men and $11.1{\pm}3.1g$ for women, as high as corresponding Japanese consumption values. Moreover, the estimated potassium excretion was $3.2{\pm}0.7g$ for men and $2.8{\pm}0.6g$ for women in Bali, significantly higher than the figures in Japan. There were no associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be due to the rare H. pylori infection. Namely, the bacterium infection seems to be a critical factor for gastric cancer rather than host or other environmental factors.

Dewan, Abhinav;Sharma, SK;Dewan, AK.;Srivastava, Himanshu;Rawat, Sheh;Kakria, Anjali;Mishra, Maninder;Suresh, T;Mehrotra, Krati 985

https://doi.org/10.7314/APJCP.2016.17.3.985 PDF KSCI

Objective of the study is to evaluate volumetric and dosimetric alterations taking place during radiotherapy for locally advanced head and neck cancer (LAHNC) and to assess benefit of replanning in them. Materials and Methods: Thirty patients with LAHNC fulfilling the inclusion and exclusion criteria were enrolled in a prospective study. Planning scans were acquired both pre-treatment and after 20 fractions (mid-course) of radiotherapy. Single plan (OPLAN) based on initial CT scan was generated and executed for entire treatment course. Beam configuration of OPLAN was applied to anatomy of interim scan and a hybrid plan (HPLAN30) was generated. Adaptive replanning (RPLAN30) for remaining fractions was done and dose distribution with and without replanning compared for remaining fractions. Results: Substantial shrinkage of target volume (TV) and parotids after 4 weeks of radiotherapy was reported (p<0.05). No significant difference between planned and delivered doses was seen for remaining fractions. Hybrid plans showed increase in delivered dose to spinal cord and parotids for remaining fractions. Interim replanning improved homogeneity of treatment plan and significantly reduced doses to cord (Dmax, D2% and D1%) and ipsilateral parotid (D33%, D50% and D66%) (p<0.05). Conclusions: Use of one or two mid-treatment CT scans and replanning provides greater normal tissue sparing along with improved TV coverage.

Rogalska, Aneta;Sliwinska, Agnieszka;Kasznicki, Jacek;Drzewoski, Jozef;Marczak, Agnieszka 993

https://doi.org/10.7314/APJCP.2016.17.3.993 PDF KSCI

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

He, Lang;Wang, Dan;Wei, Na;Guo, Zheng 1003

https://doi.org/10.7314/APJCP.2016.17.3.1003 PDF KSCI

Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

Basmaci, C;Pehlivan, M;Tomatir, AG;Sever, T;Okan, V;Yilmaz, M;Oguzkan-Balci, S;Pehlivan, S 1009

https://doi.org/10.7314/APJCP.2016.17.3.1009 PDF KSCI

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis.

Payandeh, Mehrdad;Shahriari-Ahmadi, Ali;Sadeghi, Masoud;Sadeghi, Edris 1015

https://doi.org/10.7314/APJCP.2016.17.3.1015 PDF KSCI

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

Chang, Chih-Chun;Su, Ming-Jang;Ho, Jung-Li;Sun, Jen-Tang;Tsai, Huang-Wen;Tang, Hui-Fei;Chu, Fang-Yeh 1019

https://doi.org/10.7314/APJCP.2016.17.3.1019 PDF KSCI

Background: Diagnostic difficulties in hematological malignancies may lead to unacceptably prolonged help-seeking to diagnostic interval as well as increased complications and poor outcomes. Proactive consultation by a clinical pathologist (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of this investigation was to evaluate the effect of PCCP on the help-seeking to diagnostic interval in hematological cancer cases. Materials and Methods: From January to November, 2015, abnormal results of hematological laboratory testing with added laboratory comment were selectively screened out, and patients with such abnormalities in hematological laboratory testing and accompanied laboratory comment with PCCP were enrolled. Results: A total of 125 aberrant results of hematological laboratory testing were given with accompanied laboratory comments with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to newly diagnosed hematological malignancies with the assistance of PCCP, and the help-seeking to diagnostic interval was also shortened from 42 days to 26 days in chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). During the monitoring interval, neither complication events nor deaths were reported in the study group. Conclusions: It was seemingly that PCCP prevented diagnostic delay in hematological malignancies via shortening the help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases. PCCP can be considered to play an essential role in prompt establishment of diagnosis in hematological malignancies for those who newly present.

Salim, Elsayed I;Hegazi, Mona M;Kang, Jin Seok;Helmy, Hager M 1023

https://doi.org/10.7314/APJCP.2016.17.3.1023 PDF KSCI

The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

Alvarado-Ruiz, Liliana;Martinez-Silva, Maria Guadalupe;Torres-Reyes, Luis Alberto;Pina-Sanchez, Patricia;Ortiz-Lazareno, Pablo;Bravo-Cuellar, Alejandro;Aguilar-Lemarroy, Adriana;Jave-Suarez, Luis Felipe 1037

https://doi.org/10.7314/APJCP.2016.17.3.1037 PDF KSCI

HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with non-tumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CC-derived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

Sultan, Sadia;Irfan, Syed Mohammed;Jawed, Syeda Narisa 1049

https://doi.org/10.7314/APJCP.2016.17.3.1049 PDF KSCI

Background: Myelodysplastic syndrome (MDS) is a clonal disorder of hemopoeitic stem cells, characterized by infective hematopoiesis, peripheral cytopenias along with hypercellularity of marrow and marked dysplastic features. Our aim was to study the spectrum of the WHO classification in adult Pakistani patients with MDS at disease presentation. Materials and Methods: This retrospective descriptive study was conducted at Liaquat National Hospital and Medical College, extending from January 2010 to December 2014. Patient data were retrieved from the maintained archives. Results: Overall, 45 patients were diagnosed at our institution with de novo MDS during the study period. There were 28 males and 17 females. Age ranged between 18 and 95 years with a mean of $57.6{\pm}17.4years$. The male to female ratio was 1.7:1. According to the WHO classification, 53.3% had refractory cytopenia with multilineage dysplasia, 22.2% had refractory cytopenia with unilineage dysplasia, 4.4% each had refractory anemia with excess of blasts-1 and II and 15.5% had MDS unclassified. The main presenting complaints were generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss (11.1%). Physical examination revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20% of patients. Hemoglobin was <10 g/dl in 41 (91.1%). Pancytopenia and bicytopenia were noted in 18 (40%) and 14 (31.1%) respectively. Conclusions: MDS in our patients presents at a relatively young age. Refractory c ytopenia with multilineage dysplasia was the dominant disease variant in our setting.

Sultan, Sadia;Irfan, Syed Mohammed;Khan, Sadia Rashid 1053

https://doi.org/10.7314/APJCP.2016.17.3.1053 PDF KSCI

Background: Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and Methods: In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count was $511{\pm}341.9{\times}10^9/l$. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.

Tongtawee, Taweesak;Dechsukhum, Chavaboon;Leeanansaksiri, Wilairat;Kaewpitoon, Soraya;Kaewpitoon, Natthawut;Loyd, Ryan A;Matrakool, Likit;Panpimanmas, Sukij 1057

https://doi.org/10.7314/APJCP.2016.17.3.1057 PDF KSCI

Background: The tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of 53. Therefore, this study aimed to determine the role of the Mdm2 SNIP 309 polymorphism in the gastric mucosal morphological patterns in patients with Helicobacter pylori associated gastritis. Materials and Methods: A prospective cross-sectional study was carried out from November 2014 through November 2015. Biopsy specimens were obtained from patients and infection was proven by positive histology. Gastric mucosa specimens were sent to the Molecular Genetics Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 polymorphism using the real-time PCR hybridization probe method. The results were analyzed and correlated with gastric mucosal morphological patterns by using C-NBI endoscopy. Results: A total of 300 infected patients were enrolled and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygosity correlated with type 1 to type 3 gastric mucosal morphological patterns (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with type 4 and type 5 (P<0.01). Conclusions: Our study finds the frequency of Mdm2 SNIP309 G/G in a Thai population is very low, and suggests that this can explain ae Thailand enigma. Types 1 to type 3 are the most common gastric mucosal morphological patterns according to the unique genetic polymorphism of MDM2 SNIP 309 in the Thai population.

Ahmad, Zubair;Idrees, Romana;Fatima, Saira;Uddin, Nasir;Ahmed, Arsalan;Minhas, Khurram;Memon, Aisha;Fatima, Syeda Samia;Arif, Muhammad;Hasan, Sheema;Ahmed, Rashida;Pervez, Shahid;Kayani, Naila 1061

https://doi.org/10.7314/APJCP.2016.17.3.1061 PDF KSCI

Context: There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. Aim: To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. Materials and Methods: 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H&E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. Results: There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. Conclusions: Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

Yip, CH;Bhoo-Pathy, N;Daniel, JM;Foo, YC;Mohamed, AK;Abdullah, MM;Ng, YS;Yap, BK;Pathmanathan, R 1077

https://doi.org/10.7314/APJCP.2016.17.3.1077 PDF KSCI

Background: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer. Materials and Methods: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22. Results: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy. Conclusions: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

Sabeena, Sasidharanpillai;Bhat, Parvati;Kamath, Veena;Mathew, Mary;Aswathyraj, Sushama;Devadiga, Santhosha;Prabhu, Suresha;Hindol, Maity;Chameetachal, Akhil;Krishnan, Anjana;Arunkumar, Govindakarnavar 1083

https://doi.org/10.7314/APJCP.2016.17.3.1083 PDF KSCI

Background: Cervical cancer is the second commonest cancer among Indian women and its association with human papilloma virus (HPV) is well established. This preventable cancer accounts for the maximum number of cancer related deaths among rural Indian women. Unlike in developed countries there are no organized cervical cancer screening programmes in India due to lack of resources and manpower. Objective: To detect genital HPV infection using urine samples among asymptomatic rural women in the age group of 18-65 years. Materials and Methods: The study area chosen was Perdoor village in Udupi Taluk, Karnataka State and all the women in the age group of 18-65 years formed the study cohort. A cross sectional study was conducted by house visits and 1,305 women were enrolled in the study. After taking written informed consent a data sheet was filled and early stream random urine samples were collected, transported to a laboratory at 4OC and aliquoted. Samples were tested using nested HPV PCR with PGMY09/11 and GP5+/6+ primers. Positive cases were genotyped by sequence analysis. Results: Study participants included 1,134 sexually active and 171 unmarried women with a mean age at marriage of 22.1 (SD=3.9) years. Study area showed high female literacy rate of 86.6%. Five urine samples tested positive for HPV DNA (0.4%). Conclusions: We found very low genital HPV infection rate among women from monogamous community. This is the first major population based study carried out among asymptomatic rural women to detect genital HPV infectio from Karnataka using urine samples.

Baloch, Abdul Hameed;Khosa, Ahmad Nawaz;Bangulzai, Nasrullah;Shuja, Jamila;Naseeb, Hafiz Khush;Jan, Mohammad;Marghazani, Illahi Bakhsh;Kakar, Masood-ul-Haq;Baloch, Dost Mohammad;Cheema, Abdul Majeed;Ahmad, Jamil 1089

https://doi.org/10.7314/APJCP.2016.17.3.1089 PDF KSCI

Breast cancer is the most commonly occurring and leading cause of cancer deaths among women globally. Hereditary cases account 5-10% of all the cases and CHEK2 is considered as a moderate penetrance breast cancer risk gene. CHEK2 plays a crucial role in response to DNA damage to promote cell cycle arrest and repair DNA damage or induce apoptosis. Our objective in the current study was to analyze mutations in the CHEK2 gene related to breast cancer in Balochistan. A total of 271 individuals including breast cancer patients and normal subjects were enrolled. All 14 exons of CHEK2 were amplified and sequenced. The majority of the patients (>95%) had invasive ductal carcinomas (IDCs), 52.1% were diagnosed with tumor grade III and 56.1% and 27.5% were diagnosed with advance stages III and IV. Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified in the current study. Both the variants identified were novel and have not been reported elsewhere.

Ramezani, Mazaher;Abdali, Elham;Khazaei, Sedigheh;Vaisi-Raygani, Asad;Sadeghi, Masoud 1093

https://doi.org/10.7314/APJCP.2016.17.3.1093 PDF KSCI

The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H & E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

Kaewpitoon, Soraya J;Kaewpitoon, Natthawut;Rujirakul, Ratana;Wakkuwattapong, Parichart;Matrakul, Likit;Tongtawee, Taweesak;Loyd, Ryan A;Norkaew, Jun;Kujapun, Jirawoot;Chavengkun, Wasugree;Ponphimai, Sukanya;Polsripradist, Poowadol;Eksanti, Thawatchai;Phatisena, Tanida 1097

https://doi.org/10.7314/APJCP.2016.17.3.1097 PDF KSCI

Background: Liver fluke infection with Opisthorchis viverrini and its associated cholangiocarcinoma constitute a serious problem in Thailand. Healthy behavior can decrease infection, therefore, the investigation of knowledge, attitude, and practice is need required in high risk areas. Objective: This study aimed to investigate the behavior and perceptions regarding liver fluke. Materials and Methods: A cross-sectional descriptive study was conducted in Chum Phuang district of Nakhon Ratchasima province, Thailand during July to November 2015. A total 80 participants who had screened with verbal screening test, stool examination, and ultrasonography, were purposive selected and completed a pre-designed questionnaire (Kruder-Richardon-20=0.80, Cronbach's alpha coefficient=0.82 and 0.79). T-test, ANOVA, and Pearson correlation test were used for analyzed data. Results: The results reveal that O. viverrini infection was 1.25%, and 3 patients had a dilated bile ducts. The participants had a high knowledge, attitude, and practice regarding liver fluke. The education, occupation, and income, were statistical significant to attitude regarding liver fluke. Nurses and television were the main sources of information regarding liver fluke, with statistical significance(p-value <0.05). Knowledge was significantly associated with attitude and practice (p-value<0.05). Conclusions: Participants had good behavior regarding liver fluke. Improvement of knowledge and attitude is influenced to practical change regarding this carcinogenic fluke. In addition, nurse and television are the main information resources for key success in increasing people perception for disease prevention and control in this area.

Kaya, Tijen Temiz;Altun, Ahmet;Turgut, Nergiz Hacer;Ataseven, Hilmi;Koyluoglu, Gokhan 1103

https://doi.org/10.7314/APJCP.2016.17.3.1103 PDF KSCI

In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.

Kaewpitoon, Soraya J;Thanapatto, Sirisuda;Nuathong, Wimonya;Rujirakul, Ratana;Wakkuwattapong, Parichart;Norkaew, Jun;Kujapun, Jirawoot;Padchasuwan, Natnapa;Kaewpitoon, Natthawut 1111

https://doi.org/10.7314/APJCP.2016.17.3.1111 PDF KSCI

Opisthorchiasis is a major problem in Thailand particularly in northeast region which also has a high incidence of cholangiocarcinomas. Since health modification is needed, this quasi-experimental study aimed to assess the effectiveness of a health education program based on self-efficacy and social support in Tha Tum district, Surin province, Thailand. A total of 70 participants were purposive selected with a history of opisthorchiasis. Participants were divided into experimental and control groups, each with 35 subjects. The experimental group received a health education program composed of: (1) knowledge improvement, lectured with multimedia, demonstration, brochure, and handbook; (2) group discussion about their health beliefs, sharing their ideas and experience; and (3) social support from village health volunteers (VHV), heads of villages (HV), friends, and members of families, and public health officer (PHO). Follow-up was by PHO/VHV/HV, with provision of certificates and flasg for household that did not eat raw fish. Data were collected by predesigned questionnaires after implementation of the program for 3 months. Comparative data was analyzed by paired simple t-test and independent t-test. The results revealed that the experimental group had mean score of knowledge higher more than before the experiment (mean difference=3.1, t=3.915, 95%CI-3.3, -1.8 p-value=0.001), and the control group (mean difference=2.5, t=4.196, 95%CI=1.4, 3.6, p-value=0.001) with statistical significance. The mean scores of practice were higher than before the experiment (mean difference=4.6, t=4.331, 95%CI-5.3, -3.1, p-value=0.001), and control group (mean difference=4.4, t=6.142, 95%CI=4.2, 7.9, p-value=0.001). The mean scores of perceived susceptibility and perceived severity of opisthorchiasis, al well as perceived benefits and perceived barriers to prevention of opisthorchiasis, were also higher than before the experiment and in the control group (p-value <0.001). In conclusion, this was a successful health education program for liver fluke avoidance. Therefore, it may useful for further behavior modification in the other epidemic areas.

Fatima, Nosheen;Zaman, Maseeh uz;Zaman, Areeba;Zaman, Unaiza;Tahseen, Rabia 1115

https://doi.org/10.7314/APJCP.2016.17.3.1115 PDF KSCI

Background: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. Materials and Methods: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis. Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. Results: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ${\leq}7.4ng/ml$ had the highest diagnostic strength to predict successful ablation in all patients. Conclusions: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline $sTg{\leq}7.4ng/ml$ is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

Seidi, Khaled;Jahanban-Esfahlan, Rana;Abasi, Mozhgan;Abbasi, Mehran Mesgari 1119

https://doi.org/10.7314/APJCP.2016.17.3.1119 PDF KSCI

Background: Punica granatum (PG) has been demonstrated to possess antitumor effects on various types of cancer cells. In this study, we determined antiproliferative properties of a seed extract of PG (PSE) from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate seeds was prepared. Total phenolic content (TPC) and total flavonoid content (TFC) were assessed by colorimetric assays. Antioxidant activity was determined with reference to DPPH radical scavenging activity. The cytotoxicity of different doses of PSE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all studied cancer cells, PSE reduced the cell viability to values below 23%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, SKOV3 ovarian cancer cells were the most responsive to antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8% vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively. Conclusions: Low doses of PSE exert potent antiproliferative effects on different human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least responsive regarding cytotoxic effects. However, the mechanisms of action need to be addressed.

Boupaijit, Kuanoon;Suprasert, Prapaporn 1123

https://doi.org/10.7314/APJCP.2016.17.3.1123 PDF KSCI

Chemotherapy is the primary treatment for advanced and recurrent cervical cancer. To evaluate the survival outcomes of chemotherapy and the prognostic factors in this setting, we conducted a retrospective study by reviewing the medical records of advanced and recurrent cervical cancer patients treated with systemic chemotherapy at our institute between January, 2008 and December, 2014. One hundred and seventy-three patients met the criteria with a mean age of 50.9 years. 4.1% of them were HIV positive. The most common initial stage was stage IVB (30.1%) and the most common histology was squamous cell carcinoma (68.6%). Ninety-two (53.2%) patients were previously treated with concurrent chemoradiation with 53% developing combined sites of recurrence. The median recurrence free interval was 16.7 months. Cisplatin + 5 fluorouracil (5FU) (53.2%) was the most frequent first line chemotherapy followed by carboplatin + paclitaxel (20.2%) with an objective response of 39.3%. Seventy-two patients received subsequent chemotherapy. The median overall survival of all studied patients was 13.2 months. Only a recurrence free interval of less than 12 months was an independent prognostic factor for survival outcome. In conclusion, chemotherapy treatment for advanced and recurrent cervical cancer patients showed modest efficacy with a shorter recurrence free survival less than 12 months as a significant poor prognosis factor.

Ngamkham, Jarunya;Boonmark, Krittika;Phansri, Thainsang 1129

https://doi.org/10.7314/APJCP.2016.17.3.1129 PDF KSCI

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human ${\beta}$-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

Alhazzazi, Turki Y 1135

https://doi.org/10.7314/APJCP.2016.17.3.1135 PDF KSCI

Background: Head and neck cancer (HNC) is one of the deadliest cancers worldwide. Early detection is a key determinant of HNC prognosis. Hence, raising awareness of this disease may improve survival rates. The present study evaluated the level of awareness and screening status for HNC in the general population of Jeddah, Saudi Arabia. Materials and Methods: An e-questionnaire was distributed during our HNC awareness campaign at the Red Sea Mall in Jeddah. The questions assessed HNC knowledge and screening status among participants. Results: Of the 112 respondents, 68% indicated that they had no knowledge of HNC. Social media was the major source of information (39%) for respondents. The majority (40%) believed that it was the joint responsibility of dentists, dental hygienists, and general physicians to screen for HNC; 82% had never been screened. Conclusions: Knowledge and awareness of HNC must be increased in the general population and among dental health professionals.

Zeng, Yan;Bai, Jian;Deng, Li-Cong;Xie, Yu-Ping;Zhao, Fen;Huang, Ying 1141

https://doi.org/10.7314/APJCP.2016.17.3.1141 PDF KSCI

Background: A large number of studies have been published to investigate the association between the null genotype of glutathione S-transferase T1 (GSTT1) with gastric cancer. However, the results were inconsistent and conflicting. The aim of this study was to estimate the relationship between this polymorphism in the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis. Materials and Methods: A literature search was performed in PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China National Knowledge Infrastructure database (CNKI). Statistical analysis was conducted by using Review Manager 5.3. Results: Thirty-nine studies with a total of 7,737 gastric cancer cases and 10,823 controls were included in this meta-analysis. The meta-analysis of total studies showed that the null genotype in GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19, 95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship between GSTT1 null genotype and gastric cancer in East-Asians, as well as in subgroup analysis of hospital-based design. On subgroup analysis by smoking status, alcohol status, Helicobacter pylori infection status, and histology type, no significant association of this polymorphism with susceptibility to gastric cancer was found. Conclusions: In conclusion, the results showed that the null genotype of GSTT1 is significantly associated with an increased risk in gastric cancer in Asian populations.

Khoo, Joon-Joon;Ng, Chen-Siew;Sabaratnam, Subathra;Arulanantham, Sarojah 1149

https://doi.org/10.7314/APJCP.2016.17.3.1149 PDF KSCI

Background: Examination of sentinel lymph node (SLN) biopsies provides accurate nodal staging for breast cancer and plays a key role in patient management. Procurement of SLNs and the methods used to process specimens are equally important. Increasing the level of detail in histopathological examination of SLNs increases detection of metastatic tumours but will also increase the burden of busy laboratories and thus may not be carried out routinely. Recommendation of a reasonable standard in SLN examination is required to ensure high sensitivity of results while maintaining a manageable practice workload. Materials and Methods: Twenty-four patients with clinically node-negative breast cancer were recruited. Combined radiotracer and blue dye methods were used for identification of SLNs. The nodes were thinly sliced and embedded. Serial sectioning and immunohistochemical (IHC) staining against AE1/AE3 were performed if initial H&E sections of the blocks were negative. Results: SLNs were successfully identified in all patients. Ten cases had nodal metastases with 7 detected in SLNs and 3 detected only in axillary nodes (false negative rate, FNR=30%). Some 5 out of 7 metastatic lesions in the SLNs (71.4%) were detected in initial sections of the thinly sliced tissue. Serial sectioning detected the remaining two cases with either micrometastases or isolated tumour cells (ITC). Conclusions: Thin slicing of tissue to 3-5mm thickness and serial sectioning improved the detection of micro and macro-metastases but the additional burden of serial sectioning gave low yield of micrometastases or ITC and may not be cost effective. IHC validation did not further increase sensitivity of detection. Therefore its use should only be limited to confirmation of suspicious lesions. False negative cases where SLNs were not involved could be due to skipped metastases to non-sentinel nodes or poor technique during procurement, resulting in missed detection of actual SLNs.

Ghahremani, Leila;Harami, Zahra Khiyali;Kaveh, Mohammad Hossein;Keshavarzi, Sareh 1157

https://doi.org/10.7314/APJCP.2016.17.3.1157 PDF KSCI

Background: Cervical cancer is known as one of the most prevalent types of cancers and a major public health problem in developing countries which can be detected by Pap test, prevented, and treated. Despite the effective role of Pap test in decreasing the incidence and mortality due to cervical cancer, it is still one the most common causes of cancer-related deaths among women, especially in developing countries. Thus, this study aimed to examine the effect of educational interventions implemented by health volunteers based on protection motivation theory (PMT) on promoting Pap test use among women. Materials and Methods: This quasi-experimental study was conducted on 60 health volunteers and 420 women. The study participants were divided into an intervention and a control group. Data were collected using a valid self-reported questionnaire including demographic variables and PMT constructs which was completed by both groups before and 2 months after the intervention. Then, the data were entered into the SPSS statistical software, version 19 and were analyzed using Chi-square test, independent T-test, and descriptive statistical methods. P<0.05 was considered as statistically significant. Results: The findings of this study showed that the mean scores of PMT constructs (i.e. perceived vulnerability, perceived severity, fear, response-costs, self-efficacy, and intention) increased in the intervention group after the intervention (P<0.001). However, no significant difference was found between the two groups regarding response efficacy after the intervention (P=0.06). The rate of Pap test use also increased by about 62.9% among the study women. Conclusions: This study showed a significant positive relationship between PMT-based training and Pap test use. The results also revealed the successful contribution of health volunteers to training cervical cancer screening. Thus, training interventions based on PMT are suggested to be designed and implemented and health volunteers are recommended to be employed for educational purposes and promoting the community's, especially women's, health.

Kotawong, Kanawut;Thitapakorn, Veerachai;Roytrakul, Sittiruk;Phaonakrop, Narumon;Viyanant, Vithoon;Na-Bangchang, Kesara 1163

https://doi.org/10.7314/APJCP.2016.17.3.1163 PDF KSCI

Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the important public health problems in Thailand with high mortality rate, especially in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of the northeastern region of the country. This study aimed to identify potential biomarkers from the plasma peptidome by CCA patients. Peptides were isolated using 10 kDa cut-off filter column and the flow-through was then used as a peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among these, 15 peptides were concerned with signaling pathways and 12 related to metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five exclusive peptides were identified as potential biomarkers, i.e. ETS domain-containing transcription factor ERF (P50548), KIAA0220 (Q92617), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784). Three of these biomarkers are signaling related molecules. A combination of these biomarkers for CCA diagnosis is proposed.

Kandaz, Mustafa;Soydemir, Gulsen;Bahat, Zumrut;Canyilmaz, Emine;Yoney, Adnan 1169

https://doi.org/10.7314/APJCP.2016.17.3.1169 PDF KSCI

Purpose: To review clinical characteristics, treatment outcomes and prognostic factors in patients with parotid gland tumors treated with surgery and postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 69 patients with parotid gland tumors, with a median follow-up of 52 months (range, 2-228 months). and a median radiotherapy dose of 60Gy (range, 30-69 Gy). Results: There were 24 (35%) females and 45 (65%) males, at a ratio of 1/1.9. Median age at presentation was $58.9{\pm}17.2$ (range 13-88) years. The most common histology was adenoid cystic carcinoma (33%) and mucoepidermoid carcinoma (28%). The mean overall survival (OS) was $65.3{\pm}8$ (95% confidence interval [CI], 49.6-81.1) months and the median overall survival was $40.0{\pm}7$ (95% CI, 26.2-53.7) months. The -1, -3, -5 and -10 year OS rates were 78%, 52.4%, 35.3% and 19.6% respectively. The mean disease free survival (DFS) was $79.2{\pm}10$ (95% CI, 59.3-97.1) months and the median disease free survival was $38{\pm}13$ (95% CI, 7.05-88.7) months. The -1,-3,-5 and -10 year DFS rates were 71.9%, 50.1%, 43.7% and 30.1% respectively. On univariate analysis, the OS was significantly better with female sex (p<0.005), < 50 age (p<0.021), T stage (p<0.0001), absence of lymph node involvement (p<0.0001), lower tumor grade (p<0.0001), absence of lymphovascular invasion (p<0.002), absence of perineural invasion (p<0.0001), absence of extracapsuler extension (p<0.0001), surgical margin negativity (p<0.006), ${\leq}60Gy$ radiotherapy dose (p<0.0001) and absence of distant metastasis (p<0.027). Conclusions: Employing existing standards of postoperative radiotherapy is a possible treatment that was found to be mainly effective in patients with parotid gland carcinomas.

Gorukmez, Orhan;Yakut, Tahsin;Gorukmez, Ozlem;Sag, Sebnem Ozemri;Karkucak, Mutlu;Kanat, Ozkan 1175

https://doi.org/10.7314/APJCP.2016.17.3.1175 PDF KSCI

The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

Uyan, Mikail;Koca, Bulent;Yuruker, Savas;Ozen, Necati 1181

https://doi.org/10.7314/APJCP.2016.17.3.1181 PDF KSCI

Background: The aim of this study is to compare the numbers of axillary lymph nodes (ALN) taken out by dissection between patients with breast cancer operated on after having neoadjuvant chemotherapy (NAC) treatment and otherswithout having neoadjuvant chemotherapy, and to investigate factors affecting lymph node positivity. Materials and Methods: A total of 49 patients operated due to advanced breast cancer after neoadjuvant chemotherapy and 144 patients with a similar stage of the cancer having primary surgical treatment without chemotherapy at the general surgery clinic of Ondokuz Mayis University Medicine Faculty between the dates 01.01.2006 and 31.10.2012 were included in the study. The total number of lymph nodes taken out by axillary dissection (ALND) was categorized as the number of positive lymph nodes and divided into <10 and ${\geq}10$. The variables to be compared were analysed using the program SPSS 15.0 with P<0.05 accepted as significant. Results: Median number of dissected lymph nodes from the patient group having neoadjuvant chemotherapy was 16 (16-33) while it was 20 (5-55) without chemotherapy. The respective median numbers of positive lymph nodes were 5 (0-19) and 10 (0-51). In 8 out of 49 neoadjuvant chemotherapy patients (16.3%), the number of dissected lymph nodes was below 10, and it was below 10 in 17 out of 144 primary surgery patients. Differences in numbers of dissected total and positive lymph nodes between two groups were significant, but this was not the case for numbers of <10 lymph nodes. Conclusions: The number of dissected lymph nodes from the patients with breast cancer having neoadjuvant chemotherapy may be less than without chemotherapy. This may not always be attributed to an inadequate axillary dissection. More research to evaluate the numbers of positive lymph nodes are required in order to increase the reliability of staging in the patients with breast cancer undergoing neoadjuvant chemotherapy.

Chien, Tsu-Ming;Lu, Yen-Man;Geng, Jiun-Hung;Huang, Tsung-Yi;Ke, Hung-Lung;Huang, Chun-Nung;Li, Ching-Chia;Chou, Yii-Her;Wu, Wen-Jeng;Huang, Shu-Pin 1187

https://doi.org/10.7314/APJCP.2016.17.3.1187 PDF KSCI

Background: The prevalence of prostate cancer (PCa) has been increasing in recent years. Treatment strategies are largely based on the results of bone scan screening. Therefore, our aim was to investigate predictors of positive bone metastasis in newly diagnosed PCa patients. Materials and Methods: After extensive review, 336 consecutive patients newly diagnosed with PCa between April 2010 and November 2013 at our institution were enlisted in the study. Patients were divided into two groups according to bone scan results. Univariate analyses (Chi-square test for discrete variables and independent t-test for continuous variables) were applied to determine the potentially significant risk factors associated with distant bone metastasis. Binary logistic regression analyses were used to further investigate the influence of these factors on bone metastasis. Results: The patient mean age was $71.9{\pm}8.6years$ (range: 48 to 94 years). The mean prostate specific antigen (PSA) level and biopsy Gleason score were $260.2{\pm}1107.8ng/mL$ and $7.4{\pm}1.5$, respectively. The body mass index (BMI) for the series was $24.5{\pm}3.4kg/m^2$. Sixty-four patients (19.0%) had a positive bone scan result. Patients with positive bone scan results had a significantly lower BMI ($23.3{\pm}3.5$ vs. $24.8{\pm}3.3$; p=0.003), a higher Gleason score ($8.5{\pm}1.1$ vs. $7.1{\pm}1.5$; p < 0.001), and a higher PSA level ($1071.3{\pm}2337.1$ vs. $69.4{\pm}235.5$; p < 0.001) than those without bone metastasis. Multivariate logistic regression analysis employing the above independent predictors demonstrated that a Gleason score of ${\geq}7$, clinical stage ${\geq}T3$, $BMI{\leq}22kg/m^2$, and an initial PSA level of ${\geq}20ng/mL$ were all independent predictors of bone metastasis. Conclusions: A bone scan might be necessary in newly diagnosed PCa patients with any of the following criteria: clinical stage T3 or higher, a Gleason score of 7 or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.

Baghestani, Ahmad Reza;Daneshvar, Tahoura;Pourhoseingholi, Mohamad Amin;Asadzadeh, Hamid 1193

https://doi.org/10.7314/APJCP.2016.17.3.1193 PDF KSCI

Background: Colorectal cancer (CRC) is the commonest malignancy in the lower gastrointestinal tract in both men and women. It is the third leading cause of cancer-dependent death in the world. In Iran the incidence of colorectal cancer has increased during the last 25 years. Materials and Methods: In this article we analyzed the survival of 447 colorectal patients of Taleghani hospital in Tehran using parametric competing-risks models. The cancers of these patients were diagnosed during 1985 - 2012 and followed up to 2013. The purpose was to assess the association between survival of patients with colorectal cancer in the presence of competing-risks and prognostic factors using parametric models. The analysis was carried out using R software version 3.0.2. Results: The prognostic variables included in the model were age at diagnosis, tumour site, body mass index and sex. The effect of age at diagnosis and body mass index on survival time was statistically significant. The median survival for Iranian patients with colorectal cancer is about 20 years. Conclusions: Survival function based on Weibull model compared with Kaplan-Meier survival function is smooth. Iranian data suggest a younger age distribution compared to Western reports for CRC.

Sanli, Yusuf Tolga;Cukurcayir, Funda;Abacigil, Fatma 1197

https://doi.org/10.7314/APJCP.2016.17.3.1197 PDF KSCI

Background: This study aimed to facilitate decision-making in cases of breast cancer radiotherapy shifts by simulating millimetric shifts and analyzing their effects on dose distribution. Methods: The study included 30 patients with left side breast cancer who were treated with three dimensional conformal radiotherapy (3D-CRT) in the Radiation Oncology Department in Hatay Public Hospital, between January 2013 and April 2015. A treatment plan shifting at three axes with six different measures was simulated. Results: The biggest difference in values was (+3mm shift) 476cGy, with a 7.7 % change for heart and 25.6% for spinal cord. The shifts in values respectively for CTV min, mean, max were -4.8%, 2.5%, 4%. The differences for lymphatic min, mean, max were 21.3%, 20.3%, -12.2%. Conclusion: The most important thing is not the treatment plan quality, but its practicality. The treatment plan must be practical and its practice must be controlled rigidly.

Velasques, Kelle;Michels, Luana Roberta;Colome, Leticia Marques;Haas, Sandra Elisa 1201

https://doi.org/10.7314/APJCP.2016.17.3.1201 PDF KSCI

Background: Excessive exposure to the sun during childhood is strongly associated with the development of skin cancer in the future. The only way to prevent the development of skin cancer is to protect against ultraviolet radiation, which can be achieved through strategic awareness during childhood and adolescence. Objective. The aim of this work was to evaluate the impact of educational activities for rural and urban students to promote the use of sunscreens and prevent skin cancer. Materials and Methods: This study was carried out with students (9-12 years) of rural (n=70) and urban (n=70) schools in Rio Grande do Sul state, Brazil. The educational interventions were lectures and games. The impact of this strategy was evaluated through the application of a questionnaire before and after the interventions. Results: Before the intervention, it was found around 50% of rural and urban students were not aware of the damage caused by sun exposure, often exposing themselves to UV radiation without use sunscreen ( ~ 25 %) and at the most critical times of the day/year. After the lectures we observed an improvement in the behavior of the students with regard to sun exposure and knowledge about skin cancer. Conclusions: The results of this study emphasize the importance of prevention strategies for skin cancer and promoting the use of sunscreens based educational strategies. The interventions were of great value in relation to disseminating knowledge on the subject.

Abiola, AO;Balogun, OS;Odukoya, OO;Olatona, FA;Odugbemi, TO;Moronkola, RK;Solanke, AA;Akintunde, OJ;Fatoba, OO 1209

https://doi.org/10.7314/APJCP.2016.17.3.1209 PDF KSCI

Background: Cigarette smoking constitutes a major threat to the health and wellbeing of teenagers. While smoking has been on decline in the developed countries, the reverse is the case in developing countries. The aim of this study was to determine the age of initiation, determinants and prevalence of cigarette smoking among teenagers in Mushin Local Government Area of Lagos state, Nigeria. Materials and Methods: This was a descriptive cross-sectional study among 475 teenagers selected by multistage sampling. A pre-tested, structured, interviewer-administered questionnaire was used for data collection. The study was carried out in November, 2014. Results: Response rate was 84.6%. Mean age of the respondents was $16.4{\pm}1.65years$. Range and mean age of initiation of cigarette smoking were 7 to 17 years and $12.0{\pm}3.32years$ respectively. Teenagers who were above 15 years (OR:5.13, 95%CI: 0.87-30.26), males (OR:5.19, 95%CI: 1.57-17.18), married (OR:8.41, 95%CI: 1.04-63.35), had ${\leq}$primary school education(OR:4.31, 95%CI: 1.07-17.33), influenced by friends(OR:308.84, 95%CI:84.87-1123.81), and influenced by advertisements (OR:27.83, 95%CI: 3.92-197.64) were more likely to have initiated cigarette smoking. Furthermore, teenagers who were males (OR:12.77, 95%CI: 2.90-56.28), married (OR:19.24, 95%CI: 2.05-180.45), had ${\leq}$primary school education(OR:7.85, 95%CI: 2.37-26.01), influenced by friends(OR:28.56, 95%CI: 10.86-75.07), and influenced by advertisements (OR:5.95, 95%CI: 1.72-20.61) were more likely to be current cigarette smokers. In addition, 24.9% had initiated cigarette smoking while 14.7% were current smokers of cigarette. Conclusions: Mean age of initiation of cigarette smoking was $12.0{\pm}3.32years$. Determinants of cigarette smoking were age, gender, marital status, educational background, friends and advertisements. Life time prevalence of cigarette smoking was higher than prevalence of current cigarette smokers. Cigarette smoking reduction programs should take these factors into consideration.

Yadav, Prasant;Mir, Rashid;Nandi, Kajal;Javid, Jamsheed;Masroor, Mirza;Ahmad, Imtiyaz;Zuberi, Mariyam;Kaza, RCM;Jain, SK;Khurana, Nita;Ray, Prakash Chandra;Saxena, Alpana 1215

https://doi.org/10.7314/APJCP.2016.17.3.1215 PDF KSCI

Background: Worldwide, breast cancer is the most common cancer among women and is a leading cause of cancer death. In the present study, we investigated the NQO1 C609T genotypic and allelic distribution in north Indian breast cancer patients. Materials and Methods: The genotypic distribution of the NQ01 C609T polymorphism was assessed in 100 invasive ductal carcinoma (IDC) breast cancer patients and 100 healthy controls using allele specific PCR (AS-PCR). Results: A lower frequency of the CC genotype was found in breast cancer patients (24%) than in the controls. On the other hand, TT genotype frequency was also found to be higher in female healthy controls (32%) than the female breast cancer patients (20%). The frequencies of all three genotypes CC, CT, TT in patients were 24%, 56% and 20% and in healthy controls 50%, 22% and 32% respectively. We did not find any significant correlation between the NQO1 C609T polymorphism and age group, grading, menopausal status and distant metastasis. A less significant association was found between the NQ01 C609T polymorphism and the stage of breast cancer (X2=5.931, P=0.05). Conclusions: The present study shows a strong association between NQO1 C609T polymorphism with the breast cancer risk in the north Indian breast cancer patients so that possible use as a risk factor should be further expel.

Chen, Jia-Yan;Zhu, Hong-Cheng;Guo, Qing;Shu, Zheng;Bao, Xu-Hui;Sun, Feng;Qin, Qin;Yang, Xi;Zhang, Chi;Cheng, Hong-Yan;Sun, Xin-Chen 1221

https://doi.org/10.7314/APJCP.2016.17.3.1221 PDF KSCI

Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Intarut, Nirun;Chongsuvivatwong, Virasakdi;McNeil, Edward 1235

https://doi.org/10.7314/APJCP.2016.17.3.1235 PDF KSCI

Background: A school-based smoke free home (SFH) program is useful in empowering the mother and child to reduce secondhand smoke exposure but the effects of pretesting on knowledge and attitude has been largely ignored. We aimed to test whether such a program can be effective in Southern Thailand with an additional assessment of the net effect of the pretest. Materials and Methods: A Solomon four-group design was used. Twelve rural primary schools were assigned to one of the four conditions (each with 3 schools): intervention with and without a pretest, control with and without the same pretest. The intervention was performed in the classroom and home over a period of 1 month. Outcomes were assessed at baseline and 3 months after the intervention on whether the home was smoke free and related knowledge and attitude. Results: The intervention could lead to a smoke-free home without statistical significance. Attitude, knowledge and self-confidence on creating a smoke-free home, and self-confidence in avoidance of secondhand smoke exposure and persuading smokers to not smoke in their home were significantly improved. No pretest effect was observed. Conclusions: Gain in attitude, knowledge and self-confidence among family members from the brief school-based education should be enhanced by other measures.

Sawair, F;Hassona, Y;Irwin, C;Stephenson, M;Hamilton, P;Maxwell, P;Gordon, D;Leonard, A;Napier, S 1243

https://doi.org/10.7314/APJCP.2016.17.3.1243 PDF KSCI

Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. Materials and Methods: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. Results: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

Rai, Harish Chandra;Ahmed, Junaid 1251

https://doi.org/10.7314/APJCP.2016.17.3.1251 PDF KSCI

Background: Oral squamous cell carcinoma (OSCC), the most common malignancy of the oral cavity, shows geographical variation with respect to the age, sex, site and habits of the population. The histolopathologic grade of the tumor is closely related to its tissue of origin. This study was conducted to establish the prevalence of OSCC in relation to patient sex, age, habits and sites of lesions. Materials and Methods: A total of 130 cases of histopathologically diagnosed OSCC were selected for the study, out of which 66, 38 and 26 were well (WD), moderately (MD)and poorly differentiated (PD), respectively. Sections were stained with haematoxylin and eosin and graded according to a modified Borders's system. Then statistically analyzed different grades of OSCC for correlations with other variables. Results: In our study the majority cases of OSCC were found in the 5th to 7th decades of life, males acconting for 53%. The most common site was the buccal mucosa and most cases had habit of tobacco use either in the form of chewing or smoking or both. When the different grades of OSCC were compared with different sites a statistically significant value was observed (P=0.029). Conclusions: The incidence of high grade PD is very much less in female patients but in males such lesions were common. In our location population the buccal mucosa is the most common site due to the tobbaco habits of the patients and majority cases of the buccal mucosa are WD whereas in tongue, floor of the mouth and palate PD are common.

Patil, Pravinkumar;Hazarey, Vinay;Chaudhari, Rekha;Nimbalkar-Patil, Smita 1255

https://doi.org/10.7314/APJCP.2016.17.3.1255 PDF KSCI

Background: Oral physiotherapy or mouth exercise is considered to be an adjunct but mandatory treatment modality for oral submucous fibrosis (OSMF). This study planned to evaluate the clinical efficacy of a newly designed mouth exercising device (MED) in OSMF patients receiving local ointment, intra-lesional drugs and surgical treatment. Materials and Methods: A total of 231 OSMF patients were selected and treated with basic regime including topical corticosteroids, oral antioxidants and the icecream-stick exercise regime and allotted randomly to two equal groups A and B. Group-A patients were additionally given MED. Subgroups A1 and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm were managed surgically. IID was measured at baseline and at 6 months recall. The change in IID measurements was calculated and statistically analyzed using 2-way ANOVA and Tukeys multiple post hoc analysis. Results: Average improvement in IID after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53) compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18) compared to 4.8 mm for B3 (n-16) (p<0.01). Conclusions: Use of the MED appears to be effective for increasing oral opening in OMSF patients in conjunction with local, injection and/or surgical treatment.

Payandeh, Mehrdad;Sadeghi, Masoud;Sadeghi, Edris;Madani, Seyed-Hamid 1261

https://doi.org/10.7314/APJCP.2016.17.3.1261 PDF KSCI

Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as ${\geq}10%$ positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 ${\geq}20%$. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.

Suprasert, Prapaporn;Aue-Aungkul, Apiwat;Pautad, Nuthaya 1265

https://doi.org/10.7314/APJCP.2016.17.3.1265 PDF KSCI

Egg white intake during chemotherapy is common advice for cancer patients for the prevention of leukopenia. However, the benefit is uncertain. We conducted this prospective study to identify the relationship of egg white intake for gynecologic cancer patients who received carboplatin and paclitaxel and the occurrence of leukopenia. Between January 2014 and January, 2015, 81 patients were interviewed regarding their intake of egg whites before receiving subsequent chemotherapy. The basic data, the details of egg white intake and the grade of leukopenia in the previous cycle were recorded. The mean age was 54.1 years and 80% of the patients had a diagnosis of ovarian or endometrial cancer. The patients were interviewed at cycles 1-3 in 45 cases, 4-6 in 45 cases and 7-9 in two cases. Subsequent dose reduction was found in 6.2% and granulocyte-stimulating growth factors was given at 4.9%. All the patients ate egg whites with variations in the number of eggs per day as follows: less than one (3), one to two (56), three to four (14) and five to six (8). Over 70% were recommended by nurses to eat egg whites and about 63% of patients received other supplemental food. Some 44.1% of the patients who ate less than or equal to two eggs per day and 36.4% who ate more than two eggs per day developed grade 2-4 leukopenia, P = 0.61. In conclusion, the data did not provide evidence in support of the conclusion that a greater egg white intake could significantly reduce the occurrence of leukopenia.

Tee, Guat Hiong;Aris, Tahir;Rarick, James;Irimie, Sorina 1269

https://doi.org/10.7314/APJCP.2016.17.3.1269 PDF KSCI

Background: Tobacco consumption continues to be the leading cause of preventable deaths globally. The objective of this study was to examine the associaton of selected socio-demographic variables with current tobacco use in five countries that participated in the Phase II Global Adult Tobacco Survey in 2011 - 2012. Materials and Methods: We analysed internationally comparable representative household survey data from 33,482 respondents aged ${\geq}15years$ in Indonesia, Malaysia, Romania, Argentina and Nigeria for determinants of tobacco use within each country. Socio-demographic variables analysed included gender, age, residency, education, wealth index and awareness of smoking health consequences. Current tobacco use was defined as smoking or use of smokeless tobacco daily or occasionally. Results: The overall prevalence of tobacco use varied from 5.5% in Nigeria to 35.7% in Indonesia and was significantly higher among males than females in all five countries. Odds ratios for current tobacco use were significantly higher among males for all countries [with the greatest odds among Indonesian men (OR=67.4, 95% CI: 51.2-88.7)] and among urban dwellers in Romania. The odds of current tobacco use decreased as age increased for all countries except Nigeria where. The reverse was true for Argentina and Nigeria. Significant trends for decreasing tobacco use with increasing educational levels and wealth index were seen in Indonesia, Malaysia and Romania. Significant negative associations between current tobacco use and awareness of adverse health consequences of smoking were found in all countries except Argentina. Conclusions: Males and the socially and economically disadvantaged populations are at the greatest risk of tobacco use. Tobacco control interventions maybe tailored to this segment of population and incorporate educational interventions to increase knowledge of adverse health consequences of smoking.

Ahmadian, Maryam;Carmack, Suzie;Samah, Asnarulkhadi Abu;Kreps, Gary;Saidu, Mohammed Bashir 1277

https://doi.org/10.7314/APJCP.2016.17.3.1277 PDF KSCI

Background: Early detection is a critical part of reducing the burden of breast cancer and breast self-examination (BSE) has been found to be an especially important early detection strategy in low and middle income countries such as Malaysia. Although reports indicate that Malaysian women report an increase in BSE activity in recent years, additional research is needed to explore factors that may help to increase this behavior among Southeastern Asian women. Objective: This study is the first of its kind to explore how the predicting variables of self-efficacy, perceived barriers, and body image factors correlate with self-reports of past BSE, and intention to conduct future breast self-exams among female students in Malaysia. Materials and Methods: Through the analysis of data collected from a prior study of female students from nine Malaysian universities (n=842), this study found that self-efficacy, perceived barriers and specific body image sub-constructs (MBSRQ-Appearance Scales) were correlated with, and at times predicted, both the likelihood of past BSE and the intention to conduct breast self-exams in the future. Results: Self-efficacy (SE) positively predicted the likelihood of past self-exam behavior, and intention to conduct future breast self-exams. Perceived barriers (BR) negatively predicted past behavior and future intention of breast self-exams. The body image sub-constructs of appearance evaluation (AE) and overweight preoccupation (OWP) predicted the likelihood of past behavior but did not predict intention for future behavior. Appearance orientation (AO) had a somewhat opposite effect: AO did not correlate with or predict past behavior but did correlate with intention to conduct breast self-exams in the future. The body image sub-constructs of body area satisfaction (BASS) and self-classified weight (SCW) showed no correlation with the subjects' past breast self-exam behavior nor with their intention to conduct breast self-exams in the future. Conclusions: Findings from this study indicate that both self-efficacy and perceived barriers to BSE are significant psychosocial factors that influence BSE behavior. These results suggest that health promotion interventions that help enhance self-efficacy and reduce perceived barriers have the potential to increase the intentions of Malaysian women to perform breast self-exams, which can promote early detection of breast cancers. Future research should evaluate targeted communication interventions for addressing self-efficacy and perceived barriers to breast self-exams with at-risk Malaysian women. and further explore the relationship between BSE and body image.

Abdel-Mohsen, Mohamed Ahmed;Ahmed, Omiama Ali;El-Kerm, Yasser Mostafa 1285

https://doi.org/10.7314/APJCP.2016.17.3.1285 PDF KSCI

Background: It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy. Purpose: The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated. Materials and Methods: Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy. Results: BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). Conclusions: The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy.

Kaewpitoon, Soraya J;Rujirakul, Ratana;Joosiri, Apinya;Jantakate, Sirinun;Sangkudloa, Amnat;Kaewthani, Sarochinee;Chimplee, Kanokporn;Khemplila, Kritsakorn;Kaewpitoon, Natthawut 1293

https://doi.org/10.7314/APJCP.2016.17.3.1293 PDF KSCI

Cholangiocarcinoma (CCA) is a serious problem in Thailand, particularly in the northeastern and northern regions. Database of population at risk are need required for monitoring, surveillance, home health care, and home visit. Therefore, this study aimed to develop a geographic information system (GIS) database and Google map of the population at risk of CCA in Mueang Yang district, Nakhon Ratchasima province, northeastern Thailand during June to October 2015. Populations at risk were screened using the Korat CCA verbal screening test (KCVST). Software included Microsoft Excel, ArcGIS, and Google Maps. The secondary data included the point of villages, sub-district boundaries, district boundaries, point of hospital in Mueang Yang district, used for created the spatial databese. The populations at risk for CCA and opisthorchiasis were used to create an arttribute database. Data were tranfered to WGS84 UTM ZONE 48. After the conversion, all of the data were imported into Google Earth using online web pages www.earthpoint.us. Some 222 from a 4,800 population at risk for CCA constituted a high risk group. Geo-visual display available at following www.google.com/maps/d/u/0/edit?mid=zPxtcHv_iDLo.kvPpxl5mAs90&hl=th. Geo-visual display 5 layers including: layer 1, village location and number of the population at risk for CCA; layer 2, sub-district health promotion hospital in Mueang Yang district and number of opisthorchiasis; layer 3, sub-district district and the number of population at risk for CCA; layer 4, district hospital and the number of population at risk for CCA and number of opisthorchiasis; and layer 5, district and the number of population at risk for CCA and number of opisthorchiasis. This GIS database and Google map production process is suitable for further monitoring, surveillance, and home health care for CCA sufferers.

Bukowska, Barbara;Rogalska, Aneta;Forma, Ewa;Brys, Magdalena;Marczak, Agnieszka 1299

https://doi.org/10.7314/APJCP.2016.17.3.1299 PDF KSCI

Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

Musri, Fatma Yalcin;Mutlu, Hasan;Eryilmaz, Melek Karakurt;Salim, Derya Kivrak;Gunduz, Seyda;Coskun, Hasan Senol 1309

https://doi.org/10.7314/APJCP.2016.17.3.1309 PDF KSCI

Inflammation can play an important role in cancer progression and the prognostic importance of neutrophil to lymphocyte ratio (NLR), a marker of inflammation, in cancer is a current investigation topic. In the present study, we aimed to determine whether there is a prognostic link between NLR and metastatic gastric cancer (mGC). A total of 143 patients from the Akdeniz University and Antalya Training and Research Hospital database were retrospectively analyzed. The median NLR value was 3.34. The median overall survival (OS) and median progression-free survival (PFS) were 11.6 and 7.9 months, respectively, in patients with NLR<3.34 while these values were 8.3 and 6.2 months respectively in patients with NLR>3.34 (p<0.001 and p=0.011, respectively). Our study showed that increased NLR is an independent prognostic factor associated with short survival in patients with mGC.

Milder, CM;Sakata, R;Sugiyama, H;Sadakane, A;Utada, M;Cordova, KA;Hida, A;Ohishi, W;Ozasa, K;Grant, EJ 1313

https://doi.org/10.7314/APJCP.2016.17.3.1313 PDF KSCI

To study the full health effects of parental radiation exposure on the children of the atomic bomb survivors, the Radiation Effects Research Foundation developed a cohort of 76,814 children born to atomic bomb survivors (F1 generation) to assess cancer incidence and mortality from common adult diseases. In analyzing radiation-associated health information, it is important to be able to adjust for sociodemographic and lifestyle variations that may affect health. In order to gain this and other background information on the F1 cohort and to determine willingness to participate in a related clinical study, the F1 Mail Survey Questionnaire was designed with questions corresponding to relevant health, sociodemographic, and lifestyle indicators. Between the years 2000 and 2006, the survey was sent to a subset of the F1 Mortality Cohort. A total of 16,183 surveys were completed and returned: 10,980 surveys from Hiroshima residents and 5,203 from Nagasaki residents. The response rate was 65.6%, varying somewhat across parental exposure category, city, gender, and year of birth. Differences in health and lifestyle were noted in several variables on comparison across city and gender. No major differences in health, lifestyle, sociodemographics, or disease were seen across parental exposure categories, though statistically significant tests for heterogeneity and linear trend revealed some possible changes with dose. The data described herein provide a foundation for studies in the future.

Jeena, Kottarapat;Liju, Vijayasteltar B;Ramanath, Viswanathan;Kuttan, Ramadasan 1325

https://doi.org/10.7314/APJCP.2016.17.3.1325 PDF KSCI

Radioprotective effects of ginger essential oil (GEO) on mortality, body weight alteration, hematological parameters, antioxidant status and chromosomal damage were studied in irradiated mice. Regression analysis of survival data in mice exposed to radiation yielded LD50/30 as 7.12 and 10.14 Gy for control (irradiation alone) and experimental (GEO-treated irradiated) mice, respectively, with a dose reduction factor (DRF) of 1.42. In mice exposed to whole-body gamma-irradiation (6 Gy), GEO pre-treatment at 100 and 500 mg/kg b.wt (orally) significantly ameliorated decreased hematological and immunological parameters. Radiation induced reduction in intestinal tissue antioxidant enzyme levels such as superoxide dismutase, catalase, glutathione peroxidase and glutathione was also reversed following administration of GEO. Tissue architecture of small intestine which was damaged following irradiation was improved upon administration of GEO. Anticlastogenic effects of GEO were studied by micronuclei assay, chromosomal aberration and alkaline gel electrophoresis assay. GEO significantly decreased the formation of micronuclei, increased the P/N ratio, inhibited the formation of chromosomal aberrations and protected agaisnt cellular DNA damage in bone marrow cells as revealed by comet assay. These results are supportive of use of GEO as a potential radioprotective compound.

Bhartiya, Deeksha;Kumar, Amit;Singh, Harpreet;Sharma, Amitesh;Kaushik, Anita;Kumari, Suchitra;Mehrotra, Ravi 1333

https://doi.org/10.7314/APJCP.2016.17.3.1333 PDF KSCI

Oral cancer is one of the most prevalent cancers in India but the underlying mechanisms are minimally unraveled. Cancer research has immensely benefited from genome scale high throughput studies which have contributed to expanding the volume of data. Such datasets also exist for oral cancer genes but there has been no consolidated approach to integrate the data to reveal meaningful biological information. OrCanome is one of the largest and comprehensive, user-friendly databases of oral cancer. It features a compilation of over 900 genes dysregulated in oral cancer and provides detailed annotations of the genes, transcripts and proteins along with additional information encompassing expression, inhibitors, epitopes and pathways. The resource has been envisioned as a one-stop solution for genomic, transcriptomic and proteomic annotation of these genes and the integrated approach will facilitate the identification of potential biomarkers and therapeutic targets.

Khan, Sara;Khan, Naveed Ali;Rehman, Ata Ur;Khan, Iqra;Samo, Khursheed A;Memon, Amjad Siraj 1337

https://doi.org/10.7314/APJCP.2016.17.3.1337 PDF KSCI

Background: There is a noticeable change in the approach with which women nowadays seek help for diseases like breast cancer, primarily due to awareness campaigns, but what happens after surgical procedures is of great significance too. This study focused on the several psychological connotations attached to mastectomy and how the patients cope. Objective: To understand the pattern of anxiety and level of depression among Pakistani patients undergoing mastectomy. Materials and Methods: The sample size consisted of 88 patients who had undergone mastectomy at the different surgical units of the Civil Hospital, Karachi, from January 2012-December 2014; The questionnaire was administered before they were discharged i.e. within 3 days of surgical procedures. The patients were asked if they were willing to participate in this study, those who agreed signed the consent form and then we preceded by asking questions with a standardized tool. A self made questionnaire was constructed keeping in mind the nature and specification of the disease, which consisted of 20 questions related to anxiety and depression, focusing on a mixture of psychological and physiological symptoms. Results: There were a total of 88 patients out of which 36 (41%) were aged 51 to 60 years, 24 (27.2%) of the patients were in the age category of 41 to 50 years, 17 aged 61 and above (19.3%) and only 11 (12.5%) 30-40 years of age, the youngest of all the age categories. The pattern of depression and anxiety was found to be similar among all age categories, severe depression and anxiety predominating over moderate level of such symptoms, with only relatively few patients sufering mild or no depression symptoms. Conclusions: It was concluded that going through mastectomy leads to moderate to severe levels of depression and anxiety, primarily because the females feel incomplete and insecure after losing a part of themselves.

Rattanata, Narintorn;Klaynongsruang, Sompong;Daduang, Sakda;Tavichakorntrakool, Ratree;Limpaiboon, Temduang;Lekphrom, Ratsami;Boonsiri, Patcharee;Daduang, Jureerut 1341

https://doi.org/10.7314/APJCP.2016.17.3.1341 PDF KSCI

Gallic acid was isolated from Caesalpinia mimosoides Lamk and the structure s identified based on spectroscopic analysis and comparison with authentic compound. In this study we compared the ability of natural gallic acid (nGA) and commercial gallic acid (cGA) to inhibit the proliferation of cholangiocarcinoma cell lines (M213, M214) and foodborne pathogenic bacteria (Salmonella spp. and Plesiomonas shigelloides). Both nGA and cGA had the same inhibitory effects on cell proliferation by inducing apoptosis of cholangiocarcinoma cell lines. In addition, nGA inhibited growth of foodborne pathogenic bacteria in the same manner as cGA. Our results suggest that nGA from Caesalpinia mimosoides Lamk is a potential anticancer and antibacterial compound. However, in vivo studies are needed to elucidate the specific mechanisms involved.

Shandiz, Fatemeh Homaei;Shabahang, Hossein;Afzaljavan, Fahimeh;Sharifi, Nourieh;Tavasoli, Alireza;Afzalaghaee, Monavar;Roshanzamir, Emane;Pasdar, Alireza 1347

https://doi.org/10.7314/APJCP.2016.17.3.1347 PDF KSCI

Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

Abdelgawad, Iman A;Radwan, Noha H;Shafik, Roxan E;Shokralla, Hala A 1351

https://doi.org/10.7314/APJCP.2016.17.3.1351 PDF KSCI

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to influence the growth and survival of malignant clones. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups and survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

Suprasert, Prapaporn;Siriaree, Sitthicha;Manopunya, Manatsawee 1357

https://doi.org/10.7314/APJCP.2016.17.3.1357 PDF KSCI

Metastatic gestational trophoblastic neoplasia (GTN) is an uncommon cancer. The principal treatment consists of chemotherapy with or without surgery or radiotherapy. We here retrospectively reviewed the outcomes of metastatic GTN treated at our institute between January, 1999 and December, 2013. Sixty-three patients met the criteria. The median age was 30.0 years and almost 90% were referral cases. Nearly 40% of the studied patients presented with vaginal bleeding while 22.2% were asymptomatic. The most common antecedent pregnancy was hydatidiform mole (57.1%) followed by term pregnancy (20.6%). The median interval time from antecedent pregnancy to the development of GTN was three months and the median pretreatment B-hCG was 58,274 mIU/ml. Stage III (74.6%) was the most common staging followed by stage IV (20.6%) and stage II (4.8%). The most frequent surgery was hysterectomy (31.7%). Thoracotomy and craniotomy were performed in three and two patients, respectively. The most common first line chemotherapy regimen was methotrexate and folinic acid (36.5%) followed by EMA (etoposide, methotrexate, actinomycin D) (34.9%), EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (17.5%) with the remission rate of 66.7%. Nearly one-third of the patients were given a subsequent chemotherapy regimen after failure with the first line therapy and showed a final response rate of 73.0%. However, in stage IV, the response to first line treatment was only 38.5%. In conclusion, the outcomes of metastatic GTN were poor especially with the higher stages.

Danial, M;Sivasangari, S;Arulappen, AL;Ong, LM 1363

https://doi.org/10.7314/APJCP.2016.17.3.1363 PDF KSCI

Human papillomavirus (HPV) is a prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available globally but unfortunately vaccine uptake is inconsistent everywhere. From this study, it was observed that the awareness of cervical cancer, HPV virus and HPV vaccination in Malaysia is high, at 83.1%, 73.9% and 73.3% of respondents, respectively. However, a considerably low percentage had undergone HPV vaccination (8.6%) compared to those who had experienced a Pap smear (32.9%). Awareness between cervical cancer and HPV virus and vaccination was low. Health care providers and the governing bodies have to play a vital role in disseminating holistic information on the vaccine and the importance of getting vaccinated to the public more vigorously in Malaysia.

Mokmeli, Sharareh;Tehrani, Golnaz Asaadi;Zamiri, Reza Eghdam;Bahrami, Tayyeb 1369

https://doi.org/10.7314/APJCP.2016.17.3.1369 PDF KSCI

Background: Platinum compounds are the main drugs for treatment of advanced gastric cancer. Previous studies have shown that clinical outcome with platinum-based compounds depends on ERCC1 polymorphisms. The aim of this study was to investigate the frequency of a common polymorphism of ERCC1 gene (C8092A) in Iranian patients with advanced gastric cancer receiving platinum chemotherapy. Materials and Methods: Genetic analysis of the ERCC1 C8092A polymorphism was performed by the PCR - RFLP method using 50 paraffin-embedded tissue specimens. Results: Of the 50 cases, 32% of individuals showed CC genotype, 24% of them had CA genotype and 44% of patients had AA genotype. Conclusions: Based on the results, using of platinum-based chemotherapy would be expected to be specifically beneficial in only 32% of patients.

Takai, Tomoaki;Inamoto, Teruo;Komura, Kazumasa;Tsujino, Takuya;Matsunaga, Tomohisa;Yoshikawa, Yuki;Uchimoto, Taizo;Saito, Kenkichi;Tanda, Naoki;Minami, Koichiro;Uehara, Hirofumi;Ibuki, Naokazu;Takahara, Kiyoshi;Nomi, Hayahito;Kiyama, Satoshi;Azuma, Hayahito 1373

https://doi.org/10.7314/APJCP.2016.17.3.1373 PDF KSCI

Background: We vigorously reviewed patients' operation record who had adhesion of the Denonvilliers' fascia and found out most of these patients had prostatic bleeding after prostatic gland biopsies. We examined the magnitude of prostatic bleeding and frequency after biopsies and the relationship with oncological outcomes. Materials and Methods: A total of 285 patients were selected for the final analyses. Inclusion criteria were as follows: receiving MRI three weeks after biopsiesand laparoscopic radical prostatectomy within 300 days after biopsy. We divided the patients into two groups with (group A) or without (group B) prostatic bleeding. We examined the magnitude of prostatic bleeding after biopsies and the relationship with operation time (OT), positive surgical margin (PSM), biochemical recurrence (BCR) and other factors. Furthermore, we created a logistic-regression model to derive a propensity score for prostatic bleeding after biopsies, which included all patient and hospital characteristics as well as selected interaction terms, and we examined the relationship with PSM and BCR. Results: In all patients, the OT in the group B was shorter than the group A (p < 0.001). Prostatic bleeding was associated with PSM (p=0.000) and BCR (p=0.036). In this propensity-matched cohort, 11 of 116 patients in the group B had PSM as compared with 36 of 116 patients from group A (match-adjusted odds ratio, 4.30; 95%CI confidence interval, 2.06 to 8.96; P=0.000). In addition, eight of 116 patients in group B encountered BCR, as compared with 18 of 116 patients in group A (match-adjusted odds ratio, 2.48; 95%CI, 1.03 to 5.96; P=0.042). Kaplan-Meier analysis in the propensity matching cohort showed a significant biochemical recurrence-free survival advantage for being free of prostate bleeding after biopsies. Conclusions: Our findings in the present cohort should help equip surgeons to pay attention to careful excision especially for those who experienced deferred prostatic bleeding.

Ramezani, Mazaher;Mohamadzaheri, Elham;Khazaei, Sedigheh;Najafi, Farid;Vaisi-Raygani, Asad;Rahbar, Mahtab;Sadeghi, Masoud 1379

https://doi.org/10.7314/APJCP.2016.17.3.1379 PDF KSCI

Background: Basal and squamous cell carcinoma (BCC and SCC) are the most common skin cancers worldwide and distinction between the two may sometimes be very difficult in routine histopathology. The present study was aimed to evaluate a reliable diagnostic method for these cancers based on immunohistochemistry (IHC). Materials and Methods: IHC was used with antibodies to Bcl-2, CD10, CEA, and EMA biomarkers, which despite non-specificity are easily available for detection of various types of tumors in pathology sections and can be used as a panel for differentiation. In this descriptive and analytic study, paraffin-embedded blocks of 29 SCC patients and 29 BCC patients were collected and sectioned for IHC staining. The results were analyzed by the STATA (version 8) statistical package using the Chi-square test. Results: BCC patients were 100%, 75.8%, 0% and 0% positive for Bcl-2, CD10, CEA and EMA markers, respectively, and for SCC patients were 3.5%, 0%, 34.5% and 82.7% positive, respectively. Using simultaneously Bcl-2 and CD10 as positive markers, detection of BCC with 88% accuracy and 100% specificity was possible, while application of CEA and EMA positivity could detect SCC with 67% accuracy and 100% specificity. Conclusions: SCC and BCC have different immunostaining profiles; therefore, Bcl-2, CD10, CEA and EMA markers can be helpful to distinguish between them.

Lopes, Tiara Cristina Romeiro;Gravena, Angela Andreia Franca;de Oliveira Demitto, Marcela;Brischiliari, Sheila Cristina Rocha;Borghesan, Deise Helena Pelloso;Agnolo, Catia Millene Dell;de Barros Carvalho, Maria Dalva;Pelloso, Sandra Marisa 1385

https://doi.org/10.7314/APJCP.2016.17.3.1385 PDF KSCI

Background: To investigate the prevalence of and factors associated with performance of annual mammography by women above 40 years of age. Materials and Methods: This cross-sectional retrospective study was conducted at an oncology reference service in Southern Brazil from October 2013 to October 2014 with 525 women aged 40 years or older. Results: The prevalence of annual mammography was 54.1%; annual mammographic screening was performed for women without private medical insurance, who were under hormone replacement therapy and who had used contraception in the past. An association was found between non-performance of breast clinical and self-examination and non-performance of mammographic screening. Conclusions: Use of mammography for breast cancer screening in the public health care setting proved to be accessible; nevertheless, the proportion of screened women was low, and they exhibited poor adherence to the basic measures of care recommended for breast assessment. Thus, control of breast cancer requires implementing actions targeting the population most vulnerable to non-adherence to screening in addition to continuously monitoring and assessing that population to reduce the prevalence of this disease.

Rafiemanesh, Hosein;Salehiniya, Hamid;Lotfi, Zahra 1393

https://doi.org/10.7314/APJCP.2016.17.3.1393 PDF KSCI

Background: Breast cancer is the most common cancer and the first cause of cancer death in women worldwide, with infiltrating duct carcinoma as the most common morphology. This study aimed to investigate trend of breast cancer incidence by age groups and histological changes in Iranian women between 2003 and 2008. Materials and Methods: This is analytic study, carried out based on re-analysis of the Cancer Registry Center report of health deputy for women's breast cancer in Iran during a 6-year period (2003-2008). Statistical analysis for incidence time trends and morphology change percentage carried out joinpoint regression analysis using the software Joinpoint Regression Program. Results: A total of 36,340 cases were reported for Iranian women in the six years. Analytical trend showed an increasing incidence trend with significant annual percentage change (APC) of 15.2 (CI: 11.6 to 18.8). The lowest and highest significant increased trend were related to age groups of 40 to 44 years and above 85 years, respectively; with APCs of 13.0 and 25.1, respectively. Of total cases, 78.7% of cases were infiltrating duct carcinoma, decreasing from 82.0% in 2003 to 76.6% in 2008, which was significant with an APC equal to -1.76 (CI:-2.7 to -0.8). Conclusions: The incidence trend of breast cancer is rising in Iranian women. The highest incidence was observed in the age groups 45-65 and 80-85. In conclusion, to reduce breast cancer incidence and its burden, preventive and screening programs for breast cancer, especially in young women, are recommended in Iran.

Kaneko, Shiho;Matsumoto, Kazumasa;Minamida, Satoru;Hirayama, Takahiro;Fujita, Tetsuo;Kodera, Yoshio;Iwamura, Masatsugu 1399

https://doi.org/10.7314/APJCP.2016.17.3.1399 PDF KSCI

We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3-3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

Lin, Chung-Ying;Pakpour, Amir H 1405

https://doi.org/10.7314/APJCP.2016.17.3.1405 PDF KSCI

Background: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (EORTC QLQ-BM22) is a recently designed supplement to EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30). Additional psychometric properties, especially using confirmatory factor analysis (CFA) and the Rasch model, are warranted. Materials and Methods: A total of 573 patients with bone metastases were enrolled from eight countries with a mean${\pm}$SD age of $55.8{\pm}13.7years$. Slightly more than two thirds of them were female (n=383; 66.8%). CFA was used to examine the BM22 framework; Rasch models were applied to understand misfit items and differential item functioning (DIF). Results: The fit indices were satisfactory in CFA (comparative fit index=0.972, Tucker-Lewis index=0.964, root mean square error of approximation=0.076, and standardized root mean square residual=0.045). All items fit well in the Rasch models (mean square values were between 0.5 and 1.5), and only one item (number 17) displayed DIF across gender. However, there were six DIF items across Canada and Taiwan, ten across Canada and Iran, and six across Taiwan and Iran. Conclusions: The BM22 has satisfactory psychometric properties, and could assess the QoL of patients with bone metastases specifically focusing on their symptoms. Clinicians may want to use it to capture the underlying QoL for patients with bone metastases. However, the score of item 17 should be interpreted with caution when comparing male and female patients. In addition, researchers should note that variation in DIF items may occur when conducting an international study.

Chu, Fang-Yeh;Liou, Ching-Biau;Sun, Jen-Tang;Bei, Chia-Hao;Liou, Tse-Hsuan;Tan, N-Chi;Yu, Yun-Chieh;Chang, Chih-Chun;Yen, Tzung-Hai;Su, Ming-Jang 1411

https://doi.org/10.7314/APJCP.2016.17.3.1411 PDF KSCI

Background: Eosinophilic pleural effusion (EPE) is an eosinophil count more than 10% on cytology of pleural samples. Recently, it was reported that malignancy had been the most prevalent cause inducing EPE. Therefore, we conducted an analysis on the prevalence and etiology of EPE and investigated the relationship between EPE and malignancy. Materials and Methods: Data for pleural cell differential count from patients receiving thoracentesis during the period from January 2008 to December 2013 were compared with clinical data and established diagnosis of patients obtained via electronic chart review. Results: A total of 6,801 requests of pleural cytology from 3,942 patients with pleural effusion who had received thoracentesis were available at Far Eastern Memorial Hospital from 2008 to 2013, and of these subjects, 115 (2.9%) were found to have EPE. The most frequent cause of EPE was malignancy (33.0%, n=38), followed by parapneumonic effusions (27.8%, n=32), tuberculosis pleuritis (13.9%, n=16), transudate effusions (12.2%, n=14) and the presence of blood or air in pleural space (10.4%, n=12). Additionally, an inverse relationship of eosinophilia in pleural fluid was identified in patients with malignancy and EPE. The cut-off eosinophil count in pleural fluid was 15% for the most accurate discrimination between malignancy and benign disorders in patients with EPE. At the cut-off level, the sensitivity and specificity were 65.8% and 67.5%, respectively. Conclusions: Pleural fluid eosinophilia was a speculative negative predictor for malignancy, despite the fact that cancers, including lung cancers and metastatic cancers to lung, were the most leading cause of pleural fluid eosinophilia. An inverse correlation was observed between the pleural eosinophil percentage and the likelihood of malignancy in patients with EPE.

Shamloo, Nafiseh;Lotfi, Ali;Motazadian, Hamid Reza;Mortazavi, Hamed;Baharvand, Maryam 1415

https://doi.org/10.7314/APJCP.2016.17.3.1415 PDF KSCI

The tongue has been globally considered as an indicator of general health for millennia. This study aimed to determine the prevalence and distribution of tongue lesions in an Iranian population. In this retrospective study, data from 6,435 oral biopsy reports over a 22-year period (1992-2014) were retrieved from archives of Oral and Maxillofacial Pathology Department, Shahid Beheshti Dental School, Tehran, Iran. These reports were analyzed according to age, sex, type of lesion and location. Prevalence of tongue lesions were reported as percentages. Out of total oral lesions, 238 (3.7%) were found in the tongue, with the incidence peak (42%) being between 41-60 years. Men constituted 53% and women 47%of patients. The youngest patient was a 3-year-old girl with pyogenic granuloma and the oldest one was a 93-year-old man with squamous cell carcinoma (SCC). SCC was the most common (25%) lesion generally found in the lateral border of the tongue with a male predilection. The second and third most prevalent lesions of the tongue were benign keratosis (frictional keratosis) (13.4%) and leukoplakia (13%).White-red lesions (38.6%) were the most frequent subgroup followed by neoplastic lesions (28%). Moreover, irritation fibroma, non-specific ulcers, squamous papilloma, and hemangioma were found as the most frequent lesions in their related subgroups.Given the high rate of SCC of the tongue in Iranian patients, this area should be examined more carefully by dental practitioners and physicians.

Iranfar, Khosro;Mokhayeri, Yaser;Mohammadi, Gohar 1421

https://doi.org/10.7314/APJCP.2016.17.3.1421 PDF KSCI

Background: There is a considerable lack of understanding of oral cancer incidence, especially its time trend in Iran. In this study, the authors aimed to analyze time trend of oral cancer incidence with a focus on differences by gender in a period of six years - from 2005 to 2010. Materials and Methods: Both population-based cancer registry and national cancer registry (NCR) data based on pathologic reports from 2005 to 2010 were obtained from the Ministry of Health and Medical Education (MOHME). Population data were also received from Statistical Centre of Iran. Age-standardized incidence rates (ASRs) based on the World Standard Population were then calculated. Finally, Negative Binomial regression was run for time trend analysis. Results: The maximum ASR for males was calculated as 2.5 per 100,000 person-years in 2008 and the minimum was observed as 1.9 per 100,000 person-years in 2005 and 2006. Meanwhile, the maximum ASR for females was estimated as 1.8 per 100,000 person-years in 2009 and the minimum was calculated as 1.6 per 100,000 person-years in 2005 and 2006. Additionally, in females, incidence risk ratio (IRR) did not show a clear decreasing or increasing trend during the six years. Nevertheless, in males an increasing trend was observed. The maximum IRR adjusted for age group and province, for females was reported in 2009 (IRR=1.05 95% CI: 0.90-1.23), and for males was estimated in 2010 (IRR=1/2 95% CI: 1.04 - 1.38). Conclusions: Our findings highlight disparities between oral cancer incidence trends in males and females over the six years from 2005 to 2010.

Chang, Chih-Chun;Sun, Jen-Tang;Chen, Jing-Yuan;Chen, Yi-Ting;Li, Pei-Yu;Lee, Tai-Chen;Su, Ming-Jang;Wu, Jiann-Ming;Yen, Tzung-Hai;Chu, Fang-Yeh 1427

https://doi.org/10.7314/APJCP.2016.17.3.1427 PDF KSCI

Background: Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. Materials and Methods: Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. Results: A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). Conclusions: Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.

Kaewpitoon, Soraya J;Rujirakul, Ratana;Sangkudloa, Amnat;Kaewthani, Sarochinee;Khemplila, Kritsakorn;Cherdjirapong, Karuna;Kujapun, Jirawoot;Norkaew, Jun;Chavengkun, Wasugree;Ponphimai, Sukanya;Polsripradist, Poowadol;Padchasuwan, Natnapa;Joosiri, Apinya;Wakkhuwattapong, Parichart;Loyd, Ryan A;Matrakool, Likit;Tongtawee, Taweesak;Panpimanmas, Sukij;Kaewpitoon, Natthawut 1433

https://doi.org/10.7314/APJCP.2016.17.3.1433 PDF KSCI

Background: Cholangiocarcinoma (CCA), a major problem of health in Thailand, particularly in Northeastern and Northern regions, is generally incurable and rapidly lethal because of presentation in stage 3 or 4. Early diagnosis of stage 1 and 2 could allow better survival. Therefore, this study aimed to provide a distribution map of populations at risk for CCA in BuaYai district of Nakhon Ratchasima province, Northeast Thailand. Materials and Methods: A cross-sectional survey was carried out in 10 sub-districts and 122 villages, during June and November 2015. The populations at risk for CCA were screened using the Korat CCA verbal screening test (KCVST) and then risk areas were displayed by using Google map (GM). Results: A total of 11,435 individuals from a 26,198 population completed the KCVST. The majority had a low score of risk for CCA (1-4 points; 93.3%). High scores with 6, 7 and 8 points accounted for 1.20%, 0.13% and 0.02%. The population at risk was found frequently in sub-district municipalities, followed by sub-district administrative organization and town municipalities, (F=396.220, P-value=0.000). Distribution mapping comprised 11 layers: 1, district; 2, local administrative organization; 3, hospital; 4, KCVST opisthorchiasis; 5, KCVST praziquantel used; 6, KCVST cholelithiasis; 7, KCVST raw fish consumption; 8, KCVST alcohol consumption; 9, KCVST pesticide used; 10, KCVST relative family with CCA; and 11, KCVST naive northeastern people. Geovisual display is now available online. Conclusions: This study indicated that the population at high risk of CCA in Bua Yai district is low, therefore setting a zero model project is possible. Key success factors for disease prevention and control need further study. GM production is suitable for further CCA surveillance and monitoring of the population with a high risk score in this area.

Nitta, Junichi;Nojima, Masanori;Ohnishi, Hirofumi;Mori, Mitsuru;Wakai, Kenji;Suzuki, Sadao;Fujino, Yoshihisa;Lin, Yingsong;Tamakoshi, Koji;Tamakoshi, Akiko 1437

https://doi.org/10.7314/APJCP.2016.17.3.1437 PDF KSCI

Background: We investigated four factors, height, weight gain since age 20, physical activity, and alcohol drinking, for associations with risk of breast cancer (BC) according to menopausal status, using the latest data of the Japan Collaborative Cohort Study (JACC Study). Materials and Methods: We confined the analysis to 24 areas available of cancer incidence information, excluding women with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367 premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189 postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox model was used to estimate a hazards ratio (HR) and its 95% confidence interval (CI) of BC risk. Results: As a result of the multivariate analysis adjusting for age at baseline survey, age at menarche, number of live births, and, age at first delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and ${\geq}10.0kg$ were significantly associated with increased risk for postmenopausal BC (HR=2.48, 95% CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly increased trend of BC risk was also observed in weight gain since age 20 (p for trend, p<0.001). Amount of ethanol intake per day${\geq}15.0g$ was significantly associated with increased risk for postmenopausal BC in the multivariable-adjusted analysis (HR=2.74, 95% CI 1.32-5.70). Conclusions: Higher weight gain in adulthood and larger amounts of ethanol intake were significantly associated with increased risk of BC in Japanese postmenopausal women. None of the investigated factors were significantly associated with BC risk in Japanese premenopausal women.

Ashrafganjoei, Tahereh;Mohamadianamiri, Mahdiss;Farzaneh, Farah;Hosseini, Maryam Sadat;Arab, Maliheh 1445

https://doi.org/10.7314/APJCP.2016.17.3.1445 PDF KSCI

Purpose: The current study aimed at assessing the association between neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) for the prognosis of the surgical outcome of epithelial ovarian cancer (EOC). Materials and Methods: EOC patient medical records of surgical operations between January, 2005 and December, 2015 were reviewed and their data of clinicopathological complete blood counts (CBCs) and surgical outcomes were collected. To assess their effects on surgical outcomes, PLR and NLR optimal predictive values were determined and then compared with each other. Results: A statistically significant relation was found between surgical outcomes and NLR and PLR (p<0.001 and p<0.001), for which new cutoff points were gained (PLR: 192,3,293; NLR: 3). The sensitivity and specificity were 0.74 and 0.67, respectively for PLR and 0.74 and 0.58, for NLR. Conclusions: NLR and PLR seem to be useful methods for the prediction of surgical outcomes in patients with EOCs. Increased NLR and PLR proved to be beneficial for poor surgical outcomes. Moreover, PLR increase showed further help in the predicting outcome of EOC suboptimal debulking.

Sookprasert, Aumkhae;Ungareewittaya, Piti;Manotepitipongse, Areesa;Wirasorn, Kosin;Chindaprasirt, Jarin 1449

https://doi.org/10.7314/APJCP.2016.17.3.1449 PDF KSCI

Background: Adult rhabdomyosarcoma (RMS) is a rare and aggressive disease with limited data compared with pediatric RMS. The goal of this study was to determine the treatment outcome and identify factors related to survival outcome in Thailand. Materials and Methods: Adult patients (${\geq}15$ years old) with the pathological diagnosis of RMS between 1985 and 2010 were reviewed. The data were retrospectively reviewed from the pathological results and medical records from Srinagarind Hospital, Khon Kaen University. Results: A total of 34 patients were identified in the study. The median age at diagnosis was 35.5 years and the most common primary sites were extremity and the head and neck region. The incidence of pleomorphic RMS increased with age and none was found in those aged younger than 20 years old. The median survival time was 9.33 months (95%CI: 5.6-13.1). The 1- and 5- year survival rates were 38.2% (22.3-54.0) and 20.6% (9.1-35.3). On multivariate analysis, age and size of tumor did not predict better outcome while chemotherapy and surgery were significantly associated with longer survival. Conclusions: Outcome of adult RMS was poor. Surgery and chemotherapy are strongly associated with better prognosis and multimodality treatment should be incorporated in the clinic.

Ronco, Alvaro L;De Stefani, Eduardo;Mendoza, Beatriz;Deneo-Pellegrini, Hugo;Vazquez, Alvaro;Abbona, Estela 1453

https://doi.org/10.7314/APJCP.2016.17.3.1453 PDF KSCI

Regarding 'mate' intake (infusion of Ilex paraguariensis herb, a staple beverage in temperate South American regions), most epidemiologic studies showed positive associations with risk of some cancers, (e.g. upper aerodigestive tract), but evidence on breast cancer (BC) risk is limited to a previous multi-site study, which reported a non significant odds ratio [OR]=0.85, 95% confidence interval [95% CI] 0.67-1.09, p for trend=0.31) for the highest quartile of intake. The present study was conducted in order to further assess associations of 'mate' intake with BC risk. We combined two databases of women belonging to public and private healthcare hospitals. The sample included 572 BC incident cases and 889 controls interviewed with a specific questionnaire featured by socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, also analyzing 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit, intensity of intake). ORs and their 95%CI were calculated through unconditional logistic regression, adjusting for relevant potential confounders. The highest quartile of 'mate' intake was inversely associated with BC risk (OR=0.40, 95%CI 0.26-0.57, p for trend <0.001). Stratified analyses also displayed strong significant inverse associations for 'mate' in frequent tea drinkers (OR=0.22), high energy intake (OR=0.23), high body mass index (OR=0.29) and in postmenopausal women (OR=0.36), among other results. As conclusions, we found evidence of a significant inverse association for 'mate' intake and BC risk.

Al-Sakkaf, Khaled Abdulla;Basaleem, Huda Omer 1463

https://doi.org/10.7314/APJCP.2016.17.3.1463 PDF KSCI

Background: The incidence of breast cancer is rapidly increasing in Yemen with recent indications of constituting one-third of female cancers. The main problem in Yemen remains very late presentation of breast cancer, most of which should have been easily recognisable. Since stage of disease at diagnosis is the most important prognostic variable, early diagnosis is an important option to be considered for control of breast cancer in low resourced settings like Yemen. In the present study, we aimed at describing breast cancer knowledge, perceptions and breast self-examination (BSE) practices among a sample of Yemeni women. Materials and Methods: This cross-sectional study covered 400 women attending four reproductive health centres in Aden, Yemen through face-to-face interview using a structured questionnaire during April - July 2014. We collected data on sociodemographic characteristics, knowledge about breast cancer, and screening practices as well as respondents' perceptions based on the five sub scales of the Health Belief Model (HBM): perceived susceptibility; perceived severity; perceived barriers; perceived benefits; and self-efficacy. The response format was a five-point Likert scale. Statistical Package for Social Sciences (SPSS 20) was used for statistical analysis. Statistical significance was set at p<0.05. Logistic regression analysis was conducted with BSE as a dependent variable. Results: The mean age of women was 26.5 (S.D=5.6) years. The majority (89.0%) had never ever performed any screening. Two-thirds of respondents had poor knowledge. Perceived BSE benefits and self-efficacy and lower BSE barriers perception were significant independent predictors of BSE practice. Conclusions: Poor knowledge and inadequate BSE practices are prevailing in Yemen. The need for implementing culturally sensitive targeted education measures is mandatory in the effort to improve early detection and reduce the burden of breast cancer.

Kadivar, Maryam;Rahimabad, Parnian Kheirkhah 1469

https://doi.org/10.7314/APJCP.2016.17.3.1469 PDF KSCI

Cancer pathology reports play an important role in choice of patient care. They provide crucial information concerning diagnosis, therapy options, and prognosis. Professional pathology institutions, such as the College of American Pathologists (CAP), have developed checklists to ensure the presence of all the required elements in reports. In this study, 438 surgical pathology reports of patients with breast (148), colon (147), and stomach cancer (143) were evaluated with respect to the presence of mandated elements according to CAP checklists. The most common missing element in all the three types of cancer was 'staging' (73.6, 53.1, and 56.6% in breast, colon, and stomach cancer reports missed 'staging', respectively). The second most missing element was 'tumor site' in breast (64.2%) and stomach cancer (30.1%), and 'procedure' in colon cancer (29.3%). 'Perineural invasion' was the third most missing element in the three types of cancer (25.7, 17.0, and 22.4% in breast, colon, and stomach cancer, respectively). Only 11.4% of reports included all key elements required by CAP. The use of checklists was associated with higher rate of completeness. This study demonstrates that the key elements requiring the information on the requisition forms from the clinicians are commonly missed, leading to ambiguity.

Kassani, Aziz;Baghbanian, Abdolvahab;Menati, Rostam;Hassanzadeh, Jafar;Asadi-Lari, Mohsen;Menati, Walieh 1473

https://doi.org/10.7314/APJCP.2016.17.3.1473 PDF KSCI

Background: Cigarette smoking is as the leading cause of cancer mortality and other chronic diseases in males worldwide. The prevalence of cigarette smoking is different across and within countries by age, education level, occupation, and so on. This study aimed to determine the prevalence of cigarette smoking and its relationship with individuals' demographic factors and BMI in adolescent men living in Tehran, Iran. Materials and Methods: This study involved secondary analysis of the 'Urban Health Equity Assessment and Response Tool-2' survey conducted in Tehran, Iran, among men aged 20+, 2011-2012. Using a multistage sampling method, 45,990 men were included in the study. The cigarette smoking status, BMI and demographic factors measured through a self-administered questionnaire. Chi-square, t-test, and logistic regression model were used to examine the relationships between the independents variables and cigarette smoking behavior, using SPSS software version 21. Results: In the total of 45,990 men, the overall prevalence of cigarette smoking was 14.6% (CI 95%: 14.29-14.94). Age (OR=0.96; CI 95%:0.94-0.98), house ownership (OR=0.68; CI 95%: 0.64-0.72), job status (OR=0.60; CI 95%: 0.46-0.86), marital status (OR=0.42; CI 95%: 0.39-0.47) and educational levels (OR=0.50; CI95%: 0.45-0.54) were associated with the prevalence of cigarette smoking. However, associations with BMI, family size, residency years, and district were not statistically significant. Conclusions: Given the relatively high prevalence of cigarette smoking in the study population, policy interventions are required to address this major public health issue, with a focus on the population demographic influences.

Temiz, Zeynep;Ozturk, Didem;Ugras, Gulay Altun;Oztekin, Seher Deniz;Sengul, Emel 1479

https://doi.org/10.7314/APJCP.2016.17.3.1479 PDF KSCI

The purpose of this study was to determine discharge learning needs of patients undergoing thyroidectomy. The population of this descriptive study consisted of patients undergoing thyroidectomy in the Endocrine Surgery Unit of a university hospital between February and December 2013. The study included 251 patients who were discharged after thyroidectomy. Data obtained using the data collection form and the Patient Leaning Needs Scale (PLNS) were analyzed by frequency, mean, standard deviation, Kruskal Wallis and student-t tests. The mean age of the patients was $47.91{\pm}13.05$ and 76.1% were females. The PLNS total mean score was $208.38{\pm}34.91$, with the maximum score of $39.23{\pm}6.80$ on the subscale of treatment and complications and the minimum score of $19.45{\pm}4.70$ on the subscale of feelings related to condition. It was found that the PLNS total score of the patients was not influenced by age, gender, marital status (p>0.05). This study demonstrated that patients had high learning needs after thyroidectomy.

Bravo, Eduardo;Contardo, Jorge;Cea, Jerson 1485

https://doi.org/10.7314/APJCP.2016.17.3.1485 PDF KSCI

Background: Chile is one of the countries with the highest prevalence of cholelithiasis worldwide, considering the Mapuche ethnicity as a risk factor for developing this pathology. Moreover, cholelithiasis is the main risk factor for developing gallbladder cancer, being the fifth cause of cancer death in Chile. The purpose of this study was to compare the frequency of cholelithiasis and biliary pathology among the population belonging to Rapanui ethnicity and non-Rapanui population living on Easter Island. Materials and Methods: In this retrospective case-control study, a total of 609 abdominal ultrasonographs performed consecutively in Hanga Roa Hospital during the period August 2012 to January 2015 were analyzed. Multiple logistic regression was used to obtain odds ratio (OR) and 95% confidence intervals (95% CI) of cholelithiasis and biliary pathology, adjusting for age, gender and referral diagnostic hypothesis. Results: In the Rapanui population the frequency for cholelithiasis and biliary pathology was 6.4% and 13%, meanwhile for the non-Rapanui population it was 13% and 22% respectively. Compared to the non-Rapanui Chilean population, the Rapanui ethnicity presented an OR of 0.53 (95% CI: 0.29-0.95) for cholelithiasis and OR of 0.52 (95% CI: 0.33-0.82) for biliary pathology. Conclusions: We found statistically significant ethnic differences in the frequency of cholelithiasis and biliary disease among the population of Rapanui and non-Rapanui ethnicity, so that this could be a protective factor for the development of biliary pathology, given the Chilean population context. Other studies including community population to determine the real prevalence of cholelithiasis and analyze the protective role of Rapanui ethnicity on this disease are necessary.

Prueksaritanond, Nisa;Cheanpracha, Patchara;Yanaranop, Marut 1489

https://doi.org/10.7314/APJCP.2016.17.3.1489 PDF KSCI

Background: Although there are no biomarkers that are routinely used in endometrial cancer (EC) management, many studies have found that serum human epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the detection of EC. The correlation of HE4 with two prognostic factors for EC, primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful in identifying EC patients at high risk of lymphatic dissemination. Objective: To evaluate the correlation of serum HE4 with PTD and DMI in patients with EC. Materials and Methods: A cross-sectional study was conducted on 70 EC patients who were scheduled for elective surgery at Rajavithi Hospital between 1st September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were investigated, and then gross measurement of PTD was taken and postoperative pathologic slides were reviewed for DMI including histologic types, grading and staging. Results: Preoperative serum HE4 levels were strongly correlated with PTD (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover, serum HE4 levels were significantly elevated in EC patients with PTD >2 cm (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC patients at low risk and high risk of lymph node metastasis was significantly better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of 80.0%. Conclusions: In EC patients, preoperative serum HE4 is significantly correlated with PTD and DMI. Serum HE4 levels could be useful in identifying endometrial cancer patients at high risk of lymphatic spread who would benefit from systemic lymphadenectomy at the cut-off value of 70 pM/L.

Zahmatkesh, Bibihajar;Keramat, Afsaneh;Alavi, Nasrinossadat;Khosravi, Ahmad;Kousha, Ahmad;Motlagh, Ali Ghanbari;Darman, Mahboobeh;Partovipour, Elham;Chaman, Reza 1493

https://doi.org/10.7314/APJCP.2016.17.3.1493 PDF KSCI

Background: Breast cancer is the most common cancer in women worldwide with a rising incidence rate in most countries. Considering the increase in life expectancy and change in lifestyle of Iranian women, this study investigated the age-adjusted trend of breast cancer incidence during 2000-2009 and predicted its incidence to 2020. Materials and Methods: The 1997 and 2006 census results were used for the projection of female population by age through the cohort-component method over the studied years. Data from the Iranian cancer registration system were used to calculate the annual incidence rate of breast cancer. The age-adjusted incidence rate was then calculated using the WHO standard population distribution. The five-year-age-specific incidence rates were also obtained for each year and future incidence was determined using the trend analysis method. Annual percentage change (APC) was calculated through the joinpoint regression method. Results: The bias adjusted incidence rate of breast cancer increased from 16.7 per 100,000 women in 2000 to 33.6 per 100,000 women in 2009. The incidence of breast cancer had a growing trend in almost all age groups above 30 years over the studied years. In this period, the age groups of 45-65 years had the highest incidence. Investigation into the joinpoint curve showed that the curve had a steep slope with an APC of 23.4% before the first joinpoint, but became milder after this. From 2005 to 2009, the APC was calculated as 2.7%, through which the incidence of breast cancer in 2020 was predicted as 63.0 per 100,000 women. Conclusions: The age-adjusted incidence rate of breast cancer continues to increas in Iranian women. It is predicted that this trend will continue until 2020. Therefore, it seems necessary to prioritize the prevention, control and care for breast cancer in Iran.

Bakshi, Hamid A;Hakkim, Faruck Lukmanul;Sam, Smitha 1499

https://doi.org/10.7314/APJCP.2016.17.3.1499 PDF KSCI

Background: Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell death at molecular level is remains unclear. In this study, we tried to unravel role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo preclinical toxicity profiling and immune stimulatory effect. Materials and Methods: CSE extract was fractionated by HPLC and crocin was isolated and characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours. Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by Western blotting after 24 hours of treatment. DNA fragmentation analysis was performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice. In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2 mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis. Results: Immunoblot analysis revealed that there was time dependent decline in anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and 9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited considerable DNA damage in MCF-7 cells at each concentration tested. In vivo toxicity profile by histological studies revealed no observable histopathologic differences in the liver, kidney, spleen, lungs and heart in CSE treated and untreated groups. Crocin treatment elicited significant dose and time dependent ex vivo yeast phagocytosis by peritoneal macrophages. Conclusions: Our study delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by CSE and crocin at the molecular level accompanied with extensive DNA damage. Further we found that normal swiss albino mice can tolerate the maximum dose of CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.

Loof-Johanson, Margaretha;Brudin, Lars;Sundquist, Marie;Rudebeck, Carl Edvard 1507

https://doi.org/10.7314/APJCP.2016.17.3.1507 PDF KSCI

Background: Risk of developing breast cancer increases with short breastfeeding and the use of hormones. The prognosis of breast cancer is better if the tumours are hormone receptor positive. Since breast feeding affects estrogen and progesterone receptors, we wanted to investigate how such reproductive factors as breastfeeding and the use of hormones interact with known prognostic markers and specific tumour characteristics in women with breast cancer. Materials and Methods: A total of 250 women treated for breast cancer from a larger cohort completed a questionnaire on breastfeeding, number and age at births and use of hormones. A logistic regression analysis was made to search for connections between known prognostic markers on the one hand (type of cancer, grade, tumor size, estrogen receptor and progesterone receptor, lymphovascular invasion and DNA-ploidy) and reproductive data, breastfeeding, and hormone use on the other. Results and Conclusions: Hormone use, but not breastfeeding, was significantly associated, also on multivariate analysis, with the prognostic variable lymphovascular invasion, connected to a worse prognosis. No other hormone use or breast feeding correlations with prognostic variables were found.

Payandeh, Mehrdad;Najafi, Safa;Shojaiyan, Fateme-Zahra;Sadeghi, Masoud 1513

https://doi.org/10.7314/APJCP.2016.17.3.1513 PDF KSCI

Background: A combination of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL patients with Iranian ethnicity. Materials and Methods: In phase III trial, patients with previously untreated stage III and IV indolent and aggressive B-cell NHL were randomly assigned by using a minimization method to receive six to eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14 (administered every 14 days with granulocyte colony-stimulating factor). Results: A total of 143 patients were randomly enrolled in our study (66 patients in R-CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs 89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant correlation for PFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. Conclusions: In our research improved survival was found with CHOP-14 as compared to CHOP-21. It is possible that drug metabolism in different races/ethnicities may be one important factor.

Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Shanmukaiah, Chandrakala;Nadkarni, Anita H 1519

https://doi.org/10.7314/APJCP.2016.17.3.1519 PDF KSCI

Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.

Sultan, Sadia;Irfan, Syed Mohammed;Murad, Sania 1531

https://doi.org/10.7314/APJCP.2016.17.3.1531 PDF KSCI

Background: Polycythaemia rubra vera (PV) is a Philadelphia chromosome negative myeloproliferative neoplasm characterized by increased red cell production, independent of the mechanisms that regulate normal erythropoiesis. The aim of this study was to analyze the clinico-epidemiological profile of Pakistani patients with PV. Materials and Methods: In this retrospective cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. They were diagnosed based on WHO criteria. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. Overall 30.7% of patients were asymptomatic. In symptomatic patients, major complaints were headache (30.8%), abdominal discomfort (23.1%), blurred vision (15.3%), pruritus (11.5%) and vascular incidents (11.5%). Physical examination revealed plethoric face and splenomegaly as predominant findings, detected in 34.6% and 30.7%, respectively, with the mean splenic span of $15.9{\pm}2.04cm$. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count $511{\pm}341.9{\times}10^9/l$. Mean erythrocyte sedimentation rate was $3.5{\pm}1.22mm/hr$. Serum lactate dehydrogenase, serum creatinine and uric acid were $552.7{\pm}309.2$, $0.8{\pm}0.17$ and $6.60{\pm}1.89$ respectively. Conclusions: PV in Pakistani patients, unlike in the West, is seen in a moderately young population. The disease is frequently seen in male gender and primarily patients present with symptoms related to hyperviscosity.

Sultan, Sadia;Irfan, Syed Mohammed 1535

https://doi.org/10.7314/APJCP.2016.17.3.1535 PDF KSCI

Background: Primary myelodysplastic syndrome (MDS) is an acquired clonal disorder of myeloid progenitor cells, characterized by peripheral cytopenias in the presence of hypercellular marrow with dysplastic features. Our aim was to study the demographical and clinicopathological features of adult Pakistani patients with MDS at disease presentation. Materials and Methods: This single centre study was conducted at Liaquat National Hospital and Medical College, extending from January 2010 to December 2014. Data were retrieved from the patient archives. Results: Overall 45 patients were diagnosed at our institution with de novo MDS during the study period. There were 28 males and 17 females. Age ranged between 18 and 95 years with a mean age of $57.6{\pm}17.4years$ and median of 64 years. The male to female ratio was 1.7:1. The main presenting complaints were generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss (11.1%). Examination was unremarkable in 42.2% of patients. Physical examination revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20%. The commonest laboratory finding was anemia (hemoglobin < 10 g/dl in 41 (91.1%) patients. Out of these, 27 (60%) patients had normocytic anemia, followed by macrocytic (22.2%) and microcytic (8.8%). Conclusions: Primary MDS in Pakistani patients demonstrates a male preponderance. The proportion of anemic patients was high in our series with predominance of normocytic anemia. However, other clinico-hematological features appear comparable to published data.

Mundhofir, Farmaditya EP;Wulandari, Catharina Endah;Prajoko, Yan Wisnu;Winarni, Tri Indah 1539

https://doi.org/10.7314/APJCP.2016.17.3.1539 PDF KSCI

Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are related to mutations in the BRCA1 gene. One hundred unrelated breast cancer patients were interviewed to obtain clinical symptoms and signs, pedigree and familial history of HBOC syndrome related cancer. Subsequently, data were calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score of BOADICEA were offered genetic testing. Eleven patients with high score of BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and 15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was subjected in all samples with aberrant graph. This study identified 10 variants in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T, c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C>T, c.2311 T>C and c.4308T>C) and one intronic mutation (c.134+35 G>T). All variants tend to be polymorphisms and unclassified variants. However, no known pathogenic mutations were found.

Allahyari, Abolghasem;Tajeri, Tarane;Sadeghi, Masoud 1547

https://doi.org/10.7314/APJCP.2016.17.3.1547 PDF KSCI

Background: Acute myeloid leukemia (AML) is a clonal hematopoietic disorder resulting from genetic alterations in normal hematopoietic stem cells. The aim of this study was to evaluate prognostic factors and survival of AML patients in the Northeast of Iran. Materials and Methods: This retrospective study covered 96 patients with AML referred to Emam Reza Hospital, Mashhad city, Iran, from 2009 to 2015. Age, sex, blood group, type of AML, fever, consumption of amphotericin B, cytogenetic forms and survival were analyzed. Also, WBC, hemoglobin and platelet levels were checked. Mean follow-up was 30.5 months (60.4% mortality). Survival was plotted by GraphPad Prism 5 with Log-rank test. Results: The mean age for all AML patients at diagnosis was 40.4 years (range, 17-77 years). Some 42.7% patients were aged <35 years and 40.6% were male. In all patients, 76% had fever and 50% consumed amphotericin. T(15;17)(q22;q21) had the most prevalence (37.7%) compared to other forms. Out of 92 patients, O+(30.4%) was the most common blood group and AML-M5 (28.3%) the most common subtype. There was a significant difference in survival based on WBC and consumption of amphotericin B (P<0.05). Conclusions: WBC level, fever and consumption of amphotericin B proved to be factors for survival of AML patients. The mean age for patients in Iran is lower than other areas in the World and also survival in this study was higher than in other studies.

Ghaffari, Seyed H.;Yousefi, Meysam;Dizaji, Majid Zaki;Momeny, Majid;Bashash, Davood;Zekri, Ali;Alimoghaddam, Kamran;Ghavamzadeh, Ardeshir 1553

https://doi.org/10.7314/APJCP.2016.17.3.1553 PDF KSCI

Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF-${\kappa}B$ signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-${\kappa}B$ and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-${\kappa}B$ down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-${\kappa}B$-mediated inhibition of survivin and telomerase activity and NF-${\kappa}B$-dependent suppression of cathepsin B, MMP-2 and MMP-9.

Ahmad, Zubair;Din, Nasir Ud;Memon, Aisha;Tariq, Mohammad Usman;Idrees, Romana;Hasan, Sheema 1565

https://doi.org/10.7314/APJCP.2016.17.3.1565 PDF KSCI

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer-Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.

Praseetha, Sugathan;Bandaru, Srinivas;Nayarisseri, Anuraj;Sureshkumar, Sivanpillai 1571

https://doi.org/10.7314/APJCP.2016.17.3.1571 PDF KSCI

Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.

Kristina, Susi Ari;Endarti, Dwi;Sendjaya, Natalia;Pramestuty, Octy 1577

https://doi.org/10.7314/APJCP.2016.17.3.1577 PDF KSCI

Tobacco use is a well-established risk factor for many types of cancers. Recent data on selected cancer incidence and mortality related to smoking in the Indonesian population are provided in this study. Morbidity and mortality data were derived from GLOBOCAN 2012 and the population attributable fraction (PAF) was estimated using the standard methodology developed by the World Health Organization. Using these data, we calculated disability adjusted life year (DALY) values for smoking-related cancer. The DALY was estimated by summation of the years lived with disability (YLD) and years life lost due to premature death (YLL). The cancer cases related to smoking in Indonesia numbered 45,132, accounting for 35,580 cancer deaths. The morbidity and mortality of lung cancer can be considered as the highest priority in both men and women. Furthermore the greatest YLD due to smoking in Indonesian men and women were from pancreas and lung cancers. For YLL among men, the highest years lost were from lung and liver cancers. On the other hand, among women lung oral cavity and lip were most important. Based on the DALY indicator, burden priorities for Indonesian men were lung cancer (298,980), liver cancer (60,367), and nasopharynx (46,185), while among Indonesian women they were lung cancer (34,119), cervix uteri (9,213) and pancreas cancer (5,433). In total, Indonesian burden of cancers attributed to smoking was 638,682 DALY. This study provides evidence about the burden of cancers caused by smoking as a rational basis for initiating national tobacco control policies in Indonesia.

yousuf, Syed Douhath;Ganie, Mohammad Ashraf;Zargar, Mohammad Afzal;Parvez, Tabasum;Rashid, Fouzia 1583

https://doi.org/10.7314/APJCP.2016.17.3.1583 PDF KSCI

Background: Polycystic ovary syndrome (PCOS) is considered to be a multifactorial disorder resulting from the interaction of several predisposing and protective genetic variants. PCOS is associated with low-grade chronic inflammation. Elevated levels of inflammatory markers including intercellular adhesion molecule-1 (ICAM-1) are demonstrated in women with PCOS. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and multifactorial diseases that have an inflammatory component. The aim of the study was to assess the possible association of Gly241Arg polymorphism of ICAM-1 gene located on chromosome 19p13 in determining risk of PCOS in Kashmiri women. Materials and Methods: Gly241Arg SNP in DNA from peripheral blood leukocytes of 220 PCOS cases and 220 age matched non-PCOS healthy controls was analysed using allel specific PCR. Results: The genotype and allele frequency distributions of Gly241Arg SNP showed insignificant difference between the PCOS cases and control women, indicating no role of this SNP in PCOS susceptibility. The odds ratio for Arg/Arg genotype was 0.87 (95% CI=0.32-2.3) [P=0.79], for Gly/Arg genotype was 0.98 (95% CI= 0.66-1.47) [P=1] and for Arg/Arg+Gly/Arg genotype was 0.97 (95% CI=0.65-1.45) [P=0.92]. The genotypic frequencies of ICAM-1codon 241 showed statistically insignificant difference between cases and controls (${\chi}^2=0.07$; p=0.96) Nor the studied polymorphism was found to affect clinical and laboratory parameters significantly. Conclusions: Although Gly241Arg polymorphism have not shown significant association with PCOS. Further, specifically designed studies on large cohorts are required to conclusively establish any role of ICAM-1 gene polymorphisms in PCOS in our study.

Saiyachak, Khamphanavanh;Tongsotsang, Sutthiporn;Saenrueang, Thitima;Moore, Malcolm A;Promthet, Supannee 1589

https://doi.org/10.7314/APJCP.2016.17.3.1589 PDF KSCI

Opisthorchis viverrini (OV) liver flukes are common parasites found in central and southern Laos and constitute a major public health problem in the country. Laos people continue to have the habit of extensively consuming raw or half-cooked fish which are intermediate hosts. This study aimed to determine the prevalence and factors associated with OV infection in the population of Thakek district, Khammouane Province. This cross-sectional analytic study covered 237 subjects who filled out structured questionnaires. Fecal examination for OV infection was performed by Kato's thick smear method. Data analysis was carried out using STATA Version 10.0. Multiple logistic regression was applied. The results showed that the infection rate of OV was 54.8%. Factors associated with OV infections were gender, a habit of defecation in fields and raw fish (goi bplaa dip) consumption. Opisthorchiasis and associated cholangiocarcinoma development thus appear to remain as important concerns in Laos.

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