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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Why Screening Rates Vary between Korea and Japan-Differences between Two National Healthcare SystemsGoto, Rei;Hamashima, Chisato;Mun, Sunghyun;Lee, Won-Chul 395
Both Japan and Korea provide population-based screening programs. However, screening rates are much higher in Korea than in Japan. To clarify the possible factors explaining the differences between these two countries, we analyzed the current status of the cancer screening and background healthcare systems. Population-based cancer screening in Korea is coordinated well with social health insurance under a unified insurer system. In Japan, there are over 3,000 insurers and coordinating a comprehensive strategy for cancer screening promotion has been very difficult. The public healthcare system also has influence over cancer screening. In Korea, public healthcare does not cover a wide range of services. Almost free cancer screening and subsidization for medical cost for cancers detected in population-screening provides high incentive to participation. In Japan, on the other hand, a larger coverage of medical services, low co-payment, and a lenient medical audit enables people to have cancer screening under public health insurance as well as the broad range of cancer screening. The implementation of evidence-based cancer screening programs may be largely dependent on the background healthcare system. It is important to understand the impacts of each healthcare system as a whole and to match the characteristics of a particular health system when designing an efficient cancer screening system. -
Background: This study was planned as comparative and descriptive in order to measure and evaluate the knowledge and attitudes regarding early diagnosis of women with and without a family history of cervical cancer. Materials and Methods: The study sample consisted of the relatives of female patients (N=253) who were admitted to Istanbul University of Medicine. Women with a family history of cervical cancer formed the case group, while those without family history of cervical cancer constituted the control group. Two distinct data collection tools, a questionnaire and the Miller Behavioral Style Scale (MBSS), were used in order to obtain data for evaluation with SPSS for Windows 20.0 statistics package program. Results: It was found that 61.0% of the case group with family history of cervical cancer and 19.0% of the control group without family history of cervical cancer were using early diagnostic methods. Thus the presence of an individual with cervical cancer in the family affected the attitudes towards early diagnosis. It was further found that the level of knowledge on cervical cancer and PAP smear test was higher in the case group, which was more sensitive with regard to being informed about cervical cancer as compared to general society. However, the average MBSS scores were not significantly different compared to the control group. Conclusions: It was noted that, women participating this study knowledgeable, but this did not necessarily transform into better behavior.
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Seker, Mehmet Metin;Deveci, Koksal;Seker, Ayse;Sancakdar, Enver;Yilmaz, Ali;Turesin, A. Kerim;Kacan, Turgut;Babacan, Nalan A. 407
Background: Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure. Materials and Methods: Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury. Results: Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/mg (p=0.243) in the oxaliplatin group. Conclusions: Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine. -
Chen, Wen-Jie;He, De-Shen;Tang, Rui-Xue;Ren, Fang-Hui;Chen, Gang 411
Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as a prognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order to clarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library with the last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies, covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression of Ki-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI: 1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67 expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-off value and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might be a predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor. -
Shayanfar, Nasrin;Bahari, Leila;Safaie-Naraghi, Zahra;Kamyab, Kambiz;Gheytanchi, Elmira;Rezaei, Nima 421
Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age$57.9{\pm}19.5years$ were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/neu was negative in 97.5% of patients with IHC and in 100% of patients with CISH technique. Only one case (2.5%) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47% of cases were in Clark level III, while the mean of Breslow thickness was$3.56{\pm}2.87mm$ . The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques. -
Shemmari, Noora Al;Shaikh, Rizwana Burhanuddin;Sreedharan, Jayadevan 427
Background: Dokha is a novel form of smoking in United Arab Emirates (UAE) on which there is very little published literature, especially among adolescents, and this form of smoking has been not been addressed adequately in the smoking cessation strategies in the UAE. Objectives: To assess the prevalence of dokha smoking among male secondary school students in Ajman UAE. Materials and Methods: A cross sectional survey was conducted among male secondary school students in Ajman, UAE. A total of 560 participants filled in self-administered questionnaires. Results: The prevalence of ever smokers was 39%; ever dokha smokers was 36% and current dokha smokers was 24%. The prevalence is very high when compared to other forms of smoking in the region and globally. Prevalence increased with increasing age and grade of students, prevalence of ever smokers, ever dokha smokers and current dokha smokers was lower in students in the science stream. 40% of the smokers used dokha, cigarettes and shisha, 30% used dokha and cigarettes, and 21% used dokha alone. 30% of the students smoked dokha on all days of the month. Conclusions: The prevalence of ever smokers, ever dokha smokers and current dokha smokers is very high. There is an urgent need for specific health promotion programs tailored to this age group on prevention of dokha smoking and policies restricting the availability of dokha to this age group. -
Al-Mutlaq, Hind M.;Bawazir, Amen Ahmed;Jradi, Hoda;Al-Dhalaan, Zeyad Abdulaziz;Al-Shehri, Ali 431
Background: Although childhood cancer is a rare disease, 100,000 children younger than 15 years of age die from cancer each year, the majority of them in developing countries. More data need to be gathered and published particularly in developing countries to better understand the scale of the problem. Aims: This study aimed to describe the patterns of childhood cancers in Saudi Arabia over a period of ten years (1999-2008). Materials and Methods: This descriptive retrospective study was based on secondary data from the Saudi Cancer Registry from 1999 to 2008. All Saudi cases (both genders), under the age of 15 years, who were diagnosed with cancer during the study period, were included in this study. Results: Childhood cancer in Saudi Arabia, in the period between 1999 and 2008, accounted for about 8% of total cancer cases. The most common encountered cancers were leukemia (34.1%), followed by lymphoma (15.2%), brain (12.4%), and kidney cancers (5.3%). The overall incidence of childhood cancers increased from 8.8 per 100,000 in 1999 to 9.8 per 100,000 in 2008. The incidence rates of cancers per 100,000 in the years 1999 and 2008 were generally higher among males, (9.4 and 11.5 in males vs. 8.3 and 8.1 in females). The highest incidence rate in the surveyed years was apparent in the birth to age 4 years group. Conclusions: Cancer is an important public health problem in Saudi Arabia and a major ascending contributor to mortality and morbidity in children. More studies are required to describe the patterns of childhood cancers and related risk factors in Saudi Arabia. -
Pan, Yan;Gao, Song;Hua, Yong-Qiang;Liu, Lu-Ming 437
Aim: To establish a pancreatic cancer stem cell model using human pancreatic cancer cells in nude mice to provide a platform for pancreatic cancer stem cell research. Materials and Methods: To establish pancreatic cancer xenografts using human pancreatic cancer cell line SW1990, nude mice were randomly divided into control and gemcitabine groups. When the tumor grew to a volume of$125mm^3$ , they treated with gemcitabine at a dose of 50mg/kg by intraperitoneal injection of 0.2ml in the gemcitabine group, while the mice in control group were treated with the same volume of normal saline. Gemcitabine was given 2 times a week for 3 times. When the model was established, the proliferation of pancreatic cancer stem cells was observed by clone formation assay, and the protein and/or mRNA expression of pancreatic stem cell surface markers including CD24, CD44, CD133, ALDH, transcription factors containing Oct-4, Sox-2, Nanog and Gli, the key nuclear transcription factor in Sonic Hedgehog signaling pathway was detected by Western blot and/or RT-PCR to verify the reliability of this model. Results: This model is feasible and safe. During the establishment, no mice died and the weight of nude mice maintained above 16.5g. The clone forming ability in gemcitabine group was stronger than that of the control group (p<0.01). In gemcitabine group, the protein expression of pancreatic cancer stem cell surface markers including CD44, and ALDH was up-regulated, the protein and mRNA expression of nuclear transcription factor including Oct-4, Sox-2 and Nanog was also significantly increased (P<0.01). In addition, the protein expression of key nuclear transcription factor in Sonic Hedgehog signaling pathway, Gli-1, was significantly enhanced (p<0.01). Conclusions: The pancreatic cancer stem cell model was successfully established using human pancreatic cancer cell line SW1990 in nude mice. Gemcitabine could enrich pancreatic cancer stem cells, simultaneously accompanied by the activation of Sonic Hedgehog signaling pathway. -
Sag, Sebnem Ozemri;Gorukmez, Ozlem;Ture, Mehmet;Gorukmez, Orhan;Topak, Ali;Sahinturk, Serdar;Ocakoglu, Gokhan;Gulten, Tuna;Ali, Ridvan;Yakut, Tahsin 443
Background: Myeloproliferative disorders (MPDs) are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of malignancy progression. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. To our knowledge, this is the first investigation of associations between the -735 C/T and -1562 C/T polymorphisms in the MMP2 and MMP9 genes, respectively, and the risk of essential thrombocytosis (ET), and polycythemia vera (PV). Materials and Methods: The case-control study included JAK2V617F mutation positive 102 ET and PV patients and 111 controls. Polymorphisms were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and electrophoresis. Results: No statistically significant differences were detected between patient (ET+PV) and control groups regarding genotype distribution for MMP2 gene-735 C/T and MMP9 gene -1562 C/T polymorphisms and C/T allele frequency (p>0.050). Statistically borderline significance was observed between PV and control groups regarding genotype distribution for the MMP9 gene -1562 C/T polymorphism (p=0.050, OR=2.26, 95%Cl=0.99-5.16). Conclusions: Consequently this study supported that CC genotype of MMP9 gene -1562 C/T polymorphism may be related with PV even if with borderline significance. -
Veisy, Afsaneh;Lotfinejad, Shirin;Salehi, Kamal;Zhian, Faegh 451
More than one million new patients suffer from breast cancer annually in the world. In developed countries, breast cancer is the most common malignancy diagnosed among women, and in developing regions, it often ranks second to cervical cancer. This study aimed to investigate the relationship between incidence of breast cancer and reproductive factors in North-West of Iran. This retrospective analytical control-case study was conducted with 235 breast cancer patients and 235 women in the control group. Data collection tools included a set of questions with interviews and patient medical records. Data were analyzed using statistical tests: t-test, Chi-square, Fisher, and Pearson correlation coefficient. Significantly increased risks were associated between breast cancer and older age at first pregnancy, age at menopause and history of contraceptive use. A trend for decreasing risk were observed with increasing parity. Findings of this study showed no association between breast cancer and age at menarche. The study results suggested that physiological and reproductive factors may play important roles in the development breast cancer among Iranian women. -
Deng, Si-Yu;Guo, Xiao-Xin;Wang, Ning;Wang, Kun-Hao;Wang, Shang 457
The pathogenesis of mantle cell lymphoma, a special subtype of lymphoma that is invasive and indolent and has a median survival of 3 to 4 years, is still partially unexplained. Much research about genes and miRNAs has been conducted in recent years, but interactions and regulatory relations of genetic elements which may play a vital role in genesis of MCL have attracted only limited attention. The present study concentrated on regulatory relations about genes and miRNAs contributing to MCL pathogenesis. Numerous experimentally validated raw data were organized into three topology networks, comprising differentially expressed, associated and global examples. Comparison of similarities and dissimilarities of the three regulating networks, paired with the analysis of the interactions between pairs of elements in every network, revealed that the differentially expressed network illuminated the carcinogenicity mechanism of MCL and the related network further described the regulatory relations involved, including prevention, diagnosis, development and therapy. Three kinds of regulatory relations for host genes including miRNAs, miRNAs targeting genes and genes regulating miRNAs were concluded macroscopically. Regulation of the differentially expressed miRNAs was also analyzed, in terms of abnormal gene expression affecting the MCL pathogenesis. Special regulatory relations were uncovered. For example, auto-regulatory loops were found in the three topology networks, key pathways of the nodes being highlighted. The present study focused on a novel point of view revealing important influencing factors for MCL pathogenesis. -
Lee, Won Sup;Yun, Jeong Won;Nagappan, Arulkumar;Jung, Ji Hyun;Yi, Sang Mi;Kim, Dong Hoon;Kim, Hye Jung;Kim, GonSup;Ryu, Chung Ho;Shin, Sung Chul;Hong, Soon Chan;Choi, Yung Hyun;Jung, Jin-Myung 465
Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and Methods: U937 human leukemic cancer cells were used. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of$200{\mu}g/mL$ and$400{\mu}g/mL$ . FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP,${\Delta}{\Psi}m$ ) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (${\Delta}{\Psi}m$ ) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells. -
Shandiz, Fatemeh Homaei;Tavassoli, Aliraz;Sharifi, Nourieh;Khales, Sima Ardalan;Kadkhodayan, Sima;Khales, Sahar Ardalan 471
Background: Male and female breast cancers were investigated for variation in the clinicopathologic characteristics and expression of steroid hormone receptors in the northeast of Iran. Materials and Methods: Tumor specimens of 17 males and 338 females with breast cancer were collected at the hospitals of Mashhad University of Medical Sciences. Immunohistochemical expression of hormone receptors and clinicopathologic features of breast cancer were compared between two groups. Results: The mean age in men was 15 years higher than women (p=0.000). Males and females were mainly in stage II and III respectively (p=0.007). Although more than 60% of male and female patients were grade II, the respective figures for grade I and III were 25% and 12.5% in men but 7.1% and 27.2% in women respectively (p=0.025). ER was significantly more positive in men against women; 82.3% versus 53.4% (p=0.016). The related measures for PR was 58.8% and 50.3%, respectively (p=0.424). Males also showed significantly more ER expression than postmenopausal females; 82.3% versus 48.9% (p=0.010). Conclusions: Breast cancer in males and females contrasted in age at diagnosis, histological type, stage, grade and ER expression which emphasize they are separate diseases with different behaviors. -
Xue, Lu-Chen;Xu, Zhi-Wen;Wang, Kun-Hao;Wang, Ning;Zhang, Xiao-Xu;Wang, Shang 475
Genes and microRNAs (miRNAs) have important roles in human oncology. However, most of the biological factors are reported in disperse form which makes it hard to discover the pathology. In this study, genes and miRNAs involved in human endometrial cancer(EC) were collected and formed into regulatory networks following their interactive relations, including miRNAs targeting genes, transcription factors (TFs) regulating miRNAs and miRNAs included in their host genes. Networks are constructed hierarchically at three levels: differentially expressed, related and global. Among the three, the differentially expressed network is the most important and fundamental network that contains the key genes and miRNAs in EC. The target genes, TFs and miRNAs are differentially expressed in EC so that any mutation in them may impact on EC development. Some key pathways in networks were highlighted to analyze how they interactively influence other factors and carcinogenesis. Upstream and downstream pathways of the differentially expressed genes and miRNAs were compared and analyzed. The purpose of this study was to partially reveal the deep regulatory mechanisms in EC using a new method that combines comprehensive genes and miRNAs together with their relationships. It may contribute to cancer prevention and gene therapy of EC. -
Moradi, Mohammad-Taher;Yari, Kheirollah;Rahimi, Zohreh;Kazemi, Elham;Shahbazi, Mehrdad 485
Background: Oxidative stress caused by the generation of reactive oxygen species plays an important role in human carcinogenesis. Manganese superoxide dismutase (MnSOD) Val-9Ala in the mitochondrial target sequence is the best known polymorphism of this enzyme. The purpose of the current research was to assess the association of MnSOD Val-9Ala genotypes with the risk of gastric cancer. Materials and Methods: This case-control study covered 54 gastric cancer patients compared to 100 cancer free subjects as controls. Extraction of DNA was performed on bioptic samples and genotypes were identified with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MnSOD Ala/Ala, Ala/Val and Val/Val genotypes in healthy individuals were 24.3, 66.7 and 9%, respectively. However, in gastric cancer patients, Ala/Ala, Ala/Val and Val/Val were observed in 24.0, 48.0 and 28.0% (p=0.01). In patients the frequency of MnSOD Val allele was higher (52%) compared to that in controls (42%). Conclusions: The results of this study show a positive association between MnSOD Val-9Ala gene polymorphism and risk of gastric cancer disease in Iranian population. -
Nurgul, Keser;Nursan, Cinar;Dilek, Kose;Over, Ozcelik Tijen;Sevin, Altinkaynak 489
Background: Once limited with face-to face courses, health education has now moved into the web environment after new developments in information technology This study was carried out in order to give training to the university academic and administrative female staff who have difficulty in attending health education planned for specific times and places. The web-supported training focuses on healthy diet, the importance of physical activity, damage of smoking and stress management. Materials and Methods: The study was carried out in Sakarya University between the years 2012-2013 as a descriptive and quasi experimental study. The sample consisted of 30 participants who agreed to take part in the survey, filled in the forms and completed the whole training. The data were collected via a "Personel Information Form", "Health Promotion Life-Style Profile (HPLSP)", and "Multiple Choice Questionnaire (MCQ). Results: There was a statistically significant difference between the total points from "Health Promotion Life-Style Profile" and the total points from the sub-scale after and before the training (t=3.63, p=0.001). When the points from the multiple choice questionnaire after and before training were compared, it was seen that the average points were higher after the training (t=8.57, p<0.001). Conclusions: It was found that web-supported health training has a positive effect on the healthy living behaviour of female staff working at a Turkish university and on their knowledge of health promotion. -
Yang, Hai-Yan;Yang, Si-Yu;Shao, Fu-Ye;Wang, Hai-Yu;Wang, Ya-Dong 495
Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings. -
Kang, Jina;Yang, Eunbae B.;Chang, Yoon Jung;Choi, Jin Young;Jho, Hyun Jung;Koh, Su Jin;Kim, Won Chul;Choi, Eun-Sook;Kim, Yeol;Park, Sung-Min 501
Background: To evaluate the effectiveness of the National Train-the-Trainers Program for Hospice and Palliative Care Experts (TTHPC) sponsored by the National Cancer Center of Korea between 2009 and 2012. This program was developed to improve the teaching skills of those in the field of hospice and palliative care (HPC). Materials and Methods: Training was offered in eight 1-day sessions between 2009 and 2012. The effect of the program was measured using Kirkpatrick's model of educational outcomes. First, levels 1 and 2 were evaluated immediately after the 1-day program (n=120). In 2012, the level-3 evaluation test was administered to trainers who offered at least one HPC training (n=78) as well as to their trainees (n=537). Results: The level-1 evaluation addressed participant reactions to and satisfaction with the program. Participants (n=120) were generally satisfied with the content, the method, and the overall course (mean range: 3.94-4.46 on a five-point Likert scale). The level-2 evaluation (learning) showed that participants gained knowledge and confidence related to teaching HPC (4.24 vs. 4.00). The level-3 evaluation (behavioral), which assessed trainers' application of teaching skills to HPC, showed that trainees rated the teaching methods of trainers (mean range: 4.03-4.08) more positively than did trainers (p<0.05). Female trainers were more likely than were male trainers to plan sessions in consideration of their trainees' characteristics (4.11 vs. 3.58; p<0.05), and nurse trainers were more likely than physician trainers to use a variety of instructional methods (4.05 vs. 3.36; p<0.05) Conclusions: We conducted systematic evaluations based on Kirkpatrick's model to assess the effectiveness of our train-the-trainers program. Our educational program was practical, effective, and followed by our HPC experts, who needed guidance to learn and improve their clinical teaching skills. -
Background: This pilot study looked into the physical, social, psychological and economic issues of Indian adult cancer survivors. Materials and Methods: Assumed cancer free patients, after cancer directed therapy (CDT), were assessed on the basis of a questionnaire developed by the investigators. The mental status of the survivors was elicited by modified MINI international neuro-psychiatric interview. This cross sectional assessment was conducted as a direct interaction with each patient for 30 to 45 minutes at a cancer hospital in 2012. Results: Thirty one adult cancer survivors participated in this study. Median age was 53 years with a median follow up duration of 21.8 months (Range 2.3-194.1 months). The majority (68%) did not receive financial support for treatment. Median interval after CDT to start of activity of daily living was 1.5 months (range: 0-24 months). Fatigue and loss of appetite were reported by 52% and 29% respectively. The cancer diagnosis and its treatment adversely impacted the financial condition in 42% of patients. Nineteen percent each showed social anxiety and post-traumatic stress disorder and another 13% patients reported depression. Conclusions: This prospective assessment highlights survivorship issues and the need to address those issues particularly in the context of developing countries where resources and manpower are limited.
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Zeng, Wen-Li;Chen, Yao-Wu;Zhou, Hui;Zhou, Jue-Yu;Wei, Min;Shi, Rong 513
Background: Growing evidence suggests that the members of the ubiquitin-proteasome system (UPS) are important for tumorigenesis. HERC4, one component, is a recently identified ubiqutin ligase. However, the expression level and function role of HERC4 in lung cancer remain unknown. Our objective was to investigate any correlation between HERC4 and development of lung cancer and its clinical significance. Materials and Methods: To determine HERC4 expression in lung cancer, an immunohistochemistry analysis of a tissue microarray containing samples of 10 lung normal tissues, 15 pulmonary neuroendocrine carcinomas, 45 squamous epithelial cancers and 50 adenocarcinomas was conducted. Receiver operating characteristic (ROC) curve analysis was applied to obtain a cut-off point of 52.5%, above which the expression of HERC4 was regarded as "positive". Results: On the basis of ROC curve analysis, positive expression of HERC4 was detected in 0/10 (0.0%) of lung normal tissues, in 4/15 (26.7%) of pulmonary neuroendocrine carcinomas, in 13/45 (28.9%) of squamous epithelial cancers and in 19/50 (38.0%) of adenocarcinomas. It showed that lung tumors expressed more HERC4 protein than adjacent normal tissues (${\chi}^2$ =4.675, p=0.031). Furthermore, HERC4 positive expression had positive correlation with pT status (${\chi}^2$ =44.894, p=0.000), pN status (${\chi}^2$ =43.628, p=0.000), histological grade (${\chi}^2$ =7.083, p=0.029) and clinical stage (${\chi}^2$ =72.484, p=0.000), but not age (${\chi}^2$ =0.910, p=0.340). Conclusions: Our analysis suggested that HERC4 is likely to be a diagnostic biomarker for lung cancer. -
Ozbilen, Ozlem;Sakarya, Derya Kilic;Bezircioglu, Incim;Kasap, Burcu;Yetimalar, Hakan;Yigit, Seyran 519
Background: We aimed to investigate whether the tumor free distance (the distance between the uterine serosa and the tumor at its deepest point) is useful in surgical staging and in predicting prognosis. Materials and Methods: Data from patients who underwent complete surgical staging for endometrial cancer between January 2006 and June 2011 were reviewed retrospectively. All demographic findings, surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion as well as abdominal cytology, cervical, adnexal, and omental involvement, and lymph node metastasis were recorded. The relations between myometrial invasion and tumor free distance from uterine serosa with prognostic factors were investigated. Results: Seventy patients were included in the study. Sixty-four (91.5%) had endometrioid type cancers and forty-four (62.9%) were grade 1. The deepest myometrial invasion was less than 1/2 in 42 patients (60%). In 18 patients (25.8%) lymphovascular invasion was noted. Eight (11.4%) were found to have cervical involvement, five (7.1%) had adnexal involvement and in 4 cases (5.7%) the peritoneal washings included malignant cells. Four patients had pelvic and one para-aortic node metastasis. We recognized that an invasion of more than 1/2 was correlated significantly with lymphovascular space involvement, histological grade, positive abdominal washing cytology, nodal and cervical involvement, but not with adnexal involvement. Tumor-free myometrial thickness was negative and statistically significant correlated with surgical stage, histological grade, lymphovascular space involvement, positive abdominal washing cytology, cervical and adnexal involvement. The importance of tumor-free myometrial thickness in determinating the lymphovascular space invasion was found to be highest in terms of sensitivity and specificity when crossing the ROC curve at 11 millimeters. Conclusions: Depth of myometrial invasion is more valuable for predicting lymph node metastasis than tumor-free myometrial thickness. The tumor-free myometrial thickness provides a better prediction for adnexal involvement. -
Background: This study was planned in an attempt to develop a scale for the quality of life in pediatric oncology patients aged 7-12, with child and parents forms. Materials and Methods: In collecting the study data, we used the Child and Parent Information Form, Visual Quality of Life Scale, Scale for Quality of Life Pediatric Oncology Patients Aged 7-12 and the Scale for the Quality of Life in Pediatric Oncology Patients Aged 7-12 for Parents. We also used Pearson correlation analysis, the Cronbach alpha coefficient, factor analysis and ROC analysis for the study data. Results: In this study, the total Cronbach alpha value of the parent form was 0.96, the total factor load being 0.54-0.90 and the total variance explained was 82.5%. The cutoff point of the parent form was 93 points. The total Cronbach alpha value for the child form was 0.96, with a total factor load of 0.55-0.91 and the total variance being explained was 78.3%. The cutoff point of the child form was 65 points. Conclusions: This study suggests that the Scale for Quality of Life in Pediatric Oncology Patients Aged 7-12 Child and Parents Forms are valid and reliable instruments in assessing the quality of life of children.
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Luan, Yun-Yan;Liu, Zi-Min;Zhong, Jin-Yi;Yao, Ru-Yong;Yu, Hong-Sheng 531
Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins (GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulation of VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore, we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VM structure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. The effects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteins of VM information were determined using western blot analysis. In vitro, the tubular networks were found in highly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number of vascular channels was significantly reduced when cells were exposed in GSPs ($100{\mu}g$ /ml) and GSPs ($200{\mu}g/mL$ ) groups (all p<0.001). Furthermore, we found that treatment with GSPs promoted transition of the mesenchymal state to the epithelial state in HCC1937 cells as well as reducing the expression of Twist1 protein, a master EMT regulator.GSPs has the ability to inhibit VM information by the suppression of Twist1 protein that could be related to the reversal of epithelial-to-mesenchymal (EMT) process. It is firstly concluded that GSPs may be an p otential anti-VM botanical agent for human TNBCs. -
Keng, Soon Lean;Wahab, Syakirah Bainun Abdul;Chiu, Lim Bee;Yusuf, Azlina 537
Background: Ovarian cancer is recognized as the fourth leading cancer in Malaysia. However, women do not always seek help in a timely manner and gaps in awareness may influence screening uptake and presentation. The purpose of this study was to determine levels of awareness of ovarian cancer risk factors in female population in Penang, Malaysia. Materials and Methods: A cross-sectional study was conducted in Penang, Malaysia from January until February 2014. Eighty-seven women were selected by convenient sampling. Awareness of risk factors of ovarian cancer was assessed using a self-administered questionnaire. Data were analyzed using statistical package for the social sciences (SPSS) version 20.0 for descriptive statistics and Pearson chi-square test for the association between socio-demographic data and awareness. A p value${\leq}0.05$ was considered statistically significant. Results: In all, 74.7% of participants answered correctly for the risk factor of increasing age, although 94.3% were unaware of increased risk of tall women. A majority, 71.3%, had a low level of awareness of ovarian cancer risk factors. There was a significant association between age and knowledge (p=0.047). Additionally, there was a significant association between higher education level and level of awareness of ovarian cancer risk factors (p=0.039). Conclusions: This study revealed that awareness of ovarian cancer risk factors among Malaysian women is low. The results show a need for improved public understanding about ovarian cancer risks and provision of important information for health professionals about initiatives needed for future awareness, prevention and screening programs. -
Hafez, Mohamed M.;Al-Shabanah, Othman A.;Al-Rejaie, Salim S.;Al-Harbi, Naif O.;Hassan, Zeinab K.;Alsheikh, Abdulmalik;Theyab, Abdurrahman I. Al;Aldelemy, Meshan L.;Sayed-Ahmed, Mohamed M. 541
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$ ) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression. -
Yan, Yue;Zhang, Ya-Xiong;Fang, Wen-Feng;Kang, Shi-Yang;Zhan, Jian-Hua;Chen, Nan;Hong, Shao-Dong;Liang, Wen-Hua;Tang, Yan-Na;He, Da-Cheng;Wu, Xuan;Zhang, Li 551
Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated. -
Latiff, Latiffah A.;Rahman, Sabariah Abdul;Wee, Wong Yong;Dashti, Sareh;Asri, Andi Anggeriana Andi;Unit, Nor Hafeeza;Li, Shirliey Foo Siah;Esfehani, Ali Jafarzadeh;Ahmad, Salwana 559
Background: The participation of women in cervical cancer screening in Malaysia is low. Self-sampling might be able to overcome this problem. The aim of this study was to assess the reliability of self-sampling for cervical smear in our country. Materials and Methods: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection. Results: The mean age of the subjects was$40.4{\pm}11.3years$ . The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment. Conclusions: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia. -
Amiri, Ahmad;Namavari, Mehdi;Rashidi, Mojtaba;Fahmidehkar, Mohammad Ali;Seghatoleslam, Atefeh 565
Breast and colorectal cancers rank high in Iran as causes of mortality. Most of the current treatments are expensive and non-specific. The potential anticancer properties of common home gecko, Cyrtopodion scabrum, were investigated in this study. The effects of C. scabrum extract on proliferation, viability and migration of the colorectal cancer (SW-742), breast cancer (MCF-7) and normal (MSC) cell lines were investigated using MTT and in vitro wound healing assay.$IC_{50}$ values calculated for the extract were$559{\pm}28.9{\mu}g/mL$ for MCF-7 and$339{\pm}11.3{\mu}g/mL$ for SW-742. No toxic effects on the normal control cells were observed. MCF-7 and SW-742 cell growth was inhibited by 32.6% and 62%, under optimum conditions, compared to the untreated control cells. The extract also decreased the motility and migration ability of both cancer cell lines, with no significant effects on the normal control cells. Data suggest C. scabrum extract as a useful natural resource for targeting cancer cells specifically. -
Liu, Xiao-Qi;Jiang, Rong;Li, Si-Qi;Wang, Jing;Yi, Fa-Ping 571
Prostate cancer is the most common cancer in men. In this study, we investigated immune responses of cytotoxic T lymphocytes (CTLs) against TRAMP-C2 prostate cancer cells after activation by dendritic cells (DCs) loaded with TRAMP-C2 freeze-thaw antigen and/or PEP-3 peptide in vitro. Bone marrow-derived DC from the bone marrow of the C57BL/6 were induced to mature by using the cytokine of rhGM-CSF and rhIL-4, and loaded with either the freeze-thaw antigen or PEP-3 peptide or both of them. Maturation of DCs was detected by flow cytometry. The killing efficiency of the CTLs on TRAMP-C2 cells were detected by flow cytometry, CCK8, colony formation, transwell migration, and wound-healing assay. The levels of the IFN-${\gamma}$ , TNF-${\beta}$ and IL-12 were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the unloaded DCs, the loaded DCs had significantly increased expression of several phenotypes related to DC maturation. CTLs activated by DCs loaded with freeze-thaw antigen and PEP-3 peptide had more evident cytotoxicity against TRAMP-C2 cells in vitro. The secretion levels of IFN-${\gamma}$ , TNF-${\beta}$ and IL-12, secreted by DCs loaded with antigen and PEP-3 and interaction with T cells, were higher than in the other groups. Our results suggest that the CTLs activated by DCs loaded with TRAMP-C2 freeze-thaw antigen and PEP-3 peptide exert a remarkable killing efficiency against TRAMP-C2 cells in vitro. -
Akbar, Shehla;Pervez, Shgufta Nasir;Shah, Walayat 579
This study was conducted on female patients with different gynecological problems attending the gynecology out-patient departments of two tertiary care hospitals in Peshawar city of Khyber Pakhtunkhwa, Pakistan between August 2012 and October 2013. The 200 patients had an age range of 21-65 years. Smears were taken with cervical brushes and preserved in preservative medium and processed for manual liquid based cytology (MLBC) for Pap staining. Out of 200 collected samples, 30 samples were found inadequate on cytology. Of the remaining 170 samples, 164 (96.47%) were normal, 5 (2.94%) were of atypical squamous cells of unknown significance (ASCUS) and 1 (0.6%) was of high grade squamous intraepithelial lesion (HSIL). On PCR all the samples were positive for beta globin gene fragment including those reported inadequate on cytology. Out of the 5 ASCUS samples, 2 samples were positive for HPV, one each for HPV 16 and HPV 18, and the rest of the 3 samples were negative for HPV DNA. The 1 sample of HSIL was positive for HPV 16 on PCR. Out of 164 normal samples on cytology, only 1 sample was HPV 16 positive. So overall, 4 (2%) out of 200 samples were positive for HPV DNA, where 3 were HPV 16 (1.5%), and 1 was HPV 18 (0.5%) positive, and thus the ratio of infection with of HPV 16 to HPV 18 was 3:1 in the general population. In conclusion, PCR based HPV detection is a more sensitive method for screening of HPV infection than cytology as sample inadequacy does not affect the results. However, it can be combined with cytology methods in a HPV positive female to achieve the maximum results. -
Vardar-Yagli, Naciye;Sener, Gul;Saglam, Melda;Calik-Kutukcu, Ebru;Arikan, Hulya;Inal-Ince, Deniz;Savci, Sema;Altundag, Kadri;Kutluk, Tezer;Ozisik, Yavuz;Kaya, Ergun Baris 585
Physical inactivity may an important outcome in the prognosis of breast cancer. Physical activity levels decrease significantly for breast cancer patients following the treatment and remain low after oncology treatment is completed. The aim of this study was to determine physical activity levels and to examine associations among physical activity, comorbidity, functional capacity, peripheral muscle strength, and psychosocial status in breast cancer patients. Forty breast cancer survivors were included in this study. Demographic and clinical characteristics were recorded. Physical activity was assessed with a short form of the International Physical Activity Questionnaire (IPAQ). We defined comorbid diseases according to the Charlson Comorbidity Index (CCI). Functional capacity was evaluated with a six-minute walk test (6MWT). Peripheral muscle strength was measured for quadriceps femoris muscle with a hand-held dynamometer. Psychosocial status was measured with the Hospital Anxiety Depression Scale (HADS). Forty percent of patients were inactive. The IPAQ total score was significantly related with quadriceps muscle strength (r=0.492; p<0.001) and HADS depression score (r=0.341; p<0.05). Marked correlations were also observed between IPAQ walking score and quadriceps muscle strength (r=0.449; p<0.001), HADS depression score (r=0.341; p<0.05), and CCI (r=-0.433; p<0.001). The CCI score was also markedly associated with quadriceps muscle strength (r=-0.413; p<0.001). 6MWT distance was not significantly correlated with any of the parameters. Regression analyses revealed that psychosocial status and peripheral muscle strength were significant predictors of physical activity estimated with the IPAQ short form and when combined, they explained 35% of the variance. Comorbidities, peripheral muscle strength and psychosocial status partially explain the variability of physical activity level in breast cancer survivors. These results suggest that physical inactivity contributes to worsening health in breast cancer survivors. -
Ni, Wei;Luo, Lin;Ping, Zuo;Yuan, Hong-Ping;Zhao, Xu-Dong;Xu, Wei 591
Background: Aberrations in gene methylation patterns play important roles in gliomagenesis. However, whether the ALDH1A3 promoter methylation is related to prognoses of primary glioblastomas (GBMs) in Western China remains unclear. Materials and Methods: Methylation levels of ALDH1A3 CpG island in 36 GBMs were identified by pyrophosphate sequencing, while ALDH1A3 expression was assessed with matched paraffin section immunohistochemistry. Survival curves were analysed by Kaplan-Meier. Results: The hypermethylation status of ALDH1A3 promoter predicted a better prognosis accompanied with low expression of ALDH1A3 protein. Conclusions: Our results indicate ALDH1A3 promoter methylation correlates with prognosis in primary GBMs. -
Hwang, In Cheol;Park, Sang Min;Shin, Doosup;Ahn, Hong Yup;Rieken, Malte;Shariat, Shahrokh F. 595
Background: Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. Results: A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Conclusions: Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted. -
Murray, Nigel P.;Reyes, Eduardo;Orellana, Nelson;Fuentealba, Cynthia;Jacob, Omar 601
Background: Prostate cancer is predominately a disease of older men, with a median age of diagnosis of 68 years and 71% of cancer deaths occurring in those over 75 years of age. While prostate cancer screening is not recommended for men >70 years, fit elderly men with controlled comorbidities may have a relatively long life expectancy. We compare the use of age related PSA with the detection of primary malignant circulating prostate cells mCPCs to detect clinically significant PC in this population. Materials and Methods: All men undergoing PC screening with a PSA >4.0ng/ml underwent TRUS 12 core prostate biopsy (PB). Age, PSA, PB results defined as cancer/no-cancer, Gleason, number of positive cores and percentage infiltration were registered. Men had an 8ml blood sample taken for mCPC detection; mononuclear cells were obtained using differential gel centrifugation and mCPCs were identified using immunocytochemistry with anti-PSA and anti-P504S. A mCPC was defined as a cell expressing PSA and P504S; a positive test as at least one mCPC detected/sample. Diagnostic yields for subgroups were calculated and the number of avoided PBs registered. Esptein criteria were used to define small grade tumours. Results: A total of 610 men underwent PB, 398 of whom were aged <70yrs. Men over 70 yrs had: a higher median PSA, 6.24ng/ml versus 5.59ng/ml (p=0.04); and a higher frequency of cancer detected 90/212 (43%) versus 134/398 (34%) (p=0.032). Some 34/134 cancers in men <70yrs versus 22/90 (24%) of men >70yrs complied with criteria for active surveillance. CPC detection: 154/398 (39%) men <70yrs were CPC (+), specificity for cancer 86%, sensitivity 88%, 14/16 with a false (-) result had a small low grade PC. In men >70 years, 88/212 (42%) were CPC (+); specificity 92%, sensitivity 87%, 10/12 with a false (-) had small low grade tumours. False (+) results were more common in younger men 36/154 versus 10/88 (p<0.02). With a PSA cutoff of 6.5ng/ml, in men <70yrs, 108 PB would be avoided, missing 56 cancers of which 48 were clinically significant. Using CPC detection, 124 biopsies would be avoided, missing only 2 clinically significant cancers. In men >70 yrs using a PSA >6.5ng/ml would have resulted in 108 PB with 34 PC detected, of which 14(41%) were small low grade tumours. Conclusions: The use of CPC detection in the fit elderly significantly decreases the number of PBs without missing clinically significant cancers, indicating superiority to the use of age-related PSA. -
Background: Chronic respiratory disease is an important factor for development of lung cancer. To explore the influence of hazy weather on respiratory diseases and its variation the present study was conducted. Materials and Methods: Data from air pollution surveillance from January to October 2014 and case records of visiting patients in the
$263^{th}$ Hospital of Chinese PLA in the corresponding period were collected to analyze the relevance between different degrees of air pollution (hazy weather) and the number of visiting patients in Department of Respiratory Disease. Results: Air quality index (AQI) of hazy weather had significantly positive association with particulate matter 2.5 ($PM_{2.5}$ ) and the number of patients with 5 kinds of respiratory diseases i and different pollutants had distinct influences on various respiratory diseases. Conclusions: The degree of air pollution in Beijing City is in close association with the number of patients with respiratory diseases, in which$PM_{2.5}$ and$SO_2$ are in more significant influences on all respiratory diseases. This could have essential implications for lung cancer development in China. -
Elmashad, Nehal;Ibrahim, Wesam Salah;Mayah, Wael Wahid;Farouk, Mohamed;AboAli, Lobna;Taha, Atef;Elmashad, Wael 613
Background: Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Insulin-like growth factor-1 (IGF-1) levels reflect hepatic function and are inversely correlated with the severity of background chronic liver disease. Objective: This study evaluated whether basal serum IGF-1 levels can predict prognosis of HCC patients according to different risks of disease progression. Materials and Methods: A total of 89 patients with hepatocellular carcinoma (HCC) were recruited in 3 groups: Group I, 30 HCC patients receiving sorafinib; Group II, 30 HCC patients with best supportive care; and Group III include 29 patients undergoing transcatheter arterial chemoembolization (TACE). All patients were investigated for serum levels of AST, ALP, Bb, Cr, BUN, AFP and IGF-I. Results: Patients with disease control had significantly higher baseline IGF-1 levels 210 (185-232.5) ng/mL (p value<0.01) than did patients without disease control. Low basal IGF-1 levels were associated with advanced HCC, such as multiple tumors and advanced stage, and low IGF-1 levels predicted shorter TTP and overall survival in patients treated with TACE. Conclusions: The levels of serum IGF-1, expressed as continuous values, may be helpful for accurately assessing hepatic function and the prognostic stratification of patients with HCC. -
Al-Bakri, Ali;Jawad, Mohammed;Salameh, Pascale;al'Absi, Mustafa;Kassim, Saba 621
Background: Smokefree laws aim to protect employees and the public from the dangers of secondhand smoke. Waterpipe premises have significantly increased in number in the last decade, with anecdotal reports of poor compliance with the smokefree law. The literature is bereft of information pertaining to waterpipe premise employees. This study aimed to opportunistically gather knowledge about the occupational health hazards associated with working in waterpipe premises in London, England. Materials and Methods: Employees from seven convenience-sampled, smokefree-compliant waterpipe premises in London were observed for occupational activities. Opportunistic carbon monoxide (CO) measurements were made among those with whom a rapport had developed. Observations were thematically coded and analysed. Results: Occupational hazards mainly included environmental smoke exposure. Waterpipe-serving employees were required to draw several puffs soon after igniting the coals, thereby providing quality assurance of the product. Median CO levels were 27.5ppm (range 21-55ppm) among these employees. Self-reported employee health was poor, with some suggestion that working patterns and smoke exposure was a contributory factor. Conclusions: The smokefree law in England does not appear to protect waterpipe premise employees from high levels of CO. Continued concerns surrounding chronic smoke exposure may contribute to poor self-reported physical and mental wellbeing. -
Xiong, Wei;Li, Wen-Hui;Jiang, Yong-Xin;Liu, Shan;Ai, Yi-Qin;Liu, Rong;Chang, Li;Zhang, Ming;Wang, Xiao-Li;Bai, Han;Wang, Hong;Zheng, Rui;Tan, Jing 627
Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature. -
Background: In the absence of routine screening program for cervical cancer in Iran and high rate of diagnosed cancer in its advanced stage, recognition of sociodemographic factors related to delayed diagnosis of cancer in Iran could be helpful in reducing the burden of disease in our community. The aim of this study was to determine the stage of cervical cancer at diagnosis and factors related to delayed diagnosis of cervical cancer in Isfahan, Iran. Materials and Methods: In this cross sectional study women diagnosed with cervical cancer for the first time by histo-pathological examination were enrolled. According to the clinical and paraclinical findings and staging of the cancer, they were classified into early and delayed diagnosis of cervical cancer. Sociodemographic factors were compared in the two groups. Results: In this study of 55 women mean age was
$48.3{\pm}12.0.$ According to our classification 6/55 (10.9%) and 49/55 (89.1%) of them had early and delayed diagnosis of cervical cancer. Delayed diagnosis of the cancer was significantly higher in patients with lower degree of education, lower socioeconomic status, having smoker and addict husband and those who did not have a history of Pap smear test (p<0.05). Conclusions: The results of this study indicated risk factors related to delayed diagnosis of cervical cancer. The affected women should be targeted for implementation of specialized educational programmes for improving knowledge and screening test. -
Parikh, Darshit;Ieso, Paolo De;Garvey, Gail;Thachil, Thanuja;Ramamoorthi, Ramya;Penniment, Michael;Jayaraj, Rama 641
Breast cancer (BC) is potentially a traumatic stressor which may be associated with negative outcomes, such as post-traumatic stress disorder (PTSD) or positive changes, such as post-traumatic growth (PTG). This study aims to identify the core issues of BC related PTSD, PTG and psychological distress by interrogating the literature in BC survivors. We have also highlighted issues related to the assessment, diagnosis and clinical management of PTSD and PTG. The authors systematically reviewed studies published from 1985 to 2014 pertaining to PTSD, psychological distress and PTG in BC survivors with particular attention paid to incidence rates and causative factors. Multiple studies intimated that women with BC have evidence of PTSD at the initial stages of diagnosis, whereas PTG develops once patients undergo treatment. Early diagnosis and treatment of PTSD/PTG is paramount from literature review but the previously mentioned relationship between PTSD and PTG in BC patients could not be verified. It is evident from the literature that a small percentage of BC patients experience PTSD, while the majority experience PTG after BC diagnosis and treatment. Future research should include prospective studies focusing on high-risk patients, causative factors and the development of psychological interventions. -
Background: Lung cancer was one of the most common cancers in both men and women all over the world. In this study, we aimed to clarify who could survive after long term chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: We enrolled 186 patients with stage IV NSCLC after long term chemotherapy from Jun 2006 to Nov 2014 diagnosed in Jiangsu Cancer Hospital. Multiple variables like age, gender, smoking, histology of adenocarcinoma and squamous-cell cancer, number of metastatic sites, metastatic sites (e.g. lung, brain, bone, liver and pleura), hemoglobin, lymphocyte rate (LYR), Change of LYR during multiple therapies, hypertension, diabetes, chronic bronchitis, treatments (e.g.radiotherapy and targeted therapy) were selected. For consideration of factors influencing survival and response for patients with advanced NSCLC, logistic regression analysis and Cox regression analysis were used in an attempt to develop a screening module for patients with elevated survival after long term chemotherapy become possible. Results: Of the total of 186 patients enrolled, 69 survived less than 1 year (short-term group), 45 one to two years, and 72 longer than 3 years (long-term group). For logistic regression analysis, the short-term group was taken as control group and the long-term group as the case group. We found that age, histology of adenocarcinoma, metastatic site (e.g. lung and liver), treatments (e.g. targeted therapy and radiotherapy), LYR, a decreasing tendency of LYR and chronic bronchitis were individually associated with overall survival by Cox regression analysis. A multivariable Cox regression model showed that metastatic site (e.g. lung and liver), histology of adenocarcinoma, treatments (e.g. targeted therapy and radiotherapy) and chronic bronchitis were associated with overall survival. Thus metastatic site (e.g. lung and liver) and chronic bronchitis may be important risk factors for patients with advanced NSCLC. Gender, metastatic site (e.g. lung and liver), LYR and the decreasing tendency of LYR were significantly associated with long-term survival in the individual-variable logistic regression model (P<0.05). On multivariate logistic regression analysis, gender, metastatic site (e.g. lung and liver) and the decreasing tendency of LYR associated with long-term survival. Conclusions: In conclusion, female patients with stage IV adenocarcinoma of NSCLC who had decreasing tendency of LYR during the course therapy and had accepted multiple therapies e.g. more than third-line chemotherapy, radiotherapy and/or targeted therapy might be expected to live longer.
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Ahmed, Hussain Gadelkarim;Suliman, Rania Saad Abdul Gader;Abd El Aziz, Mohammed Siddig;Alshammari, Fawaz D. 653
Background: Nasopharyngeal carcinoma (NPC) is an aggressive disease and tends to involve surrounding tissues, and biomarkers for better management are yet to be identified. Materials and Methods: One hundred and fifty tissue samples with NPC diagnosis were were investigated using pan cytokeratin (CK) and epithelial membrane protein 2 (EMP2) antibodies. Results: Immunohistochemical expression of CK was identified in 144/150 (96%) and of EMP2 in 120/150 (80%). Conclusions: There is a high loss of EMP2 in NPC, especially high grade examples. Loss of CK expression is also linked to high grade NPC types. -
Korkmaz, Huseyin;Findik, Duygu;Ugurluoglu, Ceyha;Terzi, Yuksel 657
Background: A diagnosis of H. pylori infection can be made by invasive or non-invasive methods. Several noninvasive diagnostic tests based on the detection of H. pylori stool antigen (HpSA) have been developed. The Genx H. pylori stool antigen card test is a new rapid, non-invasive test that is based on monoclonal immunochromatographic assay. The aim of this study was to determine its sensitivity, specificity, and diagnostic accuracy for diagnosing H. pylori infection in adult patients. Materials and Methods: A total of 162 patients were included in the study. A gastric biopsy was collected for histopathology and rapid urease testing. Stool specimens for HpSA testing were also collected. Patients were considered H. pylori positive if two invasive tests (histological and rapid urease tests) were positive. Results: Using the reference test, 50.6% of the samples were positive for H. pylori infection. The Genx H. pylori antigen test was positive in 19.7% of patients. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the Genx H. pylori antigen test were 51.6%, 96.0%, 88.8%, 76.1%, and 79.0%, respectively. Conclusions: The Genx H. pylori stool antigen card test is a new non-invasive method that is fast and simple to perform but provides less reliable results. -
Chen, Tao;Zhang, Min-Gui;Yu, Xian-Jun;Liu, Liang 661
Background: Postoperative carbohydrate antigen 19-9 (CA19-9) is an independent predictor of survival for pancreatic ductal adenocarcinoma (PDAC), and more powerful than preoperative CA19-9. However, making decisions just dependent on postoperative CA19-9 may result in necessary treatments not being performed. Materials and Methods: A total of 178 patients with resected PDAC were eligible for this retrospective study, classified into two corresponding subgroups according to postoperative CA19-9. Prognostic significance of all clinicopathologic factors was evaluated by univariate and multivariate analyses. Results: Postoperative CA19-9, preoperative CA125 and lymph node status were independent predictors. Better predictive performances for overall survival (OS) and recurrence-free survival (RFS) were achieved by postoperative CA19-9 compared to preoperative CA125 and lymph node status. Particularly, preoperative CA125 was associated with poor OS (p<0.001 for the normalized CA19-9 patients, p=0.012 for the elevated) and RFS (p=0.005 for the normalized, p=0.004 for the elevated). Moreover, preoperative CA125 levels related with survival in double-negative patients. Conclusions: Normalization of CA19-9 is not tantamount to be cured. Preoperative CA125 is a critical predictor for PDAC patients, especially in double-negative patients. -
Al-Naggar, Redhwan A.;Al-Kubaisy, Waqar;Yap, Bee W.;Bobryshev, Yuri V.;Osman, Muhamed T. 667
Background: Colorectal cancer (CRC) is the third most common malignancy in Malaysia, where data are limited regarding knowledge and barriers in regard to CRC and screening tests. The aim of the study was to assess these parameters among Malaysians. Materials and Methods: The questionnaires were distributed in the Umra Private Hospital in Selangor. The questionnaire had four parts and covered social-demographic questions, respondent knowledge about CRC and colorectal tests, attitude towards CRC and respondentaction regarding CRC. More than half of Malay participants (total n=187) were female (57.2%) and 36.9% of them were working as professionals. Results: The majority of the participants (93.6%) never had a CRC screening test. The study found that only 10.2% of the study participants did not consider that their chances of getting CRC were high. A high percentage of the participants (43.3%) believed that they would have good chance of survival if the cancer would be found early. About one third of the respondents did not want to do screening because of fear of cancer, and concerns of embarrassment during the procedure adversely affected attitude to CRC screening as well. Age, gender, income, family history of CRC, vegetable intake and physical activity were found to be significant determinants of knowledge on CRC. Conclusions: The major barriers identified towards CRC screening identified in our study were fear of pain and embarrassment. The findings have implications for understanding of similarities and differences in attitude to CRC amongst elderly patients in other cultural/geographic regions. -
Haseen, Syed Danish;Khanam, Aziza;Sultan, Naheed;Idrees, Farah;Akhtar, Naheed;Imtiaz, Fauzia 675
Background: There are several validated risk factors for breast cancer. However the legitimacy of elevated fasting blood glucose (FBG) is not well established. This study was designed to assess this parameter as a risk factor for breast cancer among pre- and post-menopausal women. Materials and Methods: This case-control study was conducted at Department of Biochemistry, University of Karachi from June 2010 to August 2014. Simple random sampling technique was used to collect data of study subjects comprising 175 diagnosed breast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachi and 175 healthy controls from various screening programs. Blood samples were analyzed for FBG and serum insulin. Results: FBG, HOMA-IR, systolic and diastolic blood pressure were significantly raised in breast cancer cases when compared to control subjects. Cases and controls were further categorized in to two groups using cutoff value of 110mg/dl to distinguish subjects into normal fasting glucose (<110mg/dl) and having impaired fasting glucose (${\geq}110-{\leq}125mg/dl$ ) or diabetes (${\geq}126mg/dl$ ). Odds ratios were found to be 1.57, 2.15 and 1.17 in overall, pre-menopausal and post-menopausal groups, respectively. (all p < 0.05). Conclusions: A statistically significant risk of breast cancer exists in women having elevated fasting blood glucose levels, corresponding to prediabetes and diabetes, among pre and postmenopausal ages, with comparatively greater effects in the premenopausal group. -
Liu, Zhong;Wang, Xin-Mei;Jia, Tong-Fu;Zhai, Yi;Sun, Ling-Yan;Cheng, Yu-Ping;Zhang, Yue-Min;Liu, Shi-Hai;Liang, Jun 679
Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC. -
Chihara, Takeshi;Shimpo, Kan;Kaneko, Takaaki;Beppu, Hidehiko;Higashiguchi, Takashi;Sonoda, Shigeru;Tanaka, Miyuki;Yamada, Muneo;Abe, Fumiaki 683
Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment. -
Frequency of EGFR Mutations in Non-small Cell Lung Cancer Patients: Screening Data from West SiberiaGervas, Polina;Ivanova, Anna;Vasiliev, Nikolay;Ananina, Olga;Zharkova, Olga;Rogovieva, Olga;Verzhbitskaya, Natalia;Didichuk, Ivan;Cheremisina, Olga;Popova, Natalia;Goldberg, Victor;Cherdyntsev, Evgeny;Choynzonov, Evgeny;Cherdyntseva, Nadezda 689
Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. Materials and Methods: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. Results: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. Conclusions: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients. -
Zhao, Xu-Ye;Cui, Yongm;Jiang, Shu-Fang;Liu, Ke-Jun;Han, Hai-Qiong;Liu, Xiao-Su;Li, Yali 693
Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test. -
Nguyen, Dinh Thang;Phan, Tuan Nghia;Kumasaka, Mayuko Y.;Yajima, Ichiro;Kato, Masashi 699
Vemurafenib has recently been used as drug for treatment of melanomas with$BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant$BRAF^{V600E}$ melanoma cell lines,$A375P^R$ ,$A375M^R$ and SKMEL-$28^R$ , were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-$28^R$ cells. Treatment of SKMEL-$28^R$ cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of$BRAF^{V600E}$ -mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells. -
Ogawa, Shimpei;Itabashi, Michio;Hirosawa, Tomoichiro;Hashimoto, Takuzo;Bamba, Yoshiko;Kameoka, Shingo 707
Background: To evaluate use of magnetic resonance imaging (MRI) and a logistic model including risk factors for lymph node metastasis for improved diagnosis. Materials and Methods: The subjects were 176 patients with rectal cancer who underwent preoperative MRI. The longest lymph node diameter was measured and a cut-off value for positive lymph node metastasis was established based on a receiver operating characteristic (ROC) curve. A logistic model was constructed based on MRI findings and risk factors for lymph node metastasis extracted from logistic-regression analysis. The diagnostic capabilities of MRI alone and those of the logistic model were compared using the area under the curve (AUC) of the ROC curve. Results: The cut-off value was a diameter of 5.47 mm. Diagnosis using MRI had an accuracy of 65.9%, sensitivity 73.5%, specificity 61.3%, positive predictive value (PPV) 62.9%, and negative predictive value (NPV) 72.2% [AUC: 0.6739 (95%CI: 0.6016-0.7388)]. Age (<59) (p=0.0163), pT (T3+T4) (p=0.0001), and BMI (<23.5) (p=0.0003) were extracted as independent risk factors for lymph node metastasis. Diagnosis using MRI with the logistic model had an accuracy of 75.0%, sensitivity 72.3%, specificity 77.4%, PPV 74.1%, and NPV 75.8% [AUC: 0.7853 (95%CI: 0.7098-0.8454)], showing a significantly improved diagnostic capacity using the logistic model (p=0.0002). Conclusions: A logistic model including risk factors for lymph node metastasis can improve the accuracy of MRI diagnosis of rectal cancer. -
Guo, Cheng-Xian;Yang, Guo-Ping;Pei, Qi;Yin, Ji-Ye;Tan, Hong-Yi;Yuan, Hong 713
Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients. -
Zhu, Fang-Lai;Ling, An-Sheng;Wei, Qi;Ma, Jie;Lu, Gang 719
Objective: To evaluate the values of 4 tumor markers in serum and ascites and their ascites/serum ratios in the identification and diagnosis of benign and malignant ascites. Materials and Methods: A total of 76 patients were selected as subjects and divided into malignant ascites group (45 cases) and benign ascites group (31 cases). Samples of ascites and serum of all hospitalized patients were collected before treatment. The levels of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), cancer antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9) were detected by chemiluminescence (CLIA). Results: CEA, AFP and CA19-9 in both serum and ascites as well as CA125 in ascites were evidently higher in the malignant ascites group than in the benign ascites group (P<0.01). Malignant ascites was associated with elevated ascites/serum ratios for AFP and CA125 (P<0.01). The areas under receiver operating characteristic (AUROCs) of CEA and CA125 in ascites and the ratios of ascites/serum of AFP, CEA, CA125 and CA19-9 were all >0.7, suggesting certain values, while those of ascites CA19-9 and serum CEA were 0.697 and 0.629 respectively, indicating low accuracy in the identification and diagnosis of benign and malignant ascites. However, the AUROCs of the remaining indexes were <0.5, with no value for identification and diagnosis. Compared with single index, the sensitivity of combined detection increased significantly (P<0.05), in which the combined detection of CEA, CA19-9 and CA125 in ascites as well as the ratio of ascites/serum of CEA, CA19-9, CA125 and AFP had the highest sensitivity (98.4%) but with relevantly low specificity. Both sensitivity and specificity of combined detection should be comprehensively considered so as to choose the most appropriate index. Conclusions: Compared with single index, combined detection of tumor markers in serum and ascites can significantly improve the diagnostic sensitivity and specificity. -
Yahaya, Nor Aziyan;Subramanian, Pathmawathi;Bustam, Anita Zarina;Taib, Nur Aishah 723
Background: This study was performed to assess patient symptoms prevalence, frequency and severity, as well as distress and coping strategies used, and to identify the relationships between coping strategies and psychological and physical symptoms distress and demographic data of cancer patients. This cross-sectional descriptive study involved a total of 268 cancer patients with various types of cancer and chemotherapy identified in the oncology unit of an urban tertiary hospital. Materials and Methods: Data were collected using questionnaires (demographic questionnaire, Medical characteristics, Memorial Symptom Assessment Scale (MSAS) and Brief COPE scales and analyzed for demographic, and disease-related variable effects on symptom prevalence, severity, distress and coping strategies. Results: Symptom prevalence was relatively high and ranged from 14.9% for swelling of arms and legs to 88.1% for lack of energy. This latter was the highest rated symptom in the study. The level of distress was found to be low in three domains. Problem-focused coping strategies were found to be more commonly employed compared to emotion-focused strategies, demonstrating significant associations with sex, age group, educational levels and race. However, there was a positive correlation between emotion-focused strategies and physical and psychological distress, indicating that patients would choose emotion-focused strategies when symptom distress increased. Conclusions: These findings demonstrate that high symptom prevalence rates and coping strategies used render an improvement in current nursing management. Therefore development of symptoms management groups, encouraging the use of self-care diaries and enhancing the quality of psychooncology services provided are to be recommended. -
Kye, Su Yeon;Kwon, Jeong Hyun;Kim, Yong-Chan;Shim, Minsun;Kim, Jee Hyun;Cho, Hyunsoon;Jung, Kyu Won;Park, Keeho 731
Background: Little is known about the news coverage of cancer risk factors in Korea. This study aimed to examine how the news media encompasses a wide array of content regarding cancer risk factors and related cancer sites, and investigate whether news coverage of cancer risk factors is congruent with the actual prevalence of the disease. Materials and Methods: A content analysis was conducted on 1,138 news stories covered during a 5-year period between 2008 and 2012. The news stories were selected from nationally representative media in Korea. Information was collected about cancer risk factors and cancer sites. Results: Of various cancer risk factors, occupational and environmental exposures appeared most frequently in the news. Breast cancer was mentioned the most in relation to cancer sites. Breast, cervical, prostate, and skin cancer were overrepresented in the media in comparison to incidence and mortality cases, whereas lung, thyroid, liver, and stomach cancer were underrepresented. Conclusions: To our knowledge, this research is the first investigation dealing with news coverage about cancer risk factors in Korea. The study findings show occupational and environmental exposures are emphasized more than personal lifestyle factors; further, more prevalent cancers in developed countries have greater media coverage, not reflecting the realities of the disease. The findings may help health journalists and other health storytellers to develop effective ways to communicate cancer risk factors. -
Thamnirat, Kanungnij;Utamakul, Chirawat;Chamroonrat, Wichana;Kositwattanarerk, Arpakorn;Anongpornjossakul, Yoch;Sritara, Chanika 737
Purpose: The study aim was to assess factors that impact on the outcome of radioiodine therapy in patients diagnosed with differentiated thyroid carcinoma (DTC). Materials and Methods: We performed a retrospective cohort study on 256 patients with DTC who underwent thyroidectomy and received radioiodine therapy during December 2003 to January 2012. All patients were followed up for at least 1 year. They were considered diseasefree by the criteria of the revised American Thyroid Association Management Guideline for Patients with Thyroid nodules and DTC (ATA guideline 2009). Results: On Cox univariate analysis, factors associated with disease-free status were age<45, stage I tumor, low risk group by histopathology, unifocal tumor involvement, stimulated serum Tg level at 1st dose of radioiodine therapy and no distant metastasis from 1st post-treatment WBS (post RxWBS). On multivariate analysis, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy < 30 ng/mL were the significant prognostic factors that increased disease-free rate by 1.73 times and 2.60 times, respectively (P-value <0.05). Conclusions: Factors affecting the outcome of radioiodine therapy in our study were age, stage, risk of recurrence by histopathology, unifocal tumor involvement and 1st postRxWBS findings. From these factors, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy were independent prognostic factors that substantial increase the disease-free rate. -
Liu, Chun-Ju;Zhang, Xia-Li;Luo, Da-Ya;Zhu, Wei-Feng;Wan, Hui-Fang;Yang, Jun-Ping;Yang, Xiao-Jun;Wan, Fu-Sheng 741
Purpose: To investigate the influence of exogenous p53 upregulated modulator of apoptosis (PUMA) expression on cell proliferation and apoptosis in human non-small cell lung cancer A549 cells and transplanted tumor cell growth in nude mice. Materials and Methods: A549 cells were divided into the following groups: control, non-carrier (NC), PUMA (transfected with pCEP4-(HA) 2-PUMA plasmid), DDP ($10{\mu}g/mL$ cisplatin treatment) and PUMA+DDP (transfected with pCEP4-(HA)2-PUMA plasmid and$10{\mu}g/mL$ cisplatin treatment). The MTT method was used to detect the cell survival rate. Cell apoptosis rates were measured by flow cytometry, and PUMA, Bax and Bcl-2 protein expression levels were measured by Western blotting. Results: Compared to the control group, the PUMA, DDP and PUMA+DDP groups all had significantly decreased A549 cell proliferation (p<0.01), with the largest reduction in the PUMA+DDP group. Conversely, the apoptosis rates of the three groups were significantly increased (P<0.01), and the PUMA and DDP treatments were synergistic. Moreover, Bax protein levels significantly increased (p<0.01), while Bcl-2 protein levels significantly decreased (p<0.01). Finally, both the volume and the weights of transplanted tumors were significantly reduced (p<0.01), and the inhibition ratio of the PUMA+DDP group was significantly higher than in the single DDP or PUMA groups. Conclusions: Exogenous PUMA effectively inhibited lung cancer A549 cell proliferation and transplanted tumor growth by increasing Bax protein levels and reducing Bcl-2 protein levels. -
Wuxiao, Zhi-Jun;Zhou, Hai-Yan;Wang, Ke-Feng;Chen, Xiao-Qin;Hao, Xin-Bao;Lu, Yan-Da;Xia, Zhong-Jun 747
Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice. -
Ay, Serden;Eryilmaz, Mehmet Ali;Aksoy, Nergis;Okus, Ahmet;Unlu, Yasar;Sevinc, Baris 753
Background: Red cell distribution width (RDW) is one of the standard parameters with blood cell counts. Much previous research has indicated that it increases in cases of systemic inflammation or cardiametabolic incident. However, information on the relation of RDW with solid tumors causing systemic inflammation is limited. In the present research, we examined the relation of RDW with malignant and benign lesions of the colon. Materials and Methods: 115 patients with colon polyps (group 1), and 30 with colon cancer (group 2) who were diagnosed histopathologically in our clinic between January 2010-January 2013 were scanned retrospectively. Patients with anemia, hematologic diseases and active inflammation were excluded. RDW, mean corpuscular volume (MCV), hemoglobin (Hgb) and platelet (Plt) measurements were recorded and their relations with the malignant and benign lesions of the colon were examined. Results: Both groups were similar in age and gender distribution. RDW values of patients with colon cancer were significantly higher than the patients with colon polyp (p=0,01). No significant differences were detected between the two groups in terms of MCV and Plt values (p>0,05). Conclusions: RDW can be used as an early warning biomarker for solid colon tumors. Further prospective research is required on the relations of cheap and easily measured RDW parameters with colon malignancies. -
Ahmad, Zubair;Din, Nasir Ud;Ahmad, Arsalan;Imran, Sheharbano;Pervez, Shahid;Ahmed, Rashida;Kayani, Naila 757
Aim: To present the epidemiologic data (age, gender, size etc) and histopathologic and immunohistochemical features of cases of rhabdomyosarcoma (RMS) reported in our department. Settings: Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. Duration: All cases of RMS diagnosed between January 1, 2003 and December 31, 2012 were included in the study. Results: A total of 277 cases were included. Embryonal rhabdomyosarcoma (ERMS) was by far the dominant histologic type (87.4%) followed by alveolar type (ARMS)(9.4%). ERMS was much more common in males (64.0%)and over 65% of cases occurred in the first decade of life (over 90% in the first two decades). Head and neck region was commonest site for ERMS (46.7%), followed by the genitourinary system (16.1%). Over 65% cases of ARMS occurred in the extremities. Over 80% cases of ARMS occurred in the first 3 decades of life. Immunohistochemical staining for Desmin and MyoD1 was positive in 96.7% and 85.4% respectively. Conclusions: The epidemiologic data and microscopic findings in our patients are similar to international published data on rhabdomyosarcoma. -
Tawil, Mirna;Bekdash, Amira;Mroueh, Mohammad;Daher, Costantine F.;Abi-Habib, Ralph J. 761
Background: In this study, we used Daucus carota oil extract (DCOE) to target acute myeloid leukemia (AML) cells. All the AML cell lines tested were sensitive to the extract while peripheral mononuclear cells were not. Analysis of mechanism of cell death showed an increase in cells positive for annexinV and for active caspases, indicating that DCOE induces apoptotic cell death in AML. Inhibition of the MAPK pathway decreased sensitivity of AML cells to DCOE, indicating that cytotoxicity may be dependent on its activity. In conclusion, DCOE induces selective apoptosis in AML cells, possibly through a MAPK-dependent mechanism. -
Sheng, Xu-Dong;Chen, Hu;Wang, Hui;Ding, Zhi-Bin;Xu, Gang-Zhu;Zhang, Jun-Feng;Lu, Wen-Chao;Wu, Tao;Zhao, Ling 769
Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas. -
Liu, Di;Xu, Wen;Zhang, Zhi-Wei;Qian, Ji;Zheng, Hui;Zhang, Jie;Su, Bo 775
Background: RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. In this study, we investigated the influence of RB1 single nucleotide polymorphisms (SNPs) on the efficacy of platinum-taxane regimens in advanced NSCLC patients. Materials and Methods: 234 cases of patients with advanced NSCLC who were treated with first-line platinum-taxane agents were enrolled in this study. Genomic DNA was extracted from patients' peripheral blood samples using a QIAamp DNA Maxi Kit, and genotyped by iSelect HD Bead-Chip. Results: Regression analyses were conducted through the univariate and multivariate Cox proportional hazards model in the 234 patients. The results showed that of the eight RB1 tagSNPs, only rs4151510 was a positive predictive factor for the advanced NSCLC patients treated with platinum taxanes regimen. The patients with G/G genotype of RB rs4151510 had longer overall survival (OS) than the non-G/G genotype (p=0.018). The histology was also correlated with OS in the whole advanced NSCLC patients. Three tagSNPs of RB1, rs4151510, rs4151465, rs9568036 were significantly associated with OS in the advanced NSCLC patients with squamous cell histology using Kaplan-Meier overall survival analysis stratified by histology. Conclusions: RB1 genomic variants were correlated with the efficacy of platinum-taxanes regimen. RB rs4151510 is an independent factor of the prognosis of NSCLC patients receiving platinum-taxane chemotherapy. -
Silay, Kamile;Akinci, Sema;Silay, Yavuz Selim;Guney, Tekin;Ulas, Arife;Akinci, Muhammed Bulent;Ozturk, Esin;Canbaz, Merve;Yalcin, Bulent;Dilek, Imdat 783
Background: Utilizing geriatric screening tools for the identification of vulnerable older patients with cancer is important. The aim of this study is to evaluate the hospitalization risk of elderly hematologic cancer patients based on geriatric assessment and laboratory parameters. Materials and Methods: In this cross sectional study 61 patients with hematologic malignancies, age 65 years and older, were assessed at a hematology outpatient clinic. Standard geriatric screening tests; activities of daily living (ADL), instrumental activities of daily living (IADL), Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE), timed up and go test (TUG), geriatrics depression scale (GDS) were administered. Demographic and medical data were obtained from patient medical records. The number of hospitalizations in the following six months was then recorded to allow analysis of associations with geriatric assessment tools and laboratory parameters. Results: The median age of the patients, 37 being males, was 66 years. Positive TUG test and declined ADL was found as significant risk factors for hospitalization (p=0.028 and p=0.015 respectively). Correlations of hospitalization with thrombocytopenia, vitamin B12 and folic acid deficiency were statistically significant (p=0.004, p=0.011 and p=0.05 respectively). Conclusions: In this study, geriatric conditions which are usually unrecognized in a regular oncology office visit were identified. Our study indicates TUG and ADL might be use as predictive tests for hospitalization in elderly oncology populations. Also thrombocytopenia, and vitamin B12 and folic acid deficiencies are among the risk factors for hospitalization. The importance of vitamin B12 and folic acid vitamin replacement should not be underestimated in this population. -
Cheraghi, Maria;Amoori, Neda;Fallahzadeh, Hosein;Rahmani, Hossein 787
Background: Non-Hodgkins lymphoma (NHL) is a heterogeneous group of malignancies, originating in the lymphatic organs, whose incidence is increasing in developed as well as developing countries. Epidemiological evidence suggests that aspirin may reduce the incidence and mortality of several cancers. The main objective of this study was to evaluate the potential relationship between using aspirin and development of NHL with a meta-analysis. Materials and Methods: A total of 7 studies were included. Outcome was calculated and reported as odds ratios (ORs). Heterogeneity was assessed with Cochrane Q and$I^2$ statistics. Dissemination bias was evaluated by funnel plot visualization and trim-and-fill analysis. Results: Our analysis showed OR of developing NHL overall of 1(95% CI: 0.87-1.16, p=0.9), and in females this was 0.81 (95%CI: 0.72-.92, p=0.001) and in males 1.01 (95%CI: 0.82-1.26, p=0.86). The odds ratio (OR) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was 0.85 (95%CI: 0.75-0.97, p=0.02), The ORs of follicular lymphoma (FL) and large B-cell lymphoma (DLBCL) in individuals exposed to aspirin were 1.12 (95%CI: 0.86-1.45, p=0.37) and 1.03 (95%CI: 0.9-1.19, p=0.6) respectively. Conclusions: In conclusion, individuals taking aspirin do not demonstrate any change in risk of Non-Hodgkins lymphoma. -
Zeeshan, Rozina;Sultan, Sadia;Irfan, Syed Muhammad;Kakar, Jamaludin;Hameed, Muhammad Asif 793
Background: Chronic lymphoid leukemia (CLL) is not an uncommon hematological malignancy which primarily affects elderly individuals. It is more common in developed world than in developing countries. The rational of this study was to determine the clinico-hematological profile in Pakistan. Materials and Methods: In this prospective cross sectional study, sixty patients with CLL were enrolled from January 2011 to June 2013. Data were analyzed with SPSS version 21. Results: The mean age was$59.0{\pm}9.2years$ (range 40-82) and the male to female ratio was 2.1:1. Peak age group was 60-70 years (38.3%) and 18.3% were under 50 years old. Major complaints were weakness (51.7%), fever (18.3%) and abdominal discomfort (13.3%). Main clinical findings were splenomegaly (46.6%), lymphadenopathy (36.6%) and pallor (26.7%). Some 16.7% were diagnosed incidentally. The mean hemoglobin was$10.8{\pm}2.4g/dl$ , with a total leukocyte count of$91.5{\pm}87.8{\times}10^9/l$ and platelets$197.8{\pm}103.2{\times}10^9/l$ . Anemia and thrombocytopenia were seen in 26.7% and 21.7% of cases, respectively. High LDH and hyperuricemia were detected in 15% each and elevated serum creatinine was seen in 11.6%. According to Rai staging 11.6% were in stage 0, 13.3% stage 1, 26.7% each for stage II and stage III while 21.7% patients were in stage IV. Conclusions: CLL in our patients in Pakistan, unlike in the West, is seen in a relatively young population with male predominance. Primarily disease is of B-cell origin and about 2/3 of the patients present at advanced stage. -
Li, Ming-Huan;Shang, Dong-Ping;Chen, Chen;Xu, Liang;Huang, Yong;Kong, Li;Yu, Jin-Ming 797
Background: The purpose of this study was to prospectively evaluate the predictive value of perfusion computed tomography (CT) for response of local advanced esophageal carcinoma to radiotherapy and chemotherapy. Materials and Methods: Before any treatment, forty-three local advanced esophageal squamous cell carcinomas were prospectively evaluated by perfusion scan with 16-row CT from June 2009 to January 2012. Perfusion parameters, including perfusion (BF), peak enhanced density (PED), blood volume (BV), and time to peak (TTP) were measured using Philips perfusion software. Seventeen cases received definitive radiotherapy and 26 received concurrent chemo-radiotherapy. The response was evaluated by CT scan and esophagography. Differences in perfusion parameters between responders and non-responders were analyzed, and ROCs were used to assess predictive value of the baseline parameters for treatment response. Results: There were 25 responders (R) and 18 non-responders (NR). Responders showed significantly higher BF (R:34.1 ml/100g/min vs NR: 25.0 ml/100g/min, p=0.001), BV (23.2 ml/100g vs 18.3 ml/100g, p=0.009) and PED (32.5 HU vs 28.32HU, P=0.003) than non-responders. But the baseline TTP (R: 38.2s vs NR: 44.10s, p=0.172) had no difference in the two groups. For baseline BF, a threshold of 36.1 ml/100g/min achieved a sensitivity of 56%, and a specificity of 94.4% for detection of clinical responders from non-responders. Conclusions: The results suggest that the perfusion CT can provide some helpful information for identifying tumors that may respond to radio-chemotherapy. -
Ahmed, Nagwa S.;Shafik, Noha M.;Elraheem, Omar Abd;Abou-Elnoeman, Saad-Eldin A. 803
Background: Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Purpose: Aim of this study was to determine the role of serum arylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between (PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Results: Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. Conclusions: serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer. -
Bhagabaty, Srabana Misra;Kataki, Amal Chandra;Kalita, Manoj;Salkar, Shekhar 811
Background: North East India has a high prevalence of tobacco consumption, but only few individuals seek help for tobacco cessation. Impact of community based tobacco cessation intervention in this part needs more research. Materials and Methods: Retrospective analysis was done on the dataset from a community-based tobacco cessation intervention pilot project conducted in Guwahati metro during 2009-10. Subjects, both male and female tobacco users, age > 15 years, permanent residents of these blocks giving consent were included in the study. Results: The sample was 800 tobacco users, of whom 25% visited any health care provider during last 12 months and 3% received tobacco cessation advice. An 18% quit rate was observed at six weeks follow up, more than the National average, with a 47% quit rate at eight months, while 52% of subjects reduced use. Conclusions: Higher tobacco quit rate and reduced tobacco use, no loss to follow up and negligible relapse was observed with this community based intervention design. Such designs should be given more emphasis for implementation in specified communities with very high tobacco consumption rates, cultural acceptance of tobacco and less motivation towards quitting. -
Ulas, Arife;Tokluoglu, Saadet;Kos, Mehmet;Silay, Kamile;Akinci, Sema;Oksuzoglu, Berna;Alkis, Necati 815
Purpose: In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC) varieties on survival rates. Materials and Methods: A retrospective study was performed in patients with NSCLC who were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Of the 844 patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in women than in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statistically significant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women and men. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs 10.0 months; p=0.006) and who had a hemoglobin level${\geq}12g/dL$ (18.0 vs 12.0 months; p=0.01) were found to have a better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 months in males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months in males (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, the median OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapy was higher in women than in men (p=0.03). Conclusions: In our study, we found that survival duration is longer and chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and who are mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences may provide clarity on this subject. -
Yan, Jian;Liu, Xiao-Long;Han, Lu-Zhe;Xiao, Gang;Li, Ning-Lei;Deng, Yi-Nan;Yin, Liang-Chun;Ling, Li-Juan;Yu, Xiao-Yuan;Tan, Can-Liang;Huang, Xiao-Ping;Liu, Li-Xin 823
The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$ , as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$ , lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$ . Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$ , and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC. -
Tumor fluid accumulation occurs in both human cancer and experimental tumor models. Solid tumors show a tendency to tumor fluid accumulation because of their anatomical and physiological features and this may be influenced by molecular factors. Fluid accumulation in the peri-tumor area also occurs in the Dunning model of rat prostate cancer as the tumor grows. In this study, the effects of tumor fluids that were obtained from Dunning prostate tumor-bearing Copenhagen rats on the strongly metastatic MAT-LyLu cell line were investigatedby examining the cell's migration and tumor fluid's toxicity and the kinetic parameters such as cell proliferation, mitotic index, and labelling index. In this research, tumor fluids were obtained from rats injected with
$2{\times}10^5$ MAT-LyLu cells and treated with saline solution, and 200 nM tetrodotoxin (TTX), highly specific sodium channel blocker was used. Sterilized tumor fluids were added to medium of MAT-LyLu cells with the proportion of 20% in vitro. Consequently, it was demonstrated that Dunning rat prostate tumor fluid significantly inhibited proliferation (up to 50%), mitotic index, and labeling index of MAT-LyLu cells (up to 75%) (p<0.05) but stimulated the motility of the cells in vitro. -
Silay, Kamile;Akinci, Sema;Ulas, Arife;Silay, Yavuz Selim;Akinci, Muhammed Bulent;Ozturk, Esin;Canbaz, Merve;Dilek, Imdat;Yalcin, Bulent 837
Background: The disclosure of a diagnosis of cancer is complex, particularly in older patients. The aim of this study was to investigate the association between age and not knowing the diagnosis, and its impact on mood. Materials and Methods: The study included 70 patients with various types of solid and hematologic cancer in early stages, which were followed up in an outpatient oncology/hematology clinic in Turkey between January, 2014 and June, 2014. Initially the caregivers of patients were asked whether the patients knew their diagnosis or not. A questionnaire for the Geriatric Depression Scale was then administered to the patients. Patient age, gender, marital status and education level were noted and analyzed with respect to knowing the diagnosis and depression. Results: Of the 70 patients, 40% of them were female. The mean age was$68.2{\pm}8.9$ . The rate of the patients who does not know their diagnosis was 37.1% (n=26). The overall depression rate with GDS was found 37.1% (n=26) among the participants. There was no association with knowing the diagnosis (p=0.208) although the association between not knowing the diagnosis and age was significant (p=0.01). Conclusions: In this study we revealed no association between not knowing the diagnosis and depression in elderly patients. Contrary to what some has thought, the patient is not protected from psychological distress by not being informed about the diagnosis. We believe this study and similar ones will help to discuss and further explore patient autonomy, the principle of respect to self-determination and end of life issues in different cultures. -
Ismaili, Ahmad;Yari, Kheirollah;Moradi, Mohammad-Taher;Sohrabi, Maryam;Kahrizi, Danial;Kazemi, Elham;Souri, Zahra 841
Background: Gastric cancer as one of the most important diseases affecting health in all worldwide. Current studies have confirmed associations of cytokine gene polymorphisms with the risk of gastric cancer development. The current research aimed to assess the association of IL-1B+3954 genotypes with the risk of gastric cancer in the Iranian population. Materials and Methods: This case-control study covered 49 gastric cancer patients compared to 53 cancer free individuals as a control group. Genomic-DNA extraction was carried out from bioptic samples of patients and peripheral blood of healthy volunteers. Polymorphism of IL-1B +3954 genotypes were analysed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of IL-1B +3954 A1A1, A1A2 and A2A2 genotypes in healthy individuals were 26.4, 66 and 7.6 %, respectively. However, in gastric cancer patients, A1A1, A1A2 and A2A2 with 4.1, 51 and 44.9% were observed (p<0.05). Conclusions: The findings of our results show a positive association between the IL-1B+3954 genotype distribution and the risk of gastric cancer disease in the Iranian population. -
Das, Lala Tanmoy;Wagner, Christina D.;Bigatti, Silvia M. 845
Cancer illness representations and screening history among residents of Kolkata, India, were investigated along with socio-demographic characteristics in an effort to understand possible motivations for health behavior. A total of 106 participants were recruited from community locations in Kolkata, India and completed surveys including demographics, the illness perception questionnaire-revised (IPQ-R), and previous experience with cancer and screening practices. Participants were 51.5% college educated, 57% female, 51.5% full-time employed with average age of 32.7 years (R: 18-60 years). Descriptive statistics were generated for the subscales of the IPQ-R, cancer-screening practices and cancer experience. Correlation analyses were conducted to investigate associations between cancer representations and socio-demographic variables. Univariate ANOVAs were calculated to determine gender differences in IPQ-R subscales and differences between participants who knew someone diagnosed with cancer versus those who did not. While 76% of participants knew someone with cancer, only 5% of the sample engaged in cancer screening. Participants perceived cancer as a serious illness with negative emotional valence. Younger age (r(100)=-.36, p<0.001) and male gender (F(1, 98)=5.22, p=0.01,${\eta}_2$ =0.05) were associated with better illness coherence. Males also reported greater personal control (F(1, 98)=5.34, p=0.02,${\eta}_2$ =0.05) were associated with better illness coherence. Low screening rates precluded analyses of the relationship between illness representations and cancer screening. Cancer was viewed as a threatening and uncontrollable disease among this sample of educated, middle class Kolkata residents. This view may act as a barrier to seeking cancer screening. Public awareness campaigns aimed at improving understanding of the causes, symptoms and consequences of cancer might reduce misunderstandings and fear, especially among women and older populations, who report less comprehension of cancer.