Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Volume 16 Issue 12
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Mansoori, Abdul Anvesh;Jain, Subodh Kumar 4803
Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users. -
Mu, Yong-Ping;Sun, Wen-Jie;Lu, Chuan-Wen;Su, Xiu-Lan 4813
Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia countries. Most GC patients have been reported with low early diagnosis rate and show extremely poor prognosis. Therefore, it is necessary to develop novel and more sensitive biomarkers to improve early diagnosis and therapy in order to provide longer survival and better quality of life for gastric cancer patients. MicroRNAs (miRNAs) play crucial roles in GC development and progression. miRNAs have emerged as a novel molecular biomarker for cancer diagnosis, prognosis and therapy with surprising stability in tissues, serum or other body fluids. This review summarizes major advances in our current knowledge about potential miRNA biomarkers for GC that have been reported in the past two years. -
Daniyal, Muhammad;Ahmad, Saeed;Ahmad, Mukhtiar;Asif, Hafiz Muhammad;Akram, Muhammad;Rehman, Saif Ur;Sultana, Sabira 4821
Gastric cancer is the 2nd most common cause of death among all cancers and is the 4th most common cancer in the world. The number of deaths due to gastric cancer is about 800,000 annually. Gastric cancer is more common in men as compared to women and is 3rd most common cancer after colorectal and breast cancers in women. A progressive rise in the incidence rate has been observed in females over the last 5 years. The highest incidence of stomach cancer is in China, South America and Eastern Europe. The incidence of gastric cancer has 20 fold variation worldwide. Global variation is linked by two factors which play important role in developing gastric cancer. One is infection with Helicobacter pylori and the$2^{nd}$ is diet. South Asia is a region with low risk, despite a high prevalence of H.pylori. Gastric carcinoma is common in southern region of India. Gastric cancer is more readily treated if diagnosed early. This study aims to provide awareness about gastric cancer as well as an updated knowledge about risk factors and epidemiology of gastric cancer in Pakistan. -
Liang, Zhong-Guo;Chen, Ze-Tan;Li, Ling;Qu, Song;Zhu, Xiao-Dong 4825
Incidence rates of nasopharyngeal carcinoma are high in Indonesia, Singapore and South-Eastern China. Chemoradiotherapy has been the standard regimen for locally advanced nasopharyngeal carcinoma according to guidelines from the National Comprehensive Cancer Network. Recently, advances in the management of nasopharyngeal carcinoma have transferred into better treatment outcomes. Most phase III clinical trials support the addition of concurrent chemotherapy to radiotherapy for the initial treatment of these patients. Studies evaluating effects and toxicity of concurrent chemotherapy with different regimens have been reported. However, the status of adding adjuvant chemotherapy or induction chemotherapy remains controversial. Recent studies have shown that adjuvant chemotherapy with two or three cycles may improve survival for nasopharyngeal carcinoma with stage N2-3 disease or with persistently detectable plasma EBV DNA after radiotherapy. This review examines the pertinent issues and latest studies concerning the management of loco-regionally advanced NPC, regarding concurrent chemotherapy, adjuvant chemotherapy, and induction chemotherapy in decades. -
Chapoval, Andrei I;Legutki, J Bart;Stafford, Philip;Trebukhov, Andrey V;Johnston, Stephen A;Shoikhet, Yakov N;Lazarev, Alexander F 4833
Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice. -
Liu, Chun-Yan;Li, Hua-Jun;Lin, Hua;Ling, Bin 4839
We conducted a retrospectively reviewed of the literature published of patients underwent fertility-preserving treatments for cervical, endometrial and ovarian cancers using the WANFANG database in Chinese. A majority were retrospective studies and case reports. With cervical cancer, radical trachelectomy(RT) in combination with pelvic lymphadenectomy could preserve the fertility of patients with early stage IA1-IB1 cancers, Tumor size${\leq}2cm$ should be emphasized as the indication of RT in considering of the higher recurrent rate in patients with tumor size >2cm. For endometrial cancers, there is much experience on it. Given accurate pretreatment assessment, hormonal therapy is feasible management option to preserve fertility in young patients with early stage lesions that limited to the endometrium and well differentiated. High dose progestin have been applied, oral medroxyprogesterone acetate (MPA), 250-500mg/day, megestrol acetate 160-480mg/day. Other therapies that have been used in a limited number of cases include GnRH analog, intrauterine devices (IUDS) containing progestogen, usually combination of these therapies. All patients should be followed up by ultrasound and/or MRI evaluation, and endometrial curettage at intervals of 3 months. With ovarian cancer, in China, fertilitypreserving surgery in patients with stage IA (grade G1) of epithelial ovarian tumor and patients with germ cell tumor and borderline ovarian tumor have been successfully performed. -
To date, cytotoxic effects of flavonoids in various cancer cells are well accepted. However, the intracellular signaling cascades triggered by these natural compounds remain largely unknown and elusive. In this mini-review, the multiplicity of molecular targets of flavonoids in blood cancer cells is discussed by demonstrating the involvement of various signaling pathways in induction of apoptotic responses. Although these data reveal a great potential of flavonoids for the development of novel agents against different types of hematological malignancies, the pleiotropic nature of these compounds in modulation of cellular processes and their interactions certainly need unraveling and further investigation.
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Qi, Ling;Ren, Kuang;Fang, Fang;Zhao, Dong-Hai;Yang, Ning-Jiang;Li, Yan 4849
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been investigated as an effective agent to treat various cancers. Cancer stem cells are resistant to TRAIL treatment, but the mechanism of TRAIL resistance remains unknown. In this study, brain cancer stem cells were isolated by CD133 magnetic sorting, and the number of CD133 positive cells detected by flow cytometry. The self-renewing capacity of brain cancer stem cells was examined by a neurosphere formation assay, and the percentage of cell death after TRAIL treatment was examined by an MTS assay. Expression of DR5, FADD, caspase 8 and BCL2 proteins was detected by western blot. The amount of CD133 positive cells was enriched to 71% after CD133 magnetic sorting. Brain cancer stem cell neurosphere formation was significantly increased after TRAIL treatment. TRAIL treatment also reduced the amount of viable cells and this decrease was inhibited by a caspase 8 inhibitor or by the pan-caspase inhibitor z-VAD (P<0.05). Brain cancer stem cells expressed lower levels caspase 8 protein and higher levels of BCL2 protein when compared with CD133 negative cells (P<0.05). Our data suggest that TRAIL resistance is related to overexpression of BCL2 and low expression of caspase 8 which limit activation of caspase 8 in brain cancer stem cells. -
Kumar, Shiyam;Burney, Ikram A;Zahid, Khawaja Farhan;Souza, Philomena Charlotte D;Belushi, Muna AL;Mufti, Taha Dawood;Meki, Waeil AL;Furrukh, Muhammad;Moundhri, Mansour S AL 4853
Background: Colorectal cancer is the most common gastrointestinal cancer in Oman with an increasing incidence. We here report the presenting features, treatment outcomes and survival in a University hospital in Oman and compare our data with regional and international studies. Materials and Methods: Medical records of patients with colorectal cancer were reviewed retrospectively between June 2000 and December 2013 and were followed until June 2014. Results: A total of 162 patients were diagnosed with colorectal cancer. The majority were males (58.6%), with a median age of 56 years. Rectum was involved in 29.6% of patients, followed by ascending and sigmoid colon. The majority of patients had stage III (42.6%) and stage IV (32.7%) disease at presentation. K-Ras status was checked for 79 patients, and 41 (51.9%) featured the wild type. Median relapse free survival was 22 months. Median overall survival for all patients was 43 months. Observed 5 year overall survival (OS) for stages I, II and III was 100%, 60% and 60% respectively. On Log rank univariate analysis, age, BMI, diabetes, hypertension, metformin use, stage, clinical nodal status for rectal cancer, pathological T and nodal status, site of metastasis, surgical intervention, chemotherapy, radiotherapy, chemotherapy regimen, no of cycles of chemotherapy, response, RFS, site of recurrence and administration of$2^{nd}$ line chemotherapy were significant factors affecting OS. On Cox regression multivariate analysis none of the factors independently affected the OS. Conclusions: The majority of patients present with advanced disease and at young age. The survival rates are comparable to the published regional and international literature. -
Demir, Melike;Can, Gulbeyaz;Kelam, Ayhan;Aydiner, Aydin 4859
Background: Fatigue, stress and pain are common symptoms among cancer patients, affecting the quality of life. The purpose of the present study was to determine the effect of distant Reiki on pain, anxiety and fatigue in oncology patients. Materials and Methods: Participants in the control group received usual medical and nursing care during their stay. The intervention group received usual care plus five distant Reiki sessions, one each night for 30 min. A face to face interview was performed and patient personal and illness related characteristics were evaluated using the Patient Characteristics form. Pain, stress and fatigue were evaluated according to a numeric rating scale. Results: The experimental group was predominantly composed of women (71.4%), married individuals (40%), and primary school graduates (40%). The control group was predominantly male (72.7%), married (60%), and primary school graduates (60%). The control group demonstrated greater levels of pain (p=0.002), stress (p=0.001) and fatigue (p=0.001). The Reiki group pain score (p <0.0001), stress score (p <0.001) and fatigue score were also significantly lower. Conclusions: The results of this study indicate that Reiki may d ecreasepain, anxiety and fatigue in oncology patients. -
Payandeh, Mehrdad;Sadeghi, Masoud;Sadeghi, Edris;Aeinfar, Mehrnoush 4863
Background: Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Materials and Methods: Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. Results: The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. Conclusions: The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate. -
Yunus, Noraini Mat;Johan, Muhammad Farid;Al-Jamal, Hamid Ali Nagi;Husin, Azlan;Hussein, Abdul Rahim;Hassan, Rosline 4869
Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis. Materials and Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia. Results: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value = 0.008) and white blood cell count (p-value = 0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value = 0.374). Conclusions: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage. -
Din, Nasir Ud;Ahmad, Zubair;Arshad, Huma;Idrees, Romana;Kayani, Naila 4873
Purpose: To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. Materials and Results: We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletcher's consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasota's algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. Conclusions: Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category. -
Thanasitthichai, Somchai;Chaiwerawattana, Arkom;Prasitthipayong, Aree 4881
A population-based relationship between low vitamin D status and increased cancer risk is now generally accepted. However there were only few studies reported on prognostic impact. To determine the effect of low vitamin D on progression of breast cancer, we conducted a cross-sectional analysis of vitamin D levels and clinico-pathological characteristics in 200 cases of breast cancer diagnosed during 2011-2012 at the National Cancer Institute of Thailand. Vitamin D levels were measured by high-performance liquid chromatography (HPLC). Clinical and pathological data were accessed to examine prognostic effects of vitamin D. We found that the mean vitamin D level was$23.0{\pm}6.61ng/ml$ . High vitamin D levels (${\geq}32ng/ml$ ) were detected in 7% of patients, low levels (<32 ng/ml) in 93% Mean vitamin D levels for stages 1-4 were$26.1{\pm}6.35$ ,$22.3{\pm}6.34$ ,$22.2{\pm}6.46$ and$21.3{\pm}5.42ng/ml$ respectively (P=0.016) and 24.1 and 21.3 ng/ml for lymph node negative and positive cases (P=0.006). Low vitamin D level (<32 ng/ml) was significantly found in majority of cases with advanced stage of the disease (P=0.036), positive node involvement (P=0.030) and large tumors (P=0.038). Our findings suggest that low and decreased level of vitamin D might correlate with progression and metastasis of breast cancer. -
Tongtawee, Taweesak;Dechsukhum, Chavaboon;Leeanansaksiri, Wilairat;Kaewpitoon, Soraya;Kaewpitoon, Natthawut;Loyd, Ryan A;Matrakool, Likit;Panpimanmas, Sukij 4885
Background: Helicobacter pylori plays an important role in gastric cancer and typical eradication regimens are no longer effective in many countries, including Thailand. The aim of our study was to compare the effect of Lactobacillus delbrueckii and Streptococcus thermophillus on tailored triple therapy for Helicobacter pylori eradication. Materials and Methods: This prospective single-center study was conducted in Thailand. Helicobacter pylori associated gastritis patients were randomized to 2 groups: group 1 (n=100) was tailored triple therapy with placebo (esomeprazole 20 mg bid, clarithromycin 500 mg bid or metronidazole 400 mg tid if clarithromycin resistance and amoxicillin 1000 mg bid), and group 2 was tailored triple therapy plus pretreatment with probiotic containing yogurt. Successful eradication was defined as both negative histology and negative rapid urease test at four weeks after treatment. Results: A total of 200 infected patients were enrolled. PP analysis involved 194 patients: 96 in the tailored triple therapy with placebo group (group 1) and 98 the in tailored triple therapy plus pretreatment with probiotic containing yogurt group (group 2). Successful eradication was observed in 170 (87.6%) patients; by PP analysis, the eradication rate was significantly higher in group 2 (P = 0.04, 95%CI; 0.02-0.13) than in group 1. ITT analysis also showed that the value was significantly higher in the tailored triple threapy plus pretreatment with probiotic containing yogurt group (group 2) (89/100; 89%) than in the tailored triple therapy with placebo group (group 1) (P= 0.01, 95%CI; 0.04-0.15). In terms of adverse events, there was no significant difference between the two groups. Conclusions: Pretreatment with probiotic containing yogurt can improve Helicobacter pylori eradication rates with tailored triple therapy. Adding probiotics does not reduce adverse effects of the medication. -
Ma, Li;Xie, Xiao-Wei;Wang, Hai-Yan;Ma, Ling-Yun;Wen, Zhong-Guang 4891
Background: To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of nonsmall cell lung cancer (NSCLC). Materials and Methods: Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Results: Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (P<0.05). The sensitivity of CEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA + CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (P<0.05) and elevation of serum CEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (P<0.05). Conclusions: Single measurement of CEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA + CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group. -
Asiedu, Gladys B;Breitkopf, Carmen Radecki;Kremers, Walter K;Ngo, Quang V;Nguyen, Nguyen V;Barenberg, Benjamin J;Tran, Vinh D;Dinh, Tri A 4895
Physician recommendation is an important predictor of HPV vaccine acceptance; however, physician willingness and preferences regarding HPV vaccination may be influenced by factors including patient age, vaccine type, and cost. A cross-sectional survey was administered to a convenience sample of health care providers in Da Nang, Vietnam, to evaluate awareness, perceptions about HPV and HPV vaccines, and willingness to vaccinate a female patient. Willingness to vaccinate was evaluated using a full-factorial presentation of scenarios featuring the following factors: vaccine cost (free vs 1,000,000 VND), patient age (12, 16, or 22 years), and HPV vaccine type (bivalent vs quadrivalent). Responses from 244 providers were analyzed; providers had a mean age of$34{\pm}11.9$ years; a majority were female, married, and had children of their own. Thirty-six percent specialized in obstetrics/gynecology and 24% were providers in family medicine. Of the three factors considered in conjoint analysis, vaccine cost was the most important factor in willingness to vaccinate, followed by patient age, and vaccine type. The most favorable scenario for vaccinating a female patient was when the vaccine was free, the patient was 22 years of age, and the HPV4 vaccine was described. In multivariable analysis, older age, being a physician, being married, and having children were all associated with increased willingness to recommend HPV vaccination (p<0.05). Provider willingness is an important aspect of successful HPV vaccination programs; identifying preferences and biases in recommendation patterns will highlight potential areas for education and intervention. -
Suprasert, Prapaporn;Suwansirikul, Songkiat;Charoenkwan, Kittipat;Cheewakriangkrai, Chalong;Suwansirikul, Songkiat 4901
The gynecologic oncology patients surveillance network program was conducted with the collaboration of 5 provincial hospitals located in the north of Thailand (Chiang Rai, Lamphun Nan, Phayao and Phrae). The aim was to identify ways of reducing the burden and the cost to the gynecologic cancer patients who needed to travel to the tertiary care hospital for follow up. The clinical data of each patient was transferred to the provincial hospital by the internet via the website www.gogcmu.or.th. All the general gynecologists who participated in this project attended the training course set up for the program. From January 2011 to February 2014, 854 patients who were willing to have their next follow-up at the network hospitals close to their home were enrolled this project. Almost of them were residents in Chiang Rai province and the most common disease was cervical cancer. After the project had been running for 1 year, 604 of the enrolled patients and 21 health-care personnel who had participated in this project were interviewed to assess its success. Some 85.3% of the patients and 100% of the health-care personnel were satisfied with this project. However, 60 patients had withdrawn, the most common reason being the lack of confidence in the follow up at the local provincial hospital. In conclusion, it is possible to initiate a gynecologic oncology patients' surveillance network program and the initiation could reduce the problems associated with and the cost the patients incurred as they journeyed to the tertiary care hospital. -
Karateke, Atilla;Kaplanoglu, Mustafa;Baloglu, Ali 4905
Background: Platelets are blood elements thought to play a role in the immune system and therefore tumor development and metastasis. Platelet activation parameters such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) can be easily evaluated with the whole blood count and have been studied as markers of systemic inflammatory responses in various cancer types. Our aim in this study was to evaluate the correlation between endometrial pathologies and MPV, PDW and PCT. Materials and Methods: A total of 194 patients who presented to our clinic with abnormal vaginal bleeding were included in our study. The patients were divided into 3 groups (endometrial hyperplasia, endometrial cancer, control) according to their pathology results. The groups were compared for MPV, PDW, and PCT values obtained from the blood samples taken on endometrial biopsy day. Results: The endometrial cancer patients were the oldest group (p=0.04). There was no significant difference between the three groups in terms of white blood cell count (WBC), platelet count (PC), and hemoglobin (Hb) level. The highest MPV (p<0.001), PDW (p=0.002), and PCT (p<0.001) levels were in the endometrial cancer group, and the lowest levels were in the control group. Conclusions: The easy evaluation of platelet parameters in patients who are suspected of having endometrial pathology is a significant advantage. We found MPV, PDW, and PCT to be correlated with the severity of endometrial pathology with the highest values in endometrial cancer. Studies to be conducted together with different laboratory parameters will further help evaluate the diagnosis and severity of endometrial cancer and precursor lesions. -
Li, Xiao-Xia;Zhang, Yong-Gang;Wang, Dong;Chen, Yun-Fang;Shan, Yan-Hua 4909
Objective: To explore the preventive effect of aspirin on the cardiovascular complications in prostate cancer after endocrinotherapy. Materials and Methods: A total of 92 patients with prostate cancer were divided into observation group (n=44) and control group (n=48). The control group was treated with medical castration plus anti-androgenic drugs. Based on the above treatment, the observation group was added aspirin. The follow-up duration was 2 years. The changes of partial prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation rate (PAG), prostate-specific antigen (PSA) and serum testosterone (T) before and after treatment as well as incidence of cardiovascular disease were observed. Results: The 2-year survival rates of patients without cardiovascular disease in observation group and control group were 95.45% (42/44) and 72.92% (35/48), respectively, and significant difference was presented between two groups by comparison to the survival rates ($x^2=8.5453$ , p=0.0035). There was no statistical significance between two groups as well as before and after treatment regarding PT (p>0.05). After treatment, APTT went down and PAG was gradually on the rise in control group, while PAG down and APTT on the rise increasingly in observation group. Significant differences were presented between two groups as well as before and after treatment (p<0.01). Both PSA and T levels were decreased significantly in two groups after treatment (p<0.01), but there was no statistical significant between two groups (p>0.05). Conclusions: Application of endocrinotherapy in prostate cancer can easily lead to occurrence of cardiovascular disease, but cardiovascular complications can be prevented by aspirin, without affecting the effect of endocrinotherapy. -
Chen, Qing-Wei;Zhang, Xiao-Mei;Zhou, Jian-Nong;Zhou, Xin;Ma, Guo-Jian;Zhu, Ming;Zhang, Yuan-Ying;Yu, Jun;Feng, Ji-Feng;Chen, Sen-Qing 4915
Background: : Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly caused by mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectal polyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-year old if total proctocolectomy is not performed. So identification of APC germline mutations has great implications for genetic counseling and management of FAP patients. In this study, we screened APC germline mutations in Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristics of Chinese FAP patients. Materials and Methods: The FAP patients were diagnosed by clinical manifestations, family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards, genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerase chain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification (MLPA) for large duplications and/or deletions. Results: We found 6 micromutations out of 14 FAP pedigrees, while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13), c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and all deletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA and two c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in the CAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5'-CCTGAACA-3', 3'-ACAAGTCC-5 palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon 1309. Conclusions: Though there were no novel mutations found as the pathogenic gene of FAP in this study, we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especially the 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene,. -
Eliyatkin, Nuket;Zengel, Baha;Yagci, Ayse;Comut, Erdem;Postaci, Hakan;Uslu, Adam;Aktas, Safiye 4921
Background: Breast cancer is the most common cancer type among women with increasing incidence rates, improved prognosis and survival. According to the localization of the tumor, breast cancer is designated as unilateral (UBC) or bilateral (BBC). BBC can be classified as synchronous (SBBC) or metachronous (MBBC) based on the time interval between the diagnosis of the first and the secondary tumors. According to the guideline of WHO 2012, BBC is generally defined as SBBC when contralateral breast carcinoma is diagnosed within 3 months. The aim of this study was to compare the characteristics and patterns of metastasis of BBC patients with UBC. Materials and Methods: A cohort of 768 patients with breast cancer treated at the Turkish Ministry of Health-Izmir Bozyaka Research and Training Hospital between 1976 and 2012 were studied. Survival analysis was performed comparing UBC and BBC patients. In addition, evaluations were performed in patients with SBBC and MBBC sub-groups. We used a 3-months interval to distinguish metachronous from synchronous. Results: When clinical and histopathological parameters were statistically evaluated, ER status, event-free and overall survival were found to be significant between UBC and BBC patients. In comparison of SBBC and MBBC patients, age, histological type of tumor, event-free and overall survival were found to be significant. Conclusions: BBC cases were found to show worse prognosis than UBC cases. Among BBC, SBBC had the worst prognosis based on overall survival rates. -
Lourembam, Deepak Singh;Singh, Asem Robinson;Sharma, T. Dhaneshor;Singh, Th Sudheeranjan;Singh, Thiyam Ramsing;Singh, Lisam Shanjukumar 4927
Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening. -
Huang, Hou-Gang;Luo, Xi;Wu, Shuai;Jian, Bin 4937
MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E-BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p-4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC. -
Ahmed, Syed Danish Haseen;Khanam, Aziza;Sultan, Naheed;Idrees, Farah;Akhter, Naheed 4945
Background: Adiponectin is a protein, synthesized by adipose tissue, which has a questionable role in breast cancer pathogenesis. This study focused on serum levels of adiponectin among cases and controls, and its possible association with breast cancer risk. Materials and Methods: This case-control study covered 175 diagnosed breast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachi and 175 healthy controls from various screening programs. Blood samples were obtained after an overnight fast and later analyzed. Results: Fasting blood glucose was significantly raised, while serum adiponectin was significantly decreased in breast cancer cases when compared to control subjects. To find the precise influence of serum adiponectin on the risk of breast cancer, subjects were divided in to quartiles based on serum levels of adiponectin. It is observed that risk of breast cancer decreased with rising quartile. Q2 (25th-50th) had the highest OR=1.76 (CI: 0.93- 3.34), Q3 (50th-75th) has OR= 0.89 (CI: 0.48-1.64), while subjects in the highest quartile Q4 (>75th) had significantly (p< 0.05) decreased risk of breast cancer having OR=0.06 (CI: 0.02-0.15), when compared to the lowest quartile. Conclusions: We demonstrated a statistically significant association of elevated serum adiponectin with decreased risk of breast cancer. This signifies a protective role of adiponectin via an intricate mechanism of masking mitogenic growth factors in breast carcinogenesis. -
Ahmed, Hanaa H;Shousha, Wafaa Gh;Shalby, Aziza B;El-Mezayen, Hatem A;Ismaiel, Nora N;Mahmoud, Nadia S 4949
The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$ ) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and$ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and$ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$ ) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC. -
Razi, Saeid;Rafiemanesh, Hosein;Ghoncheh, Mahshid;Khani, Yousef;Salehiniya, Hamid 4955
Background: Skin cancer is the most common type of cancer worldwide. It has an increasing trend. This study investigated the epidemiological trend and morphological changes in skin cancer in Iran. Materials and Methods: This study was done using existing data, extracted from the National Cancer Registry System and the Disease Management Center of Iranian Ministry of Health between 2003 and 2008. Data on epidemiologic trend was analyzed using Joinpoint software package. Results: The incidence of skin cancer is increasing in Iran, and more in men than women. There was a declining trend for basal cell carcinoma. Basal squamous cell carcinoma and melanoma had an increasing trend. The increase of skin cancer was related to squamous cell carcinoma. Conclusions: Our findings indicated that the increase of skin cancer was attributed to squamous cell carcinoma. It is necessary to be planning for the control and prevention of this disease as a priority for health policy makers. -
Doval, Dinesh Chandra;Sharma, Anila;Sinha, Rupal;Kumar, Kapil;Dewan, Ajay Kumar;Chaturvedi, Harit;Batra, Ullas;Talwar, Vineet;Gupta, Sunil Kumar;Singh, Shailendra;Bhole, Vidula;Mehta, Anurag 4959
Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ. -
Meka, Phanni bhushann;Jarjapu, Sarika;Nanchari, Santhoshi Rani;Vishwakarma, Sandeep Kumar;Edathara, Prajitha Mohandas;Gorre, Manjula;Cingeetham, Anuradha;Vuree, Sugunakar;Annamaneni, Sandhya;Dunna, Nageswara Rao;Mukta, Srinivasulu;Triveni, B;Satti, Vishnupriya 4965
LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients. -
Sanam, Moradan;Majid, Mir Mohammad Khani 4971
Background: Several methods have been presented for the evaluation of the endometrium in patients with abnormal uterine bleeding, which include minimal invasive and invasive approaches such as diagnostic curettage or endometrial biopsy by Pipelle. Many studies have been performed in order to compare two methods; diagnostic curettage and outpatient endometrial biopsy. This investigation compared sampling adequacy, endometrial histopathology, failure rates, duration and costs between diagnostic curettage in a hospital and endometrial biopsy. Materials and Methods: This single blind clinical trial was performed on 130 patients older than 35 years who was referred to Amir training hospital in 2013 for elective diagnostic curettage because of abnormal uterine bleeding. For all patients eligible for the study, an endometrial sample by Pipelle was taken without anesthesia or dilatation. Then under general anesthesia diagnostic curettage was performed by sharp curette. Sampling duration was calculated and both samples were sent to the same pathologist. The diagnostic values of two methods in the diagnosis of normal endometrium, endometrial hyperplasia and carcinoma were compared. The costs of these two methods were also compared. Data analysis was performed by SPSS (version 16.0) software. Chi-Square, Fisher, and Pearson tests were used and were considered statistically significant at P values less than 0.05. Results: Two methods were agreed upon 88% of sampling adequacy and 94% of pathological results. Specificity of 100% and sensitivity of 90% for detection of proliferative endometrium, secretory endometrium, simple hyperplasia without atypia and 100% for cancer were recorded. Pipelle diagnostic accuracy in comparison with curettage, have been reported over 97%, so the failure rate in this study was below 5%. Sensitivity of Pipelle for detection of atrophic endometrium was reported below 50%. Duration and cost was lower in Pipelle versus curettage. Conclusions: It is concluded that due to high agreement and cohesion coefficient between curettage and Pipelle on the issue of sampling adequacy, histopathology finding (except atrophic endometrium), low failure rate, duration of sampling and cost, Pipelle can be introduced as a suitable alternative of diagnostic curettage. -
Perksanusak, Thitichaya;Sananpanichkul, Panya;Chirdchim, Watcharin;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun 4977
Background: ASC-US cases are managed according to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guideline in which a human papillomavirus (HPV) test and repeat Pap smear are performed in the next 1 year. Colposcopy in cases of positive high risk HPV and persistent ASC-US or more in subsequent Pap smear is recommended. The HPV test is more expensive and still not currently a routine practice in Thailand. Objective: To identify the risk factors of persisted abnormal Pap smear and the colposcopic requirement rate in women with ASC-US. Materials and Methods: During 2008-2013, this study was conducted in Prapokklao Hospital, Chanthaburi, Thailand. Participants were women who attended gynaecology clinic for cervical cancer screening. Women who had cytological reports with ASC-US were recruited. During the study period, 503 cases were enrolled. Colposcopic requirement was defined as those who were detected with an ASC-US or more in subsequent Pap smears up to 1 year follow-up. Results: The colposcopic referral rate was 23.2 (85/365) percent at 12 months. Prevalence of cervical intraepithelial neoplasia (CIN) 2/3 was 3.3 (12/365) percent. Loss follow-up rate of subsequent Pap smear and colposcopic appointment were 27.4 (138/503) and 48.2 (41/85) percent, respectively. There was no invasive cancer. High risk factors for persisted abnormal Pap smears in subsequent test were premenopausal status, HIV infected patients and non-oral contraceptive pills (COC) users. Conclusions: Referral rate for colposcopy in women with ASC-US reports was rather high. Loss to follow-up rate was the major limitation. Immediate colposcopy should be offered for women who had high risk for silent CIN. -
Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat (
$10{\mu}M$ ). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma. -
Otokozawa, Seiko;Tanaka, Ryoichi;Akasaka, Hiroshi;Ito, Eiki;Asakura, Sumiyo;Ohnishi, Hirofumi;Saito, Shigeyuki;Miura, Tetsuji;Saito, Tsuyoshi;Mori, Mitsuru 4987
Background: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. Materials and Methods: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. Results: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low ($P_{trend} < 0.001$ ). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low ($P_{trend}=0.005$ ). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low ($P_{trend}=0.004$ ). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low$P_{trend} < 0.001$ ). Conclusions: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer. -
Yuan, Yuan;Zhang, Yan;Shi, Lin;Mei, Jing-Feng;Feng, Jif-Eng;Shen, Bo 4993
Background: To evaluate the efficacy and safety of albumin-bound paclitaxel-based chemotherapy in treatment for patients with advanced esophageal cancer who failed in first-line chemotherapy. Materials and Methods: We collected29 advanced esophageal cancer patients who received albumin-bound paclitaxel-based chemotherapy fromJune 2009 to September 2013, and the efficacy and safety of the compound were evaluated. These patients were treated with$100-150mg/m^2$ nab-paclitaxel on days 1,8. The cycle was repeated every 3 weeks. Clinical efficacy was evaluated every two cycles. Results: Of the 29 patients, two persons interrupted treatment because of adverse reactions, failed to evaluate efficacy effect. The rest of 27 patients who could be evaluated for short-term response, 10 patients (37%) achieved partial response, 2 (7.4%) remained stable disease, and 15 (55.6%) had progressivedisease. The objective response rate was 37%, and the disease control rate was 44.4%.The median time to progression was 6.6 months.The major adverse reactions includedalopecia (62.07%), neutropenia (65.5%), gastrointestinalreaction (10.3%) andsensory neuropathy(6.8%). Conclusions: The albumin-bound paclitaxel-based chemotherapy is efficacy and safety in treatment for patients with advanced esophageal cancer who failed in first-line chemotherapy. -
Al-Maweri, Sadeq Ali;Al-Sufyani, Ghadah A;Tarakji, Bassel;Abdulrab, Saleem 4997
Advanced oral squamous cell carcinoma (SCC) is a possible risk factor for myiasis, a parasitic infestation of vital tissue of humans or other mammals by dipterous larvae (maggots). Oral myiasis is a rare entity, and is mostly associated with various medical and anatomical conditions, such as neglected mandibular fracture, lip incompetence, cerebral palsy, poor oral hygiene, suppurative lesions, and cancerous wounds. Larvae cause itching and irritation due to their crawling movements and can destroy vital tissues, inducing serious or even life-threating hemorrhage. The aim of the present article was to highlight the occurrence of oral myiasis in association with squamous cell carcinoma and also to highlight the treatment and preventive approaches for such cases. A literature search was performed using MEDLINE for articles published in English relating to the occurrence of oral myiasis in oral SCC. Our search revealed 6 reports on myiasis associated with oral SCC. The surgical debridement of infected tissue with the removal of maggots is the treatment of choice in most cases of oral myiasis. -
Aue-Aungkul, Apiwat;Suprasert, Prapaporn 5001
The Reid colposcopic index (RCI) helps physicians for interpret the results of colposcopic examination. To compare the accuracy of RCI in colposcopic evaluation between general and oncologic gynecologists, this prospective trial was conducted by invited women over 20 years of age who were scheduled for a colposcopy at Chiang Mai University Hospital between August, 2008 and May, 2014 to participate. Pregnant patients or those having a history of hysterectomy or conization were excluded. During the colposcopy, all patients were simultaneously evaluated by general and oncologic gynecologists utilizing the RCI. Further management with either a biopsy or LEEP in each patient was dependent on the decision of the attending oncologic gynecologist. The accuracy of the RCI in diagnosing HSIL or more was calculated by the comparison with the final histology. Finally, 135 patients were recruited into this study. The sensitivity, specificity, PPV, NPV, and accuracy of RCI in diagnosing HSIL or more in general gynecologists were 45.2%, 80.7%, 41.1%, 83.2% and 72.6% while in the oncologic gynecologists were 51.6%, 85.6%, 51.6%, 85.6% and 77.8%, respectively. The difference in accuracy between evaluator groups was not significant (p-value=0.28). Of 3 patients with invasive cervical cancer, all were undetected by the general gynecologists using RCI while only 1 invasive cervical cancer was missed via RCI by the oncologic gynecologists. We conclude that RCI could be used by general gynecologists in provincial hospitals with major concerns about missing invasive cervical cancer. A short training period regarding colposcopy might help to resolve this problem. -
Imani-Saber, Zeinab;Ghafouri-Fard, Soudeh 5005
Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2. -
Awwad, Nemah;Yousef, Al-Motassem;Abuhaliema, Ali;Abdalla, Ihab;Yousef, Muhammad 5007
Background: Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormality of DNA methylation is a possible mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation. Our aim was to study the association between genetic polymorphisms of MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanian females. Materials and Methods: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique and sequencing were conducted to determine the genotypes. Results: There was a significant difference in genotype frequency of C677T in the 41-60 year age category [cases: CC (37.4%), CT (49.5%) and TT (13.2%); controls: CC (56.3%), CT (35.6%) and TT (8%), p= 0.04;$OR_{TT\;vs.\;CC}$ : 2.5, 95% CI: (0.9-6.9);$OR_{at\;least\;on\;T$ : 2.1, 95%CI: (1.2-3.9)]. There was no significant difference in genotype frequency of A1298C between cases and controls [cases: AA (46.6%), AC (41.8%) and CC (11.6%); controls: AA (43%), AC (47.4%) and CC (9.6%); p= 0.6]. There was a significant difference of MTHFR genetic polymorphism haplotypes among breast cancer cases and controls [cases/control: CA: 38.3/45.4%; CC: 28.9/25.2%; TA: 29.2/21; TC: 3.6/8.3; p value= 0.01;$OR_{TA\;vs.\;CA}=1.6$ ; 95% CI (1.1-2.5); p= 0.02]. Conclusions: Genetic polymorphism of MTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TA haplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate the role of MTHFR genetic polymorphisms in breast cancer. -
Duangnapasatit, Boonlerd;Rattarittamrong, Ekarat;Rattanathammethee, Thanawat;Hantrakool, Sasinee;Chai-Adisaksopha, Chatree;Tantiworawit, Adisak;Norasetthada, Lalita 5013
Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective: To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and Methods: All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results: One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions: Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN. -
Swamy, Shanmugam Thirumalai;Radha, Chandrasekaran Anu;Arun, Gandhi;Kathirvel, Murugesan;Subramanian, Sai 5019
Background: The purpose of this study was to assess the dosimetric and clinical feasibility of volumetric modulated arc based hypofractionated stereotactic radiotherapy (RapidArc) treatment for large acoustic schwannoma (AS >10cc). Materials and Methods: Ten AS patients were immobilized using BrainLab mask. They were subject to multimodality imaging (magnetic resonance and computed tomography) to contour target and organs at risk (brainstem and cochlea). Volumetric modulated arc therapy (VMAT) based stereotactic plans were optimized in Eclipse (V11) treatment planning system (TPS) using progressive resolution optimizer-III and final dose calculations were performed using analytical anisotropic algorithm with 1.5 mm grid resolution. All AS presented in this study were treated with VMAT based HSRT to a total dose of 25Gy in 5 fractions (5fractions/week). VMAT plan contains 2-4 non-coplanar arcs. Treatment planning was performed to achieve at least 99% of PTV volume (D99) receives 100% of prescription dose (25Gy), while dose to OAR's were kept below the tolerance limits. Dose-volume histograms (DVH) were analyzed to assess plan quality. Treatments were delivered using upgraded 6 MV un-flattened photon beam (FFF) from Clinac-iX machine. Extensive pretreatment quality assurance measurements were carried out to report on quality of delivery. Point dosimetry was performed using three different detectors, which includes CC13 ion-chamber, Exradin A14 ion-chamber and Exradin W1 plastic scintillator detector (PSD) which have measuring volume of$0.13cm^3$ ,$0.009cm^3$ and$0.002cm^3$ respectively. Results: Average PTV volume of AS was 11.3cc (${\pm}4.8$ ), and located in eloquent areas. VMAT plans provided complete PTV coverage with average conformity index of 1.06 (${\pm}0.05$ ). OAR's dose were kept below tolerance limit recommend by American Association of Physicist in Medicine task group-101(brainstem$V_{0.5cc}$ < 23Gy, cochlea maximum < 25Gy and Optic pathway <25Gy). PSD resulted in superior dosimetric accuracy compared with other two detectors (p=0.021 for PSD. -
Bahgat, Nermine Ahmed;Kamal, Manal Mohamed;Abdelaziz, Ashraf Omar;Mohye, Mohamed Ahmed;Shousha, Hend Ibrahim;ahmed, Mae Mohamed;Elbaz, Tamer Mahmoud;Nabil, Mohamed Mahmoud 5025
Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN-${\gamma}$ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN${\gamma}$ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN${\gamma}$ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-${\gamma}$ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-${\gamma}$ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4). -
Zahir, Shokouh Taghipour;Aalipour, Ezatollah;Barand, Poorya;Kaboodsaz, Mansoureh 5031
Background: Adrenal tumors are relatively uncommon, and have different presentations, so we decided to evaluate the clinico-pathological characteristics of benign and malignant tumors in a ten-year period. Materials and Methods: This cross sectional-analytical study was conducted on adrenal resection samples taken during 2004-2014 in three hospitals in Yazd province. Data were analyzed using SPSS software, version 17. Chi-square and Fisher's exact test were used as appropriate Results: A total of 71 patients with adrenal tumors were analyzed, including 32 (45.1%) men and 39 (54.9%) women with an overall mean age$37.7{\pm}19.9$ (range: 6-75 years). Some 50.7% of lesions were benign and 49.3% were malignant. Neuroblastoma was the most malignant lesion (32.3%) followed by adrenocortical carcinoma (8.4%). Among the benign lesions pheochromocytoma was the most common (25.3%) followed by adrenocortical adenoma (12.6%). While 64% of tumors were functional 36% were non functional. Significant correlation was seen between the age of patient and type of tumor (P=0.001). In patients between 14-40 years old no malignant lesions was found, although under 14 years old all of the tumors were malignant. Malignant lesions mostly presented with abdominal pain, abdominal mass and anorexia (57.2%, 45.7% and 45.7%) respectively. Benign lesions mostly presented with paroxysmal hypertension, headache and abdominal pain (61.2%, 47.2% and 44.4%) respectively. Conclusions: Since the trend of adrenal tumors is on the rise based on this and other studies, suspected cases should undergo prompt hormonal and radiological assessment. Early diagnosis and treatment could prevent tumor progression and reduce mortality and morbidity rates. -
Rattanaburi, Athithan;Boonyapipat, Sathana;Supasinth, Yuthasak 5037
Background: An hCG regression curve has been used to predict the natural history and response to chemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestational trophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/CO resistance in GTN. Materials and Methods: Eighty-one women with GTN treated with EMA/CO were classified as primary high-risk GTN (n = 65) and single agent-resistance GTN (n = 16). The hCG levels prior to each course of chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves. Diagnostic performance was evaluated for an optimal cut-off value. Results: The median hCG levels were 264,482 mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN, respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course of chemotherapy, respectively. The hCG level of${\geq}118.6mIU/mL$ mIU/mL at the 5thcourse of EMA/CO predicted the EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%. Conclusion: EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curve in combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy. -
Abolhasani, Maryam;Salarinejad, Sareh;Asgari, Mojgan 5043
Background: Relatively little is known with certainty about the status and role of p53 or MDM2 in predicting prognosis and survival of renal cell carcinoma. The present study aimed to determine the value of P53 and MDM2 over-expression, alone and simultaneously, to predict five-year survival of patients with kidney cancer in Iran. Materials and Methods: Patients with kidney cancer referred to Hasheminejad Kidney Center between 2007 and 2009, underwent radical nephrectomy and had pathology reports of clear cell, papillary or chromophobe renal cell carcinoma were included in our cohort study. Other histological types of renal cell carcinoma were not included. The patients with missed, incomplete or poor quality paraffin blocks were also excluded. Overall ninety one patients met the inclusion and exclusion criteria. To assess the histopathological features of the tumor, immunohistochemical (IHC) staining of formalin fixed, paraffin-embedded tumor samples were performed. The five-year survival was determined by the patients' medical files and telephone following-up. Results: In total, 1.1% of all samples were revealed to be positive for P53. Also, 20.8% of all samples were revealed to be positive for MDM2.The patients were all followed for 5 years. In this regard, 5-year mortality was 30.5% and thus 5-year survival was 85.3%. According to the Cox proportional hazard analysis, positive P53 marker was only predictor for patients' 5-year survival that the presence of positive p53 increased the risk for long-term mortality up to 2.8 times (HR=2.798, 95%CI: 1.176-6.660, P=0.020). However, the presence of MDM2 could not predict long-term mortality. In this regard, analysis by the ROC curve showed a limited role for predicting long-term survival by confirming P53 positivity (AUC=0.610, 95%CI: 0.471-.750, P=0.106). The best cutoff point for P53 to predict mortality was 0.5 yielding a low sensitivity (32.0%) but a high specificity (97.9%). In similar analysis, measurement of MDM2 positivity could not predict mortality (AUC=0.449, 95%CI: 0.316-.583, P=0.455). Conclusions: The simultaneous presence of both P53 and MDM2 markers in our population is a rare phenomenon and the presence of these markers may not predict long-term survival in patients who undergoing radical nephrectomy. -
Sharifian, Abdolhamid;Pourhoseingholi, Mohamad Amin;Emadedin, Majid;Nejad, Mohammad Rostami;Ashtari, Sara;Hajizadeh, Nastaran;Firouzei, Seyed Alireza;Hosseini, Seyed Jalil 5049
Background: Breast cancer (BC) is the leading cause of oncological death for women, in both developed and developing countries. In Iran, breast cancer ranks first among cancers diagnosed in women. The aim of this study was to present the burden of this cancer including incidence, mortality and years life lost (YLL) due to breast cancer in Iranian women. Materials and Methods: National incidence data from the Iranian annual National Cancer Registration reports from 2003 to 2009 and national death statistics reported by the Ministry of Health and Medical Education from 1995 to 2010, stratified by age group, were included in this analysis. Also calculated YLLs provided by the Institute for Health Metrics and Evaluation (IHME) for the years 1990, 1995, 2000, 2005 and 2010 were employed to express the years lost due to BC for Iranian women. Results: The general mortality rate of breast cancer increased during these years from 0.96 to 4.33 per 100,000 and incidence increased from 16.0 to 28.3 per 100,000 for the years under study. YLLs calculated by IHME showed both increasing and decreasing patterns, with a tendency for stabilization. Conclusions: The burden of breast cancer for Iranian women is still increasing. Thus, health education programs to inform women regarding the signs and risk factors, and national screening to facilitate early diagnosis are needed for the female community in Iran. -
Sabeena, Sasidharanpillai;Bhat, Parvati V;Kamath, Veena;Aswathyraj, Sushama;Arunkumar, Govindakarnavar 5053
Background: Cervical cancer is one of the commonest cancers among women all over the world. The association of cervical cancer with human papilloma virus (HPV) is well established. Knowledge about the causal relationship between HPV and cervical cancer is important to make appropriate, evidence-based health care choices. In this context we conducted a community based study among women about the knowledge, attitude and practice about HPV infections and their health effects. Materials and Methods: A cross sectional interview based house to house survey was conducted with a validated data collection tool covering sociodemographic factors, knowledge, attitude and practice about HPV and its health effects, among 1020 women from a rural village, Perdoor, in Udupi district, Karnataka, India in 2013-14. Results: The mean age of participants was 38.9 years (SD=12.6). Study participants showed a high literacy rate (85.7%). Only 2.4% of sexually exposed women had undergone Pap smear testing. Partners of 4.4%women had undergone circumcision and they belonged to the Muslim community. Male condom usage was reported by 26 women (2.6%). However, none of the participants had heard of HPV and its health effects. Conclusions: This community based study found complete ignorance about HPV among rural South Indian women in spite of a high literacy level. -
Mehde, Atheer Awad;Yusof, Faridah;Mehdi, Wesen Adel;Zainulabdeen, Jwan Abdulmohsin 5059
Background: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. Aim and objectives: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. Materials and Methods: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione-s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. Results: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Conclusions: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL. -
Chong, Vui Heng;Telisinghe, Pemasari Upali;Bickle, Ian;Abdullah, Muhamad Syafiq;Lim, Ediwn;Chong, Chee Fui 5063
Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is a significant cause of mortality. Its incidence is generally increasing in Asia. Reports from the West have indicated that the incidence of rectal cancer is increasing in the younger population. This study assessed the time trend of CRC in Brunei Darussalam specifically assessing the different age groups at which the incidences start to increase. Materials and Methods: The National Cancer registry was reviewed (1991 to 2014). The age standardized rate (ASR) and the age specific incidence rates (ASIRs) for three time periods (1991-1998), (1999-2006) and (2007-2014) were calculated. Results: The mean age of diagnosis was$59.3{\pm}14.6$ years old, incidences being slightly higher amongst men (57.6%) and Malays (67.1%). The most common tumor type was adenocarcinoma (96.4%). Rectal cancers accounted for 35.2% (n=372/1,056) of all cancers of the large bowel; more men were affected than women. The proportion of rectal cancer was also high among the indigenous group. In the three time periods, the ASR for CRC increased from 16 per 100,000 (1991-1998) to 19.6 per 100,000 (1999-2006) and 24.3 per 100,000 (2007-2014). The ASIRs for CRC increased markedly between the time periods 1998-2006 and 2007-2014, beginning in the 40-44 years age group. For rectal cancers, the ASIRs started to increase in the 25-29 age group onward whereas for colon cancers, the increase was observed at a later age, starting from the 45-49 age group. Conclusions: Our study showed an increase in the incidence of CRC including in the younger age groups. The increase was seen earlier in rectal cancer compared to colon cancer. These data mirror the trends reported from the West. -
Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit 5069
The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population. -
Pathy, Sushmita;Kumar, Lalit;Pandey, Ravindra Mohan;Upadhyay, Ashish;Roy, Soumyajit;Dadhwal, Vatsla;Madan, Renu;Chander, Subhash 5075
Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco-regional control with a conventional schedule. Materials and Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin$40mg/m^2$ . High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin$20mg/m^2/day$ was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were$65{\pm}12$ and$48{\pm}4$ days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade${\geq}3$ toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable. -
Baghestani, Ahmad Reza;Shahmirzalou, Parviz;Zayeri, Farid;Akbari, Mohammad Esmaeil;Hadizadeh, Mohammad 5081
Background: Breast cancer is a malignant tumor that starts from cells of the breast and is seen mainly in women. It's the most common cancer in women worldwide and is a major threat to health. The purpose of this study was to fit a Cox proportional hazards model for prediction and determination of years of survival in Iranian patients. Materials and Methods: A total of 366 patients with breast cancer in the Cancer Research Center were included in the study. A Cox proportional hazard model was used with variables such as tumor grade, number of removed positive lymph nodes, human epidermal growth factor receptor 2 (HER2) expression and several other variables. Kaplan-Meier curves were plotted and multi-years of survival were evaluated. Results: The mean age of patients was 48.1 years. Consumption of fatty foods (p=0.033), recurrence (p<0.001), tumor grade (p=0.046) and age (p=0.017) were significant variables. The overall 1- year, 3-year and 5-year survival rates were found to be 93%, 75% and 52%. Conclusions: Use of covariates and the Cox proportional hazard model are effective in predicting the survival of individuals and this model distinguished 4 effective factors in the survival of patients. -
Malek, Mahrooz;Pourashraf, Maryam;Gilani, Mitra Modares;Gity, Masoumeh 5085
Background: The aim of this study was to assess the role of the presence of a choline peak in 3 Tesla 1H magnetic resonance spectroscopy (MRS) for differentiating benign from malignant adnexal masses. Materials and Methods: A total of 46 adnexal masses (23 malignant and 23 benign) underwent 1H MRS study prior to surgery to assess the presence of choline peak. Results: A choline peak was detected in 16 malignant masses (69.5%) and was absent in the other 7 (30.5%). A choline peak was only detected in 6 (26%) of the benign adnexal masses. The presence of an MRS choline peak had a sensitivity of 69.5%, a specificity of 74%, a positive predictive value (PPV) of 72.7%, and a negative predictive value (NPV) of 71% for diagnosing malignant adnexal masses. A significant difference between the frequency of mean choline peaks in benign and malignant adnexal masses was observed (P value < 0.01). Conclusions: A 1H MRS choline peak is seen in malignant adnexal masses more frequently than the benign masses, and may be helpful for diagnosing malignant adnexal masses. -
Du, Yong;Yan, Shu-Mei;Gu, Wan-Yi;He, Fan;Huang, Li-Yun;Li, Mei;Yuan, Yan;Chen, Ren-Hui;Zhong, Qian;Li, Man-Zhi;Li, Yong;Zeng, Mu-Sheng 5089
FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC. -
Chen, Jian;Chen, Jie;Ding, Hong-Yan;Pan, Qin-Shi;Hong, Wan-Dong;Xu, Gang;Yu, Fang-You;Wang, Yu-Min 5095
Background: The statistical methods to analyze and predict the related dangerous factors of deep fungal infection in lung cancer patients were several, such as logic regression analysis, meta-analysis, multivariate Cox proportional hazards model analysis, retrospective analysis, and so on, but the results are inconsistent. Materials and Methods: A total of 696 patients with lung cancer were enrolled. The factors were compared employing Student's t-test or the Mann-Whitney test or the Chi-square test and variables that were significantly related to the presence of deep fungal infection selected as candidates for input into the final artificial neural network analysis (ANN) model. The receiver operating characteristic (ROC) and area under curve (AUC) were used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. Results: The prevalence of deep fungal infection from lung cancer in this entire study population was 32.04%(223/696), deep fungal infections occur in sputum specimens 44.05%(200/454). The ratio of candida albicans was 86.99% (194/223) in the total fungi. It was demonstrated that older (${\geq}65$ years), use of antibiotics, low serum albumin concentrations (${\leq}37.18g/L$ ), radiotherapy, surgery, low hemoglobin hyperlipidemia (${\leq}93.67g/L$ ), long time of hospitalization (${\geq}14$ days) were apt to deep fungal infection and the ANN model consisted of the seven factors. The AUC of ANN model($0.829{\pm}0.019$ )was higher than that of LR model ($0.756{\pm}0.021$ ). Conclusions: The artificial neural network model with variables consisting of age, use of antibiotics, serum albumin concentrations, received radiotherapy, received surgery, hemoglobin, time of hospitalization should be useful for predicting the deep fungal infection in lung cancer. -
Xu, Chuan;Lv, Peng-Hua;Huang, Xin-En;Wang, Shu-Xiang;Sun, Ling;Wang, Fu-An 5101
Background: This systemic analysis was conducted to evaluate tumor recurrence rate and one-year survival rate for patients with liver metastases received radiofrequency ablation after transarterial chemoembolization and introduce a new method of radiofrequency ablation by puncture navigation technology for single liver metastases after transarterial chemoembolization. Materials and Methods: Clinical studies evaluating tumor recurrence rate and one-year survival rate. Appling the innova trackvision software to process one liver metastases received transarterial chemoembolization and using radiofrequency ablation by puncture navigation technology to treat the liver metastases. Results: 3 clinical studies which including 235 patients with liver metastases after transaeterial chemoembolization were considered eligible for inclusion. Systemic analysis suggested that tumor recurrence rate was 23% (54/235), one-year survival rate was 76% (178/235). The new procedure was performed successfully and the patient received a good prognosis. Conclusions: This systemic analysis suggests that radiofrequency ablation is a good method for liver metastases after transarterial chemoembolization and could receive a relatively good prognosis. -
Bal, Manjit Singh;Bodal, Vijay Kumar;Kaur, Jaspreet;Kaur, Mohanvir;Sharma, Swati 5107
The State of Punjab has been in focus because of aperceived increasing rate of cancer. Both print and electronic media have created an impression that Punjab, especially the cotton belt of Malwa Region, has become a high incidence cancer region. Actually the increased number of cancer patients might be at least partly because of increasing population and heightened health awareness and reporting. The purpose of this study is to find out the pattern of cancer amongst patients registered in Mukh Mantri Punjab Cancer Rahat Kosh Scheme (MMPCRKS), under cancer registry at Rajindra Hospital Patiala from the various districts of Punjab. The study covers 500 cancer patients registered under MMPCRKS at Rajindra Hospital Patiala, for free cancer treatment. Information regarding age, gender, religion, method of diagnosis and affected sites was obtained. Results were analyzed statistically. Of the 500 patients, 65% were females and 35% were males. The most affected female age groups were 50-54 and 60-64; while males in the age groups of 65-69 and 60-64 had the highest risk. The leading cancers in females were breast followed by cervix and ovary where as in males they were were colon followed by esophagus and tongue. The commonest histological type was adenocarcinoma followed by squamous cell carcinoma. The increasing trend of cancer in Punjab is alarming. Since this study is a preliminary investigation, it could provide a leading role in prevention, treatment and future planning regarding cancer in Punjab. -
He, Zhan-De;Huang, Xin-En;Zhou, Jian-Nong 5111
Background: To investigate the diagnostic and treatment methods for Chinese patients with gastrointestinal stromal tumor (GIST). Materials and Methods: From January 2004 to June 2014, patients diagnosed with primary GIST and treated by a single medical team in the Department of Digestive Disease of XuYi Hospital of Traditional Chinese Medicine were retrospectively recruited. Re-examination and follow-up was conducted regularly and abdominal enhanced CT, blood biochemistry and responses to surgery or imatinib were recorded. Results: A total of 15 patients were enrolled, including 9 male and 6 female patients, with an average age of 54 years (ranging from 32-81 years). The primary symptoms were abdominal uncomfortable in 5 patients, abdominal pain in 6 patients as well as nausea and vomiting in 4 patients. One patient was diagnosed with bowl obstruction at the first visit. All patients were treated with surgery, and tumor site was confirmed 1 esophagus, 6 stomach, 4 small bowel, and 4 colorectal and all patients were pathologically diagnosed with GIST. Immunochemical test positive for CD 117 was found 12 patients, and positive for CD 34 in7 patients. The median follow-up time was 24 months (range of 3-63). Three metastasis were confirmed 1.5, 2 and 2.6 years postoperatively. Three patients were treatment by imatinib postoperatively. Conclusions: Surgery remains the main treatment method for Chinese patients with GIST and imatinib could be feasible and safe for treating Chinese patients with GIST. -
Background: The
$p16^{INK4a}$ is a protein that expressed in Liquid-based cervical cytology specimens and has been proved link to cervical cancer. The$p16^{INK4a}$ could be detection by piezoelectric immunosensor and the immobilization of the$p16^{INK4a}$ antibody influence the sensitivity of the piezoelectric immunosensor. Materials and Methods:$5{\mu}L$ mouse polyclonal antibody against$p16^{INK4a}$ was bound onto the surface of immonosensor through two methods. (directly immobilized method; protein A method). Absorb of the$p16^{INK4a}$ antibody on the surface of immonosensor caused a shift in the resonant frequency of the immunosensor and The frequency changes recorded showed a better reproducibility. The activity of the immobilization antibody with the directly method and protein A method was tested with$p16^{INK4a}$ antigen. Results: The resonant frequency for different antibody immobilization methods were different, and the sensitivity for$p16^{INK4a}$ detection also different. Conclusions: The protein A method was found to be much more better than the directly method for the immobilization of the p16INK4A antibody on the gold electrode of the quartz crystal for cervical lesion detection. The Protein A method created more reproducible and stable immobilization antibody layers with p16INK4A antigen. -
Tay, SK;Tesalona, KC;Mohamed Rashid, N;Tai, EYS;Mohd Najib, S 5119
Background: HPV vaccination in Singapore is voluntary and physician prescription-based. This study investigated the current status and intention for HPV vaccination among Singapore nurses. Materials and Methods: All female nurses in a general hospital were given an anonymous questionnaire on HPV vaccination experience and intention of vaccinating their daughters. The influence of age, knowledge and perceived-risk of cervical cancer, and cultural background on mother's intention of vaccinating their daughters was analyzed. Results: Of 2,000 nurses, 1,622 (81.1%) responded and analysis was performed on 1,611 with valid data. They showed good awareness on association of cervical cancer with multiple sexual partners (81.9%), history of sexually transmissible diseases (78.2%), and history of genital warts/HPV infection (73.5%), and on cervical cancer preventive effects of HPV vaccination (54.6%). The prevailing misconceptions of the vaccines were: investigational nature (38.9%), side effects (27.9%) and indicated for women at high risk for cervical cancer (20.5%). Conclusions: Misconceptions on the nature, role and safety of HPV vaccines low vaccine up-take rates and daughters. Dissemination of adequate and accurate HPV vaccine information and a review for school-based vaccination are needed for optimal delivery of HPV vaccines in Singapore. -
Xin, Yue;Li, Xiao-Yu;Sun, Shi-Ran;Wang, Li-Xia;Huang, Tao 5125
Background: Total fat intake may be associated with increased risk of breast cancer, and fish oil has been suggested as a protection factor to breast cancer. But the effect of vegetable oils is inconclusive. We aimed to investigate the association with high vegetable oils consumption and breast cancer risk, and evaluated their dose-response relationship. Design: We systematically searched the MEDLINE, EMBASE, Cochrane databases, and CNKI updated to December 2014, and identified all observational studies providing quantitative estimates between breast cancer risk and different vegetable oils consumption. Fixed or random effect models were used to estimate summary odds ratios for the highest vs. lowest intake, and dose-response relationship was assessed by restricted cubic spline model and generalized least-squares trend (GLST) model. Results: Five prospective cohort studies and 11 retrospective case-control studies, involving 11,161 breast cancer events from more than 150,000 females, met the inclusion criteria. Compared with the lowest vegetable oils consumption, higher intake didn't increased the risk of breast cancer with pooled OR of 0.88 (95% CIs:0.77-1.01), and the result from dose-response analyses didn't show a significant positive or negative trend on the breast cancer risk for each 10g vegetable oil/day increment (OR=0.98, 95% CIs: 0.95-1.01). In the subgroup analyses, the oils might impact on females with different strata of BMI. Higher olive oil intake showed a protective effect against breast cancer with OR of 0.74 (95% CIs: 0.60-0.92), which was not significant among the three cohort studies. Conclusions: This meta-analyses suggested that higher intake of vegetable oils is not associated with the higher risk of breast cancer. Olive oil might be a protective factor for the cancer occurrence among case-control studies and from the whole. Recall bias and imbalance in study location and vegetable oils subtypes shouldn't be ignored. More prospective cohort studies are required to confirm the interaction of the impact of vegetable oils on different population and various cancer characteristic, and further investigate the relationship between different subtype oils and breast cancer.