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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Kim, Yun Ju;Kim, Sung Hun;Choi, Byung Gil;Kang, Bong Joo;Kim, Hyeon Sook;Cha, Eun Suk;Song, Byung Joo 2939
Background: While many studies have shown that hormones can influence background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI), only few have directly address the effect of radiotherapy. The purpose of this study was to evaluate the impact of radiotherapy on BPE in breast MRI. Materials and Methods: A retrospective search identified 62 women with unilateral breast cancer who had a breast MRI both before and after radiotherapy following breast-conserving surgery. In our study, we assumed that systemic therapy affected both breasts equivalently. We rated the level of BPE of both breasts using a four-point categorical scale. A change in the level of BPE prior to and after treatment was compared in the diseased and contralateral breasts. Results: All patients received a 4256 to 6480 cGy dose of whole breast radiotherapy over 3-7 weeks. The mean timing of the follow-up study was 6.6 months after completion of radiotherapy. Although the BPE showed a decrease in both breasts after treatment, there was a significant reduction of BPE in the irradiated breast compared with the contralateral breast (1.18 versus 0.98 average reduction in BPE level, p=0.042). Conclusions: Radiotherapy is associated with decrease in BPE with MRI. -
Lee, Su Jin;Park, Jong Hyock;Park, Bo Young;Kim, So Young;Lee, Il Hak;Kim, Jong Heun;Koh, Dai Ha;Kim, Chang-Hoon;Park, Jae Hyun;Sohn, Myong Sei 2945
Background: This study compared risk factors for depression and suicidal ideas among cancer patients for comparison with the general population, and identified influencing factors. Materials and Methods: We analyzed data from 2,472 cancer patients in the National Cancer Center and nine Regional Cancer Centers and frequency-matched data for age and sex from 2,349 members of the general population who completed the National Health and Nutrition Examination Survey in 2008. Logistic regression analysis was used to identify factors affecting depression and suicidal ideas. Results: Cancer patients were not likely to have more depression (OR=0.96, 95%CI=0.79-1.18) and were less likely to have suicidal ideas (OR=0.64, 95%CI=0.53-0.79) compared to the general population. Female sex, more stress, and lower quality of life were influencing factors. The additional risk factors for suicidal ideas among cancer patients included income (OR=0.62, 95%CI=0.43-0.91), smoking (OR=1.63, 95% CI=1.06-2.50), recurrence (OR=1.50, 95%CI=1.15-1.95), and chemotherapy (OR=1.66, 95%CI=1.26-2.19). Conclusions: No differences appeared in depression rates between cancer patients and the general population, and cancer patients were less likely to have suicidal ideas. However, cancer patients were likely to have more risk factors than the general population, and those classified as being at high risk of suicide should receive distress management and social economic support, from early in the treatment process. -
Pan, Xiong-Fei;Wen, Ying;Loh, Marie;Wen, Yuan-Yuan;Yang, Shu-Juan;Zhao, Zhi-Mei;Tian, Zhi;Huang, He;Lan, Hui;Chen, Feng;Soong, Richie;Yang, Chun-Xia 2951
Background: Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China. Materials and Methods: We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS. Results: Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of$57.7{\pm}10.6$ ($mean{\pm}SD$ ) and$57.6{\pm}11.1$ years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC. Conclusions: Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region. -
Park, Boyoung;Shin, Aesun;Jung-Choi, Kyunghee;Ha, Eunhee;Cheong, Hae-Kwan;Kim, Hyun Jeong;Park, Kyung Hwa;Jang, Sungmi;Moon, Byung-In;Ha, Mina 2959
While several reproductive and lifestyle-related factors are already well-known as established risk factors for breast cancer, environmental factors have attracted attention only recently. The objective of the current study was to assess the association between the breast cancer incidences in females, the mortality rate and the number of motor vehicles on the one side and the consumption of gasoline which could work as a major source of air pollution at the other side. The breast cancer incidences and the mortality trends were compared with various indices of westernization like dietary patterns or industrialization with 10 years lag of time. Geographical variations with 10, 15 and 20 years lag of time were assessed between the breast cancer incidence in 2010 and the number of motor vehicles as well as the consumption of gasoline. The upward trend of motor vehicle numbers proved to be comparable to those of breast cancer incidence and mortality. However, the consumption of gasoline started to decrease since the mid-1990s. The geographic distribution of motor vehicle numbers and gasoline consumption in 1990 is in a positive correlation with the breast cancer incidence rates in 2010 and the 20-year lag time ($R^2$ 0.379 with the number of motor vehicles and 0.345 with consumption of gasoline). In a linear relationship between the breast cancer incidences in 2010 and the log transformed number of motor vehicles, the log transformed consumption of gasoline in 2000 also showed a positive relationship ($R^2$ 0.367 with the number of motor vehicles and 0.329 with consumption of gasoline). The results of the current study indicate that there may be a positive relation between the number of vehicles, gasoline consumption and the incidence of breast cancer from the aspects of long-term trends and geographical variation. -
Demir, Nalan;Enon, Serkan;Turksoy, Vugar Ali;Kayaalti, Zeliha;Kaya, Seda;Cangir, Ayten Kayi;Soylemezoglu, Tulin;Savas, Ismail 2965
Background: To evaluate association of lung cancer with arsenic and cadmium levels measured in tumor tissue. Materials and Methods: Ninety-five patients with lung cancer tumor tissue obtained surgically were included in this study. Arsenic and cadmium levels were measured and levels of metals were compared among types of lung cancer and with reference to patient data. Results: The histopathologic diagnoses of the 95 cases were SCC, 49, adenocarcinoma, 28, large cell, 11 and SCLC, 1. Mean tumor arsenic and cadmium levels were$149.3{\pm}129.1{\mu}g/kg$ and$276.3{\pm}219.3{\mu}g/kg$ , respectively. Cadmium levels were significantly associated with smoking (p=0.02), histopathologic type (p=0.005), and TNM staging (r=0.325; p=0.001), although arsenic was not related to any parameter (p>0.05). There was no relation between metal levels and mortality (p>0.05). Conclusions: We found a significant association between tumor cadmium levels of patients with lung cancer and smoking, histopathologic type and staging, although there was no relation with arsenic levels. -
Liu, Jiang-Hua;Chen, Gang;Dang, Yi-Wu;Li, Chun-Jun;Luo, Dian-Zhong 2971
Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC. -
Shi, Liang;Wu, Li-Li;Yang, Jian-Rong;Chen, Xiao-Fei;Zhang, Yi;Chen, Zeng-Qiang;Liu, Cun-Li;Chi, Sheng-Ying;Zheng, Jia-Ying;Huang, Hai-Xia;Yu, Fu-Jun;Lin, Xiang-Yang 2979
Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC. -
Ismail, Rehana;Rashid, Rabiya;Andrabi, Khurshid;Parray, Fazl Q.;Besina, Syed;Shah, Mohd Amin;Hussain, Mahboob Ul 2987
Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer. -
Jung, Hyun Il;Jo, Mi Jeong;Kim, Hyung-Rak;Choi, Yung Hyun;Kim, Gun-Do 2993
Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells. -
Zhai, Jing-Ming;Sun, Shi-Jun;Wang, Wei;Zeng, Chao 3001
Annexin A3 has been identified as a novel biomarker in different types of cancers. However, little is known about its clinical significances and and biological roles in gastric cancer. In this study, we assessed annexin A3 expression in 80 patients with gastric cancer and explore its correlation with prognosis Moreover, correlations with Ki-67, Bcl-2 and Bax were also investigated. Expression of annexin A3 was increased in gastric cancer compared with that in normal gastric tissues. Annexin A3 expression was significantly associated with tumor volume and TNM stage (p<0.05). and inversely correlation with prognosis of patients. More interestingly, expression of annexin A3 was positive correlated with Ki-67 and Bcl-2 expression. Our study showed annexin A3 might be a potential prognostic marker for gastric cancer and involved in tumorigenesis by regulating apoptosis and proliferation. -
Tang, Xiao-Kui;Wang, Ke-Jian;Tang, Yu-Kui;Chen, Li 3005
The aims of this study were to investigate the influence of ubiquitin- conjugating enzyme E2C (UBE2C) on biological behavior of lung cancer cells. Using MTT, flow cytometry and invasion assays, we detected UBE2C expression and evaluated its biological properties in these cells, including effects on proliferation, the cell cycle profile and invasive capability. Compared with control cells, the UBE2C transfected cells demonstrated increased cellular proliferation (p<0.05). UBE2C transfected cells also had a lower percentage in G1 phase and a higher percentage in S phase (p<0.05). Importantly, the UBE2C transfected cells had a notable enhancement of cell numbers penetrating the basement membrane compared with the control group (p<0.05). Ectopic up-regulation UBE2C promoted the growth of lung cancer cells in vivo. Furthermore, we found UBE2C increased the expression of cyclin D1 and MMP-2. These results show UBE2C may represent a potential therapeutic target for lung cancer. -
Antic, Ljiljana Gojko;Djikanovic, Bosiljka Svetozar;Antic, Dragan Zivojin;Aleksopulos, Hristos Georgios;Trajkovic, Goran Zivojin 3011
Background: Level of midwife knowledge is particularly important because of their role in the cervical cancer prevention programme. The aim of this study was to examine differences in the level of knowledge among health care students, midwives and women in the general population of Serbia. Materials and Methods: A cross-sectional approach was used with health care students of the medical shool, midwives in their practice, and women visiting a chosen general practitioner as respondents. Results: In comparison with the students and midwives, women had lower level of knowledge of causative agents of the cervical cancer, genital warts, HPV types, screening for cervical cancer as well as about the target population for vaccine and its role. Differences in the numbers of right answers of respondents were statistically significant (p<0.001). Four or more correct answers were obtained from 22.7% women, 35.3% from midwives and 83.8% from students. Conclusions: Midwives should improve their own level of knowledge related to preventive practice for cervical cancer, as well as their personal compliance with recommended practices, in order to be qualified and credible promoters of cervical cancer control among women in Serbia. -
Honarmand, Marieh;Hajihosseini, Alireza;Akbari, Forugh 3017
Background: Oral carcinoma is one of the common types of cancer and one of the 10 leading causes of death around the world. This study was conducted to evaluate senior dental student knowledge about oral cancerous lesions in Zahedan Dental School. Materials and Methods: In this cross-sectional research, all the students in the last academic year at the School of Dentistry were studied during year of 2013. The study questionnaire covered demographic data as well as 12 questions concerning the knowledge of oral cancer. Data were collected and analyzed with SPSS18 using independent t-test, one way ANOVA. Significance level was considered as$p{\leq}0.05$ . Results: Of the 104 senior dental students, with an average age of$27.34{\pm}7.79$ years, who participated in this study, 32 (30.8%) were female and 72 (69.2%) were male. The mean score of the students regarding the knowledge of oral cancer was$7.24{\pm}2.61.20$ students (19.2%) had a weak knowledge, 45 students (43.3%) had a moderate knowledge, and 39 students (37.5%) had a good knowledge. Conclusions: The student knowledge of oral cancer is not satisfactory and they need to receive additional information and education. -
Wu, Dan-Dan;Zhang, Ji-Xiang;Li, Jiao;Dong, Wei-Guo 3021
Background: The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). Materials and Methods: A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. Results: Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. Conclusions: This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings. -
Background: Dynamic changes of cancer-related fatigue (CRF) among hospitalized patients with colorectal cancer were determined. Materials and Methods: This longitudinal, descriptive study involved 96 hospitalized patients with colorectal cancer, all recruited from a tertiary general hospital in Guangzhou, China. Patients completed questionnaires three times to assess the degree of fatigue, and measurement points were within one week of admission, at 2 to 3 days after surgery and 3 weeks after surgery. Results: Significant differences among the three measurement points (p<0.01) were observed. The scores of fatigue in the second survey were the highest, followed by the third and first surveys. Colon cancer patient scores were higher than those of rectal cancer patients with a significant difference (p<0.05). Colorectal patients experienced different degrees of fatigue at different periods during hospitalization. Conclusions: This study highlights the importance of interventions that are carefully tailored to patients based on the characteristics at different periods to alleviate fatigue.
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Luqman, Muhammad;Javed, Muhammad Mohsin;Daud, Shakeela;Raheem, Nafeesa;Ahmad, Jamil;Khan, Amin-Ul-Haq 3035
Background: Lung cancer is one of the most prevalent malignancies in the world and both incidence and mortality rates are continuing to rise in Pakistan. However, epidemiological studies to identify common lung cancer determinants in the Pakistani population have been limited. Materials and Methods: In this retrospective case-control study, 400 cases and 800 controls were enrolled from different hospitals of all provinces of Pakistan. Information about socio-demographic, occupational, lifestyle and dietary variables was extracted by questionnaire from all subjects. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated. and dose-response associations were also assessed for suitable factors. Results: Strong associations were observed for smoking (OR=9.4, 95%CI=6.9-12.8), pesticide exposure (OR=5.1, 95%CI=3.1-8.3), exposure to diesel exhaust (OR=3.1, 95%CI=2.1-4.5), red meat consumption (OR=2.9, 95%CI=1.8-4.7) and chicken consumption (OR=2.8, 95%CI=1.7-49). Other associated factors observed were welding fumes (OR=2.5, 95%CI=1.0-6.5), sedentary living (OR=2.0, 95%CI=1.6-2.6), family history (OR=2.0, 95%CI=0.8-4.9), wood dust (OR=1.9, 95%CI=1.2-3.1), tea consumption (OR=1.8, 95%CI=1.2-2.6), coffee consumption (OR=1.8, 95%CI=1.1-2.8), alcoholism (OR=1.7, 95%CI=1.1-2.5) and asbestos exposure(OR=1.5, 95%CI=0.5-4.4). Consumption of vegetables (OR=0.3, 95%CI=0.2-0.4), juices (OR=0.3, 95%CI=0.3-0.4), fruits (OR=0.7, 95%CI=0.5-0.9) and milk (OR=0.6, 95%CI=0.5-0.8) showed reduction in risk of lung cancer. Strongest dose-response relationships were observed for smoking ($X^2=333.8$ ,$p{\leq}0.0000001$ ), pesticide exposure ($X^2=50.9$ ,$p{\leq}0.0000001$ ) and exposure to diesel exhaust ($X^2=51.8$ ,$p{\leq}0.0000001$ ). Conclusions: Smoking, pesticide exposure, diesel exhaust and meat consumption are main lung cancer determinants in Pakistan. Consuming vegetables, fruits, milk and juices can reduce the risk of lung cancer risk, as in other countries. -
Medina-Jaime, Alma Delia;Reyes-Vargas, Francianella;Martinez-Gaytan, Victoria;Zambrano-Galvan, Graciela;Portillo-DelCampo, Eduardo;Burciaga-Nava, Jorge Alberto;Reyes-Romero, Miguel;Sifuentes-Alvarez, Antonio 3041
The aim of this work was to analyze methylation of the promoter sites of the ESR1 and PGR genes and to determine correlations with immunohistochemical expression of estrogen and progesterone receptors in ductal and lobular breast cancers. An observational, descriptive, molecular study was conducted on 20 ductal and 20 lobular breast cancer samples with immunohistochemical determination of estrogen and progesterone receptor expression. The methylation analysis of ESR1 and PGR promoter sites was carried-out by methylation-specific PCR. For correlation analysis, Kendall's tau coefficient was determined. Positive correlations were found between estrogen and progesterone receptors, estrogen receptor and unmethylated progesterone receptor, progesterone receptor, and unmethylated progesterone receptor. Negative correlations were found between estrogen receptor and methylated progesterone receptor, progesterone receptor and methylated progesterone receptor, methylated and unmethylated estrogen receptor, and methylated and unmethylated progesterone receptor. The results suggest that methylation of promoter sites of ESR1 and PGR is a relatively uncommon event in ductal and lobular breast cancer, and also suggest that the determination of epigenetic states of ESR1 and PGR could represent an alternative or complement to the histopathological expression analysis. -
Xu, Han-Feng;Chen, Lei;Liu, Xian-Dong;Zhan, Yun-Hong;Zhang, Hui-Hui;Li, Qing;Wu, Bin 3045
Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis. -
Wang, Hong-Li;Liu, Mei-Mei;Ma, Xin;Fang, Lei;Zhang, Zong-Feng;Song, Tie-Fang;Gao, Jia-Yin;Kuang, Ye;Jiang, Jing;Li, Lin;Wang, Yang-Yang;Li, Pei-Ling 3051
Previous studies have demonstrated that JMJD2A is a potential oncogene and is overexpressed in human tumors. However, its role in the endometrial carcinoma remains largely unknown. In this study, we discovered that JMJD2A was overexpressed in endometrial carcinoma, using immunohistochemistry, quantitative realtime polymerase chain reaction, and western blotting. Downregulation of JMJD2A led to reduced endometrial carcinoma RL95-2 and ISK cell proliferation, invasion and metastasis as asessed with cell counting kit-8, cell migration and invasive assays. Collectively, our results support that JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target. -
Tantraworasin, Apichat;Lertprasertsuke, Nirush;Kongkarnka, Sarawut;Euathrongchit, Juntima;Wannasopha, Yutthaphan;Saeteng, Somcharoen 3057
Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity. -
Gheytanchi, Elmira;Mehrazma, Mitra;Madjd, Zahra 3065
Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type. -
Wang, Zeng;Cai, Xin-Jun;Shi, Liang;Li, Fei-Yan;Lin, Neng-Ming 3071
Background: To investigate the related risk factors of postoperative nosocomial pneumonia (POP) in patients withI-IIIa lung cancer. Methods: Medical records of 511 patients who underwent resection for lung cancer between January 2012 to December 2012 were retrospectively reviewed. Risk factors of postoperative pneumonia were identified and evaluated by univariate and multivariate analyses. Results: The incidence of postoperative pneumonia in these lung cancer patients was 2.9% (15 cases). Compared with 496 patients who had no pneumonia infection after operation, older age (>60), histopathological type of squamous cell carcinoma and longer surgery time (>3h) were significant risk factors by univariate analysis. Other potential risk factors such as alcohol consumption, history of smoking, hypersensitivity, hypertension, diabetes mellitus and so on were not showed such significance in this study. Further, the multivariate analysis revealed that old age (>60 years) (OR 5.813, p=0.018) and histopathological type of squamous cell carcinoma (OR 5.831, p<0.001) were also statistically significant independent risk factors for postoperative pneumonia. Conclusions: This study demonstrated that being old aged (>60 years) and having squamous cell carcinoma histopathological type might be important factors in determining the risk of postoperative pneumonia in lung cancer patients after surgery. -
Zhang, Fang;Wang, Chuan-Sheng;Sun, Bo;Tian, Guang-Bo;Cao, Fang-Li;Cheng, Yu-Feng 3075
Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI<$24.00kg/m^2$ and$BMI{\geq}24.00kg/m^2$ ). Results: There were 41 patients in the low/normal BMI group (BMI<$24.00kg/m^2$ ) and 19 in the high BMI group ($BMI{\geq}24.00kg/m^2$ ). No significant differences were observed in patient characteristics between these. We found no difference in 2-year OS and DFS associated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysis revealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymph node status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic. There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708) between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFS associated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking, tumor location, the status of lymph node metastases and BMI. Conclusions: BMI was not associated with survival in patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factor for patients undergoing CRT for ESCC. -
Nazik, Evsen;Nazik, Hakan;Ozdemir, Funda;Soydan, Selen 3081
The aim of this study was to determine the level of social support and quality of life in Turkish patients with gynecologic cancer using a cross-sectional survey design. A total of 108 patients admitted to the gynecologic oncology clinic at a university hospital from September 2011 to January 2012 were included. Data were collected using patient information forms, the Multidimensional Scale of Perceived Social Support (MSPSS) and The Quality of Life-Cancer Survivors Instrument (QOL-CS). Average age was$54.5{\pm}10.8$ years and it was determined that 65.7% of patients had ovarian cancer and 19.4% had cervical cancer. The total QOL-CS mean score was$5.59{\pm}1.10$ . Average score of total MSPSS was found to be$69.7{\pm}14.64$ . Comparing socio-demographic and clinical characteristics of patients and average scores of QOL-CS and MSPSS, it was found that there was not a statisticaly significant corelation (p>0.05). Statistically significant relation was found between the average scores of QOL-CS and MSPSS. These results showed that quality of life was moderate and perceived social support was high in Turkish patients with gynecologic cancer. -
Kash, Deep Par;Lal, Murli;Hashmi, Altaf Hussain;Mubarak, Muhammed 3087
Purpose: To determine the utility of digital rectal examination (DRE), serum total prostate specific antigen (tPSA) estimation, and transrectal ultrasound (TRUS) for the detection of prostate cancer (PCa) in men with lower urinary tract symptoms (LUTS). Materials and Methods: All patients with abnormal DRE, TRUS, or serum tPSA >4ng/ml, in any combination, underwent TRUS-guided needle biopsy. Eight cores of prostatic tissue were obtained from different areas of the peripheral prostate and examined histopathologically for the nature of the pathology. Results: PCa was detected in 151 (50.3%) patients, remaining 149 (49.7%) showed benign changes with or without active prostatitis. PCa was detected in 13 (56.5%), 9 (19.1%), 26 (28.3%), and 103 (74.6%) of patients with tPSA <4 ng/ml, 4-10 ng/ml, 10-20 ng/ml and >20 ng/ml respectively. Only 13 patients with PCa had abnormal DRE and TRUS with serum PSA <4 ng/ml. The detection rate was highest in patients with tPSA >20 ng/ml. The association between tPSA level and cancer detection was statistically significant (p<0.01). Among 209 patients with abnormal DRE and raised serum PSA, PCa was detected in 128 (61.2%). Conclusions: The incidence of PCa increases with increasing serum level of tPSA. The overall screening and detection rate can be further improved by using DRE, TRUS and TRUS-guided prostate needle biopsies. -
Liu, Hong-Sheng;Tan, Wen-Bin;Yang, Ning;Yang, Yuan-Yuan;Cheng, Peng;Liu, Li-Juan;Wang, Wei-Jie;Zhu, Chang-Liang 3093
Background: Cancer is a major threat to the public health whether in developed or in developing countries. As the most common primary malignant tumor, the morbidity and mortality rate of lung cancer continues to rise in recent ten years worldwide. Chemotherapy is one of the main methods in the treatment of lung cancer, but this is hampered by chemotherapy drug resistance, especially MDR. As a component of the 60S large ribosomal subunit, ribosomal protein L39-L gene was reported to be expressed specifically in the human testis and human cancer samples of various tissue origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible A549 cells was isolated, and real time quantitative RT-PCR were used to indicate the transcribe difference between amycin resistant and susceptible strain of A549 cells. Viability assay were used to show the amycin resistance difference in RPL39-L transfected A549 cell line than control vector and null-transfected A549 cell line. Results: The ribosomal protein L39-L transcription level was 8.2 times higher in drug-resistant human lung cancer A549 cell line than in susceptible A549 cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells showed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions and Implications for Practice: The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells. -
Dong, Jun;Xiao, Li;Sheng, Lu;Xu, Jun;Sun, Zhong-Quan 3099
TMPRSS2:ERG gene fusions in prostate cancer have a dominant prevalence of approximately 50.0%, but infomration is limited on differences among ethnic and geographical groups. Some studies focusing on Japanese and Korean patients reported a lower incidence. Investigations concerning Chinese revealed controversial results. We evaluated TMPRSS2:ERG, TMPRSS2:ETV1 and TMPRSS2:ETV4 fusions in more than 100 Eastern Chinese prostate cancer patients. Paraffin blocks of needle biopsy and radical prostatectomy were collected from 91 and 18 patients respectively. All patients' clinicopathologic factors were gathered. TMPRSS2:ERG, TMPRSS2:ETV1 and TMPRSS2:ETV4 fusions were tested by multi-probe fluorescence in situ hybridization (FISH) assay. TMPRSS2:ERG fusions was present in 14.3% biopsy specimens and 11.1% radical prostatectomy patients. Neither TMPRSS2:ETV1 nor TMPRSS2:ETV4 fusion was found in any case. Altogether, 13 (86.7%) TMPRSS2:ERG fusion positive cases possessed deletion pattern and 7 (46.6%) and insertion pattern. Some 5 cases had both deletion and insertion patterns. While 38.5% (5/13) patients with deletion pattern had distant metastasis, except for one metastatic case harboring both deletion and insertion, there were no patients with insertion pattern accompanied with metastasis. There were no differences between fusion positive and negative cases in the distribution of age, PSA, Gleason score and TNM stage. Eastern Chinese prostate cancer patients have a significantly low incidence of TMPRSS2:ERG fusion. They also lack TMPRSS2:ETV1 and TMPRSS2:ETV4 fusion. There are more deletion pattern than insertion pattern in TMPRSS2:ERG positive cases. Fusion positive and negative patients have no clinicopathologic factor differences. -
Beckmann, Kerri Rose;Roder, David Murray;Hiller, Janet Esther;Farshid, Gelareh;Lynch, John William 3105
Purpose: To examine breast cancer (BC) incidence trends in relation to mammographic screening and risk factor prevalence in South Australia (SA). Materials and Methods: Trends in annual BC incidence rates were calculated using direct standardisation and compared with projected incidence derived from Poisson regression analysis of pre-screening rates. Annual percentage change and change time points were estimated using Joinpoint software. Biennial mammography screening participation rates were calculated using data from BreastScreen SA. Trends in overweight/obesity, alcohol use and hormone replacement therapy (HRT) use were examined using 1991-2009 Health Omnibus Survey data. Trends in total fertility were examined using data from the Australian Bureau of Statistics. Results: BC incidence increased around the time BreastScreen commenced and then stabilised in the mid-1990s. However rates have remained higher than projected, even though the proportion and age distribution of first time screening attendees stabilised around 1998. A decrease in BC incidence was observed among women aged 50-59yrs from the late-1990's but not among older women. Obesity and alcohol use have increased steadily in all age groups, while HRT use declined sharply from the late-1990s. Conclusions: BC incidence has remained higher than projected since mammography screening began. The sustained elevation is likely to be due to lead time effects, though over-diagnosis cannot be excluded. Declining HRT use has also impacted incidence trends. Implications: Studies using individual level data, which can account for changes in risk factor prevalence and lead time effects, are required to evaluate 'over-diagnosis' due to screening. -
Altun, Ahmet;Turgut, Nergiz Hacer;Kaya, Tijen Temiz 3113
Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration ($IC_{50}$ ) was$4.28{\times}10^{-8}mol/L$ . Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects. -
Li, Lin-Jing;Li, Guang-Di;Wei, Hu-Lai;Chen, Jing;Liu, Yu-Mei;Li, Fei;Xie, Bei;Wang, Bei;Li, Cai-Li 3123
The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells. -
rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han ChineseZhang, Lin-Lin;Sun, Liang;Zhu, Xiao-Quan;Xu, Yong;Yang, Kuo;Yang, Fan;Yang, Yi-Ge;Chen, Guo-Qiang;Fu, Ji-Cheng;Zheng, Chen-Guang;Li, Ying;Mu, Xiao-Qiu;Shi, Xiao-Hong;Zhao, Fan;Wang, Fei;Yang, Ze;Wang, Bin-You 3129
Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$ , p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$ , p=0.042/$OR_{recessive}=1.99$ , p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$ ). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$ ,$P_{tumorstage}=0.048$ ). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population. -
Albasri, Abdulkader;Yosef, Hala;Hussainy, Akbar Shah;Sultan, Saud Ahmad;Alhujaily, Ahmed 3133
Background: To determine the histopathological pattern of colorectal cancer (CRC) among Saudi patients with a view to determine various epidemiological and histopathological features of the disease. Materials and Methods: We retrospectively collected and analyzed the demographic and histopathological data of all the patients with CRC diagnosed at King Fahad Hospital, Madinah, Saudi Arabia over a period of 8 years from January 2006 to December 2013. Results: Of 324 cases of CRC reviewed, 200 cases (61.7%) were males while 124 cases (38.3%) were females giving a male to female ratio of 1.6: 1. Age of the patients ranged from 20 to 100 years with a mean age 57.9 years. The rectosigmoid region was the most frequent anatomical site (13.6%) involved and adenocarcinoma (88.6%) was the most common histopathological type. The majority of adenocarcinomas (87.3%) were moderately differentiated. A total of 47.8% of patients were in stage B and 43.5% of patients were in stage C of the Aster-Coller classification. Most patients (75.7%) presented with large size tumors. Lymphovascular invasion and lymph node metastasis were recorded in 67.9% and 43.6% of cases, respectively. Conclusions: Colorectal cancer is common in our environment and the majority of patients present late with an advanced stage. Screening programs regarding CRC should be enhanced to improve the outcome of the patients. -
Tas, Demet;Uncu, Dogan;Sendur, Mehmet Ali;Koca, Nuran;Zengin, Nurullah 3139
Background: Medical treatment for eliminating the side effects of cancer therapy may not always be efficacious. Acupuncture is one of the most widely accepted alternative and complementary therapies in use today. In this study, we investigated the efficacy of acupuncture in patients experiencing cancer treatment side effects, including nausea, vomiting, pain, poor sleep quality and anxiety. Materials and Methods: A total of 45 inpatients who underwent chemotherapy between February and April 2013 in the Oncology Department of Numune Hospital were included in our study. Acupuncture was administered to the patients one day prior to chemotherapy, on the day of chemotherapy and one day after chemotherapy. The patients were evaluated on nausea, vomiting, pain, sleep quality and anxiety before the chemotherapy and on the$4^{th}$ day of chemotherapy. Results: Of the 45 patients included in the study, 18 (40%) were female and 27 (60%) were male. A total of 25 (55.6%) had an elementary school education; 32 patients (71%) had stage 4 cancer and were treated with palliative chemotherapy (the patient characteristics are shown in Table 1). Statistically significant decreases (p<0.001) in pain, nausea, vomiting, insomnia and anxiety scores were observed after the acupuncture treatment compared to baseline. There were no differences in the age, gender, education level, stage or metastasis levels between the patient groups whose symptoms improved or were unchanged. Conclusions: Our study showed that acupuncture has positive effects in cancer treatment patients who experience nausea, vomiting, pain, poor sleep quality and anxiety as side effects of chemotherapy. Chemotherapy-related side effects in cancer patients could be decreased by the concurrent use of acupuncture. -
Gene expression profiling facilitates the understanding of biological characteristics of gliomas. Previous studies mainly used regression/variance analysis without considering various background biological and environmental factors. The aim of this study was to investigate gene expression differences between grade III and IV gliomas through partial least squares (PLS) based analysis. The expression data set was from the Gene Expression Omnibus database. PLS based analysis was performed with the R statistical software. A total of 1,378 differentially expressed genes were identified. Survival analysis identified four pathways, including Prion diseases, colorectal cancer, CAMs, and PI3K-Akt signaling, which may be related with the prognosis of the patients. Network analysis identified two hub genes, ELAVL1 and FN1, which have been reported to be related with glioma previously. Our results provide new understanding of glioma pathogenesis and prognosis with the hope to offer theoretical support for future therapeutic studies.
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Fu, Si-Rui;Zhang, Ying-Qiang;Li, Yong;Hu, Bao-Shan;He, Xu;Huang, Jian-Wen;Zhan, Mei-Xiao;Lu, Li-Gong;Li, Jia-Ping 3151
Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD. -
Varol, Umut;Dirican, Ahmet;Yildiz, Ibrahim;Oktay, Esin;Degirmenci, Mustafa;Alacacioglu, Ahmet;Barutca, Sabri;Karabulut, Bulent;Uslu, Ruchan 3157
Background: Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. Materials and Methods: We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. Results: Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. Conclusions: Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status. -
Teh, Yew-Ching;Shaari, Nor Elina Noor;Taib, Nur Aishah;Ng, Char-Hong;See, Mee-Hoong;Tan, Gie-Hooi;Jamaris, Suniza;Yip, Cheng-Har 3163
Background: Breast-conserving surgery (BCS) plus radiotherapy is equivalent to modified radical mastectomy (MRM) in terms of outcome. However there is wide variation in mastectomy rates dependent both on tumour and patient characteristics. Objective: This study aimed to assess the determinants of surgery choice in Asian patients with early breast cancer in a middle-income country. Materials and Methods: 184 patients with early breast cancer treated between Jan 2008 and Dec 2010 were recruited to complete a questionnaire. Chi-square test was used to analyze the association between surgery choice and demographic and tumour factors, surgeon recommendation, family member and partner opinions, fear of recurrence, avoidance of second surgery, fear of disfigurement, interference with sex life, fear of radiation and loss of femininity. Results: 85 (46%) had BCS while 99 (54%) had mastectomy. Age >60, Chinese ethnicity, lower education level, and larger tumour size were significantly associated with mastectomy. Surgeon recommendation was important in surgery choice. Although both groups did not place much importance on interference with sex life, 14.1% of the BCS group felt it was very important compared to 5.1% in the mastectomy group and this was statistically significant. There was no statistical difference between the two groups in terms of the other factors. When analyzed by ethnicity, significantly more Malay and Indian women considered partner and family member opinions very important and were more concerned about loss of femininity compared to Chinese women. There were no statistical differences between the three ethnic groups in terms of the other factors. Conclusions: When counseling on surgical options, the surgeon has to take into account the ethnicity, social background and education level, age and reliance on partner and family members. Decision-making is usually a collective effort rather than just between the patient and surgeon, and involving the whole family into the process early is important. -
Li, Jia-Xin;Huang, Shao-Min;Wen, Bi-Xiu;Lu, Tai-Xiang 3169
Background: To investigate factors associated with overall survival in patients with newly diagnosed metastatic nasopharyngeal carcinoma. Materials and Methods: Two hundred and two consecutive patients with pathologically confirmed nasopharyngeal carcinoma with distant metastasis at diagnosis seen between December 2007 and May 2011 were reviewed. Patient, tumor and treatment factors were analyzed for their significance regarding overall survival. Results: The median follow-up time was 22 months. At the time of this report, 116 patients had died. For 112 patients, cause of death was nasopharyngeal carcinoma. The 1, 2, 3, and 4-year overall survival rates were 75.6%, 50.2%, 39.2%, and 28.2%, respectively. Cox regression multivariate analysis showed that T-stage (p=0.045), N-stage (p=0.014), metastasis number (p<0.001) and radiotherapy for nasopharynx and neck (p<0.001) were significant factors for overall survival. Conclusions: Early T-stage and N-stage, solitary metastasis in a single organ were good prognostic factors for patients with newly diagnosed metastatic nasopharyngeal carcinoma. Radiotherapy should be strongly recommended in systemic treatment. -
Xian, Shu-Lin;Cao, Wei;Zhang, Xiao-Dong;Lu, Yun-Fei 3175
Background: Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. Aim: To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Materials and Methods: Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). Results: 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p<0.05), with no significant difference between the high dose and 5-FU groups (p>0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p<0.05); there was no significant difference between 5-FU group and medium dose group (p>0.05), but there was between the 5-FU and high dose groups (p<0.05). Conclusions: This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice. -
Kim, Hana;Youk, Ji Hyun;Kim, Jeong-Ah;Gweon, Hye Mi;Jung, Woo-Hee;Son, Eun Ju 3179
Background: The purpose of study was to evaluate radiologic or clinical features of breast cancer undergoing ultrasound (US)-guided 14G core needle biopsy (CNB) and analyze the differences between underestimated and accurately diagnosed groups. Materials and Methods: Of 1,898 cases of US-guided 14G CNB in our institute, 233 cases were proven to be cancer by surgical pathology. The pathologic results from CNB were invasive ductal carcinoma (IDC) (n=157), ductal carcinoma in situ (DCIS) (n=40), high-risk lesions in 22 cases, and benign in 14 cases. Among high-risk lesions, 7 cases of atypical ductal hyperplasia (ADH) were reported as cancer and 11 cases of DCIS were proven IDC in surgical pathology. Some 29 DCIS cases and 157 cases of IDC were correctly diagnosed with CNB. The clinical and imaging features between underestimated and accurately diagnosed breast cancers were compared. Results: Of 233 cancer cases, underestimation occurred in 18 lesions (7.7%). Among underestimated cancers, CNB proven ADH (n=2) and DCIS (n=11) were diagnosed as IDC and CNB proven ADH (n=5) were diagnosed at DCIS finally. Among the 186 accurately diagnosed group, the CNB results were IDC (n=157) and DCIS (n=29). Comparison of underestimated and accurately diagnosed groups for BI-RADS category, margin of mass on mammography and US and orientation of lesion on US revealed statistically significant differences. Conclusions: Underestimation of US-guided 14G CNB occurred in 7.7% of breast cancers. Between underestimated and correctly diagnosed groups, BI-RADS category, margin of the mass on mammography and margin and orientation of the lesions on US were different. -
Kacan, Turgut;Altun, Ahmet;Altun, Gulsah Gultekin;Kacan, Selen Baloglu;Sarac, Bulent;Seker, Mehmet Metin;Bahceci, Aykut;Babacan, Nalan 3185
Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and$6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and$25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and$IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an$IC_{50}$ value of$32.0{\mu}M$ ; in contrast with lapatinib the$IC_{50}$ was$136.6{\mu}M$ . When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer. -
Wang, Chao;Xiao, Qian;Li, Yu-Wen;Zhao, Chao;Jia, Na;Li, Rui-Li;Cao, Shan-Shan;Cui, Jia;Wang, Lu;Wu, Yin;Wen, Ai-Dong 3191
Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic. -
Zhao, Li-Wei;Zhong, Xiu-Hong;Yang, Shu-Yan;Zhang, Yi-Zhong;Yang, Ning-Jiang 3195
Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, p<0.01). A sub-$G_1$ peak (apoptotic cells) of HeLa cells was detected after treatment and the apoptosis rate with the concentration and longer incubation time (r=1.0, p<0.01), while the percentage of cells in S phase and$G_2$ /M phase decreased significantly. Immunocytochemistry assay showed that the expression of cyclin E and bcl-2 in the treated cells significantly decreased, while the expression of p27 and bax obviously increased, compared with the control group (p<0.05). The results of our research indicate that inotodiol isolated from Inonotus obliquus inhibited the proliferation of HeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer. -
Stosic, Ivana;Grujicic, Darko;Arsenijevic, Slobodan;Brkic, Marija;Milosevic-Djordjevic, Olivera 3201
The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions. -
Gogia, Ajay;Raina, Vinod;Deo, Suryanarayan Vishnu;Shukla, Nootan Kumar;Mohanti, Bidhu Kalyan;Sharma, Daya Nand 3207
Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterized by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d'orange appearance. It accounts for 1-3% of all newly diagnosed cases of breast cancer in the west. Data on IBC from India are lacking. The aim of our study was to assess the clinical-pathological parameters and outcome of IBC at, All India Institute of Medical Sciences, a large tertiary care centre. Materials and Methods: We screened 3,650 breast cancer cases registered from January 2004 to December 2012 and found 41 cases of IBC. Data included demographics as well as clinical, radiological and histopathological characteristics, and were collected from clinical case records using the International Classification of Diseases code (C-50). Patients who presented with IBC as a recurrence, or who had a neglected and advanced breast cancer that simulated an IBC were excluded from this study. Results: The median age was 45 years (range 23-66). The median duration of symptoms was 5 months. The American Joint Committee on Cancer stage (AJCC) distribution was Stage III - 26 and IV - 15 patients. Estrogen receptor (ER), progesterone receptor (PR) positivity and human epidermal growth factor receptor 2 (HER2/neu) positivity were 50%, 46% and 60%, respectively. Triple negativity was found in 15% of the cases. All the non metastatic IBC patients received anthracycline and/ or taxane based chemotherapy followed by modified radical mastectomy, radiotherapy and hormonal therapy as indicated. Pathological complete remission rate was 15%. At a median follow-up of 30 months, the 3 year relapse free survival and overall survival were 30% and 40%respectively. Conclusion: IBC constituted 1.1% of all breast cancer patients at our centre. One third of these had metastatic disease at presentation. Hormone positivity and Her2 neu positivity were found in 50% and 60% of the cases, respectively. -
Yao, Jian-Xin;Yao, Zhi-Feng;Li, Zhan-Feng;Liu, Yong-Biao 3211
Background: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Materials and Methods: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose ($D_0$ ), quasi-threshold dose ($D_q$ ) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM). Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. Results: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Conclusions: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA-MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis. -
Zhu, Yu;Liu, Xing-Jun;Yang, Ping;Zhao, Meng;Lv, Li-Xia;Zhang, Guo-Dong;Wang, Qin;Zhang, Ling 3219
Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2.${\beta}$ -catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells. -
Tuna, Arzu;Avdal, Elif Unsal;Yucel, Sebnem Cinar;Dal, Nursel Alp;Dicle, Aklime;Ozkan, Arife;Sezgin, Handan;Gumus, Aysun Babacan;Turgay, Ayse San;Degirmenci, Mustafa 3227
Background: This research evaluated the effectiveness of an online education model in teaching breast self-examination to university staff and students. Materials and Methods: 1,679 women participated in a breast self-examination online training program. Breast self-examination knowledge evaluation forms developed by Maurer (1997) were used in the research and were evaluated on a 100 point scale. Paired t-test and McNemar's Test statistics were employed. Results: The participants scored an average of 46.5 (14.0%) on knowledge on breast self-examination before training, but 77.4 (11.0%) one month after education and 76.7 (9.52%) after six months. There was a clear significant difference between these knowledge levels (p<0.05). Similarly, while the rate for systematic practice of breast self-examination among women was 30.8% before training it increased to 47.8% afterwards. Again the difference was significant (p<0.05). Conclusions: Online education is an effective method for teaching breast self-examination to women. -
Sipetic-Grujicic, Sandra Branko;Murtezani, Zafir Hajdar;Neskovic-Konstatinovic, Zora Borivoje;Marinkovic, Jelena Milutin;Kovcin, Vladimir Nikola;Andric, Zoran Gojko;Kostic, Sanja Vladeta;Ratkov, Isidora Stojan;Maksimovic, Jadranka Milutin 3233
Background: The aim of this study was to analyze the demographic and clinical characteristics of male breast cancer patients in Serbia, and furthermore to determine overall survival and predictive factors for prognosis. Materials and Methods: In the period of 1996-2006 histopathological diagnosis of breast cancer was made in 84 males at the Institute for Oncology and Radiology of Serbia. For statistical analyses the Kaplan-Meier method, long-rank test and Cox proportional hazards regression model were used. Results: The mean age at diagnosis with breast cancer was$64.3{\pm}10.5$ years with a range from 35-84 years. Nearly 80% of the tumors showed ductal histology. About 44% had early tumor stages (I and II) whereas 46.4% and 9.5% of the male exhibitied stages III and IV, respectively. Only 7.1% of male patients were grade one. One-fifth of all patients had tumors measuring${\leq}2cm$ , and 14.3% larger than 5 cm. Lymph node metastasis was recorded in 40.4% patients and 47% relapse. Estrogen and progesterone receptor expression was positive in 66.7% and 58.3%, respectively. Among 14.3% of individuals tumor was HER2 positive. About two-thirds of all male patients had radical mastectomy (66.7%). Adjuvant hormonal (tamoxifene), systematic chemotherapy (CMF or FAC) and adjuvant radiotherapy were given to 59.5%, 35.7% and 29.8% patients respectively. Overall survival rates at five and ten years for male breast cancer were 55.0% and 43.9%, respectively. According to the multivariate Cox regression predictive model, a lower initial disease stage, a lower tumor grade, application of adjuvant hormone therapy and no relapse occurrence were significant independent predictors for good overall survival. Conclusions: Results of the treatment would be better if disease is discovered earlier and therefore health education and screening are an imperative in solving this problem. -
Wang, Shao-Ming;Zhang, Shao-Kai;Pan, Xiong-Fei;Ren, Ze-Fang;Yang, Chun-Xia;Wang, Zeng-Zhen;Gao, Xiao-Hong;Li, Man;Zheng, Quan-Qing;Ma, Wei;Zhao, Fang-Hui;Qiao, You-Lin;Sivasubramaniam, Priya 3239
Background: College students are recommended as the target groups for catch-up human papillomavirus (HPV) vaccination. Systematical exploration of awareness, acceptability, and decision-making factors of HPV vaccination among Chinese college students has been limited. Materials and Methods: A multi-center survey was conducted in mainland China between November 2011 and May 2012. College students aged 18-22 years were stratified by their grade, gender, and major for sampling. Socio-demographic and HPV-related information such as knowledge, perceptions, acceptability, and attitudes were collected through a questionnaire. Results: A total of 3,497 undergraduates completed the questionnaire, among which 1,686 were males. The acceptability of the HPV vaccine was high (70.8%). Undergraduates from high-level universities, at lower grade, or with greater prior knowledge of HPV vaccines showed higher acceptability of HPV vaccination ($p_{trend}$ <0.001). Additionally, undergraduates with vaccination experience outside the National Expanded Program on Immunization (OR=1.29; 95%CI: 1.10-1.51) or fear of HPV-related diseases (OR=2.79; 95%CI: 2.28-3.41) were more willing to accept HPV vaccination. General knowledge of HPV vaccine was low among undergraduates, and safety was a major concern (71.05%). The majority of students wished to pay less than 300RMB for HPV vaccine and chose the Chinese Center for Disease Control and Prevention as the most appropriate venue for vaccination. Conclusions: Although most undergraduates demonstrate positive attitudes towards HPV vaccination, challenges pertaining to introduction exist in China. Corresponding proactive education and governmental subsidy to do so are urgently needed by this age-group population. Suggestions and potential strategies indicated may help shape the future HPV vaccination program in China. -
Cheng, Da-Ye;Hao, Yi-Wen;Zhou, Wen-Ling;Ma, Yi-Ran 3247
Background: Genetic factors have been shown to play an important role in the development of cancers. However, individual studies may fail to completely demonstrate complicated genetic relationships because of small sample size. Therefore, we performed a meta-analysis to evaluate the association of E-selectin Ser128Arg (S128R) with cancer risk. Materials and Methods: A literature search in PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases was carried out to identify studies of the association between E-selectin S128R polymorphism and cancer risk. The odds ratio (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of association. Results: A total of eight studies involving 1,675 cancer cases and 2,285 controls were included in the meta-analysis. In overall populations, S128R polymorphism seemed to be associated with cancer risk (Arg allele vs Ser allele: OR=1.65, 95%CI =1.33-2.04, p<0.01; Arg/Arg+Arg/Ser vs Ser/Ser: OR=1.87, 95%CI =1.48-2.36, p<0.01; Arg/Ser vs Ser/Ser: OR=1.80, 95%CI =1.51-2.14, p<0.01). Similarly, subgroup analysis by ethnicity and source of control also revealed that this polymorphism was related to cancer risk. Conclusions: Our meta-analysis revealed that there was association between the E-selectin S128R polymorphism and the risk of cancer. Further large and well-designed studies are needed to confirm this association. -
Phukan, Rup Kumar;Saikia, Bhaskar Jyoti;Borah, Prasanta Kumar;Zomawia, Eric;Sekhon, Gaganpreet Singh;Mahanta, Jagadish 3253
Background: A case-control study was conducted to evaluate the effect of household exposure, dietary habits, smoking and Glutathione S-Transferases M1, T1 polymorphisms on lung cancer among women in Mizoram, India. Materials and Methods: We selected 230 newly diagnosed primary lung cases and 460 controls from women in Mizoram. Multivariate logistic regression analysis was performed to estimate adjusted odds ratio (OR). Results: Exposure of cooking oil fumes (p<0.003), wood as heating source for cooking (p=0.004), kitchen inside living room (p=0.001), improper ventilated house (p=0.003), roasting of soda in kitchen (p=0.001), current smokers of tobacco (p=0.043), intake of smoked fish (p=0.006), smoked meat (p=0.001), Soda (p<0.001) and GSTM1 null genotype (p=0.003) were significantly associated with increased risk of lung cancer among women in Mizoram. Significantly protective effect was observed for intake of bamboo shoots (p=<0.001) and egg (p<0.001). A clear increase in dose response gradient was observed for total cooking dish years. Risk for lung cancer tends to increase with collegial effect of indoor environmental sources (p=0.022). Significant correlation was also observed for interaction of GST polymorphisms with some of dietary habits. Conclusions: We confirmed the important role of exposure of cooking oil emission and wood smoke, intake of smoked meat, smoked fish and soda (an alkali preparation used as food additives in Mizoram) and tobacco consumption for increase risk of lung cancer among Women in Mizoram. -
Srivastava, Vikas Kumar;Gara, Rishi Kumar;Rastogi, Namrata;Mishra, Durga Prasad;Ahmed, Mohd Kaleem;Gupta, Shalini;Goel, Madhu Mati;Bhatt, Madan Lal Brahma 3261
Background: To evaluate serum VEGF-A levels in squamous cell carcinoma of head and neck (SCCHN) patients and relationships with response to therapy. Materials and Methods: Serum VEGF-A levels in patients (n=72) treated with radiotherapy (RT) or radio-chemotherapy (RCT) and controls (n=40) were measured by ELISA. Results: Serum VEGF-A levels of the SCCHN cases were significantly higher (p=0.001) than in healthy controls, and in patients with positive as compared to negative lymph node status (p=0.004). Similarly, patients with advanced stage (Stage III-IV) disease had more greatly elevated levels of serum VEGF-A level than their early stage (Stage I-II) counterparts (p=0.001). In contrast, there was no significant difference (p=0.57) in serum level of VEGF-A in patients with advanced T-stage (T3-4) as compared to early stage (T1-2). Similarly, patients with distant metastasis had no significant (p=0.067) elevation in serum VEGF-A level as compared to non-metastatic disease. However, the non-responder patients had significantly higher serum VEGF-A level as compared to responders (p=0.001). Conclusions: Our results suggest that the serum VEGF-A level may be a useful biomarker for the prediction of response to therapy in SCCHN. -
Background: Several studies have investigated the association between methionine synthase reductase (MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. Therefore, we performed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibility to breast cancer. Materials and Methods:Case-control studies investigating the relationship between MTRR A66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Database. Either fixed-effects or random-effects models were applied to calculate odds ratios(ORs) and 95% confidence intervals (CIs) by RevMan5.2 software. Results: A total of 9 studies bearing 7,097 cases and 7,710 controls were included in the meta-analysis. The results were that the combined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16) and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. We also performed subgroup analysis by specific ethnicity. The results of the combined analysis of MTRR 66AG, GG, (AG+GG) genotypes and breast cancer in Asian descent were Z=0.50, 0.53 and 0.21, with p all>0.05; for breast cancer in Caucasian descent, the results were Z=1.14, 1.65 and 0.43, with p all>0.05. Conclusions: Our findings suggested that MTRR A66G polymorphism was not associated with breast cancer susceptibility.
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Zhang, Xiao-Lian;Lu, Yu;Yang, Shi;Peng, Qi-Liu;Wang, Jian;Xie, Li;Deng, Yan;He, Yu;Li, Tai-Jie;Qin, Xue;Li, Shan 3273
Background: Various studies have evaluated the relationship between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusions have been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whether XRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted from PubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included in the study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluate XRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030 controls were involved in our meta-analysis. The results demonstrated that there was significant association between Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG: OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroup analyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vs GG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) and Caucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934, p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC risk especially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role against HCC among Caucasians. -
Kang, Minsun;Yoo, Ki-Bong;Park, Eun-Cheol;Kwon, Kisung;Kim, Gaeun;Kim, Doo Ree;Kwon, Jeoung A 3279
Background: Cancer is one of the leading causes of death in Korea. To reduce cancer incidence, the Korean National Cancer Center (KNCC) has been expanding its organized cancer screening program. In addition, there are opportunistic screening programs that can be chosen by individuals or their healthcare providers. The purpose of this study was to investigate factors associated with participation in organized and opportunistic cancer screening programs, with a particular focus on socioeconomic factors. Materials and Methods: We used data from the Korea National Health and Nutrition Examination Survey (KNHANES), a cross-sectional nationwide study conducted by the Korean Ministry of Health and Welfare from 2007 to 2011. The study included information from 9,708 men and 12,739 women aged 19 years or over. Multinomial logistic regression analysis was conducted, adjusting for age, year of data collection, residential region, current smoking status, current alcohol consumption status, exercise, marriage status, job status, perceived health status, stress level, BMI, limitation of activities, cancer history, health insurance type, and private insurance status, to investigate the association between education level, economic status, and cancer screening participation. Results: In terms of education level, disparities in attendance were observed only for the opportunistic screening program. In contrast, there was no association between education level and participation in organized screening. In terms of economic status, disparities in opportunistic screening participation were observed at all income levels, but disparities in organized screening participation were observed only at the highest income level. Conclusions: Our findings reveal that socioeconomic factors, including educational level and economic status, were not significantly associated with participation in organized cancer screening, except at the highest level of income. -
Cheah, Phaik-Leng;Looi, Lai-Meng;Teoh, Kean-Hooi;Rahman, Nazarina Abdul;Wong, Li-Xuan;Tan, Soo-Yong 3287
Background: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between$1^{st} $ January 2005 and$31^{st}$ December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121${\geq}50$ -years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type. -
Chen, Wei-Qiang;Xu, Bin;Mao, Jian-Wen;Wei, Feng-Xiang;Li, Ming;Liu, Tao;Jin, Xiao-Bao;Zhang, Li-Rong 3293
Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. Methods: In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that${\alpha}$ -pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Taken together, these findings indicate that${\alpha}$ -pinene may be useful as a potential anti-tumor drug. -
Wu, San-Yun;Yu, Ming-Xia;Li, Xiao-Gai;Xu, Shu-Fang;Shen, Ji;Sun, Zhen;Zhou, Xin;Chen, Xing-Zhen;Tu, Jian-Cheng 3299
Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients. -
Ihira, Hikaru;Mizumoto, Atsushi;Makino, Keitarou;Yasuda, Keisuke;Miyabe, Yoko;Saitoh, Shigeyuki;Ohnishi, Hirofumi;Furuna, Taketo 3305
Background: A cancer survivor is defined as anyone who has been diagnosed with cancer, from the time of diagnosis through the rest of their life. The purpose of this study was to examine whether physical functions, health-related outcomes, nutritional status and blood markers in community-dwelling cancer survivors aged 75 years and older are different from those who do not have cancer Materials and Methods: Two hundred seventy-five participants were asked by physicians, nurses, and physical therapists, questions regarding cancer history in a face-to-face interview. Data were collected for demographic information, physical functions, such as handgrip strength, knee extension power, abdominal muscle strength, static standing balance, walking speed and the timed-up-and-go test, health-related outcomes, nutritional status, and blood markers. The measured parameters of survivor diagnosed with cancer were compared with those without a history of cancer. Results: Thirty-seven older adults were previously diagnosed with cancer. Female cancer survivors had lower knee extension power (p<0.05), abdominal muscle strength (p<0.05), walking speed (p<0.05), timed-up-and-go test score (p<0.05), and time to spend on walking per day (p<0.05) than older women without a history of cancer. In men, none of the measured parameters were significantly different between cancer survivors and older men with no history of cancer. Conclusions: The present study shows that partial physical function of women cancer survivors aged 75 years and older differs from that in women with no history of cancer. -
Hooshmand, Somayeh;Ghaderi, Abbas;Yusoff, Khatijah;Thilakavathy, Karuppiah;Rosli, Rozita;Mojtahedi, Zahra 3311
Background: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDI${\alpha}$ ) activity on migration and invasion of estrogen receptor positive ($ER^+$ ) and negative ($ER^-$ ) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDI${\alpha}$ and other proteins interacting directly or indirectly with RhoGDI${\alpha}$ in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. Materials and Methods:$ER^+$ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDI${\alpha}$ using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDI${\alpha}$ . Results: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDI${\alpha}$ in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDI${\alpha}$ in MCF7, while only one protein was identified in the upregulation of RhoGDI${\alpha}$ in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-${\alpha}$ activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Conclusions: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDI${\alpha}$ with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration. -
Chin, Sheray Nicole;Green, Cheryl;Strachan, Georgiana Gordon;Wharfe, Gilian 3319
Breast cancer is the most common cancer in Jamaican women. This study assessed the clinicopathologic features of cases in a hospital-based specialist clinic in Kingston, Jamaica. A retrospective chart review was performed for the 2-year study period and relevant clinical and surgico-pathologic data were recorded and analyzed. Median age of the 121 breast cancer patients was 52 years (range 22-84, IQR 20) and there was 1 case of male breast cancer. Most patients (65%) were referred from the surgical service after definitive breast cancer surgery, 20% were referred for pre-operative systemic therapy, and 15% had a diagnosis of metastatic disease. The surgico-pathologic group comprised 78 women who were referred for adjuvant therapy. The majority had presented with a palpable breast lump (91%), with median tumour size 3.5cm (range 0.4-13, IQR 4). Most tumours were node positive (56%). Approximately one-third of patients had stage III disease (33%). Most women presented with large palpable tumours and had lymph node involvement confirmed on surgicopathological evaluation, indicative of limited early breast cancer detection. A national screening mammography programme is recommended for detection of earlier lesions. Pre-operative systemic therapy should be considered as an option for eligible patients. -
Chin, Sheray Nicole;Green, Cheryl May Antoinette;Gordon-Strachan, Georgiana Marie;Wharfe, Gilian Helen Frances 3323
Breast cancer is the most common cancer in Jamaican women. Locally advanced breast cancer (LABC) is associated with aggressive biology and poor prognosis, and has a predilection for African-American women. In this retrospective review, we assessed the prevalence of LABC as a breast cancer presentation in a population of mainly Afro-centric ethnicity, and determined disease characteristics and response to pre-operative chemotherapy. LABC was prevalent (20%), and had a low pathological response rate to pre-operative chemotherapy, with a high risk of disease recurrence. Increased utilization of breast cancer screening may help detect cancer at less advanced stages, and optimizing pre-operative chemotherapy is recommended to improve response rates and ultimately survival. -
Naz, Iram;Mahmood, Muhammad Khurram;Akhtar, Farhan;Nagi, Abdul Hannan 3327
Background: The purpose of the study was to analyse the clinicopathological spectrum of benign and malignant odontogenic tumours (OT) in Pakistan. Materials and Methods: This retrospective study was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi. Seven years archival records of histologically diagnosed odontogenic tumours, both benign and malignant, were collected and the lesions re-diagnosed histologically in accordance with the WHO classification of head and neck tumours (2005). Clinical as well as histological data were analysed and frequency of each type of OT was calculated using computer software programme SPSS (version 17). Mean tumour size was calculated and Chi-square test was applied to find associations of age, gender and site with each histological type of tumour. Results: Only 1.7% of the odontogenic tumours diagnosed in this said period were malignant while the remaining 98.3% were benign. Amongst benign lesions, ameloblastoma was the most common (61.3%) type while primary intraosseous squamous cell carcinoma (1.7%) was the only reported malignant tumour. Mean age of the affected patients was$31.7{\pm}16.7$ years with posterior mandible as the commonest site involved. Conclusions: Our study revealed ameloblastoma and primary intraosseous squamous cell carcinoma as the commonest diagnosed benign and malignant tumours respectively. There was a significant difference in age and site of origin of different types of OT at the time of their presentation. However, all the tumours showed male predominance. -
Lin, Lin;Yang, Jing;Ding, Yan;Wang, Jing;Ting, Liu 3331
Background: The results of previous researches that analyzed the association between genetic polymorphisms of transcription factor-7-like 2 (TCF7L2, rs7903146) and polycystic ovary syndrome (PCOS) were conflicting. Current systematic analysis was conducted to re-explore this association using updated materials. Materials and Methods: The PubMed database was used for data collection and the final search was conducted on January 3, 2014. For TCF7L2 rs7903146, a non-signficiant slight increase in risk of PCOS development was observed under three genetic models (dominant model: OR=1.06, 95%CI: 0.93-1.21, p>0.05; recessive model: OR=1.12, 95%CI: 0.87-1.43, p> 0.05; homozygous model: OR=1.14, 95%CI: 0.87-1.47, p>0.05). In the subgroup analyses in Asian group, allele susceptibility of PCOS was calculated (allele model: OR=1.00, 95%CI: 0.74-1.35, p>0.05; dominant model: OR=0.98, 95%CI: 0.71-1.35, p>0.05; recessive model: OR=1.79, 95%CI: 0.33-9.84, p>0.05; homozygous model: OR=1.78, 95%CI: 0.32-9.80, p>0.05), the differences were again not statistically significant. Conclusions: The findings of this systemic analysis suggest that the polymorphism of TCF7L2 rs7903146 may not be associated with the susceptibility to PCOS. -
Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin 3335
Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean,$12.75{\mu}mol/L$ ) with compared to TA6/6 (mean,$9.92{\mu}mol/L$ ) with p<0.05. Conclusions: Our study support the conclusion that patients with a$UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the$UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.