Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1

We studied the relationship between IL28B gene-related SNP rs12979860 and early viral kinetics (day 0–28) during peginterferon and ribavirin treatment, in 173 African Americans (AA) and 188 Caucasian Americans (CA) with HCV genotype 1

Ubiquitous activation of <i>Ras</i> and Jak/Stat pathways in human HCC

Background &amp; Aims: Although the natural history and pathologic characteristics of human hepatocellular carcinoma (HCC) are well documented, the molecular pathogenesis of HCC remains poorly understood. Here, we define the role for Ras and Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathways in human HCC. Methods: Promoter and genomic status of Ras and Jak/Stat inhibitors were assessed in 80 HCCs by methylation-specific polymerase chain reaction and microsatellite analysis. Activation of Ras and Jak/Stat signaling pathways was determined by DNA sequencing, Western blot, and immunoprecipitation analysis. Suppression of Ras and Jak/Stat pathways in HCC cell lines was evaluated by viability and apoptosis assays. Results: Activation of Ras and Jak/Stat pathways was enhanced in all HCCs when compared with nonneoplastic surrounding and normal livers coincidently with the suppression of at least 1 Ras (RASSF1A and/or NORE1A) and 2 Jak/Stat inhibitors (cytokine-inducible SH2-protein [CIS]; suppressor of cytokine signaling [SOCS]1, 2, 3; and SH2-containing phosphatases [SHP1]). HCC associated with cirrhosis showed significantly higher frequency of RASSF1A, CIS, and SOCS1 promoter methylation than HCC without cirrhosis (P &lt; .002, P &lt; .02, and P &lt; .02, respectively). Furthermore, aberrant methylation of NORE1A and SOCS3 promoters was observed only in a subclass of HCC with poor survival, suggesting that inactivation of these 2 genes might be involved in HCC progression. Combined treatment of HCC cell lines with Ras and Jak/Stat inhibitors as well as with the demethylating agent zebularine induced a strong apoptotic response. Conclusions: These data demonstrate the ubiquitous activation of Ras and Jak/Stat pathways in HCC and suggest the potential use of Ras and Jak/Stat inhibitors and demethylating agents as therapeutic modality for human liver cancer

Engaging Individuals with Sickle Cell Disease in Patient-Centered Outcomes Research: A Community Health Ambassador Training Model

Developing innovative strategies to engage patients as research partners is a priority in efforts to reduce health disparities in underserved communities. We describe the development and implementation of a training model to prepare Community Health Ambassadors (CHAs) to serve as liaisons to engage individuals with sickle cell disease (SCD) in patient-centered outcomes research. We trained CHAs on research guidelines, human subjects\u27 protection, and SCD self-management. Community Health Ambassadors then employed community-level strategies to engage individuals with SCD and their families (N=432) residing in rural and urban communities throughout Tennessee. By engaging the SCD community, CHAs identified areas of burden for self-management and patientpreferred strategies to engage members of underserved minority groups in research. This community-based training model, which places CHAs as liaisons between researchers and [End Page 353] the community, holds promise for scaling-up for replication and implementation in studies seeking to engage underserved populations with a chronic disease in health research

Georgia Southern: Engaging Individuals with Sickle Cell Disease in Patient-Centered Outcomes Research

Article about Georgia Southern faculty member Tilicia Mayo-Gamble contribution to the academic article, Engaging Individuals with Sickle Cell Disease in Patient-Centered Outcomes Research: A Community Health Ambassador Training Model .https://digitalcommons.georgiasouthern.edu/hpch-facmedia/1004/thumbnail.jp

Patient Centered Outcomes Research Tennessee Sickle Cell Disease Network: An Operational Manual for Engaging Sickle Cell Patient Families in Patient Centered Outcomes Research

Research Objective: Despite the high prevalence of individuals affected by SCD, comprehensive care, education, and training for people diagnosed with SCD is not as widely available as health care services for individuals managing other chronic illnesses. Our study engaged the SCD community stakeholders in PCOR as an essential mechanism for advancing care and meaningful research for this rare disease population. A statewide SCD network was developed to offer social support and increase access to education, medical care, engagement in research activities that affect the lives of SCD patients and their caregivers. Study Design: We systematically identified patient partners with SCD in rural and urban communities in TN to establish a vibrant and sustainable infrastructure through a partnership with the Sickle Cell Foundation of Tennessee to engage urban and rural areas, with specific focus on connecting the SCD community through a potential service providing community based organization (CBO) to provide: 1) information on how to connect with other families; and be informed about SCD community activities, or educational offerings; 2) training in basic research principals and 3) opportunities to contribute to PCOR, including feedback on effective and practical ways for providing input on research efforts through patient centered input, comparing urban and rural area preferences Population Studied: SCD patient partners aged 18-50, of which 30% came from rural areas throughout the state of Tennessee. Additionally, an executive committee, comprised of 87 stakeholders across the 3 regions of Tennessee were recruited to assist in the development of the statewide network, and eventually serve as the governing body of the TN-SCD Network. These representatives include local physicians, community leaders, adults with SCD and parents of children with SCD. Principal Findings: We engaged 432 patient partners were recruited across all three regions, and 35 executive committee members. Community health ambassadors have utilized health fairs, clinic days at various hospitals and community centers, and social media to spread awareness of the project, in addition to boosting the recruitment process. Conclusion: Most rural and urban families affected SCD have no systematic way to engage in, or lend their expertise to, patient-centered outcomes research (PCOR). A statewide network of patient partners, community stakeholders, researchers, and medical professionals will ultimately increase the standard of care for patients, and provide valuable insight for sickle cell disease research. Implications for Policy or Practice: The opportunity to create the underpinnings for coordinated patient-centered education and linking of individuals living with SCD and their caregivers, as well as SCD stakeholders throughout the state of TN holds promise for developing a scalable PCOR process model for replication and implementation in other states the success enabling other states with rare disease populations to emulate this model

Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, accounting for an estimated 600,000 deaths annually. Aberrant methylation, consisting of DNA hypomethylation and/or promoter gene CpG hypermethylation, is implicated in the development of a variety of solid tumors, including HCC. We analyzed the global levels of DNA methylation as well as the methylation status of 105 putative tumor suppressor genes and found that the extent of genome-wide hypomethylation and CpG hypermethylation correlates with biological features and clinical outcome of HCC patients. We identified activation of Ras and downstream Ras effectors (ERK, AKT, and RAL) due to epigenetic silencing of inhibitors of the Ras pathway in all HCC. Further, selective inactivation of SPRY1 and -2, DAB2, and SOCS4 and -5 genes and inhibitors of angiogenesis (BNIP3, BNIP3L, IGFBP3, and EGLN2) was associated with poor prognosis. Importantly, several epigenetically silenced putative tumor suppressor genes found in HCC were also inactivated in the nontumorous liver. Our results assign both therapeutic and chemopreventive significance to methylation patterns in human HCC and open the possibility of using molecular targets, including those identified in this study, to effectively inhibit HCC development and progression