tbuckley/cabot-search huggingface dataset:
Abstract 1757: IFN-γ signaling in myeloid and fibroblastic cells regulates pancreatic cancer growth and metastasis
Authors: Elena Ivleva, Ashley Crisostomo, Natalia Andreeva, Sergei Grivennikov
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) represents a significant healthcare problem which is on the rise, primarily because of the late stage diagnosis, early metastasis, and rapidly emerging resistance to therapy. As cancer cells in a typical pancreatic tumor are outnumbered by stromal and immune cells, the role of tumor microenvironment in cancer growth and progression is essential. One of the key regulators of tumor microenvironment in numerous cancers is IFN-γ signaling pathway, which is implicated into regulation of multiple cell types. Using a genetic murine model with conditional IFN-γR2 deficiency in myeloid cells, we performed an orthotopic injection of cell line derived from Pdx1Cre-Kras-P53 model (“KPC” cells). The absence of IFN-γ signaling in myeloid cells led to an increase of tumor burden and size of tumors in these mice. Further analysis demonstrated that IFN-γR2 deletion in myeloid cells changes the differentiation of cancer cells in primary tumors, resulting in a loss of characteristic histological pattern and shifting it towards more aggressive phenotype. Subsequent intrasplenic injection/liver spread model revealed that loss of IFN-γR2 in myeloid cells led to increased metastatic outgrowth of PDAC KPC cells. This effect was partially dependent on the gut microbiota. Deficiency of IFN-γR2 in myeloid cells increases recruitment and infiltration of monocytes in normal and tumor liver tissue. Meanwhile, deletion of IFN-γR2 in several subsets of cancer-associated fibroblasts demonstrated that IFN-γ signaling in different subsets of fibroblast/myofibroblasts may play opposing role in PDAC tumor growth. Our data identifies cell type specific IFN-γ signaling pathway as an important regulator of pancreatic cancer progression and metastasis, that can be potentially exploited as a novel immunooncology target or a biomarker of the disease progression. Citation Format: Elena Ivleva, Ashley Crisostomo, Natalia Andreeva, Sergei Grivennikov. IFN-γ signaling in myeloid and fibroblastic cells regulates pancreatic cancer growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1757.
Abstract 2159: Oscillating p53 temporal dynamics enable proliferative recovery of cells following DNA damage
Authors: Dan Lu, Alba Jimenez, Ashwini Jambhekar, Galit Lahav
Journal: Cancer Research (2021)

Abstract The transcription factor and tumor suppressor protein p53 regulates cellular outcomes (e.g. cell cycle arrest, senescence or apoptosis) following DNA damage. Cellular outcomes can be influenced by modulating the temporal expression dynamics of p53, which in turn alters target gene mRNA expressions patterns. However, it is not clear how changes in such mRNA dynamics would eventually results in differences in temporal protein expression dynamics, which ultimately determines the cell outcome. By quantifying mRNA and protein by RNA-Seq and mass-spectrometry, respectively over time, we systematically categorized the different dynamics which could arise of p53 target mRNAs and proteins. We show that while p53 target proteins plateaus under pulsatile dynamics, the majority of target proteins are enhanced and accumulates under sustained dynamics including many regulators of terminal cell fates such as apoptosis and senescence. Next we derived synthesis and degradation rates based on empirical measurements to model how different p53 dynamics could lead to the assortment of subsequent target protein dynamics. We show that target protein dynamics are highly governed by protein degradation rate, implying the temporal selection of target gene expression is not pre-determined by the initiating stress signal, but rather through differences in the inherent protein degradation rates. Furthermore, we identify multiple unique signaling network motifs which results in target protein accumulation only under sustained (persistent) but not pulsatile (oscillatory) p53 dynamics. Our results highlight the diversity of mechanisms cells evolved to decode transcription factor dynamics as well as the role of p53 in governing cellular outcome, important both in understanding cellular information processing as well as therapeutic implications for cancer treatments. Citation Format: Dan Lu, Alba Jimenez, Ashwini Jambhekar, Galit Lahav. Oscillating p53 temporal dynamics enable proliferative recovery of cells following DNA damage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2159.
Abstract 2040: Analysis of DNA damage repair gene alterations and their association with tumor mutation burden in 1427 hepatocellular carcinoma patients
Authors: Mengmei Yang, Wenzhuan Xie, Mengli Huang, Xinhua Zhu
Journal: Cancer Research (2021)

Abstract Background: DNA damage repair (DDR) pathway have attracted much attention because they modulate cancer risk, progression and therapeutic response. DDR deficiency sensitize the tumor to poly ADP-ribose polymerase inhibitors (PARPi). Also alterations in DDR genes are associated with higher tumor mutation burden (TMB) and better response to immune checkpoint inhibitors (ICI). Here we conduct a large-scale genomic analysis to clarify the landscape of DDR gene mutations in hepatocellular carcinoma and the correlation between individual gene mutation and tumor mutation burden. Methods: Tumor samples from 1427 patients with advanced hepatocellular carcinoma were assayed through next-generation sequencing with 381 cancer-related genes including 30 predefined DDR genes: MRE11A, RAD50, BARD1, BLM, BRCA1, BRCA2, BRIP1, PALB2, MLH1, MSH2, MSH6, PMS2, POLD1, ATM, ATR, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCG, FANCF, FANCL, RAD51, CUL3, ERCC1, POLE, MUTYH, and PRKDC. TMB (mutations per megabase [mut/Mb]) was calculated based on nonsilent somatic mutations in coding regions. Wilcoxon test was used for the comparisons and statistical significance was set at p = 0.05. Results: Somatic DDR gene alterations were found in 18.8% of the HCC patients. The most common mutational types were copy number variation (30.54%), frameshift (21.89%), and nonsense (20%). The most frequently altered DDR genes are ATM (2.6%) and BRCA2 (2.2%), followed by FANCA (0.9%), PALB2 (0.8%), and MLH1 (0.7%). As to different functional pathways of DDR, the gene alteration frequency from high to low is HRR (6.1%), DS (3.2%), FA (2.5%), MMR (2.2%), BER (0.6%), NHEJ (0.6%), and NER (0.3%). The TMB of patients carrying somatic DDR gene alterations was significantly higher than those without somatic DDR gene alterations (7.26 vs 6.45 mut/MB, p&amp;lt;0.001). As to individual gene, alterations in RAD50, MLH1, MSH2, CHEK2, and FANCE were significantly correlated with higher tumor mutation burden while alterations in other DDR genes were not. Conclusion: This is the largest study to clarify the landscape of DDR gene mutations in hepatocellular carcinoma. This study confirms that mutations in DDR genes are relatively common and are correlated with higher tumor mutation burden. This also indicates not all DDR genes are equal since mutations of certain individual genes were associated with higher TMB whereas others were not; further studies are needed to confirm this. Citation Format: Mengmei Yang, Wenzhuan Xie, Mengli Huang, Xinhua Zhu. Analysis of DNA damage repair gene alterations and their association with tumor mutation burden in 1427 hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2040.
Abstract 2663: Determining the role of altered redox metabolism in lung tumorigenesis
Authors: Alex Camai
Journal: Cancer Research (2021)

Abstract The purpose of this study is to determine the pathways by which short-term cigarette smoke exposure induces expression of the cystine-glutamate antiporter xCT (SLC7A11) and its downstream implications in carcinogenesis. BEAS-2B lung epithelial cells and their tumorigenic counterpart, B39-TL cells, were exposed to cigarette smoke condensate (CSC) for 3-15 days. Cells were also exposed to a range of inhibitors. Erastin and buthionine sulfoximine (BSO) are inhibitors of various steps in the glutathione synthesis pathway, found to be hyperactive in xCT-overexpressing cells. Cells were also exposed to the drug mito-2-hydroxybenzoic acid (mito-2-HOBA), which scavenges isolevuglandins, reactive γ-ketoaldehydes implicated in oxidative stress and carcinogenesis. Expression of xCT and related proteins was measured using Western blotting. Glutathione levels were detected using the luciferase-based GSH-Glo assay (Promega). Oxidative stress was detected using dihydroethidium (DHE) fluorescence. It was found that CSC exposure significantly increased the expression of xCT and SLC1A5, a transporter that potentially works in synergy with xCT, and that tumorigenic B39-TL cells had significantly increased xCT and SLC1A5 expression compared to BEAS-2B cells. In addition, BEAS-2B cells exposed to CSC and a glutathione synthesis inhibitor such as erastin or BSO showed faster depletion of glutathione than cells treated with only inhibitor. Finally, it was found that BEAS-2B cells treated for 3 days with CSC did not show increased levels of superoxide compared to control cells. However, cells treated with CSC and mito-2-HOBA together showed significantly increased superoxide. These data suggest that CSC induces an antioxidant response which is ablated by mito-2-HOBA. This antioxidant response seems to at least partially rely on glutathione synthesis fueled by xCT, as evidenced by inhibitor studies. The response also seems to be activated by isolevuglandins, because removing these molecules significantly raises oxidative stress. The mechanistic link between CSC exposure, isolevuglandin generation, and xCT/glutathione induction will be clarified in further experiments. Citation Format: Alex Camai. Determining the role of altered redox metabolism in lung tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2663.
Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial
Authors: Xiaotian Zhang, Han Liang, Ziyu Li, Yingwei Xue, Yanong Wang, Zhiwei Zhou, Jiren Yu, Zhaode Bu, Lin Chen, Yian Du, Xinbao Wang, Aiwen Wu, Guoli Li, Xiangqian Su, Gang Xiao, Ming Cui, Dan Wu, Li Chen, Xiaojiang Wu, Yanbing Zhou, Lianhai Zhang, Chengxue Dang, Yulong He, Zhongtao Zhang, Yihong Sun, Yong Li, Huanqiu Chen, Yuxian Bai, Changsong Qi, Peiwu Yu, Guanbao Zhu, Jian Suo, Baoqing Jia, Leping Li, Changming Huang, Fei Li, Yingjiang Ye, Huimian Xu, Xin Wang, Yannan Yuan, Jian-Yu E, Xiangji Ying, Chen Yao, Lin Shen, Jiafu Ji
Journal: The Lancet Oncology (2021)
Facial Numbness, Dysarthria, Muscle Atrophy, and Weakness in a Young Patient
Authors: Yan Liu, Jing Luo, Fei Xiao
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Thrombopoietin receptor agonists for acquired thrombocytopenia following anti-CD19 CAR-T-cell therapy: a case report
Authors: Rebecca Baur, Regina Jitschin, Soraya Kharboutli, Andrej Stoll, Simon Völkl, Maike Büttner-Herold, Daniela Schmidt, Wolf Rösler, Andreas Mackensen, Dimitrios Mougiakakos
Journal: Journal for ImmunoTherapy of Cancer (2021)

Chimeric antigen receptor (CAR)-modified T-cells targeting CD19 represent a promising therapy for relapsed or refractory (r/r) lymphoma and leukemia. The most common adverse events are immune related and include cytokine release syndrome and neurotoxicity. However, early and late hematological toxicity has emerged as a substantial clinical hurdle leading among others to an increased risk for infections or bleeding. The underlying pathophysiology remains elusive and supportive measures comprise stem cell support or the use of growth factors. Here, we report a 66-year-old woman with r/r diffuse large B-cell lymphoma that received anti-CD19 CAR-T-cells achieving a complete metabolic remission. At month 3 after adoptive cell transfer, the patient still exhibited a grade 3 anemia and a grade 4 thrombocytopenia. The latter required regular platelet transfusions. Bone marrow smear revealed hypocellularity without dysplasia. Despite reduced megakaryopoiesis, immature platelet fraction was elevated indicating an at least partially consumptive underlying component. Based on the successful use of Romiplostim, a thrombopoietin receptor-agonist, in aplastic anemia and immune thrombocytopenia, we treated our patient accordingly. Platelet count (and hemoglobin levels) increased and the patient remains transfusion-free. Taken together, our therapeutic approach could represent a novel strategy for managing CAR-T-cell-related hematotoxicity but, self-evidently, requires further controlled clinical studies.
Abstract 3125: Analysis of intratumoral protein and gene expression heterogeneity in gastric cancer with a clustering analysis
Authors: Gen Tsujio, Masakazu Yashiro, Yurie Yamamoto, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Mami Yoshi, Tasuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Shigeru Lee, Kazuya Muguruma, Masaichi Ohira
Journal: Cancer Research (2021)

Abstract Background/Aim: Intratumoral heterogeneity has been reported in various cancer types and may cause cancer metastasis and chemotherapy treatment resistance, including resistance to molecular targeted therapy. In gastric cancer, the intratumoral heterogeneity of cancer-associated molecules, such as HER2, has been reported and relates to the acquisition of chemotherapy resistance. To reveal whether intratumoral heterogeneity is related to cancer etiology, such as the mechanism of metastasis, and the development of new treatment strategies, such as combination therapy, we investigated intratumoral heterogeneity of gastric cancer with operative specimen and Cancer Genome Atlas (TGCA) data. Methods: The study included 503 patients who underwent gastrectomy and immunohistochemical staining for gastric cancer between 2001 and 2006 and TGCA data. We conducted clustering analysis based on protein and gene expression data for FGFR2IIIb (FGFR2), HER2(ERBB2), CXCR2(CXCR2), CXCR4(CXCR4), cMet(MET), TGFβ1(TGFB1), IGF1R(IGF1R), and p-smad2(SMAD2), and we analyzed the relation of FGFR2IIIb (FGFR2) and HER2(ERBB2) expression with the expression of other proteins and genes. Additionally, we investigated clinicopathological feature correlations. Result/Discussion: We divided gastric cancer specimens into nine clusters by immunohistochemical staining and 11 clusters using TCGA data. According to immunohistochemical staining, the high HER2 and FGFR2IIIb expression groups formed a cluster with high expression of various proteins. Analysis of stage 3-4 samples revealed more high protein expression clusters than the analysis of stage1-2, and this suggests that cancer acquires heterogeneity with cancer progression. In the TGCA data of stage 3-4, high FGFR2 and MET and high ERBB2 and SMAD2 or IGF1R expression formed clusters, which is consistent with the clustering analysis that was performed with immunohistochemical staining results. Conclusion: Our findings suggest that the existence of a combination of intratumoral heterogeneity and clusters may change with cancer progression. Citation Format: Gen Tsujio, Masakazu Yashiro, Yurie Yamamoto, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Mami Yoshi, Tasuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Shigeru Lee, Kazuya Muguruma, Masaichi Ohira. Analysis of intratumoral protein and gene expression heterogeneity in gastric cancer with a clustering analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3125.
FcεRI 架橋後のヒトおよびマウスのマスト細胞トランスクリプトームにおけるC-Cケモカイン遺伝子形質発現の著しい増加
Authors: Saito H, Nakajima T, Yoshikawa M, Matsumoto K, Akasawa A, Tsujimoto G, Nagai H, Matsuda H
Journal: Journal of Allergy and Clinical Immunology (2002)
Microdissection Testicular Sperm Extraction (mTESE) vs. multiple needle-pass percutaneous Testicular Sperm Aspiration (TESA) in men with non-obstructive azoospermia: A randomized clinical trial
Authors: C.F.S. Jensen, D.A. Ohl, M. Fode, N. Jørgensen, A. Giwercman, A. Elenkov, A. Klajnbard, C.Y. Andersen, L. Aksglaede, M.L. Grøndahl, M.C. Bekker, J. Sønksen
Journal: European Urology (2021)
Mobile app validation: a digital health scorecard approach
Authors: Ramy Sedhom, Michael J. McShea, Adam B. Cohen, Jonathan A. Webster, Simon C. Mathews
Journal: npj Digital Medicine (2021)

Abstract While digital health solutions continue to grow in number and in complexity, the ability for stakeholders in healthcare to easily discern quality lags far behind. This challenge is in part due to the lack of a transparent and standardized approach to validation. Evaluation of mobile health applications (apps) is further burdened by low barriers to development and direct-to-user marketing, leading to a crowded and confusing landscape. In this context, we investigated the pragmatic application of a previously described framework for digital health validation, the Digital Health Scorecard, in a cohort of 22 popular mobile health oncology apps. The apps evaluated using this framework performed poorly, scoring 49.4% across all evaluation criteria as a group. Performance across component domains varied considerably with cost scoring highest at 100%, usability at 56.7%, technical at 37.3%, and clinical at 15.9%. satisfaction of prospectively determined end-user requirements derived from patient, family, and clinician consensus scored 37.2%. While cost outperformed consistently and usability was adequate, the results also suggested that apps suffered from significant technical limitations, were of limited clinical value, and generally did not do what end users wanted. These large gaps further support the need for transparent and standardized evaluation to help all stakeholders in healthcare improve the quality of mobile health.
Abstract 2254: Coding and noncoding RNA determinants of invasion and migration in papillary thyroid cancer
Authors: Michelle Carnazza, Sina Dadafarin, Augustine Moscatello, Raj Tiwari, Jan Geliebter
Journal: Cancer Research (2021)

Abstract Papillary thyroid cancer (PTC) is now the 8th most common cancer in women in the United States and has been increasing in incidence over the last few decades. While it is often curable, aggressive forms of PTC that are not adequately treated by current therapeutic modalities invade into surrounding tissue, with a poor prognosis. Thus, the identification of genes involved in PTC migration and invasion is an unmet need. Differentially expressed (PTC vs. matched, normal) coding and noncoding genes from our own biobank were ranked, comparing invasive vs noninvasive, and lymph node positive vs lymph node negative samples. This analysis was supplemented with the interrogation s of The Cancer Genome Atlas (TCGA) PTC gene expression database for survival-associated genes (Kaplan Meier survival curves) utilizing the Xena Browser. This meta-analysis identified genes with a significant impact on survival, that correlated with lymph node metastasis and tumor invasion. SPOCK3, a Ca+2-binding proteoglycan protein with metalloendopeptidase activity, with a role in both extracellular matrix (ECM) degradation and ERK signaling, correlated with both invasiveness and lymph node spread. SLC30A3 (Solute Carrier Family 30 Member 3), involved in the accumulation of zinc in synaptic vesicles and the transport of sugars, bile salts, organic acids, metal ions and amine compounds, also correlated with both invasiveness and lymph node spread. COL26A1, was found to be correlated to tumor invasion and codes for collagen type XXVI α1 chain with known roles in degradation of the ECM and collagen chain trimerization. Long noncoding RNAs (lncRNAs) have vast implications in different cancer types with roles in gene expression via modulation of coding and noncoding RNAs, and are cell, tissue and stage-specific. lncRNAs were identified that correlated with differentiation, invasion and lymph node spread. CRISPR guides were designed and introduced into thyroid cancer cell lines and decreased the invasion and migration capacity of the thyroid cancer cells. This implies their potential use as prognostic markers and actionable therapeutic targets for small molecule inhibitors. Citation Format: Michelle Carnazza, Sina Dadafarin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Coding and noncoding RNA determinants of invasion and migration in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2254.
Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model
Authors: Miguel Martínez-Lacalzada, Adrián Viteri-Noël, Luis Manzano, Martin Fabregate, Manuel Rubio-Rivas, Sara Luis García, Francisco Arnalich-Fernández, José Luis Beato-Pérez, Juan Antonio Vargas-Núñez, Elpidio Calvo-Manuel, Alexia Constanza Espiño-Álvarez, Santiago J. Freire-Castro, Jose Loureiro-Amigo, Paula Maria Pesqueira Fontan, Adela Pina, Ana María Álvarez Suárez, Andrea Silva-Asiain, Beatriz García-López, Jairo Luque del Pino, Jaime Sanz-Cánovas, Paloma Chazarra-Pérez, Gema María García-García, Jesús Millán Núñez-Cortés, José Manuel Casas-Rojo, Ricardo Gómez-Huelgas, Luis F. Abrego-Vaca, Ana Andreu-Arnanz, Octavio A. Arce-García, Marta Bajo-González, Pablo Borque-Sanz, Alberto Cózar-Llistó, Beatriz Del Hoyo-Cuenda, Alejandra Gamboa-Osorio, Isabel García-Sánchez, Óscar A. López-Cisneros, Borja Merino-Ortiz, Elisa Riera-González, Jimena Rey-García, Cristina Sánchez-Díaz, Grisell Starita-Fajardo, Cecilia Suárez-Carantoña, Svetlana Zhilina Zhilina
Journal: Clinical Microbiology and Infection (2021)

We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes.