bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A91: IKBKE signaling in pancreatic tumorigenesis
Authors: Rajurkar Mihir , Mao Junhao 
Published: October 2015

Abstract
Oncogenic activation of Kras is an important event in Pancreatic Ductal Adenocarcinoma (PDAC), that leads to activation of multiple signaling pathways. Although Kras is conceptually an attractive therapeutic target for PDAC, attempts made to target Kras using small molecules have been mostly unsuccessful. Another approach in treating pancreatic cancer is to target downstream effectors of Kras. We have previously shown that non-canonical activity of the Gli transcription factors downstream of Kras is required for the initiation and progression of pancreatic tumors, and that Gli drives a unique pancreas specific transcriptional program in the context of oncogenic Kras. Here, we demonstrate that the IkB Kinase Epsilon (IKBKE) is a novel transcriptional target of Gli that is essential for pancreatic transformation. Using genetically modified mouse models, we show that IKBKE activity, while dispensable for pancreatic development, is required for oncogenic transformation in the pancreas. We find that the genetic knockout of IKBKE leads to a dramatic inhibition of initiation and progression of pancreatic intraepithelial neoplasia (PanIN) precursor lesions in mice carrying pancreas specific activation of oncogenic Kras. Furthermore, we find that although IKBKE is a known NF-kB activator, it only modestly regulates NF-kB activity in PDAC. In contrast we find that IKBKE strongly promotes Akt phosphorylation in PDAC in vitro and in vivo, indicating that this may be the primary mechanism of IKBKE induced tumorigenesis. Our findings support the evaluation of IKBKE as a novel therapeutic target in treatment of pancreatic cancer.
Citation Format: Mihir Rajurkar, Junhao Mao. IKBKE signaling in pancreatic tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A91.
Abstract A94: Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer
Authors: Kapoor Avnish , Yao Wantong , Ying Haoqiang , Hua Sujun , Liewen Alison , Sadanandam Anguraj , Al-Khalil Ramsey , Viale Andrea , Pettazzoni Piergiorgio , Sanchez Nora , Protopopov Alexei , Zhang Jianhua , Heffernan Timothy , Johnson Randy L. , Chin Lynda , Wang Y. Alan , Draetta Giulio , DePinho Ronald A. 
Published: October 2015

Abstract
Activating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible KrasG12D-driven mouse model of PDAC has established a critical role for sustained KrasG12D expression in tumor maintenance, providing a model to determine the potential for, and underlying mechanisms of, KrasG12D–independent PDAC recurrence. We utilized MRI imaging to monitor regression of advanced pancreatic tumors measuring at least 8 mm in diameter at time of doxycycline withdrawal. Here we show that some tumors undergo spontaneous relapse and are devoid of KrasG12D expression, downstream canonical MAPK signaling but instead acquired amplification and overexpression of the transcriptional co-activator Yap1. Enforced Yap1 expression can substitute for oncogenic Kras-driven tumor maintenance and associated tumor cell proliferation without activation of canonical Kras signaling surrogates. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving KrasG12D–independent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models indicates that the oncogenic Kras-independent relapse tumors generated in response to KrasG12D extinction closely resemble the quasimesenchymal-subtype of human PDAC and rely on alternative oncogenic mechanisms including Yap1 for their growth.
Citation Format: Avnish Kapoor, Wantong Yao, Haoqiang Ying, Sujun Hua, Alison Liewen, Anguraj Sadanandam, Ramsey Al-Khalil, Andrea Viale, Piergiorgio Pettazzoni, Nora Sanchez, Alexei Protopopov, Jianhua Zhang, Timothy Heffernan, Randy L. Johnson, Lynda Chin, Y. Alan Wang, Giulio Draetta, Ronald A. DePinho. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A94.
Abstract B120: Wnt expression and the association with autophage protein in pancreatic cancer
Authors: Lee Myung Ah , Park Jin Hee 
Published: October 2015

Abstract
Background: Aberrant wnt signaling pathway and contribution of autophagy have been documented in many types of human cancers. However, the association between and autophage-related protein has not been studied in pancreatic cancer. We analyzed the expression of wnt protein and autophage-related protein in pancreatic cancer to determine the association and its clinical significance.
Materials and Methods: From January 2001 to December 2009, paraffin embedded blocks from 74 patients undergone pancreatic resection for the treatment of pancreatic cancer were used in the present study. We performed immunohistochemical staining for wnt3, wnt5a, ß-catenin in wnt signaling pathway and Atg5, Ambra1, Beclin-1, LC3, Bif-1 in the fields of autophage related protein. We reviewed the clinicopathologic characteristics and analyzed the association between wnt signaling pathway and the autophage.
Results: In 74 patients, the expression rates of wnt protein were 68.9% for wnt3, 83.8% for wnt5a and 54.9% for ß-catenin. The wnt3 expression was more frequent in pancreatic head than in body or tail (p = 0.039) and ß-catenin was more commonly expressed in negative lymphatic invasion (p = 0.032). The wnt 3 expression is positively associated with ATG5 (p=0.004), Ambra1 (p=0.004), Beclin (p=0.022), and LC3 (p=0.002). The wnt5 expression also showed the correlation with ATG5 (p=0.01), Ambra1 (p=0.026), Beclin (p=0.012), and LC3 (p=0.003). There was no prognostic significance association between survival outcome and wnt expression.
Conclusion: In pancreatic cancer, wnt protein expression was very high, showing association with autophage-related protein. To determine the clinical significance of these protein expressions, we are currently ongoing further research.
Note: This abstract was not presented at the conference.
Citation Format: Myung Ah Lee, Jin Hee Park. Wnt expression and the association with autophage protein in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B120.
Abstract B16: Contributions of Ras and EZH2 in acinar to ductal metaplasia and ductal carcinoma in transgenic mouse pancreas
Authors: Ellis Jayne , Sandgren Eric P. , Grippo Paul J. , Figueiredo Marxa L. 
Published: October 2015

Abstract
Activating mutations of the ras protooncogene is the most frequent and an early genetic alteration associated with pancreatic cancer. To examine the link between mutant ras oncogenes and exocrine pancreatic cancer, and to develop mouse models of PanINs and also of lesions that progress to malignancy, we generated transgenic mice expressing either Kras or Hras in pancreas. The tetracycline transactivator system expression was targeted to the pancreatic acinar cells via the elastase promoter element. The transactivation target ras genes were placed under the control of the tetracycline-response element. Most double transgenic founder mice displayed perinatal pancreatic acinar cell hyperplasia and dysplasia. However, only adult mice expressing Hras displayed preinvasive pancreatic neoplastic lesions with ductal morphology. Therefore, these Kras and Hras models each represent useful models in which either the lesion histotype and agressiveness (Hras) or the initiating genetic alteration overlap with the human disease (Kras). More recently, we have developed and are characterizing the contributions of expressing enhancer of zeste 2 homolog (EZH2), a histone methyl transferase and key regulator of cell differentiation and tissue regeneration, in modifying aggressiveness of mutated ras genes in vivo. Our findings suggest that ras mutations are associated with development of early stage duct-like lesions in pancreas, which vary in severity depending on the mutated ras gene expressed and the stage of development and growth of pancreas tissue.
Citation Format: Jayne Ellis, Eric P. Sandgren, Paul J. Grippo, Marxa L. Figueiredo. Contributions of Ras and EZH2 in acinar to ductal metaplasia and ductal carcinoma in transgenic mouse pancreas. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B16.
Abstract B61: CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models
Authors: Zhu Yu , Brett Knolhoff , Melissa Meyer , Brian West , David Linehan , DeNardo David 
Published: October 2015

Abstract
The immune system is a promising therapeutic target that can be modulated to improve pancreatic ductal adenocarcinoma (PDAC) patient outcomes. Unfortunately, attempts to use immunotherapeutics as single agents have achieved very limited clinical benefits in PDAC. One major obstacle is the presence of an immunosuppressive tumor microenvironment. Critical drivers of this immunosuppressive microenvironment include tumor-associated macrophages, monocytic myeloid-derived suppressor cells, and immature granulocytes/granulocytic. In addition to instigating immune suppression, these tumor-infiltrating leukocytes can impart resistance to cytotoxic therapies and promote metastatic dissemination. As a consequence, high numbers of these myeloid cells are often associated with early metastatic relapse and poor survival in pancreatic cancer patients. Therefore, approaches that reprogram myeloid responses to potentiate antitumor immunity and/or bolster immunotherapy could hold significant therapeutic potential. In this report, we demonstrate that inhibition of colony stimulating factor 1 receptor (CSF1R) signaling functionally reprograms macrophage responses to enhance antigen presentation, thereby stimulating anti-tumor T cell responses. However, this immune reprograming also leads to the upregulation of T cell checkpoint molecules, including PDL1 and CTLA4, which significantly limits the potential of the CSF1R blockade to induce anti-tumor responses. While both programmed cell death protein 1 and CTLA4 antagonists show limited efficacy as single agents to restrain PDAC growth in a mouse model, the combination of these agents with CSF1R blockade achieves disease regression even in well-established tumors. These data suggest that reprograming myeloid responses through CSF1R blockade can improve the efficacy of checkpoint-based immunotherapeutics in pancreatic cancer.
Citation Format: Yu Zhu, Knolhoff Brett, Meyer Melissa, West Brian, Linehan David, David DeNardo. CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B61.
Abstract B97: A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer
Authors: Le Dung , Laheru Daniel , Diaz Luis A. 
Published: October 2015

Abstract
Background: Triplet chemotherapy has been shown to delay the emergence of resistance and extend survival in patients with metastatic pancreatic adenocarcinoma. Four drug regimens, even at low doses, may further improve survival by simultaneously targeting multiple oncogenic pathways.
Methods: A phase II study of GTX-C (capecitabine 500 mg bid on days 1-14, and the combination of gemcitabine 500 mg/m2 (10 mg/m2/min), taxotere 20 mg/m2 and cisplatin 20 mg/m2 on days 4 and 11) was initiated in newly diagnosed untreated metastatic pancreatic cancer patients. The primary endpoint was progression-free survival rate at 6 months and designed such that the regimen would be considered active if the 6-month PFS rate was &gt;75% and inactive if &lt; 50%.
Results: Twenty-eight patients were enrolled. All patients were ECOG 0-1. Eighty-six percent of patients had evidence of liver metastases and 25% had biliary stents in place at time of study initiation. Median CA19-9 was 6,159 U/mL (37-154,323 U/mL). Median length of follow-up was 10.1 months. Grade 3/4 related adverse events included: nausea/vomiting (7%), transaminitis (10%), anemia (14%), thrombocytopenia (24%), and neutropenia (55%). However, febrile neutropenia occurred in only 3 patients (10%) and not until cycles 6, 14, and 15. PFS rate at 6 months was 74.2% (95% CI: 53.3% - 86.8%). The partial response (PR) rate was 50%, stable disease (SD) rate was 39% and the disease control rate (DCR) was 89%. CA19-9 declines of &gt;80% occurred in 77% of patients with measurable levels. Estimated median PFS was 8.4 months (95% CI: 6.1-10.6 months) and OS was 12.9 months (95% CI: 10.0-NA months) as of 11/14/2013. Ten additional patients have been enrolled onto an expansion cohort in which the period off between cycles has been changed from 7 to 14 days.
Conclusions: GTX-C is highly active and well-tolerated in patients with metastatic pancreatic cancer and should be tested in a larger, comparative study. Clinical trial information: NCT01459614.
Citation Format: Dung Le, Daniel Laheru, Luis A. Diaz, Jr. A phase II trial of low-dose multiagent chemotherapy with gemcitabine, taxotere, xeloda, and cisplatin (GTX-C) in subjects with metastatic pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B97.
Abstract A06: Guided tours of a “Super Colon” increase knowledge and willingness to discuss colon cancer among residents of Appalachian Ohio
Authors: Fickle Darla K. , Randall Katherine E. , Jordan Audra L. , Torres Norma A. , Paskett Electra D. 
Published: October 2015

Abstract
Introduction: Due to the elevated colorectal cancer incidence and mortality rate in Appalachia Ohio, the “Blue Star Healthy Colon Initiative” was conducted to provide an interactive format to educate lay community members about colon cancer and colon cancer screening.
Methodology: The ‘Super Colon’ walk-through model was set up at two community events in Meigs County Ohio – an Appalachian county. At each event, participants were given tours of the Super Colon exhibit by nurses and public health professionals. Surveys on colon cancer knowledge, screening knowledge, testing intentions, and willingness to discuss colon cancer with others were collected from participants before and after tours. Information on age, colon cancer screening history, and insurance status of participants were also collected via survey before touring the Super Colon.
Data were analyzed with X2 tests to compare responses collected before touring the supercolon to responses collected after touring the supercolon.
Results: Over the two events, 227 pre-tour and 240 post-tour questionnaires were collected from respondents. The mean age of respondents was 57.0 years, 72.7% were at least fifty years of age, and 72.2% were female, 30.3% received Medicare, 19.2% received Medicaid, 9.2% had no health insurance, and 52.7% of respondents indicated that they had some form of private health insurance--including supplements to Medicare.
Of those respondents aged fifty years and older, 76.4% reported receiving encouragement from their doctor to screen for colon cancer, 74.7% reported undergoing a screening test, and 57.6% were up-to-date on colon cancer screening. After viewing the Super Colon, respondents showed improvement in colon cancer knowledge, specifically knowledge about colon polyps (p&lt;0.001), colon cancer (p&lt;0.001), colon cancer progression (p&lt;0.001), colon cancer survival (p&lt;0.001), and colon cancer screening tests (p&lt;0.001).
After touring the Supercolon, respondents also reported greater willingness to discuss colon cancer with grandparents (p=0.004), relatives (p&lt;0.001), peers (p&lt;0.001), community members (p&lt;0.001), and people at risk (p&lt;0.001).
Discussion/Conclusions: Guided tours of the ‘Super Colon’ walk-through model appear to be effective educational and motivational tools in colon cancer screening promotion in underserved populations.
Citation Format: Darla K. Fickle, Katherine E. Randall, Audra L. Jordan, Norma A. Torres, Electra D. Paskett. Guided tours of a “Super Colon” increase knowledge and willingness to discuss colon cancer among residents of Appalachian Ohio. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A06.
Abstract A19: SHARE speaks: English, Japanese, Spanish, and cultures too
Authors: Walker Desiree 
Published: October 2015

Abstract
The poster will portray the many languages SHARE speaks both linguistically and culturally to meet the needs of underserved communities. The main focus will be on one of their latest special projects which is the Ambassador Program. It is a grassroots effort to reach medically underserved Latino/Hispanic and African American communities in New York City. Through educational presentations, trained survivors and other trained health advocates build public awareness and health empowerment regarding breast and ovarian cancers. The message is Be Informed, Empowered and Know Your Body! During outreach, women of African Ameican and Caribbean heritage frequently voiced they were looking for a support group with “people that look like me”. As a result of these comments, SHARE has begun to fill a void with the creation of a breast and ovarian cancers support group in the Harlem neighborhood of New York City.
SHARE's mission is to create and sustain a supportive network and community of women affected by breast or ovarian cancer. SHARE brings these women and their families and friends together with others who have experienced breast or ovarian cancer, and provides participants with the opportunity to receive and exchange information, support, strength and hope. SHARE's work focuses on empowerment, education and advocacy to bring better healthcare, an improved quality of life, and a cure for these diseases.
SHARE offers monthly educational programs on breast and ovarian cancers by medical professionals, researchers and health practitioners. LatinaSHARE is celebrating 20 yrs. of service to both the English and Spanish speaking Latino communities. They have breast and ovarian cancers helplines in English and Spanish. They offer breast and ovarian cancers support groups with some groups focused on women of African American and Caribbean, Japanese and Latino heritages.
Another one of SHARE's special projects is the Survivor Patient Navigators. It has two bilingual breast cancer survivors who work at Bellevue Hospital Breast Clinic and Mt. Sinai/St. Luke's Hospital Breast Clinic respectively. They help newly diagnosed patients especially Latina patients who only speak Spanish understand their diagnosis and empower them to be involved in their treatment decisions.
Citation Format: Desiree Walker. SHARE speaks: English, Japanese, Spanish, and cultures too. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A19.
Abstract A22: Using community-based participatory research to develop a culturally relevant resource for African American women affected by breast cancer
Authors: Bradley Patricia , Hanson Arin Ahlum , Guglielmino Janine Caplan , Henry Catherine Creme 
Published: October 2015

Abstract
Background: Research indicates that African-American women are more likely to die from breast cancer, be diagnosed at later stages and receive worse care than their white counterparts. In 1997, Living Beyond Breast Cancer (LBBC) wrote the booklet, Getting Connected: African-Americans Living Beyond Breast Cancer to address these issues. Changes over the last decade in breast cancer treatment, research on cancer disparities, and perceptions of breast cancer among African-Americans motivated LBBC to undertake a full revision of Getting Connected. In 2010 LBBC conducted a comprehensive, consumer-driven needs assessment engaging African-American women affected by breast cancer from across the country.
Methods/Approach: LBBC engaged stakeholders across the breast cancer continuum in the revision. The process included 1) Convening a national advisory committee of medical and advocacy experts to provide oversight 2) Holding five group interviews Philadelphia, Chicago and Little Rock with 44 African-American women diagnosed recently diagnosed with breast cancer 3) Interviewing eight key community informants who work closely with African-American survivors. Transcripts and notes were analyzed and salient themes were used to revise Getting Connected. The resource was redesigned using “plain language” principles and interactive elements were added.
Results: In October 2011, the second edition of Getting Connected was published. This 50 page, plain language, culturally relevant resource is designed to be used by African-American breast cancer survivors, their support network and their healthcare providers. This booklet promotes informed decision-making, while providing support, encouragement, and inspiration. Getting Connected addresses how one can live positively beyond breast cancer through the use of spirituality, developing and maintaining positive connections and reaching out to others.
Conclusions: Using a community-based participatory research process ensures that the resource is culturally relevant. This model can be replicated to produce resources for other populations. The personal and direct approach of Getting Connected makes this booklet a valuable resource for healthcare providers working with African-American women affected by breast cancer.
Citation Format: Patricia Bradley, Arin Ahlum Hanson, Janine Caplan Guglielmino, Catherine Creme Henry. Using community-based participatory research to develop a culturally relevant resource for African American women affected by breast cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A22.