ABSTRACT
Gestational trophoblastic diseases (GTD) are group of pregnancy-related tumors characterized by abnormal levels of 'ß-hCG' with higher incidence in South-East Asia, especially India. Our laboratory has reported that wild-type BRCA1 transcriptionally regulates ß-hCG in triple negative breast cancers (TNBCs). These factors culminated into analysis of BRCA1 status in GTD, which would emanate into elucidation of BRCA1- ß-hCG relationship and unraveling etio-pathology of GTD. BRCA1 level in GTD is down-regulated due to the over-expression of DNMT3b and subsequent promoter hypermethylation, when compared to the normal placentae accompanied with its shift in localization. There is an inverse correlation of serum ß-hCG levels with BRCA1 mRNA expression. The effects of methotrexate (MTX), which is the first-line chemotherapeutic used for GTD treatment, when analyzed in comparison with plumbagin (PB) revealed that PB alone is efficient than MTX alone or MTX-PB in combination, in showing selective cytotoxicity against GTD. Interestingly, PB increases BRCA1 levels post-treatment, altering DNMT3b levels and resultant BRCA1 promoter methylation. Also, cohort study analyzed the incidence of GTD at Sree Avittom Thirunal (SAT) Hospital, Thiruvananthapuram, which points out that 11.5% of gestational trophoblastic neoplasia (GTN) cases were referred to Regional Cancer Centre, Thiruvananthapuram, for examination of breast lumps. This has lend clues to supervene the risk of GTD patients towards BRCA1-associated diseases and unveil novel therapeutic for GTD, a plant-derived naphthoquinone, PB, already reported as selectively cytotoxic against BRCA1 defective tumors.
Subject(s)
BRCA1 Protein/genetics , Chorionic Gonadotropin, beta Subunit, Human/metabolism , DNA Methylation , Gestational Trophoblastic Disease/pathology , Mutation , Placenta/metabolism , Promoter Regions, Genetic , Adult , Antineoplastic Agents/pharmacology , Apoptosis , BRCA2 Protein/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Proliferation , Chorionic Gonadotropin, beta Subunit, Human/genetics , Cohort Studies , Female , Gene Expression Regulation, Neoplastic , Gestational Trophoblastic Disease/drug therapy , Gestational Trophoblastic Disease/genetics , Gestational Trophoblastic Disease/metabolism , Humans , Placenta/drug effects , Placenta/pathology , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/genetics , Pregnancy Complications/metabolism , Pregnancy Complications/pathology , Prognosis , Trophoblastic Neoplasms/drug therapy , Trophoblastic Neoplasms/genetics , Trophoblastic Neoplasms/metabolism , Trophoblastic Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
Applications based on silver nanoparticles (AgNPs) are limited by low temperatures, which cause aggregation of the nanoparticle fraction, leading to reduced efficacy of their products. We aimed at studying AgNP synthesis by psychrotolerant bacteria, its stability under long-term storage, and larvicidal activity under low-temperature conditions. Electron and atomic force microscopy studies revealed that 6 among 22 psychrotolerant isolates synthesized AgNPs with an average diameter of 1.9-14.1 nm. Pseudomonas mandelii SR1 synthesized the least-sized AgNPs with an average diameter of 1.9-10 nm, at temperatures as low as 12 °C without aggregate formation, and the synthesized nanoparticles were stable for up to 19 months of storage period. On studying their larvicidal activity, LC90 (lethal concentration) values against Anopheles subpictus and Culex tritaeniorhynchus larvae were at 31.7 and 35.6 mg/L, respectively. Stable non-aggregate AgNPs at low-temperature conditions from P. mandelii SR1, coupled with their larvicidal property, can be applied to control larval populations in water bodies located in seasonal or permanently cold environments.
