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Glioblastoma is the most fatal of all primary human brain tumors, with a 14-month median survival. The mainstay therapy for this tumor involves temozolomide, surgery, radiotherapy, and tumor-treating electric field. Cancer resistance to commonly available chemotherapeutics remains a major challenge in glioblastoma patients receiving treatment and unfavorably impacts their overall survival and outcome. However, the lack of progress in this area could be attributed to the lack of tools to probe unbiasedly at the genome-wide level the coding and non-coding elements’ contribution on a large scale for factors that control resistance to chemotherapeutics. Understanding the mechanisms of resistance to chemotherapeutics will enable precision medicine in the treatment of cancer patients. CRISPR Cas9a has emerged as a functional genomics tool to study at the genome level the factors that control cancer resistance to drugs. Recently, we used genome-wide CRISPR-Cas9a screen to identify genes responsible for glioblastoma susceptibility to etoposide. We extended our inquiry to understanding genes that control glioblastoma response to temozolomide using the genome-scale CRISPR. This study shows that the unbiased genome-wide loss of function approach can be applied to discover genes that influence tumor resistance to chemotherapeutics and contribute to chemoresistance in glioblastoma.

Background Black Americans have long been considered a hard-to-reach population for research studies, whether quantitative surveys or for clinical research. Studies have explored multiple rationales for why Blacks are hard to reach, and the explanations have included historical mistrust, the need to assess the benefits from participating in research, and the expense of spending time participating in research, among others. What has not been explored is the continuous merging of all individuals who identify as Black, particularly when exploring reasonings for a lower interest in participating in research. This paper addresses this issue by investigating the participation rate of individuals identifying as Black in New York City in a study exploring dietary practices as a predictor of colorectal cancer screening behavior. Participants were asked to self-report screening behavior, intent to screen, and dietary and other lifestyle practices. In this analysis, we discuss the unique experience encountered in recruiting Black American participants to participate in this study, particularly amid a worldwide pandemic of COVID-19. Methods The methodology for this study included a systematic review of the literature, a two-part recruitment process, and data analysis. The first part of the recruitment process involved registering individuals who were interested in participating in the study and consented to be contacted and reminded to come to the location where they were recruited on a scheduled date to complete the actual survey. With this part of the recruitment process, we engaged with n = 488 Black men and women between November 2019 and February 2020. The second part of the recruitment process utilized availability sampling outside of NYC subway stations and other high traffic areas as well as large community events. We engaged with n = 319 individuals. Total engagement with n = 807 individuals yielded a sample size for the survey of 504 completed surveys. Results Of the total engaged (n = 807), 14% declined to participate due to a lack of time, 11% chose not to participate in the study because the incentive was not enough to compensate for their time 0.02% declined due to not trusting institutions conducting research, and 0.03% did not feel comfortable understanding the questions due to a language barrier. We had a sample size of (n = 504) of the total 807 individuals engaged. Conclusions Recruiting Black Americans into our colorectal cancer study did not prove to be challenging with the two-tiered model of recruitment that involved consistent engagement and having the primary researcher lead this recruitment process. Extracting within race differences is critical in demystifying the conclusion of numerous studies that African Americans specifically are hesitant to participate due to historical mistrust related to tragedies such as the Tuskegee Experiment and numerous other occurrences of African Americans being treated as guinea pigs for the advancement of research. This data contributes knowledge to this field regarding understanding recruitment challenges in the Black population, but further work needs to be conducted. Mistrust in this study primarily came from the individuals engaged in Caribbean neighborhoods, where many expressed more comfort with home remedies and bush doctors when asked about colorectal cancer screening and declined to participate. Innovative communication, qualitative research, and recruitment strategies tailored to the Caribbean population are needed in future studies to address this recruitment challenge that we experienced.

MicroRNAs play an important role in modulating normal cellular functions through protein-protein interaction in addition to regulating gene expression via mRNA degradation or translational repression.PVT1is a non-protein coding gene that encodes six annotated microRNAs (miRNAs), including miR-1207-3p, a demonstrated modulator in PCa. MiR-1207-3p is significantly underexpressed in PCa cells when compared to normal prostatic cells and directly targets fibronectin type III domain containing 1 (FNDC1), which was found to be overexpressed in PCa cells along with concomitant overexpression of fibronectin (FN1)/androgen receptor (AR)/c-MYC. To better understand the role of FNDC1/FN1/AR/c-MYC in PCa progression we examined the interaction between FNDC1/FN1/AR/c-MYC. Coimmunoprecipitation study showed direct physical interaction between FNDC1/FN1/AR/c-MYC in PCa cells and FN1/AR/cMYC in normal prostatic cell. Knockdown of FN1, AR and cMYC not only confirmed FN1/FNDC1/AR/cMYC interaction but also gave rise to the possibility of a complex. We also examined the spatial localization of the FNDC1/FN1/AR/c-MYC pathway by performing immunofluorescence staining in PCa cells. Single staining analysis revealed that FNDC1, AR and c-MYC localize to the nucleus and cytoplasm while FN1 localizes only to the cytoplasm in PCa cells but not in the non-tumorigenic prostate cells. However, our findings show that miR-1207-3p has no direct effect on the FNDC1/FN1/AR/cMYC interaction. Understanding this molecular interaction can reveal additional insights into the role of FNDC1/FN1/AR/cMYC interaction in PCa progression.

Breast, lung, and colorectal cancer resistance to molecular targeted therapy is a major challenge and unfavorably impacts clinical outcomes, leading to hundreds of thousands of deaths yearly. In ERBB2+ cancers regardless of the tissue of origin, ERBB2 is the driver oncogene of resistance. We discovered that the ERBB2+ cancers are enriched with poly U sequences on their 3’UTR AU rich elements which are mRNA stabilizing sequences. We developed a novel technology, in which we engineered these ERBB2 mRNA stabilizing sequences to unstable forms and specifically controlled and degraded ERBB2 transcript and protein across multiple cancer types both in the wildtype and drug resistance settings in vitro and in vivo, offering a unique novel modality to control ERBB2 and other pervasive oncogenic signals where other therapies fail.One-Sentence SummaryEngineered destabilized 3’UTR ARE of ERBB2 degrades ERBB2 in many cancer types and controlled resistance.Graphical abstractA. Depiction represents multiple ERBB2 expressing cancer cells with stable 3’UTR ARE and the signaling cascade known to cause chemo resistance. B. Depiction of the engineered destabilized 3’UTR ARE of ERBB2 and the destabilization and degradation of the ERBB2 transcript, protein and kinases involved in mediation of drug resistance

Prostate cancer is the most common cancer in men and the second leading cause of cancer death among men in the United States according to the National Cancer Institute. Current treatment modalities involve prostatectomy, androgen receptor blockade and supportive/palliative care. Despite these treatment options, metastatic castration resistant prostate cancer and neuroendocrine prostate cancer still have very dismal clinical outcomes. Therefore, there is a need to understand the biology of the aggressive prostate cancer subtypes to identify novel targetable molecules. The castration resistant prostate cancer, neuroendocrine prostate cancer and the metastatic prostate cancers that recur have c-MYC amplification. These cancers are not responsive to androgen blockade or deprivation therapy. Attempts to target c-MYC have been difficult due to the intrinsic disordered nature of c-MYC. Various approaches have been attempted to control c-MYC; namely RNAi which has high off target effects, anti-sense oligonucleotides (ASO) which have low cellular penetrance and needs phosphorothioate modification, G-quadruplex inhibitors which are unspecific as they block POLII, the BRD4 and CDK inhibitors which are indirect inhibitors of c-MYC. Only OmoMyc a bHLH domain mutant with enhanced leucine zipper dimerization is in phase 1 trials with limited bioavailability. To explore the possibility of targeting c-MYC in these difficult-to-treat prostate cancers, we transfected C4-2B, a cellular model of metastatic castration resistant prostate cancer, with engineered destabilized 3‘UTR AU rich element of c-MYC. We found that we degraded c-MYC transcript and protein and killed the cancer cells. Taken together, we offer preliminary evidence that we can directly target c-MYC and inhibit these difficult-to-treat cancers. In vivo studies to validate these findings are ongoing. Citation Format: Chidiebere U. Awah, Olorunseun O. Ogunwobi. Targeting cMYC in metastatic castration resistant and neuroendocrine prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4504.

Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate cancer and brain cancers combined. This is primarily due to its metastatic abilities to organs such brain, liver, bones, and adrenal glands leading to death of the patient. And there are no clinically approved drugs that can target metastasis. NSCLC with EGFR T790M overexpressing HER2 shows resistance to osimertinib and trastuzumab starting 10-18 months after therapy. For these patients, prospects are grim. To address the challenge of HER2+ drug resistant NSCLC, we have developed an innovative approach based on genome engineering of the 3’ untranslated region (3’UTR) of the HER2 gene to destabilize and degrade HER2 transcript, protein expression, HER2 dependent kinases and interactome. We report the development of two very effective HER2 destabilizing constructs which when transfected into cells lead to the specific loss of HER2 transcript, protein, downstream kinases, and loss of cell viability. In vivo, we administered the constructs complexed with a nanocage to mice bearing NSCLC. We achieved very significant control of primary tumors p=0.0001 and inhibited liver and lung metastasis and prevented hepatomegaly in mice bearing tumors that received our engineered constructs. Mechanistically, the destabilized mRNA creates premature termination codon which triggers the upregulation of nonsense mediated decay proteins UPF3B and then there is subsequent uncapping of the mRNA and the exonucleases XRN1 and CNOT1 degrades the transcript specifically and the proteins are not made available. The exogenous destabilized constructs are continuously transcriptionally active dominant negative which outcompetes the native endogenous HER2 and co-opts its mRNA for degradation. The loss of HER2 leads to loss of WNK1 and YES1 leading to activation of caspase 3,9 mediated cell death. The migration and invasion of the tumor is impaired. The constructs safely integrated into non-coding regions of the genome and caused no genome rearrangements, and we found no blood, renal, liver or electrolytes toxicities in the animals that received them. Taken together, we have developed a novel therapeutic agent that inhibits the growth of primary NSCLC and metastasis to the liver and lung. Citation Format: Chidiebere U. Awah, Joo Sun Mun, Baris Boylu, Alooka Paragodaarachchi, Chika Ochu, Junfei Zhang, Hiroshi Matsui, Olorunseun O. Ogunwobi. Nanocage delivered engineered destabilized HER2 3UTR ARE reduced growth of primary EGFR T790M HER2 overexpressing osimertinib and trastuzumab resistant non small cell lung cancer and inhibited liver and lung metastasis in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3417.

Breast cancer is the most common form of cancer in women with mortality of about 58% in developing countries. HER2+ breast cancers are treated with trastuzumab in various forms in combination with chemotherapy and has been successful in targeting HER2 overexpression in HER2+ breast cancer and improving survival as a standard first line therapy for more than a decade. However, about 25% of early and 75% of late stage HER2 driven breast cancers are resistant to trastuzumab. For these patients, the clinical outcomes are grim. We report the destabilization of HER2 3‘UTR ARE which degraded oncogene HER2 transcript, protein expression, HER2 dependent kinases and interactome. In vitro, we transfected the engineered destabilizing HER2 constructs into BT474 clone 5 trastuzumab resistant breast cancer and within days, we inhibited cancer cell growth and degraded HER2 transcript and protein. The degradation of HER2 leads to loss of many kinases especially YES1 and WNK1 that are known causes of chemoresistance in HER2 positive trastuzumab resistant breast cancer. In vivo, we administered the destabilizing constructs as naked constructs or as complexed with nanocages to mice bearing tumors of BT474 clone 5 trastuzumab resistant cells. We found that our constructs, both the naked and nanocage-delivered, conferred significant survival (p values: 0.0178 and 0.00492) to about 60% of the exceptionally surviving mice compared to the controls. Taken together, we have developed a new therapy to target trastuzumab resistant HER2+ metastatic breast cancers with increased survival outcomes. Citation Format: Chidiebere U. Awah, Joo Sun Mun, Baris Boylu, Alooka Paragodaarachchi, Chika Ochu, Hiroshi Matsui, Olorunseun O. Ogunwobi. In vivo inhibition of metastatic HER2 positive trastuzumab resistant breast cancer using engineered destabilized 3UTR ARE of HER2 improves survival outcomes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3900.

Obesity is a risk factor for Barrett’s oesophagus and oesophageal adenocarcinoma. Adipose tissue secretes the hormone leptin. Leptin is a growth factor for several cell types, including Barrett’s cells and oesophageal adenocarcinoma cells. Statins are associated with reduced rates of Barrett’s oesophagus and oesophageal cancer and exhibit anti-cancer effects in vitro. The mechanisms of these effects are not fully established. We have examined the effects of leptin and the lipid-soluble statin, atorvastatin, on signalling via monomeric GTP-binding proteins and Akt. Proliferation and apoptosis were assessed in OE33 cells. Akt activity was quantified by cell-based ELISA and in vitro kinase assay. Specific small-molecule inhibitors and a dominant-negative construct were used to reduce Akt activity. Small GTPases were inhibited using transfection of dominant-negative plasmids, prenylation inhibitors and pretreatment with atorvastatin. Leptin stimulated Akt activity and cell proliferation and inhibited camptothecin-induced apoptosis in an Akt-sensitive manner. Leptin induced phosphorylation of Bad and FOXO1 in an Akt-sensitive manner. Leptin activated Ras, Rac, RhoA and cdc42. Transfection of dominant-negative plasmids confirmed that leptin-induced Akt activation required Ras, RhoA cdc42 but not Rac. Atorvastatin inhibited leptin-induced activation of Ras, RhoA, cdc42 and Akt. Co-treatment with mevalonate prevented these effects of atorvastatin. The protein kinase Akt is essential to the growth-promoting and anti-apoptotic effects of leptin in oesophageal adenocarcinoma cells. Akt is activated via Ras-, Rho- and cdc42-dependant pathways. Atorvastatin reduces leptin-induced Akt activation by inhibiting prenylation of small GTPases. This may explain the reduced incidence of oesophageal adenocarcinoma in statin-users.

Genetic variation in susceptibility to complex diseases, such as cancer, is well-established. Enrichment of disease associated alleles in specific populations could have implications for disease incidence and prevalence. Prostate cancer (PCa) is a disease with well-established higher incidence, prevalence, and worse outcomes among men of African ancestry in comparison to other populations. PCa is a multi-factorial, complex disease, but the exact mechanisms for its development and progression are unclear. The gene desert located on chromosome 8q24 is associated with aggressiveness of PCa. Interestingly, the non-protein coding gene locus Plasmacytoma Variant Translocation (PVT1) is present at chromosome 8q24 and is overexpressed in PCa. PVT1 gives rise to multiple transcripts with potentially different molecular and cellular functions. In an analysis of the PVT1 locus using data from the 1000 Genomes Project, we found the chromosomal region spanning PVT1 exons 4A and 4B to be highly differentiated between African and non-African populations. We further investigated levels of gene expression of PVT1 exons 4A and 4B and observed significant overexpression of these exons in PCa tissues relative to benign prostatic hyperplasia and to normal prostate tissues obtained from men of African ancestry. These results indicate that PVT1 exons 4A and 4B may have clinical implications in PCa a conclusion supported by the observation that transient and stable overexpression of PVT1 exons 4A and 4B significantly induce greater prostate epithelial cell migration and proliferation. We anticipate that further exploration of the role of PVT1 exons 4A and 4B may lead to the development of diagnostic, therapeutic, and other clinical applications in PCa.

Background: The existing body of literature suggests that modifiable lifestyle behaviors such as alcohol consumption and dietary behaviors were linked to viral hepatitis B/C and liver cancer. So far, most of the liver cancer awareness campaigns and behavioral interventions have focused on preventive behaviors such as screening, vaccination, and early diagnosis. Not enough efforts have been made to raise awareness of behavioral mechanism of liver cancer prevention, especially in the medically underserved populations. Methods: We used the community-based participatory research (CBPR) approach to implement an education initiative regarding the promotion of liver cancer among the African, Asian, and Hispanic populations within the Philadelphia metropolitan area and New York City. In this study, we used data from the pre-education surveys and follow-up assessments at 6 months post-education to assess the changes in dietary behaviors and alcohol consumption among participants. Results: The study sample includes 344 participants recruited through community-based organizations. The sample consists of 31 African Americans, 174 Asian Americans, and 139 Hispanic Americans. Among the African Americans participants, the consumption of scores such as fruits (2.710 to 3.581) and poultry (2.613 to 3.677) increased significantly, while vegetables and red meats decreased. In Asian Americans, the consumption of non-refined cereals (3.362 to 4.282), red meats (2.655 to 3.195), and dairy (2.851 to 3.701) products decreased. Lastly, among the Hispanic American participants poultry (2.173 to 3.554), dairy products (2.101 to 3.863), and olive oil (3.022 to 3.849) increased, as well as the consumption of alcohol. Conclusion: This community-based educational imitative generated different impacts in the three populations, further highlighting the needs for more targeted, culturally tailored efforts in health promotion among these underprivileged communities. Citation Format: Tamar Tertulien, Ellen J. Kim, Wenyue Lu, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-Chin Yeh, Lin Zhu, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Reducing liver cancer risk through dietary change: Positive results from a community-based educational initiative in three racial/ethnic groups [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C069.

Background: Colorectal cancer (CRC) screening such as colonoscopy and stool test has been shown to be effective in reducing CRC burden, especially in the underprivileged communities. However, CRC awareness and screening uptake remained suboptimal, especially in racial/ethnic minority populations and non-Hispanic whites. Both CRC incidence and mortality rates are highest in non-Hispanic blacks (approximately 20% and 40%, respectively), and CRC screening uptake rates are lower in racial/ethnic minorities relative to non-Hispanic whites (NHWs). The cause for the disparities in incidence and mortality is multifactorial. One important aspect is the suboptimal knowledge and awareness of risk factors. Methods: To increase awareness of CRC prevention and screening, we collaborated with community-based organizations (CBOs) to develop culturally tailored educational materials targeting African/Black Americans (BAs), Asian Americans (AAs), and Hispanic Americans (HAs). The topics included essential CRC and screening knowledge, a healthy diet (Mediterranean diet), and at-home workout routines. Eligible participants from the Greater Philadelphia area and New York City participated in one-time education. Pre- and post-intervention surveys were designed based on the Colorectal Cancer Quiz provided by the Centers for Disease Control and Prevention (CDC) and were administered to assess the immediate impact of the educational sessions. Results: The analysis sample included 413 participants, among which 388 completed the post-survey. One in ten (10.3%) reported a family history of CRC, and a half (50.6%) had never had a colonoscopy. The baseline CRC knowledge score was 9.5 out of 16, indicating a moderately low level of knowledge. Participants scored particularly low on the age of CRC screening initiation, needs for screening even without symptoms, and the impact of physical activity on CRC risk. The knowledge score significantly increased to 10.9 (p < .001) at post-survey, indicating a significant impact of the educational workshops. Conclusion: The findings of our project confirm that the CRC screening rates are low in racial/ethnic minorities compared to the U.S. national rate of 71.6%. Meanwhile, it also confirmed that culturally tailored, community-based educational initiatives can effectively raise knowledge of CRC in medically underserved populations. Citation Format: Ellen J. Kim, LIn Zhu, Wenyue Lu, Safa Ibrahim, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-Chin Yeh, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Increasing knowledge of colorectal cancer (CRC) risk factors and screening through a community-based education initiative [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B056.

African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the U.S. Factors that may be contributing to these high rates, however, remain poorly understood. Specifically, this study assessed the relationship between dietary habits and colorectal cancer screening behavior and intent among individuals who identify as Black, with their ethnicity as African-American, Caribbean, and African. There are many factors that influence dietary habits, and a salient factor is culture. Many studies have experienced challenges recruiting in communities of color for various reasons. The purpose of this presentation is to describe recruitment methods utilized for this study in the midst of the COVID-19 pandemic, and to discuss challenges, strategies that were implemented and lessons learned that can inform and improve future recruitment efforts. Effective recruitment strategies included partnership, consistent engagement, and meeting people in places where they frequent and felt comfortable. Utilizing faith-based locations, barbershops, hair salons, and pivotal community locations allowed individuals to trust the researchers, and also eliminated the need to retain study subjects over a period of time, due to on-site data collection. Though our findings are limited to Black families in predominantly minority neighborhoods, we have identified successful strategies for this specific high-risk population and potentially similar others. Citation Format: Cicely K. Johnson, Grace X. Ma, May May Leung, Olorunseun O. Ogunwobi. Effective recruitment strategies utilized in the midst of a COVID-19 pandemic to examine dietary practices and colorectal cancer screening practices of Blacks in New York City [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B037.

Background Hispanic, Asian, and African Americans experience greater burden of liver cancer, and research has shown that these three populations experience multiple level barriers to liver cancer awareness and prevention. Chronic infections with hepatitis B (HBV) and hepatitis C virus (HCV) are the most common risk factors of liver cancer. As a critical component of The Synergistic Partnership for Enhancing Equity in Cancer Health (SPEECH), Community Outreach Core (COC) aims to (1) strengthen community engagement in cancer outreach research through evidence-based community cancer education initiatives and outreach activities, and (2) provide a robust and sustainable community-based participatory research (CBPR) infrastructure for the SPEECH Partnership. Objectives This presentation aims to describe the use of CBPR principles and how these methods impacted the planning and implementation of multilevel community initiatives on liver cancer prevention through community engagement to address liver cancer disparities in low-income, underserved minority communities. Methods Guided by CBPR principles and built on well-established collaboration with community-based organizations in Pennsylvania, New Jersey, and New York City, the COC team actively engaged community advisory board (CAB), healthcare workers, and community members in multiple phases of (1) liver cancer prevention educational initiative, (2) city-wide bus campaign with on-bus posters advertising HBV/HCV screening and liver cancer prevention, and (3) community health fairs, in which information and education about HBV, HCV, and liver cancer was provided to the community member attendees. Results The educational workshops in the community initiative significantly improved community members’ knowledge about HBV/HCV, behaviors on HBV/HCV screening, as well as dietary patterns. Specifically, 21% of the patients who did not have an HBV test at baseline had a test at 6 months, while 11% of the patients who did not have an HCV test at baseline had a test at 6 months. In the bus campaign, the COC team collected evaluation forms from bus riders. Among the 173 respondents, 22.7% reported seeing the ad. Riders who saw the ad were significantly more likely to get screened for HBV/HCV than those who did not (86.5% vs 58.3%). Regarding the community health fair, among 44 participants who received our on-site education, 77.3% of them reported that they would talk to their doctors about getting HBV/HCV screenings. The comprehensive engagement of CAB, healthcare workers, and community members significantly benefited community capacity building on cancer research and health promotion. Conclusions Our findings indicate that CBPR-guided community initiative, campaign, and health fairs have remarkable positive impacts on promoting liver cancer awareness and prevention among underserved racial/ethnic minorities. Moreover, community participation was built on trust and previous relationships, which would finally empower the community with increased health promotion capacity. Citation Format: Wenyue Lu, Lin Zhu, Di Zhu, Evelyn Gonzalez, Marilyn A. Fraser, Ming-chin Yeh, Steven Zhu, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Promoting liver cancer awareness and prevention initiative in underserved racial/ethnic minority populations via community-based participatory research strategies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B040.

Background: The Temple University Fox Chase Cancer Center and Hunter College Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership) is a comprehensive collaborative cancer health research infrastructure in Pennsylvania, New Jersey, and New York City (PNN) Region. Its goals are to enhance equity in cancer health through rigorous and sustainable cancer research, train the next generation of researchers, and establish community outreach programs. Establishing and strengthening a bidirectional academic-community partnership is a key component of this partnership. While such collaborative relationships have been strongly endorsed by the National Institutes of Health (NIH), little has been documented demonstrating how such partnership can be created and maintained. Objectives: Building on previous established collaborative relationships with the community-based organizations (CBOs), we created and expanded a bidirectional, academic–community partnership in African American, Asian American, and Latinx communities in the PNN region to (1) assess the level of awareness of cancer prevention knowledge; (2) identify community needs and barriers to cancer prevention healthcare services; (3) jointly develop and implement community-based educational initiatives to promote cancer prevention in medically underserved communities. Methods: In this presentation, we established a comprehensive evaluation metric to assess the bidirectional partnership. The metric, its outputs, and outcomes were adapted from the Evaluation Metrics Manual published by the National Institute of Environmental Health Services of NIH. We also formed a Community Advisory Board (CAB) to guide our bidirectional communication and jointly develop a community-driven cancer education agenda. Results: The CAB played a critical role in the development of the bidirectional partnership. They provided key inputs in identifying the goals and benchmarks of the educational initiative, and in facilitating the recruitment and implementation of the initiative. Our evaluation indicated that a bidirectional partnership is an interactive and non-linear process that requires constant feedback and communication. We identified several successes and challenges during our co-learning and co-implementing process. We also identified areas for improvement, specifically, establishing a more efficient channel for information and resource sharing, and greater efforts on dissemination of scientific findings to the community. Conclusions: Actively engaging CAB and CBOs in the cancer prevention educational initiatives from the onset enhanced the efficacy of the initiatives and strengthened the research training capacity of the academic institutions. We will share best practices in our bidirectional, academic–community partnership building and discuss next steps in adaptation and further development of the partnership. Citation Format: Lin Zhu, Ellen J. Kim, Steven Zhu, Nathaly Rubio-Torio, Evelyn González, Marilyn A. Fraser, Ming-chin Yeh, Marsha Zibalese-Crawford, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Evaluating a bidirectional academic–community partnership with multiple racial/ethnic communities for cancer prevention initiatives and cancer health disparities research [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR010.

Objective Susceptibility of patients with cancer to COVID-19 pneumonitis has been variable. We aim to quantify the risk of hospitalisation in patients with active cancer and use a machine learning algorithm (MLA) and traditional statistics to predict clinical outcomes and mortality. Design Retrospective cohort study. Setting A single UK district general hospital. Participants Data on total hospital admissions between March 2018 and June 2020, all active cancer diagnoses between March 2019 and June 2020 and clinical parameters of COVID-19-positive admissions between March 2020 and June 2020 were collected. 526 COVID-19 admissions without an active cancer diagnosis were compared with 87 COVID-19 admissions with an active cancer diagnosis. Primary and secondary outcome measures 30-day and 90-day post-COVID-19 survival. Results In total, 613 patients were enrolled with male to female ratio of 1:6 and median age of 77 years. The estimated infection rate of COVID-19 was 87 of 22 729 (0.4%) in the patients with cancer and 526 of 404 379 (0.1%) in the population without cancer (OR of being hospitalised with COVID-19 if having cancer is 2.942671 (95% CI: 2.344522 to 3.693425); p Conclusions Active cancer diagnosis has a threefold increase in risk of hospitalisation with COVID-19. Increased age, urea and CRP predict mortality in patients with cancer. MLA complements traditional statistical analysis in identifying prognostic variables for outcomes of COVID-19 infection in patients with cancer. This study provides proof of concept for MLA in risk prediction for COVID-19 in patients with cancer and should inform a redesign of cancer services to ensure safe delivery of cancer care.

Glioblastoma is the most fatal of all primary human brain tumors with 14 months survival, at best. The mainstay therapy for this tumor involves temozolomide, surgery, radiotherapy and tumor treating electric field. Cancer resistance to commonly available chemotherapeutics remains a major challenge in glioblastoma patients receiving treatment and unfavorably impact their overall survival and outcome. However, the lack of progress in this area could be attributed to lack of tools to probe unbiasedly at the genome wide level the coding and non-coding elements contribution on a large scale for factors that control resistance to chemotherapeutics. Understanding the mechanisms of resistance to chemotherapeutics will enable precision medicine in the treatment of cancer patients.CRISPR Cas9a has emerged as a functional genomics tool to study at genome level the factors that control cancer resistance to drugs. Recently, we used genome wide CRISPR-Cas9a screen to identify genes responsible for glioblastoma susceptibility to etoposide. We extended our inquiry to understand genes that control glioblastoma response to temozolomide by using genome scale CRISPR. This study shows that the unbiased genome-wide loss of function approach can be applied to discover genes that influence tumor resistance to chemotherapeutics and contribute to chemoresistance in glioblastoma.

Nop2/Sun RNA methyltransferase (NSUN6) is an RNA 5 - methyl cytosine (5mC) transferase with little information known of its function in cancer and response to cancer therapy. Here, we show that NSUN6 methylates both large and small RNA in glioblastoma and controls glioblastoma response to temozolomide with or without influence of the MGMT promoter status, with high NSUN6 expression conferring survival benefit to glioblastoma patients and in other cancers. Mechanistically, our results show that NSUN6 controls response to TMZ therapy via 5mC mediated regulation of NELFB and RPS6BK2. Taken together, we present evidence that show that NSUN6 mediated 5mC deposition regulates transcriptional pause (by accumulation of NELFB and the general transcription factor complexes (POLR2A, TBP, TFIIA, TFIIE) on the preinitiation complex at TATA binding site to control translation machinery in glioblastoma response to alkylating agents. Our findings open a new frontier into controlling of transcriptional regulation by RNA methyltransferase and 5mC.

In this multidisciplinary study, we explored relationships between demographic factors, dietary habits and gallic acid, a polyphenolic biomarker that correlates with self-reported dietary behaviors and negatively correlates with the incidence of cancer. Thirty-three (33) participants were recruited from a senior center in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH)-validated survey questionnaire was used to gather dietary behavior data, alongside demographic and cancer history information. Urine samples were obtained from participants for analyzing gallic acid content level. All 33 recruited participants completed the survey and twenty-five (25) of them provided urine samples for gallic acid analysis. Associations between demographic factors and intake of certain foods were observed. Specifically, age was negatively associated with French fries/fried potatoes, cooked dried beans, and tomato soup intake (p

Emerging data indicate that the nervous system plays an important role in carcinogenesis. However, more studies are required to help further elucidate the mechanisms involved in the neural regulation of carcinogenesis. Some recent findings describing the neural regulatory mechanisms of action in prostate cancer, pancreatic cancer and hepatocellular carcinoma are discussed, with a focus on the sympathetic, parasympathetic, and sensory neuronal elements of the nervous system. Norepinephrine, which is released by the sympathetic nervous system and binds to the beta-adrenergic receptor, regulates cellular responses in both normal and tumor cells. It has also been shown that the destruction of sensory neurons can prevent or at least slow pancreatic cancer. Cortisol, the main stress hormone, is also discussed and how it could potentially be involved in hepatocellular carcinoma development. The importance of studying other signaling molecules in the nervous system, such as oxytocin and its receptor, the oxytocin receptor, and how they might be involved in carcinogenesis when aberrantly expressed is highlighted. This is an area of study which clearly needs further investigation. A clearer understanding of the detailed mechanisms of how the nervous system is involved in carcinogenesis could potentially aid in the identification of novel biomarkers and development of novel preventative and therapeutic strategies in various cancers.

PURPOSE: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related deaths with a very poor prognosis. Consequently, there is an urgent need for better understanding the molecular mechanisms, novel prognostic biomarkers, and more effective treatment options. There is an emerging link between oxytocin (OXT), the oxytocin receptor (OXTR), and cancer. However, the role of OXT or the OXTR in HCC remains unknown. The research question of this study was: Are there genetic alterations in the oxytocin (OXT) and oxytocin receptor (OXTR) genes in hepatocellular carcinoma (HCC) patients and do these alterations impact overall survival and disease-free survival. METHODS: In this retrospective study, we reviewed 360 individual HCC patient data from The Cancer Genome Atlas (TCGA) using cBioPortal accessed in April 2018. The data in The Cancer Genome Atlas are from various institutions in the United States RESULTS: We found that 3% (11 of 360) of cases showed genetic alterations in the OXTR gene. The median months survival was lower for HCC cases with genetic alterations in the OXTR gene as compared to cases without genetic alteration in this gene (33.0 versus 60.84, respectively. Additionally, the median months disease-free survival was lower in cases with genetic alterations in the OXTR gene as compared to cases without alterations (8.64 versus 21.55, respectively). CONCLUSIONS: OXTR is a promising prognostic biomarker for HCC, and OXTR antagonists could have a future role as therapeutic agents for a subset of HCC patients. Further study of the detailed molecular mechanisms of OXT and OXTR in HCC is warranted.

Foreign-born African immigrants bear a large burden of hepatitis B virus (HBV)-related liver disease in the U.S. However, HBV awareness and knowledge of HBV screening and vaccination among this population is limited. This study aimed to provide a better understanding of HBV burden in this vulnerable population and to identify risk factors for the implementation of more effective prevention and treatment programs. We conducted a cross-sectional survey among 71 first-generation African Americans in New York City. Participants’ sociodemographic characteristics, HBV screening and vaccination history, knowledge of HBV transmission, and other related issues were asked. The study sample included 46 men and 23 women, with an average age of 32.75. Of the sample, 87.50% participants migrated from sub-Saharan Africa and 79.10% had lived in the U.S. for 10 or fewer years. Almost half of participants never underwent HBV screening (44.29%) or HBV vaccination (49.23%). About two-thirds (60.87%) of participants never received any HBV screening or vaccination recommendation from doctors. Multivariable analysis results showed that having a college degree and being currently married were significantly associated with HBV screening, while having health insurance was significantly associated with HBV vaccination. Survey data further indicated that first-generation African immigrants had very limited knowledge of HBV transmission, suggesting that this population would benefit from greater awareness of HBV risk factors and modes of transmission. The influence of education, marriage and spousal support, and access to health insurance on HBV screening and vaccination should be noted and further examined in future public health interventions and research.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells, immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.

Minority populations disproportionately bear the burden of cancers in the United States of America. The Synergistic Partnership for Enhancing Equity in Cancer Health (SPEECH) was established to focus on research, workforce development and community-based activities relevant to cancer health disparities in the Philadelphia-New Jersey-New York City (PNN) corridor. SPEECH’s overarching goal is to impact cancer health disparities through research and training, and by improving community health, cancer awareness, and access to good quality healthcare.

Prostate cancer (PCa) is the most commonly diagnosed solid organ cancer in men worldwide. Current diagnosis of PCa includes use of initial prostate specific antigen assay which has a high false positive rate, low specificity, and low sensitivity. The side effects of unnecessary prostate biopsies that healthy men are subjected to, often result in unintended health complications. New PCa biomarkers are being discovered to address this unmet need. Here, we report on the creation of a composite score (Prostac) based on three recently discovered PCa biomarkers, Plasmacytoma Variant Translocation 1 (PVT1) exons 4A, 4B, and 9. Statistical analysis of copy numbers derived from a real-time quantitative polymerase chain (qPCR) reaction - based assay, showed these PCa biomarkers to be linearly separable and significantly over expressed in PCa epithelial cells. We train a supervised learning algorithm using support vector machines to generate a classification hyperplane from which a user-friendly composite score is developed. Cross validation of Prostac using data from prostate epithelial cells (RWPE1) and PCa cells (MDA PCa 2b) accurately classified 100% of PCa cells. Creation of the Prostac score lays the groundwork for clinical trial of its use in PCa diagnosis.

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors in vivo. To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced in vitro and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.

BACKGROUND: Breast lymphomas are rare extranodal lymphomas. They constitute a tiny percentage of malignant tumors of the breast and a small subset of extranodal lymphomas. The rarity of breast lymphomas is attributed to the very scanty lymphoid tissue content of the chest wall. AIMS OF STUDY: This case report aims to provide an up-to-date review of the literature on breast lymphomas and clinicians to consider the possibility of this disease entity while treating a breast mass. CASE PRESENTATION: A case is reported of primary mammary non-Hodgkin lymphoma in a 52-year-old man. Fine needle aspiration cytology (FNAC) was inconclusive. Incisional biopsy-confirmed primary breast lymphoma was diagnosed as the diffuse large B-cell type: non – Hodgkin lymphoma. He had complete disease remission in response to chemotherapy – Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (CHOP). After that, the patient did not require further surgical intervention. He was followed up at two-monthly intervals for eighteen months in the surgical outpatient clinic with no disease recurrence and satisfactory clinical outcome, following which he discontinued follow-up visits. CONCLUSION: While assessing breast masses, clinicians must recognize primary non-Hodgkin lymphoma as a potential differential diagnosis. A core biopsy of breast masses is needed to exclude it, and appropriate treatment must be given if diagnosed.

Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to primary tumor cell lines. Whether increased FN1 expression is directly required for CTC migration, and the specific role of FN1&rsquo, s regulation of integrin B1 (ITGB1) and SLUG (SNAI2) in CTC migration remains unclear. Here, for the first time, we report that the knockdown of FN1, ITGB1, or SLUG expression in CTCs leads to a significant decrease in CTC migration. Knocking down two or all three of these proteins simultaneously did not further inhibit migration. We observed a corresponding increase in CTC migration when recombinant FN1 was added to CTCs. This effect was significantly impeded by prior knockdown of ITGB1 or SLUG. Using knock down experiments and western blotting analysis, we confirmed FN1&rsquo, s regulation of ITGB1 and SLUG to occur via two separate, independent pathways. Consequently, we can conclude that FN1-dependent enhanced migration of CTCs requires downstream signaling through either ITGB1 or SLUG and that FN1 regulation of ITGB1 and SLUG may have important implications for cancer progression and metastasis.

PurposeDiet and nutrition are important for cancer prevention. To investigate associations between dietary behavior, demographics, and risk of cancer, we assessed dietary behavior and urinary concentration of gallic acid, a polyphenol with anticancer properties found in various fruits and vegetables, in racial and ethnic minorities.MethodsNinety-one (91) participants were recruited from senior centers in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH)—validated dietary survey questionnaire—was used to collect dietary fruits and vegetables consumption data. Demographic and cancer information were also collected. All 91 participants completed the survey and forty-five (45) participants provided urine samples for gallic acid analysis.ResultsGender differences were significantly associated with dietary behavior and urinary gallic acid concentration (UGAC). Female participants had a higher total daily intake of fruits and a significantly higher UGAC compared to male participants (p p p p p ConclusionThe observed differences in dietary behavior and UGAC in this study provide limited information on the association between demographic differences and cancer prevalence in elder racial and ethnic minorities. Future research should investigate this association further for potential implications in cancer prevention.

Pancreatic ductal carcinoma has a 5-year survival rate of 9%. This makes it the 4th leading cause of cancer-related death in the United States. Advanced-stage diagnosis and limited treatment options contribute to poor prognosis. Thus, there is an urgent need for new approaches to treatment. Enhancer of Zeste 2 (EZH2), a catalytic subunit of the multi-protein histone methyltransferase, known as the polycomb repressive complex, has been implicated in carcinogenesis. E2H2's downregulation has been shown to have a therapeutic effect in B cell lymphomas.We examined the effect of EZH2 downregulation in combination with irradiation on the proliferation and apoptosis of pancreatic cancer cells (PANC-1 and MIA PaCa-2)EZH2 downregulation resulted in the decreased proliferation of PANC-1 and MIA PaCa-2 cells within short-term assays with maximal reduction at 72 hr. Irradiation reduced cell proliferation beginning at 96 hr and continued over the long-term. Irradiation with EZH2 downregulation reduced cell proliferation between 48 and 72 hr. This combined treatment reduced cell proliferation by 3 to 14% as compared to those treated with irradiation alone at two weeks. PANC-1 and MIA PaCa-2 cells exhibited similar responses to EZH2 downregulation and irradiation, but to different degrees. siRNA or EPZ were equally effective in EZH2 downregulation.EZH2 downregulation in combination with irradiation reduces PANC-1 and MIA PaCa-2 cell proliferation more than irradiation alone. This study affirms the role of EZH2 downregulation for radiosensitization in pancreatic cancer treatment.

Background: Though a largely preventable disease, liver cancer is now the fastest-increasing cause of cancer death in the US, and it is highly fatal. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and it disproportionally affect racial/ethnic minorities, especially the medically underserved. Most HCC cases are associated with hepatitis B virus (HBV) and hepatitis C virus (HCV). Methods: To increase awareness of liver cancer prevention and screening, we partnered with community-based organizations through NCI funded U54 TUFCCC/HC Cancer Partnership Community Outreach Core, in the greater Philadelphia metropolitan and New York City to design and conduct a liver cancer prevention project. Pre- and post- survey data was collected from underserved Asian, African, and Hispanic American community members who participated in educational workshops. This abstract will report the 473 eligible participants' knowledge on HBV, HCV, and liver cancer both before and after the education. We conducted wilcoxon Signed-rank, Kruskal-Wallis, and Wilcoxon sum-rank tests. Results: Knowledge of risk factors increased significantly in all three communities from the pre-survey to the post-intervention survey (2.15 vs. 3.69, p Citation Format: Wenyue Lu, Lin Zhu, Safa Ibrahim, Kerry Traub, Ellen Kim, Ada Wong, Nathaly Rubio-Torio, Evelyn Gonzalez, Marilyn A. Fraser, Ming-Chin Yeh, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Increasing liver cancer prevention knowledge through a community-based education initiative to improve liver cancer prevention for underserved African, Asian, and Hispanic communities [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-058.

Background: The Temple University Fox Chase Cancer Center and Hunter College Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership) is a collaborative effort to develop a regional comprehensive collaborative cancer health equity research infrastructure in Pennsylvania, New Jersey and New York City (PNN) Region and to establish rigorous and sustainable cancer research, education, and outreach programs at both institutions. One key component of the training efforts of this Partnership is the annual Summer Cancer Research Institute (SCRI), an 8-week intensive summer program that includes hands-on research training in laboratories or research centers under the mentorship of established investigators supplemented with cancer seminars, skill-building workshops, journal clubs, social activities, poster sessions and presentations. Methods: The goal of this study was to evaluate the recruitment process and the outcome of the first three cohorts of the SCRI. We assessed the previous recruitment and implementation process to identify successes and lessons learned. We also conducted program evaluation through pre-program and post-program evaluation, and long-term annual follow-up survey, and other formal and informal feedback among the 3 cohorts from the previous 3 years. Results: Through targeted multi-institutional recruitment strategies and by utilizing social media (e.g., Twitter, Instagram, institutional newsletters), the program received increasing numbers of applications each year, from 64 applications received in 2019, to 179 in 2020, and 345 in 2021. The number of students accepted were 10 in 2019 (admission rate 15.6%), 10 in 2020 (5.6%), and 15 in 2021 (4.3%). Among the 34 SCRI trainees, 10 (29.4%) identified as Black/African American, 6 (17.5%) as Hispanic/Latinx, 10 (29.4%) as Asian, and the rest as non-Hispanic white. Students come from a variety of majors, including biology, nutrition, biochemistry, bioengineering, public health, sociology, and medical geography. The SCRI trainees reported a high level of satisfaction with the overall SCRI program as well as the specific seminars, workshops, and journal clubs. The long-term follow-up survey data showed that among the first two cohorts (20 trainees), 4 applied to graduate or medical school, 9 completed graduate school, and 7 accepted a full-time or part-time job position. Trainees particularly enjoyed the hands-on experience in basic, translation, and population research, the skill-building workshops, and the annual symposium to gain presentation experience. Conclusion: The Partnership evaluation has identified strengths (e.g., hands-on research experience under established mentorship, multidisciplinary training) for implementing the SCRI program. Updates are being made to refine recruitment processes and adjust program components. Citation Format: Lin Zhu, Gargi Pal, Taylor Kazaoka, Rubia Shahbaz, Marsha Zibalese-Crawford, Sarah-Jane Dodd, Carolyn Y. Fang, Yin Tan, Grace X. Ma, Olorunseun O. Ogunwobi. Educating the next generation of cancer researchers: Evaluation of a cancer research partnership research training program [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-212.

Background: There is an increasing body of literature that suggests a relationship between modifiable dietary behaviors and alcohol use and liver cancer. We designed and implemented a culturally tailored community-based education program to promote liver cancer prevention. Methods: Through NCI funded U54 TUFCCC/HC Cancer Partnership Community Outreach Core program, using CBPR approach, we engaged community-based organizations and community stakeholders serving underserved African, Asian, and Hispanic American communities in the Philadelphia metropolitan area and New York City. The community-based education incorporated in-person and virtual hybrid education workshops to address COVID-19 pandemic barriers. We conducted pre-education surveys and follow-up assessments at 6 months post-education. Participants' dietary behaviors, alcohol use, and sociodemographic characteristics were examined at both time points. Results: 526 participants were recruited including 92 African Americans, 247 Asian Americans, and 187 Hispanic Americans, with an average age of 59. We found that at 6-month follow-up assessment, participants had average decreased intake of red meat (3.148/6 vs. 2.685/6, p < 0.001), and average increased intake of vegetables (4.484/6 vs. 5.044/6, p < 0.001) and fruits (4.327/6 vs. 4.877/6, p < 0.001), compared to their intake at pre-education assessment. Additionally, average change in beer (-0.252) and spirit (-0.905) consumption substantively decreased from pre-intervention to 6-month follow-up assessment. Conclusion: This community-based education showed significant effects in improving healthy dietary behaviors and reducing alcohol intake among community members through CBPR community engagement from the two metropolitan areas. Future efforts are needed to sustain the positive changes in modifiable lifestyle behaviors and liver cancer prevention in these medically underserved communities. Citation Format: Tiffany Li, Wenyue Lu, Lin Zhu, Ellen Kim, Kerry Traub, Steven Zhu, Nathaly Rubio-Torio, Evelyn Gonzalez, Marilyn A. Fraser, Ming-Chin Yeh, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. A community-based liver cancer education initiative led to healthier dietary and alcohol use behaviors among racial/ethnic minority community members [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-161.

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (mCRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). Resistance to second generation ADTs leads to the progression to AR-independent treatment related-neuroendocrine PCa (t-NEPC), which is observed in nearly 1 in 5 men with mCRPC and is associated with very poor outcomes. PCa neuroendocrine differentiation (PCND) occurs in t-NEPC that is characterized by amplification of Aurora A kinase (AurA). However, the mechanisms that drive t-NEPC are poorly understood. Further understanding PCND in ADT resistance may prevent poorer outcomes. The 8q24 chromosomal locus is an important PCa susceptibility region containing genetic variants associated with increased PCa incidence and aggressiveness. PVT1 is a gene located within this region that encodes microRNA-1205 (miR-1205), whose function is largely unknown. We previously reported miR-1205 underexpression in a cohort of histologically confirmed PCa tissue when compared to normal tissue and that exogenous miR-1205 significantly inhibited tumor growth in CRPC in vivo, suggesting that miR-1205 is a tumor suppressor. To understand the molecular mechanism of miR-1205, we first identfied Fry-like (FRYL) as a direct molecular target of miR-1205. FRYL is predicted to regulate dendritic branching which led us to hypothesize that it is involved in PCND. A Weill Cornell Medicine cohort of 29 benign prostate, 66 localized PCa, 73 CRPC, and 36 NEPC samples whose transcriptome was profiled by RNA-seq, we observed significant overexpression of FRYL in NEPC when compared to localized PCa and benign prostate. After validating FRYL as a target, we examined miR-1205 regulation of FRYL in PCND by culturing LNCaP androgen sensitive PCa cells under androgen deprivation conditions. We observed FRYL mRNA overexpression and significant underexpression of miR-1205 in LNCaP-PCND cells when compared to undifferentiated LNCaP cells. To further characterize this mechanism, miR-1205 was inhibited in RWPE-1 non-tumorigenic and LNCaP cells. As a result, FRYL and AurA protein expression was increased along with NEPC marker expression (Neuron specific enolase 2) when compared to cells transfected with a negative control, suggesting that miR-1205 targets FRYL and AurA to promote PCND. However, RNA pulldown analysis showed that AurA is not a direct target of miR-1205. We observed that FRYL and AurA interaction occurs in LNCaP but not in RWPE-1 cells via co-immunoprecipitation. Interestingly, transfection with miR-1205 mimic inhibits FRYL expression, but not AurA in LNCaP. However, miR-1205 mimic inhibits AurA binding to FRYL. Altogether, these data show that miR-1205 modulates FRYL:AurA protein interaction suggesting that miR-1205 regulation of FRYL:AurA interactions may be important in PCND and t-NEPC. Citation Format: Michelle K. Naidoo, Fayola Levine, Princesca Dorsaint, Andrea Sboner, Olorunseun Ogunwobi. MicroRNA-1205 modulates FRYL/Aurora A kinase protein-protein interaction in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2363.

Summary: Prostate cancer (PCa) is the most commonly diagnosed solid organ cancer in men worldwide. Current diagnosis of PCa includes use of initial prostate specific antigen assay which has a high false positive rate, low specificity, and low sensitivity. Consequently, it results in overdiagnosis and overtreatment, leaving patients with unintended health complications from the side effects of unnecessary prostate biopsies and treatment. PCa biomarkers are being discovered to address this unmet need. Here, we report creation of a composite score based on three PCa biomarkers, plasmacytoma variant translocation 1 exon 4A, exon 4B, and exon 9. Statistical analysis of copy numbers derived from a real-time quantitative polymerase chain reaction - based assay showed these PCa biomarkers to be linearly separable. We trained a supervised learning algorithm using support vector classifiers to generate a classification hyperplane from which a composite score is developed. Our aggregate score when applied to test data from non-cancerous prostate epithelial cells and PCa cells accurately classified 100% PCa cells. Creation of this 3-biomarker based composite score lays the groundwork for clinical trial of its use in PCa diagnosis. Citation Format: Gargi Pal, Emmanuel Asante-Asamani, Leslie Liu, Olorunseun O. Ogunwobi. Computation of a user-friendly composite score from three prostate cancer biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2391.

Triple negative breast cancer (TNBC) is a lethal molecular subtype of invasive breast cancer (BC) that is ER-, PR- and HER2-. Claudin low (CL) TNBC, a distinct molecular subtype of TNBC, has the worst prognosis compared to other BC subtypes. Aberrant expression of claudin proteins disrupts the function of tight junctions. Consequently, inducing epithelial-to-mesenchymal transition (EMT) in cancers, an important factor for enhanced motility and metastasis. Therefore, understanding the molecular mechanisms that modulate claudin expression in TNBC is crucial. The 8q24 genomic locus is an important cancer susceptibility locus that is associated with poor clinical outcomes in cancer due to common amplification events that occur in many malignant diseases. This locus contains the PVT1 gene, which encodes a long noncoding RNA (lncRNA) that has been implicated in multiple cancers including BC. PVT1 consists of 12 exons that are alternatively spliced to generate lncRNAs. Although previous research has implicated PVT1 as an important player in BC, the underlying molecular mechanisms of PVT1 in CL TNBC is unknown. To examine the role of PVT1 in CL TNBC, we assessed PVT1 expression in T47D (ER+), MDA MB 231 (CL) and MDA MB 468 (claudin high (CH)) BC cells. We observed that PVT1 exons 4A, 4B, and 9 are significantly overexpressed in CL MDA MB 231 and significantly underexpressed in CH MDA MB 468 in comparison to T47D cells, suggesting a protumorigenic role of PVT1 in CL TNBC. We analyzed the functional consequences of siRNA targeting of PVT1 exon 9 expression in CL TNBC cells. siRNA targeting of PVT1 exon 9 expression in the MDA MB 231 CL TNBC cells led to a significant reduction in migration and the re-expression of claudin 4. To determine the role of PVT1 on EMT, we assessed the expression of EMT markers (vimentin, fibronectin, and E-cadherin) in MDA MB 231 cells. We observed no changes in the expression of EMT markers when PVT1 exon 9 is knocked down. However, our data show that mesenchymal markers are more highly expressed in MDA MB 231 cells in comparison to MDA MB 468 cells. Further, knockdown of PVT1 exon 9 did not induce apoptosis in MDA MB 231 cells as assessed by caspase 3 and caspase 9 expression. Taken together, our data indicate that PVT1 exon 9 regulates claudin expression and migration in CL TNBC, and may have implications for clinical outcomes in TNBC. Citation Format: Fayola A. Levine, Olorunseun O. Ogunwobi. Targeting PVT1 exon 9 transcript is not pro-apoptotic but induces claudin 4 expression and inhibits migration in triple negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2387.

One of six deaths globally is due to cancer. In 2018, prostate cancer (PCa) represented 1.28 million cases worldwide, the second most frequent cancer diagnosis and fifth leading cause of death in men. Currently, the mortality rate of PCa has experienced a steady increase due to the progression of metastatic castration-resistant prostate cancer (mCRPC). As an androgen driven disease, androgen deprivation therapies (ADTs) have been employed for treatment. However, despite ADTs, mCRPC develops by maintaining AR signaling, which can eventually lead to progression of AR-independent neuroendocrine PCa (NEPC). NEPC is observable in 1 in 5 men with mCRPC and associated with poor outcome. Therefore, further understanding the mechanisms of progression to mCRPC and NEPC is required. The 8q24 human chromosomal region associated with Increased PCa incidence and aggressiveness contains the PVT1 (Plasmocytoma Variant Translocation 1) locus. The PVT1 locus encodes six microRNAs, including microRNA-1205 (miR-1205) in PCa. Our laboratory previously confirmed that miR-1205 is underexpressed in PCa tissue in comparison to normal prostatic tissue and in CRPC cells in comparison to non-CRPC cells. To understand the molecular mechanism of miR-1205, we performed RNA pull down and RNA sequencing analysis to identify miR-1205 molecular targets in non-tumorigenic RWPE-1 prostate epithelial cells and PCa cells (MDA PCa 2b (metastatic PCa), PC-3 (NEPC), and C4-2B (CRPC)). We identified one cut homeobox 2 (ONECUT2 or OC2) as a direct molecular target of miR-1205. ONECUT2 is a master regulator of transcriptional factors that drives NEPC by through regulating hypoxia signaling or inducing neuroendocrine markers. ONECUT2 enrichment was approximately 3-fold higher in RWPE-1 (P=0.26), 2-fold in PC-3 (P=0.06), 1-fold in C4-2B (P=0.05) and MDA PCa 2b (P=0.02) cells. The significant binding of miR-1205 to ONECUT-2 in the PC-3 NEPC cell line suggests that miR-1205 regulation of ONECUT2 may be an important molecular mechanism in NEPC. Consequently, further study of miR-1205 and ONECUT2 in NEPC is required. Citation Format: Bachelard Dieujuste, Michelle Naidoo, Olorunseun Ogunwobi. MicroRNA-1205 directly targets ONECUT2 in neuroendocrine prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2364.

OBJECTIVE We evaluated the influence of psychosocial factors on HBV screening. METHODS Sample consisted of 1716 Vietnamese participants in our previous HBV intervention trial, recruited from 36 community-based organizations in Pennsylvania, New Jersey, and New York City between 2009 and 2014. Using the Health Belief Model and Social Cognitive Theory, we measured self-efficacy, knowledge, perceived barriers, perceived benefits, perceived severity, and risk susceptibility. Analysis of covariance was used to compare pre- and post-intervention changes of psychosocial variables. Structural equation modeling was used to explore the direct and indirect effects of the psychosocial variables on HBV screening. RESULTS Knowledge, self-efficacy, perceived benefits, and perceived barriers were directly associated with HBV screening; knowledge had the strongest effect. Perceived severity and risk susceptibility had indirect association with HBV screening through other variables. Indirect paths among the 6 psychosocial variables were also identified. CONCLUSION To promote HBV screening among Vietnamese Americans, intervention efforts should focus on increasing knowledge, self-efficacy, and perceived benefits, decreasing perceived barriers, and accounting for the dynamic cognitive processing.

Prostate cancer is the second most commonly diagnosed male cancer in the world. The molecular mechanisms underlying its development and progression are still unclear. Here we show analysis of a prostate cancer RNA-sequencing dataset that was originally generated by Ren et al. [3] from the prostate tumor and adjacent normal tissues of 14 patients. The data presented here was analyzed using our RNA-sequencing bioinformatics analysis pipeline implemented on the bioinformatics web platform, Galaxy. The relative expression of fibronectin (FN1) and the androgen receptor (AR) were calculated in fragments per kilobase of transcript per million mapped reads, and represented in FPKM unit. A subanalysis is also shown for data from three patients, that includes the relative expression of FN1 and AR and their fold change. For interpretation and discussion, please refer to the article, "miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin" [1] by Das et al.

Background One of the most important susceptibility loci for cancer is the 8q24 human chromosomal region. The non-protein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in prostate cancer. PVT1 gives rise to multiple transcripts which may have different functions. Here, we describe a real-time quantitative polymerase chain reaction (qPCR)-based assay for copy number-based quantitation of PVT1 exons 4A, 4B, and 9 to enable accurate, reproducible, and quantifiable detection. Methods PVT1 exons 4A, 4B, and 9 were cloned into a plasmid vector to create standards for subsequent creation of linear standard curves representing a broad range of concentrations. PCR was carried out using SYBR-Green signal detection to quantify PVT1 exons 4A, 4B, and 9. The efficacy of this assay was evaluated by using it to detect these transcripts in prostate epithelial and prostate cancer cell lines, normal and cancerous human prostate tissues, human serum, mouse plasma, and urine samples. Results The results indicate that the assay can be used to quantify both low and high copy numbers of PVT1-derived transcripts. This is the first report of a copy number-based quantification assay for non-invasive detection of PVT1 derived transcripts. Conclusions This novel assay holds promise for routine non-invasive testing in diseases where PVT1 is dysregulated.

Increasingly cancer is being viewed as a channelopathy because the passage of ions via ion channels and transporters mediate the regulation of tumor cell survival, death, and motility. As a result, a potential targeted therapy for cancer is to use venom peptides that are selective for ion channels and transporters overexpressed in tumor cells. Here we describe the selectivity and mechanism of action of terebrid snail venom peptide, Tv1, for treating the most common type of liver cancer, hepatocellular carcinoma (HCC). Tv1 inhibited the proliferation of murine HCC cells and significantly reduced tumor size in Tv1-treated syngeneic tumor-bearing mice. Tv1&rsquo, s mechanism of action involves binding to overexpressed transient receptor potential (TRP) channels leading to calcium dependent apoptosis resulting from down-regulation of cyclooxygenase-2 (COX-2). Our findings demonstrate the importance of modulating ion channels and the unique potential of venom peptides as tumor specific ligands in the quest for targeted cancer therapies.