SiRNA-HIF-1α delivered by attenuated Salmonella enhances the efficacy of Lenvatinib against hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.

Development and psychometric properties of the HPV Impact Profile (HIP) to assess the psychosocial burden of HPV.

OBJECTIVE: A comprehensive questionnaire designed to assess the full spectrum of potential human papillomavirus (HPV)-related psychosocial effects in women does not exist. The HPV Impact Profile (HIP) was developed to determine the psychosocial impact of HPV infection and related interventions. RESEARCH DESIGN AND METHODS: Draft instrument items and domains were developed using a literature review and cognitive debriefing interviews with women who had experienced HPV-related conditions. An importance rating questionnaire guided item ranking and reduction. A draft questionnaire was pilot-tested for comprehension and ease of completion. Psychometric evaluation of the final HIP was conducted in a survey of 583 women. Data quality, item acceptability, scale acceptability, reliability, and discriminate construct validity were assessed. OUTCOME MEASURE: The final HIP contained 29 items rated on a 0-10 point discretized visual analog scales grouped into seven hypothesized domains. RESULTS: Total HIP scores ranged from 0 (no impact) to 100 (worst impact). Data quality was high, with missing data for items ranging from 0 to 0.7% and over 99% of the scores were computable. Cronbach's alpha ranged from 0.64 to 0.90 and was > or =0.7 for 5/7 domains. Discriminant construct validity was demonstrated. Appropriate modifications could potentially be made to improve some aspects of the HIP, including modification to include other HPV diseases such as head and neck, anal, and vulvovaginal cancers and HPV disease in men. CONCLUSIONS: The disease-specific HIP has favorable reliability and construct validity and a good ability to discriminate among disease severity.

Prevalence and incidence of HPV genital infection in women.

BACKGROUND: A prophylactic quadrivalent human papillomavirus (HPV) vaccine could benefit adult women if they are susceptible to incident genital HPV infections and are acquiring new infections with vaccine HPV types to which they were previously not exposed. This report presents baseline and prospective data from a randomized, double-blind, placebo-controlled trial of the safety, immunogenicity, and efficacy of the quadrivalent HPV (Type 6/11/16/18) vaccine in women ages 24 to 45. METHODS: We present the results of an epidemiologic analysis of 3730 women enrolled in a quadrivalent HPV vaccine efficacy trial between June 18, 2004 and April 30, 2008. Subjects were enrolled from 7 countries (Colombia, France, Germany, Philippines, Spain, Thailand, and the United States) through community and academic health centers and primary health care providers. RESULTS: Average baseline prevalence of anogenital infection and/or seropositivity was 32.8% for >or=1 vaccine HPV types and 0.3% for all vaccine HPV types. Incidence of anogential infection with any vaccine HPV type was approximately 10.5%. The rate of persistent infection was approximately 5% over a 30-month period among women in the placebo arm naïve to the relevant type at baseline. Predictors of incident infection included younger age, marital status other than first marriage, higher number of lifetime and recent sex partners, and Chlamydia/gonorrhea infection at baseline. CONCLUSIONS: These findings indicate that women up to age 45 are susceptible to vaccine HPV types and some are acquiring anogenital infections with vaccine HPV types. Future study concerning incident and prevalent HPV infection among women up to age 45 is warranted (Trial NCT number NCT00090220).