Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma.

OBJECTIVE: Osteosarcoma is considered the most common primary malignant tumor that develops from the primary osteoblasts. MiRNAs are small non-coding RNAs that play a key role in tumorigenesis. The aim of this study was to detect the possible relationship between expression levels of miRNA-34a and levels of Signal transducer and activator of transcription 3 (STAT3) and interleukin-6 receptor (IL-6R) in osteosarcoma and the possible role of this relationship in development of metastases in these patients. METHODS: A total of thirty-six (36) bone samples were included in the study. They were divided into 3 groups: Group (I): Twelve normal bone samples as control group. Group (II): Twelve patients with non-metastatic osteosarcoma. Group (III): Twelve patients with metastatic osteosarcoma. MiRNA-34a expression levels were estimated using qRT-PCR. STAT3 and IL-6R levels were measured by ELISA. RESULTS: Expression level of miRNA-34a was downregulated in osteosarcoma groups compared to control group. STAT3 and IL-6R levels were upregulated in osteosarcoma groups compared to control group. This difference in expression levels was found to be more significant in the metastatic group than the non-metastatic one (P<0.001 each). There was a significant positive correlation between STAT3 and IL-6R (r=0.868, P<0.001), and a significant inverse correlation between IL6 and miRNA-34a (r=-0.993, P<0.001). CONCLUSION: miRNA-34a, STAT3 and IL-6R feedback loop could be a potential target for treatment of osteosarcoma and can be used as prognostic indicator for this disease.

Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.

BACKGROUND: Serum Prostate-specific antigen (PSA) has been used for screening and diagnosis of prostate cancer (PCa) but it is burdened by its low accuracy, creating a need for reliable diagnostic markers. Despite prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) being widely expressed in the tissue of PCa, no definite conclusion regarding their use as clinical biomarkers due to their lacking organ specificity. Therefore, this study aimed to evaluate the peripheral blood levels of PSMA and PSCA mRNAs and examine their diagnostic significance as non-invasive integrated markers.

Materials and Methods: 125 subjects were enrolled in this study. They were divided into 25 healthy controls, 25 BPH patients, and 75 PCa patients. The expression levels of PSMA and PSCA were determined using quantitative RT- PCR, in addition to measuring serum PSA.

Results: Levels of PSMA and PSCA were over-expressed in PCa patients compared to controls and BPH patients and were found to be associated with increased susceptibility to PCa. Moreover, the diagnostic values of PSMA and PSCA to distinguish PCa patients from BPH patients and controls were inferior to that of PSA. However, the combination of PSMA and PSCA with PSA enhanced the efficacy of the latter.

Conclusion: This study suggests that these genes were associated with malignant susceptibility. Concerning the duality of PSMA-PSA or PSCA-PSA, this implies the significance of their investigation together in peripheral blood of prostate patients.

Gene-Gene Interaction Study Between Genetic Polymorphisms of Folate Metabolism and MTR SNPs on Prognostic Features Impact for Breast Cancer.

Background: Breast Cancer (BC), the second leading cause of cancer mortality after lung cancer and varied across the world due to genetic and environmental factors. In this study, we evaluated the interaction between the polymorphisms in genes encoding enzymes of folate metabolism: methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR) with the BC prognostic factors. Methods: This study was conducted on 160 Egyptian subjects, 60 controls and 100 cases. Sequencing, RFLP analysis in addition to statistical analysis including Chi-squared test, haplotype analysis was used to evaluate associations with BC risk and its clinicopathological parameters. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Results: Strong significant association with breast cancer risk was observed for the haplotype (T-C-G) of MTHFR C677T/ MTHFR A1289C and MTRA2576G and hormonal receptor expression (ER-/PR-/HER2+), bigger and advanced tumor and metastatic lymph nodes. However, no significant difference was observed for age. Conclusion: The combination of SNPs from MTHFR and MTR genes has a more synergistically genetic effect on BC disease progression. These SNPs could be used as tumor aggressiveness markers among Egyptian females with BC and could help in saving money and time.

Micro RNA-148a Targets Bcl-2 in Patients with Non-Small Cell Lung Cancer.

OBJECTIVE: Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide. MicroRNAs regulate more than 60% of human genes, including tumor suppressor genes and oncogenes. Accordingly, they can affect cancer risk. This study aimed to evaluate the role of serum miR-148a as a non-invasive biomarker in non-small cell lung cancer (NSCLC) patients and to assess the correlation between miR-148a and Bcl-2, as one of its target proteins. MATERIALS AND METHODS: A total of 50 newly diagnosed NSCLC cases and 30 apparently healthy controls were recruited in this study. MiR-148a level was measured by TaqMan- Real time RT-PCR assay and Bcl-2 level was measured by ELISA. RESULTS: Significant lower expression of serum miR-148a and higher serum Bcl-2 levels were observed in NSCLC patients as compared to the control group (p.

Strong Correlation of MTHFR Gene Polymorphisms with Breast Cancer and its Prognostic Clinical Factors among Egyptian Females.

INTRODUCTION: Globally, Breast cancer (BC) is considered the second most common type of cancer and the principal cause of death among affected women. AIM: In this study, we targeted to demonstrate the association of MTHFR single gene polymorphisms (SNPs) with the susceptibility of breast cancer, in addition to its correlation with the clinical patient features. PATIENTS AND METHODS: This work was conducted on 100 Egyptian females with breast cancer and 60 healthy matched controls. Clinical examinations and pathological investigations were recorded. Genotyping of MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) by using Restriction Fragment length Polymorphisms (RFLP) and Sequencing assays were performed. Univariate, Multivariate and Haplotype analysis for the allelic frequencies and the association with clinicopathological features of BC were assessed. RESULTS: The present data showed a strong significant association between the CT and TT of MTHFR (C677T), and AC and CC of (A1289C) with the susceptibility of BC showing highly statistical P- value (0.001). It was also demonstrated that the most frequent haplotype of the two loci of MTHFR (rs1801133-rs1801131) was TC. The latter was strongly associated with the aggressive clinical features of each of tumor size, advanced stage, involvement of cancer in lymph nodes, overexpression of HER2neu and dual negativity of both ER and PR hormones. CONCLUSIONS: SNPs within the MTHFR gene (C677T) and (A1289C) have strong correlation with BC among Egyptian females; These SNPs should be considered as important prognostic markers for identifying the individuals at high risk of developing BC and its progression.

The relation between regular outpatient follow-up and frequency of emergency department visits in sickle cell pediatric patients.

OBJECTIVE: To evaluate the relationship between the frequency of ED visits and outpatient department (OPD) follow-up in sickle cell disease (SCD) pediatric patients. METHODS:   A retrospective cohort study included 247 SCD pediatric patients between January 2016 and December 2018 at the Maternity and Children Hospital, Department of Pediatrics, Al Medinah Al Munawarah, Saudi Arabia. Data were extracted from electronic medical record system; patient demographics, medications, frequency of emergency department (ED) and OPD visits. Pearson correlation coefficient, linear regression and independent sample t-test were applied. RESULTS: There was no significant correlation (95% CI [-0.013- 0.233]; p=0.07) between the frequency of ED and OPD visits. However, a significant correlation was found between ED visits and missed OPD appointments. Thus, linear regression was applied and indicated that one missed OPD appointment is associated with 1.92 ED visits, (95% CI: 0.19-0.42; p less than 0.001). Also, a higher rate of ED visits was observed when compared with other studies, with a high ED reliance of 43%. CONCLUSION: This study found that regular OPD visits could improve SCD management, as a directly proportional relationship between the frequency of ED visits and missed OPD appointments along with high ED reliance.

Prognostic Significance of Serum Vitamin D Levels in Egyptian Females with Breast Cancer

Objective: To determine the frequency and prognostic significance of vitamin D deficiency in Egyptian women with breast cancer (BC). Methods: This prospective study included 50 women with primary invasive, non-metastatic BC. The serum level of 25-hydroxy vitamin D [25(OH)D was measured by ELISA at diagnosis, before any cancer treatment. Vitamin D deficiency was defined as 25(OH) D<20 ng/mL. Patients were followed up for a median of 30 months (range: 18-48). Results: The median level of 25(OH)D was 29.0 ng/mL (range: 10.0-55.0 ng/mL). Fifteen patients (30%) had vitamin D deficiency, which was positively associated with larger tumor size (p < 0.001), higher grade (p = 0.014), advanced stage (p = 0.001), lymph node positivity (p = 0.012), and HER2/neureceptor expression (p = 0.002). It was also linked with worse overall survival (OS) and disease free survival (DFS) (p = 0.026, and p = 0.004, respectively). On multivariate analysis, DFS was independently affected by vitamin D deficiency with an HR of 2.8 (95% CI: 1.6-7.0, p = 0.022) and advanced stage, i.e. stage II had worse survival compared to stage I with an HR of 4.8 (95%CI: 1.1-21.7, p = 0.042). Conclusion: Vitamin D deficiency had a negative effect on overall and disease-free survival in our breast cancer cases, being related to tumor size, stage, grade, nodal status and HER2/neu receptor expression.

Regression of fibrosis in paediatric autoimmune hepatitis: morphometric assessment of fibrosis versus semiquantiatative methods.

BACKGROUND: Regression of hepatic fibrosis in patients with autoimmune hepatitis (AIH) has been described in response to immunosuppressive therapy. These studies, however, besides being few in number, were conducted on adult populations. Our aim was to assess the regression of hepatic fibrosis, using morphometric assessment of fibrosis versus semi-quantitative methods, in children with AIH who achieved clinical and biochemical remission. Thirteen patients who achieved clinical and biochemical remission were included in the study, out of 62 children with AIH. Repeat biopsy was performed after 6 to 12 months of clinical and biochemical remission. Morphometric assessment of fibrosis was performed and correlated with METAVIR and Ishak semi-quantitative scores. RESULTS: The study group included eight male and five female patients. The median age at presentation was 4 years (range 2 to 12 years). The mean duration of treatment was 22 +/- 7.3 months, and the mean interval between biopsies was 26.2 +/- 6.5 months. Following therapy, there was significant reduction in aspartate aminotransferase, ALT and IgG levels as well as improvement of necroinflammation. The mean fibrosis scores were significantly decreased from 4.5 +/- 1.19 and 2.9 +/- 0.7 before therapy to 2.7 +/- 1.16 and 2 +/- 0.8 after treatment as assessed by Ishak and METAVIR scores, respectively (P = 0.001 and 0.004). The mean morphometric assessment of fibrosis before treatment was 20% +/- 9.7 and following therapy it decreased to 5.6% +/- 3.9 (P = 0.000). CONCLUSION: Significant regression of fibrosis in paediatric AIH could occur with current therapeutic regimens. Morphometric assessment of fibrosis is more sensitive than semi-quantitative methods to identify changes in fibrosis.