Molecular and Genetic Medicine

ISSN: 1747-0862

Open Access

Article in Press

Volume 15, Issue 6 (2021)

    Review Article Pages: 1 - 3

    Biosynthetic Gene Clusters in Organism: The Sole Source of New Drug Discovery

    Chakraborty P, Chakraborty A

    Various microorganisms e.g., bacteria, fungi and higher organism e.g., plant during their metabolism produces both primary and secondary metabolites, needed for their survival and defense. Often these secondary metabolites are being used in drug discovery. The genes for the enzymes of these secondary metabolic pathways are generally grouped together as biosynthetic gene clusters (BGCs) and hidden away in organism’s genome. Genome mining of the unexplored microbes, medicinal plants, and underexplored human microbiota with emerging genomics research involving next-generation sequencing technology along with bioinformatics tools like anti-SMASH (antibiotics and Secondary Metabolite Analysis Shell), planti-SMASH, may help in finding many BGCs and subsequently in the discovery of many new drugs in future.

    Research Article Pages: 1 - 4

    Gender and Burnout Syndrome among Health Care Workers in Ethiopia - A Systematic Review and Meta-Analysis

    Tegegne KT, Tegegne ET, Tessema MK and Bagajjo WS

    The purpose of this meta-analysis was to assess the association between Gender and Burn out syndrome among health care workers in Ethiopia. Previous findings on the association of gender and burn out syndrome have reported different results. We use data from four studies to do a metaanalysis. We applied the random-effects analytic model and calculated a pooled odds ratio. The odds ratios for all studies revealed no statistically significant association of Burn out syndrome with Male relative to Female (OR = 1.15; 95% CI: 0.48–2.71, Heterogeneity: Tau² = 0.55; Chi² = 12.17, df = 3 (P = 0.007); I² = 75%, Test for overall effect: Z = 0.31 (P = 0.76). The proportion of Burn out syndrome among male and female health professionals is 31.31% (578). 35.43% (302) respectively. The overall proportion of Burn out syndrome among health professionals is 32.73% (880).

    Research Article Pages: 1 - 5

    Treatment Outcomes and Toxicity Profile of Carfilzomib in Multiple Myeloma: A Single Institution Experience

    Thakur R, Nina Kohn and Brown MH

    Carfilzomib is an irreversible proteasome inhibitor (PI), first approved in 2012 for treatment of relapsed refractory multiple myeloma (RRMM). The real-world use of carfilzomib in treatment of RRMM is important to assess. The objectives of this study are to evaluate the real-world outcome in overall response rates (ORR), progression-free survival (PFS), and adverse drug events (ADEs), including cardiotoxicity and nephrotoxicity for RRMM patients treated with carfilzomib. We retrospectively analyzed the charts of patients with a diagnosis of MM treated with carfilzomib between January 2013 and December 2018. Demographics, cytogenetics, fluorescence in situ hybridization (FISH), and treatment history were collected. Sixty-six patients fit the study criteria, with median age of 65 years (range 48 - 84). Using the Revised International Staging System (R-ISS), 7 (10.6%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) stage III. Cytogenetics showed 33 (48.5%) were high risk. Eight (12.12%) patients were pretreated with more than 4 treatment lines and 27 (40.95) had an autologous stem cell transplant (ASCT) prior to carfilzomib. Prior treatments included lenalidomide, bortezomib, and cyclophosphamide-based regimens. The ORR was 77.2%, with 4 (6.2%) complete responses (CR). Ten patients (15%) received ASCT after carfilzomib for progression of disease (POD). The majority with POD received daratumumab (40%) or pomalidomide (46%). Grade 2 hypertension was noted in 9 (13.6%) patients, acute renal failure (ARF) in 11 (16.7%) and heart failure (HF) in 12 (18.2%). The median PFS on Carfilzomib was 6.96 months. This study showed carfilzomib improved PFS in patients with RRMM; however, there is increased risk for cardiac and renal toxicity, greater than previously reported in the literature. This study reinforces the importance for oncologists to be aware of these toxicities. Astute awareness, early monitoring, and prevention may favorably impact outcomes with use of carfilzomib.

    Review Article Pages: 1 - 11

    TP53 Gene Signaling Pathways and Protein Interactions with MDM2 and HPV in Oral Cancers?? A Review

    Diaga SP, Demba DJP, Yacouba D, Abdoul BAS, Mawulolo GF, Silly T, Babacar M, Maguette SN, Oumar F, Alioune D and Rokhaya ND

    Oral cancers are heterogeneous group of tumors in topography (they can be localized at on the lips, tongue, upper and lower gums, hard and soft palates, floor of mouth, retromolar region, or inside of cheek), histologic forms (that can be carcinoma, sarcoma, lymphoma, melanoma or cylindroma) and clinical outcomes (good or poor prognosis). However, more than 50% of these cancer phenotypes express a mutation at TP53 gene while in the other 50% of cases; the TP53 protein pathway is often partially inactivated. In cancerous tissues, particularly in oral squamous cells, the loss of function at TP53 gene is associated with three molecular causes: (1) The genotoxic effect of risk factors such as alcohol abuse, tobacco smoking or betel nut chewing, (2) The inhibitory effect of the TP53 antagonist genes such as MDM2, or (3) The action of oncoproteins of high-risk human papillomavirus (HPV). This paper attempts firstly to make an exhaustive review of TP53 gene signalling pathways in normal and stressed cells, and secondly to describe in oral cancers the genetic events that occur at different steps of carcinogenesis after a loss of function in TP53 encoded protein.

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