University of Texas Health Science Center at Houston

About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.

PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer

Abstract: PIK3CA mutations are reported to be present in approximately 25% of breast cancer (BC), particularly the estrogen receptor-positive (ER+) and HER2-overexpressing (HER2+) subtypes, making them one of the most common genetic aberrations in BC. In experimental models, these mutations have been shown to activate AKT and induce oncogenic transformation, and hence these lesions have been hypothesized to render tumors highly sensitive to therapeutic PI3K/mTOR inhibition. By analyzing gene expression and protein data from nearly 1,800 human BCs, we report that a PIK3CA mutation-associated gene signature (PIK3CA-GS) derived from exon 20 (kinase domain) mutations was able to predict PIK3CA mutation status in two independent datasets, strongly suggesting a characteristic set of gene expression-induced changes. However, in ER+/HER2- BC despite pathway activation, PIK3CA mutations were associated with a phenotype of relatively low mTORC1 signaling and a good prognosis with tamoxifen monotherapy. The relationship between clinical outcome and the PIK3CA-GS was also assessed. Although the PIK3CA-GS was not associated with prognosis in ER- and HER2+ BC, it could identify better clinical outcomes in ER+/HER2- disease. In ER+ BC cell lines, PIK3CA mutations were also associated with sensitivity to tamoxifen. These findings could have important implications for the treatment of PIK3CA-mutant BCs and the development of PI3K/mTOR inhibitors.

53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination

Abstract: The mammalian protein 53BP1 is activated in many cell types in response to genotoxic stress, including DNA double-strand breaks (DSBs). We now examine potential functions for 53BP1 in the specific genomic alterations that occur in B lymphocytes. Although 53BP1 was dispensable for V(D)J recombination and somatic hypermutation (SHM), the processes by which immunoglobulin (Ig) variable region exons are assembled and mutated, it was required for Igh class-switch recombination (CSR), the recombination and deletion process by which Igh constant region genes are exchanged. When stimulated to undergo CSR, 53BP1-deficient cells exhibited no defect in C(H) germline transcription or AID expression, however these cells had a profound decrease in switch junctions. The current findings, in combination with the known 53BP1 functions and how it is activated, implicate the DNA damage response to DSBs in the joining phase of class-switch recombination.

Discovery of Some of the Biological Effects of Nitric Oxide and Its Role in Cell Signaling (Nobel Lecture)

Abstract: A unique simple molecule with an array of signaling functions: NO. The free radical nitric oxide not only mediates a long list of biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis from GTP, but can also interact with transition metals such as iron, thiol groups, other free radicals, oxygen, superoxide anion, unsaturated fatty acids, and other molecules. Furthermore, NO can function as an intracellular messenger, an autacoid, a paracrine substance, a neurotransmitter, or a hormone that can be carried to distant sites for effects.

Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection.

Abstract: Hepatitis C virus (HCV) has emerged as a major pathogen among patients with human immunodeficiency virus (HIV) Morbidity and mortality were compared among 263 patients with HIV alone, 166 patients with HIV and HCV, and 60 patients with HCV alone (mean duration of follow-up, 2 years and 10 months) No differences in HIV loads and CD4 cells counts were observed between the HIV and HIV/HCV groups Alanine aminotransferase levels were higher (52 U/L versus 35 U/L; P<05) and albumin levels were lower (35 g/dL versus 38 g/dL; P <02) among coinfected patients than they were among patients with HIV alone Liver decompensation developed in 10% of patients with HIV/HCV coinfection In contrast, no liver-related deaths or decompensation occurred in patients without coinfection (P<05) Of the patients with HIV alone, 7% died, compared with 11% of the coinfected patients (P<02); 47% of the deaths in the latter group were due to liver-related causes In summary, HCV infection causes increased morbidity and mortality in patients with HIV infection

POU domain factor Brn-3b is required for the development of a large set of retinal ganglion cells

Abstract: The three members of the Brn-3 family of POU domain transcription factors are found in highly restricted sets of central nervous system neurons. Within the retina, these factors are present only within subsets of ganglion cells. We show here that in the developing mouse retina, Brn-3b protein is first observed in presumptive ganglion cell precursors as they begin to migrate from the zone of dividing neuroblasts to the future ganglion cell layer, and that targeted disruption of the Brn-3b gene leads in the homozygous state to a selective loss of 70% of retinal ganglion cells. In Brn-3b (-/-) mice other neurons within the retina and brain are minimally or not at all affected. These experiments indicate that Brn-3b plays an essential role in the development of specific ganglion cell types.