bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract I03: Immune contexture of human pancreatic cancer
Authors: Coussens Lisa M. 
Published: March 2020

Abstract
The concept that leukocytes are critical components of solid tumors is now generally accepted; however, their role(s) in regulating aspects of neoplastic progression, and/or response to cytotoxic, targeted, and/or immune therapy is only beginning to be understood. Utilizing de novo mouse models of organ-specific solid tumor development (mammary, cutaneous, and pancreas carcinomas and mesothelioma), we now appreciate that adaptive leukocytes differentially regulate myeloid cell recruitment, activation, and effector function, and in turn, activated tumor-infiltrating myeloid cells engage tissue-based programs to foster malignancy and repress antitumor immunity by a diversity of mechanisms. Treatment of tumor-bearing mice with therapeutic agents that disrupt lymphocyte-myeloid cell interaction, myeloid cell activation, or myeloid cell functionality generally slow primary tumor growth kinetics when combined with cytotoxic therapy; however, their impact on metastases is variable. Similar to organ-specific regulatory programs co-opted to foster primary tumor growth, regulation of metastatic seeding and outgrowth is also regulated by tissue- and organ-specific mechanisms. Based on this, it stands to reason that therapeutic strategies may not be efficacious in both primary and metastatic locations. To be presented will be our recent insights into organ- and tissue-specific regulation of primary and metastatic cancer development by adaptive and innate immune cells, how systemic regulation of humoral immunity and complement-mediated pathways regulate pro- versus antitumor immune responses, and new studies evaluating how attenuating protumor properties of select lymphoid and myeloid cells can be exploited to enhance therapeutic responses to cytotoxic and immune-based therapy. (LMC acknowledges generous support from the NIH/NCI, the Department of Defense Breast Cancer Research Program, Susan G. Komen Foundation, the Breast Cancer Research Foundation, and the Brenden-Colson Center for Pancreatic Health.)
Citation Format: Lisa M. Coussens. Immune contexture of human pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I03.
Abstract I08: Molecular subtypes - bench to bedside
Authors: Yeh Jen Jen 
Published: March 2020

Abstract
Recent treatment advances in chemotherapy and targeted therapy regimens have provided pancreatic cancer patients and providers with better options. Molecular subtyping for pancreatic cancer has made substantial progress in recent years. With these advances, there is now an opportunity to enable precision medicine approaches for patients with pancreatic cancer. Transcriptomic molecular subtyping is currently an active area of study where several subtyping schemas have been proposed. This talk will present some of these schemas and attempt to reconcile them. Many subtyping approaches rely on the clustering of a new sample with an existing group of samples, the ability to determine the subtype of an individual tumor is limited. In addition, in order to use molecular subtypes in the clinic, subtypes need to be clinically replicable, robust, and have clinical implications. Developing a robust method for subtype classification is needed in order to study the role of molecular subtypes in the context of future clinical trials.
Citation Format: Jen Jen Yeh. Molecular subtypes - bench to bedside [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I08.
Abstract I09: Tumor-specific T cells reprogram mononuclear phagocytes for destruction of checkpoint blockade-resistant pancreatic cancer
Authors: Dougan Stephanie K. 
Published: March 2020

Abstract
Like virally infected cells, tumors can evade CD8 T-cell recognition by downregulation of MHC class I. Loss of MHC class I and IFNg sensing are major causes of primary and acquired resistance to checkpoint blockade immunotherapy. The cellular (c)-IAPs regulate classical and alternative NF-kB signaling, and induction of noncanonical NF-kB signaling using IAP antagonists mimics costimulatory signaling, augmenting antitumor immunity. We now show that induction of noncanonical NF-kB signaling promotes antitumor immunity across a range of orthotopic and spontaneous pancreatic cancer models, and induces T cell-dependent immune responses even in b2m-/- tumors, demonstrating that direct CD8 T-cell recognition of tumor cell expressed MHC class I is not required. Here we show that MHC class I negative tumors can be controlled in a T-cell dependent fashion by repolarized intratumoral phagocytes. In wild-type mice, but not mice incapable of mounting antigen-specific T cell responses, treatment with IAP antagonists increases phagocytosis of tumor cells, as determined by flow cytometry, imaging flow cytometry, and quantitative immunofluorescence. This mechanism of action inspired combination therapy with CD47 blockade, a strategy that induced curative responses in otherwise refractory preclinical models. To our knowledge, this is the first example of antigen specific immunotherapy for tumors that are refractory to checkpoint blockade due to loss of MHC class I or IFNg sensing.
Citation Format: Stephanie K. Dougan. Tumor-specific T cells reprogram mononuclear phagocytes for destruction of checkpoint blockade-resistant pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I09.
Abstract I23: Identifying metabolic dependencies in pancreatic cancer
Authors: Kimmelman Alec 
Published: March 2020

Abstract
Pancreatic cancers are highly resistant to currently available therapeutics, which results in a 5-year survival rate of approximately 6%. We believe that this resistance points toward altered cell metabolic pathways. In this regard we have previously shown that that oncogenic Kras promotes a rewiring of pancreatic cancer metabolism, allowing carbon sources to be utilized in a variety of biosynthetic pathways. Importantly, several of these metabolic pathways are critical for tumor growth and therefore represent potential therapeutic targets. Ongoing studies from our group are exploring targeting various aspects of metabolism as therapeutic approaches. Additional studies from our group have demonstrated pancreatic cancers have elevated basal autophagy, which is required for their continued growth. Importantly, inhibition of autophagy pharmacologically or genetically leads to decreased oxidative phosphorylation, a drop in ATP production, and ultimately growth inhibition. These findings have implicated autophagy as a key component of pancreatic cancer metabolism and have motivated the opening of multiple clinical trials assessing the efficacy of hydroxychloroquine as an autophagy inhibitor in pancreatic cancer. These trials are now showing activity of autophagy inhibition in this disease. Recently, we have identified an autophagy/lysosome-dependent metabolic crosstalk that exists between pancreatic tumor cells and the surrounding stroma. Ongoing work from our group seeks to understand the metabolic contributions that autophagy makes in pancreatic tumors as well as further define the metabolic crosstalks. These and other aspects of pancreatic cancer metabolism will be discussed.
Citation Format: Alec Kimmelman. Identifying metabolic dependencies in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I23.
Abstract ES1-2: Detecting and Managing Immunotherapy-related Toxicities Wisely
Authors: Schmid P 
Published: March 2020

Abstract
With the increasing use of immunotherapy, multidisciplinary breast cancer teams have to get used to recognising and managing immune-related side effects. Although immune checkpoint inhibitors are generally well tolerated, they can cause a wide range of side effects which often differ from those commonly seen with other types of cancer treatment. These immune-mediated side effects include inflammatory or autoimmune reactions which can resemble autoimmune diseases. Side effect patterns can be highly variable in terms of timing, severity and organ manifestation. They appear at any time, sometimes even months after the last treatment, and can affect any part of the body. The risk of developing immune-related side effects generally increases with longer treatment-duration. Most commonly affected body systems are skin, endocrine organs, the gastrointestinal tract, liver and lungs, but even very rare manifestations such as neurological disorders or myocarditis need to be considered as they can be serious. Before considering patients for immunotherapy, they should be carefully assessed with regards the risk of developing immune-related side effects. Patients with a history of autoimmune disorders are generally at risk of worsening of their autoimmune disease with immunotherapy. Early recognition and intervention are critical for the effective management which often includes the use of corticosteroids and occasionally additional immunosuppressive agents. Interdisciplinary working within oncology groups as well as with associated specialties is critical for optimal patients management. With effective management most immune-related side effects resolve and patients can continue their treatment.
Citation Format: P Schmid. Detecting and Managing Immunotherapy-related Toxicities Wisely [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES1-2.
Abstract OT3-12-01: Effect of home-based high-intensity interval training and behavioral modification using information and communication technology on cardiorespiratory fitness and exercise habits among sedentary breast cancer survivors: The habit-B randomized controlled trial in progress
Authors: Tsuji Katsunori , Ochi Eisuke , Shimizu Yoichi , Kuchiba Aya , Narisawa Tomomi , Ishino Yuri , Okubo Ryo , Ueno Taro , Shimazu Taichi , Kinoshita Takayuki , Sakurai Naomi , Matsuoka Yutaka 
Published: March 2020

Abstract
Maintaining high levels of physical activity not only helps to maintain and improve physical health and quality of life, but also plays a role in reducing adverse effects due to cancer treatments. Moreover, a greater degree of cardiorespiratory fitness is associated with reduced risk of all-cause mortality in breast cancer survivors. However, there are no home-based programs for improving cardiorespiratory fitness using body weight exercises for breast cancer survivors. This study assesses the efficacy of the newly developed habit-B program (12-weeks, high-intensity interval training exercise, exercise counseling + guidance, home-based exercise support using information and communication technology, and a wearable device (fitbit versa®)) on peak oxygen uptake (VO2peak; mL/kg/min) compared with treatment as usual. This is a parallel-group, single blind, randomized controlled trial. Subjects are sedentary women aged 20 to 59 years who have received breast surgery in the past 2 to 13 months after diagnosis of invasive breast cancer (Stage I-IIa) and have never received chemo-therapy except for hormone therapy. The primary outcome is difference of change in VO2peak between the groups after 12 weeks. The planned sample size is 60 patients to detect the increase of 2.0 ml/kg/min change in VO2peak with a one-sided significance level of 2.5% and 80% power. The effects of this program on exercise habits, physical activity, physical fitness, fatigue, health-related quality of life, and psychological distress are also be investigated. We have already enrolled 6 subjects as of 2019.7.2, and study will be planned to be finished by 2020 April.
Citation Format: Katsunori Tsuji, Eisuke Ochi, Yoichi Shimizu, Aya Kuchiba, Tomomi Narisawa, Yuri Ishino, Ryo Okubo, Taro Ueno, Taichi Shimazu, Takayuki Kinoshita, Naomi Sakurai, Yutaka Matsuoka. Effect of home-based high-intensity interval training and behavioral modification using information and communication technology on cardiorespiratory fitness and exercise habits among sedentary breast cancer survivors: The habit-B randomized controlled trial in progress [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-12-01.
Abstract P1-07-01: Cholinergic receptor muscarinic 3 (CHRM3) contributes to breast cancer tumorigenesis through angiogenesis regulation
Authors: Chen Jiawei , Shin Vivian Y , Cheuk Isabella , Siu Jennifer , Kwong Ava 
Published: March 2020

Abstract
Objectives: Cholinergic muscarinic receptors are widely distributed in different human organs with various biological functionals such as synaptic transmission. Accumulating evidence revealed the overexpression of these receptors especially cholinergic receptor muscarinic 3 (CHRM3) with multiple roles in cancer behaviors such as proliferation, apoptosis, angiogenic phenotypes and even epithelial-mesenchymal transition (EMT) through various signaling pathways. However, its roles in breast cancer and angiogenesis still remain elusive.
Methods: Gene expression and patient survival data were from the TCGA and the GTEx projects database. Cells were transfected with scrambled shRNA or CHRM3 shRNA to knockdown gene expression. pcDNA1.3 empty expression vector or CHRM3 expressing vector was used for ectopic expression in the cells. Cell proliferation was examined in different treatment groups by MTT assay and further subjected to cell cycle and apoptosis assay. Expression levels of CHRM3 in paired breast cancer tissues and different cell lines as well as angiogenesis-related markers in cells with different treatments were investigated by qRT-PCR.
Results: CHRM3 expressions were significantly upregulated in triple negative breast cancer (TNBC) subtype, but not other subtypes of breast cancer, and was consistent with the data in TCGA database. Further investigation in different breast cancer cells revealed that CHRM3 expressions were higher in MDA-MB-231 and MDA-MB-468, which are both TNBC cell lines. After treatment with CHRM3-specific inhibitor, 4-DAMP, cell viability was significantly decreased in both MDA-MB-231 and MDA-MB-468 cells. G1-phase arrest and decreased S-phase cell populations and early apoptosis were increased upon 4-DAMP. Moreover, angiogenic markers such as ANG1 and VEGFD were significantly decreased upon CHRM3 knockdown in breast cancer cells or human umbilical vein endothelial cells (HUVEC). Gene correlation analysis from TCGA database indicated a significant positive correlation between CHRM3 and ANG1. Furthermore, CHRM3 shRNA or 4-DAMP treatment inhibited cell proliferation in both MDA-MB-231 and HUVEC.
Conclusions: We found that CHRM3 is upregulated in TNBC tissues and cell lines. CHRM3 confers tumor oncogenic roles, and for the first time, we identified a potential relationship between CHRM3 and angiogenesis in breast cancer. Further experiments are warranted to explore the underlying mechanism of CHRM3 in regulating angiogenesis.
Citation Format: Jiawei Chen, Vivian Y Shin, Isabella Cheuk, Jennifer Siu, Ava Kwong. Cholinergic receptor muscarinic 3 (CHRM3) contributes to breast cancer tumorigenesis through angiogenesis regulation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-07-01.
Abstract P3-01-24: The cancer-associated TRPC5 opposite strand protein, a novel regulatory factor for cell proliferation in triple negative breast cancer
Authors: Cui Yangyang , Peng Jinghui , Huang Yue , Fu Ziyi , Xie Hui , Wang Shui 
Published: March 2020

Abstract
Background: Breast cancer is the most common malignant tumors worldwide and the leading cause of cancer death among female. Microproteins, a kind of protein which is nearly 100 amino acids in length, have been demonstrated to play important roles in biology and disease. Here, we present a potential microprotein TRPC5 opposite strand (TRPC5OS), which may exert function in breast cancer progression. Methods: Differential expression of TRPC5OS in breast cancer was measured via Immunohistochemistry (IHC) in breast cancer samples and quantitative real-time PCR (qRT-PCR) in cell lines. The effects of TRPC5OS on proliferation and cell cycle progression of breast cancer cells were evaluated by using Cell counting kit-8 (CCK-8), colony formation assay and cell cycle analysis by flow cytometry. The tumor growth in vivo was observed in xenograft model. Co-immunoprecipitation (Co-IP), western blot analysis and immunofluorescent staining were performed to validate the interaction between TRPC5OS and ENO1. Glucose uptake was measured by liquid scintillation spectrometry and involvement of the PI3K and AKT pathways was investigated by western blot analysis. Results: TRPC5OS showed an enhanced expression in breast cancer patient samples predominantly in HER-2 negative breast cancer, especially in triple negative breast cancer (TNBC). Overexpression TRPC5OS increased TNBC cell proliferation, promoted cell cycle progression, enhanced xenograft tumor growth, and associated with PI3K-AKT pathway. In addition, TRPC5OS could enhance glucose uptake via interacting with alpha-enolase (ENO1) and increase the protein level of ENO1, and ENO1 was found to be the functional target of TRPC5OS in TNBC cells. Conclusions: This study demonstrates that TRPC5OS promotes proliferation by interacting with ENO1 and may provide a strategy for future diagnosis of human breast cancer, a new potential therapeutic target for TNBC patients as well. Key words: breast cancer, TRPC5OS, proliferation, ENO1, glucose uptake
Citation Format: Yangyang Cui, Jinghui Peng, Yue Huang, Ziyi Fu, Hui Xie, Shui Wang. The cancer-associated TRPC5 opposite strand protein, a novel regulatory factor for cell proliferation in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-24.
Abstract P5-04-28: Targeting TIGIT and PD-1 in triple negative breast cancer
Authors: Pandey Apurva Kumari , Chauvin Joe Marc , Brufsky Adam , Pagliano Ornella , Ka Mignane , Menna Carmine , McAuliffe Priscilla , Zarour Hassane 
Published: March 2020

Abstract
Background: Triple negative breast cancer is aggressive and has poor prognosis. Tumor infiltrating lymphocytes (TILs) have a prognostic value in triple negative breast cancer. Increased TILs are associated with better disease-free survival and overall survival in triple negative breast cancer (TNBC). Newly approved immunotherapy drug for metastatic triple negative breast cancer patients, Atezolizumab, has shown 10 months improvement in overall survival in for PD-L1 positive group in combination with nab-paclitaxel compared to placebo and paclitaxel. Beyond PD-1 inhibitors, there is a need to improve immunotherapy options in TNBC. TIGIT gene expression in triple negative breast cancer is associated with immune function is linked with improved relapse free survival and overall survival. CD155, a high affinity receptor for TIGIT, is expressed on tumor cells including lung and melanoma. We aim to evaluate the role of TIGIT in regulating immune response to TNBC, TIGIT cooperation with PD-1 in impeding T cell responses to TNBC, and expression of TIGIT ligands on TNBC.
Methods: Fresh TNBC tumor samples were obtained from 10 untreated patients and were used for single cell suspension and multi parameter flow cytometry.
Results: CD8+ and CD4+ TILs in TNBC exhibited higher PD-1 and TIGIT, yet lower CD226 expression as compared to circulating T cells. LAG-3 and TIM3 were expressed at low frequency in CD 8+ and CD 4+ cells. TNBC Tregs display high expression of TIGIT, PD-1, TIM3 but low CD226 expression. TIGIT interacts with CD155 and CD112 with high affinity and both were found to be highly expressed by TNBC tumor cells and APCs. PD-1−TIGIT+ CD8+ TILs are present at high frequency and appear to represent an activated T cell subset. PD-1+Tim-3+TIGIT+ produced less cytokines including interferon gamma, IL-2, and TNF than other CD8+ T cell subsets, representing a dysfunctional T cell subset.
Conclusions: TIGIT is highly upregulated by TNBC CD8+ and CD4+ TILs while the TIGIT ligands are highly expressed by tumor cells and APCs in TNBC. In sharp contrast with metastatic melanoma, high frequency PD-1−TIGIT+CD8+ TILs are present in TNBC. Additional studies will investigate the role of dual PD-1/TIGIT blockade in increasing CD8+ TIL function in TNBC. Such data may support the dual PD-1/TIGIT blockade in TNBCs.
Citation Format: Apurva Kumari Pandey, Joe Marc Chauvin, Adam Brufsky, Ornella Pagliano, Mignane Ka, Carmine Menna, Priscilla McAuliffe, Hassane Zarour. Targeting TIGIT and PD-1 in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-28.
Abstract P6-13-02: Subcutaneous trastuzumab for the treatment of HER2+ breast cancer in Canada: A cost-minimization study
Authors: Coombes Megan , Yin Lori , Liu Ingrid , Shek Norman , Rusu Flavia , Mukherjee Som 
Published: March 2020

Abstract
Background: There is an urgent need to alleviate the pressure on healthcare resources and decrease treatment burden for patients. Recently, a new fixed dose subcutaneous (SC) formulation of trastuzumab was approved by Health Canada for use in HER2-positive breast cancer (HER2+ BC) patients. Studied in multiple trials and treatment settings, the totality of evidence demonstrated similar safety and efficacy to the IV formulation as well as a strong preference for trastuzumab SC by patients and health care professionals.
Objective: To estimate the incremental costs/savings associated with the use of trastuzumab SC for the treatment of HER2+ BC if reimbursed with the same provincial funding criteria as trastuzumab IV in Ontario, Canada.
Methods: An Excel-based cost-minimization and budget impact model was developed to determine the economic impact of trastuzumab SC in comparison to trastuzumab IV in Ontario. Direct medical costs in the analysis included drug acquisition, drug preparation, drug administration, central venous access device (CVAD), and systemic therapy suite costs.
Results: Early and metastatic HER2+ BC patients treated with trastuzumab SC are expected to generate a net cost savings to the health system compared to treatment with trastuzumab IV. Savings are estimated at $11,943 per eBC patient and $11,943 per mBC patient, representing total savings of $15.8M in Year 1, $19.4M in Year 2, and $23.0M in Year 3. The use of trastuzumab SC in these populations enhances the ability of the payer to manage drug and medical resources, while offering a therapy that is aligned with patient and clinician preferences.
Citation Format: Megan Coombes, Lori Yin, Ingrid Liu, Norman Shek, Flavia Rusu, Som Mukherjee. Subcutaneous trastuzumab for the treatment of HER2+ breast cancer in Canada: A cost-minimization study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-02.