bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3580: Integrative genomics of checkpoint blockade response in advanced non-small cell lung cancer
Authors: Ravi Arvind , Gainor Justin , Arniella Monica , Stewart Chip , Freeman Sam , Awad Mark M. , Forde Patrick , Anagnostou Valsamo , Henick Brian , Riess Jonathan W. , Gibbons Don , Pennell Nathan , Velcheti Vamisdhar , Leshchiner Ignaty , Kim Jaegil , Digumarthy Subba , Mino-Kenudson Mari , Heymach John , Vokes Natalie , Griffin Andrew , Ricciuti Biagio , Rizvi Naiyer , Herbst Roy , Velculescu Victor , Brahmer Julie , Schalper Kurt , Janne Pasi , Wolchok Jedd , Shaw Alice , Hacohen Nir , Getz Gad , Hellmann Matthew D. 
Published: June 2022

Abstract
The introduction of checkpoint blockade therapy, specifically anti-PD-1/PD-L1 agents, has transformed the treatment landscape of advanced Non-Small Cell Lung Cancer (NSCLC). While our understanding of the biology underlying immunotherapy in NSCLC is still incomplete, studies to date have established central roles for Tumor Mutation Burden (TMB) and PD-L1 Tumor Proportion Score (PDL1-TPS). In order to expand our understanding of the molecular features underlying response in NSCLC, we describe here the first joint analysis of the Stand Up 2 Cancer-Mark Foundation (SU2C-MARK) Cohort, a collection of 393 patients with whole exome and/or RNA sequencing along with matched checkpoint blockade response annotation. We identify a number of significant associations between molecular features and response, including: 1) favorable and unfavorable genomic subgroups; 2) distinct immune infiltration signatures associated with wound healing (unfavorable) and immune activated (favorable) microenvironments; and 3) a novel de-differentiated tumor-intrinsic subtype characterized by high TMB, immune activation, and enhanced response rate. Taken together, results from this cohort extend our understanding of NSCLC-specific predictors, providing a rich set of molecular and immunologic hypotheses with which to further our understanding of the biology of checkpoint blockade in NSCLC.
Citation Format: Arvind Ravi, Justin Gainor, Monica Arniella, Chip Stewart, Sam Freeman, Mark M. Awad, Patrick Forde, Valsamo Anagnostou, Brian Henick, Jonathan W. Riess, Don Gibbons, Nathan Pennell, Vamisdhar Velcheti, Ignaty Leshchiner, Jaegil Kim, Subba Digumarthy, Mari Mino-Kenudson, John Heymach, Natalie Vokes, Andrew Griffin, Biagio Ricciuti, Naiyer Rizvi, Roy Herbst, Victor Velculescu, Julie Brahmer, Kurt Schalper, Pasi Janne, Jedd Wolchok, Alice Shaw, Nir Hacohen, Gad Getz, Matthew D. Hellmann. Integrative genomics of checkpoint blockade response in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3580.
Abstract 360: Methyl-cantharidimide (MCA) can induce apoptosis by activating UNC5B-Netrin-1-DAPK pathway in hepatocellular carcinoma
Authors: Li Yi-Dong , Mao Yong , Dong Xing-Duo , Lei Zi-Ning , Yang Yuqi , Lin Lizhu , Yang Dong-Hua , Chen Zhe-Sheng 
Published: June 2022

Abstract
In this study, we investigated the underlying mechanism of action of methyl-cantharidimide (MCA), a cantharidin (CTD) analog, as an anticancer drug, in resistant cancer cells overexpressing either ABCB1 or ABCG2 and in cisplatin-resistant cancer cells. The results indicated that: (i) MCA was efficacious in the ABCB1-overexpressing cell line, KB-C2, the ABCG2-overexpressing cell line, NCI-H460/MX20 and in the cisplatin resistant cancer cell lines, KCP-4 and BEL-7404/CP20; (ii) MCA induced apoptosis in both BEL-7404 and BEL-7404/CP20 cancer cells and arrested both BEL-7404 and BEL-7404/CP20 cancer cells in the G0/G1 phase of the cell cycle; (iii) MCA upregulated the expression level of the protein, unc-5 netrin receptor B (UNC5B) in HepG2 and BEL-7404 cancer cells. (iv) MCA can activate UNC5B-Netrin-1-DAPK apoptosis pathway in hepatocellular carcinoma cells. Overall, our results indicated that MCA's efficacy in multiple cancer cell lines is due to the activation of UNC5B-Netrin-1-DAPK apoptosis pathway and cell cycle arrest in the G0/G1 phase.
Citation Format: Yi-Dong Li, Yong Mao, Xing-Duo Dong, Zi-Ning Lei, Yuqi Yang, Lizhu Lin, Dong-Hua Yang, Zhe-Sheng Chen. Methyl-cantharidimide (MCA) can induce apoptosis by activating UNC5B-Netrin-1-DAPK pathway in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 360.
Abstract 3615: TREM2+ macrophages mediate immunosuppression in tumors
Authors: Molgora Martina , Luccia Blanda Di , Khantakova Darya , Jaeger Natalia , Czepielewski Rafael Sanguinetti , da Silva Cristiane Secca , Bando Jennifer , Gilfillan Susan , Cella Marina , Schreiber Robert , Colonna Marco 
Published: June 2022

Abstract
Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer’s disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2-/- mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.
Citation Format: Martina Molgora, Blanda Di Luccia, Darya Khantakova, Natalia Jaeger, Rafael Sanguinetti Czepielewski, Cristiane Secca da Silva, Jennifer Bando, Susan Gilfillan, Marina Cella, Robert Schreiber, Marco Colonna. TREM2+ macrophages mediate immunosuppression in tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3615.
Abstract 3640: Adipocyte age dependent metabolic programming dictates melanoma metastatic burden and tropism
Authors: Gurung Shilpa 
Published: June 2022

Abstract
The aged skin microenvironment and aged fibroblasts contribute to melanoma progression. A key hallmark of skin ageing is the loss of subcutaneous fat. Because previous work has established that lipids contribute to melanoma invasion and proliferation, we studied whether aged adipocytes contribute to the poor outcome of aged patients. We compared the distinct lipid secretory profile of young and aged human subcutaneous adipocytes, and discovered young and aged adipocytes contribute different lipids to the melanoma microenvironment, activating aged-dependent signaling pathways and driving distinct metabolic programms in melanoma cells.
To test how aged and young adipocytes affect melanoma, we obtained human preadipocytes from donors of different ages and differentiated them to functional adipocytes in vitro. We studied the morphological, transcriptomic, proteomic, and lipid profile of adipocytes by age, then exposed melanoma cells to the young or aged adipocyte secretome. We observed melanoma cells exposed to young adipocyte secretome increased the rate of proliferation, invasion, and migration compared to melanoma cells exposed to aged adipocyte secretomes. This effect was linked to a greater amount of total lipids secreted by young adipocytes, as well as a unique ratio of lipids by age, which were taken up by melanoma cells. Critically, lipid transfer led to distinct signaling pathway activation and metabolic reprogramming. In vivo, these differences led to a greater rate of metastasis and distinct tropism of melanoma cells exposed to aged or young adipocyte secretomes. Finally, we systematically tested the contribution of differentially secreted lipids by age and identified the specific lipids that function as signaling molecules to switch metabolic dependencies and fuel proliferation, invasion, and migration of melanoma cells
Citation Format: Shilpa Gurung. Adipocyte age dependent metabolic programming dictates melanoma metastatic burden and tropism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3640.
Abstract 3646: Distinct functions of pancreatic stellate cells in PDAC stromal evolution
Authors: Onate M. Kathrina Casapao , Schleisman Matthew , Xia Zheng , Sherman Mara H. 
Published: June 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year relative survival rate of 10.8%. After surgery, radiation and chemotherapy are the next lines of therapy. However, these treatments have not significantly improved clinical outcomes due in part to its unique and characteristic desmoplasia, which limits treatment efficacy. Cancer-associated fibroblasts (CAFs) have been shown to contribute in PDAC’s stromal reaction in part viasecretion of extracellular matrix (ECM) components and growth factors, suggesting that CAFs are pro-tumorigenic. This understanding led to several CAF ablation preclinical studies; surprisingly, these studies demonstrated tumor-suppressive potential for CAFs, highlighting the functional heterogeneity among CAFs in PDAC. This emphasizes the need for greater developmental understanding of this influential cell population. Lineage tracing via our recently established Fabp4-Cre;Rosa26mTmG mouse model revealed that pancreatic stellate cells (PSCs), thought to be the main cellular origin of PDAC CAFs, contribute to a minor faction of CAFs yet appear to have non-redundant functions to alternatively-derived CAFs. Here we delve further into the specific functions of PSC-derived CAFs via single-cell RNA sequencing of pancreatic stellate cells in healthy and tumor pancreas with our Fabp4-Cre;Rosa26mTmG mouse model. To our surprise, initial scRNA-seq analysis illustrated that quiescent pancreatic stellate cells from healthy tissue appear to be more heterogeneous to PSC-derived CAFs, with quiescent pancreatic stellate cells clustering into three “super clusters” while PSC-derived CAFs clusters into one “super cluster”. Additionally, clusters specific to normal pancreas tissue revealed potential transcripts-of-interest that are anti-tumorigenic. Current efforts seek to analyze stromal evolution with respect to CAF cell of origin in pre-malignant lesions and throughout stepwise tumorigenesis to metastasis. Furthermore, we are investigating the functional significance of potentially anti-tumorigenic factors lost from the PSC compartment upon differentiation to a CAF phenotype during PDAC progression. These findings shed light on the increasingly appreciated heterogeneity of PDAC CAFs, whilst suggesting that PSC-derived CAFs may be specifically targeted as a singular cell population for therapeutic treatment. Importantly, these findings help gain a greater understanding of PDAC disease progression and development in order to better serve patient care.
Citation Format: M. Kathrina Casapao Onate, Matthew Schleisman, Zheng Xia, Mara H. Sherman. Distinct functions of pancreatic stellate cells in PDAC stromal evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3646.
Abstract 3648: Hedgehog represses angiogenesis in PDAC through a paracrine cascade mediated by Wif1
Authors: Hasselluhn Marie C. , Decker Amanda R. , Garcia Alvaro Curiel , Maurer Carlo , Thomas Dafydd H. , Olive Kenneth P. 
Published: June 2022

Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an extremely heterogeneous tumor microenvironment (TME) paired with a sparse and compromised vascular network. These features of the TME shape drug responses and contribute to PDAC’s distinctive chemotherapeutic resistance. Prior work demonstrated that inhibition of the Hedgehog (Hh) signaling pathway using Smoothened (Smo) inhibitors led to increased angiogenesis. However, the precise mechanisms through which the Hh pathway regulates angiogenesis has remained elusive and subsequent studies with different agents and timepoints yielded conflicting data. Frustratingly, the phenotype could not be recreated in simple co-culture models.
In order to maintain the cellular heterogeneity and spatial organization that characterizes PDAC, we developed a novel tumor explant system for short-term cultures of both murine and human PDAC. Briefly, we cultured intact 300 μm slices of PDAC tissue on a modified gelatin platform system with a novel culture medium informed by the metabolic composition of PDAC tumor interstitial fluid. This system replicates some of the nutrient/waste gradient of PDAC and enables tumors to be cultured up to one week maintaining the representation of multiple cell types. Studies in explants were complemented by work in the Kras-LSL.G12D/+, p53-LSL.R172H/+, Pdx1-Cre (KPC) genetically engineered model of PDAC.
Comparison of short versus long-term Smo inhibition in KPC mouse pancreatic tumors revealed a robust increase in vessel density in short-term treatment that is lost at later timepoints. Studies in murine and human PDAC explants employing different Smo inhibitors demonstrated increased endothelial tip cell formation upon two days of treatment, resulting in increased vessel density after four days. Computational analyses of human PDAC single cell RNAseq data identified candidate cellular subsets potentially involved in the signaling cascade. RNAseq of pre- and on-treatment tumor samples from KPC mice identified Wif1 as a candidate Hh pathway target gene that effected these programs. Mechanistic studies in tumor explants reveal a complex, multi-step mechanism involving several cell types that led to suppression of angiogenesis in PDAC. These studies both provide a candidate mechanism for Hh-mediated angiosuppression and also demonstrated how the tumor explant platform can elucidate complex intercellular signaling cascades in both murine and human PDAC.
Citation Format: Marie C. Hasselluhn, Amanda R. Decker, Alvaro Curiel Garcia, Carlo Maurer, Dafydd H. Thomas, Kenneth P. Olive. Hedgehog represses angiogenesis in PDAC through a paracrine cascade mediated by Wif1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3648.
Abstract 3652: Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis
Authors: Marley Andrew R. , Domingues Allison , Ghosh Taumoha , Turcotte Lucie M. , Spector Logan G. 
Published: June 2022

Abstract
Introduction: Pediatric cancer incidence has steadily increased concurrent with the rise in adult obesity, however, associations between maternal obesity and associated comorbidities and pediatric cancer risk remain understudied.
Methods: A comprehensive and systematic literature search in PubMed and EMBASE databases from their inception to March 15th, 2021. Eligible studies reported risk estimates, sample sizes, and provided sufficient description of outcome and exposure ascertainment. Studies were excluded if not complete, published, peer-reviewed studies, or if provided incompatible exposure data. Data quality was assessed according to Newcastle-Ottawa Scale (NOS) guidelines and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects models were used to estimate pooled effects.
Results: Thirty-four studies were included, covering 3,404,747 subjects and 14,706 pediatric cancer cases for pre-pregnancy BMI; 14,748,772 subjects and 44,628 pediatric cancer patients for maternal diabetes; and 2,124,647 participants and 15,915 pediatric cancer cases for gestational weight gain. Pre-pregnancy BMI was significantly associated with leukemia risk in offspring (OR per 5-unit BMI increase =1.07 [95% CI = 1.04-1.11] I2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia risk (OR=1.46 [95% CI = 1.28-1.67] I2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR [95% CI] = 1.74 [1.29-2.34] I2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR=0.73 [95% CI = 0.55-0.97] I2 = 0.0%). Pre-gestational diabetes (OR=1.57 [95% CI = 1.11-2.24] I2 = 26.8%) and gestational diabetes (OR=1.40 [95% CI = 1.12-1.75] I2 = 0.0%) were also significantly associated with acute lymphoblastic leukemia risk. No significant associations were observed for gestational weight gain and pediatric cancer risk.
Conclusions: Maternal obesity and diabetes may be etiologically linked to pediatric cancer, particularly leukemia and central nervous system tumors. Our findings support appropriate weight management and glycemic control as important components of maternal care and offspring health. Further validation studies are warranted.
Citation Format: Andrew R. Marley, Allison Domingues, Taumoha Ghosh, Lucie M. Turcotte, Logan G. Spector. Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3652.
Abstract 3656: Breast cancer care quality in Peru
Authors: Anampa-Guzman Andrea , Perez-Mendez Rushmely Gaby , Huaccho-Rojas Juan , Villar-Lopez Martha , Mini-Diaz Elsy 
Published: June 2022

Abstract
Although many studies indicate that the use of complementary medicine by cancer patients is common and widespread, few studies focused on patients' quality of care using complementary therapies. The overall health care quality perception of patients in Lima, the capital of Peru, was reported to be 68.9% according to the SERVQUAL questionnaire, which grades as acceptable. Breast cancer is the most common cancer in Peru. This study aims to determine the perception of health care quality for breast cancer patients in Lima. This is a cross-sectional study. The perspectives of 182 breast cancer patients about the quality of care at the largest hospital in Lima were assessed. One hundred seventeen patients (64.29%) were only seen at the Oncology Department, and 65 patients (35.71%) were seen at both the Oncology Department and Complementary Medicine Department. The quality perception is based on five dimensions: Reliability, responsiveness, assurance, empathy, and tangibility. The percentage has to be 60 to be an acceptable level. The average age was 58.81 years. The overall and oncology-only groups quality perceptions were not acceptable, 57.32%, and 53.65%, respectively. The oncology and the complementary patient group reported adequate general perception (63.92%). Perception of empathy and assurance were at acceptable levels for both groups. Reliability and tangibility did not receive a satisfactory grade in any group. The responsiveness level was only adequate in the complimentary and oncology group. The breast cancer patients’ perception of the health care quality who received Complementary Medicine services was significantly higher than the oncology-only group. We did not find a significant difference between the dimensions of quality and educational level, type of insurance, and the professional who attended the patient. In conclusion, the patients who were seen at the oncology and complementary medicine reported a better perception of the quality of healthcare. More studies are needed to improve healthcare in breast cancer patients.
Citation Format: Andrea Anampa-Guzman, Rushmely Gaby Perez-Mendez, Juan Huaccho-Rojas, Martha Villar-Lopez, Elsy Mini-Diaz. Breast cancer care quality in Peru [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3656.
Abstract 3688: Survival benefit of adjuvant radiotherapy among women with high comorbidity burden and low-risk breast cancer: SEER-MHOS analysis
Authors: Lee Eunkyung , Hines Robert B. , Zhu Jianbin , Montan Kayla , Rovito Michael J. 
Published: June 2022

Abstract
Background: The National Comprehensive Cancer Network Breast Cancer Guidelines Committee has suggested that adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) could be omitted among older women with low-risk breast cancer (early-stage, node-negative, and ER-positive) if they were treated with endocrine therapy. However, the effect of RT among older women with multimorbidity is not clearly understood.
Objective: We examined the effect of adjuvant RT on survival outcomes among older women. We also assessed whether the association between RT and survival is modified by comorbidity burden.
Methods: A total of 1105 older women (65+) diagnosed with low-risk breast cancer in 1998-2012 and who received BCS were identified from the population-based Surveillance, Epidemiology, and End-Results-Medicare Health Outcomes Survey (SEER-MHOS) data resource. A propensity score-based inverse probability of treatment weight (IPTW) was calculated with weighting applied to Cox regression models to obtain hazard ratios for the association of RT with survival outcomes. Stratified analysis was conducted to examine differential effects according to the comorbidity burden class, which was identified using the latent class analysis.
Results: Over a 5-year follow-up period, a total of 117 deaths occurred (25 cancer-related and 92 noncancer-related). The IPTW-adjusted Cox proportional hazard analysis showed that RT omission did not significantly increase the risk for 5-year cancer-specific deaths (P=0.202). However, RT omission increased the risk for 5-year noncancer death by 1.84-fold (95% CI=1.35, 2.51) and all-cause death by 1.49-fold (95% CI=1.41, 1.95). The stratified analysis showed that the effect of RT omission on the risk of breast cancer-specific deaths was similar across the different comorbidity groups. For noncancer and all-cause deaths, the effect of RT omission varied by comorbidity burden. In Class 1, RT omission was not associated with an increased risk of noncancer and all-cause deaths. However, in Classes 2 and 3, RT omission is significantly associated with an increased risk of 5-year all-cause deaths in a dose-response manner: by 1.66-fold (95% CI=1.07, 2.56) in Class 2 and 1.96-fold in Class 3 (95% CI=1.13, 3.41). Similar results were observed for 10-year survival.
Conclusions: RT omission does not increase the risk of cancer-specific death and appears to be a valid clinical decision for older women with low-risk breast cancer and multimorbidity.
Citation Format: Eunkyung Lee, Robert B. Hines, Jianbin Zhu, Kayla Montan, Michael J. Rovito. Survival benefit of adjuvant radiotherapy among women with high comorbidity burden and low-risk breast cancer: SEER-MHOS analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3688.