tbuckley/cabot-search huggingface dataset:
Abstract 3541: Metabolic signature characterization in prostate cancer mediated by heme-oxygenase 1
Authors: Valeria G. Antico Arciuch, Nicolas Anselmino, Federico Schuster, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez
Journal: Cancer Research (2017)

Abstract Prostate cancer (PCa) is the second leading cause of cancer-associated death in men, being bone metastases the main cause of mortality. Energetic metabolism alterations have become a new hallmark of cancer, since variations in a single gene can orchestrate changes in metabolic pathways and confer an adaptive advantage. Heme-oxygenase 1 (HO-1) exerts an antitumoral role in PCa inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this work was to assess the role of HO-1 in the metabolic signature of PCa. Through RNA-Seq we found a set of metabolic genes deregulated under pharmacological induction (hemin treatment) or genetic induction of HO-1 in PC3 cells. STAR and ATP5L2 were found upregulated, while HMGCS2, PRODH and ACOT12 were downregulated. These genes encode for steroid hormone metabolism, ATP synthesis, ketogenesis, proline and lipid metabolism. The analysis of the deregulated genes (2-fold) under HO-1 modulation by Gene Ontology revealed alterations in several metabolic pathways such as steroid, tyrosine and lipid metabolism, and ion transport. Bone is the only site of PCa progression, and bone cells are able to produce factors that increase the growth and survival of tumor cells favoring progression. However, the molecular nature of this interaction remains to be elucidated. Our preliminary results performed on co-cultures of PC3 cells (treated or not with hemin) with Raw264.7 (pre-osteoclastic) or MC3T3 (pre-osteoblastic) cells demonstrate that HO-1 is able to direct the metabolic fate of bone precursor cells due to the deregulation of glycolytic genes. HO-1 induction in PC3 cells downregulated the expression of PKM2 and LDHA in co-cultured Raw264.7 and MC3T3 cells (p&amp;lt; 0.05). Based on our results, we propose HO-1 as a key regulator of the metabolic status of PCa cells and a powerful mediator capable of redefining the metabolic signature of bone precursor cells, thus, favoring the establishment of a less aggressive phenotype. Note: This abstract was not presented at the meeting. Citation Format: Valeria G. Antico Arciuch, Nicolas Anselmino, Federico Schuster, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez. Metabolic signature characterization in prostate cancer mediated by heme-oxygenase 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3541. doi:10.1158/1538-7445.AM2017-3541
Unusual Presentation of Postradiation Sarcoma With Subsequent Intestinal Metastasis Revealed by 18F-FDG PET/CT
Authors: Tse-Hao Lee, Cheng-Pei Chang, Yuan-Hung Wu, Wen-Sheng Huang
Journal: Clinical Nuclear Medicine (2017)

Radiation-related sarcoma is a rare but serious complication for patients after receiving radiation therapy initially for their primary malignancy. However, it usually takes several years and needs enough in-field radiation dose to develop this sarcoma. We describe a 60-year-old man with right axillary sarcoma revealed by whole-body F-FDG PET/CT 1 year after chemoradiotherapy, which presented ultrashort latency period and did not match the consensus definition of radiation-related sarcoma. Besides, metastatic sarcoma to small intestine was accidentally noted in the F-FDG PET/CT image.
Abstract 96: Didhydropyrimdine dehydrogenase (DPYD) provides resistance to 5-flurouracil in mutant p53 (mtp53) expressing colorectal cancer cells
Authors: Prashanth Ravishankar Gokare, Niklas Finnberg, David Dicker, Maureen Murphy
Journal: Cancer Research (2017)

Abstract 5-Flurouracil (5-FU) is a mainstay of colorectal cancer therapy. Even though much is known about the 5-FU mechanism of action, very little is known about the genetic determinants which provide sensitivity and resistance to 5-FU. Here we provide first insights into p53, a major predictor of 5-FU response, modulating nucleotide catabolism specifically through the control of the rate limiting enzyme dihydropyrimidine dehydrogenase (DPYD). Colorectal cancer cells expressing mtp53 specifically show higher expression of DPYD as compared to the wildtype p53 (wtp53) carrying cells. Higher expression of DPYD in mtp53 cells specifically provides increased resistance to 5-FU as indicated by cellular proliferation and long term clonogenic assays. Furthermore, knockdown of DPYD in mtp53 cells preferentially resensitizes them to 5-FU as opposed to cells expressing Wtp53 by decreasing the viability and increasing apoptosis observed in these cells. Pharmacological inhibition of DPYD with gimeracil, clinical inhibitor of 5-FU phenocopies the effects seen by siRNA/shRNA mediated knockdown of DPYD. Finally, invivo studies with tumor xenograft from mtp53 carrying cells shown increase resistance to 5-FU therapy which is abrogated by stable knockdown of DPYD expression or in combination gimeracil. Preliminary analysis of TCGA patients treated with 5-FU indicate differential expression of DPYD based on specific Tp53 mutation status. Taken together our study provides first insights into crosstalk between nucleotide catabolism and mtp53 under conditions of DNA damage and metabolic stress having major implications on the therapeutic response to 5-FU the in the clinic. Citation Format: Prashanth Ravishankar Gokare, Niklas Finnberg, David Dicker, Maureen Murphy. Didhydropyrimdine dehydrogenase (DPYD) provides resistance to 5-flurouracil in mutant p53 (mtp53) expressing colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 96. doi:10.1158/1538-7445.AM2017-96
Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy
Authors: Juan Acosta, Juan Fernández-Armenta, Roger Borràs, Ignasi Anguera, Felipe Bisbal, Julio Martí-Almor, Jose M. Tolosana, Diego Penela, David Andreu, David Soto-Iglesias, Reinder Evertz, María Matiello, Concepción Alonso, Roger Villuendas, Teresa M. de Caralt, Rosario J. Perea, Jose T. Ortiz, Xavier Bosch, Luis Serra, Xavier Planes, Andreas Greiser, Okan Ekinci, Luis Lasalvia, Lluis Mont, Antonio Berruezo
Journal: JACC. Cardiovascular imaging (2017)
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.Long-Term Follow-up after Acute Respiratory Distress Syndrome. Insights for Managing Medical Complexity after Critical Illness
Authors: Margaret S. Herridge
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Critical illness is not a discrete disease state or syndrome. It is the culmination of a multiplicity of heterogeneous disease states and their varied health trajectories leading to extreme illness that requires advanced life support in a distinct geographic location in the hospital. It is a marker of newly acquired or worsened medical complexity and multimorbidities. Fifty years ago, distinguished critical care colleagues identified a syndrome of severe lung injury that united a group of patients with disparate admitting diagnoses. Acute respiratory distress syndrome continues to represent an important, incremental insult and risk modifier of acute and longer-term outcome, but it does not solely define our patients or their outcomes in isolation. Over the next 50 years, our research and clinical agenda needs to sharpen our lens on the fundamental importance of our patients' pre-critical illness health status, their intrinsic susceptibilities to tissue injury, and their innate and varied resiliencies. We need to take responsibility for the contribution that we make to morbidity through our practice in the intensive care unit each day. Engagement in frank and transparent communication with our patients and their caregivers about the very real and morbid consequences of being this sick is essential. We must enforce explicit consent about the morbidity of innovative, experimental, or high-risk medical and surgical procedures and ensure that our ongoing level of treatment aligns with patients' and caregivers' goals and values. Interprofessional and multidisciplinary collaboration is crucial to modify existing complex care pathways for our patients and their families to foster optimal rehabilitation and reintegration into the workplace and community.
Abstract 5128: Induction of immunogenic cell death and tumor regression in murine animal models by a novel cytolytic compound, LTX-401
Authors: Brynjar Mauseth, Liv-Marie Eike, Ji-Hua Shi, Ketil Camilio, Heng Zhou, Allan Sauvat, Lígia C Gomes-da-Silva, Sylvèr Durand, Sabrina Forveille, Kristina Iribarren, Takahiro Yamazaki, Sylvie Souquere, Lucillia Bezu, Kevin Müller, Marion Leduc, Peng Liu, Liwei Zhao, Aurélien Marabelle, Laurence Zitvogel, Oliver Kepp, Guido Kroemer, Øystein Rekdal, Pål-Dag Line, Baldur Sveinbjørnsson
Journal: Cancer Research (2017)

Abstract LTX-401 is a de novo designed cytolytic compound that shares many chemical features with anticancer peptides, such as amphipathicity, hydrophobicity and overall net charge. In vitro cytotoxicity studies revealed that LTX-401 was highly active against a panel of malignant cells including murine and human cancer cell lines while displaying selectivity towards human red blood cells. Furthermore, LTX-401 was found to induce immunogenic cell death as demonstrated by the release of Damage-Associated Molecular Pattern molecules, or ‘danger signals’, such as High-Mobility Group Box-1 protein, ATP and cytochrome c. Flow cytometric and confocal microscopy studies also demonstrated reduced signal from lysosomal dye Lysotracker-DND-26, hence indicating loss of lysosomal integrity upon induction of cell death. The latter was supported using transmission electron microscopy, showing distinct morphological characteristics of necrosis. Moreover, at low concentrations, LTX-401 selectively enriched in the Golgi apparatus and initiated a lethal signaling event that in part could be inhibited by Brefeldin A. Complete tumor regression has been obtained in several rodent models, including the B16 mouse melanoma model and the JM1 rat hepatocellular carcinoma model by intratumoral injection with LTX-401. Additionally, previously cured animals showed protection against rechallenge with live tumor cells, indicating the induction of tumor-specific immune memory. The increased survival benefit of LTX-401-treated animals provides a rationale for further evaluation of the compound as an immunotherapeutic agent against solid malignancies. Citation Format: Brynjar Mauseth, Liv-Marie Eike, Ji-Hua Shi, Ketil Camilio, Heng Zhou, Allan Sauvat, Lígia C Gomes-da-Silva, Sylvèr Durand, Sabrina Forveille, Kristina Iribarren, Takahiro Yamazaki, Sylvie Souquere, Lucillia Bezu, Kevin Müller, Marion Leduc, Peng Liu, Liwei Zhao, Aurélien Marabelle, Laurence Zitvogel, Oliver Kepp, Guido Kroemer, Øystein Rekdal, Pål-Dag Line, Baldur Sveinbjørnsson. Induction of immunogenic cell death and tumor regression in murine animal models by a novel cytolytic compound, LTX-401 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5128. doi:10.1158/1538-7445.AM2017-5128
Abstract 5807: Disseminated tumor cell clearance by the immune system
Authors: Raziye Piranlioglu, Eun Mi Lee, Maria Ouzunova, Ali S. Arbab, Paulo C. Rodriguez, Asm L. Iskander, Hasan Korkaya
Journal: Cancer Research (2017)

Abstract The classical model of metastasis suggests that the tumor cell dissemination occurs late in tumor development, however accumulating evidence coming from mouse studies and clinical data provide striking evidence that tumor cells start to disseminate during the initial steps of tumor development. However, the dissemination from the primary area does not always result in metastasis. Due to the non-permissive nature of microenvironment in distant sites, these early disseminated tumor cells might be cleared or maintained in a non-proliferative/dormant state. The mechanism by which some early disseminated tumor cells colonize and generate metastatic growth while some remain dormant is not well known. In order to understand the underlying factors that may contribute to the metastatic growth, we performed time course experiments by utilizing murine mammary tumors (4T1 as metastatic and EMT6 as less metastatic) in a syngeneic mouse model. Luciferase expressing 4T1 or EMT6 tumor cells were orthotopically implanted into the fat pads and tumor cell dissemination was analyzed over 3-week time points. We determined that both 4T1 and EMT tumors disseminated as early as one to two-week post implantation, however only 4T1 tumor develop metastasis in distant organs. Moreover, we also resected primary tumors 1, 2 and 3-week post implantation of EMT6-Luci or 4T1-Luci tumors and observed distant metastasis via optical imaging of luciferase expression in live animals. Although the majority of 4T1 tumor-bearing mice (&amp;gt;80%) develop pulmonary metastasis when 4T1 tumors resected 2 and 3 weeks post-implantation only 10% of mice develop metastasis when primary tumor resected one-week post implantation. In contrast, EMT6 tumors following resection only relapsed in the primary tumor site but failed to develop metastasis. Furthermore, EMT6 tumor-bearing mice efficiently cleared tail vein injected EMT6-luci cells in the lungs. We investigated the possible mechanism by which EMT6 tumor-bearing mice clears disseminated tumor cells in the lung. We provide evidence that pulmonary infiltrated mMDSCs mediate tumor cell killing via secretion of high levels of cytotoxic granules, granzyme A, granzyme B, perforin. This was confirmed by mouse transcriptome and qPCR analyses as well as biochemistry using in vivo samples and in vitro co-culture samples. Our studies provide a new paradigm in the understanding of the fate of disseminated tumor cells in secondary organs and the role of the immune system in this process. Citation Format: Raziye Piranlioglu, Eun Mi Lee, Maria Ouzunova, Ali S. Arbab, Paulo C. Rodriguez, Asm L. Iskander, Hasan Korkaya. Disseminated tumor cell clearance by the immune system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5807. doi:10.1158/1538-7445.AM2017-5807
Outcomes in South Asia Matter for the World
Authors: Neelam Sekhri Feachem, Saate S. Shakil
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Abstract 5104: A novelN-mustard-quinoline conjugate is a potent agent against colorectal cancer
Authors: Tai-Lin Chen, Yan-Bo Chen, Chia-Ning Shen, Tsann-Long Su, Te-Chang Lee
Journal: Cancer Research (2017)

Abstract Colorectal cancer (CRC) is the third leading cancer worldwide. The prognosis of patients diagnosed with CRC at the stage IV is poor with a 5-year survival rate less than 10%. Combination chemotherapy with platinum-based drugs and 5-fluorouracil (5-FU) remains the first line treatment, while the chemotherapy combined target therapeutic agents were decreasing the mortality of CRC patients. However, the efficacy of platinum-based drugs has often been limited because of the substantial risk for severe toxicities, including nephrotoxicity or neurotoxicity. Therefore, there is an unmet need to develop a novel drug for improving the treatment of advance colorectal cancer. We have previously designed and synthesized several series of DNA-directed alkylating agents with potent antitumor activity. Recently, one derivative of N-mustard-quinoline conjugates with hydrazinecarboxamide as a linker, designated as SL-1, was selected to explore its anti-colorectal cancer (CRC) activity because it was highly cytotoxic to a panel of CRC cell lines in culture. Flow cytometric analysis showed that treatment of CRC cells with SL-1 induced G2/M arrest and triggered apoptosis. We further demonstrated that SL-1 preferentially targeted on the selective guanine sequence by sequencing gel electrophoresis. By the aid of comet assay, SL-1 in combination with 5-FU resulted in increased DNA tail moments and induced more DNA damage. Evaluation of the potency of antitumor activity both in culture and in xenograft models, we observed that SL-1 was more potent than 5-FU and oxaliplatin against SW620, RKO and RKO-E6 (an oxaliplatin resistant-subline) cells. Notable, SL-1+5-FU were more efficacious than oxalipatin+5-FU in suppression the growth of RKO or SW620 in xenograft models. We further found that SL-1 enhanced 5-FU and induced more apoptosis by c-caspase 3 and TUNNEL staining. Additionally, histopathological examination showed that SL-1 by itself has no obvious kidney and liver toxicity in ICR mice comparing to cisplatin, oxaliplatin or 5-FU. Taken together, SL-1 alone or in combination with 5-FU may warrant our further development as a potential antitumor agent for the treatment of CRC patients. Citation Format: Tai-Lin Chen, Yan-Bo Chen, Chia-Ning Shen, Tsann-Long Su, Te-Chang Lee. A novel N-mustard-quinoline conjugate is a potent agent against colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5104. doi:10.1158/1538-7445.AM2017-5104
Abstract 376: Biospecimen and data resources for cancer research from NCI’s BPV program
Authors: Ping Guan, Helen M. Moore
Journal: Cancer Research (2017)

Abstract The Biospecimen Preanalytical Variables (BPV) Program was initiated by the National Cancer Institute’s Biorepositories and Biospecimen Research Branch to evaluate the impact of preanalytical factors on the molecular integrity of biospecimens. Selected preanalytical factors including cold ischemic time (delay to formalin fixation (DTF)), time in formalin (TIF), freezing methods, and storage temperatures and durations were examined for their potential effects on molecular profiles from surgical resection tissues and matched blood from four cancer types (kidney, ovary, colon and lung). The BPV program has collected tumor specimens from 364 cancer patients. Each specimen was annotated with 300+ data elements that cover steps in the collection, handling, and processing procedures, pathology review, and clinical information. NCI conducted multiple studies using these specimens to evaluate the preanalytical impacts on different analytical platforms including gene expression profiling, copy number variation, proteomics and metabolomics profiling. The program invites interested organizations to work with NCI through collaboration to further evaluate preanalytical effects on molecular analyses (https://techtransfer.cancer.gov/availabletechnologies/e-000-2013). The remaining specimens are available to support relevant research focusing on biospecimen science and/or clinical biomarker assay development (https://specimens.cancer.gov/search/). The IT infrastructure that was developed to support BPV biospecimen collection and management has been further developed into open source products (https://github.com/NCIP/CDR and https://github.com/NCIP/CDR-Lite). The controlled vocabulary that records the terms and definitions used in describing the overall biospecimen collection efforts has been refined and published at publicly accessible CDE repositories: NCI’s caDSR (https://cdebrowser.nci.nih.gov/CDEBrowser/ ) and NIH’s CDE portal (https://cde.nlm.nih.gov/cde/search ). An ongoing collaboration with an academic ontology consortium will map the CDEs to existing biobanking ontology frameworks and make them publicly available. The BPV program has generated a wide range of ~omics data. We are preparing a BPV data compendium to be submitted to dbGaP at NCBI. These data will be used as the experimental evidence to develop evidence-based best practices for fit-for-purpose collection, processing, and storage of biospecimens for cancer research. Citation Format: Ping Guan, Helen M. Moore. Biospecimen and data resources for cancer research from NCI’s BPV program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 376. doi:10.1158/1538-7445.AM2017-376
Abstract 3980: Ly6G+neutrophils and polymorphonuclear myeloid derived suppressor cells promote the survival of tumor cells
Authors: Sarah Herlihy, Cindy Lin, Maria Ozeriva, Alfred Garfall, Dan Vogl, Dmitry Gabrilovich, Yulia Nefedova
Journal: Cancer Research (2017)

Abstract A heterogeneous group of immature myeloid cells which suppress the immune system are termed myeloid derived suppressor cells (MDSC). Collectively a MDSC population is comprised of monocyte-like MDSC and polymorphonuclear MDSC (PMN-MDSC). MDSC are increased in the presence of a number of different tumors. We previously demonstrated that PMN-MDSC represent the majority of MDSC in tumor-bearing mice. In a mouse model of multiple myeloma (MM) depletion of myeloid cells in vivo results in increased survival. Direct co-culture of neutrophils (CD11b+Gr1+ cells from tumor-free mice) or PMN-MDSC (CD11b+Gr1+ cells from tumor-bearing mice) and MM cells increases the survival of the MM cells from chemotherapeutic-induced death. Cell-cell contact is not necessary for the protective effect. Neutrophil and PMN-MDSC supernatants protect MM cells from cell death, suggesting the factor protecting tumor cells is soluble. Results in the mouse were confirmed using human MM cells and replicated on breast cancer cells with neutrophils or PMN-MDSC. Several cytokines and growth factors, such as IL-6 and fibroblast growth factor, are implicated in chemoresistance. The role of these neutrophil and PMN-MDSC soluble factors and the identification of novel contributors to chemoresistance are under investigation. Citation Format: Sarah Herlihy, Cindy Lin, Maria Ozeriva, Alfred Garfall, Dan Vogl, Dmitry Gabrilovich, Yulia Nefedova. Ly6G+ neutrophils and polymorphonuclear myeloid derived suppressor cells promote the survival of tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3980. doi:10.1158/1538-7445.AM2017-3980