GW Douglas

Graft versus host disease (GVHD), mediated by donor T cells, is a significant source of morbidity and mortality following allogeneic stem cell transplantation. Mesenchymal stem cells (MSC) can successfully treat ongoing graft versus host disease, presumably due to their ability to suppress donor T cell proliferation. Little is known about the potential of MSC to prevent GVHD. Here we show that bone marrow-isolated MSC can suppress the development of GVHD if given after donor T cell recognition of antigen. IFN-gamma was required to initiate MSC efficacy. Recipients of IFN-gamma(-/-) T cells did not respond to MSC treatment and succumbed to GVHD. MSC, pre-treated with IFN-gamma, became immediately active and could suppress GVHD more efficiently than a fivefold-greater number of MSC that were not activated. When given at the time of bone marrow transplantation, activated MSC could prevent GVHD mortality (100% survival, p=0.006). MSC activation was dependent on the magnitude of IFN-gamma exposure, with increased IFN-gamma exposure leading to increased MSC suppression of GVHD. Activated MSC present a new strategy for preventing GVHD using fewer MSC.

We assessed the barriers and facilitators to highly active antiretroviral therapy adherence and determined their prevalence among HIV/AIDS patients in Hyderabad, India. We conducted a cross-sectional study among HIV-infected adults prescribed highly active antiretroviral therapy and receiving care from nine clinics. Depression was screened using Patient Health Questionnaire 9 and facilitators of HIV medication adherence were assessed using an 11-item scale which yielded a total positive attitude to disease score. Prevalence ratios of non-adherence between different categories of potential risk factors were calculated. We compared mean 'facilitators to adherence' scores between the adherent and non-adherent population. Multivariable Poisson regression with robust variance was used to identify independent risk factors. Among the 211 respondents, nearly 20% were non-adherent, approximately 8% had either moderately severe or severe depression and mean score for combined facilitators to medication adherence was 33.35 (±7.88) out of a possible 44 points. Factors significantly associated with non-adherence included older age, female sex worker, moderate-to-severe depression and the combined facilitators to medication adherence score. These data from a broad range of clinical settings in Hyderabad reveal that key groups to focus on for adherence intervention are female sex workers, older persons and those with depression.

Abstract Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death in both sexes in the United States. While the overall CRC incidence rates have declined over the past 10 years, the disparity between African Americans (AAs) and non-Hispanic whites has increased and the incidence in AAs remains higher than in other populations. Very few studies have specifically addressed CRC in AAs, and important studies on CRC almost never include significant numbers of AAs to draw any firm conclusions. Objective: To establish a large, robust and well-characterized database and bio-repository collection of CRC from AA patients and controls strengthening a collaborative working group, the Chicago Colorectal Cancer Consortium (CCCC), which spans 5 of the main hospitals of the Chicago area. We collect clinical, demographic and dietary data; and a biological repository of specimens consisting of tumor and non-tumor genomic DNA, RNA, plasma, serum, and paraffin-embedded samples. Specific Aims: The primary goal of the project is to study how genetic and environmental factors and their interaction result in the development of CRC. We will also study prognosis determinants in the AA population. Results: Recruitment and data collection: So far we have recruited 56 AA and 17 white-non Hispanic adenocarcinoma colorectal patients. We have also recruited 84 AAs and 32 white patients with adenomatous polyps, and 44 AAs and 30 white controls (individuals without polyps or previous history of polyps). From all individuals we have collected demographic/socioeconomic data, clinical data, family history of cancer, medication and toxic substance history, and dietary data using the Block Brief 2000 Food Frequency Questionnaire. Preliminary analyses: To identify potential variables that could influence the cancer disparity between AAs and whites, we performed a preliminary analysis of all these data using a Fisher exact test. A systematic molecular analysis of BRAF and KRAS mutations, microsatellite instability and presence of CpG island methylation phenotype in all CRC tumors is being performed. We are also analyzing protein expression of the mismatch repair genes through immunohistochemistry. We will test for an association between these molecular features and clinical variables. Moreover, 1 year follow-up data is already available and being collected on 23 cases. Therefore, we will soon be able to start investigating the relationship of those molecular features with survival and specific chemotherapy response. Summary: The preliminary analysis has highlighted some significant differences between AA and white CRC patients. In comparison with white patients, a higher proportion of AA patients are less than 50 years at diagnosis, take NSAIDS, and fulfill Bethesda criteria, which is a set of criteria to select out patients to be pre-screened for mismatch repair deficiency and eventually for genetic testing to rule out Lynch syndrome. It has also highlighted that CRC patients have a lower level of education than cancer-free individuals in both ethnicities. This type of sociocultural disparities could potentially be associated with different life styles. In fact, AA CRC cases consumed more carbohydrates than controls reflecting this potential life style difference. Cancer Relevance: Understanding the key molecular features and environmental factors that impact CRC development in the AA population is of paramount importance given the scarce information available. Understanding the role genetic factors will be crucial to help risk stratify patients, recommend screening modalities, and recommend preventive measures. When this information is combined with environmental factors, such as dietary habits, we will be able to offer a comprehensive personalized medicine approach for AA CRC patients. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B73.