tbuckley/cabot-search huggingface dataset:
In vitro response of primary breast carcinoma cultures to sunitinib.
Authors: S. L. Suchy, L. M. Hancher, S. L. Brower
Journal: Journal of Clinical Oncology (2010)

e11524 Background: Sunitinib is a small molecule inhibitor that targets multiple receptor tyrosine kinases, aiming to block tumor proliferation and/or angiogenesis. The proteins and pathways inhibited by sunitinib include: PDGFRα, PDGFRβ, VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, CSF-1R, and RET. Sunitinib is FDA-approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST). It is currently being evaluated for clinical efficacy in other solid tumor types, such as breast. Because the reported clinical response rates of sunitinib are low to moderate, an integrated biomarker that aids in identifying patients likely to exhibit a positive response to the drug would be a useful clinical tool. The current study investigates the use of an in vitro biological response marker to predict the response of primary cultures of human breast tumors to sunitinib. Methods: In order to characterize the performance of sunitinib in vitro, initial development was performed using the immortalized ovarian carcinoma cell line SKOV3. Subsequently, thirty-nine (39) primary breast carcinoma cultures were studied. All primary specimens treated with sunitinib consisted of a majority of epithelial cells (>65%) as determined by immunocytochemistry. A 10 dose range of drug concentrations was used to treat the cells for 72 hours. After treatment, the cultures were fixed with ethanol, and stained with DAPI. Any cells remaining adherent after treatment were considered live, and the DAPI stained nuclei were counted. The resulting dose response curves were analyzed. Results: The cell line SKOV3 was found to exhibit a consistent response to sunitinib. Dose response curves of the 39 breast specimens revealed that 7.6% (3 of 39) were responsive to sunitinib, 20.5% (8 of 39) of specimens exhibited an intermediate response, and 71.7% (28 of 39) were non-responsive to the drug. Conclusions: The data collected from the primary breast carcinoma cultures and cell line were consistent with the reported clinical response rate of sunitinib in breast cancer. The described biological response marker may contribute to the current chemotherapy identification and selection process for oncologists and their patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Precision Therapeutics
Association of ADT for older men with biochemical recurrence of prostate cancer with obese frailty and falls: A case-control study.
Authors: W. Dale, K. A. Bylow, J. Hemmerich, S. G. Mohile, S. Sajid, W. M. Stadler
Journal: Journal of Clinical Oncology (2010)

4675 Background: ADT for PCa has many associated adverse effects including fatigue, weakness, adiposity, and sarcopenia. It also has no survival advantage in older men with BCR. These side effects mirror a geriatric phenopyte known as obese frailty and can lead to falls. We tested the hypothesis that older men on ADT for BCR will develop obese frailty and have more falls after at least 3 months of ADT. Methods: We conducted a case-control study of men 60+ attending a medical oncology clinic, comparing men on ADT for BCR (n=52) versus PCa survivors without BCR (n=71) for obese frailty and falls. Participants completed a questionnaire and had a BMI and frailty assessment at the time of a clinic visit. Clinical information such as disease course, treatment history, and comobidities came from the medical record. Obese frailty prevalence is measured using a modification of Fried's Frailty. Self-reported falls in the previous year was recorded. Results: The sample is older (age: 70.9 ± 6.5) and 40% African American. A higher percentage of men on ADT were obese/severely obese (BMI >30; 47.8% vs. 21.6%; p=0.008). Self-report of a fall in the last year was higher for the ADT group (19.2% vs. 5.6%; p=0.03). In regression analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trends in the hypothesized direction for “obese” frailty (p = 0.08). Falls are not associated with ADT use (OR = 5.15; p = 0.20), but are with a comorbidity index (OR = 1.82; p = 0.04). Conclusions: These pilot data support the higher prevalence of obese frailty and falls in older men on ADT for BCR compared with controls. Given the lack of mortality gains in men with low-risk PCa on ADT, these consequences are concerning. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen
Effect of phosphoinositide-phospholipase c beta1 monoallelic deletion in low-risk MDS patients treated with darbepoetin.
Authors: P. Spadaro, V. Pitini, C. Arrigo, M. Ingemi
Journal: Journal of Clinical Oncology (2010)

6609 Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic diseases with a variable risk of evolution into acute myeloid leukemia, moreover recent results proved that phosphoinositide- phospholipase (PI-PLC) C beta1 monoallelic deletion is associated with a higher risk of AML evolution. We examined the treatment outcome of low-risk MDS pts with beta1 monoallelic deletion treated with EPO. Methods: Before treatment, by FISH analysis we assessed the presence of PI-PLCbeta1monoallelic deletion in thirty low-risk MDS pts (16 male 14 female median age 65 years) who received EPO (darbepoetin 40,000 every 2 weeks). Results: The PI-PLCbeta1 mono-allelic deletion was found in 9/30 low risk MDS pts; four of them showed a rapid evolution into AML, whilst the remaining five pts did not respond to EPO treatment. Conclusions: The PI-PLCbeta1 mono-allelic deletion is associated with a worse clinical outcome even in low-risk MDS patients who apparently have a good response profile for EPO (recent diagnosis, absence of transfusion dependence, EPO levels < 500). No significant financial relationships to disclose.
Особливості мікробіоценозу товстої кишки та рівня фекального кальпротектину у хворих на хронічні запальні захворювання кишечника залежно від нутритивного статусу
Authors: N.V. Vinnyk, O.M. Tatarchuk, M.V. Stoikevych, V.Ye. Kudriavtseva, O.V. Sorochan
Journal: GASTROENTEROLOGY (2016)

Стаття присвячена актуальній проблемі — стану мікрофлори товстої кишки та рівня фекального кальпротектину у хворих на хронічні запальні захворювання кишечника з різним нутритивним статусом. Проведено обстеження 76 пацієнтів із хронічними запальними захворюваннями кишечника, серед яких 28 хворих на хворобу Крона та 48 — на неспецифічний виразковий коліт. Проаналізовано отримані дані залежно від нозології та нутритивного статусу. Встановлено, що серед хворих досліджених груп переважали пацієнти з субкомпенсованою формою дисбіозу. Зниження концентрації біфідобактерій у вмісті товстої кишки у хворих ІІІ групи виявляли найчастіше — у 78,9 % випадків. Дефіцит лактобактерій найчастіше спостерігався у хворих ІІ групи (92,3 %). Вміст кальпротектину був суттєво підвищеним у 84,2 % пацієнтів, позитивно корелював із ступенем тяжкості перебігу захворювання і не залежав від їх нутритивного статусу.
Case 54-1963
Authors: William H. Baker, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A twenty-nine-year-old man was admitted to the hospital because of the sudden onset of numbness of the right hand and incoherence of speech.Five years before entry the patient experienced intermittent jaundice. Several months later he entered another hospital because of the development of pruritus and diarrhea, and exploratory laparotomy revealed adenocarcinoma of the head of the pancreas. A few weeks later the duodenum, the distal portion of the common bile duct, the head of the pancreas and a small segment of the jejunum were resected. Fourteen months later partial gastrectomy was performed because of . . .
HIV-Infected Surgeons
Authors: Scott H. Isaacman
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Public concern about HIV-infected physicians continues to increase. Few cases have reached the courts, but more are likely in the future. Physicians need to be aware of the recent<i>Behringer</i>case<sup>1</sup>as hospitals start to restrict the clinical privileges of HI Vinfected physicians. <i>Behringer</i>is a trial court decision in which a surgeon claimed the hospital unjustly suspended his operating privileges. The court decided that the restriction was justified because of the severe prognosis of HIV infection and the possibility of transmission during invasive procedures. Within the long opinion, the judge pontificated about a proposed informed consent that included disclosing the physician's diagnosis to patients. In extensive dicta, the court endorsed this novel concept of informed consent. The AMA<sup>2</sup>and the CDC<sup>3</sup>suggest a role for consent in procedures that may carry a risk of HIV transmission to patients. Like the dicta in<i>Behringer</i>
Estrogen Replacement Therapy in Breast Cancer Survivors-Reply
Authors: Robert F. Berris
Journal: JAMA (1995)

<h3>In Reply.</h3> —We thank the many authors of letters written in response to our work. Meta-analyses, which overcome type II error, have not demonstrated an association between ERT and risk of breast cancer. In general, prospective studies are preferable to case-control studies. However, there are problems with all studies, including prospective ones. For example, the Nurses' Health Study found an increase in breast cancer risk only in those who were drinking alcohol.<sup>1</sup>The Swedish study wasn't a true prospective cohort trial.<sup>2</sup>Files from a prescription database were merged with files from a cancer registry. It is not known whether "hormone users" were actually taking hormones. We need to weigh the entire body of evidence. We should not discount the results of 25 case-control studies because we think two prospective ones are better. Most studies of adjuvant tamoxifen in postmenopausal women evaluated tamoxifen vs no treatment, whereas those in
Novel PI3K Inhibitor Compound A Induces Myeloma Cell Apoptosis and Shows Synergistic Cytotoxicity with Dexamethasone In Multiple Myeloma
Authors: Yuhuan Zheng, Jing Yang, Liang Zhang, Jianfei Qian, Jairo Matthews, Michael Wang, Larry Kwak, Qing Yi
Journal: Blood (2010)
High-Throughput Testing of Novel–Novel Combination Therapies for Cancer: An Idea Whose Time Has Come
Authors: Uciane K. Scarlett, Dennis C. Chang, Thomas J. Murtagh, Keith T. Flaherty
Journal: Cancer Discovery (2016)

Combination therapies are essential to address the genetic complexity, plasticity, and heterogeneity of tumors and to overcome resistance mechanisms that confound single-agent approaches, and are a paradigm that became well established in the era of conventional cytotoxic chemotherapies. Today, we are well equipped to address many of the scientific, clinical, and collaboration challenges that have existed historically; however, the pace of testing rational combinations is modest. Our analysis shows that the volume of clinical trials testing multiple investigational pipeline agents ("novel-novel" combinations) is dismally low, as out of approximately 1,500 phase I to III investigational combination trials initiated in 2014-2015, only 80 were for novel-novel combinations, and only 9 of those involved more than one company. The Collaborative Novel-Novel Combination Therapies (CoNNCT) initiative aims to alleviate this bottleneck by developing a new, faster paradigm for early investigation of scientifically informed, novel-novel drug combinations. The initiative kicked off on March 7, 2016, when representatives from top academic centers, biopharma, nonprofits, the FDA, and other groups gathered to define an actionable path forward. Cancer Discov; 6(9); 956-62. ©2016 AACR.
Oncologic patients' assesment of the doctor–patient communicacion.
Authors: F. G. Gercovich, D. Gercovich, H. Hirsch, P. Lopez, D. Bortolato, P. Margiolakis, M. Morgenfeld, E. L. Morgenfeld, L. Rosell, E. Gil Deza
Journal: Journal of Clinical Oncology (2010)

e16530 Background: The study of doctor-patient communication has received an increasing interest in the past decade. Most of the studies have been centered in the communication characteristics and the physicians' perspective and skills. However, there are few studies that evaluate the patients' expectations and preferences. The aim of this study is to describe these aspects through an ad-hoc questionnaire designed specifically for this purpose. Methods: An ad-hoc questionnaire evaluating matters related to the patients' perceived changes in the physician's body language and speech, the patients' preferred way of receiving disease-related information from the doctors, and central aspects in the doctor-patient communication was developed. A total of 436 consecutive ambulatory patients treated at IOHM answered the survey. Results: Six percent of the patients perceived changes in the physician's posture when communicating disease-related information, while 10% perceived changes in the used language. Regarding the patients' preference of receiving information, the highest ranked options were: veracity (36%), clarity (20%) and frankness (18%). Lastly, concerning the aspects regarded by the patients as central in the communication with the physician, the most chosen options were that the doctor must be up to date with the latest investigations and that he be honest with the seriousness of the illness. Conclusions: This study allows for an exploratory approach to the expectations and preferences of the patients. It would be important in future stages to relate the findings in patient-centered studies to those oriented toward the physicians and the doctor-patient interaction. No significant financial relationships to disclose.
Yellow fever outbreaks, vaccine shortages and the Hajj and Olympics: call for global vigilance
Authors: Habida Elachola, John Ditekemena, Jiatong Zhuo, Ernesto Gozzer, Paola Marchesini, Mujeeb Rahman, Samba Sow, Rana F Kattan, Ziad A Memish
Journal: The Lancet (2016)
Informed Consent and the Reasonable-Patient Standard
Authors: Barry G. Main, Angus McNair, Jane M. Blazeby
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells
Authors: Bing Z. Carter, Po Yee Mak, Hong Mu, Hongsheng Zhou, Duncan H. Mak, Wendy Schober, Joel D. Leverson, Bin Zhang, Ravi Bhatia, Xuelin Huang, Jorge Cortes, Hagop Kantarjian, Marina Konopleva, Michael Andreeff
Journal: Science Translational Medicine (2016)

Inhibition of BCL-2, MCL-1, and BCL-X L eradicates CML stem cells in a mouse model and primary blast crisis samples.
Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy
Authors: Zhan-Peng Huang, Yan Ding, Jinghai Chen, Gengze Wu, Masaharu Kataoka, Yongwu Hu, Jian-Hua Yang, Jianming Liu, Stavros G. Drakos, Craig H. Selzman, Jan Kyselovic, Liang-Hu Qu, Cristobal G. dos Remedios, William T. Pu, Da-Zhi Wang
Journal: Cardiovascular Research (2016)

Ischemic cardiomyopathy (ICM) resulting from myocardial infarction is a major cause of heart failure (HF). Recently, thousands of long non-coding RNAs (lncRNAs) have been discovered and implicated in a variety of biological processes. However, the role of most lncRNAs in HF remains largely unknown. The aim of this study is to test the hypothesis that the expression and function of lncRNAs are differentially regulated in diseased hearts. In this study, we performed RNA deep sequencing of protein-coding and non-coding RNAs from cardiac samples of patients with ICM ( n = 15) and controls ( n = 15). Genome-wide transcriptome analysis confirmed that many protein-coding genes previously known to be involved in HF were altered in ICM hearts. Among the 145 differentially expressed lncRNAs identified in ICM hearts, we found a set of 35 lncRNAs that display strong positive expression correlation. Expression correlation coefficient analyses of differentially expressed lncRNAs and protein-coding genes revealed a strong association between lncRNAs and extracellular matrix (ECM) protein-coding genes. We overexpressed or knocked down selected lncRNAs in cardiac fibroblasts and our results suggest that lncRNAs are important regulators of fibrosis and the expression of ECM synthesis genes. Moreover, we show that lncRNAs participate in the TGF-β pathway to modulate the expression of ECM genes and myofibroblast differentiation. Our studies demonstrate that the expression of many lncRNAs is dynamically regulated in ICM. lncRNAs regulate the expression and function of ECM and cardiac fibrosis during the development of ICM. Our results further indicate that lncRNAs may represent novel regulators of heart function and cardiac disorders, including ICM.
Phase I trial and pharmacokinetic study of oral gimatecan in adults with malignant glioma
Authors: F. H. Hochberg, J. Supko, A. Amato, N. Salem, P. Carminati, P. Wen
Journal: Journal of Clinical Oncology (2006)

1559 Background: Gimatecan (GT) is an orally available camptothecin analogue with potent preclinical antitumor activity. A phase I trial was conducted to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of GT in patients (pts) with recurrent malignant glioma. Methods: GT was given orally once daily for 5 days every 28 days. The starting dose, 1.6 mg/m 2 over 5 days, was independently escalated in pts who were and were not concurrently receiving enzyme inducing antiseizure drugs (±EIASD). PK samples were obtained up to 24 after dosing on day 1 and 168 h after dosing on day 5 of cycle 1. Results: A total of 43 pts were enrolled, 18 in the +EIASD arm and 25 in the -EIASD arm, with a median age of 51 years (range, 23–70) and median KPS of 80 (range, 60–100). All pts had prior irradiation and 84% had prior chemotherapy. Dose levels evaluated were 1.6, 3.2, 5.3, 8.0, 11.2, and 15.0 mg/m 2 in the +EIASD arm and 1.6, 3.2, 5.3, 6.1, and 8.0 mg/m 2 in the -EIASD arm. No dose-limiting toxicities (DLTs) occurred during 49 cycles of therapy in the +EIASD arm with dose escalation terminated at 15.0 mg/m 2 . Grade 3–4 myelosuppression was the DLT in the -EIASD arm, occurring in 1/11 pts at the MTD of 6.1 mg/m 2 , and 2/3 pts at 8.0 mg/m 2 . Gastrointestinal disorders, the most common side effects, were grade &gt;3 in only 7% of pts. Pts in the +EIASD arm received a median of 6 cycles of therapy and there were 2 partial responses and 6 pts with stable disease. Pts in the -EIASD arm received a median of 2 cycles of therapy and 11 pts had stable disease. GT exhibited linear PK. EIASDs significantly affected the PK, decreasing the biological half-life 2-fold from 53 ± 25 to 25 ± 12 h (mean ± SD) and increasing the apparent oral clearance (CL/F) nearly 5-fold from 1.3 ± 1.7 L/h to 6.2 ± 4.3 L/h. CL/F was independent of body surface area. Conclusions: The MTD of GT for pts not receiving EIASDs is 6.1 mg/m 2 and an MTD was not established for pts receiving EIASDs due to practical limitations on dose administration. Median duration of disease stabilization or response was 6 cycles for 44% of +EIASD pts and 2 cycles for 44% of -EIASD pts. [Table: see text]
Imatinib Significantly Enhances Long-Term Outcomes In Philadelphia Positive Acute Lymphoblastic Leukaemia; Final Results of the UKALLXII/ECOG2993 Trial
Authors: Adele K. Fielding, Georgina Buck, Hillard M. Lazarus, Mark R. Litzow, Selina Luger, David I. Marks, Andrew McMillan, Anthony V. Moorman, Elisabeth Paietta, Susan M Richards, Martin S. Tallman, Jacob M. Rowe, Anthony H. Goldstone
Journal: Blood (2010)
Very Low-Calorie Diets
Authors: Richard L. Atkinson
Journal: JAMA (1993)

Objective.  —To provide an overview of the published scientific information on the safety and efficacy of very low-calorie diets (VLCDs) and to provide rational recommendations for their use.  Data Sources and Extraction.  —Original reports obtained through a MEDLINE search for 1966 through 1992 on VLCDs or reducing diets plus obesity, supplemented by a manual search of bibliographies and the opinions of experts in the field of nutrition and weight loss therapy for obesity. Only studies of humans were cited.  Data Synthesis.  —Current VLCDs are usually provided in the context of comprehensive treatment programs, during which usual food intake is completely replaced by specific foods or liquid formulas containing 3350 kJ/d (800 kcal/d) or less. Weight loss on VLCDs averages 1.5 to 2.5 kg/wk; total loss after 12 to 16 weeks averages 20 kg. These results are superior to standard low-calorie diets of 5020 kJ/d (1200 kcal/d), which lead to weight losses of 0.4 to 0.5 kg/wk and an average total loss of only 6 to 8 kg. There is little evidence that intakes of less than 3350 kJ/d (800 kcal/d) result in better weight losses than 3350 kJ. Intake of at least 1 g/kg of ideal body weight per day of protein of high biologic value appears to be important in helping to preserve lean body mass. Serious complications of modern VLCDs are unusual, cholelithiasis being most common.  Conclusions.  —Current VLCDs are generally safe when used under proper medical supervision in moderately and severely obese patients (body mass index [weight in kilograms divided by height in meters squared] >30) and are usually effective in promoting significant short-term weight loss, with concomitant improvement in obesity-related conditions. Long-term maintenance of weight lost with VLCDs is not very satisfactory and is no better than with other forms of obesity treatment. Incorporation of behavioral therapy and physical activity in VLCD treatment programs seems to improve maintenance.  ( JAMA . 1993;270:967-974)
Response to: ‘Let's stop fooling ourselves. In RA, only ACR/EULAR criteria define remission and equate with absence of disease!’ by Boers
Authors: P Emery, C O Bingham, G R Burmester, V P Bykerk, D E Furst, X Mariette, D van der Heijde, R van Vollenhoven, C Arendt, I Mountian, O Purcaru, D Tatla, B VanLunen, M E Weinblatt
Journal: Annals of the Rheumatic Diseases (2016)

We would like to thank Dr Boers for his critical comments on our study raised in his eLetter,1 and address his concerns regarding our manuscript.2

First, we would like to emphasise that we are in support of the statements in the guidelines issued by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) in early 2011,3 and acknowledge that the Disease Activity Score 28 erythrocyte sedimentation rate (DAS28(ESR)) based definition of clinical remission (DAS28(ESR) <2.6) is less stringent than the simple disease activity index (SDAI)- and Boolean-based definitions.

However, our manuscript does not make any claims that DAS28(ESR)-based remission is reflective …