Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases.

Modern vaccinology has experienced major conceptual and technological advances over the past 30 years. These include atomic-level structures driving immunogen design, new vaccine delivery methods, powerful adjuvants, and novel animal models. In addition, utilizing advanced assays to learn how the immune system senses a pathogen and orchestrates protective immunity has been critical in the design of effective vaccines and therapeutics. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a workshop in September 2020 focused on next generation assays for vaccine development (Table 1). The workshop focused on four critical pathogens: severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and human immunodeficiency virus (HIV)-which have no licensed vaccines-and tuberculosis (TB) and influenza-both of which are in critical need of improved vaccines. The goal was to share progress and lessons learned, and to identify any commonalities that can be leveraged to design vaccines and therapeutics.

Minority Participation in Biobanks: An Essential Key to Progress.

Biobanks are critical resources for biomedical research and will be a driving force behind personalized medicine. Although biobanking efforts are increasing across the USA and the world, minority populations are frequently underrepresented in biobanks, which undermines their value. A number of factors have been linked to low rates of minority participation in biobanks, including mistrust of researchers, concerns about privacy and confidentiality, logistical barriers to participation, and inadequate opportunities to participate. There are several strategies biobankers can use to increase participation of minority and underserved populations and optimize the value of their biospecimen collection for research.

Use of Community Health Workers and Patient Navigators to Improve Cancer Outcomes Among Patients Served by Federally Qualified Health Centers: A Systematic Literature Review.

Introduction: In the United States, disparities in cancer screening, morbidity, and mortality are well documented, and often are related to race/ethnicity and socioeconomic indicators including income, education, and healthcare access. Public health approaches that address social determinants of health have the greatest potential public health benefit, and can positively impact health disparities. As public health interventions, community health workers (CHWs), and patient navigators (PNs) work to address disparities and improve cancer outcomes through education, connecting patients to and navigating them through the healthcare system, supporting patient adherence to screening and diagnostic services, and providing social support and linkages to financial and community resources. Clinical settings, such as federally qualified health centers (FQHCs) are mandated to provide care to medically underserved communities, and thus are also valuable in the effort to address health disparities. We conducted a systematic literature review to identify studies of cancer-related CHW/PN interventions in FQHCs, and to describe the components and characteristics of those interventions in order to guide future intervention development and evaluation. Method: We searched five databases for peer-reviewed CHW/PN intervention studies conducted in partnership with FQHCs with a focus on cancer, carried out in the United States, and published in English between January 1990 and December 2013. Results: We identified 24 articles, all reporting positive outcomes of CHW/PNs interventions in FQHCs. CHW/PN interventions most commonly promoted breast, cervical, or colorectal cancer screening and/or referral for diagnostic resolution. Studies were supported largely through federal funding. Partnerships with academic institutions and community-based organizations provided support and helped develop capacity among FQHC clinic leadership and community members. Discussion: Both the FQHC system and CHW/PNs were borne from the need to address persistent, complex health disparities among medically underserved communities. Our findings support the effectiveness of CHW/PN programs to improve completion and timeliness of breast, cervical, and colorectal cancer screening in FQHCs, and highlight intervention components useful to design and sustainability.

Cancer education and effective dissemination: information access is not enough.

Education is the main avenue for disseminating new research findings into clinical practice. Understanding factors that affect translation of research into practice may help cancer educators design programs that facilitate the time it takes for research-indicated practices to become standard care. To understand various factors, the National Cancer Institute (NCI) Office of Education and Special Initiatives (OESI)(1) with individual cooperation from Oncology Nursing Society (ONS), American Society of Clinical Oncology (ASCO), and Association of Oncology Social Work (AOSW) administered a Practitioner Information Needs survey to five different types of practitioners involved in cancer care. While most of the 2,864 practitioners (83%) agreed they had access to current practice information, practitioners in large practice settings were more likely to report having access to research than those small practice settings. However, only 33% indicated that they had adequate time to access the information. Colleagues or experts within the organization were cited as the most frequently relied on information resource (60%), and peer-reviewed journals were cited as second (57%). Overall, 66% strongly or somewhat agreed that their organizations exhibit effective change management practices. A majority (69%) agreed that implementation of new practices is hindered by the lack of available staff time. Financial factors and the characteristics of the information presented were also believed to be factors contributing to research implementation. Group differences were observed among practitioner groups and practice settings for some factors.

Increases in luteinizing hormone are associated with declines in cognitive performance.

Questions surrounding estrogen therapy for post-menopausal cognitive decline and dementia led us to examine the role of luteinizing hormone that becomes elevated after menopause. We examined hippocampal-associated cognitive performance, as measured with the Y-maze task, in two strains of transgenic mice, one (Tg-LHbeta) which over-expresses luteinizing hormone and another (LHRKO), which has increased circulating luteinizing hormone levels, but its receptors are silenced. Our results demonstrate that Tg-LHbeta, but not LHRKO mice, show decreased Y-maze performance when compared to aged-matched wild-type animals. These findings indicate that increased luteinizing hormone levels, in the presence of functional receptors may, at least in part, be responsible for cognitive decline after menopause. As such, modulation of luteinizing hormone or its receptor levels may prove to be useful therapeutic strategies for cognitive decline associated with aging and age-related neurodegenerative diseases such as Alzheimer disease.

EB1089, a vitamin D receptor agonist, reduces proliferation and decreases tumor growth rate in a mouse model of hormone-induced mammary cancer.

1,25-Dihydroxyvitamin D3 and several of its analogs, such as EB1089, induce growth arrest and apoptosis of breast cancer cells in culture. EB1089 has also been shown to limit growth of xenografts in nude mice and carcinogen-induced mammary tumors in rats. Coupled with the fact that the vitamin D receptor is highly expressed in a large proportion of breast tumors, these data suggest that it may be a broad spectrum therapeutic target. We utilized a transgenic model of hormone-induced mammary cancer, the LH-overexpressing mouse, to assess, for the first time, the efficacy of EB1089 in a spontaneous tumor model. Similar to human breast cancers, the pre-neoplastic mammary glands and mammary tumors in these mice express high levels of vitamin D receptor. Treatment with EB1089 decreased proliferation of mammary epithelial cells in pre-neoplastic glands by 35%. Moreover, half of hormone-induced mammary tumors treated with EB1089 demonstrated a decreased rate of growth, with a subset of these tumors even regressing, suggesting that 1,25-dihydroxyvitamin D3 analogs may be effective chemopreventive and chemotherapeutic agents for breast cancer.

Ovarian hyperstimulation by LH leads to mammary gland hyperplasia and cancer predisposition in transgenic mice.

Many risk factors for breast cancer are associated with hormonally regulated events. Although numerous mouse models of mammary cancer exist, few address the roles of hormones in spontaneous tumor formation. Here we report that transgenic mice that overexpress LH, resulting in ovarian hyperstimulation, undergo precocious mammary gland development. A significant increase in proliferation leads to ovary-dependent mammary gland hyperplasia. Transgenic glands morphologically mimic those of wild-type pregnant mice and expression levels of multiple milk protein genes are comparable with what is observed at d 14 of pregnancy. In addition to sustained hyperplasia, spontaneous mammary tumors were observed with a mean latency of 41 wk, indicating that chronic hormonal stimulation causes mammary cancer. Although hormonally induced, these tumors lack expression of progesterone receptor, suggesting that following initiating events, the tumors may become hormone independent. This mouse model likely holds great potential as a tool for discovery of hormone-mediated mechanisms of breast cancer and identification of future targets for breast cancer prevention and treatment.