The Megacomplex protects ER-alpha from degradation by Fulvestrant in epithelial ovarian cancer.

Ovarian cancer, a significant contributor to cancer-related mortality, exhibits limited responsiveness to hormonal therapies targeting the estrogen receptor (ERα). This study aimed to elucidate the mechanisms behind ERα resistance to the therapeutic drug Fulvestrant (ICI182780 or ICI). Notably, compared to the cytoplasmic version, nuclear ERα was minimally degraded by ICI, suggesting a mechanism for drug resistance via the protective confines of the nuclear substructures.

Characterization and clustering of kinase isoform expression in metastatic melanoma.

Mutations to the human kinome are known to play causal roles in cancer. The kinome regulates numerous cell processes including growth, proliferation, differentiation, and apoptosis. In addition to aberrant expression, aberrant alternative splicing of cancer-driver genes is receiving increased attention as it could lead to loss or gain of functional domains, altering a kinase's downstream impact.

Cell Death and the p53 Enigma During Mammalian Embryonic Development.

Twelve forms of programmed cell death (PCD) have been described in mammalian cells, but which of them occurs during embryonic development and the role played by the p53 transcription factor and tumor suppressor remains enigmatic. Although p53 is not required for mouse embryonic development, some studies conclude that PCD in pluripotent embryonic stem cells from mice (mESCs) or humans (hESCs) is p53-dependent whereas others conclude that it is not. Given the importance of pluripotent stem cells as models of embryonic development and their applications in regenerative medicine, resolving this enigma is essential.

Developmental Acquisition of Functions.

Remarkably, the transcription factor, referred to as "the guardian of the genome", is not essential for mammalian development. Moreover, efforts to identify -dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential.

Molecular Cytogenetic Classification of Down Syndrome and Screening of Somatic Aneuploidy in Mothers.

Down Syndrome (DS) caused by trisomy 21 results in various congenital and developmental complications in children. It is crucial to cytogenetically diagnose the DS cases early for their proper health management and to reduce the risk of further DS childbirths in mothers. In this study, we performed a cytogenetic analysis of 436 suspected DS cases using karyotyping and fluorescent in situ hybridization.

Molecular analysis of severe hemophilia B in Indian families: Identification of mutational hotspot and novel variants.

Introduction: Hemophilia B is associated with molecular heterogeneity, with more than 1200 unique variants in the F9 gene. We hereby describe the mutational spectrum of severe hemophilia B patients presenting in a tertiary-care center in India.

Method: DNA was extracted from peripheral blood samples of 35 diagnosed severe hemophilia B patients belonging to 32 families, and were subjected to Sanger sequencing.

Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.

Background: The heterogeneous subtypes and stages of epithelial ovarian cancer (EOC) differ in their biological features, invasiveness, and response to chemotherapy, but the transcriptional regulators causing their differences remain nebulous.

Methods: In this study, we compared high-grade serous ovarian cancers (HGSOCs) to low malignant potential or serous borderline tumors (SBTs). Our aim was to discover new regulatory factors causing distinct biological properties of HGSOCs and SBTs.

Cell cycle arrest and apoptosis are not dependent on p53 prior to p53-dependent embryonic stem cell differentiation.

Previous efforts to determine whether or not the transcription factor and tumor suppressor protein p53 is required for DNA damage-induced apoptosis in pluripotent embryonic stem cells (ESCs) produced contradictory conclusions. To resolve this issue, p53+/+ and p53-/- ESCs derived by two different methods were used to quantify time-dependent changes in nuclear DNA content; annexin-V binding; cell permeabilization; and protein expression, modification, and localization. The results revealed that doxorubicin (Adriamycin [ADR]) concentrations 10 to 40 times less than commonly used in previous studies induced the DNA damage-dependent G2-checkpoint and completed apoptosis within the same time frame, regardless of the presence or absence of p53, p21, and PUMA.

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome.

Purpose: In the present study, we reported two cases of TS with mosaic ring X chromosome showing common clinical characteristics of TS like growth retardation and ovarian dysfunction. The purpose of the present study was to cytogenetically characterize both cases.

Methods: Whole blood culture and G-banding were performed for karyotyping the cases following standard protocol.

Maternal risk for down syndrome and polymorphisms in the promoter region of the DNMT3B gene: a case-control study.

Background: Epigenetic changes leading to improper methylation of the pericentromeric region of chromosome 21 may contribute to the nondisjunction of this chromosome. Polymorphisms in the DNA Methyltransferase 3B (DNMT3B) gene, one of the crucial gene of the folate metabolism, affects the activity of the enzyme and increases the susceptibility of nondisjunction in mothers of Down syndrome children (MDS).

Methods: Considering this hypothesis we investigated the association of single nucleotide polymorphisms in the promoter region of the DNMT3B gene (rs1569686 -579G>T; rs2424913 -149C>T) with a predisposition of mothers to deliver a Down syndrome (DS) child.

Co-occurrence of mosaic supernumerary isochromosome 18p and intermittent 2q13 deletions in a child with multiple congenital anomalies.

The present study deals with karyotpye-phenotype correlations in a six month old child with multiple congenital abnormalities. Cytogenetic analysis revealed mosaicism of a small metacentric supernumerary marker chromosome with a karyotype mos 47,XY+mar[34]/46,XY[31]. Cytogenetic microarray result showed three copies of chromosome 18p (15,400 kb in size).