tbuckley/cabot-search huggingface dataset:
High incidence of cardiovascular mortality caused by acute and early chronic progressive doxorubicin toxicity: Retrospective analysis of 606 patients.
Authors: W. Jurczak, M. Sobocinski, M. Joks, M. Komarnicki, J. Drozd-Sokolowska, P. Boguradzki, J. Dzietczenia, T. Wrobel, G. Mazur, W. Spychalowicz, B. Kumiega, W. Knopinska-Posluszny, A. B. Skotnicki
Journal: Journal of Clinical Oncology (2011)

e18532 Background: Cardiovascular (CVS) system disorders in Poland are responsible for 52% of all deaths and 18% loss of DALY (disability-adjusted life year), compared to 38% and 11% in US respectively. A retrospective analysis was performed to investigate whether the high incidence of CVS disorders in Poland would translate into increased mortality related to cardiotoxicity of doxorubicin based chemotherapy regimens. Methods: Patients (N=606) from 7 hematological centers received the average of 6.7 (1-11) chemotherapy cycles, with cumulative dose of doxorubicin 330 mg/m2 (range 25 – 850); 146 (24%) patients were subjected to further treatment (transplant or radiotherapy) as consolidation or in relapse. Initial cardiac assessment was based on medical histories including echocardiography in 340 (56%) cases. All patients or they families were additionally questioned at the time of analysis about symptoms and signs of left ventricular failure (LVF), or the causes of death. Results: Acute cardiotoxicity was reported in 32 (5%) patients: ten of them died (1.6%), chemotherapy had to be postponed, prematurely terminated or the doses reduced in further 22 cases (3.4%0. The average Left Vetricular Ejection Fraction (LVEF), assessed by echochardiography decreased from 62% (range 40-85%) at diagnosis to 56% (range 20-75%) at the end of treatment (p<0.001). Cardiac impairment was significantly less pronounced in 30 patients treated with liposomal doxorubicin (average LVEF 56.4 and 54.7 respectively, p< 0.001). At the average observation time of 3 years, early chronic progressive cardiotoxicity was responsible for 18 cardiac deaths (2.9%) and further 81 patients (13.3%) required cardiological treatment including 22(3%) cases of acute coronary syndromes. At the time of analysis 40 (43%) patients died due to disease progression. Conclusions: In our retrospection CVS disorders are already the second most common cause of mortality in lymphoma patients (28/92 – 30% of all deaths, 28/606 – 4.6% of all cases). With the expected increased incidence of late chronic progressive cardiotoxicity we would estimate cardiac mortality to be at least doubled at 10 years.
The unique aspects of acute promyelocytic leukemia.
Authors: R M Stone, R J Mayer
Journal: Journal of Clinical Oncology (1990)

Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML.
HEATR1 Negatively Regulates Akt to Help Sensitize Pancreatic Cancer Cells to Chemotherapy
Authors: Tongzheng Liu, Yuan Fang, Haoxing Zhang, Min Deng, Bowen Gao, Nifang Niu, Jia Yu, SeungBaek Lee, JungJin Kim, Bo Qin, Fang Xie, Debra Evans, Liewei Wang, Wenhui Lou, Zhenkun Lou
Journal: Cancer Research (2015)

Elucidating mechanisms of chemoresistance is critical to improve cancer therapy, especially for the treatment of pancreatic ductal adenocarcinoma (PDAC). Genome-wide association studies have suggested the less studied gene HEAT repeat-containing protein 1 (HEATR1) as a possible determinant of cellular sensitivity to different chemotherapeutic drugs. In this study, we assessed this hypothesized link in PDAC, where HEATR1 expression is downregulated significantly. HEATR1 silencing in PDAC cells increased resistance to gemcitabine and other chemotherapeutics, where this effect was associated with increased AKT kinase phosphorylation at the Thr308 regulatory site. Mechanistically, HEATR1 enhanced cell responsiveness to gemcitabine by acting as a scaffold to facilitate interactions between AKT and the protein phosphatase PP2A, thereby promoting Thr308 dephosphorylation. Consistent with these findings, treatment with the AKT inhibitor triciribine sensitized HEATR1-depleted PDAC cells to gemcitabine, suggesting that this therapeutic combination may overcome gemcitabine resistance in patients with low HEATR1 expression. Clinically, we found that HEATR1 downregulation in PDAC patients was associated with increased AKT phosphorylation, poor response to tumor resection plus gemcitabine standard-of-care treatment, and shorter overall survival. Collectively, our findings establish HEATR1 as a novel regulator of AKT and a candidate predictive and prognostic indicator of drug responsiveness and outcome in PDAC patients.
Abstract 889: MicroRNA-21-5p upregulation in urine samples serves as novel biomarkers for early stage renal cell carcinoma patients diagnosis
Authors: Wei Meng, Hansjuerg Alder, Kirsteen Maclean, Simon Kirste, Petra Stegmaier, Anca Grosu, Arnab Chakravarti, Tim Lautenschlaeger
Journal: Cancer Research (2014)

Abstract Early prevention of renal cell carcinoma needs a reliable and robust bioassay to evaluate kidney cancer patients. As a novel class of regulatory molecules in cellular activity, the recent studies showed that microRNAs had tissue-specific patterns and were able to distinguish the cancer from benign disease. We explored the diagnostic value of urine microRNAs from a cohort of 160 individuals: 80 patients with renal clear cell carcinoma and 80 normal control individuals. Material and methods: The renal clear cell carcinomas cohort included 63% stage I cases, 10% stage II cases, 19% stage III cases, 7% stage IV cases, 1% unknown cases. Normal control cohort included 34% diverticulosis cases, 15% bariatric surgery cases, 14% diverticulitis cases, 15% hernia surgery cases, 10% hemorrhoids cases and 12% other non-cancer conditions. Every 10 urine samples were pooled together and subjected to microRNA extraction. The Norgen Biotek urine microRNA purification kit was used for total microRNA extraction (including free floating microRNAs and microRNAs from exfoliated cells) in the pooled urine samples. Urine microRNA expression profiling was performed using nCounter miRNA Expression Assay. After ligation and purification, hybridized microRNAs sequences were label by specific color codes and quantified using nCounter Digital Analyzer, then the data were normalized to the sum of the microRNAs within each pooled sample before statistic analysis. Result: comparing to normal control urine samples, microRNA-21-5p expression showed upregulation in kidney urine samples, which is consistent with TCGA kidney cancer tissue profiling results. Some recent studies also demonstrated that microRNA-21 may act as an oncomir in prostate, lung and colorectal cancers. We also observed that microRNA-1268a and microRNA-549 were highly expressed in urine samples from renal cell carcinoma patients. Conclusion: These findings indicate that in urine microRNA-21-5p may serve as a potential molecular marker for renal cell carcinoma and provide a new approach in the diagnosis of kidney cancer. Note: This abstract was not presented at the meeting. Citation Format: Wei Meng, Hansjuerg Alder, Kirsteen Maclean, Simon Kirste, Petra Stegmaier, Anca Grosu, Arnab Chakravarti, Tim Lautenschlaeger. MicroRNA-21-5p upregulation in urine samples serves as novel biomarkers for early stage renal cell carcinoma patients diagnosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2014-889
Comparison of the prognostic significance between the number of metastatic lymph nodes and nodal stage based on their location in patients with gastric cancer.
Authors: T Ichikura, S Tomimatsu, Y Okusa, K Uefuji, S Tamakuma
Journal: Journal of Clinical Oncology (1993)

To determine which is the better prognostic determinant in gastric cancer: number of positive metastatic lymph nodes or current nodal stage.Seven hundred seventy-seven patients who underwent potentially curative resections for gastric cancer were divided into three groups according to the depth of invasion. The influence of the number of positive nodes on their survival rate was analyzed. A multivariate analysis by the Cox proportional hazards model was used to determine independent prognostic factors.A decreased survival rate was associated with an increased number of positive nodes in all of the subjects and in each of the three groups. Patients with one to three positive nodes had as good a prognosis as those without nodal involvement when each of the three groups was analyzed separately. Using a multivariate analysis in the patients with four or more positive nodes, we found that the number of positive nodes was the most important prognostic determinant (P < .0001), followed by the depth of invasion (P < .02), and that the nodal stage was not significantly prognostic. Further multivariate analysis in the patients with one to three positive nodes showed that nodal stage and number of positive nodes were not significantly prognostic.The number of metastatic nodes should be adopted for classification of nodal stage in gastric cancer.
<i>CELF4</i>Variant and Anthracycline-Related Cardiomyopathy: A Children’s Oncology Group Genome-Wide Association Study
Authors: Xuexia Wang, Can-Lan Sun, Adolfo Quiñones-Lombraña, Purnima Singh, Wendy Landier, Lindsey Hageman, Molly Mather, Jerome I. Rotter, Kent D. Taylor, Yii-Der Ida Chen, Saro H. Armenian, Naomi Winick, Jill P. Ginsberg, Joseph P. Neglia, Kevin C. Oeffinger, Sharon M. Castellino, Zoann E. Dreyer, Melissa M. Hudson, Leslie L. Robison, Javier G. Blanco, Smita Bhatia
Journal: Journal of Clinical Oncology (2016)

Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk.
Cytogenetic findings in T-cell lymphoma of angioimmunoblastic lymphadenopathy.
Authors: A Younes
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.7.2188 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8683255 Cytogenetic findings in T-cell lymphoma of angioimmunoblastic lymphadenopathy. A YounesxA YounesSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.7.2188 PDF "Cytogenetic findings in T-cell lymphoma of angioimmunoblastic lymphadenopathy.." Journal of Clinical Oncology, 14(7), pp. 2188–2189© 1996 by American Society of Clinical Oncology
Will Medicare 2004 reimbursement (as predicted by ASCO) markedly affect economics of non-small cell lung cancer (NSCLC) chemotherapy
Authors: P. A. Grusenmeyer, G. A. Masters, R. J. Gralla
Journal: Journal of Clinical Oncology (2004)

6073 Background: Economic and clinical issues with NSCLC, the leading cause of US cancer death, can have a major impact on oncology care. Marked reimbursement changes were expected based on reduction in drug payments and some increases in chemotherapy administration charges. Two-drug platinum-containing regimens are considered the standard of care, with several regimens FDA approved* and others, felt to have similar outcomes, commonly utilized (Schiller, NEJM, 2002; Kelly, JCO, 2001; Raftopoulos, Proc ASCO, 2002). Controversy continues regarding survival and quality of life with carboplatin regimens (Rosell, Ann Oncol, 2002; Fosella, JCO, 2003). This analysis compares Medicare reimbursements with the implementation of the Medicare Prescription Drug Act 2003. Methods: Medicare 2003 reimbursement was developed using the Center for Medicare and Medicaid Services (CMS) HCPCS Drug Pricing File effective April 2003 (the Single Drug Pricer) and the Medicare Physician Fee Schedule (Delaware) (MPFS.) Predicted Medicare 2004 reimbursement was developed using the ASCO Estimated 2004 AWP Payments chart and MPFS with increases based on ACCC estimates. Reimbursement was calculated on six cycles of treatment. Actual 2003 and predicted 2004 reimbursements are compared in the table below: Results: Conclusions: 1) Predicted total Medicare 2004 reimbursements appear to be only minimally different from those of 2003 (mean difference -$18). 2) Reimbursements will be similar among the chemotherapy combinations, with FDA approved regimens reimbursed at a lower rate than the non-approved regimen. 3) Additional analysis will be conducted when the final Medicare 2004 reimbursements are released by CMS. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; GlaxoSmithKline Aventis; GlaxoSmithKline
A phase II study of erlotinib as first-line treatment of advanced non-small cell lung cancer
Authors: G. Giaccone, T. Lechevalier, N. Thatcher, E. Smit, M. Janmaat, J. Rodriguez, D. Oulid-Aissa, J. C. Soria
Journal: Journal of Clinical Oncology (2005)

7073 Background: Erlotinib (TarcevaTM) is an orally available selective EGFR tyrosine-kinase inhibitor. In patients with advanced NSCLC, 2nd/3rd-line erlotinib significantly prolonged survival (Shepherd et al. ASCO 2004) with a response rate (RR) of 9%. This phase II trial evaluated the efficacy and safety of 1st line erlotinib in patients with advanced NSCLC. Methods: Chemotherapy-naïve, stage IIIB/IV, PS 0–2, NSCLC patients have been enrolled to receive erlotinib 150 mg/day until disease progression or withdrawal. The primary endpoint of the study was the rate of non-progression in >50% of patients after 6 weeks of treatment. Secondary endpoints included objective response, disease control rate, duration of response, time to progression, survival and safety. Exploratory analyses included QoL, EGFR expression and mutation analysis, and FDG-PET response at 3 weeks in a subset of patients. Results: 54 patients were enrolled from January to July 2004 from 3 institutions. 53 patients received erlotinib and are assessable. Demographics: M/F 20/33; median age 61; PS 0/1/2 13/32/8; pathology adeno 23, squamous cell 9, bronchioloalveolar (BAC) 6, large cell 8, other 7; smoking status current/former/never 10/25/18. The non-progression rate was 55%. Best response was: 1CR, 12 PR, 16 SD, 17 PD, 7 NE (RR 24.5%; 95% CI 13.8–38.3). To date, 14 patients have not progressed and 12 have been treated for 6 months or longer. Responses were observed in males (1CR, 3 PR) and in females (9 PR), mostly in adenocarcinoma (7) and in BAC (4), in non or former smokers (12). The most common adverse events were diarrhea and rash (28 patients each), primarily of grades 1/2. Five patients had a grade 3 event: 2 rash, 1 lethargy, 1 diarrhea, 1 conjunctivitis. No grade 4 events. Bilirubin elevation was reported for 6 patients (4 grade 1, 2 grade 2). EGFR and PI3K mutations were not found in 15 patients so far assessed (1 responder) but 8 had K-ras mutations. Conclusions: Erlotinib is active and well tolerated as first-line monotherapy in advanced NSCLC. Responses were seen in both genders including a CR in a male with adenocarcinoma, but were more common in women, adenocarcinomas/BAC and non-smokers. Further assessment of erlotinib in this setting is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Roche AstraZeneca, Roche AstraZeneca, Roche
Actions of epoxygenase metabolites on the preglomerular vasculature.
Authors: J D Imig, L G Navar, R J Roman, K K Reddy, J R Falck
Journal: Journal of the American Society of Nephrology (1996)

Epoxygenase metabolites of arachidonic acid are produced by the kidney and have been implicated in the control of renal blood flow. This study examined the preglomerular actions of various epoxyeicosatrienoic acids (EET). By use of the in vitro blood-perfused juxtamedullary nephron preparation, interlobular and afferent arteriolar diameter responses to 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET were determined. Diameters of interlobular and afferent arterioles preconstricted with 0.5 microM norepinephrine averaged 24 +/- 1 microns (N = 27) and 17 +/- 1 microns (N = 32), respectively, at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.01 to 100 nM 11,12-EET caused graded increases in diameters of the interlobular and afferent arterioles. At a dose of 100 nM, 11,12-EET increased the diameters of the interlobular and afferent arterioles by 18 +/- 2% (N = 10) and 20 +/- 3% (N = 9), respectively. The vasodilatory response to 11,12-EET was stereoselective because 11,12(R,S)-EET but not 11,12(S,R)-EET increased the diameters of the interlobular and afferent arterioles. 14,15-EET had a much smaller effect and increased the diameters of the these vessels by 10%; 8,9-EET did not significantly affect vascular diameters. In contrast, 5,6-EET constricted the interlobular and afferent arterioles by 16 +/- 3% (N = 6) and 21 +/- 3% (N = 7), respectively. The corresponding diols, 5,6-DIHETE and 11,12-DIHETE, had no effect on diameters of the interlobular and afferent arterioles at concentrations up to 1 microM. The vasodilatory response to 11,12-EET was not affected by removal of the endothelium or by inhibition of cyclooxygenase with indomethacin. In contrast, the vasoconstrictor response to 5,6-EET was abolished by both removal of the endothelium or cyclooxygenase inhibition. The thromboxane/ enderoperoxide receptor inhibitor, SQ 29,548, resulted in a 60% attenuation of the afferent arteriolar vasconstriction to 5,6-EET. These results indicate that the preglomerular vasoconstriction to 5,6-EET is cyclooxygenase dependent and requires an intact endothelium, whereas the vasodilation to 11,12-EET is stereoselective and is the result of direct action of the epoxide on the preglomerular vascular smooth muscle.
贯彻《国务院关于建立全科医生制度的指导意见》 促进全科医生队伍建设
Authors: 秦怀金
Journal: BMJ (2011)

【编者按】2011年7月15日，中华医学会、中国医师协会共同在北京召开贯彻《国务院关于建立全科医生制度的指导意见》（《指导意见》）座谈会。卫生部部长、中华医学会会长陈竺和中国医师协会会长殷大奎与会并做了重要讲话，卫生部多位领导、数十名我国医学教育领导和专家、临床医学专家和全科医生到会。本栏目内的7篇文章均是根据座谈会上的讲话整理而成，除表达出对《指导意见》颁布的欣喜心情外，还从不同的角度论述了我国现阶段全科医生培养中的问题，以及未来如何在《指导意见》的指导下建立全科医生制度并推进全科医学的发展。
More Than Tiny Sacks
Authors: Raj Kishore, Mohsin Khan
Journal: Circulation Research (2016)

Stem cell therapy provides immense hope for regenerating the pathological heart, yet has been marred by issues surrounding the effectiveness, unclear mechanisms, and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been used with varied success. Cell-free components, such as exosomes enriched in proteins, messenger RNAs, and miRs characteristic of parental stem cells, represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively used to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes, including their potential benefits and limitations to develop a potentially viable therapy for cardiovascular problems.
A Highly Sensitive Determination of Lenalidomide in Human Plasma by Liquid Chromatography with Fluorescence Detection
Authors: Shuuji Hara, Aiko Nagase, Kentaro Ogata, Masanobu Uchiyama, Taichi Matsumoto, Shiro Jimi, Yasushi Takamatsu, Kazuo Tamura
Journal: Annals of Oncology (2014)
Age is a major risk factor of venous thromboembolism (VTE)
Authors: Nicolas Bizien, Elise Noel-Savina, Cecile Tromeur, Aurelien Delluc, Dominique Mottier, Christophe Leroyer, Francis Couturaud
Journal: European Respiratory Journal (2011)

Introduction: Age is a major risk factor of developing a first episode of VTE; however, the impact of age on the risk of recurrent VTE remains controversial.

Method: In a prospective cohort of 607 patients with a first episode of proximal deep vein thrombosis of pulmonary embolism, we aimed to evaluate if age of VTE was an independent risk factor of recurrent VTE. The role of other risk factors was analyzed: sex, the clinical presentation as PE or proximal DVT, the presence or the absence of provoking risk factors, factor V Leiden (FVL) and prothrombin gene mutation (PGM) was analyzed. All the episodes of first VTE and recurrent VTE were diagnosed according to predefined, validated and standardized criteria.

Results: During of a mean follow-up of 36 months, 95 (15.6%) patients had recurrent VTE. In multivariate analysis, for each year that the patient was older, the incidence of recurrent VTE increased by 3.0% (OR=1.03; 95%CI [1.01-1.05], p<0.001); when age of patients was divided into quartiles, the relative risks of VTE were as follows: [64-74 years]: OR=2.9; 95%CI [1.3-6.9]; [75-99 years]: OR=3.1; 95%CI [1.3-7.5], p=0.01; quartile of reference [18-44 years]. Men and women had similar risks of recurrence, excepted women who had VTE in association with hormonal change (contraception, pregnancy or hormonal substitution treatment): OR=0.2; 95%CI [0.1-0.4] p<0.0001). FVL and PGM were not associated with an increased risk of recurrent VTE (OR=1.1; 95%CI [0.5-2.1]; p=0.9).

Conclusion: Age is a major independent risk factor of recurrent VTE.
Abstract 14649: Impact of a Weight Management Intervention for Overweight and Obese Cardiac Patients Participating in Rural Cardiac Rehabilitation Programs
Authors: Susan A Barnason, Carol Pullen, Lufei Young, Lani Zimmerman, Paula Schulz
Journal: Circulation (2013)

Background: Cardiac rehabilitation (CR) is recommended for secondary CVD prevention after cardiac revascularization [coronary artery bypass surgery (CABS) or percutaneous coronary intervention (PCI...