Background: Increasing trend of breast cancer incidence worldwide is a known fact. This curable disease may become fatal if drug resistance is developed leading to metastatic cancerous tissue. Objective: This is a two parts study; a meta-analysis exploring association of drug resistance (mdr1 and ABCG2) genes with breast cancer and mutational association with molecular subtypes of cancer. Methods: PCR-SSCP for genomic polymorphisms and RT-PCR for expression analysis were performed. Results: C3435T polymorphism of mdr1 gene was most commonly studied mutation with contradictory results. Association of ABCG2 gene mutations with untreated breast cancer was reported only by one study so far. Regarding current genomic analysis of mdr1 gene, three novel mutations were found in exon 12 and 2 mutations were found in exon 26. In ABCG2 gene, addition of C and T were found in intron 8 at the intron-exon junction. A positive correlation was observed between these mutations and tumor grade. Levels of mRNA expression revealed that they were over expressed in cancerous tissues compared with controls. Conclusion: These findings suggest that these genes are associated with breast cancer. Keywords: Expression; mutations; mdr1; ABCG2; breast cancer.
Background: Breast cancer initiation is an unresolved phenomenon although many genes are known to be involved in its initiation but its exact etiology is still unexplained in many aspects and recently microRNAs are found to regulate many genes expressions. Method: This case control study has been designed to evaluate the role of selected miRNAs in gene expression and subsequent association with drug resistance. Genetic polymorphisms were confirmed by PCR-SSCP followed by sequencing and microRNA expression was measured by realtime PCR with specific primers. Follow up was done for patients whose samples were used in the study. Results: This study revealed 15 germline mutations in mdr1, 5 in ABCG2, 8 in BRCA1 and 8 in PTEN gene. These mutations were significantly associated with breast cancer compared with control tissues (P<0.05). miR-21, miR-146a and miR-328 were over expressed whereas miR-451 was under expressed. Progression free survival (PFS) was linked with reduced polymorphisms in genes as well as microRNAs. Conclusion: Over expression of miRNA-21 and miRNA-146a may lead towards lower expression of PTEN and BRCA1 genes causing cancer progression. miRNA-328 and miRNA-451 reduced expression resulted in overexpressed ABCG2 and MDR1 genes in this study.
The ameboflagellate Neigleria fowleri, also known as brain eating amoeba is responsible for fatal primary amoebic meningoencephalitis (PAM) infection in humans. Cell division proteins (CDPs) in N. fowleri have been uncharacterized until now, despite their importance in the initiation of cell division and proliferation of the pathogen. Here, we report characterization and structural assembly of eight such proteins associated with division and docking them with anti-amoebic quassinoid compounds. Quassinoids have been implicated as inhibitors of cell proliferation of amoeboid species as well as tumor cells. Here, they were screened computationally to find interaction mechanism as well as binding energies with CDPs of N. fowleri. The identified inhibitors could play a role in prevention of cell division and hence, stop N. fowleri growth and proliferation during infection. This study supports CDPs as a target for anti-amoebic intervention and identifies quassinoid phytochemical compounds as suitable for optimization into a new therapy against N. fowleri.
Mycobacterium chelonae is a rapidly growing mycobacterium present in the environment. It is associated with skin and soft tissue infections including abscess, cellulitis and osteomyelitis. Other infections by this bacterium are post-operative/transplant-associated, catheter, prostheses and even concomitant to haemodialytic procedures. In this study, we employ a subtractive genomics approach to predict the potential therapeutic candidates, intended for experimental research against this bacterium. A computational workflow was devised and executed to procure core proteome targets essential to the pathogen but with no similarity to the human host. Initially, essential Mycobacterium chelonae proteins were predicted through homology searching of core proteome content from 19 different bacteria. Druggable proteins were then identified and Nacetylglucosamine-1-phosphate uridyltransferase (GlmU) was chosen as a case study from identified therapeutic targets, based on its important bifunctional role. Structure modeling was followed by virtual screening of phytochemical library (N > 2200), from 500 medicinal plants, against it. A biflavonoid daphnodorin G from Daphne odora was screened as having best potential for binding GlmU. Phytotherapy helps curb the menace of antibiotic resistance so treatment of Mycobacterium chelonae infection through this method is recommended.
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