Abstract:
:Gestational trophoblastic diseases (GTD) are group of pregnancy-related tumors characterized by abnormal levels of 'β-hCG' with higher incidence in South-East Asia, especially India. Our laboratory has reported that wild-type BRCA1 transcriptionally regulates β-hCG in triple negative breast cancers (TNBCs). These factors culminated into analysis of BRCA1 status in GTD, which would emanate into elucidation of BRCA1- β-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 β-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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Nadhan R,Vaman JV,Sengodan SK,Hemalatha SK,Chellappan N,Sadasivan S,Pasuthottiyil Varkey A,Yesodharan S,Raji Sathyanpillai K,Bhuvaneswari Venugopal AK,Prameelakumari Sreenivasan S,Rajan A,Latha NR,Varghese GR,Thankappan R,Adoi
10.1093/carcin/bgz117subject
Has Abstractpub_date
2020-07-10 00:00:00pages
611-624issue
5eissn
0143-3334issn
1460-2180pii
5521148journal_volume
41pub_type
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