Prevalence of Androgen Receptor in Invasive Breast Cancer and Its Association with Clinicopathologic Features in East Azarbaijan Province of Iran: A Cross-Sectional Study.

Background: Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in females. Accordingly, the evaluation of new prognostic markers and therapeutic targets is of vital importance. Here, we aimed to detect androgen receptor (AR) status and define its association with clinicopathologic parameters in patients with invasive breast cancer. Materials and Methods: In this study, AR status was studied in 104 patients with invasive breast carcinoma by immunohistochemistry. Besides, its association with clinicopathologic factors, i.e., age, menopausal status, tumor size, lymph node involvement, tumor stage, tumor grade and estrogen receptor (ER), progesterone receptor (PR), Her2/neu, Ki-67and P53 were investigated. Results: AR was positive in 84 patients (80.8%), and its expression in ER-positive (85.7%) and PR-positive (85.6%) patients were remarkably higher than in ER-negative (46.2%) and PR-negative (50%) patients (p= 0.001 and p=0.002, respectively). AR expression was noticeably lower in Her2/neu-positive (25%) patients compared to Her2/neu-negative (87.9%) ones (p=0.000). AR expression was also higher in patients with smaller, earlier stage, and low mitotically active tumors, but the association was not statistically significant. Conclusion: The expression of AR in patients with breast cancer was found to be high and its association with ER-positive, PR-positive, and HER2/neu-negative tumors was found to be significant. In that light, this receptor may play an important role in the determination of prognosis and targeted therapy in breast cancer.

Profiling the expression of pro-metastatic genes in association with the clinicopathological features of primary breast cancer.

BACKGROUND: Metastasis accounts for ninety percent of breast cancer (BrCa) mortality. Cortactin, Ras homologous gene family member A (RhoA), and Rho-associated kinase (ROCK) raise cellular motility in favor of metastasis. Claudins (CLDN) belong to tight junction integrity and are dysregulated in BrCa. Thus far, epidemiologic evidence regarding the association of different pro-metastatic genes with pathological phenotypes of BrCa is largely inconsistent. This study aimed to determine the possible transcriptional models of pro-metastatic genes incorporate in holding the integrity of epithelial cell-cell junctions (CTTN, RhoA, ROCK, CLDN-1, CLDN-2, and CLDN-4), for the first time, in association with clinicopathological features of primary BrCa. METHODS: In a consecutive case-series design, 206 newly diagnosed non-metastatic eligible BrCa patients with histopathological confirmation (30-65 years) were recruited in Tabriz, Iran (2015-2017). Real-time RT-PCR was used. Then fold changes in the expression of target genes were measured. RESULTS: ROCK amplification was associated with the involvement of axillary lymph node metastasis (ALNM; ORadj. = 3.05, 95%CI 1.01-9.18). Consistently, inter-correlations of CTTN-ROCK (ß = 0.226, P < 0.05) and RhoA-ROCK (ß = 0.311, P < 0.01) were determined among patients diagnosed with ALNM+ BrCa. In addition, the overexpression of CLDN-4 was frequently observed in tumors identified by ALNM+ or grade III (P < 0.05). The overexpression of CTTN, CLDN-1, and CLDN-4 genes was correlated positively with the extent of tumor size. CTTN overexpression was associated with the increased chance of luminal-A positivity vs. non-luminal-A (ORadj. = 1.96, 95%CI 1.02-3.77). ROCK was also expressed in luminal-B BrCa tumors (P < 0.05). The estrogen receptor-dependent transcriptions were extended to the inter-correlations of RhoA-ROCK (ß = 0.280, P < 0.01), ROCK-CLDN-2 (ß = 0.267, P < 0.05), and CLDN-1-CLDN-4 (ß = 0.451, P < 0.001). CONCLUSIONS: For the first time, our findings suggested that the inter-correlations of CTTN-ROCK and RhoA-ROCK were significant transcriptional profiles determined in association with ALNM involvement; therefore the overexpression of ROCK may serve as a potential molecular marker for lymphatic metastasis. The provided binary transcriptional profiles need more approvals in different clinical features of BrCa metastasis.

Study of long non-coding RNA highly upregulated in liver cancer (HULC) in breast cancer: A clinical & in vitro investigation.

Background & objectives: Breast cancer remains the most common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in tumour initiation and progression. This study was aimed to evaluate the potential role of lncRNA highly upregulated in liver cancer (HULC) in breast cancer. Methods: The expression of HULC was evaluated in breast cancer patients and cell lines using real-time quantitative reverse transcription polymerase chain reaction. Small interfering RNA-based knockdown was also employed to study the potential role of HULC in breast cancer cell lines including ZR-75-1, MCF7 and MDA-MB-231. Results: HULC was significantly upregulated in tumour tissues compared to non-tumoural margins (P <0.001). The receiver operating characteristic (ROC) curve analysis demonstrated the biomarker potential of HULC (ROCAUC=0.78, P <0.001). The HULC knockdown induced apoptosis and suppressed cellular migration in breast cancer cell lines. Interpretation & conclusions: Our results indicated that HULC was upregulated in breast cancer and might play a role in tumourigenesis. The HULC may have a potential to be exploited as a new biomarker and therapeutic target in breast cancer.

Predictive Value of CD44 for Prognosis in Patients with Breast Cancer.

BACKGROUND: Breast Cancer (BC), is one of the most common malignancies around the world. CD44 expression correlates with cell proliferation, infiltration, angiogenesis, metastasis and prognosis in breast cancer but the exact mechanism of CD44 function is still not clear. The present study evaluates the expression of CD44 in primary HER2-positive breast cancer. The results can be used to determine the disease-free and overall survival of patients with breast cancer. METHODS: We studied specimens from 100 patients with HER2-positive invasive breast cancer between March 2011 and June 2019. Immunohistochemical staining for CD44 was performed in all the specimens. Their CD44 association with clinicopathologic parameters and prognosis was evaluated. RESULTS: The high CD44 was expression in 68(68%) of the patients and Low expression in 32(32%). CD44 expression was significantly associated with stage (p=0.007). There were no significant associations between the DFS, OS and other clinicopathologic parameters except for the stage, respectively (HR= 3.67, 95% CI =1.16-11.56, P = 0.03) (HR= 0.8.56, 95% CI =2.22-32.90, P = 0.002).20% of patients had died by the end of the follow-up. There were no significant association between DFS, OS and CD44 expression, respectively. (Log-rank p=0.13). (Log-rank p=0.10). CONCLUSION: The results from this study suggest that CD44 is clinically associated with stage of breast cancers. From the survival analysis, there was no statistical difference in overall survival and disease free survival with respect to CD44 expression. Further studies larger sample sizes are recommended for further investigation.

The contribution of dietary and plasma folate and cobalamin to levels of angiopoietin-1, angiopoietin-2 and Tie-2 receptors depend on vascular endothelial growth factor status of primary breast cancer patients.

The aim of this study was to determine the association of dietary folate and cobalamin with plasma levels of Angiopoietins (ANG), vascular endothelial growth factor-C (VEGF-C) and tyrosine kinase receptor-2 (Tie-2) of primary breast cancer patients. Women (n = 177), aged 30 to 75 years diagnosed with breast cancer were recruited from an ongoing case series study. Dietary intake of nutrients was estimated by using a validated food frequency questionnaire. Enzyme-linked immunosorbent assay was applied to measure biomarkers. MCF-7 cell cultures were supplemented with folic acid (0-40 µM) for 24 h to measure cell viability and fold change of expression by the real-time reverse transcriptase-polymerase chain reaction. Structural equation modeling was applied to analyze the structural relationships between the measured variables of nutrients and Angiopoietins. Dietary intake of folate and cobalamin showed a significant inverse correlation with plasma ANG-1 and ANG-2 (P < 0.05), particularly in subjects with estrogen-receptor positive tumors or low plasma VEGF-C. Plasma folate was positively associated with the ratio of ANG-1/ANG-2 (P < 0.05). Residual intake levels of total cobalamin were inversely associated with plasma ANG-1 when plasma stratum of VEGF-C was high (P < 0.05). Structural equation modeling identified a significant inverse contribution of folate profiles on the latent variable of Angiopoietins (coefficient ß = -0.99, P < 0.05). Folic acid treatment resulted in dose-dependent down-regulations on ANGPT1 and ANGPT1/ANGPT2 ratio but VEGF and ANGPT2/VEGF were upregulated at folic acid >20 µM. Studying the contributing role of dietary folate to pro-angiogenic biomarkers in breast cancer patients can infer the preventive role of folate in the ANGs/VEGF-C-dependent cascade of tumor metastasis. By contrast, high concentrations of folic acid in vitro supported VEGF-C-dependent ANGPT2 overexpression might potentiate micro-lymphatic vessel development to support malignant cell dissemination.

Dietary protein sources and tumoral overexpression of RhoA, VEGF-A and VEGFR2 genes among breast cancer patients.

BACKGROUND: High protein intake may promote angiogenesis giving support to the development of metastasis according to the experimental data. However, nutritional epidemiologic evidence is inconsistent with metastasis. Therefore, we aimed to study the association between dietary intake of protein and tumoral expression levels of Ras homologous gene family member A (RhoA), vascular endothelial growth factor-A (VEGF-A), and VEGF receptor-2 (VEGFR2) in primary breast cancer (BC) patients. METHODS: Over this consecutive case series, 177 women primary diagnosed with histopathologically confirmed BC in Tabriz (Iran) were enrolled between May 2011 and November 2016. A validated food frequency questionnaire was completed for eligible participants. Fold change in gene expression was measured using quantitative real-time PCR. Principal component factor analysis (PCA) was used to express dietary groups of proteins. RESULTS: Total protein intake was associated with the expression level of VEGF-A in progesterone receptor-positive (PR+: ß = 0.296, p < 0.01) and VEGFR2 in patients with involvement of axillary lymph node metastasis (ALNM+: ß = 0.295, p < 0.01) when covariates were adjusted. High animal protein intake was correlated with overexpression of RhoA in tumors with estrogen receptor-positive (ER+: ß = 0.230, p < 0.05), ALNM+ (ß = 0.238, p < 0.05), and vascular invasion (VI+: ß = 0.313, p < 0.01). Animal protein intake was correlated with the overexpression of VEGFR2 when tumors were positive for hormonal receptors (ER+: ß = 0.299, p < 0.01; PR+: ß = 0.296, p < 0.01). Based on the PCA outputs, protein provided by whole meat (white and red meat) was associated inversely with RhoA expression in ALNM+ (ß = - 0.253, p < 0.05) and premenopausal women (ß = - 0.285, p < 0.01) in adjusted models. Whole meat was correlated with VEGFR2 overexpression in VI+ (ß = 0.288, p < 0.05) and premenopausal status (ß = 0.300, p < 0.05) in adjusted models. A group composed of dairy products and legumes was correlated with the overexpression of RhoA (ß = 0.249, p < 0.05) and VEGF-A (ß = 0.297, p < 0.05) in VI+. CONCLUSIONS: Based on the multivariate findings, the dietary protein could associate with the overexpression of RhoA and VEGF-VEGFR2 in favor of lymphatic and vascular metastasis in BC patients.

Clinical and in vitro Study of Novel Long Non-Coding RNA lncUSMycN in Breast Cancer

Background: Despite recent advances in diagnosis and treatment, breast cancer remains a leading cause of death in women worldwide. Long non-coding RNAs are a new class of RNA molecules that have been shown to participate in tumorigenesis. The aim of this study was to investigate the expression of lncUSMycN in tumor samples and to evaluate its potential role in the breast cancer cell line. Methods: Real-time polymerase chain reaction was employed to assess lncUSMycN expression in breast tumor tissues and cancer cell lines. Furthermore, small interfering RNA was used to knockdown lncUSMycN. Results: The data showed the significant up-regulation of lncUSMycN in tumor tissues compared to non-tumor specimens (95% CI, p = 0.002). Receiver operating characteristic (ROC) curve analysis demonstrated the biomarker potential of lncUSMycN (ROCAUC = 0.70, p < 0.001) for invasive breast ductal carcinoma. Furthermore, lncUSMycN knockdown induced apoptosis and suppressed cellular migration in breast cancer cells (p < 0.01). Conclusion: The findings highlight the pivotal role of lncUSMycN in tumorigenesis, providing a new potential target for breast cancer therapy.

Association of clinicopathologic characteristics and outcomes with EZH2 expression in patients with breast cancer in East Azerbaijan, Iran.

BACKGROUND: Recently, it was found that the overexpression and mutation status of EZH2 affect cancer progression and patient outcome in several human tumors. We aimed to evaluate the clinicopathologic significance of EZH2 in patients with breast cancer. METHODS: This was an analytical descriptive study of surgical specimens of primary breast tumors. Specimens were analyzed immunohistochemically for EZH2, estrogen receptor, progesterone receptor, Ki-67, P53, and human epidermal growth factor receptor 2 (HER2) expressions. Regression analysis was performed to calculate hazard ratios (HRs) and 95% CIs. Kaplan-Meier and Cox regression models were used to estimate the overall survival (OS) and disease-free survival (DFS). RESULTS: We included 100 patients with breast cancer (mean age 51.05±9.54 years). The multivariate regression analysis showed that HER2-positive patients had approximately twice the levels of EZH2 expression compared with HER2-negative patients (HR 2.16, 95% CI 0.48-11.49). The likelihood of EZH2 expression was significantly higher in patients with lymph node involvement than in those without (HR 8.44, 95% CI 3.06-23.33; P≤0.05). EZH2 expression did not have any significant effect on the OS, although the mean OS in high EZH2 expression was shorter than for those with low EZH2 expression (655 vs 787 days; log-rank P=0.336). The mean DFS was 487 days for patients with high EZH2 expression compared with 908 days for those with low EZH2 expression (log-rank P=0.188). CONCLUSION: There was no association found between EZH2 expression and OS and DFS in our patients. Further studies involving larger sample sizes, and conducted in different populations, are needed to validate this hypothesis.

Gene Expression Analyses of HER-2/neu and ESR1 in Patients with Breast Cancer

ABSTRACT Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

Gene Expression Analyses of HER-2/neu and ESR1 in Patients with Breast Cancer

ABSTRACT Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration.

INTRODUCTION: Breast carcinoma is the most prevalent tumors among women. Transformation of inflated cells in immune response leads to increase in inflammatory cells such as macrophages, mast cells (MC) and fibroblasts. The aim of this study was to determine the relationship between grades of invasive carcinoma of the breast ducts and MC infiltration around tumoral cells. METHODS: During the present study, 75 female patients suffering from invasive ductal carcinoma who underwent surgery or diagnostic biopsy during 2010 and 2013 in Educational-Medical centers of Tabriz University of Medical Sciences, were included in the study. Based on Bloom-Richardson grading system, 25 cases were selected from each grade. To better observe of MCs, samples were stained by Toluidine blue and MCs were counted in 10 40 × 10 fields. RESULTS: The mean age was 47.56 ± 10.84 and the number of MCs was between 6 and 96 and their overall average was 43.01. Average count of MCs in grade 1, 2 and 3 were 15.92 ± 10.07, 45.32 ± 10.47, and 67.8 ± 20.70, respectively. There was a significant relationship between the number of MCs and increase in disease grade (P < 0.001). With increasing grade of malignancy, the number of MCs had grown. No significant relationship was observed between age and grade of disease or age and number of MC. CONCLUSION: According to obtained results, number of MC around tumoral cells increased significantly with an increase in the grade of disease. In order to treat in the first stages of the disease, recognizing primary changes in the stroma of cells could be helpful.

DNA methylation assessment as a prognostic factor in invasive breast cancer using methylation-specific multiplex ligation dependent probe amplification.

DNA methylation of promoter regions is a common molecular mechanism for inactivation of tumor suppressor genes that participates in carcinogenesis. Determining the methylation status of genes in cancer and their association with clinical features play an essential role in early diagnosis, prognosis and determine appropriate treatment for patients. The purpose of the present study was to evaluate the methylation of tumor suppressor genes in patients with invasive ductal carcinoma (IDC). Furthermore, we evaluated the association between clinical parameters and DNA methylation as a biomarker in diagnostic IDC patients. The methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) assay was used to analyze the methylation profile of 24 genes in formalin-fixed paraffin embedded (FFPE) tissue samples from 75 patients with IDC. Each of the patients showed a distinctive methylation profile. We observed higher methylation in the RASSF1 (48 %), CDH13 (44 %) and GSTP1 (36 %) genes. Some of the methylated genes were associated with clinical features. Methylation of GSTP1 (P=0.028) and RASSF1 (P=0.012) were related with lymph node metastasis. Methylation of GSTP1 (P=0.005) was associated with high histological grade. Moreover, concurrent methylation of GSTP1 and CDH13 was observed in IDC patients (p<0.001). Hierarchical cluster analysis based on the methylation profile revealed two main clusters of patients, the highly methylated cluster being significantly associated with high histological grade and lymph node metastasis. The results of this study indicate that the methylation status of RASSF1 and CDH13 and GSTP1 can be a prognostic marker to better management of IDC patients.

Methylation Analysis of BRCA1 and APC in Breast Cancer and It's Relationship to Clinicopathological Features.

BACKGROUND: Promoter methylation of tumor suppressor genes is an important epigenetic alteration that occurs in the primary stages of human tumors, including breast cancer. Identification of methylated genes and their relationship to clinical features can contribute to the prognosis and early detection of tumors. In this study, we explored the methylation status of APC and BRCA1 genes and their relationship to clinical factors in breast cancer patients. METHODS: BRCA1 and APC promoter methylation was examined by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay in formalin-fixed paraffin embedded (FFPE) breast tissue from 75 patients. RESULTS: APC promoter methylation was detected in 30.67% breast cancer tissues and BRCA1 was methylated in 9.33% of breast tumors. Methylation of APC was associated with low histological grade (p = 0.006) and methylation of BRCA1 was related with lymph node metastasis (p = 0.017). CONCLUSIONS: These findings suggest that the methylation status of APC and BRCA1 can be a predictive marker for early detection and better management of breast cancer patients.

Personalized Gene Expression Analyses of SMAD7 and KLF10 In Breast Cancer

Many cancer researchers use gene expression analysis for differentiation between tumor and normal cells for diagnostic, prognostic and therapeutic purposes. Most of studies compare either tumor cell lines by normal cell lines or tumor tissue of affected individuals by normal healthy control tissue. But expression of each special gene is unique in different individuals and also in different tissue of same individual. For this reason, here we compare the gene expression levels of SMAD7 and KLF10 in tumor cells and its adjacent normal tissue of breast cancer patients and compared them. For this purpose, a total of 40 tumor and matched tumor-free margin samples were obtained during surgery. The SMAD7 and KLF10 mRNA expression levels in tumor and marginal samples were examined by real-time quantitative PCR. Results are not concordant with previous studies and comparison of only SMAD7 or KLF10 is not useful for differentiating between tumor and margin cells, but ratio analysis of these two genes, SMAD7/ KLF10, can be indicative than study of one gene alone. We concluded that gene expression analysis of tumor cells with adjacent normal tissue are essential for precise identification and interpretation of cancer alterations and have important implications for the diagnostic and therapeutic management of cancer patients.

Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model.

BACKGROUND: Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method. OBJECTIVES: The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model. MATERIALS AND METHODS: Eighteen adult Iranian mixed breed male dogs were used to conduct this experimental study. Full thickness articular cartilage defects (diameter 6 mm, depth 5 mm) were created in the weight bearing area of femoral condyles of both hind limbs in all dogs (n = 72). Twelve dogs were randomly selected to receive treatment and their right and left hind limb defects were treated by L-PRP and L-PRF implantation respectively, while no treatment was undertaken in six other dogs as controls. The animals were euthanized at 4, 16 and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. At each sampling time, 4 treated dogs and 2 control dogs were euthanized, therefore 8 defects per group were evaluated. RESULTS: Mean macroscopic scores of the treated defects were higher than the controls at all sampling times with significant differences (P < 0.05) observed between L-PRF treated and control defects (10.13 vs. 8.37) and L-PRP treated and control defects (10 vs. 8.5) at 4 and 16 weeks, respectively. A similar trend in mean total microscopic scores was observed with a significant difference (P < 0.05) between L-PRP treated and control defects at 4 (9.87 vs. 7.62) and 16 (13.38 vs. 11) weeks. No significant difference was observed between the platelet concentrate treated defects in either mean macroscopic scores or mean total microscopic scores. CONCLUSIONS: Both L-PRP and L-PRF could be used to effectively promote the healing of articular cartilage defects of the knee.

Primary hydatid cyst of the right maxillary sinus: a case report.

INTRODUCTION: A hydatid cyst of the head and neck is a very rare condition, even in areas where Echinococcus infestation is endemic. CASE REPORT: We report a rare case of primary hydatid cyst of the right maxillary sinus in a 40-year-old man. The initial diagnosis of the presence of a cystic mass was the result of physical examination and computed tomography (CT) scan. We resected the cystic mass using the Caldwell-Luc procedure. A definitive diagnosis was confirmed by postoperative histopathologic examination. CONCLUSION: Hydatid cyst of the maxillary sinus is an extremely rare presentation. However, this condition should be considered in differential diagnosis of cystic lesions of the maxillary sinus.

Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population.

The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA, essential for p53 stabilization and induction upon DNA damage. Single nucleotide polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which strengthens the role of WRAP53 in the pathogenesis of human malignancies. In fact, WRAP53 has been considered as a candidate cancer susceptibility gene. Accordingly, we performed a study to examine the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population. A case-control association study, including 206 cases and 203 controls from Iranian-Azeri population, was conducted. Genomic DNA was extracted from peripheral blood and tumor samples by salting-out method. SNP genotyping was carried out by polymerase chain reaction-based single-strand conformational polymorphism (PCR-SSCP) technique. The sequence variation of SSCP banding patterns was determined by sequencing. The collected data were analyzed through statistical package for the social sciences software, using Chi-square (χ (2)) or Fisher's exact tests, with a significance level of 0.05. No significant differences in the allele and genotype frequencies between cases and controls were detected. Similarly, no significant associations between genotypes and clinicopathological data were observed. Concisely, no significant overall associations between rs2287499 and breast cancer risk and prognosis were detected in the studied population. The rs2287499 SNP is not associated with breast cancer predisposition in Iranian-Azeri women; it also cannot be used as a molecular biomarker to predict breast cancer prognosis in Iranian-Azeri population.

Effect of autologous platelet rich fibrin on the healing of experimental articular cartilage defects of the knee in an animal model.

The effect of autologous platelet rich fibrin (PRF), a second generation platelet product, on the healing of experimental articular cartilage lesions was evaluated in an animal model. Full thickness cartilage lesions with a diameter of 6 mm and depth of 5 mm were created in the weight bearing area of femoral condyles of both hind limbs in 12 adult mixed breed dogs. Defects in the left hind limb of each dog were repaired by PRF implantation whereas those in the right hind limb were left empty. The animals were euthanized at 4, 16, and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. The results of macroscopic and histological evaluations indicated that there were significant differences between the PRF treated and untreated defects. In conclusion, the present study indicated that the use of platelet rich fibrin as a source of autologous growth factors leads to improvement in articular cartilage repair.

Prognostic value of tumor-infiltrating mast cells in outcome of patients with esophagus squamous cell carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) of the esophagus is one of the most common malignancies of the gastrointestinal tract and carries poor prognosis. The role of mast cell density (MCD) in the prognosis of most human tumors is partly known, and there is a growing body of studies addressing it. However, the prognostic value of MCD has not been investigated in esophageal SCC, and thus, it was the subject during this study. METHODS: In this study, 78 patients with esophageal SCC in pT = 3 were selected, their MCD was evaluated with toluidine blue staining, and the relationship with survival rate was analyzed. Patients were compared in identical groups of lymph node involvement and post-surgery complementary therapy. RESULTS: Survival rate was significantly decreased in patients with high MCD based on Kaplan-Meier analysis (P < 0.001). This relationship was also found in groups with similar lymph node involvement and post-surgery therapies. CONCLUSIONS: The results of the current study showed that high MCD in the invasive edge of tumor is related to tumor progression and decreased survival rate following surgery.

Immunohistochemical study of cyclooxygenase-2 in skin tumors.

INTRODUCTION: Anti-cancerous effects of cyclooxygenase-2 (COX-2) inhibitors have been reported in different cancers. High expression of COX-2 has been demonstrated in various neoplasms such as colorectal, gastric, esophageal, breast, non-small cell lung cancers, and pre-neoplastic lesions such as colorectal adenomas and Barrett's esophagus. GOAL: The purpose of this study was to investigate percentage of positive COX-2 expression in skin tumors, including pre-malignant and malignant tumors. METHODS: This is an analytic cross-sectional study that includes 62 skin tumor samples, among which 49 samples were malignant and 13 were pre-malignant. After study for determination of pathologic kind of tumors, samples underwent immunohistochemical study for COX-2 expression. The DakoCytomation EnVision+System-HRP is a two-step extremely sensitive IHC staining technique which we used in this study. RESULTS: Among the skin tumors, a considerable number of COX-2 expression were found in squamous cell carcinomas (SCC) (16 of 17; 94%), basal cell carcinomas (BCC) (28 of 32; 87.5%), Bowen's disease (BD) (8 of 9; 89%), and actinic keratosis (AK) (4 of 4; 100%). CONCLUSION: COX-2 expression was positive in skin tumors including malignant and pre-malignant skin lesions. This study strongly suggests that COX-2 can be one of the molecular targets in treating various skin tumors.