US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials

PURPOSE:: Participation of racial and ethnic minority groups (REMGs) in cancer trials is disproportionately low despite a high prevalence of certain cancers in REMG populations. We aimed to identify notable practices used by leading US cancer centers that facilitate REMG participation in cancer trials. METHODS:: The National Minority Quality Forum and Sustainable Healthy Communities Diverse Cancer Communities Working Group developed criteria by which to identify eligible US cancer centers-REMGs comprise 10% or more of the catchment area; a 10% to 50% yearly accrual rate of REMGs in cancer trials; and the presence of formal community outreach and diversity enrollment programs. Cancer center leaders were interviewed to ascertain notable practices that facilitate REMG accrual in clinical trials. RESULTS:: Eight cancer centers that met the Communities Working Group criteria were invited to participate in in-depth interviews. Notable strategies for increased REMG accrual to cancer trials were reported across five broad themes: commitment and center leadership, investigator training and mentoring, community engagement, patient engagement, and operational practices. Specific notable practices included increased engagement of health care professionals, the presence of formal processes for obtaining REMG patient/caregiver input on research projects, and engagement of community groups to drive REMG participation. Centers also reported an increase in the allocation of resources to improving health disparities and increased dedication of research staff to REMG engagement. CONCLUSION:: We have identified notable practices that facilitate increased participation of REMGs in cancer trials. Wide implementation of such strategies across cancer centers is essential to ensure that all populations benefit from advances in an era of increasingly personalized treatment of cancer

Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish

Zebrafish, a popular model for embryonic development and for modelling human diseases, has so far lacked a systematic functional annotation programme akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created the first central repository to store and process zebrafish developmental functional genomic data. Our Data Coordination Center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and reanalysed published genomics data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements in development, including novel classes with distinct features dependent on their activity in time and space. We delineated the distinction between regulatory elements active during zygotic genome activation and those active during organogenesis, identifying new aspects of how they relate to each other. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predict functional relationships between them beyond sequence similarity, extending the utility of zebrafish developmental genomics to mammals

Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro

<p>Abstract</p> <p>Background</p> <p>The leaves of <it>Strobilanthes crispus </it>(<it>S. crispus</it>) which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of <it>S. crispus </it>was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines.</p> <p>Methods</p> <p>The dichloromethane extract of <it>S. crispus </it>was chromatographed on silica gel by flash column chromatography. The ability of the various sub-fractions obtained to induce cell death of MCF-7, MDA-MB-231, PC-3 and DU-145 cell lines was determined using the LDH assay. The dose-response effect and the EC₅₀values of the active sub-fraction, SC/D-F9, were determined. Apoptosis was detected using Annexin V antibody and propidium iodide staining and analysed by fluorescence microscopy and flow cytometry, while caspase 3/7 activity was detected using FLICA caspase inhibitor and analysed by fluorescence microscopy.</p> <p>Results</p> <p>Selected sub-fractions of the dichloromethane extract induced death of MCF-7, MDA-MB-231, PC-3 and DU-145 cells. The sub-fraction SC/D-F9, consistently killed breast and prostate cancer cell lines with low EC₅₀values but is non-cytotoxic to the normal breast epithelial cell line, MCF-10A. SC/D-F9 displayed relatively higher cytotoxicity compared to tamoxifen, paclitaxel, docetaxel and doxorubicin. Cell death induced by SC/D-F9 occurred via apoptosis with the involvement of caspase 3 and/or 7.</p> <p>Conclusions</p> <p>A dichloromethane sub-fraction of <it>S. crispus </it>displayed potent anticancer activities <it>in vitro </it>that can be further exploited for the development of a potential therapeutic anticancer agent.</p

Paternal effects on early embryogenesis

Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field