• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1277-1280
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• 2015

Aim: To report epidemiologic and anatomoclinical transitions of inflammatory breast cancer (IBC) in Tunisia. Materials and Methods: Data including clinico-pathological data for 208 cases of T4d or PEV 3 non-metastatic breast cancer diagnosed between 2005 and 2010 were collected from patient records. Chi2 and Z tests were used to compare variables with two Tunisian historical series and a series about Arab-American patients. Results: Thirty three percent of our patients had their first child before 23 years of age and 56% had their menarche before 12 years, 75% never receiving oral contraception. Obesity was observed in 42% of women and IBC occurred during pregnancy in 13% of cases. Tumor grade was II-III in 90% of cases, HR was negative in 52%, HER2 was over expressed in 31% and invasion of more than 3 axillary nodes occurred in 18% of patients. We observed a pCR rate of 19% after neoadjuvant treatment (anthracyline-taxane used in 79%, trastuzumab in 27% ). Compared to historical Tunisian series (since 1996), IBC epidemiology remained stable in terms of median age, menopausal status and obesity. However we observed a significant decrease in median clinical tumor size and number of positive axillary lymph nodes. Comparison to IBC in Arab-Americans showed a significant difference in terms of median age, menopausal status, positivity of hormonal receptors and educational level. Conclusions: Our assessment of epidemiologic transition showed a reduction of clinco-pathological stage of IBC, keeping the same characteristics as compared to Tunisian historical series over a period of 14 years. Features seem to be different in Arab-American patients, probably related to migration, "occidentalization" of life style and improvement in socio-economic level.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4439-4445
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• 2015

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5069-5074
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• 2012

Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.931-935
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• 2012

Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2219-2224
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• 2012

Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of $CD4^+$, $CD19^+$, $CD44^+$, $CD25^+$, NK cells, and an increased $CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating $CD19^+$ lymphocytes compared to those with low $CD19^+$ lymphocytes (P=0.037), with $CD19^+$ showing an important cutoff of $7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2319-2324
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• 2012

Aim: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. Methods: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. Results: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. Conclusion: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2739-2742
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• 2013

Background: This survey aim was to evaluate the epidemiology and outcomes of neuroblastoma patients in one the most important children referral hospitals in Iran as a model from developing countries. Materials and Methods: This retrospective, non-randomized analytic study was conducted on 219 newly diagnosed neuroblastoma cases. Results: The age of patients ranged from 1-156 months with the average of $40.5{\pm}2.44$, with a male/female ratio of 1.9/1. Of the total, 172 (78.5%) were children and 47 (21.5%) were infants The adrenals were the most common primary site (60%). Stage 4 at diagnosis accounted for about 54% of all enrolled patients. Infants had significantly better cumulative survival ($85{\pm}8%$) than children ($33{\pm}7%$) during the follow up period and the survival rate improved from $33{\pm}7%$ in 1974-1994 to $58{\pm}9%$ in 1995-2005. Conclusions: This study indicates that our patient population with neuroblastomas tends to have more advanced disease, perhaps with poor biologic markers, but our analysis shows that the outcomes have improved over 32 years although the overall survival of Iranian neuroblastoma patients is still lower than developed countries. Late diagnosis, inability to determine risk group during the years of study and using single protocol for all enrolled patients can be the reasons of lower survival rate.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3289-3292
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• 2013

Introduction: The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. Materials and Methods: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. Results: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was $69.2{\pm}7.3$ years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among thowse with a low PSA level less than 20ng/ml, and less than 10ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml)+1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=$2.718^x/1+2.718^x$. Conclusion: Newly diagnosed prostate cancer patients with a PSA level of 10ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3369-3375
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• 2016

MicroRNAs, a novel class of small non-coding RNAs, are key players in many cellular processes, including cell proliferation, differentiation, invasion and regeneration. Tissue and circulatory microRNAs could serve as useful clinical biomarkers and deregulated expression levels have been observed in various cancers. Gene variants may alter microRNA processing and maturation. Thus, we aimed to investigate the association of MIR-196a2 rs11614913 (C/T), MIR-499a rs3746444 (A/G) polymorphisms and their combination with cancer susceptibility in an Egyptian population. Sixty five renal cell carcinoma (RCC) and 60 hepatocellular carcinoma (HCC) patients and 150 controls were enrolled in the study. They were genotyped using real-time polymerase chain reaction technology. Both $miR-196a2^*T$ and $miR-499a*G$ were associated with RCC risk, but only $miR-196a^*T$ was associated with HCC development. Carriage of the homozygote combinations ($MIR196a2^*TT+MIR499a^*AA$) and ($MIR196a2^*CC+MIR499a^*GG$) was associated with 25 and 48 fold elevation of likelhood to develop RCC, respectively. The miR-196a2 SNP was also linked with larger tumor size in RCC and advanced tumor stage in HCC. miR-196a2 and miR-499a combined genotypes were associated with RCC and HCC. Further functional analysis of SNPs is required to confirm relationships between genotypes and phenotypes.