Unraveling Roles of miR-27b-3p as a Potential Biomarker for Breast Cancer in Malay Women via Bioinformatics Analysis.

Abnormal miRNA expression has been associated with breast cancer. Knowing miRNA and its target genes gives a better understanding of the biological mechanism behind the development of breast cancer. Here, we evaluated the potential prognostic and predictive values of miRNAs in breast cancer development by analyzing Malay women with breast cancer expression profiles. Seven differentially expressed miRNAs (DEMs) were subjected to miRNA‒target interaction network analysis (MTIN). A comprehensive MTIN was developed by integrating the information on miRNA and target gene interactions from five independent databases, including DIANA-TarBase, miRTarBase, miRNet, miRDB, and DIANA-microT. To understand the role of miRNAs in the progress of breast cancer, functional enrichment analysis of the miRNA target genes was conducted, followed by survival analysis to assess the prognostic values of the miRNAs and their target genes. In total, 1416 interactions were discovered among seven DEMs and 1274 target genes with a confidence score (CS) > 0.8. The overall survival analysis of the three most DEMs revealed a significant association of miR-27b-3p with poor prognosis in the TCGA breast cancer patient cohort. Further functional analysis of 606 miR-27b-3p target genes revealed their involvement in cancer-related processes and pathways, including the progesterone receptor signaling pathway, PI3K-Akt pathway, and EGFR transactivation. Notably, six high-confidence target genes (BTG2, DNAJC13, GRB2, GSK3B, KRAS, and UBR5) were discovered to be associated with worse overall survival in breast cancer patients, underscoring their essential roles in breast cancer development. Thus, we suggest that miR-27b-3p has significant potential as a biomarker for detecting breast cancer and can provide valuable understanding regarding the molecular mechanisms of the disease.

BRAF V600E and Mismatch Repair Proteins Expression in Sporadic Young-onset Colorectal Cancer in Kelantan, Malaysia.

OBJECTIVES: We sought to determine the immunohistochemistry expression of mismatch repair (MMR) and BRAF V600E proteins in sporadic young-onset colorectal cancer (CRC) and their association with clinicopathological features in the Kelantan population. METHODS: This was a cross-sectional study of sporadic young-onset CRC over 11 years from 1 January 2006 to 31 December 2017 in Kelantan. Formalin-fixed paraffin-embedded tissue blocks were immunohistochemically stained with antibodies for MMR (MLH1, MSH2, MSH6, and PMS2) and BRAF V600E. These expressions were correlated with clinicopathological parameters. RESULTS: Our patient sample included 31 patients with a mean age of 31.5 years. More than half (61.3%) of the patients were women. The majority presented with abdominal pain (41.9%), and 71.0% had a tumor located on the right side of the colon, with 83.9% being moderately differentiated adenocarcinoma. The majority of patients presented at stage IV (54.8%). The most frequent pattern was all MMR protein expressions, which constituted patients in the microsatellite stable group (64.5%). Nine (29.0%) were microsatellite instability (MSI-high), and two (6.5%) were MSI-low. Positive BRAF V600E expression was observed in 83.9% of patients. Only histopathological subtypes revealed a significant association with BRAF V600E positive expression (p = 0.015). CONCLUSIONS: The majority of sporadic young-onset CRC presented with abdominal pain and advanced cancer stage. Most were microsatellite stable, and most cases showed positive expressions in all MMR markers and BRAF V600E by immunohistochemistry method. This finding will pave the way for further research on this disease.

Protective effects of bee bread on testicular oxidative stress, NF-κB-mediated inflammation, apoptosis and lactate transport decline in obese male rats.

Oxidative stress, chronic inflammation and apoptosis are associated with obesity. Herein, we investigated the potential protective effect of bee bread, a natural bee product, on testicular oxidative stress, inflammation and apoptosis, as well as lactate transport in the testis of high-fat diet (HFD)-induced obese rats. Adult male Sprague-Dawley rats were either fed with normal chow (NC), HFD, HFD + bee bread (0.5 g/kg b.w./day) or HFD + orlistat (10 mg/kg b.w./day) for 12 weeks. Our results show significant decreases in the activities and mRNA expression of antioxidant genes (Nrf2, Sod, Cat and Gpx), with significant increase in pro-inflammatory (Nf-κb, Tnf-α, iNos, Il-1ß) and pro-apoptotic (p53, Bax, Bax/Bcl2, Caspase-8, Caspase-9 and Caspase-3) genes in the testis of HFD group relative to the NC group. Furthermore, proliferating cell nuclear antigen (PCNA) was poorly expressed in the testis of the HFD group relative to the NC group. Similarly, the mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc) decreased significantly, with decrease in lactate utilisation. Treatment with bee bread upregulated testicular antioxidant enzymes, downregulated inflammation and apoptosis, and increased PCNA immunoexpression, in addition to improving lactate transport. Taken together, our results suggest that bee bread is a promising natural product with the potential to improve male fertility.

Microvessel density and vascular endothelial growth factor receptors in breast carcinoma under the influence of rapamycin and platelet factor 4.

BACKGROUND: Vascular endothelial growth factor receptors (VEGFRs) are major endothelial growth factor receptors that influence the growth of a tumor. Microvessel density. (: MVD) is the quantification method of various aspects of tumor vasculature that indicates angiogenic activity. This study aims to analyze the correlation between MVD to the expression of VEGFRs on breast cancer tissue. MATERIALS AND METHOD: A total of 60 N-methyl-N-nitrosourea (MNU)-induced breast carcinomas in rats were suppressed by using antiangiogenic drugs. The rats were then sacrificed, and the tumor was fixed in 10% formalin, paraffin embedded, and immunohistochemistry stained using VEGFRs and CD34. RESULT: One-way ANOVA test showed a significant difference in all markers that have been used (P < 0.05) on MNU-breast tumor treated with rapamycin (M= 90.1664, SD= 7.4487), PF4 (M= 93.7946, SD= 7.1303) and rapamycin + PF4 (M= 93.6990, SD= 1.8432). We obtained a significant reduction of MVD count on breast carcinoma for rapamycin group (M= 25.6786, SD= 9.7075) and rapamycin + PF4 group (M= 30.5250, SD= 13.6928) while PF4 group (M=47.7985, SD=4.8892) showed slightly increase compared to control (M= 45.1875, SD= 4.4786). There was a moderately strong, positive correlation between angiogenic markers; Flt-1 (r= 0.544, n=60, P < 0.005) and Flt-4 (r= 0.555, n= 60, P < 0.005) while Flk-1 (r= 0.797, n= 60, P < 0.005) showed a strong, positive correlation with MVD. CONCLUSION: MVD was strongly correlated to the VEGFRs expression on breast carcinoma.

Solid variant of papillary thyroid carcinoma in a 14-year-old girl.

Solid variant of papillary thyroid carcinoma (PTC) is a rare, poorly characterised variant and predominantly reported in children with a history of radiation exposure. This variant has a high propensity for extra-thyroidal extension and cervical lymph node metastases. A 14-year-old Malay girl who had no history of radiation exposure, presented with multiple cervical lymphadenopathy and it was clinically suspicious for tuberculosis or lymphoma. An incisional biopsy revealed a metastatic PTC. The patient underwent total thyroidectomy with bilateral lateral neck dissection and histopathology report was solid variant of PTC. Whole-body I(131) scan was performed which revealed an intense tracer uptake in the neck. She was planned for radioactive iodine ablation and now on regular follow-up for monitoring of possible tumour metastasis.