Colorectal Cancer Screening Behaviors among American Indians in the Midwest

Colorectal cancer is the second most diagnosed cancer among American Indians and is also the second leading cause of cancer death. We used a community-based participatory approach to conduct a mixed methods study to examine colorectal cancer screening behaviors. Here we report on the screening behaviors of our focus group participants (n=153). There were significant gender differences in the colorectal cancer screening rates for FOBT and colonoscopy. Although over 80% of participants reported having health insurance, only 35% of males over 50 years old and 57% of females reported ever having a colonoscopy. More research is needed to identify the causes of gender differences in colorectal cancer screening rates among American Indians. The results of the current study provide new information on the prevalence of colorectal cancer screening among American Indians living in the Midwestern (Kansas and Missouri) portion of the country

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.R01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSPublished versio

Internet Use for Health Information among American Indians: Facilitators and Inhibitors

Our research team explored Internet use among a heterogeneous American Indian (AI) population to determine Internet use in relation to health information seeking behaviors. Participants examined an AI culturally-tailored tobacco website as an example to explain what they wanted in an AI Internet health site. Using community-based participatory research, we conducted 10 focus groups with non-college AI men and women (N=96), stratified by age (18-29, 30-49, and 50 and over) to better understand their perceptions of Internet use and health information needs. We found that Internet use varied greatly among all strata. Participants referenced WebMD© more than any other website, but participants were not pleased with the design and navigation. When examining the sample website, participants across strata stressed that recreational and traditional tobacco use should be discussed. Participants in all strata desired a simple website design with easy to read text accompanied by images. In order to gain and maintain cultural respect, participants stated that web designers should be aware that some images hold cultural meaning, particularly tobacco. Baseline data are needed for AI’s use of the Internet to obtain health information; this research is helpful to address health inequalities among AI, particularly access to web-based health information

BCL-W has a fundamental role in B cell survival and lymphomagenesis.

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B cell apoptosis. Moreover, Bcl-w loss profoundly delayed MYC-mediated B cell lymphoma development due to increased MYC-induced B cell apoptosis. We also determined that MYC regulates BCL-W expression through its transcriptional regulation of specific miR. BCL-W expression was highly selected for in patient samples of Burkitt lymphoma (BL), with 88.5% expressing BCL-W. BCL-W knockdown in BL cell lines induced apoptosis, and its overexpression conferred resistance to BCL-2 family-targeting BH3 mimetics. Additionally, BCL-W was overexpressed in diffuse large B cell lymphoma and correlated with decreased patient survival. Collectively, our results reveal that BCL-W profoundly contributes to B cell lymphoma, and its expression could serve as a biomarker for diagnosis and aid in the development of better targeted therapies

Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection.

The interplay between a highly polymorphic set of MHC-I alleles and molecular chaperones shapes the repertoire of peptide antigens displayed on the cell surface for T cell surveillance. Here, we demonstrate that the molecular chaperone TAP-binding protein related (TAPBPR) associates with a broad range of partially folded MHC-I species inside the cell. Bimolecular fluorescence complementation and deep mutational scanning reveal that TAPBPR recognition is polarized toward the α2 domain of the peptide-binding groove, and depends on the formation of a conserved MHC-I disulfide epitope in the α2 domain. Conversely, thermodynamic measurements of TAPBPR binding for a representative set of properly conformed, peptide-loaded molecules suggest a narrower MHC-I specificity range. Using solution NMR, we find that the extent of dynamics at "hotspot" surfaces confers TAPBPR recognition of a sparsely populated MHC-I state attained through a global conformational change. Consistently, restriction of MHC-I groove plasticity through the introduction of a disulfide bond between the α1/α2 helices abrogates TAPBPR binding, both in solution and on a cellular membrane, while intracellular binding is tolerant of many destabilizing MHC-I substitutions. Our data support parallel TAPBPR functions of 1) chaperoning unstable MHC-I molecules with broad allele-specificity at early stages of their folding process, and 2) editing the peptide cargo of properly conformed MHC-I molecules en route to the surface, which demonstrates a narrower specificity. Our results suggest that TAPBPR exploits localized structural adaptations, both near and distant to the peptide-binding groove, to selectively recognize discrete conformational states sampled by MHC-I alleles, toward editing the repertoire of displayed antigens

Breast cancer screening practices among American Indians and Alaska Natives in the Midwest

American Indian and Alaska Native (AI/AN) women currently have some of the highest mortality rates from breast cancer for any racial/ethnic group in the United States and some of the lowest screening rates. However, current data are not available for regional differences in screening, which can result in dramatically different stage at diagnosis and mortality. We conducted surveys with 120 focus group participants in a needs assessment of mammography among AI/AN in the greater Kansas City metropolitan area and parts of Northeast Kansas. We found that among women under age 40, for whom recommended screenings include only annual clinical breast examination and breast self-examination, more women reported breast self-examination than clinical breast examination (85.3% versus 55.0% in the past year). Among women age 40 and older, more women reported breast self-examination (80.0% in the past year) than either clinical breast examination or mammography (50.8% and 46.9%, respectively, in the past year). These low rates of breast cancer screening are consistent with low rates reported around the country among AI/AN and have strong implications for stage at diagnosis and prognosis for AI/AN breast cancer patients

Views, Barriers, and Suggestions for Colorectal Cancer Screening Among American Indian Women Older Than 50 Years in the Midwest

OBJECTIVE: Although colorectal cancer (CRC) mortality rates in the US population have shown a decline, American Indian (AI) CRC mortality rates appear to be increasing. CRC screening rates of AIs remain low when compared with other ethnic groups. The research team explored women's perceptions toward CRC screening, existing barriers, and suggestions to promote education and screening among AI women in Kansas and Missouri. METHODS: Using a community-based participatory research approach, the authors conducted 7 focus groups with AI women older than 50 years (N = 52) to better understand their perceptions of and attitudes toward CRC screening. RESULTS: Women recognized barriers to screening, such as embarrassment, privacy issues, fear, insurance, and cost. They countered perceived barriers through inventive suggestions for education and awareness via social support systems and intergenerational relationships. DISCUSSION: CRC screening interventions for AI must be culturally tailored

American Indian Men\u27s Perceptions of Breast Cancer Screening for American Indian Women

Screening, especially screening mammography, is vital for decreasing breast cancer incidence and mortality. Screening rates in American Indian women are low compared to other racial/ethnic groups. In addition, American Indian women are diagnosed at more advanced stages and have lower 5-year survival rate than others. To better address the screening rates of American Indian women, focus groups (N=8) were conducted with American Indian men (N=42) to explore their perceptions of breast cancer screening for American Indian women. Our intent was to understand men’s support level toward screening. Using a community-based participatory approach, focus groups were audio-taped, transcribed verbatim, and analyzed using a text analysis approach developed by our team. Topics discussed included breast cancer and screening knowledge, barriers to screening, and suggestions to improve screening rates. These findings can guide strategies to improve knowledge and awareness, communication among families and health care providers, and screening rates in American Indian communities

Perceptions, Barriers, and Suggestions for Creation of a Tobacco and Health Website among American Indian/Alaska Native College Students

Information concerning American Indian/Alaska Native (AI/AN) Internet use and health information needs is dearth. Our research team explored Internet use among AI/AN college students to determine Internet use in relation to health information seeking behaviors. We used a tobacco site example for participants to describe what they desired in a health site designed specifically for AI/AN. Using a community-based participatory research approach, we conducted 14 focus groups with AI/AN college students (N=108), to better understand their perceptions of and attitudes toward Internet use and health information needs. Daily Internet use was reported across strata yet health topics investigated differed among groups. Participants in all strata desired a health website that was easy to navigate and interactive. Respectful representation of Native culture was a concern, yet no consensus was reached for a multi-tribal audience. Participants felt a website should use caution with cultural depictions due to the possible misinterpretation. Overall, participants agreed that recreational and traditional tobacco use should be differentiated and the variation of traditional use among tribes acknowledged. Data concerning Internet use for health information among AI/AN college students are needed to establish baseline indicators to effectively address disparities

American Indian/Alaska Native Willingness to Provide Biological Samples for Research Purpose

This article examines the willingness of American Indian/Alaska Natives (AI/AN) to provide biological samples for research purposes. Prior cases of abuse and misuse of individuals, materials, and data highlight ethical research concerns. Investigators may be hesitant to engage AI/ANs in research projects. We conducted a survey of AI/ANs in the central plains region of the US over 1 year. This convenience sample completed a series of questions on biological samples and research. Survey results (N = 998) indicate that 70.15% of AI/ANs would be willing to provide saliva/spit for a specific study with the proper consent and control of samples. In conclusion, researchers should find ways to work with and for AI/ANs, assuring participant input in the research process