tbuckley/cabot-search huggingface dataset:
Abstract 1900: Preconditioning in Cynomolgus Monkey Heart Protects Against Both Ischemic and Reperfusion Injury
Authors: Xi-Ming Yang, Yanping Liu, Yongge Liu, Narendra Tandon, Junichi Kambayashi, James M Downey, Michael V Cohen
Journal: Circulation (2008)

Ischemic preconditioning (IPC) and postconditioning (IPoC) are equally cardioprotective in some species tested but IPoC has been less protective in others. Although IPoC decreases infarct size in humans, no comparable data exist for IPC making a comparison impossible. We therefore compared IPoC and IPC in sub-human primate hearts which would be expected to most closely mimic that of humans. Cynomolgus monkeys underwent a 90-min occlusion of a coronary artery and 4h of reperfusion. In IPC 2 cycles of 10-min coronary occlusion/10-min reperfusion preceded the 90-min occlusion, and in IPoC 6 cycles of 30-sec reperfusion/30-sec coronary reocclusion were performed immediately after the 90-min occlusion. The regression line for the infarct-risk zone plot was very linear (r=0.99) and intersected the risk zone axis at 0.82 cm 3 . Collateral flow averaged only 6.6% of preocclusion flow and did not influence infarction. In control monkeys 44% of the risk zone infarcted indicating cynomolgus myocardium is much more resistant to infarction than that of rabbits or rats. While IPC reduced infarct size to near zero (2.4±0.9% infarction of risk zone), IPoC was much less protective (27.5±4.8% infarction of risk zone). Increasing the number of IPoC cycles to 10 did not increase salvage. When wortmannin was administered at the end of the ischemic period to block any protection that IPC might elicit during reperfusion, infarct size increased to only 28%. These findings suggest that only half of IPC’s protection in monkey heart derives from prevention of cell death during reperfusion. The other half of IPC’s salvage would have derived from suppression of cell death during the prolonged ischemic period. If human heart is similar to cynomolgus heart, then interventions applied at reperfusion such as IPoC may be much less effective than would be predicted from the non-primate animal studies. Effective clinical salvage may require cardioprotective interventions that target both the ischemic phase as well as reperfusion injury.
P-34 The randomized, double-blind, placebo-controlled phase 3 trial KEYNOTE-975: Pembrolizumab vs placebo in patients with esophageal carcinoma receiving concurrent definitive chemoradiotherapy
Authors: M. Moehler, P. Enzinger, J. Bennouna, T. Doi, L. Shen, K. Kato, A. Adenis, H. Mamon, X. Fu, B. Cho, A. Desai, P. Bhagia, C. Shih, M. Shah
Journal: Annals of Oncology (2020)
Liver injury is independently associated with adverse clinical outcomes in patients with COVID-19
Authors: Terry Cheuk-Fung Yip, Grace Chung-Yan Lui, Vincent Wai-Sun Wong, Viola Chi-Ying Chow, Tracy Hang-Yee Ho, Timothy Chun-Man Li, Yee-Kit Tse, David Shu-Cheong Hui, Henry Lik-Yuen Chan, Grace Lai-Hung Wong
Journal: Gut (2020)

Data on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains unclear.This was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death.We identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir-ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation.ALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir-ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.
P-269 Lenvatinib in hepatocellular carcinoma: QoL surveys and radiological imaging markers predicting clinical outcome in patients with hepatocellular carcinoma treated with lenvatinib as first-line treatment (SULENVA-HCC)
Authors: A. Nappi, N. Zanaletti, L. Silvestro, A. Cassata, A. De Stefano, R. Casaretti, C. Romano, F. Calabrese, F. Lzzo, F. Fiore, None M. Piccirillo, A. Avallone
Journal: Annals of Oncology (2020)
Cancer Survivorship—Considering Mindsets—Reply
Authors: Laurence H. Baker, Erin Peregrine Antalis, Denise Reinke
Journal: JAMA Oncology (2020)

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 Oncology 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 Oncology journal
SO-28 A randomized phase II trial of mFOLFOX6-based standard of care alone or in combination with Ad-CEA vaccine plus avelumab in patients with previously untreated metastatic colorectal cancer
Authors: J. Redman, S. Gandhy, M. Gatti-Mays, H. Abdul Sater, Y. Tsai, R. Donahue, L. Cordes, S. Steinberg, J. Marte, S. McMahon, R. Madan, F. Karzai, M. Bilusic, S. Rabizadeh, J. Lee, P. Soon-Shiong, S. Kim, J. Marshall, B. Weinberg, J. Schlom, J. Gulley, J. Strauss
Journal: Annals of Oncology (2020)
Association of Adherence to Weight Telemonitoring With Health Care Use and Death
Authors: Sarah C. Haynes, Daniel J. Tancredi, Kathleen Tong, Jeffrey S. Hoch, Michael K. Ong, Theodore G. Ganiats, Lorraine S. Evangelista, Jeanne T. Black, Andrew Auerbach, Patrick S. Romano
Journal: JAMA Network Open (2020)

Adherence to telemonitoring may be associated with heart failure exacerbation but is not included in telemonitoring algorithms.
Vgamma4 gamma-delta T cells are essential for gamma-delta T cell-mediated tumor immune surveillance
Authors: Yunfei Gao, Weifang He, Rebecca L. O’Brien, Willi K. Born, Zhinan Yin
Journal: Cancer Research (2006)

4777  Vg1 and Vg4 are the two dominant subsets of peripheral gd T cells. It has been demonstrated that these two subsets have different roles in regulating CD4+ T cell Th1/Th2 responses, which in turns regulates airway inflammation and cardiac inflammation. However, the role of Vg1 versus Vg4 gd T cells in tumor immune surveillance is unclear. Based upon our early studies that gd T cells play a critical role in tumor immune surveillance through providing the early source of IFN-g, we hypothesize that Vg1 and Vg4 gd T cells may play a different role in anti-tumor immune responses. C57BL/6 (B6) mice were injected intravenously with anti-Vg1 antibody (clone 2.11) or anti-Vg4 antibody (UC3) (200 mg/mouse) for 2 times, with 5 days intervals. Our preliminary studies show complete depletion of Vg1 or Vg4 gd T cells and the depletion lasted for at least 2 weeks. Depletion of Vg4, but not Vg1, gd T cells rendered mice highly susceptible to B16 tumor cell growth. Notably, depletion of Vg4 gd T cells significantly reduced the tumor infiltration of ab T cells, and the reduced infiltration of ab T cells could be recovered by local administration of IFN-g-inducible protein 10 (IP-10). Furthermore, locally administration of IP-10 also reduced tumor incidence and tumor growth rate. Consistently, Vg4 gd T cells produced more IFN-g and less IL-4, which is in sharp contrast to Vg1 gd T cells, which produced less IFN-g and more IL-4. Therefore, our work demonstrate for the first time that Vg4 gd T cells play a critical role in tumor immune surveillance through regulating ab T cell infiltration, which is IP-10 mediated.
Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice
Authors: Seung-Chul Choi, Josephine Brown, Minghao Gong, Yong Ge, Mojgan Zadeh, Wei Li, Byron P. Croker, George Michailidis, Timothy J. Garrett, Mansour Mohamadzadeh, Laurence Morel
Journal: Science Translational Medicine (2020)

Gut microbiota dysbiosis induces lupus-like autoimmunity in mice through altered tryptophan catabolism.
Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using <i>BRCA2</i> Exon 3 as a Model System
Authors: Hélène Tubeuf, Sandrine M. Caputo, Teresa Sullivan, Julie Rondeaux, Sophie Krieger, Virginie Caux-Moncoutier, Julie Hauchard, Gaia Castelain, Alice Fiévet, Laëtitia Meulemans, Françoise Révillion, Mélanie Léoné, Nadia Boutry-Kryza, Capucine Delnatte, Marine Guillaud-Bataille, Linda Cleveland, Susan Reid, Eileen Southon, Omar Soukarieh, Aurélie Drouet, Daniela Di Giacomo, Myriam Vezain, Françoise Bonnet-Dorion, Violaine Bourdon, Hélène Larbre, Danièle Muller, Pascal Pujol, Fátima Vaz, Séverine Audebert-Bellanger, Chrystelle Colas, Laurence Venat-Bouvet, Angela R. Solano, Dominique Stoppa-Lyonnet, Claude Houdayer, Thierry Frebourg, Pascaline Gaildrat, Shyam K. Sharan, Alexandra Martins
Journal: Cancer Research (2020)

Abstract BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T&amp;gt;G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons. Significance: These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
T1 Mapping Tissue Heterogeneity Provides Improved Risk Stratification for ICDs Without Needing Gadolinium in Patients With Dilated Cardiomyopathy
Authors: Shiro Nakamori, Long H. Ngo, Jennifer Rodriguez, Ulf Neisius, Warren J. Manning, Reza Nezafat
Journal: JACC. Cardiovascular imaging (2020)
P-313 Management of frail patients with metastatic pancreatic ductal adenocarcinoma: A single-institution experience
Authors: A. Plaja Salarich, A. Ferrando Díez, A. Pous Badia, L. Notario Rincon, S. España Fernández, F. Pérez Martín, C. Hierro Carbó, C. Bugés Sánchez, J. Manzano Mozo, L. Layos Romero
Journal: Annals of Oncology (2020)
O-5 Efficacy and safety of nivolumab + ipilimumab in Asian patients with advanced hepatocellular carcinoma: Subanalysis of the CheckMate 040 study
Authors: T. Yau, C. Hsu, Y. Kang, T. Kim, M. Hou, H. Lim, Y. Chao, Y. Kim, M. Ikeda, S. Choo, J. Neely, Y. Shen, M. Tschaika, M. Kudo
Journal: Annals of Oncology (2020)
Use of zoledronate, a bisphosphonate, to inhibit development of lung metastasis in a mouse model of breast cancer
Authors: Kathy Carter, Barbara Fingleton
Journal: Cancer Research (2008)

1198  Bisphosphonates are the current standard of care for breast cancer patients with evidence of skeletal metastasis, however they are not used for soft tissue metastasis. There are various types of bisphosphonate drugs with the newer nitrogen-containing versions (e.g. zoledronate and pamidronate) having additional properties as well as higher potency than the previous drugs (e.g. clodronate). Recent evidence suggests that zoledronate not only targets osteoclast activity in the bone, but can also inhibit production and activity of the matrix metalloproteinase MMP9 in macrophages. Since we have data indicating that inflammatory cell-expressed MMP9 is critical for the development of lung metastases in the MMTV-PyMT model of breast cancer, we wished to test if zoledronate could limit lung metastasis in this model. We have assigned a cohort of female MMTV-PyMT transgenic mice to one of three treatment groups: vehicle, low-dose or high-dose zoledronate. In an attempt to model the clinical situation, the mice are not started on therapy until a mammary tumor is palpable. The cellular target of interest in these studies is the macrophage, thus blood samples could possibly be used to screen for drug efficacy. For this reason, we collected plasma samples from pre, mid and post-treatment to monitor the effectiveness of the treatment in altering MMP9 levels as assessed by an ELISA for murine pro-MMP9. Unfortunately, it appears that plasma MMP9 levels are regulated more by overall primary tumor burden rather than drug exposure. Zoledronate treatment, either high or low dose, does not reduce the size, growth rate or overall burden of primary mammary tumors in the MMTV-PyMT model. However, the ratio of lung metastases to mammary tumor burden is reduced with zoledronate treatment. Thus, there appears to be a specific impact of zoledronate on development of metastatic lesions in this model. These results are consistent with our previous data implicating MMP9 in development of lung metastasis and suggest that zoledronate is effective at inhibiting soft tissue metastasis.
A specific aggregation-induced emission-conjugated polymer enables visual monitoring of osteogenic differentiation
Authors: Zhenyu Zheng, Taotao Zhou, Rong Hu, Minjun Huang, Xiang Ao, Jun Chu, Tao Jiang, Anjun Qin, Zhongmin Zhang
Journal: Bioactive Materials (2020)

Osteogenic differentiation is the basis of bone growth and repair related to many diseases, in which evaluating the degree and ability of osteogenic transformation is quite important and highly desirable. However, fixing or stopping the growth of cells is required for conventional methods to monitor osteogenic differentiation, which cannot realize the full investigation of the dynamic process. Herein, a new anion conjugated polymer featuring aggregation-induced emission (AIE) characteristics is developed with excellent solubility for in-situ monitoring the process of osteogenic differentiation. This novel polymer can bind with osteogenic differentiated cells, and the intracellular fluorescence increases gradually with the enhancement of osteogenic differentiation. Moreover, it possesses good biosafety with negligible effect on cell activity and osteogenic differentiation, which cannot be realized by the typical method of Alizarin Red S staining. Further study shows that the polymer crosses the cell membrane through endocytosis and enriches in lysosomes, whereas no obvious fluorescence is detected with other cells, including non-differentiated osteoblast cells, under the same conditions, demonstrating the high selectivity. This is the first fluorescent probe with excellent specificity to realize real-time observation of the process of osteogenic differentiation. Therefore, PTB-EDTA shows great promise in the study of osteogenic differentiation and related applications.
O-4 NTRK gene fusions in bilio-pancreatic cancers
Authors: A. Demols, L. Perez-Casanova, L. Rocq, M. Charry, N. De Nève, A. Verrellen, A. Ramadhan, C. Van Campenhout, S. De Clercq, C. Maris, J. Closset, V. Lucidi, I. Salmon, N. D'Haene
Journal: Annals of Oncology (2020)
Abstract 10013: Usefulness of Cardiac Ultrasound Strain Analysis for Determining the Appropriateness of Coronary Intervention in Assessing Underlying Myocardial Ischemia
Authors: Toshihiko Hamada, Hiroyasu Uzui, Yuka Ootake, Hiroyuki Ikeda, Kentarou Ishida, Hideki Kimura, Hiroshi Tada
Journal: Circulation (2019)

Background and Aim: Strain analysis using two-dimensional speckle tracking (2DS) echocardiography (EC) is rapidly growing as a method to assess local and overall cardiac function. For stenotic coro...
Abstract TMIM-076: OMENTAL MACROPHAGES REGULATE OVARIAN CANCER METASTATIC COLONIZATION THROUGH THE CCL6-CCR1 SIGNALING AXIS
Authors: Venkatesh Krishnan, Supreeti Tallapragada, Bruce Schaar, Anita Chanana, Carrie Rinker-Schaeffer, Oliver Dorigo
Journal: Clinical Cancer Research (2019)

Abstract BACKGROUND: Metastatic ovarian cancer remains an urgent clinical problem. The homing and invasion of cancer cells into the omental adipose tissue, which is the preferred site of ovarian cancer metastasis, is a critical step in disease progression. Omental adipose tissue contains adipocytes, blood vessels, and clusters of leukocytes known as milky spots. We have previously demonstrated in several mouse models that intraperitoneally injected ovarian cancer cells localize to the omentum and specifically to the milky spots. However, we found that B, T, or NK cells were not required for omental colonization. We hypothesize that macrophages within the milky spots play a crucial role in promoting ovarian cancer progression. METHODS AND RESULTS: Depleting macrophages disrupts cancer cells' localization to the omentum. This result supports our hypothesis that macrophages play an essential role in attracting ovarian cancer cells to the omental milky spots. Correspondingly, factors secreted by omental macrophages promote ovarian cancer migration in vitro, in contrast to factors secreted by macrophages isolated from other peritoneal adipose tissues. In order to understand the specific mechanism(s) that regulate metastatic colonization of the omentum, we performed RNA-Seq of CD45+CD11b+F4/80+ flow-sorted macrophages from the omentum and the mesenteric fat of naïve and cancer-bearing mice. We found that omental macrophages have a distinct and dynamic gene expression pattern even when compared to a very similar cell type. The chemokine CCL6 is one of the most highly upregulated genes during metastatic colonization. The human homolog of CCL6 is CCL23 and is also expressed by human omental macrophages. Genomic inactivation of CCR1, the gene encoding receptor for CCL6 in mice and CCL23 in humans, in mouse ovarian cancer cells abolishes their ability to home to omental milky spots. Our findings establish a role for chemokine signaling in the early colonization of the omentum by ovarian cancer. CONCLUSION: We demonstrate that omental milky spots are the preferential sites for cancer colonization of peritoneal adipose. Further, we have identified omental macrophages as the critical mediators of colonization via the CCL6/CCR1 chemokine axis. Future studies are focused on understanding the cancer cell-macrophage interactions that can be targeted therapeutically to disrupt metastatic growth and extend disease-free survival. Citation Format: Venkatesh Krishnan, Supreeti Tallapragada, Bruce Schaar, Anita Chanana, Carrie Rinker-Schaeffer, Oliver Dorigo. OMENTAL MACROPHAGES REGULATE OVARIAN CANCER METASTATIC COLONIZATION THROUGH THE CCL6-CCR1 SIGNALING AXIS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-076.
P-246 Taxane cross-resistance: An exploratory analysis of second-line chemotherapy for metastatic gastric cancer
Authors: P. Di Nardo, M. Guardascione, D. Basile, L. Foltran, E. Ongaro, G. Miolo, V. Fanotto, C. Lisanti, B. Michele, A. Parnofiello, F. Cortiula, E. Bertoli, S. Buriolla, M. De Scordilli, A. Michelotti, F. Puglisi, A. Buonadonna
Journal: Annals of Oncology (2020)
Moving quickly in pandemics
Authors: Richard Hurley
Journal: BMJ (2020)

Moving quickly in pandemics Richard Hurley features and debates editorSpeed is of the essence in responding to the covid-19 pandemic.But in Leicester lockdown has been reimposed because information was shared too slowly.Local authorities lacked centrally held data to detect a rise in cases and act swiftly.In an editorial this week Mike Gill, Devi Sridhar, and Fiona Godlee describe a "chaotic system" in England that seems to focus on increasing test numbers instead of establishing a local testing strategy designed to contain the virus and save lives. 1 They blame the government's "paternalistic, centralising tendency" and lack of trust in local professionals.
SO-5 Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: A retrospective analysis
Authors: M. Javle, S. Sadeghi, S. Roychowdhury, A. El-Khoueiry, L. Goyal, P. Philip, R. Kelley, I. Borbath, T. Macarulla, W. Yong, S. Tanasanvimon, A. Li, M. Howland, A. Pande, G. Abou-Alfa
Journal: Annals of Oncology (2020)
Best Practices in Robotic-assisted Repair of Vesicovaginal Fistula: A Consensus Report from the European Association of Urology Robotic Urology Section Scientific Working Group for Reconstructive Urology
Authors: Marco Randazzo, Linda Lengauer, Charles-Henry Rochat, Achilles Ploumidis, Darko Kröpfl, Jens Rassweiler, Nicolo Maria Buffi, Peter Wiklund, Alexandre Mottrie, Hubert John
Journal: European Urology (2020)
Abstract 10246: Chronic Beta3-Adrenergic Receptor Antagonist Therapy Rescues Diabetic Cardiomyopathy Through Ca2+/Calmodulin-Dependent Protein Kinase II Inhibition
Authors: Heng-Jie Cheng, Yixi Liu, Zhe Chen, Xiaowei Zhang, Dalane Kitzman, Donald A McClain, Che Ping Cheng
Journal: Circulation (2019)

Background: Ca2+/calmodulin-dependent kinase II (CaMKII) overactivity in the pathophysiology of diabetic cardiomyopathy (DCM) makes CaMKII an attractive therapeutic target. CaMKII inhibition with K...