OBJECTIVEHypothesis showed that women have higher risks of lung cancer than men when given similar levels of tobacco exposure, implying that sex-related hormones might have a role to play. The study is to identify the influence of female hormones on risk of lung cancer.

METHODSWe evaluated the association between lung cancer risk and menstrual/reproductive factors on a subset of self-responding females in a population based case-control study in Eastern Gansu, 1994 - 1998. The analysis included 109 lung cancer cases and 435 controls selected from the census list and matched to cases on age and prefecture.

RESULTSOdds ratios were lower for later ages at menarche (trend, P = 0.015) and later ages at menopause (trend, P = 0.074).

CONCLUSIONDespite limitations, these findings suggested a possible role related to hormones in the etiology of lung cancer in females.

Adult ; Age Factors ; Aged ; Carcinoma, Small Cell ; epidemiology ; etiology ; Case-Control Studies ; China ; epidemiology ; Contraception Behavior ; Female ; Humans ; Incidence ; Logistic Models ; Lung Neoplasms ; epidemiology ; etiology ; Menarche ; Menopause ; Middle Aged ; Odds Ratio ; Parity ; Risk Factors

This article describes Viet Nam Ministry of Health’s (VMoH) activities to prepare for and respond to the threat Zika virus (ZIKV), including the adaptation of existing surveillance systems to encompass ZIKV surveillance.

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.
Apoptosis ; drug effects ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Humans ; Ligands ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; genetics ; metabolism ; Oximes ; metabolism ; pharmacology ; Protein Conformation ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrazoles ; metabolism ; pharmacology ; Retinoid X Receptor alpha ; chemistry ; genetics ; metabolism ; Thiazoles ; metabolism ; pharmacology ; Transcription, Genetic ; drug effects ; Transcriptional Activation ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism