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Item Immunodeficiency in Pancreatic Adenocarcinoma with Diabetes Revealed by Comparative Genomics(American Association for Cancer Research, 2017-10-15) Yan, Yuanqing; Gao, Ruli; Trinh, Thao L.P.; Grant, Maria B.; Ophthalmology, School of MedicinePurpose: Pancreatic adenocarcinomas (PAAD) often are not diagnosed until their late stages, leaving no effective treatments. Currently, immunotherapy provides a promising treatment option against this malignancy. However, a set of immunotherapy agents benefit patients with many types of cancer, but not PAAD. Sharing the origin in the same organ, diabetes and PAAD tend to occur concurrently. We aimed to identify the impact of diabetes on immunotherapy of PAAD by conducting a comparative genomics analysis.Experimental Design: We analyzed level 3 PAAD genomics data (RNAseq, miRNAseq, DNA methylation, somatic copy number, and somatic mutation) from The Cancer Genome Atlas (TCGA) and Firehose. The differential molecular profiles in PAAD with/out diabetes were performed by the differential gene expression, pathway analysis, epigenetic regulation, somatic copy-number alteration, and somatic gene mutation.Results: Differential gene expression analysis revealed a strong enrichment of immunogenic signature genes in diabetic individuals, including PD-1 and CTLA4, that were currently targetable for immunotherapy. Pathway analysis further implied that diabetic individuals were defective in immune modulation genes. Somatic copy-number aberration (SCNA) analysis showed a higher frequency of amplification and deletion occurred in the cohort without diabetes. Integrative analysis revealed strong association between differential gene expression, and epigenetic regulations, however, seemed not affected by SCNAs. Importantly, our somatic mutation analysis showed that the occurrence of diabetes in PAAD was associated with a large set of gene mutations encoding genes participating in immune modulation.Conclusions: Our analysis reveals the impact of diabetes on immunodeficiency in PAAD patients and provides novel insights into new therapeutic opportunities.Item Introduction to a review series on emerging immunotherapies for hematologic diseases(American Society of Hematology, 2018-06-14) Paczesny, Sophie; Pavletic, Steven Z.; Bollard, Catherine M.; Pediatrics, School of MedicineImmune therapies are fast becoming paradigm-changing treatment options for patients with hematologic cancers. The field has grown exponentially as it expands to nonmalignant blood diseases. This Perspective article introduces the review series describing some of the latest advances in this field and highlighting some of the current obstacles and new opportunities for the future. Specifically, the series provides in-depth discussion on a selection of emerging immunotherapies now available to patients for hematologic diseases, including cancer vaccines, chimeric antigen receptor T cells, and immunotherapies to regulate inflammation in nonmalignant blood disorders.Item Physicians' human papillomavirus vaccine recommendations in the context of permissive guidelines for male patients: a national study(American Association for Cancer Research, 2014-10) Malo, Teri L.; Giuliano, Anna R.; Kahn, Jessica A.; Zimet, Gregory D.; Lee, Ji-Hyun; Zhao, Xiuhua; Vadaparampil, Susan T.; Department of Pediatrics, School of MedicineBACKGROUND: Little is known about physicians' human papillomavirus (HPV) vaccine recommendations for males while the Advisory Committee on Immunization Practices' (ACIP) permissive guidelines for male vaccination were in effect. The purpose of this study was to examine and explore factors associated with U.S. physicians' HPV vaccine recommendations to early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) males. METHODS: Nationally representative samples of family physicians and pediatricians were selected in 2011 (n = 1,219). Physicians reported the frequency with which they recommended HPV vaccine to male patients ["always" (>75% of the time) vs. other] for each age group. Statistically significant predictors of vaccine recommendation were identified using multivariable logistic regression. RESULTS: The prevalence of physicians reporting they "always" recommended HPV vaccination for males was 10.8% for ages 11 to 12, 12.9% for ages 13 to 17, and 13.2% for ages 18 to 26. Pediatrician specialty and self-reported early adoption of new vaccines were significantly associated with recommendation for all patient age groups. In addition, physician race and patient payment method were associated with physician recommendations to patients ages 11 to 12, and patient race was associated with recommendations to ages 13 to 17 and 18 to 26. CONCLUSIONS: Less than 15% of physicians surveyed reported "always" recommending HPV vaccine to male patients following national guidelines for permissive vaccination. Vaccine financing may have affected physicians' vaccine recommendations. IMPACT: If these recommendation practices continue following the ACIP's routine recommendation for males in October 2011, then interventions designed to increase recommendations should target family physicians and possibly use early adopters to encourage support of HPV vaccination guidelines.Item Use of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) in Young Adult Women(PLOS, 2014-06-14) Dempsey, Amanda F.; Fuhrel-Forbis, Andrea; Konrath, Sara H.; School of PhilanthropyBackground Validated measures that can accurate describe young adults’ HPV vaccination attitudes and how these relate to vaccination intention and receipt are needed for developing interventions to improve low HPV vaccination levels. The Carolina HPV Immunization Attitudes Scale (CHIAS) is a validated measure of these outcomes that was originally designed for parents. Objective To assess the performance of the CHIAS among young adult women using an exploratory factor analysis. Methods A convenience sample of 139 young adult women (age 18–26 years) were given the CHIAS measure at baseline. Factor analysis was used to determine attitudinal factor groupings and the association of these factors with HPV vaccination intention. A 6-month follow up assessment examined the stability of the CHIAS over time and the association of baseline vaccine factors with vaccine receipt. Results Five factors loaded on to the CHIAS in young adults - “Barriers,” “Harms,” “Effectiveness,” “Risk Denial” and “Uncertainty,” - which was similar to the factor loadings of CHIAS for parents. “Harms” was the factor most consistently associated with vaccination intention at all time points assessed. Only 5 women had received or made an appointment to receive the vaccine at the 6-month follow-up. Conclusions In terms of categorizing HPV vaccination attitudes, the CHIAS appears to have similar performance among young adults as in parents. However, additional studies are needed to assess the utility of the CHIAS for predicting HPV vaccine receipt among the young adult population.