bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B87: Cell lines generated from PDAC transgenic mice reveal integrin αvβ6 modifies the invasive phenotype of pancreatic cancer
Authors: Reader Claire S. , Vallath Sabari , Morton Jennifer , Steele Colin , Kocher Hemant M. , Keyse Stephen M. , Sansom Owen , Marshall John F.
Published: October 2015

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the UK. Five-year survival rates are less than 3% and haven’t improved over the last 40 years. Thus novel approaches are required urgently. We have found that high expression of the integrin β6 subunit gene (ITGB6) correlates with a significant reduction (Hazard Ratio 1.74; Logrank p=6x10-4) in overall survival from PDAC. Thus we have begun to examine the biological functions mediated by αvβ6 in a transgenic model of PDAC.

A panel of cell lines were generated from PDAC tumors of a novel transgenic mouse and characterized for markers of tissue identity, integrin expression and ability to invade using 3D-organotypic assays. Cell populations appeared to contain both epithelial (E-cadherin positive) and mesenchymal (vimentin positive) characteristics, highlighting their polyclonality. In addition, two cell populations, KVC1 and KPCD3, expressed low levels of αvβ6 and were studied further. KVC1 and KPCD3 cells were labeled with 10D5 (anti-αvβ6) and sorted by FACS to obtain high-αvβ6 expressing monoclonal cell lines. The resulting cell lines after four rounds of sorting (S4) demonstrated mean MFI values of approximately 4.5-fold (KVC1 vs. KVC1 S4 A+) and approximately 3-fold (KPCD3 vs. KPCD3 S4 E+) higher than their parental counterparts. To compare the invasion profile of the parental populations and S4 monoclonal cell lines, cells were placed in 3D organotypic assays with mouse embryonic fibroblasts (MEFs) for 14 days before gels were fixed and processed to paraffin. H&E stained sections revealed that parental populations KVC1 and KPCD3 formed invasive, single-cell walled ductal structures that had penetrated into the matrigel-collagen mix, but only in the presence of MEFs. In contrast, αvβ6-positive S4 populations, KVC1 S4 A+ and KPCD3 S4 E+, also demonstrated strong invasion but the invasive ductal phenotype was lost, the cells invading as small cohesive groups and individual cells. These data suggest that the pattern of PDAC tumour invasion may be modulated by expression of the integrin αvβ6. Current studies explore the mechanisms by which these phenotypic changes are generated.

Citation Format: Claire S. Reader, Sabari Vallath, Jennifer Morton, Colin Steele, Hemant M. Kocher, Stephen M. Keyse, Owen Sansom, John F. Marshall. Cell lines generated from PDAC transgenic mice reveal integrin αvβ6 modifies the invasive phenotype of 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 B87.
Abstract B89: Polyisoprenylated cysteinyl amide inhibitors of PMPMEase inhibit pancreatic cancer cell viability and migration: Implications for pancreatic cancer therapy
Authors: Nkembo Augustine T. , aguilar Byron J. , Duverna Randolph , Amissah Felix , Lamango Nazarius S.
Published: October 2015

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly neoplasms due to lack of effective targeted therapies. This vacuum stems from the fact that over 90% of pancreatic cancer cases harbor the K-Ras mutation which has been very challenging to drug. The numerous efforts to drug oncogenic Ras have involved inhibiting the post-translational modifications that are essential to its proliferative activity. These drug discovery efforts have largely ignored a critical step in the metabolism of Ras and related proteins involving polyisoprenylated methylated protein methyl esterase (PMPMEase).

The objectives of these studies were to test the hypothesis that PMPMEase hyperactivity promotes pancreatic cancer progression. The potential for polyisoprenylated cysteinyl amide inhibitors (PCAIs) of PMPMEase as potential anticancer agents was evaluated against PDAC cell lines MIAPaCa-2 with K-Ras mutation and BxPC-3 with wild type K-Ras for their effects on cell viability, migration, and cytoskeletal organization.

The PCAIs inhibited the viability of MIAPaCa-2 and BxPC-3 cells with 48 h EC50 values as low as 1.9 and 3.2 µM, respectively. Erlotinib and Salirasib (FTS) were ineffective at concentrations in excess of 20 µM. The PCAIs also inhibited MIAPaCa-2 cell migration by up to 50% at 0.5 µM and disrupted F-actin organization at 5 µM. Further investigations showed that at the EC50 concentrations the PCAIs caused the pancreatic cancer cells to die by apoptosis. The cell cycle analysis for MIAPaCa-2 cells showed that the PCAIs block the cells growth at G0/G1 phase.

The results showed that the PCAIs are over 10-fold more effective than Salirasib and Erlotinib against PDAC cell viability. Furthermore, their effects against cell migration and actin filament organization suggest their potential for treating tumor growth and metastasis in not only PDAC but other cancers with oncogenic Ras.

Citation Format: Augustine T. Nkembo, Byron J. aguilar, Randolph Duverna, Felix Amissah, Nazarius S. Lamango. Polyisoprenylated cysteinyl amide inhibitors of PMPMEase inhibit pancreatic cancer cell viability and migration: Implications for pancreatic cancer therapy. [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 B89.
Abstract B90: Hapten enhanced personalized chemoimmunotherapy by ultra-minimum incision personalized intratumoral chemoimmuno-therapy: UMIPIC-therapy in advanced pancreatic cancer
Authors: Yu Baofa , Gao Feng , Han Wei , Ma Zhenlu
Published: October 2015

Backgound: To evaluate the clinical effectiveness of hapten enhanced chemoimmunotherapy in the treatment of advanced pancreatic cancer by ultra-minimum incision personalized intratumoral chemoimmuno-Therapy (UMIPIC-Therapy) and to further analyze its role as an immune adjuvant.

Method: Patients with late stage pancreatic cancer (92 cases) were treated with UMIPIC-Therapy or just intratumoral Chemotherapy (ITCT) , UMIPIC-Therapy is a proprietary therapeutic regimen which is composed of three components (i.e. an oxidant, a cytotoxic drug and a hapten) that is utilized in chemotherapeutic modulation. The patients (at end of study, 47 patients with complete response analysis data and 45 patients with complete survival data were in the randomly divided two groups: Control group of ITCT alone with an oxidant and a cytotoxic drug without hapten and the experimental group receiving UMIPIC-Therapy with an oxidant, a cytotoxic drug plus hapten.

Result: In the ITCT (control) and UMIPIC (experimental) groups, the clinical response rates were 92.86% and 82.88% respectively; the median survival time and 6-month survival rate were 4.98 months vs 6.45 months and 45% vs 64%, respectively. While all of above mentioned showed no statistical difference (P>0.05), 1-year survival rate of the ITCT group was 5% while those of the ITCIT group was 28% and statistically significant (P<0.05).

Conclusion: The hapten enhanced immunotherapy by ultra-minimum incision personalized intratuoral chemoimmuno-therapy (UMIPIC-Therapy) is shown to be effective in the pancreatic cancer. Our data suggests that the hapten plays an important role in prolonging the patient survival time is could be very valuable in future clinic applications.

Citation Format: Baofa Yu, Feng Gao, Wei Han, Zhenlu Ma. Hapten enhanced personalized chemoimmunotherapy by ultra-minimum incision personalized intratumoral chemoimmuno-therapy: UMIPIC-therapy in advanced 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 B90.
Abstract IA20: Harnessing the immune reaction associated with pancreas carcinoma for therapy
Authors: Beatty Gregory L.
Published: October 2015

Macrophages are a prominent feature of many solid malignancies. However, their presence within tumors most often portends a poor prognosis due to their ability to promote tumor growth, invasion and metastasis. In pancreatic ductal adenocarcinoma (PDAC), macrophages are observed at disease conception and are present throughout all stages of tumor development including metastasis. Strategies to target macrophages in cancer have focused on approaches to 1) deplete macrophages or their precursors, 2) block myeloid cell recruitment to tumor tissues, and 3) inhibit tumor-promoting functions directed by macrophages. However, macrophage biology is largely dependent on cues received from the surrounding microenvironment such that macrophages can be polarized with either tumor promoting or tumor suppressing properties. In this regard, we have previously demonstrated that macrophages can be redirected in vivo with anti-tumor properties leading to depletion of tumor-associated fibrosis and major tumor regressions in both mice and humans. Macrophages responding to systemic activation of the CD40 pathway using an agonist CD40 monoclonal antibody were required for tumor regressions observed in a spontaneous model of murine PDAC. However, not all murine PDAC lesions responded to CD40 therapy. Similarly, treatment response heterogeneity detected on 18FDG-PET/CT was observed in patients with newly diagnosed chemotherapy-naive PDAC who were treated with a fully human CD40 agonist. These findings demonstrate that macrophages associated with PDAC can be harnessed for therapy but also emphasize the importance of tumor intrinsic properties in regulating the efficacy of macrophage immunotherapy in PDAC. Current studies will be presented that investigate 1) the mechanism of action by which macrophages facilitate stromal depletion and 2) potential mechanisms of resistance to macrophage immunotherapy in PDAC.

Citation Format: Gregory L. Beatty. Harnessing the immune reaction associated with pancreas carcinoma for therapy. [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 IA20.
Abstract IA21: The basis of immune suppression in murine pancreatic ductal adenocarcinoma
Authors: Fearon Douglas T.
Published: October 2015

Immune therapy of human pancreatic ductal adenocarcinoma (PDAC) with the T cell checkpoint antagonists, anti-CTLA-4 and anti-PD-L1, has been unsuccessful. To determine the reason for this, we studied the KPC mouse model of autochthonous PDAC in which cancer cells express KrasG12D and p53R172H, and have lost the wild type p53 allele (LOH). These tumors resemble human PDAC in not responding to treatment with anti-CTLA-4 or anti-PD-L1. PDAC-bearing mice have CD8+ T cells specific for antigen(s) expressed by cancer cells. Thus, the ineffectiveness of T cell checkpoint antagonist immune therapy is not explained by the absence of an anti-tumor immune response, and immune suppression in the tumor microenvironment must occur mainly by another means. We have shown that this immune suppressive process depends on the stromal cell known as the “cancer-associated fibroblast” (CAF) that is identified by the membrane protein marker, “fibroblast activation protein” (FAP). Conditionally depleting the FAP+ CAF (Kraman M, et al., Science 2010) leads to T cell-mediated slowing of PDAC growth, and co-treatment with anti-PD-L1 enhances this effect (Feig C, et al. PNAS 2013). Three observations directed attention to the chemokine, CXCL12, as the mediator of immune suppression: the FAP+ CAF is the source of CXCL12 mRNA in PDACs; CXCL12 protein selectively “coats” the cancer cells; and T cells are excluded from the CXCL12-coated cancer cell-containing regions of the tumor. We treated PDAC-bearing mice for 24 hr with AMD3100/Plerixafor, a small molecule antagonist of the CXCL12 receptor, CXCR4, alone or together with anti-PD-L1. Tumors from AMD3100-treated mice exhibit frequent T cells within cancer cell-containing regions, and tumors from dual treated mice have even more T cells. Importantly, whereas tumor volume doubles in control mice in 6 days, AMD3100 alone arrests tumor growth, and AMD3100 + anti-PD-L1 treatment decreases tumor volume by 15%. Both therapies eliminate almost all cancer cells, leaving a residual mass containing only PanIN, inflammatory cells, and desmoplastic matrix. These findings may be relevant not only to human PDAC, but also to colorectal and ovarian carcinoma, all of which also contain FAP+ CAFs and CXCL12-coated cancer cells, demonstrate exclusion of T cells from the vicinity of cancer cells, and are resistant to therapy with anti-PD-1/anti-PD-L1.

Citation Format: Douglas T. Fearon. The basis of immune suppression in murine pancreatic ductal adenocarcinoma. [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 IA21.
Abstract PR07: Transcriptome meta-analysis identifies new 5-gene classifier for early detection of pancreatic cancer
Authors: Bhasin Manoj , Bucur Octavian , Ndebele Ken , Plati Jessica , Bullock Andrea , Gu Xuesong , Castan Eduardo , Najarian Robert , Yeh Jen Jen , Der Channing , Haines Jon Cody , Ruping Karl , Miksad Rebecca , Khosravi-Far Roya , Libermann Towia Aron
Published: October 2015

Background: Pancreatic ductal adenocarcinoma (PDAC) is a truly devastating disease, primarily due to late diagnosis when curative resection is no longer possible and the lack of accurate early detection biomarkers. Therefore, increasing PDAC survival depends heavily on improving the accuracy and effectiveness of early PDAC detection.

Methods:Key PDAC biomarkers were identified through an optimized meta-analysis strategy of raw data in 4 PDAC transcriptome datasets (training sets). Application of identical normalization and statistical testing procedures for each dataset generated a list of differentially expressed genes by empirical Bayes moderated t-statistic. The top ranking PDAC-specific genes from this list that were consistently differentially expressed in these training sets were used for developing a classifier for PDAC. The biomarker panel with the highest sensitivity and specificity in the training sets was validated for diagnostic performance in nine independent validation datasets. A subset of genes in the panel were evaluated by immunohistochemistry (IHC) in human PDAC tissue sections. Cell based assays assessed the effect of two genes on PDAC migration and invasion.

Results and Conclusions: A 5-gene classifier panel was identified that disntinguished between PDAC and normal pancreas with high sensitivity, specificity and accuracy in the four training sets. Validation of this 5-gene predictor in 9 independent test sets confirmed the diagnostic accuracy to not only discriminate accurately between PDAC and healthy controls, but also between pancreatitis and PDAC. IHC analysis of two of the proteins encoded by the panel confirmed enhanced expression in PDAC cells. Cell-based experiments demonstrated that both proteins enhance migration and invasion of PDAC cells as well as soft agar growth, suggesting a causal link to PDAC development and progression. The immediate clinical utility upon further prospective validation of this PDAC biomarker panel will be accurate PDAC diagnosis in patients with pancreatic abnormalities on imaging, risk stratification and evaluation of the risk of malignancy in pancreatic cysts.

This abstract is also presented as Poster B26.

Citation Format: Manoj Bhasin, Octavian Bucur, Ken Ndebele, Jessica Plati, Andrea Bullock, Xuesong Gu, Eduardo Castan, Robert Najarian, Jen Jen Yeh, Channing Der, Jon Cody Haines, Karl Ruping, Rebecca Miksad, Roya Khosravi-Far, Towia Aron Libermann. Transcriptome meta-analysis identifies new 5-gene classifier for early detection of 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 PR07.
Abstract PR08: Pulling out all the stops: Exploiting macropinocytosis inhibition for the treatment of pancreatic cancer
Authors: Commisso Cosimo , Ramirez Craig , Soydaner-Azeloglu Rengin , Bajor David L. , Vonderheide Robert H. , Bar-Sagi Dafna
Published: October 2015

Oncogenic Ras stimulates macropinocytosis, an endocytic mechanism of fluid-phase uptake that produces large intracellular vesicles known as macropinosomes. Recently, we have linked the macropinocytic uptake of extracellular albumin and its subsequent degradation to amino acid supply and proliferation in Ras-transformed cells. The ability of albumin to serve as a nutrient source in oncogenic Ras-expressing cells is blocked by inhibiting its internalization via treatment with 5-(N-Ethyl-N-isopropyl) amiloride (EIPA). We determined that EIPA treatment diminished the growth of pancreatic tumor xenografts and that this effect was selective for tumors with a high macropinocytic index. Currently, we are exploring the feasibility of employing macropinocytosis inhibition as an anticancer therapeutic modality utilizing an autochthonous mouse model of pancreatic cancer. In these autochthonous tumors, macropinocytosis is a prominent feature of pancreatic cells found in mid- to late-stage PanIN lesions, as well as in fibroblasts and immune cells residing within the tumor stroma. We have found that EIPA treatment results in a rapid and robust reduction in proliferative capacity both in tumor cells and the surrounding stromal cells. Intriguingly, our preliminary data indicates that EIPA treatment reduces the number of activated fibroblasts associated with PanIN lesions, decreases collagen deposition and results in an increase in blood vessel diameter. Studies have demonstrated that targeting components of the extracellular matrix within the tumor stroma can cause expansion of the vasculature, which can be harnessed to improve drug delivery and permeability to the tumor. Altogether, our findings suggest that macropinocytosis inhibition could be exploited not only to target the tumor cells, but also to target the tumor stroma and enhance the delivery of chemotherapeutics.

This abstract is also presented as Poster B37.

Citation Format: Cosimo Commisso, Craig Ramirez, Rengin Soydaner-Azeloglu, David L. Bajor, Robert H. Vonderheide, Dafna Bar-Sagi. Pulling out all the stops: Exploiting macropinocytosis inhibition for the treatment of 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 PR08.
Abstract PR10: Re-engineering immunity to treat pancreas cancer
Authors: Stromnes Ingunn M. , Brockenbrough Scott , Schmitt Thomas M. , Hotes Jennifer D. , Carlson Markus A. , Cuevos Carlos , Greenberg Philip D. , Hingorani Sunil R.
Published: October 2015

Designing T cells to effectively and safely target pancreatic ductal adenocarcinoma (PDA) has therapeutic promise, especially if combined with approaches to modify the desmoplastic and immunosuppressive tumor environment. We cloned and expressed a panel of enhanced affinity PDA-specific T cell receptors and the fate and function of such engineered tumor-specific T cells have been tracked in vivo using a genetically engineered mouse model of PDA (KPC) that we have backcrossed to C57Bl/6. Engineered T cells preferentially accumulate in PDA and express markers indicative of antigen recognition only in tumors and not peripheral sites. The transfer of engineered PDA-specific T cells significantly increased tumor cell apoptosis and remodeled the tumor matrix. However, over-time, persisting tumor-infiltrating, engineered T cells expressed markers associated with chronic antigen signaling and exhibited dysfunction as compared to donor T cells isolated from the periphery of the same host, indicating selective immunosuppression at the tumor site. Ongoing studies have identified distinct populations of immunosuppressive cells in PDA that are selectively being targeted to reveal how to sustain and enhance the activity of tumor-specific T cells. Our studies aim to elucidate the cellular and molecular signals impacting the activity of T cells specific to naturally occurring antigens overexpressed by PDA that will help to provide essential insights for the engineering of human lymphocytes and the design of clinical trials to translate our findings to patient treatment.

This abstract is also presented as Poster B58.

Citation Format: Ingunn M. Stromnes, Scott Brockenbrough, Thomas M. Schmitt, Jennifer D. Hotes, Markus A. Carlson, Carlos Cuevos, Philip D. Greenberg, Sunil R. Hingorani. Re-engineering immunity to treat pancreas 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 PR10.
Abstract PR11: CD4+ T lymphocyte ablation prevents pancreatic carcinogenesis in mice
Authors: Zhang Yaqing , Yan Wei , Mathew Esha , Bednar Filip , Wan Shanshan , Collins Meredith A. , Evans Rebecca A. , Welling Theodore H. , Vonderheide Robert H. , Magliano Marina Pasca di
Published: October 2015

Pancreatic cancer, one of the deadliest human malignancies, is associated with oncogenic Kras and is most commonly preceded by precursor lesions known as Pancreatic Intraepithelial Neoplasias (PanINs). PanIN formation is accompanied by the establishment of an immune-tolerant microenvironment. However, the immune contribution to the initiation of pancreatic cancer is currently poorly understood. Here, we show that oncogenic Kras-expressing epithelial cells drive the establishment of an immunosuppressive microenvironment through the recruitment and activity of CD4+ T cells. We further show that CD4+ T cells functionally repress the activity of CD8+ T cells. Elimination of CD4+ T cells uncovers CD8+ T cells anti-neoplastic function, and blocks the onset of pancreatic carcinogenesis. Thus, our studies uncover essential and opposing roles of immune cells during PanIN formation, and provide rationale to explore immune-modulatory approaches in pancreatic cancer.

This abstract is also presented as Poster A48.

Citation Format: Yaqing Zhang, Wei Yan, Esha Mathew, Filip Bednar, Shanshan Wan, Meredith A. Collins, Rebecca A. Evans, Theodore H. Welling, Robert H. Vonderheide, Marina Pasca di Magliano. CD4+ T lymphocyte ablation prevents pancreatic carcinogenesis in mice. [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 PR11.
Abstract PR13: Pancreatic tumor stem cells resistant to inhibition of oncogenic signaling are dependent on mitochondrial function
Authors: Viale Andrea , Pettazzoni Piergiorgio , Lyssiotis Costas , Ying Haoqiang , Sánchez Nora , Marchesini Matteo , Carugo Alessandro , Green Tessa , Seth Sahil , Giuliani Virginia , Heffernan Timothy , Kimmelman Alec , Wang Huamin , Fleming Jason , Cantley Lewis , DePinho Ronald , Draetta Giulio
Published: October 2015

Pancreatic ductal adenocarcinoma (PDAC) continues to have a poor prognosis despite extensive characterization of underlying genetic lesions. Although KRAS mutation is a signature driver event required for tumor development and maintenance, all the attempts made to target oncogene-driven signaling pathways have been met with minimal impact on survival and tumors eventually relapse, suggesting that ablation of oncogenic pathways fails to eradicate tumor cells. We used a genetically engineered mouse model of PDAC in which we could control the expression of mutant KRAS in a time- and tissue-specific manner to study the effects of ablating oncogenic signaling on PDAC cells. As previously described (Ying et al. 2012), this model showed rapid tumor growth when KRAS was expressed, followed by robust tumor regression upon oncogene ablation. However a small population of tumor cells survive genetic and pharmacological inactivation of KRAS. These surviving cells are tumor stem cells able to remain in a quiescent state for months before repopulating the original tumor upon reactivation of KRAS signaling. In depth transcriptomic and metabolomic analyses revealed surviving cells have different metabolic features with respect to the bulk of tumor cells, showing a prominent expression of genes governing mitochondrial function, β-oxidation and autophagy, as well as strong reliance on mitochondrial respiration, yet these cells also displayed impaired glycolytic capacity. In accord with their decreased dependence on glycolysis for cellular energetics and their complete absence of glycolytic reserve, these PDAC surviving tumor stem cells show high sensitivity to oxidative phosphorylation inhibitors, which prevented tumor recurrence. Our integrated analysis paves the way for new therapeutic strategies combining KRAS signaling and oxidative phosphorylation inhibition to completely eradicate pancreatic ductal adenocarcinoma.

This abstract is also presented as Poster A87.

Citation Format: Andrea Viale, Piergiorgio Pettazzoni, Costas Lyssiotis, Haoqiang Ying, Nora Sánchez, Matteo Marchesini, Alessandro Carugo, Tessa Green, Sahil Seth, Virginia Giuliani, Timothy Heffernan, Alec Kimmelman, Huamin Wang, Jason Fleming, Lewis Cantley, Ronald DePinho, Giulio Draetta. Pancreatic tumor stem cells resistant to inhibition of oncogenic signaling are dependent on mitochondrial function. [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 PR13.
Abstract A07: Included in the debate: Women's perspectives on mammography after experiencing a false positive screen
Authors: Thomson Maria D.
Published: October 2015

Background: The utility of mammography screening as an efficacious tool for early detection is being contested due to the risk of potential harms including false positives and over-diagnosis. Yet there is little research regarding women's experiences, values or preferences for participating in mammography programs. Our aim was to explore women's actual experiences of a false positive mammography screen and their perceptions of the value, risks and benefits given their recent experience among a diverse group of mammography screeners.

Methods: Semi-structured interviews were completed with 40 women who experienced a recent false positive mammogram at an academic hospital that provides care to low-income, medically underserved women. Interviews were recorded and transcribed verbatim. A directed content analysis was used to identify and explore primary themes. Knowledge of breast cancer risk was also assessed.

Findings: Unlike most cancer screening samples, women in our study were quite diverse; 45% were African American, 27% were uninsured or insured through Medicare/Medicaid and 22.5% reported incomes less than $30,000. Receiving a false positive mammography screen generated worry among 60% (n=24) of women. Yet 70% maintained that mammography screening was necessary despite the worry incurred. Women also described the experience as stimulating greater interest in additional cancer prevention activities (32.5%; n=13) and one third discussed needing more information about the risks and benefits of mammography screening. Less than one quarter of women (22.5%; n=9) correctly identified a women's lifetime risk of developing breast cancer, 20% (n=8) overestimated and 57.5% (n=23) underestimated this risk.

Conclusion: Our findings represent the experiences of a diverse sample of women whose voices are typically underrepresented and often excluded from the ongoing and contentious medical dialogue regarding mammography. Women reported needing more information about the risks and benefits of mammography screening but also considered false positives an acceptable risk. It is clear that women require and are demanding, more information regarding breast cancer prevention in general and mammography screening in particular. Further, our results suggest that breast cancer screening programs may provide a unique opportunity to deliver additional breast cancer prevention interventions.

Citation Format: Maria D. Thomson. Included in the debate: Women's perspectives on mammography after experiencing a false positive screen. [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 A07.
Abstract A10: Community navigators for breast and cervical cancer screening and follow up
Authors: Simon Melissa A. , Tom Laura S. , Riva Erika E. de la , Malin Emily L.
Published: October 2015

Purpose: Recent multi-site trials evaluating the efficacy of patient navigation programs have found only modest effects on reducing follow-up time among patients with abnormal breast and cervical cancer screening tests. However, patient navigators in these efficacy trials have primarily been situated within a hospital or clinic – not nested within the community. We sought to further elucidate the potential impact of patient navigation by exploring how patient navigation initiatives in various community settings can address complex barriers to care.

Methods: We present four case studies to provide insight on the value of community-nested navigators in increasing breast and cervical cancer screening and follow-up. Case studies include: (1) a community-level adaptation of patient navigation to Chicago's Chinatown; (2) a community navigation and outreach program in the racially/ethnically diverse Chicago Lawn; (3) a county-wide dissemination of navigation in suburban DuPage County; and (4) a state-wide scaling of a patient navigation model to the Illinois Department of Health and Family Services. Case study data were derived from focus groups, key informant interviews, medical records review, and patient surveys.

Results: Case studies describe the roles of community navigators and the challenges of navigating immigrant, non-English proficient patients in particular. Translating clinic-based patient navigators into community navigators to guide women through clinics, specialty referrals, diagnostic/testing sites, and wrap around services (e.g., transportation, housing, support groups, legal counseling) may help alleviate complex barriers to care in resource-thin environments.

Conclusion: Community navigators are promising connectors and advocates for health care services delivery and prevention for culturally and linguistically isolated populations as well as communities with limited health care safety net systems. The community, county, and state-wide scaling of patient navigation described in these case studies serve as viable models for future patient navigation initiatives in low-resource settings to reduce cancer disparities.

Citation Format: Melissa A. Simon, Laura S. Tom, Erika E. de la Riva, Emily L. Malin. Community navigators for breast and cervical cancer screening and follow up. [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 A10.
Abstract A33: The association between breast cancer treatment decisions, fertility and emotional well-being among premenopausal women: An original data collection
Authors: Campbell Angela Gale , Hillemeier Marianne , Anderson Roger
Published: October 2015

Women in their reproductive years, ages 14 through 44, account for 15% of all breast cancer cases in the United States (Tomao et al, 2010). The 5-year survival rate for women diagnosed during these years is on average 85% (“Cancer Survival by Age”, 2014). Breast cancer treatment often leads to infertility (Tomao et al, 2010). Therefore, many survivors will become infertile without reaching their desired family size. Unfortunately, prior studies reveal low patient awareness of the infertility risks associated with cancer treatment until after they have completed treatment (Crawshaw et al, 2009). This suggests a potential decrease in quality of life once they enter remission. This paper outlines the process of developing a survey for original data collection among women in Pennsylvania who are registered as breast cancer survivors and who were diagnosed during their reproductive years. The central focus of the study is whether breast cancer treatment and remission is associated with a change in family size expectations among pre-menopausal women and if this is associated with the information a woman receives before she begins treatment. Additionally, we will be asking if the change in family size expectations pre and post-treatment are associated with feelings of regret, satisfaction or depression. Questions are taken largely from surveys focused on medical decision making. An original conceptual model is developed.

Citation Format: Angela Gale Campbell, Marianne Hillemeier, Roger Anderson. The association between breast cancer treatment decisions, fertility and emotional well-being among premenopausal women: An original data collection. [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 A33.
Abstract A46: SOURCE: Strengthening Our Understanding of Research through Community Engagement
Authors: Gonzalez Evelyn , Fleisher Linda G. , Washington Armenta , Ortiz Rosa , King Andrea
Published: October 2015

Each year research finding from clinical trials advance the quality of care provided to cancer patients. Yet, participation in the United States remains under 3% for the general population and lower rates of participation amongst racial and ethnic minority groups. A significant amount of research has been conducted to evaluate barriers to participation. Our team set out to explore motivators and/or facilitators to participation in addition to barriers. SOURCE: Strengthening Our Understanding of Research through Community Engagement is an NCI funded pilot project designed to explore community responses to actual clinical trial studies by African American and Hispanic/Latino audiences. Utilizing a series of scenarios, participants were introduced to four studies including a biospecimen tobacco study, a longitudinal prevention study, and two randomized treatment trials. The mechanism used to gain this information is community dialogues and group discussions with guidance from a steering committee comprised of community leaders and behavioral and basic scientists from Fox Chase Cancer Center. Results from the targeted questions used to prompt responses and discussion will be used to tailor recruitment efforts, education and outreach, and professional training. In total, four sessions occurred and 96 participated in our community dialogues; 71% were female, 48% Hispanic/Latino and the average age was 57. Both qualitative and quantitative data was collected, the later via ARS (automatic response systems). During our session we will share information regarding concerns the groups expressed, information they seek initially when presented with the option of participation in a clinical trials and share the recommendations provided by participants to keep the community and patients informed and engaged.

Citation Format: Evelyn Gonzalez, Linda G. Fleisher, Armenta Washington, Rosa Ortiz, Andrea King. SOURCE: Strengthening Our Understanding of Research through Community Engagement. [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 A46.
Abstract A51: Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients
Authors: Somerson Jeremy , Kim Isaac , Rajani Rajiv
Published: October 2015

Introduction: Racial and ethnic disparities in limb-salvage surgery have been reported among adult sarcoma patients. The purpose of this work was to explore treatment patterns by ethnicity and gender in a cohort of pediatric sarcoma patients

Methods: A retrospective review was conducted of all consecutive patients under the age of 18 treated for sarcoma at the study institution with diagnoses from 1999 to 2011 who underwent surgery for limb salvage or amputation. Statistical analysis of patient demographics (age, sex, ethnicity and BMI) was performed to assess for factors associated with limb salvage surgery.

Results: 51 records were identified as pediatric patients who underwent surgery for extremity sarcoma in the defined study period. 5 records were excluded due to inadequate availability of body site or surgery type documentation, leaving a cohort of 46 patients. Hispanic patients were more likely to undergo amputation (10 of 36) compared to non-Hispanics (5 of 10; p = 0.03). Female patients were more likely to have had limb salvage (8 of 17) than males (7 of 29; p = 0.04). Logistic regression analysis showed no difference between likelihood of limb salvage and amputation when stratified by BMI or age.

Conclusions: Hispanic ethnicity and male gender were predictors of amputation in a cohort of pediatric sarcoma patients undergoing surgical treatment. Further study should be devoted to identifying underlying factors for ethnic and gender discrepancies between treatment groups.

Citation Format: Jeremy Somerson, Isaac Kim, Rajiv Rajani. Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients. [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 A51.
Abstract A60: My advocacy ecosystem
Authors: Nix Melanie A.
Published: October 2015

My poster is a summary of my 20+ years of advocacy but specifically focuses on my work with (inter)national cancer research, survivorship and advocacy organizations in the last 6 years since my triple negative breast cancer diagnosis. As a mutated BRCA1 gene carrier and fifth generation breast cancer patient whose family has been disproportionately impacted by cancer death, I have been on both sides of the bed as caregiver and patient. My experiences as both caregiver and patient have driven my focus on survivorship and a high quality of life.

My advocacy focus is ensuring that scientists and advocates understand our interdependent roles in the cancer fighting ecosystem and our imperative to collectively work together to effect change and progress.

My poster outlines my advocacy priorities that include:

working with support groups to help other high risk women overcome their fears and becoming their best health advocates by understanding their breast cancer risk factors, attending routine doctor exams, conducting breast self-exams, having routine mammograms and obtaining detailed information about their healthcontinuing my role as a patient advocate as a member of the Advisory Panel on Patient Engagement for Patient-Centered Outcomes Research Institute ensuring continued and multiple opportunities for patient representation and collaboration in research studiespartnering with more national organizations to continue to meet with policymakers to request increased federal funding for cancer research.focusing on clinical trials advocacy ensuring the reduction of barriers that can lead to increased minority participation in clinical trials

Citation Format: Melanie A. Nix. My advocacy ecosystem. [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 A60.
Abstract A65: Proteomics of normal, pancreatitis and pancreatic cancer human tissues
Authors: Mohammed Sulma , Hammons George , Lyn-Cook Beverly D.
Published: October 2015

Pancreatic cancer is one of the most aggressive malignancy with an increased in incidence predicted, particularly in African Americans. Pancreatic cancer is considered a silent disease with poor prognosis and a lack of early biomarkers for detection. Proteomics has been applied in a number of diseases for identifying or discovering biomarkers. It has long been suggested that chronic pancreatitis may put some individuals at risk for developing pancreatic cancer. This study identified proteins that are increased in pancreatic cancer samples using proteomic technology. Proteins were extracted from tissues and separated in 2-D PAGE and imaged. PDQuest 2D image analysis software (Bio-Rad, USA) was used for the automated detection of spots. Representative proteins, overexpressed in tumor and not in the normal tissues, were excised from gels, subjected to in-gel digestion, and analyzed by MALDI-TOF mass spectrometry. Proteins identified included transferrin (Access number (AN) 4557871), ER-60 protein (AN 2245365), proapolipoprotein (AN 178775), tropomyosin 1 (AN 27597085), alpha 1 actin precursor (AN 4501881), ACTB protein (AN 15277503), gamma 2 propeptide (AN 4501889) and an unnamed protein product (AN 921757045). Albumin was abundantly expressed in pancreatic cancer compared to normal samples. Several proteins, which were shown in pancreatic cancer, were also observed in pancreatitis samples. Understanding the role of these specific proteins and their mechanistic action will give insights into their involvement in pancreatic cancer.

Citation Format: Sulma Mohammed, George Hammons, Beverly D. Lyn-Cook. Proteomics of normal, pancreatitis and pancreatic cancer human tissues. [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 A65.
Abstract A66: A population-based study of racial/ethnic differences in survival among patients with endometrial cancer
Authors: Do ThuyQuynh Ngoc , Rodriguez Ana R. , Perez Norma
Published: October 2015

Endometrial cancer is the fourth most common cancer in women in the United States with more minority women being diagnosed with more aggressive cancer than non-Hispanic Whites. Asians and Hispanics are two of the fastest growing racial/ethnic groups in the United States, but they remain one of the most poorly understood minorities in terms of endometrial cancer. Numerous studies have shown that racial/ethnic variation in endometrial cancer can be associated with socioeconomic status, reproductive history and use of exogenous estrogens, the basis for racial/ethnic differences in survival is not as clearly defined. Using public use data from population-based Surveillance, Epidemiology and End Results (SEER) Program, we investigated racial/ethnic differences in cancer-specific survival of women diagnosed with endometrial cancer from 2000-2010. A total of 81,645 women were diagnosed with endometrial cancer. Survival differences were examined using Kaplan-Meier and Cox proportional hazards models. The median cancer-specific survival was 40 months with survival worst among non-Hispanic Blacks. Compared to non-Hispanic Whites, cancer-specific survival was 33% less for non-Hispanic blacks, 10% less for Hispanics and 9% less for Asians after adjustment. About 29% of the racial/ethnic disparity is explained by the absence of any treatment. Racial/ethnic differences in survival may partially explained by differences in treatment and stage diagnosis.

Citation Format: ThuyQuynh Ngoc Do, Ana R. Rodriguez, Norma Perez. A population-based study of racial/ethnic differences in survival among patients with endometrial 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 A66.
Abstract A71: Metagenomic studies of bacterial agents in prostate cancer racial disparities
Authors: Porter Corey M. , Yu Shu-Han , Sfanos Karen
Published: October 2015

Prostate cancer is the most common type of noncutaneous cancer diagnosed in men in the United States and the second leading cause of cancer-related death. African American (AA) men are more likely to be diagnosed with and are more than twice as likely to die from prostate cancer compared to white men. The reasons for this difference are complex. While socio-economic factors and access to care may have some influence, they cannot fully explain this disparity. There is evidence of genetic factors as well as environmental, diet, and lifestyle factors being important contributors to the higher rate of prostate cancer and prostate cancer deaths in AA men. Inflammation has emerged as a potential contributory factor in both the initiation and progression of prostate cancer. Furthermore, previous studies indicate that inflammation and the overexpression of genes involved in inflammatory pathways may be more prevalent in the prostates of AA men versus white men. We hypothesize that prostatic inflammation may contribute to the increase in prostate cancer mortality rates in AA men and that the stimulus for the overexpression of genes involved in inflammatory pathways may be infectious agents. Infections, including sexually transmitted infections (STIs), can cause inflammation and, indeed, our previous studies have detected the presence of microorganisms in prostate tissue. Past infection with an STI as well as increased numbers of sexual partners are both associated with an increased risk of prostate cancer. With the advent of “metagenomic” sequencing technologies (i.e., the determination of all microbial species present in a sample using next-generation sequencing), we are now able to fully determine the variety of microbial species present in a prostate tissue sample. As an initial strategy, we are currently utilizing 16S ribosomal RNA (rRNA) sequencing to comprehensively evaluate the presence of bacterial rRNA in post-surgical prostatectomy tissue specimens from both AA and white men. The results of these analyses will be compared to presence, type, and extent of inflammation in the corresponding surgical tissue specimen and we will be developing strategies to localize microorganism(s) of interest in prostate tissues. The results of our studies stand to provide a wealth of information regarding the prostate tumor microenvironment in AA men and will begin to allow for a mechanistic understanding of the role of inflammation and infections in this prostate cancer racial disparity.

Citation Format: Corey M. Porter, Shu-Han Yu, Karen Sfanos. Metagenomic studies of bacterial agents in prostate cancer racial disparities. [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 A71.