tbuckley/cabot-search huggingface dataset:
Pharmacologic Management of Irritable Bowel Syndrome
Authors: Vijaya L. Rao, Adam S. Cifu, Leslie W. Yang
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
Clinical trial participants’ strategies for coping with prescription drug costs: A companion study to CALGB 80405
Authors: D. Schrag, M. Naughton, A. Kesselheim, L. Archer, D. Niedzwiedcki, D. Romanus, R. Goldberg, A. Venook
Journal: Journal of Clinical Oncology (2009)

9503 Background: The strategies used by clinical trial participants to cope with the high costs of prescription drugs are poorly characterized. Methods: We identified a cohort of newly metastatic CRC patients participating in CALGB 80405, a phase III trial comparing first-line systemic chemotherapy with Bevacizumab, Cetuximab or both agents. We surveyed trial participants about their prescription drug insurance status and strategies they used to cope with out-of-pocket prescription drug costs. We surveyed patients before trial initiation and again 3 months later to assess the extent to which embarking on chemotherapy imposes additional financial burden requiring use of coping strategies. Results: Out of 1422 trial participants, 806 (57%) completed the baseline survey. The 515 enrolled before 09/01/2007 were asked to repeat the survey by phone at 3 months; 409/505 alive at 3 months (81%) did so. The 409 patients in the analytic cohort had similar clinical and demographic features to those not surveyed. 60/409 (15%) lacked prescription drug coverage and only 48/409 (12%) discussed prescription drug costs with their physicians. Conclusions: In the context of a trial in which costs of chemotherapy are covered and most participants had prescription drug insurance, patients rarely discuss prescription drug costs with their physicians. Although a considerable minority report having used coping strategies to lessen the cost burden, only a very small minority newly adopt such strategies after starting chemotherapy on trial. [Table: see text] [Table: see text]
Locally secreted Fc-OX40L is superior to systemic, antibody mediated, OX40 costimulation for combination immunotherapy
Authors: George Fromm, Jason Rose, Suresh Desilva, Taylor Schreiber
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The dramatic clinical success of checkpoint inhibitory therapy (anti-CTLA-4 and anti-PD-1) in a small percentage of patients has highlighted the need to identify combination approaches that may increase the frequency of responders. Two immunotherapy modalities that are proposed to
Comprehensive <i>Ex Vivo</i> Transposon Mutagenesis Identifies Genes That Promote Growth Factor Independence and Leukemogenesis
Authors: Yabin Guo, Barrett L. Updegraff, Sunho Park, Deniz Durakoglugil, Victoria H. Cruz, Sarah Maddux, Tae Hyun Hwang, Kathryn A. O'Donnell
Journal: Cancer Research (2015)

Abstract Aberrant signaling through cytokine receptors and their downstream signaling pathways is a major oncogenic mechanism underlying hematopoietic malignancies. To better understand how these pathways become pathologically activated and to potentially identify new drivers of hematopoietic cancers, we developed a high-throughput functional screening approach using ex vivo mutagenesis with the Sleeping Beauty transposon. We analyzed over 1,100 transposon-mutagenized pools of Ba/F3 cells, an IL3-dependent pro-B-cell line, which acquired cytokine independence and tumor-forming ability. Recurrent transposon insertions could be mapped to genes in the JAK/STAT and MAPK pathways, confirming the ability of this strategy to identify known oncogenic components of cytokine signaling pathways. In addition, recurrent insertions were identified in a large set of genes that have been found to be mutated in leukemia or associated with survival, but were not previously linked to the JAK/STAT or MAPK pathways nor shown to functionally contribute to leukemogenesis. Forced expression of these novel genes resulted in IL3-independent growth in vitro and tumorigenesis in vivo, validating this mutagenesis-based approach for identifying new genes that promote cytokine signaling and leukemogenesis. Therefore, our findings provide a broadly applicable approach for classifying functionally relevant genes in diverse malignancies and offer new insights into the impact of cytokine signaling on leukemia development. Cancer Res; 76(4); 773–86. ©2015 AACR.
Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology
Authors: F. Jaisser, N. Farman, Rhian M. Touyz
Journal: Pharmacological Reviews (2015)

The mineralocorticoid receptor (MR) and its ligand aldosterone are the principal modulators of hormone-regulated renal sodium reabsorption. In addition to the kidney, there are several other cells and organs expressing MR, in which its activation mediates pathologic changes, indicating potential therapeutic applications of pharmacological MR antagonism. Steroidal MR antagonists have been used for decades to fight hypertension and more recently heart failure. New therapeutic indications are now arising, and nonsteroidal MR antagonists are currently under development. This review is focused on nonclassic MR targets in cardiac, vascular, renal, metabolic, ocular, and cutaneous diseases. The MR, associated with other risk factors, is involved in organ fibrosis, inflammation, oxidative stress, and aging; for example, in the kidney and heart MR mediates hormonal tissue-specific ion channel regulation. Genetic and epigenetic modifications of MR expression/activity that have been documented in hypertension may also present significant risk factors in other diseases and be susceptible to MR antagonism. Excess mineralocorticoid signaling, mediated by aldosterone or glucocorticoids binding, now appears deleterious in the progression of pathologies that may lead to end-stage organ failure and could therefore benefit from the repositioning of pharmacological MR antagonists.
P0776 : Efficacy of 12 or 18 weeks of grazoprevir plus elbasvir with ribavirin in treatment-naive, noncirrhotic HCV genotype 3-infected patients
Authors: E. Gane, R. Nahass, V. Luketic, P. Hwang, M. Robertson, J. Wahl, E. Barr, B. Haber
Journal: Journal of Hepatology (2015)
Tasquinimod triggers an early change in the polarization of tumor associated macrophages in the tumor microenvironment
Authors: Anders Olsson, Jessica Nakhlé, Anette Sundstedt, Pascale Plas, Anne-Laure Bauchet, Valérie Pierron, Luce Bruetschy, Adnan Deronic, Marie Törngren, David Liberg, Fabien Schmidlin, Tomas Leanderson
Journal: Journal for ImmunoTherapy of Cancer (2015)

Tasquinimod (a quinoline-3-carboxyamide) is a small molecule immunotherapy with demonstrated effects on the tumor microenvironment (TME) involving immunomodulation, anti-angiogenesis and inhibition of metastasis. A target molecule of tasquinimod is the inflammatory protein S100A9 which has been shown to affect the accumulation and function of suppressive myeloid cell subsets in tumors. Given the major impact of myeloid cells to the tumor microenvironment, manipulation of this cell compartment is a desirable goal in cancer therapeutics.To understand the consequences of tasquinimod treatment on the TME, we evaluated early treatment effects in tumor infiltrating myeloid cells. Cellular phenotypes were studied by flow cytometry while gene expression both in tumor tissue and in isolated CD11b(+) cells or tumor cells were measured by real time-PCR. Effects on angiogenesis were monitored by changes in CD31 levels and by gene expression in tumor tissue. Effects on cytokine levels in tumor tissue and serum were determined by multiplex analysis.The MC38-C215 colon carcinoma tumors showed a substantial infiltration of primarily myeloid cells that were dominated by Ly6C(low)F4/80(+)CD206(+) M2-polarized tumor associated macrophages (TAMs), an immuno-suppressive and pro-angiogenic cell population. Here, we show that tasquinimod treatment induces an anti-tumor effect which is subsequent to a reduction in tumor infiltrating CD206(+) M2 macrophages and a simultaneous increase in M1 macrophages expressing MHC class II and CD86. The tasquinimod-induced changes in TAM polarization were evident within 24 h of exposure, emphasizing the ability of tasquinimod to rapidly reprogram the tumor microenvironment. This change in the tumor associated myeloid compartment preceded an increased IL12-production within the tumor and a decrease in tumor neovascularization. The switch in TAM polarization by tasquinimod was confirmed in the 4T1 breast cancer model where tasquinimod also reduce lung metastasis development.Our data show that tasquinimod affects tumor infiltrating myeloid cells early after exposure, leading to a change in phenotype from pro-angiogenic and immunosuppressive M2-like TAMs to pro-inflammatory M1-like macrophages. These changes are consistent with the effects of tasquinimod seen on tumor vascularization, immune suppression and metastasis giving further insights to the anti-tumor mechanism of action of tasquinimod.
Where is West Nile fever? Lessons learnt from recent human cases in northern Italy
Authors: F Gobbi, G Napoletano, C Piovesan, F Russo, A Angheben, A Rossanese, A M Cattelan, L Gallo, M Valsecchi, A Piazza, G Venturi, Z Bisoffi
Journal: Eurosurveillance (2009)

West Nile disease in humans has been detected for the first time in Italy in two regions, Emilia-Romagna and Veneto. We conclude that also West Nile fever cases should be specifically targeted by surveillance.
Induction of the S100 Chemotactic Protein, CP-10, in Murine Microvascular Endothelial Cells by Proinflammatory Stimuli
Authors: Tina Yen, Craig A. Harrison, Jannine M. Devery, Sharon Leong, Siiri E. Iismaa, Teizo Yoshimura, Carolyn L. Geczy
Journal: Blood (1997)
Fludarabine, Cyclophosphamide and Rituximab As First Line Treatment In Follicular Lymphoma
Authors: Fátima de la Cruz Vicente, Estrella Carrillo Cruz, María Solé Rodríguez, Ana Marín Niebla, Eduardo Ríos Herranz, María Luz Martino Galiana, Jose Falantes González, Isabel Montero Cuadrado, Jose González Campos, Ildefonso Espigado Tocino, Jose A Pérez-Simón
Journal: Blood (2013)
Genomics in Conservation: Case Studies and Bridging the Gap between Data and Application
Authors: Brittany A. Garner, Brian K. Hand, Stephen J. Amish, Louis Bernatchez, Jeffrey T. Foster, Kristina M. Miller, Phillip A. Morin, Shawn R. Narum, Stephen J. O’Brien, Gretchen Roffler, William D. Templin, Paul Sunnucks, Jeffrey Strait, Kenneth I. Warheit, Todd R. Seamons, John Wenburg, Jeffrey Olsen, Gordon Luikart
Journal: Trends in Ecology & Evolution (2015)
Distribution Studies in Mice Following the Intravenous Injection of Diethyl β-Iodoethyl Amine Hydrochloride Prepared with Radioactive Iodine&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: A M SELIGMAN, A M RUTENBURG, O M FREIDMAN
Journal: JNCI Journal of the National Cancer Institute (1949)

Distribution Studies in Mice Following the Intravenous Injection of Diethyl β-Iodoethyl Amine Hydrochloride Prepared with Radioactive Iodine Get access Arnold M. Seligman, Arnold M. Seligman assistant professor of surgery Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexander M. Rutenburg, Alexander M. Rutenburg assistant resident in surgery Search for other works by this author on: Oxford Academic PubMed Google Scholar Orrie M. Friedman Orrie M. Friedman research fellow in chemistry Kirstein Laboratory for Surgical Research, Beth Israel Hospital, Boston, the Department of Surgery, Harvard Medical School, and the Chemical Laboratory, Harvard University Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 4, February 1949, Pages 261–270, https://doi.org/10.1093/jnci/9.4.261 Published: 01 February 1949 Article history Received: 17 July 1948 Published: 01 February 1949
Combined Antitumor Therapy with Metronomic Topotecan and Hypoxia-Activated Prodrug, Evofosfamide, in Neuroblastoma and Rhabdomyosarcoma Preclinical Models
Authors: Libo Zhang, Paula Marrano, Bing Wu, Sushil Kumar, Paul Thorner, Sylvain Baruchel
Journal: Clinical Cancer Research (2015)

Tumor cells residing in tumor hypoxic zones are a major cause of drug resistance and tumor relapse. In this study, we investigated the efficacy of evofosfamide, a hypoxia-activated prodrug, and its combination with topotecan in neuroblastoma and rhabdomyosarcoma preclinical models.Neuroblastoma and rhabdomyosarcoma cells were tested in vitro to assess the effect of evofosfamide on cell proliferation, both as a single agent and in combination with topotecan. In vivo antitumor activity was evaluated in different xenograft models. Animal survival was studied with the neuroblastoma metastatic tumor model.All tested cell lines showed response to evofosfamide under normoxic conditions, but when exposed to hypoxia overnight, a 2- to 65-fold decrease of IC50 was observed. Adding topotecan to the evofosfamide treatment significantly increased cytotoxicity in vitro In neuroblastoma xenograft models, single-agent evofosfamide treatment delayed tumor growth. Complete tumor regression was observed in the combined topotecan/evofosfamide treatment group after 2-week treatment. Combined treatment also improved survival in a neuroblastoma metastatic model, compared to single-agent treatments. In rhabdomyosarcoma xenograft models, combined treatment was more effective than single agents. We also showed that evofosfamide mostly targeted tumor cells within hypoxic regions while topotecan was more effective to tumor cells in normoxic regions. Combined treatment induced tumor cell apoptosis in both normoxic and hypoxic regions.Evofosfamide shows antitumor effects in neuroblastoma and rhabdomyosarcoma xenografts. Compared with single-agent, evofosfamide/topotecan, combined therapy improves tumor response, delays tumor relapse, and enhances animal survival in preclinical tumor models. Clin Cancer Res; 22(11); 2697-708. ©2015 AACR.
Abstract 18683: Satellite Cells are a Major Source of the Receptor for Advanced Glycation End Products in the Ischemic Leg and Play a Role in Collateral Growth
Authors: Laura M Hansen, Alicia N Lyle, Giji Joseph, Daiana Weiss, W. Robert Taylor
Journal: Circulation (2014)

Both coronary artery and peripheral vascular disease are growing health concerns that can lead to impaired blood flow and tissue ischemia, though neovascularization and growth of collateral vessels can help to restore blood flow and preserve tissue function, thus improving outcomes. Collateral formation is a complex process which includes both angiogenesis and arteriogenesis and involves cytokine signaling, inflammatory cells, cell proliferation and migration, and matrix remodeling. One factor that has been associated with negative effects on collateral growth is the receptor for advanced glycation end products (RAGE); however, the cellular source and the mechanism of RAGE regulation in ischemic regions is not fully understood. The goal of this study was to determine if RAGE is increased in the ischemic leg using the hind limb ischemia (HLI) model of collateral growth and to investigate the mechanism regulating its expression using both in vivo and in vitro systems. Following ligation of the femoral artery in the HLI model, RAGE mRNA expression was increased 12.2 ± 3.9 fold in the ischemic versus non-ischemic leg at day 5 (n=6, p=0.007). However, the infusion of PEG-Catalase to decrease hydrogen peroxide significantly blunted the increase (1.4 ± 0.5 versus 12.2 ± 3.9 fold increase (ischemic/non-ischemic) in the PEG-Catalase treated versus control mice, n=6, p=0.0007). These results suggest that RAGE expression is increased by hydrogen peroxide. In situ hybridization revealed that satellite cells are the source of RAGE in the ischemic limb. A primary cell line of satellite cells was established and stimulation with exogenous hydrogen peroxide showed a 2.3 ± 0.3 fold increase in RAGE mRNA expression at 4 hours, as quantified by qRT-PCR. Furthermore, cultured satellite cells also have a 4.0 ± 1.9 fold increase in monocyte chemoattractant protein-1 (MCP-1) at 4 hours and osteopontin was increased 4.5 ± 2.0 fold at 18 hours. Thus, in addition to being a major source of RAGE in the ischemic limb, satellite cells may serve as a novel source of paracrine factors that regulate collateral vessel formation.
The impact of primary Gleason pattern on survival following brachytherapy for Gleason score 7 prostate cancer
Authors: E. Adamovich, G. S. Merrick, R. Galbreath, W. Butler, K. Wallner, Z. Allen, S. Gutman
Journal: Journal of Clinical Oncology (2007)

15588 Background: A recent radical prostatectomy series reported lower rates of biochemical control and cause-specific survival in Gleason score 7 patients with primary Gleason pattern 4. In this study, we evaluated the impact of Gleason 4+3 versus 3+4 on cause-specific, biochemical progression-free and overall survival in patients managed with permanent prostate brachytherapy. Methods: From April 1995 to June 2003, 530 prostate cancer patients underwent brachytherapy for clinical stage T1b-T3c (2002 AJCC) prostate cancer with Gleason score 3+4 (n=300) or Gleason score 4+3 (n=230) histology. All patients underwent brachytherapy more than three years prior to analysis. The mean and median follow-up was 6.0 and 5.7 years, respectively (range 3.2–11.2 years). Of the evaluated cohort, 412 (77.7%) received supplemental XRT and 177 (33.4%) received androgen deprivation therapy. No statistical differences were discerned between the use of XRT, however, Gleason 4+3 patients were more likely (37.4% versus 30.3%, p=0.002) to receive ADT. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free and overall survival. Results: At 10 years, primary Gleason 3+4 versus 4+3 did not predict for cause-specific survival (96.7% versus 93.3%, p=0.506), biochemical progression-free (97.0 versus 92.9%, p=0.085) or overall survival (77.0% versus 78.0%, p=0.9333). Cox linear regression analysis demonstrated no significant predictors for cause-specific survival while pre-treatment PSA, prostate volume and clinical stage predicted for biochemical progression-free survival. Patient age, tobacco use and diabetes were the strongest predictor for overall survival. To date, 57 patients have died (25 with Gleason 4+3 and 32 with Gleason 3+4). Of the deaths, 76% were due to cardiovascular events or second malignancies. To date, 4 patients (2 in each cohort) have died of metastatic prostate cancer. Conclusions: Following brachytherapy, the primary Gleason pattern did not impact cause-specific, biochemical progression-free or overall survival in Gleason score 7 prostate cancer. Cardiovascular disease and second malignancies were responsible for 9 times more deaths than prostate cancer. No significant financial relationships to disclose.
Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain.
Authors: R Kaplan, W C Parris, M L Citron, D Zhukovsky, R F Reder, B J Buckley, R F Kaiko
Journal: Journal of Clinical Oncology (1998)

PURPOSE This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain. PATIENTS AND METHODS Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent). RESULTS Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.
Search for Oncogenic Properties in Various Viruses Found in Man; Positive Results with Adeno Virus Types 12 and 18
Authors: D L MCLEOD, A W HAM
Journal: JAMA (1963)

Since the inoculation of newborn hamsters with polyoma virus results both in necrotizing lesions and virus-free tumours the possibility was raised that necrotizing viruses found in man acted similarly. Accordingly a group of viruses found in man were tested for oncogenic activity by injecting them into newborn hamsters. Most were observed for more than a year. As yet only Adenovirus Types 12 and 18 have induced tumours; the oncogenic properties of these were reported by Trentin et al., and Huebner et al., respectively, while this study was in progress. The significance of the findings with regard to man cannot as yet be evaluated but the point is made that Adenovirus Types 12 and 18, like polyoma and SV40 virus, only cause neoplasia under special circumstances. Further work will be required to discover if these circumstances or their equivalent occur under conditions of the natural spread of infection.