tbuckley/cabot-search huggingface dataset:
Continuous versus intermittent chemotherapy in metastatic colorectal cancer
Authors: C. G. Alexopoulos, A. A. Kotsori
Journal: Journal of Clinical Oncology (2006)

3582 Background: The current policy concerning the duration of chemotherapy in metastatic colorectal cancer (MCC) varies considerably (Clin Oncol 1997;9:248) while no benefit of continuous versus intermittent 5-FU was found in a published randomized study (Lancet 2003;361:457). Serious cumulative toxicity is not usually a problem with long-term 5-FU/FA, but this is not the case with contemporary triple regimens (FOLFIRI, FOLFOX). We, therefore, performed a randomized study of continuous versus intermittent FOLFIRI as first line chemotherapy in MCC. Methods: Patients with MCC and ECOG 0–2 were given 6 biweekly courses of FOLFIRI (Irinotecan 180mg/m 2 + De Gramont). Patients with response or stable disease were randomized to continue with another 6 FOLFIRI (group A) or discontinue until relapse when 6 FOLFIRI were readministered (group B). Time to progression (TTP) was calculated from study entrance until 1 st progression for group A, and 2 nd progression for group B, and overall survival (OS) from study entrance until death. Results: Fifty eight (M=38, F=20) patients entered into the study. Two (3.4%) withdrew before evaluation, 1 (1.7%) died of stroke, 1 (1.7%) was lost to FU and 15 (26%) progressed before or at the completion of 6 FOLFIRI. Thirty nine (67%) patients (M=25, F=14), median age 69 (38–79) responded (21=54%) or had stable disease (18=46%) and were randomized: 19 (49%) to group A and 20 (51%) to group B. Median TTP was 8 months 95% CI: 5.3–10.7) for group A and 9 (95% CI: 7.8–10) for group B (p=NS). 10/19 (52%) in group A received 2 nd line chemotherapy vs 7/20 (35%) in group B (p=NS). With a median follow-up of 13 months, 21 patients are alive (12 in group A and 9 in group B). Median OS was 21 months (95% CI: 15 - 26.7) in group A vs 15 (95% CI: 12.6 - 17.3) in group B (p=NS), and 18 months (95% CI: 15.5 - 21) for all 39 patients. Conclusions: In MCC, when response or stability has been achieved after 6 courses ofFOLFIRI there seemstobe little more benefit from continuing chemotherapy than from retreating patients at relapse No significant financial relationships to disclose.
Synergistic antitumor activity of the CD122-biased immunostimulatory cytokine NKTR-214 when combined with anti-PD-1 in murine tumor models
Authors: Addepalli Murali, John L Langowski, Pena Rhoneil, Priyam Jha, Deborah H Charych, Stephen K Doberstein, Ute Hoch
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts NKTR-214 is an immunotherapeutic drug that exerts its biological activity by binding and activating the interleukin-2 (IL-2) receptor beta subunit (IL-2Rb), thereby causing expansion of memory effector T cells in the tumor. NKTR-214 consists of 4-6 releasable polyethylene glycol (
Noninvasive Quantitative Tissue Characterization of Carotid Plaques Using Color-Coded Mapping Based on Ultrasound Integrated Backscatter
Authors: Mika Bando, Hirotsugu Yamada, Kenya Kusunose, Daiju Fukuda, Rie Amano, Rina Tamai, Yuta Torii, Yukina Hirata, Susumu Nishio, Junichiro Satomi, Shinji Nagahiro, Masataka Sata
Journal: JACC. Cardiovascular imaging (2015)
Abstract 20331: Microparticles Inhibit Angiogenic Activities of Microvascular Endothelial Cells via a CD36 Dependent Signaling Pathway Involving Reactive Oxygen Species
Authors: Devi Prasadh Ramakrishnan, Rula Hajj-Ali, Roy Silverstein
Journal: Circulation (2014)

CD36 interactions with thrombospondin-1 and related proteins inhibit angiogenic signaling in microvascular endothelial cells (MVEC). Phosphatidylserine (PS) exposed on microparticles (MP) shed from vascular cells by activation or apoptosis, is also a ligand for CD36 so we hypothesized that CD36-MP interactions would inhibit angiogenesis. MP prepared  in vitro  from THP1 monocytes, erythrocytes, MVEC, or human umbilical vein endothelial cells (HUVEC) were exposed to MVEC to assess their effect on tube formation and migration. MP derived from all of these cell types inhibited tube formation by >50% (p 80% (p in vivo  can inhibit angiogenic processes. ROS generation has been implicated in macrophage and platelet CD36 mediated signaling. We found that MP exposure induced MVEC ROS by 2 fold at 1hr (p 95%) and partially (33%) reversed inhibition of migration (p 95% and partially (25%) reversed inhibition of migration (p
Oral contraceptive effects on the breast. (Letter to the editor)
Authors: Fechner Re
Journal: JAMA (1973)

The letter from Drs. Kovi and Viola in the Journal of the American Medical Association (223: 802 1973) emphasizes our limited knowledge on the effects of long-term oral contraceptive hormone (OCH) therapy on the breast.  The suggestion that the lobular sclerosis in their case reflected a premature menopausal alteration stimulated me to review 8 cases of cancer in women 35 years of age or younger in whom the breast was removed prior to the oral contraceptive  era.  Lobular sclerosis identical to the type illustrated in their letter was seen in 1 and focal sclerosis was seen in 2 others.  It is possible that young patients with breast cancer who have a long history of OCH ingestion may have even a greater frequency of lobular sclerosis but this will require more than 1 case to prove and there should be proper controls.  Parenthetically 1 previously reported case of breast cancer in a 28-year-old woman taking OCH for 7 1/2 years failed to show lobular sclerosis (Cancer 26: 1204 1970).  One other point deserves comment.  The most consistent change in normal mammary tissue in patients is not lobular hyperplasia with true acinus formation.  This was in the breasts of only 2 of 709 patients in which it was specifically sought (American Journal of Clinical Pathology 53: 857 1970).  When acinar formation is seen in the breast of a nulligravid woman it can be attributed to the hormone therapy but in point of fact it is uncommonly seen.(FULL TEXT)
Predicting survival using health related quality of life scores in glioblastoma cancers: Findings from an international phase III randomised controlled trial
Authors: A. Bottomley, M. Taphoorn, C. Coens, D. Osoba, K. van Steen, F. Efficace, M. van Den Bent, B. Baumert, W. Mason, R. Stupp
Journal: Journal of Clinical Oncology (2005)

9601 Background: Few studies have explored the prognostic value for survival of baseline health-related quality of life (HRQOL) parameters in glioblastoma multiforme (GBM) patients. We investigated this issue using data from a recently conducted randomized controlled trial (RCT) of radiotherapy with concomitant and adjuvant temozolomide in newly diagnosed GBM patients compared to standard radiotherapy alone. Methods: 573 newly-diagnosed GBM patients were randomized to radiotherapy alone or radiotherapy and concomitant and adjuvant temozolomide (Stupp et al. PASCO 2004, abstract 2). HRQOL data was collected using the EORTC QLQ-C30 and Brain Cancer Module. Baseline scores were examined for the relationship with length of survival. Differences between survival curves were assessed using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analyses. Treatment type was also included as a fixed covariate in the starting model for the multivariate analyses, along with all the covariates from the univariate analyses. Results: The clinical trial results demonstrate a significant improvement on survival for patients undergoing radiotherapy with concomitant and adjuvant temozolomide (p<.0001) without any detrimental effect to HRQOL. The prognostic factor analysis was conducted on baseline questionnaires available in 85.7% (n = 490) patients. Univariate analyses revealed both age and extent of surgery as significant predictors of survival along with six HRQOL factors. The final multivariate model confirmed that the clinical variables of age (p=.001) and extent of surgery (p<.001) predicted survival. HRQOL parameters also independently contributed in predicting survival, namely, cognitive (p< .001), social (p< .001), dyspnea (p=.01) and physical (p=.016) functioning. Conclusion: This is the first large scale, international study that shows HRQOL data appears to have a prognostic value in newly diagnosed GBM. Additional analyses, using newly developed statistical model average techniques could be useful to further investigate the stability of the final multivariate model.
Prioritizing Proteomics Assay Development for Clinical Translation
Authors: Maggie P.Y. Lam, Vidya Venkatraman, Quan Cao, Ding Wang, T. Umut Dincer, Edward Lau, Andrew I. Su, Yi Xing, Junbo Ge, Peipei Ping, Jennifer E. Van Eyk
Journal: Journal of the American College of Cardiology (2015)
Outcomes for Patients with Metastatic Renal Cell Carcinoma Achieving a Complete Response on Targeted Therapy: A Registry-based Analysis
Authors: Tomas Buchler, Zbynek Bortlicek, Alexandr Poprach, Tomas Pavlik, Veronika Veskrnova, Michaela Honzirkova, Milada Zemanova, Ondrej Fiala, Katerina Kubackova, Ondrej Slaby, Marek Svoboda, Rostislav Vyzula, Ladislav Dusek, Bohuslav Melichar
Journal: European Urology (2015)
Effects of Low-Dose Bisphenol A on DNA Damage and Proliferation of Breast Cells: The Role of c-Myc
Authors: Daniella Pfeifer, Young Min Chung, Mickey C-T. Hu
Journal: Environmental Health Perspectives (2015)

BackgroundHumans are exposed to low-dose bisphenol A (BPA) through plastic consumer products and dental sealants containing BPA. Although a number of studies have investigated the mammary gland effects after high-dose BPA exposure, the study findings differ. Furthermore, there has been a lack of mechanistic studies.ObjectiveThe objective of this study was to investigate the effect and the mechanism of low-dose BPA in mammary gland cells.MethodsWe evaluated DNA damage following BPA exposure using the comet assay and immunofluorescence staining, and used cell counting and three-dimensional cultures to evaluate effects on proliferation. We examined the expressions of markers of DNA damage and cell-cycle regulators by immunoblotting and performed siRNA-mediated gene silencing to determine the role of c-Myc in regulating BPA's effects.ResultsLow-dose BPA significantly promoted DNA damage, up-regulated c-Myc and other cell-cycle regulatory proteins, and induced proliferation in parallel in estrogen receptor-α (ERα)-negative mammary cells. Silencing c-Myc diminished these BPA-induced cellular events, suggesting that c-Myc is essential for regulating effects of BPA on DNA damage and proliferation in mammary cells.ConclusionsLow-dose BPA exerted c-Myc–dependent genotoxic and mitogenic effects on ERα-negative mammary cells. These findings provide significant evidence of adverse effects of low-dose BPA on mammary cells.CitationPfeifer D, Chung YM, Hu MC. 2015. Effects of low-dose bisphenol A on DNA damage and proliferation of breast cells: the role of c-Myc. Environ Health Perspect 123:1271–1279; http://dx.doi.org/10.1289/ehp.1409199
Abstract P232: Worse Cardiometabolic Health in African Immigrants than African-Americans: Reconsideration of the Healthy Immigrant Effect
Authors: Anne E Sumner, Michelle Y O'Connor, Caroline K Thoreson, Madia Ricks, Amber B Courville, Francine Thomas, Jianhua Yao, Peter T Katzmarzyk
Journal: Circulation (2014)

In decades past, African immigrants were considered to have better cardiometabolic health than African Americans. Whether this health advantage continues to exist in the 21st century is unknown. To explore differences in markers of cardiometabolic health, oral glucose tolerance tests, blood pressure (BP), visceral adipose tissue (VAT) volume and the waist circumference (WC) which predicts insulin resistance were compared in 210 men (134 African immigrants, 76 African Americans, mean age 36±9y (mean±SD), range 20-64y) who self-identified as healthy. Insulin resistance was defined by the lowest quartile of the insulin sensitivity index (SI≤2•28mU/L-1.min-1). Receiver operating characteristic curves and the Youden Index were used to identify the WC which optimally predicts insulin resistance. BMI was lower in African immigrants than African Americans (27.4±3.9 vs. 29.3±5.5kg/m2, P&lt;0.01). Adjusting for BMI, WC did not differ between groups (93±5 vs. 94±5cm, P=0.55); but African immigrants had more visceral adipose tissue (VAT) (P&lt;0.001) higher BP (P≤0.01), higher fasting glucose (P≤0.001) and 2h glucose (P&lt;0.001) as well as a higher prevalence of previously undiagnosed diabetes (7% (9 of 134) vs. 0% (0 of 76), P&lt;0.01) and pre-diabetes (35% (47 of 134) vs. 22% (17 of 76), P&lt;0.01). Degree of insulin resistance did not differ in African immigrants and African Americans (4.17±2.88 vs. 4.24±2.61 (mU/L)-1 .min-1, P=0.88). Yet, the WC which optimally predicted insulin resistance was lower in African immigrants than African Americans, specifically 92 cm and 102 cm, respectively. As African immigrants had higher VAT, BP and glucose levels than African Americans, the healthy immigrant effect may no longer be a valid concept. As insulin resistance occurred at a lower WC in African immigrants than African Americans, lower BMI in African immigrants does not appear to provide protection from cardiometabolic risk.
Who Gets Adjuvant Treatment for Stage II and III Rectal Cancer? Insight From Surveillance, Epidemiology, and End Results–Medicare
Authors: Deborah Schrag, Sarah E. Gelfand, Peter B. Bach, Jose Guillem, Bruce D. Minsky, Colin B. Begg
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To examine the relationship between patient characteristics and the use of adjuvant pelvic radiation with and without chemotherapy among patients aged 65 years and older with stage II and III rectal cancer. PATIENTS AND METHODS: A retrospective cohort study using the Surveillance, Epidemiology, and End Results–Medicare linked database identified 1,411 patients aged 65 and older with resected stage II and III rectal cancers diagnosed between 1992 and 1996. From claims submitted to Medicare, we measured the use of pelvic radiation therapy with or without chemotherapy and pre- or postoperatively. RESULTS: Fifty-seven percent of patients received radiation, 42% received chemotherapy and radiation, and 7% had treatment delivered preoperatively. Age was the strongest determinant of treatment: 73% of patients aged 65 to 69, 66% aged 70 to 75, 52% aged 75 to 79, 39% aged 80 to 84, and 21% aged 85 to 89 received radiation. The age trend remained strong after adjusting for other factors that predict receipt of treatment and after exclusion of patients with any evident comorbidity (P &lt; .001). Patients were more likely to receive radiation treatment if they had an abdominal perineal resection, stage III disease, or a T4 tumor. CONCLUSION: Because pelvic recurrences are a substantial cause of morbidity, further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding adjuvant treatment.
Autoimmunity and Atrioventricular Block of Unknown Etiology in Adults
Authors: Roger Villuendas, Alejandro Olivé, Gladys Juncà, Iñaki Salvador, Melania Martínez-Morillo, Irene Santos-Pardo, Damià Pereferrer, Elisabet Zamora, Antoni Bayes-Genis
Journal: Journal of the American College of Cardiology (2014)
From Shame to Guilt to Love
Authors: Peter J. Pronovost, O. Joseph Bienvenu
Journal: JAMA (2015)

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
John Anthony Chappel
Authors: David Chappel
Journal: BMJ (2016)

John Anthony Chappel was born in Yorkshire, the grandson of a miner. His father worked in banks and moved the family to London just after the war. John gained his first MB at school and deferred entrance to medical school until he had done national service as a radiographer with the Royal Army Medical Corps in Egypt.

He qualified from the Westminster Hospital and started to work in thoracic medicine. Having worked in London, he saw an advertisement for a post at Stoke Mandeville Hospital in …
An innate antiviral pathway acting before interferons at epithelial surfaces
Authors: Marie B Iversen, Line S Reinert, Martin K Thomsen, Ieva Bagdonaite, Ramya Nandakumar, Natalia Cheshenko, Thaneas Prabakaran, Sergey Y Vakhrushev, Malgosha Krzyzowska, Sine K Kratholm, Fernando Ruiz-Perez, Steen V Petersen, Stanislas Goriely, Bo Martin Bibby, Kristina Eriksson, Jürgen Ruland, Allan R Thomsen, Betsy C Herold, Hans H Wandall, Sebastian Frische, Christian K Holm, Søren R Paludan
Journal: Nature Immunology (2015)
No reflow and the quest to achieve optimal perfusion during the acute phase of myocardial infarction**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Bernard R. Chaitman, Michael J. Lim
Journal: Journal of the American College of Cardiology (2004)
Abstract 983: Gas6/Axl mediation of prostate cancer cell dormancy requires cooperation with additional bone marrow niche components
Authors: Haley Axelrod, Kenneth J. Pienta
Journal: Cancer Research (2015)

Abstract Early metastatic events are often responsible for the recurrence and lethality of prostate cancer. The most frequent site of metastasis is the bone marrow, where small populations of disseminated tumor cells (DTCs) preferentially take residence in the hematopoietic stem cell (HSC) niche. These micro-metastases may survive in a benign, dormant state for years before they become “reawakened” to form full metastases, and are thus difficult to detect and treat. It is unknown what induces and maintains DTC dormancy, and it remains a key question with regard to metastatic prostate cancer treatment and prevention strategies. An essential component of the HSC niche is the osteoblast population to which DTCs bind for support and uptake of secreted factors. We have previously shown that dormant DTCs in the HSC niche display high levels of the receptor tyrosine kinase Axl, and are bound to osteoblasts that secrete its ligand, Gas6. The requirement of Gas6/Axl in DTC dormancy is striking in vivo, but in vitro is not replicable. Addition of Gas6 to prostate cancer cells expressing Axl does not have a significant inhibitory effect on cell proliferation, suggesting the cooperation with other niche factors absent in culture. As the elements of the DTC niche are still being actively explored, this study further supports the complex nature of the mechanisms governing DTC dormancy and preferential survival in the bone marrow niche. Selective targeting of these elements may allow for long term maintenance of the benign, dormant state of DTCs, or coerced reawakening to a more chemotherapy-sensitive state. Citation Format: Haley Axelrod, Kenneth J. Pienta. Gas6/Axl mediation of prostate cancer cell dormancy requires cooperation with additional bone marrow niche components. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 983. doi:10.1158/1538-7445.AM2015-983
Surgical techniques, biomaterials, and patient variables that impact peri-operative nipple necrosis in nipple-sparing mastectomy.
Authors: Daniel J. Gould, Kelly Hunt, Jun Liu, Henry Mark Kuerer, Melissa Crosby, Steven J. Kronowitz
Journal: Journal of Clinical Oncology (2012)

152 Background: Nipple sparing mastectomy is for treatment of early stage breast cancer and risk reduction in patients at high risk for breast cancer. A high rate of nipple loss after NSM (10% to 30%) has slowed incorporation of NSM into clinical practice. No study has evaluated whether clinical and technical factors contribute to nipple loss by decreasing blood supply to the nipple areola complex (NAC). The objective here was to determine the impact of patient variables and surgical factors on survival of the nipple following NSM and to compare rates of complications of NSM to those of SSM. Methods: We evaluated 233 cases of immediate breast reconstruction following mastectomy at MD Anderson Cancer Center between September 2003 and May 2011. 113 NSM procedures were randomly matched to 120 SSMs based on stage, comorbidities, and age. The NSM group was analyzed for variables that correlated with partial or total nipple loss. Results: In the NSM group, the complication rate was 28%, compared to 27% in SSM (p &gt; 0.99). The nipple loss rate in NSM was 20%. In SSM, axillary node dissection increased complications compared to sentinel lymph node biopsy (p = 0.01). Body mass index, breast ptosis, breast cancer pathology, distance of the lesion to the NAC and use of neoadjuvant chemo or radiation therapy had no effect on nipple loss. Vascular comorbidities and smoking lead to increased nipple loss, with borderline p values (p = 0.09 and p = 0.08, respectively). When compared to A- and B-cup breasts, larger breasts had higher nipple loss (6% and 34%, respectively; p=0.003). Surgical incision location did not affect nipple loss, neither did number of prior NSM procedures performed by the breast surgeon (p = 0.86). Axillary lymphadenectomy (p = 0.13), separate axillary incision (p = 0.25), type of breast reconstruction (p = 0.23), and application of bioprosthetic sling (p = 0.27) may have impacted nipple loss if a larger sample size was studied. Conclusions: Patient variables and surgical technique can alter the rate of nipple loss with NSM. This study helps to define patient populations that may be at risk for necrosis and informs surgeon’s as to the best techniques for reconstruction to decrease the occurrence of nipple loss.