bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-05-02: Conditional inactivation of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) in the mouse mammary epithelium alters mammary gland development
Authors: Sheng L , Turner AG , Tarulli GA , Barratt K , Kremer R , Morris HA , Callen DF , Anderson PH
Published: March 2017

The biologically active form of vitamin D (1,25(OH)2D) regulates proliferation, differentiation, and apoptosis in diverse cell types. We have previously identified anti-proliferative activities of 1,25(OH)2D in human breast tissue, as well as 1,25(OH)2D target gene expression consistent with reports that elevated vitamin D levels may protect against cancer. In mouse studies, vitamin D signaling modulates normal mammary gland development, including ductal outgrowth and branching, and protects against tumorigenesis. Degradation of 1,25(OH)2D is initiated by the enzyme Cyp24a1 in target tissues, providing critical local control of 1,25(OH)2D bioactivity. In vitro, blockade of Cyp24a1 activity potentiates the anti-proliferative effects of 1,25(OH)2D. However, the extent to which endogenous Cyp24a1 activity within the mammary epithelium regulates local 1,25(OH)2D levels to modulate normal mammary gland development, with possible implications for cancer, has not been investigated. We generated a novel mouse model with conditional knockout of the Cyp24a1 gene specifically in the mammary epithelium (MMTV-Cre x Cyp24a1lox/lox). Ablation of Cyp24a1 activity in the mammary epithelium does not alter either gland or body weight at 4, 6 or 10 weeks of age. Preliminary analyses of mammary gland whole mounts indicate that virgin knockout mice form fewer terminal end buds compared to glands from wild-type littermates at 4 and 6 weeks of age (P<0.05). Moreover, the width of the ducts proximal to the central lymph node of knockout mice was less than that of wild-type mice at 4 and 10 weeks of age (P<0.05 and P<0.01, respectively). In addition, the number of secondary and tertiary branching points is reduced in mammary glands from knockout mice at 6 weeks of age (P<0.05 and P<0.01, respectively). In summary, our findings suggest that Cyp24a1 activity within epithelial cells plays a crucial role to modulate postnatal mammary gland development, presumably by limiting the local accumulation of 1,25(OH)2D.

Citation Format: Sheng L, Turner AG, Tarulli GA, Barratt K, Kremer R, Morris HA, Callen DF, Anderson PH. Conditional inactivation of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) in the mouse mammary epithelium alters mammary gland development [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-05-02.
Abstract P5-07-06: A novel non-canonical Notch1-IKKα-mTORC2-AKT pathway maintains survival in triple negative breast cancer cells and cancer stem-like cells
Authors: Hossain F , Peng Y , Pannuti A , Backus K , Golde T , Osborne B , Miele L
Published: March 2017

Triple negative breast cancer (TNBC) is a heterogeneous group of clinically aggressive breast cancers. TNBC patients have high risk of recurrence and metastasis, and current treatment options remain limited. There is strong evidence for the involvement of Notch signaling in TNBC and in breast cancer stem-like cells (CSCs). Notch1 is highly expressed in Basal-like 1 (BL1) and especially Mesenchymal-Stem-Like (MSL) TNBCs. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Treatment of TNBC with dual mTORC1/2 inhibitors leads to resistance through activation of Notch1. Expression of Notch1 protein correlates with pAKT and nuclear NF-κB in TNBC. Here, we demonstrate that Notch1 promotes cell survival in MDA-MB-231 cells, representative of MSL TNBC, in part by activating NF-κB. Notch activation by Jagged1-expressing stromal cells enhances transcription of the anti-apoptotic gene cIAP-2 (BIRC3), a known NF-κB target. This event is dependent on recruitment to the cIAP-2 promoter of NF-κB subunits, IKKα and Notch1. Short term exposure of MDA-MB-231 cells (MSL, PTEN wild-type), but not MDA-MB-468 cells (BL1, PTEN-null) to recombinant Jagged1 leads to rapid AKT phosphorylation. This is suppressed by dual mTORC1/2 inhibitors, AKT inhibitors and IKKα inhibitors but not Everolimus (mTORC1-selective inhibitor). Rapid AKT phosphorylation downstream of Notch1 requires mTORC2, PI3K and IKKα, and contributes to NF-κB activation. These observations support a model where canonical and non-canonical mechanisms downstream of Notch1 trigger rapid AKT phosphorylation and NF-κB activation in PTEN wild-type TNBC cells. Both arms of this pathway require IKKα. CSCs derived from MDA-MB-231 cells have increased Notch1, pAKT and pIKKα expression. Combined pharmacological inhibition of Notch and AKT or Notch and IKKα completely blocks secondary mammosphere formation. These data and published literature suggest that: 1) IKKα connects the Notch and mTORC2/AKT pathways in some TNBC subtypes; 2) IKKα is also required for nuclear Notch1-mediated NF-kB activation and may be a critical node in the Notch signaling network; 3) A feedback mechanism may exist in some TNBC cells between mTORC2/AKT and Notch1; 4) The non-canonical Notch-IKKα-AKT pathway has a potential therapeutic role in targeting CSCs of selected TNBC subtypes.

Citation Format: Hossain F, Peng Y, Pannuti A, Backus K, Golde T, Osborne B, Miele L. A novel non-canonical Notch1-IKKα-mTORC2-AKT pathway maintains survival in triple negative breast cancer cells and cancer stem-like cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-07-06.
Abstract P6-11-12: Subgroup Analysis by prior treatment and disease burden in MONARCH 1: A phase 2 study of monotherapy abemaciclib, a CDK4 & 6 inhibitor, in patients with HR+/HER2 metastatic breast cancer (MBC) following chemotherapy
Authors: Rugo H , Nanda S , Koustenis A
Published: March 2017

Background: The MONARCH 1 (NCT0210249) study demonstrated durable single agent activity of abemaciclib in patients (pts) with HR+/HER2- breast cancer, with an objective response rate of 19.7% and median duration of response of 8.6 months1. The MONARCH 1 study population was heavily pretreated and had a high disease burden: all pts had previously received endocrine therapy and chemotherapy, had median of 3 prior systemic therapies for metastatic disease 90.2% had visceral disease and 85.6% had ≥ 2 metastatic sites.

Methods: MONARCH 1 was a phase 2 single-arm study designed to evaluate safety and efficacy of abemaciclib monotherapy in women with HR+/HER2- MBC whose disease progressed on/after endocrine therapy and chemotherapy. Abemaciclib (200 mg) was administered orally on a continuous schedule every 12 hours until disease progression. The primary objective planned to evaluate investigator-assessed objective response rate (ORR= complete response [CR] + partial response [PR]) in a sample size of approximately 128 pts) using RECIST v1.1. Subgroup analyses evaluating ORR by prior treatment and disease burden were performed.

Results: A total of 132 pts were treated with abemaciclib monotherapy. Analyses of subgroups based on prior treatment and disease burden are summarized in Table 1.

Conclusions: Abemaciclib monotherapy administered on a continuous schedule has consistent single agent activity across the subgroups analyzed.

Table 1. Objective Response Rate Subgroup Analyses Number of PatientsObjective Response (CR + PR) n(%)ITT13226 (19.7)Number of Prior chemotherapies for metastatic disease  16714 (20.9)26411 (17.2)311 (100.0)Taxane use in the metastatic setting  Yes9119 (20.9)No417 (17.1)Capecitabine use in the metastatic setting  Yes7616 (21.1)No5610 (17.9)Number of prior endocrine therapies for metastatic disease  0173 (17.6)1489 (18.8)2 or more6714 (20.9)Fulvestrant use in the metastatic setting  Yes6715 (22.4)No6511 (16.9)Number of metastatic sites  1194 (21.1)24610 (21.7)3 or more6712 (17.9)Liver metastases  Yes9320 (21.5)No396 (15.4)References: 1. Dickler, M. et al. American Society of Clinical Oncology (ASCO), abstract #510 (2016).

Citation Format: Rugo H, Nanda S, Koustenis A. Subgroup Analysis by prior treatment and disease burden in MONARCH 1: A phase 2 study of monotherapy abemaciclib, a CDK4 & 6 inhibitor, in patients with HR+/HER2 metastatic breast cancer (MBC) following chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-12.
Abstract S6-04: The PI3K inhibitor, taselisib, has enhanced potency in PIK3CA mutant models through a unique mechanism of action
Authors: Friedman LS , Edgar KA , Song K , Schmidt S , Kirkpatrick DS , Phu L , Nannini MA , Hong R , Cheng E , Crocker L , Young A , Sampath D
Published: March 2017

Alterations of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway occur broadly in cancer via multiple mechanisms including mutational activation of the PIK3CA gene. The dysregulation of this pathway has been implicated in tumor cell growth and survival, thus PI3K is a promising therapeutic target with multiple inhibitors in clinical trials. Taselisib (GDC-0032), a novel, oral, selective inhibitor of p110alpha, sparing inhibition of p110beta, is more potent against cancer cells bearing mutations in the PIK3CA gene than those with wildtype PIK3CA. The mechanism leading to this enhanced mutant selectivity is revealed in these preclinical studies.

Uniquely among PI3K inhibitors, taselisib has a gain of potency in PIK3CA mutant SW48 isogenic cells compared to wildtype SW48 parental cells. Pathway inhibition and increased apoptosis are associated with the enhanced activity observed in PIK3CA mutant cells. In PIK3CA mutant cell culture-derived and patient-derived xenograft (PDX) models taselisib induces tumor regressions. In comparison to other clinical-stage PI3K inhibitors, taselisib confers superior anti-tumor activity in PIK3CA mutant xenografts when treated at a Maximum Tolerated Dose (MTD) in vivo.

We have discovered that taselisib has a dual mechanism of action, both blocking kinase signaling and inducing down-regulation of the mutant p110alpha protein level in a dose-dependent and time-dependent manner. Taselisib treatment leads to the specific degradation of mutant p110alpha without significant change in wildtype p110alpha protein in cultured cells and in mutant xenograft models including PDX. Other clinical PI3K inhibitors, including PI3Kalpha selective and pan-PI3K inhibitors are unable to induce degradation of mutant p110 alpha.

The taselisib-induced degradation of mutant p110a protein is ubiquitin-mediated and proteasome-dependent. These unique mechanistic effects of taselisib are most pronounced when comparing signaling suppression and p110a protein levels at 24 hours vs. 1 hour of drug exposure in PIK3CA mutant cell lines. This discovery indicates that PI3K inhibitors which trigger degradation of mutant p110a protein can more effectively suppress the signaling pathway in response to feedback, and may result in greater activity and improved therapeutic index.

Citation Format: Friedman LS, Edgar KA, Song K, Schmidt S, Kirkpatrick DS, Phu L, Nannini MA, Hong R, Cheng E, Crocker L, Young A, Sampath D. The PI3K inhibitor, taselisib, has enhanced potency in PIK3CA mutant models through a unique mechanism of action [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S6-04.
Abstract A38: California State University Fullerton and the University of California Irvine Chao Family Comprehensive Cancer Center Partnership for Cancer Health Disparities Research
Authors: Tanjasiri Sora Park , Hubbell F. Allan
Published: March 2017

Background: An important goal of the NIH is to increase the pipeline of investigators into cancer health disparities research. CSUF and UCI-CFCCC established a partnership to conduct pilot research projects in multi-ethnic populations and to mentor early stage investigators and students. The goals were to increase cancer health disparities research and encourage investigators and students to pursue careers in this field.

Methods: The Partnership selects projects for funding using NIH criteria. In addition to scientific merit, they must include one investigator from each institution, relate to cancer health disparities, and describe plans to publish scientific manuscripts and to develop extramural grant proposals. An Executive Committee and an Internal Advisory Committee facilitate communication within the Partnership. An external reviewer evaluates the Partnership yearly using the Logic Model.

Results: The Partnership has funded six pilot research projects and mentored four early stage investigators and 31 students. The project are: 1) Disparities in Social Support, Isolation and Coping in Cervical Cancer Survivors, 2) Equipping Medical Professionals to Reduce Treatment Related Anxiety and Increase Treatment Procedural Understanding for Children with Autism Spectrum Disorder Receiving Cancer Treatment, 3) Molecular and Epigenetic Mechanisms of Gender Disparities in Early Onset Melanoma, 4) Mi Salud, Mi Vida: A Self-Discovery Tool for Latina Breast Cancer Survivors, 5) National and Local Retail Advertising of E-Cigarettes Aimed at Ethnic Minorities and 6) Collecting HPV Vaccine Decision Narratives and Communication Channel Preferences.

Conclusion: The Partnership is achieveing its goals of increasing cancer health disparities research and mentoring early stage investigators and students. We are opitmisic that the national goal of advancing cancer heatlh equity through these efforts will be achieved.

Citation Format: Sora Park Tanjasiri, F. Allan Hubbell. California State University Fullerton and the University of California Irvine Chao Family Comprehensive Cancer Center Partnership for Cancer Health Disparities Research. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A38.
Abstract A39: Using a stepped wedge design to describe the adoption of a cancer education program in male correctional facilities
Authors: Valera Pamela , Mackey Daniel , McLaughlin William , Brotzman Laura
Published: March 2017

Introduction

Nearly nine million Americans pass through the criminal justice system (i.e., prison, jail, parole, and probation). Several reports have indicated that approximately 60-80% of inmates in the U.S. have histories of tobacco use, compared to 30% of the general population. This is significant, because, despite declining smoking rates in the general population, tobacco use is still the leading cause of preventable mortality and morbidity in the nation. Moreover, tobacco use by inmates has not been the focus of cancer health studies. That being said, this study describes the implementation strategy to support the adoption of a cancer health disparities education program, called Cancer 101 aimed at improving cancer health among underserved populations.

Methods/Design

Cancer 101 will be offered to three male correctional facilities in New York and Pennsylvania using a stepped wedge design. Due to adopting Cancer 101 in a real-world environment with plenty of logistical and structural constraints, the order in which different cohorts receive the intervention will be determined at random; however, all groups will receive the intervention. Data analysis will include the following descriptive statistics: correlations, ANOVA, and chi-square tests.

Discussion

The stepped wedge design may be appropriate for evaluating the effectiveness of a cancer health disparities program in a controlled setting. The stepped wedge design enables all designated correctional sites to eventually receive Cancer 101 during the study. We expect that Cancer 101 will prove to be a feasible program for reducing cancer health disparities in underserved men in correctional settings.

Citation Format: Pamela Valera, Daniel Mackey, William McLaughlin, Laura Brotzman. Using a stepped wedge design to describe the adoption of a cancer education program in male correctional facilities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A39.
Abstract A42: Breast and cervical cancer screening adherence among Latina women living in South Texas: Results from the Esperanza y Vida (Hope and Life) intervention
Authors: Brown Jameisha B. , Hurd Thelma C. , Sunil Thankham S.
Published: March 2017

PURPOSE The evidence-based Esperanza y Vida [EyV] (Hope and Life) program was developed to increase awareness of screening methods among Latinas living in South Texas and explore social and contextual influences that may contribute to disproportionate breast cancer (BC) and high cervical cancer (CC) incidence. This study aimed to identify sociodemographic characteristics of participants, including religion and church attendance, within the larger EyV study, who reported barriers to BC and CC screening. METHODS Lay health advisors were trained to deliver the program to promote BC and CC awareness and screening. Participants (N=227) completed questionnaires that assessed knowledge, screening adherence: breast self-exam [BSE], clinical breast exam [CBE], mammography, Papanicolaou (pap) test, and health beliefs about BC and CC and were contacted for follow-up to assess screening and offer assistance in obtaining exams. RESULTS There was no association among Latinas who participated in BSE (N=118, chi-squared=8.978, p=.344), CBE (N=119, chi-squared=1.875, p=.392), and mammogram (N=98, chi-squared=8.978, p=.344) in the past 12-months and church attendance. Latinas that received a pelvic exam (N=109) and pap test (N=139) did so as part of their yearly exam. The most prevalent barriers (N=62) to screening adherence were cost (N=45) and lack of adequate health insurance (N=44). Eligible Latinas (N=174) that reported barriers to breast exams in the past 12-months believed 1) healthcare professionals felt neutral (p=.099) and 2) their friends not interested (p=.055) in screening Hispanic/Latinas for BC and CC, 3) weekly church attendance (p=.071) and 4) no education (p=.097). Eligible Latinas (N=175) that reported barriers to pap testing in the past 12-months believed 1) healthcare professionals felt not interested (p=.248) and 2) their friends either not interested (p=.092) or neutral (p=.126) in screening Hispanic/Latinas for BC and CC, 3) weekly church attendance (p=.161) and 4) age (p=.014) were factors. CONCLUSIONS These findings have implications for further culturally-tailored BC and CC education, screening interventions and patient navigation. Additional exploration of the influence of healthcare professionals and social networks in screening behaviors among this population is warranted.

Citation Format: Jameisha B. Brown, Thelma C. Hurd, Thankham S. Sunil. Breast and cervical cancer screening adherence among Latina women living in South Texas: Results from the Esperanza y Vida (Hope and Life) intervention. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A42.
Abstract A56: Physician consultations, prostate cancer knowledge, and PSA screening in African American men: Are the conversations effective?
Authors: Woods-Burnham Leanne , Stiel Laura , Wilson Colwick , Montgomery Susanne , Casiano Carlos A.
Published: March 2017

African American (AA) men are more likely to develop and die from prostate cancer (PCa) yet less likely to receive information about screening from physicians. Although guidelines espouse shared decision-making regarding PCa screening and PSA testing, studies reveal lack of consistency. Several studies demonstrate that PCa knowledge strongly influences informed decisions, and that engaging interactions are especially important for AA men who are more likely to progress from early stage to aggressive end-stage PCa at an earlier age and faster rate than other populations. This study evaluated the frequency of physician-patient conversations among AA men and whether this translated into increased PCa knowledge and PSA testing. In this study, self-identified Black men ages 21-85 donated blood and completed a health survey (n=414) via Project C.H.A.N.G.E. (Changing Health in Adult Men with New and Great Experiences), a transdisciplinary cross-sectional study conducted at Loma Linda University. PCa knowledge following physician conversations in light of socio-economic and health care variables was evaluated using univariate, bivariate, and multiple regression analyses. PSA values were measured with ELISA. Our results revealed that 52.7% of participants had never discussed the pros and cons of PCa screening with their physicians. The likelihood of physician-patient conversations increased with age (p.001), and health insurance positively predicted these discussions (p.001). Multiple regression analysis indicated ethnicity and high school education as predictors of improved PCa knowledge (p.001). We found that 38.5% of men who had discussed PCa screening with a physician and 28.5% who had not discussed PCa screening had PSA values that could be considered high-risk for PCa diagnosis. These findings expose a remaining deficiency in physician compliance regarding national guidelines for shared decision-making conversations with high-risk men. This is problematic as a large group of AA men at evident risk for PCa have not ever discussed this disease with their physicians and may be harboring undetected PCa. Encouraging more effective interactions between AA men and their physicians concerning PCa screening and PSA testing has the potential to reduce PCa health disparities.

Citation Format: Leanne Woods-Burnham, Laura Stiel, Colwick Wilson, Susanne Montgomery, Carlos A. Casiano. Physician consultations, prostate cancer knowledge, and PSA screening in African American men: Are the conversations effective? [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A56.
Abstract A82: Cancer Diagnosis and the Effect of Joint Family in Rural India
Authors: Koirala Sushant
Published: March 2017

With cancer being an ever prevalent problem in modern society, there have been a large number of cancer related studies mainly dedicated to the medical effects and remedies. However, studies that relate demographics and living pattern to cancer sparsely exist, but are mostly on human behaviors. Social behavior, such as drinking, as well as those relating to family types also holds importance in the effectiveness of medical treatments on cancer. Studies on the effects of these behaviors, however, are completely ignore. This is especially true when considering whether the person lives in a nuclear or joint family. As such, this study seeks to add to the limited amount of literature linking family living type to cancer diagnosis. Henceforth, the objective of this research is to estimate the effect of joint family on cancer diagnosis. Using a logit estimation model, the paper estimates how family living type and daily behaviors affect the risk of cancer diagnosis. This study employed a total of 251 surveyed data obtained from Karnataka Lingiat Educational (KLE) Society University at Handiganur village, located in the South Western state of Karnataka in India. The estimated result showed that a person living in a joint family would lower its log-odds of being detected of a cancer by 1.293 units against living in nuclear family. Further, the estimated marginal effect found that a 1% change in joint family will reduce the likelihood of being diagnosed with cancer by 7.24%. Among the other behavioral variables studies, the study also found that public well for water supply will increase the likelihood of being diagnosed with cancer by 0.933 units. Similarly, a person who drinks alcohol regularly increases their likelihood of risk of being diagnosed with cancer by 1.260 units. Two possible reasons for the results are that because there are biological and behavioral implications of living in a joint family that can help mitigate the chances of developing cancer-such as healthier living habits supported by family members, and that ceteris paribus, a joint family will have less income per person in the household meaning that hospital visits happen less frequently. Hence, the finding of this study should have a huge implication in developed countries where nuclear family syndrome dominates. A future study with a field based experimental data that has treatment and controlled group with a large sample size is recommended.

Citation Format: Sushant Koirala. Cancer Diagnosis and the Effect of Joint Family in Rural India. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A82.
Abstract B19: Pediatric Cancer Late Effects Clinic Patients in Utah: Potential Barriers to Care
Authors: Ou Judy Y. , Smits-Seemann Rochelle R. , Wright Jennifer A. , Kirchhoff Anne C.
Published: March 2017

Background: Cancer late effects clinics are important to manage health complications experienced by cancer survivors, but little is known about potential barriers to attendance in rural states where many patients live far away from cancer centers. We identify demographic, clinical and residency factors associated with clinic attendance at the only pediatric cancer late effects clinic in Utah.

Methods: Medical records identified survivors diagnosed with cancer at age ≤25 years from 1986-2011 who currently reside in Utah. We linked records to the late effects clinic patient registry, available from 2010 to present. Participants were geocoded using their most recent residential zip code according to medical and driver's license records. The Euclidean distance between the clinic and the centroid of each zip code were calculated. Participants were classified into median income brackets based on the same zip code information. Log-linear models identified associations between attendance and the demographic and clinical factors. Generalized estimating equations were used in analyses for zip-code level residential distance and income with attendance.

Results: Of 1,935 survivors, only 10% had ≥1 clinic visit. Attendance is associated with leukemia/lymphoma diagnosis (odds ratio [OR]=1.65; 95% confidence interval [CI]=1.14-2.39 vs. other solid tumors) and current age between 19-30 years (OR=3.01; 95% CI=1.33-6.79 vs. ≥30 years). Hispanic ethnicity was not associated with late effects clinic attendance (OR=0.94; 95% CI =0.47-1.87 vs Non-Hispanic). Living in a zip code with a residential distance of less than 20 miles (OR=1.37, 95% CI=0.73-2.58 vs. ≥60 miles), and living in zip codes with median income between $60,000 and $70,000 (OR=1.45, 95% CI=0.67-3.11 vs. >$50,000/year) showed positive, non-significant associations with attendance.

Conclusions: Late effects clinics are not widely attended by childhood and adolescent cancer survivors in Utah. Current age and previous cancer diagnosis are associated with attendance. Area of residence and income show possible associations with clinic attendance, although more investigation is needed to examine how these access-related factors influence attendance. Outreach efforts may be needed to connect cancer survivors with late effects clinics. Further investigation is needed to identify potential economic and geographic barriers to care.

Citation Format: Judy Y. Ou, Rochelle R. Smits-Seemann, Jennifer A. Wright, Anne C. Kirchhoff. Pediatric Cancer Late Effects Clinic Patients in Utah: Potential Barriers to Care. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B19.
Abstract B41: Metformin and indole-3-carbinol (I3C) modulate regulation of genes involved in dedifferentiation in chemo-resistant pancreatic cancer cells
Authors: Lyn-Cook Beverly , Cooper George , Word Beverly , Hammons George
Published: March 2017

Pancreatic ductal adenocarcinoma remains one of the deadliest cancers and is projected to become the second leading cause of cancer death by 2020. More alarming, is the projection of death in minority populations for this cancer. Although several risk factors have been associated with the etiology of this cancer, such as smoking, diet, obesity and recently nicotine, it continues to steadily increase. Numerous studies have shown the importance of cancer stem cells in cancer resistance and self-renewal. Dedifferentiation of cancer cells requires key factors to be present in the tumor environment. These factors are regulated by key transcription factors that are known to control cancer stem cells and dedifferentiation. Using a human embryonic stem cell RT2 Profiler gene array, numerous stem cell genes expressed in pancreatic cancer cell lines (MIAPaca2, Panc1) can be identified. However, this study focused on those involved in dedifferentiation of cancer cells. Although both cell lines, Panc-1 and MIAPaCa2 (Mia), expressed high levels of SOX 2, NANOG, CD44, GATA 2, POU5F1 (OCT4), and other genes, differences were noted in the expression of GATA6. GATA6 is a zinc finger transcription factor that is known to play a role in regulating cellular differentiation and organogenesis in gut, lung and heart development and has been found to be overexpressed in pancreatic, gastric and esophageal cancers. A pathogenic gene signature has emerged for genes regulated by GATA6 that could provide potential drug targets. Mia cells, which are less resistance to the standard drug used for pancreatic cancer, gemcitabine, expressed higher levels of GATA6 compared to Panc1, a more resistance phenotype. Treatment of cells with I3C alone at 100 or 200 µM inhibited the expression of GATA6 in Mia cells, compared to Panc 1 cells. Treatment with metformin alone and in combination with I3C showed similar results. Modulation of other gene expressions was noted with treatment of I3C and metformin, such as DPPA2, THY1, CCNA2 and DPPA2. This study has shown that the dietary agent, I3C, alone and in combination with metformin down-regulate critical stem cell genes involved in dedifferentiation of cancer cells that should affect the maintenance of their pluripotency and self-renewal.

Citation Format: Beverly Lyn-Cook, George Cooper, Beverly Word, George Hammons. Metformin and indole-3-carbinol (I3C) modulate regulation of genes involved in dedifferentiation in chemo-resistant pancreatic cancer cells. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B41.
Abstract C22: Race does not influence outcome in triple negative breast cancer
Authors: Butler Shaunte , Chagpar Anees B.
Published: March 2017

INTRODUCTION: While it is known that Black women are more likely to get triple negative breast cancer (TNBC) which carries a poor prognosis, it is less clear whether race affects outcome in this subtype independent of other factors. We sought to determine, in a national database, the relative impact of race and socioeconomic status on overall survival in women diagnosed with TNBC.

METHODS: The National Cancer Database was queried to determine factors affecting overall survival of patients diagnosed with TNBC between 2004 and 2013. Kaplan-Meier and Cox proportional hazards models were performed using SPSS Version 21.

RESULTS: 64,839 patients with TNBC (excluding other malignancies) were included in the analysis. Median patient age was 57 (range; 19-90). Of these, 47,124 (72.7%) were white, and 14,541 (22.4%) were black. Black women were more likely to be uninsured (5.2% vs. 3.0%, p<0.001) and in the lowest household income quartile (<$38,000; 39.9% vs. 13.7%, p<0.001). In addition, blacks were less likely to present with Stage 1 disease (31.6% vs. 41.2%, p<0.001), and more likely to have high grade tumors (85.3% vs. 80.2%, p<0.001). On average, blacks also had a longer time interval between diagnosis and initiation of treatment (34 vs. 28 days, p<0.001). Blacks had a mean overall survival of 94 months, compared to 98 months for whites (p<0.001). On multivariate Cox regression modelling controlling for age, stage, grade, time to first treatment, income, insurance status, comorbidities (measured by Charlson score), and region, race was no longer predictive of overall survival in patients with TNBC (black vs. white OR: 1.04; 95% CI: 0.98-1.11, p=0.199). Patients with private insurance were significantly less likely to die than those who were uninsured (OR: 0.66; 95% CI: 0.59-0.75, p<0.001) independent of other factors. Similarly, those in the highest income quartile were less likely to die than those in the lowest (OR: 0.79; 95% CI: 0.73-0.85, p<0.001). Patient age (p<0.001), stage (p<0.001), grade (p<0.001), region (p<0.001), Charlson score (p<0.001) and time to treatment (p=0.001) all remained significant in the model.

CONCLUSION: While black race is associated with higher stage and grade disease, longer time to treatment and lower socioeconomic status, when controlling for these factors, race does not independently affect overall survival in women with TNBC. Disparities in breast cancer outcomes in this population therefore appear to be mediated more by socioeconomic factors than by race alone.

Citation Format: Shaunte Butler, Anees B. Chagpar. Race does not influence outcome in triple negative breast cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C22.
Abstract C35: Differential inflammatory cytokine secretion between African American and Caucasian colon cancer cell lines
Authors: Sanchez Jenny Elizabeth Paredes , Munoz-Sagastibelza Maria , Peing Ji , Martello-Rooney Laura , Williams Jennie
Published: March 2017

Colorectal cancer (CRC) incidence and mortality rates in African Americans (AAs) are up to 38% higher than in Caucasian Americans (CAs). Moreover, our previous studies reported that AAs have hypermethylated DNA regions in inflammatory genes such as NELL1, GDF1, ARHGEF4, and ITGA4; suggesting that AAs have differences in their inflammation patterns when compared to CAs. Therefore, we used two AA tumor-derived cell lines, which were generated in Dr. Williams' laboratory, and two CA tumor-derived cell lines to study the production of the pro-inflammatory IL-8 and anti-inflammatory IL-10 cytokines as they relate to possible differences in the inflammatory response. The inflammatory inducers IL-1B and TNF-alpha as well as Lipopolysaccharide from E. coli were used to mimic colonic inflammatory niches and induce cytokines secretion in these four cell lines. As hypothesized, our results show a significantly higher inflammatory cytokine production of IL-8 in the CA cell lines in response to all the treatments when compared to the AA cell lines. In contrast, secretion of IL-10 between the cell lines was within the same range. We could then propose that AA colon tumors secrete less IL-8 than CA colon tumors as a consequence of their DNA hypermethylated genes and this leads to deficient recruitment of neutrophils and macrophages, key cells for pathogen elimination and T cell activation. Further studies are needed to elucidate the differences in inflammation patterns between AAs and CAs and their role in CRC health disparities.

Citation Format: Jenny Elizabeth Paredes Sanchez, Maria Munoz-Sagastibelza, Ji Peing, Laura Martello-Rooney, Jennie Williams. Differential inflammatory cytokine secretion between African American and Caucasian colon cancer cell lines. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C35.
Abstract C65: Promoting colorectal cancer screening in rural Appalachian emergency department
Authors: Hatcher Jennifer , Brandford Arica , Aroh Adaeze , Adegboyega Adebola , Combs Brenda , Schoenberg Nancy
Published: March 2017

Objective: To provide a conceptual description of an Emergency Department (ED) placed randomized controlled trial designed to reduce the disproportionate burden of colorectal cancer (CRC) among rural Appalachian residents.

Background: Residents of rural Appalachia have a higher incidence and mortality rate from CRC than residents of any other region of the country. The Centers for Disease estimate that as many as 60% of CRC deaths could be prevented if everyone aged 50 and up were screened regularly. One of the primary barriers to CRC screening for rural Appalachian residents is limited access to the health care system resulting in infrequent recommendations for screening and inadequate screening education. Given the propensity of rural Appalachians to accept health related information from trusted community members we designed an intervention to be delivered by local community health workers in the ED while individuals waited for non urgent care or waited with a family member. The ED provides services to a segment of the population that is traditionally hard to reach and at high risk for underutilization of preventive services. ED visits may be the sole point of contact with the health care system for these vulnerable individuals and provides a venue and opportunity for CRC screening promotion and education.

Methods: This ED-placed RCT, designed and implemented in collaboration with community members and health care providers in rural Eastern Kentucky, is one of the first to use the ED as a site to promote colorectal cancer screening using a community health worker trained to deliver a motivational interviewing intervention to persons waiting for non urgent care or with a family member, in the ED of rural Appalachian hospitals.

Results: We provide a conceptual overview to key elements of the intervention, including intervention development and refinement, theoretical foundations, intervention approach and implementation and evaluation procedures.

Conclusion: This RCT has recruited more than 150 persons from rural Appalachian EDs who have not been screened for CRC in accordance with guidelines. It provides promise that CRC screening promotion activities are appropriately placed in rural EDs and provides a solid platform from which researchers and providers may launch efforts to develop targeted preventative health interventions in innovative public health settings.

Citation Format: Jennifer Hatcher, Arica Brandford, Adaeze Aroh, Adebola Adegboyega, Brenda Combs, Nancy Schoenberg. Promoting colorectal cancer screening in rural Appalachian emergency department. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C65.
Abstract IA11: Cancer patterns among US Latino subpopulations defined by country of origin
Authors: Stern Mariana C.
Published: March 2017

Latinos are the fastest growing minority ethnic group in the US and are predicted to account for ~25% of the US population by the year 2050. In spite of this, knowledge about cancer determinants and predictors of cancer outcomes in this population are lagging behind other racial/ethnic groups in the US. Importantly, most existing studies consider US Latinos as one group; however, in spite of the shared language and history, there is significant variability within this group in terms of cultural factors, genetic ancestry, and degree of assimilation to the US lifestyle. Lack of consideration of this heterogeneity may mask important cancer patterns within this population. Consideration of country of origin, using cancer registry data, might partially capture some of these indicators of heterogeneity, and may serve as a starting point to identify important differences among US Latinos. For example, there is emerging evidence that cancer incidence for some of the main cancer types differ across Latino subpopulations defined by country of origin. For several cancers, U.S.-born Latinos have higher cancer incidence than foreign-born Latinos, and Puerto Rican and Cuban Latinos seem to have higher incidence rates than Mexican Latinos. Similarly, differences can be observed across Latino subpopulations defined by country of origin in the distribution of age at diagnosis, sex, socioeconomic status, stage, tumor localization, and overall survival. These findings might be explained by the complex relationship between differences in the prevalence of cancer risk factors, both in the US and in the country of origin of foreign-born Latinos, genetic susceptibility, and access and attitudes towards health care. Elucidating these complex interactions will be critical to identify the most relevant cancer determinants and treatment strategies for US Latinos.

Citation Format: Mariana C. Stern. Cancer patterns among US Latino subpopulations defined by country of origin. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA11.
Abstract IA44: Colorectal cancer in Nigeria
Authors: Kingham T. Peter , Alatise Olusegun Isaac
Published: March 2017

Colorectal cancer (CRC) is a growing problem in low- and middle-income countries (LMICs). We began studying CRC in Nigeria in 2011. We chose CRC because its incidence is growing rapidly in Nigeria and other LMICs. The one-year mortality rate is over 50% after patients present to centers in our consortium. We also found Nigerian patients had a higher rate of peritoneal metastases compared to American patients. In addition, patients presented at later stages, which may be due to poor access to care or differences in tumor biology. To determine the etiology of these differences we have created an NCI-recognized consortium (ARGO) that now comprises 5 hospitals in Nigeria in partnership with MSK. Late in 2013 we began to prospectively collect data and tissue from patients with CRC, funded by a pilot grant from the NCI (Nigerian IRB#ERC/2013/09/01). In addition, we have a prospective colonoscopy screening study (IRB #ERC/2013/02/17). Both studies have demonstrated obstacles to banking, tracking, and studying tissue specimens in Nigeria that we have overcome. Our data now suggests some biologic differences in CRC in Nigeria may explain poor responses to 5-FU based chemotherapy and poorer outcomes compared to similar stage American patients. We have also validated a risk model for identifying patients at high risk for colorectal cancer to attempt to limit the number of patients that should be offered colonoscopy.

Citation Format: T. Peter Kingham, Olusegun Isaac Alatise. Colorectal cancer in Nigeria. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA44.
Abstract A09: PDXovo: Ultra-fast in vivo drug sensitivity matrices for renal cell carcinoma patients prior to administration of targeted therapy
Authors: Lowerison Matt , Leong Hon S. , Fedyshyn Yaroslav , Chambers Ann F. , Lacefield James , Power Nicholas E.
Published: March 2017

Our next generation PDX model of renal cell carcinoma (RCC) offers the ability to pre-determine de novo drug resistance in fresh patient tumor samples prior to targeted therapy. Implantation of tumor specimens into the chorioallantoic membrane (CAM) of the chicken embryo results in high engraftment efficiencies within two days permitting large-scale “tumor avatar” studies due to its angiogenic microenvironment. Functional tumor heterogeneity studies can be performed in context of drug resistance within two weeks, an approach that could guide the selection of drugs and anticipate outcomes for RCC patients. This ultrafast PDX model is mirrored by high-frequency ultrasound imaging that permits quantitation of tumor volume and tumor vascularity in a high-throughput manner. Using this “tumor avatar” model paired with a prospective RCC patient cohort, we observe intratumoral functional heterogeneity in the context of Sunitinib treatment as determined by high-frequency ultrasound imaging, highlighting its interventional potential in the clinic.

Citation Format: Matt Lowerison, Hon S. Leong, Yaroslav Fedyshyn, Ann F. Chambers, James Lacefield, Nicholas E. Power. PDXovo: Ultra-fast in vivo drug sensitivity matrices for renal cell carcinoma patients prior to administration of targeted therapy. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A09.