NAC1 promotes stemness and regulates myeloid-derived cell status in triple-negative breast cancer.

Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated protein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Additionally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFß, IL-6). Intriguingly, the impact of NAC1 on tumor growth varies with the host immune status, showing diminished tumorigenicity in natural killer (NK) cell-competent mice but increased tumorigenicity in NK cell-deficient ones. This highlights the important role of the host immune system in TNBC progression. In addition, high NAC1 level in MDSCs also supports TNBC stemness. Together, this study implies NAC1 as a promising therapeutic target able to simultaneously eradicate CSCs and mitigate immune evasion.

Cancer disparities in Appalachian Kentucky.

PURPOSE: Cancer is the second leading cause of death in the United States, and the disease burden is elevated in Appalachian Kentucky, due in part to health behaviors and inequities in social determinants of health. This study's goal was to evaluate Appalachian Kentucky's cancer burden compared to non-Appalachian Kentucky, and Kentucky compared to the United States (excluding Kentucky). METHODS: The following data were analyzed: annual all-cause and all-site cancer mortality rates from 1968 to 2018; 5-year all-site and site-specific cancer incidence and mortality rates from 2014 to 2018; aggregated screening and risk factor data from 2016 to 2018 for the United States (excluding Kentucky), Kentucky, non-Appalachian Kentucky, and Appalachian Kentucky; and human papilloma virus vaccination prevalence by sex from 2018 for the United States and Kentucky. FINDINGS: Since 1968, the United States has experienced a large decrease in all-cause and cancer mortality, but the reduction in Kentucky has been smaller and slower, driven by even smaller and slower reductions within Appalachian Kentucky. Appalachian Kentucky has higher overall cancer incidence and mortality rates and higher rates for several site-specific cancers compared to non-Appalachian Kentucky. Contributing factors include screening rate disparities and increased rates of obesity and smoking. CONCLUSIONS: Appalachian Kentucky has experienced persistent cancer disparities, including elevated all-cause and cancer mortality rates for 50+ years, widening the gap between this region and the rest of the country. In addition to addressing social determinants of health, increased efforts aimed at improving health behaviors and increased access to health care resources could help reduce this disparity.

Piloting an Oral History Approach to Investigate Cancer Perspectives Among Residents of Appalachian Kentucky.

Introduction: Kentucky ranks first in the U.S. in overall cancer incidence and mortality rates. Areas of the state that fall within the Appalachian Region, along Kentucky's eastern border, experience disproportionately high rates of cancer compared to non-Appalachian counties. Purpose: This pilot study investigates whether oral history interviews can be used to understand perspectives on cancer among residents of Appalachian Kentucky. Methods: In 2020, participants (n = 5) who identified as being from and/or having strong connections to Appalachian Kentucky were recruited to participate in this pilot study. Participants included individuals working in cancer-related fields, oncology professionals, and those with personal cancer experience. Using an oral history approach, subjects were asked about challenges within Appalachia that contribute to high rates of cancer regionally. Interviews were analyzed using qualitative content analysis, and data were condensed into themes, subthemes, and subtopics. Relational content analysis was then used to illustrate relationships between the problems being faced in Appalachia and their contributing factors, with potential solutions to those problems. Results: Six key themes emerged from analysis of the oral history interviews: (1) problems being faced in Appalachia; (2) contributing factors; (3) potential solutions; (4) Appalachian disposition; (5) experiences with and thoughts on cancer; and (6) defining success v. the future without changes (intervention). A further 25 subthemes were identified from within these themes. Taken together, these themes and subthemes point to potential areas for specific intervention to shift Appalachia's cancer burden. Implications: This pilot study demonstrates potential benefit in using oral history interviews to elucidate Appalachian Kentuckians' perspectives on cancer. From the nuanced insights gained through this method, a set of culturally appropriate interventions were identified that could address the disproportionate cancer burden in the region. Future studies using an oral history approach could aim to reveal other specific aspects of how cancer impacts individuals, families, and communities.

Impact of a Cancer Education Curriculum on Appalachian Kentucky Middle and High School Students.

Appalachian Kentucky is disproportionately affected by elevated cancer incidence and mortality rates. This disparity is driven by inequities in health behaviors and social determinants of health including decreased education attainment levels that cause lower health literacy. To increase cancer literacy in the region, a three-part cancer education curriculum was designed for Appalachian Kentucky middle and high school students. This study was designed to evaluate the effect the curriculum had on students' cancer literacy. The curriculum lessons were disseminated to Appalachian Kentucky middle and high school teachers who engaged 223 students with the material. For each lesson, students filled out a 10-question pretest and an identical 10-question posttest. The average and median percent of correct responses from the pre- to posttests were analyzed. The average percentage of correct responses significantly increased from 40% to 70%, 52% to 69%, and 33% to 53% on lessons 1, 2, and 3, respectively. A significant increase in the average percentage of correct responses on each individual question was also observed. The results demonstrate that the three-part cancer education curriculum intervention can significantly increase Appalachian Kentucky middle and high school students' cancer literacy. Increased cancer knowledge has the potential to encourage behavioral modifications that could reduce cancer incidence and mortality rates over time. Future work will include further improving the content relative to the target age/grade level and implementing the material with a broader group of teachers and students.

A Qualitative Study of Participant Perceptions of a Cancer Research Education Program.

Kentucky ranks first in the nation in cancer incidence and mortality rates, with the greatest burden of disease being in the Appalachian region. The cancer disparities in the Appalachian region of the state are tied to high poverty rates, low education attainment, low health care access, and high rates of poor health behaviors, such as tobacco use. The University of Kentucky (UK) Markey Cancer Center (MCC) developed the Appalachian Career Training in Oncology (ACTION) program to address the cancer and education disparities in the region. ACTION is a two-year program that focuses on cancer education and training for high school and undergraduate students from Appalachian Kentucky and features a variety of cancer-focused training activities, including faculty-mentored cancer research, clinical shadowing opportunities, cancer education activities, career development support, and community outreach projects. ACTION has been funded by the National Cancer Institute as a Youth Enjoy Science R25 research education program since 2018. The qualitative study herein used a semi-structured interview approach to identify participants' perceptions of the program including the influential aspects that have helped students pursue their desired academic career paths. Ten ACTION alumni were chosen to participate in the study, including students currently in medical school, graduate school, physician assistant school, and pharmacy school. Thematic analysis generated five themes: motivation for participation, career development, mentorship and future opportunities, knowledge gained, and program improvements. Overall, this study demonstrates that the ACTION program is having a significant impact on students' career preparation.

Lung and Colorectal Cancer Disparities in Appalachian Kentucky: Spatial Analysis on the Influence of Education and Literacy.

Low educational attainment and high cancer incidence and mortality rates have long been a challenge in Appalachian Kentucky. Prior studies have reported disparities in cancer incidence and mortality between Appalachian and non-Appalachian populations, but the influence of education on this disparity has not been extensively studied. Herein, all cancers and two cancer sites with available screenings (colorectal and lung) were joined with education indicators (educational attainment and literacy) and one geographic indicator across all 120 Kentucky counties. This dataset was used to build choropleth maps and perform simple linear and spatial regression to assess statistical significance and to measure the strength of the linear relationship between county-level education and cancer-related outcomes in Appalachian and non-Appalachian Kentucky. Among all cancer sites, age-adjusted cancer incidence and mortality was higher in Appalachian versus non-Appalachian Kentucky. The percentage of the population not completing high school was positively correlated with increased colorectal and lung cancer incidence and mortality in Appalachia. Similarly, counties with a higher percentage of the population lacking basic literacy had the strongest correlation with colorectal and lung cancer incidence and mortality, which were concentrated in Appalachian Kentucky. Our findings suggest a need for implementing interventions that increase educational attainment and enhance basic literacy as a means of improving cancer outcomes in Appalachia.

An examination of cancer literacy among Appalachian versus non-Appalachian Kentucky college students.

OBJECTIVE: Examine factors contributing to high rates of Appalachian female cancer incidences and mortalities by examining cancer literacy and associated sociological influences among Appalachian university students. PARTICIPANTS: This study evaluated Appalachian and non-Appalachian undergraduate students in Eastern Kentucky. METHODS: A Qualtrics survey was disseminated which categorized questions into three parts: demographic, female focused cancer literacy, and cancer care access. RESULTS: Overall cancer literacy was low (67.45%, 139 respondents); no difference was found in Appalachian standing. Male students had lower scores (p < 0.05), and both cancer-related majors (p < 0.001) and enhanced academic years (p < 0.05) improved cancer literacy. Limited awareness of mobile cancer screening units was found across respondents, along with, decreased access to health services indicated by Appalachian students (p < 0.05). CONCLUSIONS: College students represent a population in need of enhanced cancer education. Improving knowledge about accessing healthcare including cancer screenings could reduce Appalachian cancer rates.

The Impact of a Virtual Tobacco Prevention and Advocacy Training Among Youth in Appalachian Kentucky Communities.

BACKGROUND: Engaging youth is an important component of comprehensive tobacco control programs. PURPOSE: This paper describes the impact of a virtual tobacco prevention training program to encourage and prepare youth in Appalachia to support tobacco prevention policies, to strengthen interpersonal confidence to address tobacco use within their communities and enhance advocacy self-efficacy for tobacco control. METHODS: A two-part evidence-informed peer-led tobacco prevention and advocacy training was implemented among 16 high school students from Appalachian counties in Kentucky. The initial training (January 2021) included an overview of the e-cigarette landscape, advocacy skills related to policy change, developing messages to decision makers, and media advocacy. A follow-up session (March 2021) included a breakdown of advocacy skills and overcoming barriers. RESULTS: Overall, participants held strong beliefs that tobacco use is an issue that needs to be addressed in their community. There was a statistically significant average difference in student interpersonal confidence between baseline and post-surveys (t = 2.016, P = .062 < .1). Students who participated in at least 1 of the provided advocacy events indicated higher self-reported advocacy. CONCLUSION: Youth in Appalachia expressed an interest to advocate for stronger tobacco policy in their communities. Youth who participated in the tobacco advocacy policy trainings reported improvements in attitudes, interpersonal confidence, advocacy self-efficacy, and self-reported advocacy. Youth engagement in tobacco policy advocacy is promising and needs to be further supported.

Examining Psychological and Knowledge Barriers to Colorectal Cancer Screening in Rural Appalachian Kentucky.

While recent rates of colorectal cancer (CRC) screening have improved in Appalachian Kentucky due to public health efforts, they remain lower compared to both KY as a whole, and the USA. Suboptimal screening rates represent a missed opportunity to engage in early detection and prevention. The purpose of this study is to determine the impact that lack of knowledge has on psychological barriers (e.g., fear and embarrassment) to CRC screening as well as the potential effect of a psychosocial intervention to reduce these barriers. Participants were recruited through faith-based organizations and other community sites. After randomizing participants to either an early or delayed group, a faith-based group education and motivational interviewing intervention was administered. Existing and pilot tested instruments were used to assess knowledge and potential psychological barriers. Data were analyzed using paired t tests and linear regression. We hypothesized that (1) psychological barriers are associated with inadequate knowledge and (2) the intervention, by improving knowledge, could reduce these barriers and increase screening rates. There was a small but significant reduction in psychological barriers (-0.11, p value = 0.015) and moderate increases in CRC knowledge scores (+0.17, p value = 0.06). There was no evidence that the intervention affected these measures (+0.10, p value = 0.58). The relationship between lower barrier scores and increased knowledge was significant at follow up (-0.05, 95% CI (-0.09, -0.00)). An increase in CRC knowledge was correlated with a small but significant decrease in psychological barriers, although there was no evidence that these changes were associated with one another. Future cognitive-based interventions may be effective in increasing CRC knowledge and reducing barriers, but new intervention approaches should be considered.

Impact of the Appalachian Career Training in Oncology (ACTION) Program on Undergraduate Participants.

Kentucky ranks first in the nation in cancer incidence and mortality. The Appalachian region of the state experiences the highest cancer disparities due to inequities in many social determinants of health. As a strategy for addressing cancer and education disparities in the region, the Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engaged 16 Appalachian-native undergraduate student participants annually in cancer-related activities. Students were recruited on an annual basis for the 2-year ACTION program. Entry, mid-point, and exit surveys were administered to participants. Classical test theory and exploratory factor analysis were used to examine the instruments used for program evaluation, whereas repeated measures ANOVA, paired t-tests, chi-squared, and post hoc analyses were used to analyze 6 years of survey data. There was a significant increase in participants' understanding of cancer-related topics among the entry, midpoint, and exit surveys (p < .001) and a significant increase in comfort with research, clinical, and outreach activities between entry and midpoint and entry and exit (p < .001), but not between midpoint and exit. With respect to research skills and perceptions of the program, increases in mean scores were observed between midpoint and exit, but these increases were not statistically significant (p = .167, p = 223, respectively). ACTION increased participants' understanding of cancer-related topics; comfort with research, clinical, and outreach activities; and research skills. These data suggest that ACTION has a significant impact on participants.

Using Culturally Focused Storytelling to Empower Appalachian Kentucky Youth to Understand and Address Cancer Disparities in Their Communities.

Kentucky has the highest cancer incidence and mortality rates in the nation with the Appalachian region of the state being most affected. These rates are driven by health behaviors and inequities in social determinants of health. Herein, Appalachian Kentucky students with the University of Kentucky's Appalachian Career Training in Oncology (ACTION) program were engaged in a storytelling exercise by writing culturally framed essays. Students discussed their personal experiences with cancer and their thoughts on the causes of and potential solutions to Appalachian Kentucky's cancer disparities. Content analysis was used to identify common themes, subthemes, and subtopics in the essays regarding cancer types, causes of cancer in Appalachia, and solutions to the high cancer rates. Common cancer types experienced by the students included breast, lung, and prostate. The most frequently identified themes that drive cancer rates in Appalachian Kentucky were identified as geography, environmental factors, tobacco use, education, poverty, prevention, and mistrust. Common proposed solutions to decrease cancer rates were to increase education and awareness, screening, and tobacco cessation. Overall, through storytelling, youth gained a better understanding of cancer in their communities and envisioned culturally tailored, community-based intervention strategies that can aid in reducing the cancer burden in Appalachian Kentucky.

Early Cancer Research Education for Underrepresented Middle School Students: A Case Study of Experiences from Youth Enjoy Science Programs.

Cancer is the second leading cause of death in the United States, and marginalized communities are disproportionately affected. There is a significant need to address cancer disparities and the determinants of health that are associated with those disparities. Increasing the diversity of the cancer research workforce is a potential mechanism to address health disparities. The National Cancer Institute's Youth Enjoy Science Research Education Program provides funding to engage middle school, high school, and undergraduate students from underrepresented student populations in cancer research education programming, conduct cancer education outreach to communities, and provide cancer research curricula to kindergarten through grade 12 educators. The ultimate goal of these programs is to motivate, prepare, and support students in pursuing cancer research careers. Herein, we describe how three academic institutions with YES Programs - the University of Kentucky, the University of Nebraska Medical Center, and Case Western Reserve University - provide cancer education programming to middle school students. Descriptions of each institutions' programing are provided. Common and unique elements were determined through an evaluation of the three programs. Although each program was developed independently, they have more common than unique elements. We provide insight into the development of middle school programs for other academic institutions.

The Impact of the Appalachian Career Training in Oncology (ACTION) Program on High School Participants.

Objective: Kentucky ranks first in the nation in cancer incidence and mortality. The Appalachian region of the state experiences the highest cancer disparities due to inequities in many social determinants of health as well as poor health behaviors. As a strategy for addressing cancer and education disparities in the region, the Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engages Appalachian-native high school students in cancer education, research, and outreach activities. Methods: Entry and exit surveys were administered to participants. Classical test theory and exploratory factor analysis were used to examine the instruments used for program evaluation, whereas repeated measures ANOVA was used to determine if there were significant differences in means between entry and exit timepoints. Results: There was an increase in students' understanding and comfort with cancer-related topics between entry and exit survey administrations. Students indicated that the program improved their research skills and career planning skills. Furthermore, students had positive perceptions of all aspects of the program. Conclusion: Data suggest that ACTION has a positive impact on high school students. Specifically, results show increased understanding and comfort with cancer-related topics, research skills, and career planning.

The Use of Virtual Research Experiences for Appalachian Career Training in Oncology (ACTION) Program High School Participants During the COVID-19 Pandemic.

Objective: Kentucky has the highest cancer incidence and mortality rates in the nation, with rates greatest in the Appalachian region due to poor health behaviors and inequities in social determinants of health. The Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engages 20 Appalachian-native high school students annually in cancer education, research, and outreach activities. During the COVID-19 pandemic, programming was disrupted, and alternative activities were implemented, including virtual research experiences. Methods: The program's goals were to improve students' biology and cancer content knowledge and research skills and help students make career decisions. Virtual laboratories were used to help accomplish these goals. This study aimed to evaluate the use of virtual laboratories embedded in the program and determine if such experiences helped reach the program's goals. A survey was used to measure students' perceptions of the virtual labs. Results: Results indicated that students perceived they gained content knowledge, obtained research skills, and considered entering science and cancer-related careers. Conclusion: The decision to incorporate virtual laboratories into the ACTION programming during the COVID-19 pandemic was a sound instructional choice. Evidence provided herein gives researchers and program developers information necessary to consider using virtual labs in their programs.

Exceptional Survival Among Kentucky Stage IV Non-small Cell Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations.

PURPOSE: To determine differences in exceptional survival (ES)-survival of 5 years or more past diagnosis-between stage IV non-small cell lung cancer (NSCLC) patients residing in the Appalachian versus non-Appalachian regions of Kentucky. METHODS: This was a population-based, retrospective case-control study of Kentucky patients, diagnosed with stage IV NSCLC between January 1, 2000, and December 31, 2011. The data were drawn from the Kentucky Cancer Registry. FINDINGS: Findings from the multivariable logistic regression revealed no significant differences in the odds of ES between patients who resided in Appalachian versus non-Appalachian Kentucky. Being female and undergoing surgery only as the first course of treatment were associated with higher odds of ES. Increasing age, unspecified histology, having poorly differentiated or undifferentiated carcinomas, and receiving radiation therapy only as the first course of treatment were associated with decreased odds of ES. CONCLUSION: Differences in the odds of ES among stage IV NSCLC patients were not related to residence in Appalachian versus non-Appalachian Kentucky. ES was associated with other nongenetic and treatment factors that warrant further investigations.

Approaches for Measuring Inclusive Demographics Across Youth Enjoy Science Cancer Research Training Programs.

The National Cancer Institute's (NCI) Youth Enjoy Science Program (YES) funds initiatives to support the cancer research training and career ambitions of middle school through undergraduate students from populations underrepresented in the biomedical sciences. The program has funded 16 institutions nationally as of January 2022. Given the program's focus on increasing diversity within the cancer research workforce, demographic characteristics of YES trainees provide essential information about the populations being served and program effectiveness. Six programs formed an interest group focused on trainee demographics and surveyed all YES grantees about their demographic data practices. Fifteen programs (94%) completed the survey. Survey data were analyzed through descriptive statistics and thematic coding. Findings revealed considerable variability in programs' approach to demographic data, including which demographics were measured, how they were operationalized, and when and how the data were collected. Half of YES programs (53%) could report underrepresented populations in biomedical research among trainees using consistent definitions. Most programs described efforts to improve their demographic data practices; however, challenges remained for the vast majority. In consideration of these findings, we offer recommendations for inclusive demographic data practices to better define and retain underrepresented populations in biomedical sciences.

Training Appalachian Kentucky Youth Cancer Advocates.

OBJECTIVES: Kentucky has the highest cancer incidence and mortality rates in the United States, with the Appalachian region experiencing the highest of those rates. Cancer advocacy, which is defined as providing support to cancer patients and their communities, represents a means of decreasing the cancer cases in Appalachian Kentucky. This exploratory study examined the effects of advocacy training and experiential learning on Appalachian high school students' cancer advocacy attitudes and self-efficacy. METHODS: The design of this study was a mixed-methods, one-group repeated measure with a group of participants from the Appalachian Career Training in Oncology (ACTION) Program (N = 9). The study assessed advocacy attitudes and self-efficacy before and after participants were provided advocacy training and participated in an advocacy event. RESULTS: Participating students' attitudes and self-efficacy did not substantially change following the training and their participation in an advocacy event. Through their comments after the event, however, students seem eager to use their voices to influence the actions of state legislators. At the same time, they worry about the apathy of their community members to their cancer advocacy message. CONCLUSIONS: Youth represent potentially powerful agents of advocacy that could help address the cancer burden in Kentucky. Participants in this study likely overestimated their advocacy abilities before learning more about advocacy and participating in the process. As such, additional trainings are likely necessary to increase students' self-efficacy, encourage them to share their stories, and help them overcome perceived barriers.

The Appalachian Career Training in Oncology (ACTION) Program: Preparing Appalachian Kentucky High School and Undergraduate Students for Cancer Careers.

The Appalachian Career Training In ONcology or ACTION Program is a National Cancer Institute (NCI) Youth Enjoy Science (YES) research education grant program that recruits and trains early-career undergraduate and high school students from underrepresented, socioeconomically distressed areas of Appalachian Kentucky in cancer research and outreach. The two-year program is a multifaceted experience that includes participation in cross-disciplinary, mentored cancer research projects. In addition to research projects, participants also shadow faculty mentors in clinical medical settings, engage in multiple types of educational activities, and participate in cancer-focused outreach projects within their communities. Participants also engage in peer-to-peer networking and receive career mentorship, training, and coaching. Highlights of program activities include a student-led photovoice project to promote cancer awareness and participant publications including a book featuring participant essays focused on their experiences and thoughts on cancer. Initial impact data show high school participants have a higher than state and county average four-year college-going rate and all undergraduate participants are gaining positive outcomes related to educational and career attainment. This article provides an overview of the significant benefits of the ACTION Program, the program's activities, and highlights from program implementation. Potential impacts of the program and barriers to implementation are also shared.