A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.
The RB and p16 INK4A tumor suppressor genes function in the same pathway of cell cycle control. Previous evidence indicates that the p16 INK4A gene is transcriptionally repressed by the RB gene product, pRB. In this study using human ovarian cancer cell lines, we found that RB protein and mRNA were expressed at higher levels in cell lines lacking p16 than in those with normal p16. Since this suggests a potential role of p16 in regulating the cellular level of pRB, we studied the e ect of wild-type p16 INK4A on expression of the RB gene. Introduction of p16 INK4A , carried by an adenovirus vector, into p16-negative cell lines dramatically decreased expression of RB protein and mRNA. Nuclei run-o assays demonstrated that p16 expression induced transcriptional downregulation of the RB gene. These results indicate that expression of RB is inversely regulated by p16. The ®ndings reveal a new dimension of pRB-p16 interaction and should have implications for p16 INK4A -mediated gene therapy.
BackgroundYunnan has the greatest share of reported human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) cases in China. In recent years, HIV prevalence and incidence remained stubbornly high in men who have sex with men (MSM). To follow the dynamics of the HIV-1 epidemic among MSM, HIV-1 genetic characteristics and genetic transmission networks were investigated.MethodsBlood samples from 190 newly diagnosed HIV-1 cases among MSM were continuously collected at fixed sites from January 2013 to December 2015 in Kunming City, Yunnan Province. Partial gag, pol and env genes were sequenced and used for phylogenetic and genotypic drug resistance analyses. The genetic characteristics of the predominant HIV-1 strains were analyzed by the Bayesian Markov Chain Monte Carlo (MCMC) method. The genetic transmission networks were identified with a genetic distance of 0.03 substitutions/site and 90% bootstrap support.ResultsAmong the 190 HIV-1 positive MSM reported during 2013–2105, various genotypes were identified, including CRF01_AE (45.3%), CRF07_BC (35.8%), unique recombinant forms (URFs) (11.6%), CRF08_BC (3.2%), CRF55_01B (2.1%), subtype B (1.6%) and CRF59_01B (0.5%). The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially from approximately 2001–2010 and 2005–2009, respectively. Genetic transmission networks were constructed with 308 pol sequences from MSM diagnosed during 2010–2015. Of the 308 MSM, 109 (35.4%) were identified in 38 distinct clusters. Having multiple male partners was associated with a high probability of identification in the genetic transmission networks. Of the 38 clusters, 27 (71.1%) contained individuals diagnosed in different years. Of the 109 individuals in the networks, 26 (23.9%) had ≥2 potential transmission partners (≥2 links). The proportion of MSM with ≥2 links was higher among those diagnosed from 2010–2012. The constituent ratios of their potential transmission partners by areas showed no significant difference among MSM from Kunming, other cities in Yunnan and other provinces. Additionally, surveillance drug resistance mutations (SDRMs) were identified in 5% of individuals.ConclusionThis study revealed the various HIV-a genotypes circulating among MSM in Kunming. MSM with more partners were more easily detected in transmission networks, and early-diagnosed MSM remained active in transmission networks. These findings suggested that the routine interventions should be combined with HIV testing and linkage to care and early antiretroviral therapy among HIV-positive MSM.
Chimeric hammerhead ribozyme to PCNA inhibits smooth muscle cell proliferation in vitro and reduces both histomorphometric and angiographic restenosis in the porcine coronary stent model when delivered locally.
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