bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.