RESUMO
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.
Assuntos
Proteína BRCA1/genética , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Metilação de DNA , Doença Trofoblástica Gestacional/patologia , Mutação , Placenta/metabolismo , Regiões Promotoras Genéticas , Adulto , Antineoplásicos/farmacologia , Apoptose , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Gonadotropina Coriônica Humana Subunidade beta/genética , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/genética , Doença Trofoblástica Gestacional/metabolismo , Humanos , Placenta/efeitos dos fármacos , Placenta/patologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Prognóstico , Neoplasias Trofoblásticas/tratamento farmacológico , Neoplasias Trofoblásticas/genética , Neoplasias Trofoblásticas/metabolismo , Neoplasias Trofoblásticas/patologia , Células Tumorais CultivadasRESUMO
A rare case of placental mesenchymal dysplasia (PMD) in a 26-year-old patient is reported. Ultrasound scan at 17 weeks of gestation showed placenta with multiple cystic spaces and a normal appearing fetus. Following delivery of a term live baby, histological examination of the placenta was suggestive of PMD. The early recognition of this rare condition by characteristic ultrasonographic findings is herein emphasized and hence that PMD is distinguished from molar pregnancy.