tbuckley/cabot-search huggingface dataset:
Chemotherapy as an alternative to radiotherapy in the treatment of stages IIA/B testicular seminoma: A Spanish Germ Cell Cancer Group study
Authors: X. Garcia Del Muro, P. Maroto, J. Gumá, M. López Brea, J. Sastre, J. A. Arranz, N. Lainez, F. López Lara, G. Berenguer, J. R. Germá-Lluch
Journal: Journal of Clinical Oncology (2004)

4530 Background: Radiotherapy (RT) is considered the standard treatment for stages IIA/B testicular seminoma. However, RT has been associated with an increased incidence of second malignancies in long-term survivors. As chemotherapy (CT) is highly effective in advanced disease and in recurrences after RT, we have developed a multicenter prospective protocol of treatment with CT in patients (pts) with stages IIA/B seminoma. Methods: We studied 71 consecutive pts with stages IIA and IIB testicular seminoma, initially treated with cisplatin-based chemotherapy, from April 1994 to March 2003 in 26 centers. 34 of these pts were previously reported within a wider series of pts with stages II-IV seminoma (Ann Oncol 2001;12:487). Patient characteristics were: median age 38 (27–84) years; 18 pts had stage IIA and 53 had stage IIB; 11 of these pts had had a relapse of a previous stage I on surveillance; 8 pts had high BHCG levels. The treatment administered was: EP (etoposide, cisplatin) in 62 and BEP (bleomycin, etoposide, cisplatin) in 9 pts. The number of cycles per patient was: 3 (9 pts), 4 (58), >4 (4). Results: There were 59 (83%) complete responses and 12 (17%) partial responses with residual mass and normal markers. 2 pts underwent resection of residual masses. After a median follow-up of 46 months, 6 pts relapsed and one of them died. Progression-free survival and overall survival at 4 years were 91% (95%CI: 83%–98%) and 98% (95%CI: 89%–100%), respectively. Hematological toxicity was: Granulocytopenia G-IV:1 pts, G-III: 3, G-II: 6; Thrombocytopenia G-III:2, G-II:2; Anemia G-III:1, G-II:1; Extrahematological toxicity was: Nausea/Vomiting G-III:6, G-II:16, Stomatitis GIII: 1, G-II: 3, Diarrhea G-III:1; Pulmonary toxicity G-III:1; Neurotoxicity G-II:4; Skin rash G-II:1. No significant late toxicity was observed. Conclusions: CT for stages IIA/B seminoma provides excellent results, is well tolerated and avoids the serious late morbidity associated with RT. Our results support the role of CT as an alternative to RT in the treatment of these pts. Comparison with RT focusing on long-term toxicities would be of great interest. No significant financial relationships to disclose.
Outcomes of beta blockers (BB) in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Linda Wu, Umut Ozbek, Grace van Hyfte, Marlene Reincke, Anuhya Gampa, Yehia I. Abugabal, Naoshi Nishida, Brooke Wietharn, Suneetha Amara, Lorenz Balcar, Matthias Pinter, Arndt Vogel, Arndt Weinmann, Anwaar Saeed, Lorenza Rimassa, Abdul Rafeh Naqash, Mahvish Muzaffar, Yi-Hsiang Huang, David James Pinato, Celina Ang
Journal: Journal of Clinical Oncology (2022)

399 Background: Portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, leading to a pro-inflammatory state, which can in turn promote progression of liver disease. However, multiple studies have shown that BB use in patients with cirrhosis can reduce the risk of developing HCC, and in patients with HCC, BB can improve overall survival (OS). In recent years, ICIs have become first-line therapy for patients with unresectable HCC, and we aimed to evaluate whether BB use conferred survival benefits in patients treated with ICIs using real-world data. Methods: We conducted a retrospective chart review of HCC patients treated with ICI from 2017 to 2019 at 13 institutions across North America, Europe, and Asia in order to evaluate the association between BB use and OS, as well as BB use and overall response rate (ORR). Univariable and multivariable logistic regression models were used to evaluate associations, and survival analyses were performed using the Kaplan-Meier method. Results: A total of 578 patients were evaluated. The median age of the cohort was 65 years, and 80% of patients were male. The majority of patients (70%) were cirrhotic. The causes of underlying liver disease were as follows: HBV (22%), HCV (36%), alcohol (20.8%), and NASH (13%). Most patients (73.5%) had Child Pugh (CP) class A liver disease, and good performance status with ECOG score either 0 (52%) or 1 (45%). The majority of patients (75%) treated with ICIs received a PD-1 inhibitor alone. There were 360 deaths (62% of patients) with a median follow-up of 30.8 months (Quartiles: 17.2-40.3 months). Two hundred and three (35%) patients had BB use at any point during ICI therapy. Fifty-one percent of these patients were on a nonselective BB whereas 49% were taking a cardio-selective BB. BB use was not significantly correlated with OS (hazard ratio, 1.12; 95% CI, 0.9-1.39; P = 0.298) or ORR (odds ratio, 0.84; 95% CI, 0.54-1.31; P = 0.451) in univariate or multivariate analyses. Conclusions: Patients who used BB while on immunotherapy for unresectable HCC did not have statistically significant differences in OS or ORR compared to patients who did not use BB. More studies are required to elucidate the effect of beta blockade on the microbiome, immune activation, and HCC.
Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathway <i>in vitro</i> and <i>in vivo</i>
Authors: Ziping Song, Haixu Song, Dan Liu, Bing Yan, Daowen Wang, Yan Zhang, Xiaojie Zhao, Xiaoxiang Tian, Chenghui Yan, Yaling Han
Journal: Theranostics (2022)

Background:The continued success of oncological therapeutics is dependent on the mitigation of treatment-related adverse events, particularly cardiovascular toxicities.As such, there is an important need to understand the basic mechanisms of drug toxicities in the process of antitumor therapy.Our aim in this study was to elucidate the underlying mechanisms of sorafenib (sor)-induced cardiomyocyte damage.Methods: Primary mouse cardiomyocytes were prepared and treated with sor and various other treatments.Cardiomyocyte necroptosis was detected by flow cytometry, western blotting, and CCK8 assays.Mitochondrial Ca 2+ uptake was detected by the Rhod-2 probe using confocal imaging.Morphological changes in mitochondria and mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) were imaged using transmission electron microscopy (TEM) and confocal microscopy.Cardiac perfusion was performed to detect cardiac specific role of MFN2 overexpression in vivo.Results: We reported that mitochondrial Ca 2+ overload, the subsequent increase in calmodulin-dependent protein kinase II delta (CaMKIIδ) and RIP3/MLKL cascade activation, contributed to sor-induced cardiac necroptosis.Excess MAM formation and close ER-mitochondria contact were key pathogenesis of sor-induced Ca 2+ overload.Sor mediated MFN2 downregulation in a concentration-dependent manner.Furthermore, we found that reduced mitofusin-2 (MFN2) level augmented sor-mediated elevated MAM biogenesis and increased mitochondria-MAM tethering in cardiomyocytes.Sor-induced Mammalian Target of Rapamycin (mTOR) inactivation, followed by the activation and nuclear translocation of Transcription Factor EB (TFEB), contributed to mitophagy and MFN2 degradation.In an in vivo model, mice subjected to sor administration developed cardiac dysfunction, autophagy activation and necroptosis; our investigation found that global and cardiac-specific overexpression of MFN2 repressed cardiac dysfunction, and sor-induced cardiomyocyte necroptosis via repressing the MAM-CaMKIIδ-RIP3/MLKL pathway. Conclusion:Sorafenib mediated cardiomyocyte necroptosis through the MFN2-MAM-Ca 2+ -CaMKIIδ pathway in vitro and in vivo.The overexpression of MFN2 could rescue sor-induced cardiomyocyte necroptosis without disturbing the anti-tumor effects.
THE MEDICAL STUDENT SECTION OF JAMA
Journal: JAMA (1991)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Pneumococcal and Influenza Vaccination Levels Among Adults Aged ≥65 Years— United States, 1993
Journal: JAMA (1996)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract P195: The Relative Contribution of Systolic Blood Pressure in Cardiovascular Risk Prediction Declines
Authors: Susanne Rospleszcz, Barbara Thorand, Tonia de las Heras Gala, Christa Meisinger, Rolf Holle, Wolfgang Koenig, Annette Peters
Journal: Circulation (2017)

Background: The Framingham Risk Score (FRS) is an established tool for the prediction of cardiovascular disease (CVD) risk. The established CVD risk factors age, HDL cholesterol, total cholesterol, systolic blood pressure (SBP), antihypertensive treatment, diabetes mellitus and smoking are used in the calculation of the FRS. The prevalence and distribution of these risk factors in the population have changed within the last decades and especially average levels of SBP have declined. However, the impact of this change on the risk prediction performance of the FRS has not been investigated. Hypothesis: We assessed the hypothesis that the relative contribution of SBP to CVD risk prediction within the FRS framework has changed from 1985 to 2000. Methods: We used N = 11 760 participants aged 30 - 65 years from four prospective population-based cohort studies enrolled in Southern Germany in 1985, 1990, 1995, and 2000. CVD risk was calculated by recalibrated equations of the original FRS. Predicted CVD risks using the actual SBP values were compared to predicted CVD risks using optimal (SBP &lt; 120 mmHg) values for each participant. We assessed the relative contribution of SBP with three performance measures: First, the median difference in predicted risks with actual and optimal SBP, second, the relative positive predictive value of the FRS using actual compared to optimal SBP values and third, the population attributable risk fraction of SBP using Levin’s formula. Results: CVD events occurred in 6.3% of male participants in 1985 and 6.2% in 2000; in women, event rates were 2.4% and 2.3%, respectively. Mean SBP levels decreased from 134 mmHg (Standard Deviation: 17 mmHg) to 132 (SD: 17) mmHg in men and from 127 (SD: 19) mmHg to 121 (SD: 18) mmHg in women. The difference in median predicted risk declined from 1.21 [Interquartile range 0.52, 3.38] in 1985 to 0.93 [0.35, 2.44] in 2000 in men and from 0.26 [-0.05, 1.45] to -0.07 [-0.19, 0.89] in women. The relative positive predictive value dropped from 0.88 to 0.73 in men and from 0.61 to 0.53 in women. The population attributable risk fraction of SBP decreased from 70.2% (95% CI: 42.1, 89.6) to 29.71% (-6.4, 64.7) in men and from 85.7% (62.9, 93.1) to 57.9% (28.0, 82.0) in women. Given the results from 1990 and 1995, the declining trend was nonlinear for all three performance measures. Conclusion: In conclusion, the relative contribution of blood pressure to cardiovascular risk prediction has decreased within the last decades. This affects the future development of CVD risk prediction methods which will have to consider the changing relative importance of SBP. Furthermore, this might also influence public health policies focusing on the management of SBP and hypertension in order to effectively prevent CVD.
Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative Data Hub
Authors: William A. Wood, Donna S. Neuberg, John Colton Thompson, Martin S. Tallman, Mikkael A. Sekeres, Laurie H. Sehn, Kenneth Anderson, Aaron D Goldberg, Nathan A Pennell, Charlotte M. Niemeyer, Emily Tucker, Kathleen Hewitt, Robert M Plovnick, Lisa K. Hicks
Journal: Blood (2020)
Congenital Erythropoietic Protoporphyria: I. Case Reports, Clinical Studies and Prophyrin Analyses in Two Brothers
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Contents
Authors: George Bartley, Suzann Pershing, Mary Goldstein, Victor Henderson, M Kate Bundorf, Ying Lu, Moshiur Rahman, Joshua Stein, Alexander Day, Jennifer Burr, Kate Bennett, Catey Bunce, Caroline Doré, Gary Rubin, Mayank Nanavaty, Jon Dishler, Stephen Slade, Stefanie Seifert, Steven Schallhorn
Journal: Ophthalmology (2020)
SUMOylation of E2F1 Regulates Expression of EZH2
Authors: Li Du, Marwan G. Fakih, Steven T. Rosen, Yuan Chen
Journal: Cancer Research (2020)

Elevated expression of EZH2, the enzymatic subunit of polycomb repressive complex 2 (PRC2), often occurs in cancer. EZH2 expression results in the silencing of genes that suppress tumor formation and metastasis through trimethylation of histone H3 at lysine 27 (H3K27me3) at their promoters. However, inhibitors of EZH2 enzymatic activity have not shown the expected efficacy against cancer in clinical trials, suggesting a need for other strategies to address EZH2 overexpression. Here, we show that SUMOylation, a posttranslational modification characterized by covalent attachment of small ubiquitin-like modifier (SUMO) proteins to a lysine (Lys) residue on target proteins, enhances EZH2 transcription. Either knockdown of the SUMO-activating enzyme SAE2 or pharmacologic inhibition of SUMOylation resulted in decreased levels of EZH2 mRNA and protein as well as reduced H3K27me3 levels. SUMOylation regulated EZH2 expression by enhancing binding of the E2F1 transcriptional activator to the EZH2 promoter. Inhibition of SUMOylation not only resulted in reduced EZH2 mRNA and protein levels but also increased expression of genes silenced by EZH2, such as E-cadherin, which suppresses epithelial-mesenchymal transition and metastasis. In more than 6,500 patient tumor samples across different cancer types, expression of UBA2 and EZH2 was positively correlated. Taken together, our findings suggest that inhibition of SUMOylation may serve as a potential strategy to address EZH2 overexpression and improve current cancer therapeutic approaches. SIGNIFICANCE: These findings provide important biological insights into the mechanism of EZH2 overexpression in cancers and suggest that inhibiting SUMOylation may improve current cancer therapeutic approaches.
JAMA Oncology
Journal: JAMA Oncology (2022)

JAMA Oncology is committed to publishing infl uential original research, opinions, and reviews that advance the science of oncology and improve the clinical care of patients with cancer.Mission Statement JAMA Oncology is the defi nitive journal for scientists, clinicians, and trainees in the fi eld of oncology worldwide.Our original, innovative, and timely scientifi c and educational content provides a deeper understanding of cancer pathogenesis and recent treatment advances for our readers.JAMA Oncology aims to eff ectively convey the fi ndings of important clinical research, major scientifi c breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community.Our goal is that successful communication of new knowledge will ultimately translate to clinical benefi t for people living with and surviving cancer.
Medical News
Journal: JAMA (1922)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Metastatic bulk to predict subclonal heterogeneity by ctDNA in RAS/RAF-wildtype colorectal cancer.
Authors: Jeremy D. Kratz, Sam Joseph Lubner, Noelle K. LoConte, Monica Arun Patel, Nataliya Volodymyrivna Uboha, Dyan M. Lesnik, Sara Ahmed, Michael J. Kelley, Kayla Lemmon, Michael Frederick Bassetti, Cristina Sanger, Dustin A. Deming
Journal: Journal of Clinical Oncology (2022)

186 Background: Distinct molecular subgroups of colorectal cancer (CRC) have been afforded with use of next-generation sequencing (NGS) as standard in clinical practice for advanced disease. We have previously demonstrated that disease bulk predicts clinical resistance to EGFR inhibition in RAS/RAF-wildtype (WT) CRC. We hypothesized bulky disease would predict advanced subclonal heterogeneity by circulating tumor DNA (ctDNA) in RAS/RAF WT CRC. Methods: Following IRB-approval, a retrospective review of molecular profiles in advanced CRC (n = 965) were compiled from the Veteran Administration’s (VA) National Precision Oncology Program (NPOP) and University of Wisconsin Precision Medicine Molecular Tumor Board (MTB). Disease bulk was defined as the longest diameter of metastatic disease or short axis for advanced lymphadenopathy. Molecular profiling was performed using commercially available platforms including Strata Oncology (MTB) and FoundationOne (NPOP). Bulky was compared as categorical (&gt; 35 cm) and continuous variable against the count of pathologic variants. Results: The population was largely representative of advanced CRC with alterations in TP53 (80.5%), KRAS (44.8%), PIK3CA (22.0%) and BRAF (12.8%). Veterans had increased frequency of alterations in PIK3CA (22.7% v. 13.0%, p &lt; 0.02) and BRAF (13.3% v. 6.9%, p &lt; 0.05). There was no difference in metastatic bulk at the time of NGS for tissue biopsy between MTB and NPOP populations (t = 0.80). Disease bulk did not predict the number of pathologic variants from tissue sampling in RAS/RAF WT CRC (n = 96, t = 0.24). RAS/RAF MT cancers had increased frequency of subclonal alterations by ctDNA (9.1±4.0) v. RAS/RAF WT (4.5±3.4, p &lt; 0.0001). Using ctDNA, bulky disease in RAS/RAF MT CRC was not predictive of increased pathologic variants (8.8±3.5 v. 9.5±4.8, t = 0.62). Bulky disease (&gt; 35mm) in RAS/RAF WT CRC predicted increased subclonal variants (6.2±3.6 v. 3.5±2.9, p &lt; 0.02). As a continuous variable, disease bulk predicted the number of pathologic variants in RAS/RAF WT CRC (R = 0.51). Conclusions: These data indicate that metastatic bulk is a predictor of subclonal heterogeneity by ctDNA in RAS/RAF WT CRC. Molecular profiling of tissue alone did not predict differences in subclonal heterogeneity when stratified by disease bulk in RAS/RAF WT CRC. Limited subclonal heterogeneity in non-bulky cancers support ongoing prospective investigations to select non-bulky cancers for early incorporation of anti-EGFR inhibition (NCT04587128).
The Von Willebrand Factor Tyr2561 Allele Is a Gain-of-Function Variant and a Potential Risk Factor for Early Myocardial Infarction
Authors: Reinhard Schneppenheim, Natalie Hellermann, Maria Alexandra Brehm, Ulrike Klemm, Tobias Obser, Volker Huck, Stefan W Schneider, Cecile V. Denis, Alexander Tischer, Matthew Auton, Winfried Maerz, Emma-Ruoqi Xu, Matthias Wilmanns, Rainer B. Zotz
Journal: Blood (2018)
Hepatocyte growth factor: Potential role of a novel vascular modulator in acute myocardial infarction patients Konstantinos I. Kapetanios, Christos E. Pitsavos, Emmanuel V. Economou, Marina G. Toutouza, Christodoulos I. Stefanadis, Pavlos K. Toutouzas. Hippokration Hospital of Athens, ATHENS, Greece, University of Athens Medical School, ATHENS, Greece
Journal: Journal of the American College of Cardiology (2001)