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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Mahachai, Varocha;Vilaichone, Ratha-Korn;Pittayanon, Rapat;Rojborwonwitaya, Jarin;Leelakusolvong, Somchai;Kositchaiwat, Chomsri;Mairiang, Pisaln;Praisontarangkul, Ong-Ard;Ovartlarnporn, Buncha;Sottisuporn, Jaksin;Pisespongsa, Pises;Maneerattanaporn, Monthira;Sony, Ravin;Sirinthornpunya, Siam;Chaiyamahapurk, Orawan;Wiwattanachang, Olarn;Sansak, Inchaya;Harnsomboon, Piyathida;Chitapanarux, Taned;Chuenrattanakul, Surapon 2351
Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes. -
Saadany, Sherif El;Mayah, Wael;Kalla, Ferial El;Atta, Tawfik 2361
Since 1980, endoscopic ultrasound (EUS) has been used as an important tool for the evaluation of malignant diseases in hollow viscus and bilio-pancreas, as well as sub-epithelial tumors. The high-resolution capacity and low penetration depth of EUS make it possible to obtain highly detailed images of the gastrointestinal wall and immediate surroundings to a depth of 4-5 cm. Thus, over the past 35 years, EUS succeeded to modify management in significant number of cases and is now considered a gold standard tool for many gastrointestinal diseases, especially in the pancreatico-biliary tract, and adjuvant needle insertion now allows access to remote lesions that were difficult to reach in the past. With the growing spectrum of indications, tissue sampling for diagnostic purposes has become common. In this review, we aim to highlight the expanding spectrum of EUS indications and uses in staging of upper gastrointestinal malignancies, especially esophageal, gastric and ampullary tumors. -
Background: Differentiated thyroid cancer (DTC) is a cancer group that shares molecular and cellular origin but shows different clinical courses and prognoses. Several prognostic factors have been reported for predicting recurrence for individual patients. This literature review aimed to evaluate prognostic scores for predicting recurrence of DTC. Materials and Methods: A search of the MEDLINE database for articles published until December 2015 was carried out using the terms "thyroid neoplasms AND (recurrent OR persistent) AND (score OR model OR nomogram)". Studies were eligible for review if they indicated the development of prognostic scoring models, derived from a group of independent prognostic factors, in predicting disease recurrence in DTC patients. Results: Of the 308 articles obtained, five were eligible for evaluation. Two scoring models were developed for DTC including both papillary and follicular carcinoma, one for papillary carcinoma, and the other two for papillary microcarcinoma. The number of patients included in the score development cohort ranged from 59 to 1,669. The number of evaluated potential prognostic factors ranged from 4 to 25. Tumor-related factors were the most common factors included in the final scores, with cervical lymph node metastases being the most common. Only two studies showed internal validation of the derived score. Conclusions: There is a paucity of prognostic scores for predicting disease recurrence in patients with DTC, in particular for follicular thyroid carcinoma. Several limitations of the created scores were found. Performance of the scores has not been adequately studied. Comprehensive validation in multiple cohorts is recommended before widespread use.
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Cancer is a major health problem in Oman. It is reported that cancer incidence in Oman is the second highest after Saudi Arabia among Gulf Cooperation Council countries. Based on GLOBOCAN estimates, Oman is predicted to face an almost two-fold increase in cancer incidence in the period 2008-2020. However, cancer research in Oman is still in its infancy. This is due to the fact that medical institutions and infrastructure that play central roles in data collection and analysis are relatively new developments in Oman. We believe the country requires an organized plan and efforts to promote local cancer research. In this paper, we discuss current research progress in cancer diagnosis using machine learning techniques to optimize computer aided cancer detection and classification (CAD). We specifically discuss CAD using two major medical data, i.e., medical imaging and microarray gene expression profiling, because medical imaging like mammography, MRI, and PET have been widely used in Oman for assisting radiologists in early cancer diagnosis and microarray data have been proven to be a reliable source for differential diagnosis. We also discuss future cancer research directions and benefits to Oman economy for entering the cancer research and treatment business as it is a multi-billion dollar industry worldwide.
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Fakhry, Amal Bahgat;Ahmed, Asmaa Ismail;AbdelAlim, Mahmoud Abdo;Ramadan, Dalia Ibrahim 2383
Background: The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene linked to several malignancies. Objective: To analyze any association between RECK gene rs10814325 single-nucleotide polymorphism (SNP) and HCC susceptibility with various clinicopathological and laboratory data. Materials and Methods: RECK gene rs10814325 SNP was estimated, using real-time PCR, in 30 HCC patients on top of HCV infection, 30 HCV related cirrhotic patients and 30 healthy controls. Results: No special pattern of association could be detected on comparing the RECK gene rs10814325 genotypes(P=0.5), or alleles(P=0.49) among the studied groups. HCC patients with TT genotype had younger age (mean of$54.1{\pm}6.0$ years vs$60.6{\pm}10.2$ years for TC/CC genotypes, P=0.035). Abdominal distension was significantly greater in TT genotype patients (75% vs 30%for TC/CC genotypes, P=0.045). The TT genotype was present in 75% of patients with lymph node metastasis. Serum GGT levels were higher in TT genotype patients [80 (48.5-134.8) IU/L vs 40 (33-87.5) IU/L for TC/CCgenotypes], and lower limb edema was observed in 60% for TT vs 20% for TC/CCgenotypes, but both just failed to reach significance (p=0.05 and p=0.06 respectively). Conclusions: RECK gene rs10814325 T>C could not be considered a risk factor for HCC development on top of HCV, but may be related to the disease progression and metastasis. -
Abdelgawad, Iman A.;Radwan, Noha H.;Shafik, Roxan E.;Shokralla, Hala A. 2389
Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth & survival of the malignant clone. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM. -
Attar, Marzieh;Azar, Saleh Shahbazi;Shahbazi, Majid 2395
Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women. -
Wong, E Ru;Idris, Fazean;Chong, Chee Fui;Telisinghe, Pemasari Upali;Tan, Jackson;Chong, Vui Heng 2401
Background: Both colorectal cancer (CRC) and diverticular disease (DD) are common in the affluent West, and their prevalence is also increasing in the rest of the world with economic development. Both diseases have common epidemiologic characteristics; increasing incidence, more common with advancing age and related to specific dietary changes. However, studies of associations between the two have generated mixed results with some showing positive correlations, whilst others have shown no or negative links. Most of these studies have been from the West with study populations that were predominantly Caucasians. Here the focus was on DD and colorectal neoplasms, including CRC, in Brunei. Materials and Methods: All patients who had undergone complete colonoscopy between 2011 and 2014 were identified and retrospectively reviewed. Patients under the age of 18 years old or had previous colonic surgeries (including previous CRC resection) were excluded. Results: The total number of colonoscopies included in the study was 2,766 (mean age$53.2{\pm}14.8$ years old, male 51.8%), of which DD, CRC and colonic polyps were detected in 17.3%, 4.7% and 28.2% respectively. The proportions of DD, polyps and CRC increased proportionally with age (<30 years, 30-49, 50-69 and${\geq}70$ ). Overall, there was no association between the presence of DD and CRC (3.6% vs. 5.0%, p=0.179) but there was a significant association between CRC and left sided DD (p=0.034 by trend). There were also a significant association between presence of DD and polyps (36.1% vs. 28.2%, p=0.001), in particular with right-sided and pan-DD (p=0.001 for trend). Conclusions: Our study showed that the prevalence of DD, CRC and polyps increases with age. There were significant associations between presence of left-sided DD with CRC and right-sided or pan-DD with colonic polyps. This suggests shared risk factors. Further studies are required to assess links in other countries of the Asian Pacific region. -
Ali, Sajid;Ahmad, Bashir;Ali, Ijaz;Mahmood, Nourin;Anwar, Naveed;Saeedi, Ilyas;Afridi, Jehan Zeb 2407
Background: Response to antiviral therapy has been linked to different genotypes and this impacts on clinical management. Data on general responses to standard interferon (IFN) against HCV infection exists but little is known regarding HCV genotype specific responses. Purpose: Therefore, we attempted to determine genotype specific responses of chronic HCV patients, having different HCV genotypes, to standard IFN and ribavirin combination therapy administered for a period of six months in Kybher Pakhtunkhwa province of Pakistan. Materials and Methods: HCV genotype was determined for all serum samples. Each patient received standard IFN combination therapy with ribavirin administered at dose of 3 MIU three times a week and 800-1200 mg/day, respectively, for a period of six months. After completion of this therapy, PCR was performed for all course completed subjects. Results: Out of total 51 selected patients the most abundant genotypes were 3a (49.0%) and 1a (21.6%) followed by 3b (9.8%), 1b (7.84%), 2a (7.84%) and untypable (3.94%). Moast responsive genotypes were 2a followed by 3a, with end of treatment responses of 77.7%, and 72.2%. Responses for 3b, 1b and untypable were 66.7%, 33.3% and 0%, respectively. Conclusions: IFN response is efficient in case of 2a and 3a genotypes while in case of untypable genotypes, further categorization is required to know about genomic sequences and to adopt some new regimes against these genotypes. -
Purpose: To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. Materials and Methods: One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. Results: CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Conclusions: Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.
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Sahami-Fard, Mohammad Hossein;Yazd, Ehsan Farashahi;Khazaei, Zahra;Neamatzadeh, Hossein 2415
E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97-1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility. -
Leila, Zaruni;Arabzadeh, Seyed Alimohammad;Afshar, Reza Malekpour;Afshar, Abbas Aghaei;Mollaei, Hamid Reza 2423
Gastric cancer (GC) is a multifactorial disease with different factors having roles in its genesis. Helicobacter pylori and Epstein-Barr virus (EBV) are known infectious agents that could contribute. In addition, there is evidence of a relationship with cytomegalovirus (CMV). Since data on CMV prevalence in gastric cancer are limited, we here evaluated the frequency of EBV and CMV in Iranian patients. Ninety paraffin blocks of GC tissues from patients in Kerman were evaluated for the presence of EBV and CMV genomes by real-time polymerase chain reaction. EBV was detected in 10 cases (11.1%) and CMV in seven. One out of 17 female patients (5.88%) and nine out of 73 male patients (12.3%) were positive for EBV, while one out of 17 female patients (5.88%) and six out of 73 male patients (8.22%) were positive for CMV. The mean age for EBV-positive patients was$60.5{\pm}14.9years$ and the mean age for CMV-positive patients was$67.9{\pm}12.3years$ . This study shows that the frequency of EBV-associated GC is high in Kerman. It also indicates that further studies of associations between GC and CMV are warranted, covering larger samples and populations from different areas of the world. -
Teama, Salwa;Fawzy, Amal;Teama, Shirin;Helal, Amany;Drwish, Amira Diyaa;Elbaz, Tamer;Desouky, Eman 2429
Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of$ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and$TGF-{\beta}1$ mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of$TGF-{\beta}1$ mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and$TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and$TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and$TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted. -
Chansing, Kochpinchon;Pakakasama, Samart;Hongeng, Suradej;Thongmee, Acharawan;Pongstaporn, Wanida 2435
Background: MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Materials and Methods: Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Results: The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. Conclusions: The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables. -
Nallathambi, Chandran;Yumkhaibam, Sobita Devi;Singh, Laishram Jaichand;Singh, Thaodem Tomcha;Singh, Indibor Yengkhom;Daniel, Nithinraj 2439
Purpose: To determine the risk factors, clinical symptoms and patterns of spread in laryngeal cancer. Materials and Methods: A cross sectional study was carried out in the Regional Cancer Centre, Imphal, Manipur, India. One hundred and sixteen patients with laryngeal cancer were retrospectively reviewed for epidemiological data and descriptive statistics were reported for various variables. Results: Median age at presentation was 65 years and 32.8% were undernourished at presentation. The male to female ratio was 5.4:1. Heavy smoking and tobacco chewing was associated in 91.4% and 33.6% of patients respectively. Tracheostomy was required in 21.5% leading to diagnosis of laryngeal cancer. Almost all were squamous cell carcinoma with neuroendocrine and verrucous carcinoma accounting for less than 2%. Supraglottic, glottic and trans-glottic tumors were 56.9%, 36.3% and 6.9% respectively. Nodal metastases were seen in 81.8% of supraglottic cancers and 31.6% of glottic cancers with supraglottic involvement. Level II neck nodes were the commonest site followed by level III. Distant metastases (only liver) were apparent in 1.7% at presentation. Including these liver metastases, unresectable cases were limited to 6% of the patients. Conclusions: Tobacco use is implicated in almost all of the cases and the sex ratio has also decreased due to increased female smokers. The supraglottis remains the commonest site and incidence of nodal metastases is higher than in other countries. There is also a higher requirement for tracheostomy at presentation in this region. -
Kittisiam, Thannaporn;Tangjitgamol, Siriwan;Chaowawanit, Woraphot;Khunnarong, Jakkapan;Srijaipracharoen, Sunamchok;Thavaramara, Thaowalai;Pataradool, Kamol 2445
Background: To evaluate knowledge of Bangkok women regarding HPV and self-sampled HPV testing, and their attitudes towards testing. Materials and Methods: Thai women who had lived in Bangkok for more than 5 years, aged 25-to-65 years old, were invited to join the study. Participating women were asked to a complete self-questionnaire (Thai language), with literate assistance as needed. The questionnaire was divided into 3 parts: (I) demographic data, (II) knowledge and (III) attitudes towards self-sampled HPV testing. Before proceeding to Part III of the questionnaire, a 15-minute educational video of self-sampled HPV testing was presented to all participants. Results: Among 2,810 women who answered the questionnaires, 33.7% reported that they did not know about HPV. The characteristic features of these women were older age (> 50 years), lower income (< 600 USD/month), unemployed status, and non-attendees at cervical cancer screening. Only small numbers of women (4.6%) responded that they had heard about self-sampled HPV testing. After having information, 59.6% would not use the self-sampled HPV testing as a method of cervical cancer screening (non-acceptance). Factors significantly associated with the non-acceptance were older age, lower income, having no knowledge about HPV or self-collected HPV testing, a perception that the testing was unreliable and a concern that they might not be able to perform it correctly. Conclusions: Nearly half and almost all Bangkok women did not know about HPV and self-sampled HPV testing, respectively. Approximately 60% of Bangkok women refused to do the self-sampled HPV testing. Significant negative attitudes were concerns that the testing would be unreliable and a lack of confidence to perform the procedure correctly. Education about HPV and self-sampled HPV testing, ease of the procedure, or the testing models may increase rate of acceptability or positive attitudes. -
Mellatyar, Hassan;Talaei, Sona;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl 2453
Background: Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. Materials and Methods: The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. Results: Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. Conclusions: PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent. -
Mandaliya, Hiren;Ansari, Zia;Evans, Tiffany;Oldmeadow, Christopher;George, Mathew 2459
Background: Cancer treatments can have long-term physical, psychological, financial, sexual and cognitive effects that may influence the quality of life. These can vary from urban to rural areas, survival period and according to the type of cancer. We here aimed to describe demographics and psychosocial analysis of cancer survivors three to five years post-treatment in rural Australia and also assess relationships with financial stress and quality of life domains. Materials and Methods: In this cross-sectional study, 65 participants visiting the outpatient oncology clinic were given a self-administered questionnaire. The inclusion criteria included three to five years post-treatment. Three domains were investigated using standardised and validated tools such as the Standard Quality of Life in Adult Cancer Survivors Scale (QLACS) and the Personal and Household Finances (HILDA) survey. Included were demographic parameters, quality of life, treatment information and well-being. Results: There was no evidence of associations between any demographic variable and either financial stress or cancer-specific quality of life domains. Financial stress was however significantly associated with the cancer-specific quality of life domains of appearance-related concerns, family related distress, and distress related to recurrence. Conclusions: This unique study effectively points to psychosocial aspects of cancer survivors in rural regions of Australia. Although the majority of demographic characteristics were not been found to be associated with financial stress, this latter itself is significantly associated with distress related to family and cancer recurrence. This finding may be of assistance in future studies and also considering plans to fulfil unmet needs. -
Rafiemanesh, Hosein;Mohammadian-Hafshejani, Abdollah;Ghoncheh, Mahshid;Sepehri, Zahra;Shamlou, Reza;Salehiniya, Hamid;Towhidi, Farhad;Makhsosi, Behnam Reza 2465
Background: This study aimed to investigate the standardized incidence and mortality rate of colorectal cancer and its relationship with the human development index (HDI) across the world in 2012. Materials and Methods: This ecologic study was conducted for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its components. Data for SIR and SMR for every country for the year 2012 were obtained from the global cancer project. We used a bivariate method for assessment of the correlation between SIR and SMR and HDI. Statistical significance was assumed at P<0.05. Statistical analyses were performed using SPSS (Version 22.0, SPSS Inc.). Results: Countries with the highest SIR of colorectal cancer in the world in 2012, were Republic of Korea, Slovakia, Hungary and countries with the highest SMR were Hungary, Croatia and Slovakia. The correlation between SIR of colorectal cancer and the HDI was 0.712 ($P{\leq}0.001$ ), with life expectancy at birth 0.513 ($P{\leq}0.001$ ), with mean years of schooling 0.641 ($P{\leq}0.001$ ) and with level of income per each person of the population 0.514 (P=0.013). In addition, the correlation between SMR of colorectal cancer and the HDI was 0.628 ($P{\leq}0.001$ ), with life expectancy at birth 0.469 ($P{\leq}0.001$ ), with mean years of schooling 0.592 ($P{\leq}0.001$ ) and with level of income per each person of the population 0.378 (P=0.013). Conclusions: The highest SIR and SMR of colorectal cancer was in the WHO Europe region. There was a positive correlation between HDI and SIR and SMR of colorectal cancer. -
Komatsuda, Akari;Matsumoto, Kazuhiro;Miyajima, Akira;Kaneko, Gou;Mizuno, Ryuichi;Kikuchi, Eiji;Oya, Mototsugu 2475
Background: Laparoscopic partial nephrectomy is one of the major surgical techniques for small renal masses. However, it is difficult to manage cutting and suturing procedures within acceptable time periods. To overcome this difficulty, we applied a three-dimensional (3D) video system with laparoscopic partial nephrectomy, and evaluated its utility. Materials and Methods: We retrospectively enrolled 31 patients who underwent laparoscopic partial nephrectomy between November 2009 and June 2014. A conventional two-dimensional (2D) video system was used in 20 patients, and a 3D video system in 11. Patient characteristics and video system type (2D or 3D) were recorded, and correlations with perioperative outcomes were analyzed. Results: Mean age of the patients was$55.8{\pm}12.4$ , mean body mass index was$25.7{\pm}3.9kg/m^2$ , mean tumor size was$2.0{\pm}0.8cm$ , mean R.E.N.A.L nephrometry score was$6.9{\pm}1.9$ , and clinical stage was T1a in all patients. There were no significant differences in operative time (p=0.348), pneumoperitoneum time (p=0.322), cutting time (p=0.493), estimated blood loss (p=0.335), and Clavien grade of >II complication rate (p=0.719) between the two groups. However, warm ischemic time was significantly shorter in the 3D group than the 2D group (16.1 min vs. 21.2min, p=0.021), which resulted from short suturing time (9.1 min vs. 15.2 min, p=0.008). No open conversion occurred in either group. Conclusions: A 3D video system allows the shortening of warm ischemic time in laparoscopic partial nephrectomy and thus may be useful in improving the procedure. -
Imran, Muhammad;Sayedalamin, Zaid;Alsulami, Salhah S;Atta, Magdi;Baig, Mukhtiar 2479
Background: This study explored the knowledge and awareness about colorectal cancer (CRC) among undergraduate students of one of the leading universities in Saudi Arabia, along with the mode of information access. Materials and Methods: The present cross-sectional study was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, among students of different faculties. The study questionnaire, containing 28 items, was adapted from surveys identified in the relevant literature. The CRC awareness questionnaire consisted of an awareness section (early CRC signs and symptoms, and risk factors) and a knowledge section. The data were analyzed using the SPSS version 21.0. Results: A total of 525 undergraduate students participated in the study. The majority were females (63.0%) and approximately half (56.8%) were medical students. The majority of the students (82.3%) were aware of CRC, and 68% thought that CRC is a preventable disease. Regarding colorectal cancer screening tests, only one-third of students (33%) had actual knowledge, while the majority of the students (77.0%) thought that there are tests which help in early detection. Only 4% of the participants had a family history of CRC. The majority of the participants (84%) thought that CRC is a disease that can be cured. Almost 50-60% participants had good awareness level regarding risk factors, and signs and symptoms. Regarding knowledge, participant responses varied for family history (52%), age (59%), chronic infection of the colon (72%), obesity and lack of exercise (66%). More than one-third of the students had received information material regarding CRC from their curriculum followed by social media (20.4%), and nearly 40% from other sources such as TV, hospital and mass media. Female participants had significantly better awareness in a few questions regarding CRC awareness as compared to their male counterparts. There was a significant difference observed between medical and non-medical students (p<0.001) in overall score of awareness and knowledge about CRC while no significant difference found in gender-wise comparison. Conclusions: Knowledge and awareness of students about CRC were not up to the mark. Medical students and female students had better knowledge in a few areas, but the overall situation is dismal. -
Rehman, Aziz Ur;Ali, Farhad;Ali, Mashhood;Alam, Ibrar;Khan, Abdul Wali 2485
The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. HCC is the sixth most common cancer and the third leading cause of cancer related death overall. Hepatitis C is a major risk factor and HCV is a rapid spreading virus which has become a problem globally, including in Pakistan. Interferon alpha therapy is used against HCV disease to regulate cell reproduction and to boost the immune system. In minute amounts interferon alpha is produced naturally by the immune system in HCV patients in response to hepatitis C virus and binds to receptors in the target cells and starts transcription of 20-30 genes due to which it develops an antiviral influence. Interferon is also administered artificially to overcome HCV disease and remove the biological effect of the virus from the infected site. The use of interferon or Peg-IFN plus Ribavirin treatment is also associated with adverse effects on body. For the current study, a convenient sample of 156 HCV positive patients of both males and females were taken. To collect blood CP and ALT, a reduction of level data and other important information were collected from the patients at regular intervals. Findings were 11.4 % in the red blood cells (RBC), 9.64 % in the total leukocyte count (WBC), 8.4 % in the hemoglobin levels (HB), 30.3 % in the platelet (Plt) count in both sexes. There was significant reduction in ALT levels due to Pegylated interferon plus ribavirin therapy. Hence strict haemotological monitoring of blood CP and ALT levels is necessary at regular intervals to reduce severe side effects which may lead to morbidity and mortality. -
Rathika, Chinniah;Murali, Vijayan;Dhivakar, Mani;Kamaraj, Raju;Malini, Ravi Padma;Ramgopal, Sivanadham;Balakrishnan, Karuppiah 2491
Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; p<$3.5{\times}10^{-4}$ ), DRB1*14-DQB1*0501 (OR=6.51; p<0.039) and A*11-B*07 (OR=3.95; p<0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; p<0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions${\beta}9$ and${\beta}37$ and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India. -
Shahbazi, Mahsa;Yari, Kheirollah;Rezania, Niloufar 2499
Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. Materials and Methods: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. Results: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4,$THR{\beta}$ , mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. Conclusions: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations. -
Erenel, Hakan;Bese, Tugan;Sal, Veysel;Demirkiran, Fuat;Arvas, Macit 2507
Purpose: To study the diagnostic accuracies of serum human epididymis protein 4 (HE-4) levels, virtual organ computer-aided analysis (VOCAL) parameters and endometrial volume in endometrial cancer cases. Materials and Methods: One hundred and seven patients (37 with endometrial cancer and 70 with benign endometrial pathology) were included in this study. VOCAL parameters and serum HE-4 levels were compared between the groups. Results: Area under the curve (AUC) values were 0.702, 0.658, 0.706 for vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI), respectively. A cut off value of 0.568 for VI demonstrated 70% sensitivity, 72% specificity, 56% positive predictive value (PPV) and a81% negative predictive value (NPV). A cut off value of 25.8 for showed a senitivith of 70% and a specificity of 58% with aPPV of 46% and NPV of 78%, and with a cut off value of 0.12 for VFI 70%, 69%, 54% and 81%, respectively. The area under the curve for HE-4 was 0.814. A cut off value of 458 pmol/L was predictive of malignancy with 86% sensitivity and 63% specificity. Conclusions: VOCAL parameters and serum HE-4 levels were statistically significantly higher in the endometrial cancer patients. Serum HE-4 levels provided a greater sensitivity compared to power doppler angiography for predicting malignancy or benign endometrial pathology. -
Benhassine, Adel;Khadhra, Hajer Ben;Khiari, Houyem;Hsairi, Mohamed;Elgaaied, Amel Benammar 2513
Background: In 2008, non-Hodgkin lymphoma ranked tenth among other malignancies worldwide with an incidence of around 5 cases per 100,000 in both genders. The latest available rates in Tunisia are from 2006. Materials and Methods: This study aimed to provide an update about NHL incidence for 2009 and its trend between 1998 and 2009 as well as a projection until 2024, using data from the Salah Azaiz Institute hospital registry and the Noth Tunisia cancer registry. Results: In 2009, the NHL incidence in the north of Tunisia was 4.03 cases per 100,000, 4.97 for men and 3.10 for women. Diffuse large B-cell lymphoma (DLBCL) accounted for 63.2% of all NHL subtypes. Between 1998 and 2009, the overall trend showed no significant change. When we compared the trend between two periods (1998-2005 and 2005-2009), joinpoint regression showed a significant decrease of NHL incidence in the first period with an annual percentage change (APC) of -6.7% (95% CI:[-11.2%;-2%]), then the incidence significantly increased from 2005 to 2009 with an APC of 30.5% (95% CI: [16.1%; 46.6%]. The analyses of the different subtype trends showed a significant decrease in DLBCL incidence between 1998 and 2000 (APC:-21.5; 95% CI: [-31.4%;-10.2%]) then the incidence significantly increased between 2004 and 2007 (APC: 18.5; 95% CI: [3,6%;35.5%]). Joint point analysis of the age-period-cohort model projection showed a significant increase between 2002 and 2024 with an APC of 4.5% (%95 CI: [1.5%; 7.5%]). The estimated ASR for 2024 was 4.55/100 000 (95% CI: [3.37; 6.15]). Conclusions: This study revealed an overall steady trend in the incidence of NHL in northern Tunisia between 1998 and 2009. Projection showed an increase in the incidence in NHL in both genders which draw the attention to the national and worldwide burden of this malignancy. -
Villegas-Ruiz, Vanessa;Moreno, Jose;Jacome-Lopez, Karina;Zentella-Dehesa, Alejandro;Juarez-Mendez, Sergio 2519
There are several existing reports of microarray chip use for assessment of altered gene expression in different diseases. In fact, there have been over 1.5 million assays of this kind performed over the last twenty years, which have influenced clinical and translational research studies. The most commonly used DNA microarray platforms are Affymetrix GeneChip and Quality Control Software along with their GeneChip Probe Arrays. These chips are created using several quality controls to confirm the success of each assay, but their actual impact on gene expression profiles had not been previously analyzed until the appearance of several bioinformatics tools for this purpose. We here performed a data mining analysis, in this case specifically focused on ovarian cancer, as well as healthy ovarian tissue and ovarian cell lines, in order to confirm quality control results and associated variation in gene expression profiles. The microarray data used in our research were downloaded from ArrayExpress and Gene Expression Omnibus (GEO) and analyzed with Expression Console Software using RMA, MAS5 and Plier algorithms. The gene expression profiles were obtained using Partek Genomics Suite v6.6 and data were visualized using principal component analysis, heat map, and Venn diagrams. Microarray quality control analysis showed that roughly 40% of the microarray files were false negative, demonstrating over- and under-estimation of expressed genes. Additionally, we confirmed the results performing second analysis using independent samples. About 70% of the significant expressed genes were correlated in both analyses. These results demonstrate the importance of appropriate microarray processing to obtain a reliable gene expression profile. -
Sensitising cancer cells and at the same time desensitizing normal cells is a double task in cancer management. Agents which can combat the debilitating side effects of cancer therapeutics and simultaneously synergize with anticancer agents in specifically targeting cancer cells are needed. Selenium, a proven anticarcinogen, gains due importance in terms of its efficacy to combat the side effects of cancer therapy. This study is a comparative analysis of the chemoprotective effects of selenium compounds, methyl selenol (generated from organic selenomethionine (5mmol/L ; METase 40U/L)) and sodium selenite (inorganic form)(
$30{\mu}M$ ) in peripheral blood human lymphocytes exposed to cisplatin and mitomycin. Biochemical alterations occurring in many cells during apoptosis include loss of plasma membrane phospholipid asymmetry, DNA fragmentation, and activation of caspase-3. The present study demonstrated that the selenium metabolite and selenite are efficient in protecting lymphocytes undergoing DNA damage and exerted their activity by reducing caspase 3 expression. Interestingly organic methylselenol (MeSe) was found to offer more protective effects compared to inorganic selenite (SeL), by reducing the induction of apoptosis by the cytotoxic agents. This suggests that MeSe and to a lesser extent selenite might have potential for assessment in clinical trials and could be considered as strong candidates in pharmacogenomics or in the nutriprotective arena. -
Hernowo, Bethy S;Suryanti, Sri;Wibisono, Fennisia 2535
Background: Most of the cervical cancer patients, including those with cervical adenocarcinomas, come at advanced stage in the developing world so its mortality is high. Radiotherapy is one of the treatment modality for advanced stage cervical adenocarcinomas, but its efficacy depends on several prognostic factors such as the stage, histopathology, presence of organ dysfunction and expression of cellular biology markers mainly involve in cell proliferation such as the epidermal growth factor receptor (EGFR). Some research indicates that activation of EGFR in malignancy (including cervical cancer) correlates with aggressive behavior, a poor prognosis and decreasing sensitivity of radiotherapy. However, the combination between targeted therapies and radiotherapy are innovative approaches which may provide a good result. This study aimed to assess any correlation between expression of EGFR and response to radiotherapy in cervical adenocarcinoma cases. Materials and Methods: A total of 32 women were registered in a retrospective study period January 2007 and May 2014. Paraffin blocks from these patients were processed by classical histological techniques and for immunohistochemical staining of EGFR, scoring being accomplished according to the immunoreactive scoring (IRS) of Remmele and Stegner. Results: Among the studied molecular factors, there was significant correlation expression of EGFR with poor response to radiotherapy (p=0.0001). Conclusions: The result of this study showed a significant correlation between expression of EGFR and sensitivity of radiation in cervical adenocarcinoma cases. Further research is necessary to obtain information about new therapeutic management. -
Aziz, Ashraf Omar Abdel;Omran, Dalia;Nabeel, Mohamed Mahmoud;Elbaz, Tamer Mahmoud;Abdelmaksoud, Ahmed Hosni;Attar, Inas El;Shousha, Hend Ibrahim 2539
Background: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. Materials and Methods: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. Results: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (p<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (p<0.001). Conclusions: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended. -
Hussain, Mudassar;Waqas, Omer;Hassan, Usman;Loya, Asif;Akhtar, Noreen;Mushtaq, Sajid;Yusuf, Muhammad Aasim;Syed, Aamir Ali 2545
Background: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left-sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan. Materials and Methods: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer. Parameters including age, gender, TNM stage, histological features and clinical outcome were analyzed. Results: The patients with right-sided colon cancer were significantly older as compared to their counterparts with left-sided cancer. They presented with a lumbar mass rather than symptoms of obstruction and perforation as seen in left-sided colon cancers, and the histology showed higher percentage of poorly differentiated tumors with advanced pT stage. Moreover, Crohn's-like reactions, intra tumoral lymphocyte responses and other poor prognostic factors like lymph vascular invasion and perineural invasion were more common in right-sided cancers. Conclusions: We found that right- and left-sided colon cancers are different from each other in terms of clinical presentation, histology and clinical behavior. Right-sided colon cancers are more aggressive and are associated with poorer clinical outcome as compared to left sided colon cancers in our population. -
Nazzal, Zaher;Sholi, Hisham;Sholi, Suha;Sholi, Mohammad;Lahaseh, Rawya 2549
Background: Early detection remains the cornerstone of breast cancer control in terms of outcome and survival. Thus far the only breast cancer screening method proven effective is mammography. The awareness of female health care workers (HCW) about breast cancer prevention is of vital importance, as their beliefs and behavior may have a major impact on other women. This study was designed to assess mammography screening uptake among female healthcare workers at primary healthcare centers, and to identify the primary motivators and barriers that affect uptake results. Materials and Methods: A cross sectional study design was used to assess mammography screening by 299 female healthcare workers who completed a self-administered questionnaire that assessed demographics, screening uptake, motivators and barriers. Results: The mean age was 46 years (within age of risk). The majority (95.1%) demonstrated adequate knowledge about breast cancer and mammography screening and 50% of the participants reported having at least one mammogram; however only 21% of them had regularly scheduled mammograms. The most frequent reported motivator was the perceived benefit that early detection of breast cancer is important for its management (89.6%), followed by the belief that mammography can detect breast cancer before its symptoms appear (84.4%). On the other hand, the most frequent barrier reported was being busy (46.7%), followed by the lack of perceived susceptibility (41.5%). Conclusions: Mammography screening was found to be sub-optimal in a population of HCW's with 50 % stating that they received a mammogram at least once, and a minority reported regular screening. There is a pressing need for educational programs aimed at removing the barriers that limit compliance with recommendations for mammography screening, and to emphasize the importance of early detection in breast cancer treatment. Ensuring the availability and accessibility of screening services, particularly for healthcare workers within their work settings are other important factors that would improve the acceptance and compliance for mammography screening programs. -
Chong, Vui Heng;Telisinghe, Pemasari Upali;Tan, Jackson;Abdullah, Muhamad Syafiq;Chong, Chee Fui 2555
Background: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. Materials and Methods: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+were considered positive. Results: Our study included 103 cases (66 males and 37 females) with a mean age of$65.1{\pm}14.8$ years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older ($70.6{\pm}19.3$ years old) than the negative cases ($64.2{\pm}13.8$ , p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). Conclusions: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis. -
Himani, Bhankar;Meera, Sikka;Abhimanyu, Sharma;Usha, Rusia 2559
Purpose: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Materials and Methods: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. Results: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, p<0.001) and was significantly higher (p<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%).$MVD/mm^2$ was also significantly (p<0.0001) higher in myeloma patients (range$62-237/mm^2$ , mean$178.0/mm^2$ ) than controls (range$5.2-50/mm^2$ , mean$18.3/mm^2$ ). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine,${\beta}2$ microglobulin and skeletal lesions. Conclusions: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy. -
Kaewpitoon, Soraya J;Rujirakul, Ratana;Wakkuwattapong, Parichart;Matrakool, Likit;Tongtawee, Taweesak;Panpimanmas, Sukij;Kujapun, Jirawoot;Norkaew, Jun;Photipim, Mali;Ponphimai, Sukanya;Chavengkun, Wassugree;Kompor, Pontip;Padchasuwan, Natnapa;Sawaspol, Sudaporn;Phandee, Mattika Chaimeerang;Phandee, Wichan;Phanurak, Wassana;Kaewpitoon, Natthawut 2565
A cross-sectional survey was conducted among 730 participants from 4 rural districts of Nakhon Ratchasima province, Thailand, with a reported high incidence of liver fluke infection. This study was aimed to examine and evaluate the nutritional status in relation to Opisthorchis viverrini infection. Participants were purposive selected from Chum Phuang, Mueang Yang, Bua Yai, and Kaeng Sanam Nang districts. Stool samples were prepared by Kato Katz technique and then assessed by microscopy. Anthropometry was evaluated according to the body mass index from weight and height. Descriptive statistics and Spearman rank correlation coefficients were used to evaluate the association between the nutritional status and O. viverrini infection. Of 1.64% infected with O. viverrini the highest proportions were found in age groups${\geq}61$ and 41-50 years old, Mueang Yang district. The majorities of participants had normal weight (32.2%), followed by class II obesity (28.1 %), class I obesity (21.8%), underweight (10.3%), and class III obesity (8.63%). Nutritional status with class II obesity (rS=0.639, p<0.01) and class I obesity (rS=0.582, p<0.05), had moderately statistical significant correlations with O. viverrini infection. Meanwhile, normal weight (rS=0.437, p<0.05) and class III obesity (rS=0.384, p<0.05) demonstrated lower statistical significance. These findings raise the possibility that infection with O. viverrini may contribute to fat deposition and thereby have long-term consequences on human health. Further studies are needed to better understand whether O. viverrini contributes directly to fat deposition and possible mechanisms. -
Liu, Xi-Jun;Lin, Xiu-Tong;Yin, Yong;Chen, Jin-Hu;Xing, Li-Gang;Yu, Jin-Ming 2573
Objective: The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer. Methods: Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues. Results: The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose. Conclusions: The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices. -
Kesrouani, Carole;Ghorra, Claude;Rassy, Marc;Kourie, Hampig Raphael;Kattan, Joseph 2579
Background: Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors. Materials and Methods: This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in$H\hat{o}tel$ Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup. Results: Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2. Conclusions: The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature. -
Objectives: To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. Methods: Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. Results: There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. Conclusions: Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted.
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Siddique, Sabeehuddin;Tariq, Kanwal;Rafiq, Sobia;Raheem, Ahmed;Ahmed, Rashida;Shabbir-Moosajee, Munira;Ghias, Kulsoom 2587
Background: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged${\leq}45$ years) with controls (>45 years). Materials and Methods: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features. Results: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls. Conclusions: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms. -
Background: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. In this study, we retrospectively evaluated the clinicopathological features, treatment options and overall survival in Kurdish MBC cases. Materials and Methods: Seventeen MBC were referred to Department of Radiation Oncology in Imam Reza Hospital, Kermanshah, Iran, between 2010 and 2016. Immunohistochemical analysis was performed for ER, PR and Her2 biomarkers and FISH for those with Her2 2+. Median follow-up period was 30 months (2-65 months). We excluded from the study patients who did not have follow-up after initial diagnosis. Treatment methods were chemotherapy, radiotherapy, hormonal therapy, target therapy and palliative care. Survival was estimated by the Kaplan Meier method (Prism 5). Results: The mean age at diagnosis was
$49.24{\pm}17$ years (range, 24-85 years). Grade II was the most grade in MBC (65%). Fourteen patients (82%) had invasive ductal carcinoma, one (6%) had ductal carcinoma in situ and 2 (12%) had invasive papillary. ER, PR and Her2 were significantly positive in 14/17, 8/17 and 2/17 cases, respectively. The treatment included modified radical mastectomy for most patients. Chemotherapy with TAC and CEF regimens was delivered to 15/17 cases. Tamoxifen therapy was delivered to 14/17 cases. Three stage IV patients received Avestin and two with Her2 3+ were given Trastuzumab (Herceptin). Patients received adjuvant radiotherapy following surgery and chemotherapy. The site of metastasis was the bone in 2 cases, lung in 1 case and liver in 1 case. Zoledronic acid (Zometa) was prescribed for patients with bone metastasis. Five-year overall survival rate was 64%. Conclusions: MBC is rare. Thus, we need larger studies are in collaboration with several research centers in the field of breast cancer. ER positive, grade II of invasive ductal carcinoma, stage II and right side happened more with MBC. Overall survival is similar to other studies. -
Cymbaluk-Ploska, Aneta;Chudecka-Glaz, Anita;Surowiec, Anna;Pius-Sadowska, Ewa;Machalinski, Boguslaw;Menkiszak, Janusz 2597
Ovarian cancer is a highly malignant neoplasm with high mortality rates. Research to identify markers facilitating early detection has been pursued for many years. Currently, diagnosis is based on the CA 125 and HE4 markers, as well as the ROMA algorithm. The search continues for new proteins that meet the criteria of good markers A total of 90 patients were included in the present study, allocated into: group 1, ovarian cancer, with 29 patients; group 2, endometrial cysts, with 30s; and group 3, simple ovarian cysts, with 31. Following histopathological verification, the CA 125, HE4, and metalloproteinase 3 (MMP3) levels were determined and the ROMA algorithm was calculated for all patients. The mean concentrations of all determined proteins, CA 125, HE4, and MMP3, as well as the ROMA values, were significantly higher in group 1 (ovarian cancer) compared to group 3 (simple ovarian cysts). The highest significant differences for the CA 125 levels (p<0.000001) and ROMA (p<0.000001) values were observed in postmenopausal women. For HE4, statistical significance was at the level of p=0.00001 compared to p=0.002 for MMP3. For the differentiation between ovarian cancer and endometrial cysts, the respective AUC ratios were obtained for CA 125, HE4, and MMP3 levels, as well as the ROMA values ( 0,93 / 0,96 / 0,75 / 0,98). After removing the post-menopausal patients, the MMP3 AUC value for ovarian cancer vs. benign ovarian cysts increased to 0.814. For post-menopausal women, the MMP3 AUC value for ovarian cancer vs. endometrial cysts was 0.843. As suggested by the results above, both the CA 125 and HE4 markers, as well as the ROMA algorithm, meet the criteria of a good diagnostic test for ovarian cancer. MMP3 seems to meet the criteria of a good diagnostic test, particularly in postmenopausal women; however, it is not superior to the tests used to date. -
Mohammed, Noorjahan;Chandran, Priscilla Abraham;Kandregula, Madhavi;Mattaparthi, Ratna Deepika;Gundeti, Sadasivudu;Volturi, Jyotsna;Darapuneni, Radhika;Raju, Sree Bhushan;Dattatreya, Palanki Satya 2605
The International Myeloma Working Group considers the serum free light chain (SFLC) assay to be an adjunct to traditional tests. Apart from the FLC ratio, the absolute values of individual free light chains also are gaining importance as they appear to be more relevant in certain clinical settings. Automated assays are available for their determination. As laboratories put new test systems into use catering to different disease populations, they are required by accreditation and certification bodies to verify or establish performance specifications, including reference intervals (RIs) representative of their population. Our aim was to establish local RIs for SFLC in a multicentre representative healthy population using a robust method. There was no significant relationship between SFLC levels and age, gender and creatinine levels. The 95% RI for${\kappa}SFLC$ was 4.81 to 33.86mg/L, for${\lambda}$ SFLC was 5.19 to 23.67mg/L and for${\kappa}/{\lambda}SFLC$ was 0.36 to 2.33, significantly higher than the values given by the manufacturer. The${\kappa}/{\lambda}$ SFLC ratio at 2.23, covering 100% of the data, showed 72% sensitivity (95% CI=39.0 - 94.0), 100% specificity (95% CI=71.5 - 100.0), 100% PPV (95% CI=21.5 - 100.0), 95% NPV (95% CI=75.4 - 99.9), and 79% accuracy (95% CI=56.0 - 93.0). In the patient group, kit RI for${\kappa}/{\lambda}$ SFLC ratio classified 45.5% (n=5) as positive vs 9.1% (n=1) positive by the study RI, while the kit RI for kappa FLC classified 90.9% (n=10) as positive vs 54.5% (n=6), indicating increased probability of false positive test results with the kit RI when applied to our patient population. Appropriate and specific reference intervals and criteria values result in fewer false-positive and false-negative results which means fewer wrong or missed diagnoses. -
Mathaiyan, Jayanthi;Jain, Tanvi;Dubashi, Biswajit;Batmanabane, Gitanjali 2611
Background: Medication errors are common but most often preventable events in any health care setup. Studies on medication errors involving chemotherapeutic drugs are limited. Objective: We studied three aspects of medication errors - prescription, transcription and administration errors in 500 cancer patients who received ambulatory cancer chemotherapy at a resource limited setting government hospital attached cancer centre in South India. The frequency of medication errors, their types and the possible reasons for their occurrence were analysed. Design and Methods: Cross-sectional study using direct observation and chart review in anmbulatory day care unit of a Regional Cancer Centre in South India. Prescription charts of 500 patients during a three month time period were studied and errors analysed. Transcription errors were estimated from the nurses records for these 500 patients who were prescribed anticancer medications or premedication to be administered in the day care centre, direct observations were made during drug administration and administration errors analysed. Medical oncologists prescribing anticancer medications and nurses administering medications also participated. Results: A total of 500 patient observations were made and 41.6% medication errors were detected. Among the total observed errors, 114 (54.8%) were prescription errors, 51(24.5%) were transcribing errors and 43 (20.7%) were administration errors. The majority of the prescription errors were due to missing information (45.5%) and administration errors were mainly due to errors in drug reconstitution (55.8%). There were no life threatening events during the observation period since most of the errors were either intercepted before reaching the patient or were trivial. Conclusions: A high rate of potentially harmful medication errors were intercepted at the ambulatory day care unit of our regional cancer centre. Suggestions have been made to reduce errors in the future by adoption of computerised prescriptions and periodic sensitisation of the responsible health personnel. -
Background: Cancer is a worldwide health problem. Arabic countries are also concerned and the burden linked to the pain related to cancer is dsiquieting. The aim of this study is to set the panel of valid tools for assessing the multiple dimensions of pain in arabic speaking countries. Materials and Methods: A systematic review on PubMed, Scopus, and Science Direct databases was conducted using as key words cancer, pain and arabic speaking population. The content of 51 articles was studied and nine articles were retained for their relevance for the issue. Results: We founf eight different questionnaires. MSAS-Leb, EORTC-C30, EORTC-BR23, MDASI, FLIC, and COOP/WONCA are dedicated to physical and psychological dimensions of pain. BPI is centered on direct items for measuring pain accurately. ABQ-II is the unique tool focusing on barriers to cancer pain control. All tools are confirmed valid and reliable in the context studied for assessing pain and disconfort linked to cancer. Conclusions: This panel of questionnaires covers all relevant aims for assessing pain in diferent arabic speaking countries with the recommendation of a cultural adaptation to local arabic languages.
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Na, Ann-Yae;Heo, Jin-Chul;Sung, Jin Young;Lee, Jong-Ha;Kim, Yoon-Nyun;Kim, Dae-Kwang 2625
ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (${\Delta}27$ ) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and${\Delta}27$ was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans. -
Malik, Saima Shakil;Kazmi, Zehra;Fatima, Iffat;Shabbir, Riffat;Perveen, Shagufta;Masood, Nosheen 2629
Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; P< 0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; P<0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor. -
Boonyarat, Chantana;Yenjai, Chavi;Reubroycharoen, Prasert;Waiwut, Pornthip 2637
Tumor necrosis factor ($TNF-{\alpha}$ ), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of$TNF-{\alpha}$ are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on$TNF-{\alpha}$ -induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (p<0.01), a concentration of$10{\mu}M$ significantly inducing cell death (p<0.01). In combination with$TNF-{\alpha}$ , nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized$TNF-{\alpha}$ -induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance$TNF-{\alpha}$ -mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway. -
Nisa, Hoirun;Hirata, Akie;Kohno, Michiko;Kiyohara, Chikako;Ohnaka, Keizo 2643
Background: High-sensitivity C-reactive protein (hsCRP) levels are lower in Japanese compared with Western subjects. Since it is uncertain whether hsCRP is a potent predictor of mortality at low CRP concentrations, the present study examined associations with all-cause and cause-specific mortality in a large population of Japanese. Materials and Methods: Subjects were 4,737 men and 6,343 women aged 49-76 years participating in the baseline survey of an ongoing cohort study of lifestyle-related diseases between February 2004 and July 2006. Hazard ratios for all-cause and cause-specific mortality associated with hsCRP levels were estimated using Cox proportional hazards regression. Results: A total of 436 all-cause deaths occurred during a median follow-up of 8 years. The main cause of death was cancer. In men, hsCRP levels were positively associated with the risk of all-cause mortality as well as deaths from cancer and cardiovascular disease (CVD). All-cause mortality hazards for the 2nd (0.34-0.84 mg/L) and the 3rd (${\geq}0.85mg/L$ ) tertiles of hsCRP were 1.27 (95% confidence interval [CI], 0.93-1.73) and 1.75 (1.30-2.37), respectively (p for trend=0.001). In women, increased risk of all-cause and cause-specific mortality associated with elevated hsCRP levels was observed, but the associations were not statistically significant. Conclusions: HsCRP may be an independent predictor of all-cause, cancer and CVD mortality in apparently healthy Japanese men, but not women. The differential effect of hsCRP in predicting mortality risk by sex warrants further investigation. -
Senhaji, Nadia;Louati, Sara;Chbani, Laila;Bardai, Sanae El;Mikou, Karima;MAAROUFI, Mustafa;Benzagmout, Mohammed;Faiz, Mohammed Chaoui El;Marie, Yannick;Mokhtari, Karima;Idbaih, Ahmed;Amarti, Afaf;Bennis, Sanae 2649
Background: Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. Materials and Methods: IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. Results: The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. Conclusions: Our results confirmed other studies published earlier for other populations with some small discrepancies. -
Missaoui, Nabiha;Abdelkarim, Soumaya Ben;Mokni, Moncef;Hmissa, Sihem 2655
Background: Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki-67, p53, Bcl-2, PSA, HER2, E-cadherin,$p21^{WAF1/Cip1}$ ,$p27^{Kip1}$ and$p16^{ink4a}$ in prostate cancer. Materials and Methods: We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. Results: Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin,$p21^{WAF1/Cip1}$ ,$p27^{Kip1}$ and$p16^{ink4a}$ was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and$p27^{Kip1}$ (p=0.04). Conclusions: The p53, Bcl-2, Ki-67 and$p27^{Kip1}$ proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer. -
Jahanafrooz, Zohreh;Motameh, Nasrin;Bakhshandeh, Behnaz 2661
Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of the examined cells under silibinin treatment. P27 mRNA expression upregulated in T47D and MCF-10A cells under silibinin treatment. PTEN mRNA in T47D and P21 and P27 mRNAsin MCF-7 were not affected by silibinin. These results suggest that silibinin has mostly different inhibitory effects in breast cancer cells and might be an effective anticancer agent for some cells linked to influence on cell cycle progression. -
Bekmukhambetov, YZ;Balmagambetova, SK;Jarkenov, TA;Nurtayeva, SM;Mukashev, TZ;Koyshybaev, AK 2667
Background: Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Cancer of the cervix is the third or even the second most common cancer in women worldwide, more than 85% of the cases occurring in developing countries, such as China and India, including the Republic of Kazakhstan. The purpose was to determine the HPV type distribution to evaluate efficacy of vaccination and adjust cancer prevention strategy in Western Kazakhstan in the future. Materials and Methods: A retrospective analysis was conducted of data obtained from PCR laboratories in 4 regional centers for the time period covering 12 months, 2013-2014, using AmpliSens$^{(R)}$ Real-Time PCR kits for HPV testing of 12 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). Results: A total of 1,661 persons were HPV tested within 2013-14, but a proprotion examined for 16 and 18 genotypes only (563) was not been included for statistic analysis of distribution and ratio of the most common genotypes. Males accounted for only a small number (N=90 in total). Conclusions: Total number of the HPV-positive appeared to be 26.0%, or 286 of N=1098. Types distribution was as follows: type 16 (10.7%), 39 (5.83%), 51 (5.27%), 31 (4.85%), 56 (4.58%), 18 (3.61%), 59 (2.64%), 58 (2.22%), 35 (1.94%), 33 (1.25%). Overall the HPV infection was highest in 16-29 years old (62.4%) and decreased with age. Total prevalence of the HR-HPVs amongst male population was 21.4% with top five types 16, 18, 39, 51, 31. Trends forcorrelations between Aktau site and type 33 (Cramer's V 0.2029), between Caucasian ethnicity and type 33 (Cramer's V .1716), and between European ethnicities in Uralsk and type 45 (Cramer's V .1752) were found. Of N 563 tested separately for 16 or 18 types, 13.6% were positive. As a whole, the distribution of 16/18 types had a ratio of 3.53:1. Given the vaccine-targeted type 16 is widely spread amongst this regional population, HPV immunization program of adolescent girls 10-13 years should be implemented appropriately. -
Leong, Lester Chee Hao;Sim, Llewellyn Shao-Jen;Jara-Lazaro, Ana Richelia;Tan, Puay Hoon 2673
Background: It is unclear as to whether the size ratio elastographic technique is useful for assessing ultrasound-detected ductal carcinoma-in-situ (DCIS) masses since they commonly lack a significant desmoplastic reaction. The objectives of this study were to determine the accuracy of this elastographic technique in DCIS and examine if there was any histopathological correlation with the grey-scale strain patterns. Materials and Methods: Female patients referred to the radiology department for image-guided breast biopsy were prospectively evaluated by ultrasound elastography prior to biopsy. Histological diagnosis was the gold standard. An elastographic size ratio of more than 1.1 was considered malignant. Elastographic strain patterns were assessed for correlation with the DCIS histological architectural patterns and nuclear grade. Results: There were 30 DCIS cases. Elastographic sensitivity for detection of malignancy was 86.7% (26/30). 10/30 (33.3%) DCIS masses demonstrated predominantly white elastographic strain patterns while 20/30 (66.7%) were predominantly black. There were 3 (10.0%) DCIS masses that showed had a co-existent bull's-eye sign and 7 (23.3%) other masses had a co-existent toothpaste sign, a strain pattern that has never been reported in the literature. Four out of 4/5 comedo DCIS showed a predominantly white strain pattern (p=0.031) while 6/7 cases with the toothpaste sign were papillary DCIS (p=0.031). There was no relationship between the strain pattern and the DCIS nuclear grade. Conclusions: The size ratio elastographic technique was found to be very sensitive for ultrasound-detected DCIS masses. While the elastographic grey-scale strain pattern should not be used for diagnostic purposes, it correlated well with the DCIS architecture. -
Kourie, Hampig Raphael;Ghorra, Claude;Rassy, Marc;Kesserouani, Carole;Kattan, Joseph 2679
Background: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in gastro-intestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NEN in a Lebanese population. Materials and Methods: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in$H\hat{o}tel$ Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site. Results: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC). Conclusions: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports. -
Putri, Herwandhani;Jenie, Riris Istighfari;Handayani, Sri;Kastian, Ria Fajarwati;Meiyanto, Edy 2683
A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV-0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with$IC_{50}$ values of$94.9{\mu}M$ and$49.0{\pm}0.2{\mu}M$ , respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent. -
Venezuela, Raul Fernando;Monetti, Marina Soledad;Kiguen, Ana Ximena;Frutos, Maria Celia;Mosmann, Jessica Paola;Cuffini, Cecilia Gabriela 2689
Background: Most studies of human papilloma virus (HPV) are aimed at the natural history of the infection and its relation to cancer; however, there are few studies to assess knowledge of the general population. Our aim was analyze the degree of knowledge of Argentinians about HPV infection and its prevention. Materials and Methods: We conducted a voluntary, anonymous and non-binding survey with 27 multiple-choice items, in twelve private and public establishments, selected to include a broad population in terms of education, age and gender. The survey consisted of three sections: individual characteristics of the volunteer, HPV infection basic knowledge, its prevention and the virus relationship with other cancers. Results: One thousand two hundred ninety seven volunteers aged 18 to 80 participated. The total number of correct answers was 45.1%. The correct answers for relationship HPV and cervical cancer was 62.1%. Almost 55% did not know about types of HPV that the vaccines for protection. Statistical analysis showed that women, single people, workers, the better educated, those who have had a STDs or HPV and receiving information through medical or educational establishments had greater knowledge of the topic. Only 0.2% of participants answered all questions correctly. Conclusions: Knowledge plays an important role in health care and the deficiency found in our population could influence the success of the measures taken in the fight against cervical cancer. In this regard, we believe it would be appropriate, not only to emphasize early diagnosis and vaccine implementation, but also incorporate new communication strategies, facilitating reception of accurate and precise information by all strata of society. -
Kandel, Bishnu Prasad;Singh, Yogendra Prasad;Ghimire, Bikal 2695
Background: Gastric cancer, the fifth most common malignancy in the world, usually affects older individuals but can occur in younger age groups. In this study we compared the clinicopathological profile of young patients of gastric cancer with that of older patients. Materials and Methods: It is a prospective study of gastric cancer patients treated over three year period (January 2012 to December 2014). Data of patients were obtained from the medical record. Clinical and pathological characters of younger patients (age 40 years or less) were compared with older patients (age more than 40 years). Results: There were total of 152 patients treated during the study period. Twenty patients (13.2%) were less than 40 years of age and 132 (86.8%) were older. The male to female ratio in younger patients was 1:1.5 whereas in older patients it was 1:0.6. In the younger age group 14 patients (70%) had poorly differentiated adenocarcinoma in contrast to 45% in the older age group (p<0.01). Some 55% of younger and 42% of older patients had stage IV disease at presentation and curative surgery was not possible. Palliative surgery for gastric outlet obstruction or bleeding from the tumor was performed on 25% and 21% respectively. Conclusions: Gastric cancer in young people aged less than 40 years has unique characters like female predominance, unfavorable tumor biology, and advanced stage at presentation. There should be a high index of suspicion of gastric cancer even in young patients. -
Khairy, Ahmed;Hamza, Iman;Shaker, Olfat;Yosry, Ayman 2699
Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. Aim: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. Materials and Methods: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30$treatment-na{\ddot{i}}ve$ chronic HCV, 25 post-HCV compensated cirrhosis and 23$treatment-na{\ddot{i}}ve$ HCC cases). Results: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (P<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. Conclusions: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC. -
Ding, Hui;Gui, Xian-Hua;Lin, Xu-Bo;Chen, Ru-Hua;Cai, Hou-Rong;Fen, Yan;Sheng, Yun-Lu 2705
Recent evidence haas indicated that meningioma-associate protein (MAC30) exhibits different expression patterns in various tumors. However, little is known about the value of MAC30 in human squamous cell carcinoma of lung (SQCLC). The purpose of our study was to investigate the expression of MAC30 and to explore its clinical significance in SQCLC patients. A total of 156 Chinese patients diagnosed with SQCLC were selected for this study. The expression of MAC30 in all tissues was confirmed by immunohistochemical staining. Quantitative real-time PCR was performed to analyze MAC30 mRNA expression in 32 cases of SQCLC patients with corresponding non-tumor lung tissues. We observed enhanced mRNA expression of MAC30 in SQCLC as compared to control samples. Further, elevated MAC30 protein expression was strongly associated with poor tumor differentiation, TNM stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression demonstrated poor overall survival. Multivariate analysis explicated that increased MAC30 expression was a valuable independent predictable factor for poor tumor differentiation and short survival in SQCLC patients. Our present study suggests that MAC30 may serve as a biomarker for poor tumor differentiation and outcomes of patients with SQCLC. -
Zhao, Tai-Yun;Tu, Jing;Wang, Yin;Cheng, Da-Wei;Gao, Xian-Kui;Luo, Hao;Yan, Bi-Chun;Xu, Xiao-Li;Zhang, Hong-Ling;Lu, Xing-Jun;Wang, Yao-Jun 2711
Background: Through search the possible randomized control trials, we make a renewed meta-analysis in order to assess the impact of aspirin in preventing the recurrence of colorectal adenoma. Materials and Methods: The Medicine/PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese biomedical literature service system (SinoMed) databases were searched for the related randomized controlled trials until to the April 2016. Three different authors respectively evaluated the quality of studies and extracted data, and we used the STATA software to analyze, investigate heterogeneity between the data, using the fixed-effects model to calculate and merge data. Results: 7 papers were included the renewed meta-analysis, among these studies, two pairs were identified as representing the same study population, with the only difference being the duration of follow-up. Thus there were only five papers included our meta-analysis, and one Chinese paper were also included the work. Results were categorized by the length of follow-up, different kinds of people, varied dose of oral aspirin. The relative of adenoma in patients taking aspirin vs placebo were 0.73 (95% CI 0.55-0.98, P=0.039) with 1 year follow up; 0.84 (95% CI 0.72-0.98, P=0.484) with greater than 1 year follow up; for the advanced adenoma, the RR 0.68 (95% CI 0.49-0.94, P=0.582),for one year; RR=0.75 (95% CI 0.52-1.07, P=0.552) for greater one year. Furthermore the white population could divided into two subgroups according to the different length of follow-up time. When the length of follow-up time less than 3-year, The RR of two subgroups respective were RR=0.86 (95% CI 0.76-0.98, P=0.332),$I^2=0%$ , RR=0.68 (95% CI 0.47-0.98, P=0.552),$I^2=64.6%$ , But with the extension of follow-up time greater than 2-year, with the white, oral aspirin without considering dose had no efficacy on preventing the recurrence of any adenoma, the RR was 0.86 (95% CI 0.71-1.05, P=0.302),$I^2=16.4%$ . Conclusions: This meta-analysis indicated that oral aspirin is associated with a remarkable decrease in the recurrence of any adenoma and advanced adenomas in patients follow-up for 1 year without concerning the dose of aspirin, but with the extension of follow-up time for greater than 1 year, oral aspirin can be effective on preventing the recurrence of any adenoma, but for the advanced adenoma, the result indicated that oral aspirin had no efficacy, According to the inclusion of ethnic groups, we also divided relevant papers into two subgroups as the yellow and white group. Then the follow-up time was less than 3 years, oral aspirin without considering the dose, had an significant efficacy on preventing the recurrence of any adenoma. But with the follow-up greater than 2 years, oral aspirin had no effect in the white. -
Shao, Juan;Fang, Peng-Hua;He, Biao;Guo, Li-Li;Shi, Ming-Yi;Zhu, Yan;Bo, Ping;Zhang, Zhen-Wen 2719
Circulatory miR-133a is a marker shared by several types of cancer. In this study we evaluated the feasibility of using miR-133a levels in gastric juice to screen for gastric cancer. A total of 204 samples of gastric juice and mucosa from gastric cancer, atrophic gastritis, gastric ulcer, superficial gastritis and healthy cases were collected by gastroscopy. The results showed that miR-133a levels in gastric juice and carcinoma tissues of patients with gastric cancer were significantly downregulated and positively correlated. Moreover, miR-133a in gastric juice has high operability, high reliability, high sensitivity, high specificity and relative stability, fit for clinical diagnosis of gastric cancer. -
Alfaifi, Mohammad Yahya;Saleh, Kamel Ahmed;El-Boushnak, Mohammed Atallah;Elbehairi, Serag Eldin I;Alshehri, Mohammed Ali;Shati, Ali Abdullah 2723
Cancer represent one of the most serious health problems and major causes of death around the world. Many anticancer drugs in clinical use today are natural products or derived from natural sources. Withania somnifera (L.) Dunal is a small shrub widely distributed in many parts of the world including Saudi Arabia. The antiproliferative activities of the methanolic extract of W. somnifera leaves collected from Faifa mountains, southwest Saudi Arabia against MCF-7, HCT116 and HepH2 cell lines were investigated. The extract showed a strong antiproliferative activity against all cell lines with$IC_{50}$ values of 3.35, 2.19 and$1.89{\mu}g/ml$ , respectively. Flow cytometry results showed that the extract arrested the cell cycle at S phase, and the increase in the caspase 3 activity suggested that the extract could induce cell apoptosis by a caspase mediated pathway. These results demonstrated that the methanolic extract of W. somnifera leaves collected from Faifa mountains has comparable strong antiproliferative activities to samples collected from different locations. -
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