tbuckley/cabot-search huggingface dataset:
A pilot study of AMP-224, a PD-L2 Fc fusion protein, in combination with stereotactic body radiation therapy (SBRT) in patients with metastatic colorectal cancer.
Authors: Austin G. Duffy, Oxana V. Makarova-Rusher, Drew Pratt, David E Kleiner, Suzanne Fioravanti, Melissa Walker, Stephanie Carey, William Douglas Figg, Seth M. Steinberg, Victoria Anderson, Elliot Levy, Venkatesh Krishnasamy, Bradford J. Wood, Jennifer Jones, Deborah E. Citrin, Tim F. Greten
Journal: Journal of Clinical Oncology (2016)

560 Background: AMP-224, a PD-L2 Fc fusion protein, binds to PD-1, an inhibitory receptor that is present on the cell surface of exhausted, activated, effector, and memory T cells. AMP-224 has a unique mechanism of action in that it binds specifically to PD-1 HI T cells (chronically stimulated / exhausted T cells) but not PD-1 LO cells which represent the normal activated T cell population. Preclinical studies have documented an increase in antitumor immunity following radiation therapy (RT), but also tumor PD-L1 expression as an escape mechanism. The aim of the study is to evaluate whether inhibition of PD-1/PDL-1 axis could improve anti-tumor immunity effects of RT. Methods: Patients with histologically confirmed metastatic colorectal cancer to liver were treated with SBRT to a site of liver metastasis at 8Gy in a single fraction (DL1) or 8Gy in 3 daily fractions (DL2). All patients received AMP-224 10mg/kg IV beginning Day 1 after SBRT preceded by cyclophosphamide 200mg/m2 (D0). Primary objective was to determine the safety and feasibility of AMP-224 in combination with stereotactic body radiation therapy (SBRT) to metastatic hepatic metastasis in patients with advanced colorectal cancer. Mandatory pre- and post-treatment biopsies were attempted on all patients. Results: N = 17 patients with refractory metastatic CRC were enrolled. N = 2 pts were unevaluable. 6pts were treated at DL1 (8Gy x 1fraction SBRT, AMP-224 10mg/kg q2-weekly) and 9pts were treated at DL2 (8Gy x 3fractions SBRT, AMP-224 10mg/kg q2-weekly) No DLT was encountered. The most common toxicity was fatigue (G1/2) in all patients in DL2. N = 3 patients experienced G2 infusion reaction which responded to standard interventions. 5/15 pts did not complete treatment due to rapid PD. No objective responses have been seen, although N = 6 pts remain on study. Pre- and post-tumor biopsies were performed on 7 of first 11 pts. Conclusions: AMP-224 in combination with SBRT to site of colorectal hepatic metastases is safe and feasible. Preliminarily no objective responses have been seen. Full clinical and correlative data including post-therapeutic radiated and non-radiated tumor biopsies will be presented. Clinical trial information: NCT02298946.
Hepatitis C
Authors: Miriam J. Alter, Richard E. Sampliner
Journal: New England Journal of Medicine (1989)

Recombinant DNA technology has brought us to a new era in research on and control of non-A, non-B hepatitis. The cloning and sequencing of what is being called hepatitis C virus1 and the development of a serologic assay to detect antibody to a part (epitope) of this virus (anti-HCV)2 have been major break-throughs in the long search for a causative agent of non-A, non-B hepatitis. These developments provide an opportunity to redefine and expand our knowledge of the epidemiology and natural history of the disease, to determine more accurately the amount of acute and chronic disease, and to evaluate preventive . . .
A phase III, multicentre, randomised, double-blind, active-controlled, parallel-group trial comparing safety and efficacy of HD203, with innovator etanercept, in combination with methotrexate, in patients with rheumatoid arthritis: the HERA study
Authors: Sang-Cheol Bae, Jinseok Kim, Jung-Yoon Choe, Won Park, Sang-Heon Lee, Yong-Beom Park, Seung-Cheol Shim, Shin-Seok Lee, Yoon-Kyoung Sung, Chan-Bum Choi, So-Ra Lee, HanYu Park, Yongho Ahn
Journal: Annals of the Rheumatic Diseases (2016)

To evaluate equivalence in efficacy for rheumatoid arthritis (RA) and compare the safety of the biosimilar HD203 with innovator etanercept (ETN) plus methotrexate (MTX) (ClinicalTrials.gov NCT01270997).Patients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III, multicentre, randomised, double-blind, parallel-group design. The primary end point was the proportion of patients achieving the American College of Rheumatology 20% response (ACR20) at week 24 for per-protocol study completer set (PPS). Secondary end points included ACR response criteria, ACRn, European League against Rheumatism (EULAR) response, change in Disease Activity Score 28 (DAS28), patient-reported outcomes, safety and immunogenicity.Of the 294 randomised patients (HD203, n=147; ETN, n=147), 233 comprised the 24-week PPS (n=115 and 118, respectively). ACR20 at week 24 was achieved by 83.48% and 81.36% of PPS patients, respectively, demonstrating equivalent efficacy within predefined margins of ±20% (treatment difference 2.12%, 95% CI -7.65% to 11.89%). Outcomes for secondary end points were consistent with the primary efficacy findings. Groups were comparable for overall incidences of treatment-emergent (all-causality) adverse events (AEs) (HD203 113 (76.9%) vs ETN 114 (78.1%) (p=0.804)), adverse drug reactions, serious AEs and discontinuations due to AEs. Few patients (HD203, n=8; ETN, n=3) tested positive for anti-drug antibodies.The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA.NCT01270997; Results.
Gene Transfer Improves Heart Function in Patients With Heart Failure
Authors: Anita Slomski
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
Bariatric surgery should be an option for treating type 2 diabetes, societies say
Authors: Susan Mayor
Journal: BMJ (2016)

Bariatric surgery should be included in guidelines as a treatment option for people with type 2 diabetes and obesity, leading diabetes societies have recommended in a joint statement that formally recognised surgery for the first time as a standard therapeutic intervention for the condition.1

A multidisciplinary group of 48 clinicians and academics, including representatives of diabetes societies, met to review the scientific and clinical evidence for bariatric surgery—which they …
Radioiodine therapy of thyrotoxicosis.
Authors: M D Gross, B Shapiro, J C Sisson
Journal: BMJ (1967)

Radioactive iodine treatment of thyrotoxicosis in considered one of, if not the most, successful therapy in Nuclear Medicine. A sixty year experience in virtually hundreds of thousands of patients supports the safety, efficacy and cost effectiveness of radioiodine. However, despite all of the data amassed since its introduction almost all aspects of its use from the indications, selection of patients, goals of therapy and selection of doses in the treatment of hyperthyroidism remain controversial and continue to be a subject of lively debate.
Management of Hodgkin's Disease
Authors: J F Desforges, C J Rutherford
Journal: New England Journal of Medicine (1968)

mortality.It would simply mean that the cause of death would be different.Enabling people to live longer-perhaps for 20 years after retirement-would create economic problems no less great than at present.There would perhaps be the com- pensation that more and more of the un- employed could be used in looking after the aged.Or will you be proposing what the Archbishop of Canterbury hinted at when financial resources really dry up ?S ELLISON London NW6A cautionary tale SIR,-'Tis with a sense of grievous shock That one observed great Stephen Lock To perpetrate the awful sin Of leaving an unchecked reference in An article that bears his name.'This blot on editorial fame Though "For Debate" is clear to see At least to Belloc and to me: It was not Lundy's noble dad Who did advise the tearful lad It was his grandpapa the Duke -Sir, what a liberty you took!
Endobronchial Electrocautery
Authors: R.G. Hooper, L. Spratling, C. Beechler, S. Schaffner
Journal: Endoscopy (1984)

Progressive respiratory failure due to massive endobronchial involvement causes death in some patients with bronchogenic carcinoma. The absence of satisfactory therapeutic modalities directed specifically at masses of endobronchial tumor has limited our ability to effectively palliate these patients. Electro-cautery is a technique which has the potential for removing large quantities of endobronchial tumor safely, painlessly , and without measurable blood loss. It is especially well suited to the patient requiring local palliation with immediate relief of airway obstruction and without a prolonged hospital stay. The report reviews: a) its use in an individual with tracheal obstruction; b) the effect of electrocautery current changes and probe type on canine trachea; and, c) the technical problems which must be considered in using endobronchial electrocautery. In the individual with tracheal obstruction, large amounts of tumor were cleared with excellent hemostasis. The canine trachea demonstrates that the amount and duration of current used are extremely important. Equipment available of gastrointestinal electrocautery can produce significant tracheal damage and must be used with great caution. Finally, fiberoptic bronchoscopes are not designed for electrocautery work, and care must be employed when performing such procedures through these instruments.
Phase II studies of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced squamous (sq) or nonsquamous (non-sq) non-small cell lung cancer (NSCLC).
Authors: Makoto Nishio, Toyoaki Hida, Kazuhiko Nakagawa, Hiroshi Sakai, Naoyuki Nogami, Shinji Atagi, Toshiaki Takahashi, Hiroshi Nokihara, Hideo Saka, Mitsuhiro Takenoyama, Shiro Fujita, Hiroshi Tanaka, Koji Takeda, Miyako Satouchi, Hiroshi Isobe, Makoto Maemondo, Koichi Goto, Tomonori Hirashima, Koichi Minato, Tomohide Tamura
Journal: Journal of Clinical Oncology (2015)

8027 Background: Nivolumab, a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in phase I and II trials in several tumor types. Recently, a phase III study (CheckMate -017) demonstrated that nivolumab improved overall survival than docetaxel in second-line of sq NSCLC. Here, we report the results of two phase II studies to evaluate the efficacy and safety of nivolumab in previously treated advanced sq (JapicCTI-No.132072) and non-sq (JapicCTI-No.132073) NSCLC pts. Methods: Both studies require pts aged ≥ 20 years with ECOG status of 0 or 1, stage IIIB/IV, or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen.Pts received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity.The primary endpoint in both studies was the objective response rate (ORR) (RECIST v1.1).Planned sample size was 30 pts for Sq and 67 pts for Non-sq, respectively(P0=0.09, P1=0.26 , P0=0.09, P1=0.20 ; α=0.025 (one-side) , 1-β=0.8). Results: From April 2013 to April 2014, a total of 111 NSCLC pts were enrolled into two studies (35 pts with sq,76 pts with non-sq, male/female: 81/30; PS 0/1: 46/55; aged 31 to 84 [median: 65.0] years; Stage IIIB/Stage IV/recurrence: 6/86/19)Grade 3-4 drug related adverse events (G3AEs) were observed in 16.2 % (18/111) pts. Most common G3AEs were lymphocyte count decreased 3.6 % (4/111), hyponatremia 1.8 % (2/111), interstitial lung disease 1.8 % (2/111), pleural effusion 1.8 % (2/111). Any grade of Interstitial lung disease was observed in 4.5 % (5/111) pts. No grade 5 AEs were observed.Efficacy data were shown in table 1. Median follow-up was 10.4 months and 8.4 months, respectively. Conclusions: Nivolumab continues to demonstrate encouraging clinical efficacy in both sq and non-sq NSCLC with a manageable safety profile. Clinical trial information: 132072 and 132073. Sq (n=35) non-Sq (n=76) (95% CI) (95% CI) ORR 25.7% (14.2-42.1) 19.7% (12.3-30.0) mPFS 128 days (44.0-215.0) 85 days (43.0-102.0) mDOR NR (135.0 - ) NR (210.0 -) mOS NR (378.0 - ) NR (- -) DOR : duration of response
Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial
Authors: Jeffrey Cui, Len Philo, Phirum Nguyen, Heather Hofflich, Carolyn Hernandez, Ricki Bettencourt, Lisa Richards, Joanie Salotti, Archana Bhatt, Jonathan Hooker, William Haufe, Catherine Hooker, David A. Brenner, Claude B. Sirlin, Rohit Loomba
Journal: Journal of Hepatology (2016)
Selective protection of renal tubular epithelial cells by heme oxygenase (HO)-1 during stress-induced injury
Authors: Yonghong Yang, Kazuhide Ohta, Masaki Shimizu, Kayoko Morimoto, Chinami Goto, Akiko Nakai, Tomoko Toma, Yoshihito Kasahara, Akihiro Yachie, Hidetoshi Seki, Shoichi Koizumi
Journal: Kidney International (2003)
Abstract OT3-02-08: Scalp cooling alopecia prevention trial (SCALP) for patients with early stage breast cancer
Authors: JR Nangia, T Wang, M Rude, C Osborne, S Papish, J Abraham, F Holmes, M Savin, R Paxman, SG Hilsenbeck, CK Osborne, M Rimawi
Journal: Cancer Research (2016)

Abstract Background Adjuvant chemotherapy treats micro-metastatic disease and decreases the risk of breast cancer recurrence. However, it may be associated with distressing side effects, including alopecia. Women with breast cancer rate chemotherapy-induced alopecia as one of the most severe, troublesome, and distressing side effects of chemotherapy. In many countries, scalp cooling has been introduced to prevent or reduce chemotherapy-induced alopecia. The theory is that scalp cooling causes cutaneous vasoconstriction, which reduces blood flow to the hair follicles during peak plasma concentrations of the chemotherapeutic agents and therefore reduces cellular uptake of these agents. It also results in reduced biochemical activity, which makes hair follicles less susceptible to the damage of the chemotherapy agents. Historically success rates are have been variable, but based on non-randomized studies, scalp cooling appears to be effective in preventing chemotherapy-induced alopecia especially in more recent studies. Methods We are conducting a prospective multi-center randomized controlled non-blinded trial to evaluate the safety and efficacy of the Orbis Paxman Hair Loss Prevention System in reducing the incidence of chemotherapy-induced alopecia. Women with stage I-II breast cancer who will receive neoadjuvant or adjuvant anthracycline- or taxane-based chemotherapy, for at least four cycles are eligible. Participants are randomized in a 2:1 ratio to scalp-cooling or no cooling. Scalp-cooling is done using the Orbis Paxman Hair Loss Prevention System prior to, during and after each chemotherapy administration. The primary efficacy endpoints are hair preservation, defined as CTCAE v4 alopecia &amp;lt;2, and device safety. Two hundred and thirty five (235) patients are planned to be enrolled which will provide 85% power to detect a 20% difference in hair preservation, 15% in control group and 35% in scalp-cooling group . Secondary endpoints include: wig/scarf use and quality of life assessed by the EORTC QLQ-30, HADS and BIS. Study participants will be followed for 5 years post-study for time to first recurrence, overall survival, site of first recurrence, and incidence of isolated scalp metastasis. Citation Format: Nangia JR, Wang T, Rude M, Osborne C, Papish S, Abraham J, Holmes F, Savin M, Paxman R, Hilsenbeck SG, Osborne CK, Rimawi M. Scalp cooling alopecia prevention trial (SCALP) for patients with early stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-08.
Multimedia: Salt, Diet and Health
Authors: Marcus Müllner
Journal: BMJ (1999)

G A MacGregor, H E de Wardener


Cambridge University Press, £14.95, pp 245 




ISBN 0 521 63545 4

———————

Rating: ★★★

Did you ever suspect that there might be an industrial conspiracy against a reduction in salt intake? MacGregor and de Wardener think so. On first browsing, their book looks like one of those populist texts, “Lose 50% of your weight in 2 weeks without effort and stay healthy.” On the other hand, both authors are well known in the world of dietary salt. Other guarantors for credibility are the well selected and presented references, with most of the cited sources being credible journals.

I was quickly engaged by one of the most informative and entertaining books that I have read. It was almost exciting to learn about the history of salt and the historical role it has played in society: the matter of how salt was used as a commercial and fiscal product to increase the revenue of the ruling authorities is addressed briefly but comprehensively. The book then swiftly moves to the heart of the matter: the adverse relation between salt intake and health.

Two recent articles in Science have concluded that there is little evidence that reducing dietary salt is beneficial, but MacGregor and de Wardener present scientific findings to support their premise in a convincing way. They manage to put the size of the problem, and its consequences, in perspective, and their presentation is spiced with a balanced view of an interesting issue: why hypertension is almost twice as common in black Americans as in white Americans in the United Sttes.

The chapter on industrial conspiracy is the most fascinating, and the authors’ allegations are well presented, discussed, and referenced. Some “good” reasons exist for the food industry not trying too hard to reduce the salt content of their products—processed foods provide us with 80% of our daily salt intake. The salt industry is a wolf in sheep’s clothing, trying to deny or obscure the evidence that links salt intake to hypertension and subsequent stroke. These allegations have already caused controversy in the BMJ, and there is potential for more. One of the authors of the Science articles, we are told, has been a consultant for the Salt Institute, a food industry organisation.

The book is written for both lay people and medical professionals. Even though the reader is informed that atherosclerosis means “furring of the arteries,” I am not sure if a lay person would feel at ease with the graphs or with terms like “plasma angiotensin” and “ACE inhibitors.” This minor reservation aside, it is clear that MacGregor and de Wardener have spent much of their scientific lives pursuing the association between salt and hypertension. They not only have a deep insight, but are able to convey their knowledge convincingly.
Abstract PR12: Mutant p53 drives early events in fallopian tube tumorigenesis through mesenchyme-associated autocrine production of matrix that supports survival and mesothelial intercalation.
Authors: Marcin P. Iwanicki, Hsing-Yu Chen, Ioannis Zervantonakis, Marian Novak, Taru Muranen, Tan A. Ince, Ronny Drapkin, Joan S. Brugge
Journal: Clinical Cancer Research (2016)

Abstract High-grade serous ovarian cancer (HGS-OvCa) harbor p53 mutations and predominantly originates from the secretory epithelial cell compartment of the fallopian tube fimbriae. From this site, tumor cells detach, survive in the peritoneal cavity, and form cellular clusters that clear the mesothelium and expand to form peritoneal masses. To examine the contribution of mutant p53 to any of these phenotypic alterations associated with HGS-OvCA tumor progression, we developed live-cell microscopy assays that recapitulate these phenotypes and examined dynamic processes regulated by depletion of p53 or gain-of-function (GOF) mutations in p53 in cultured secretory fallopian tube epithelial cells. Expression of GOF mutant variants of p53, but not depletion of endogenous wild-type p53, promoted survival and cell-cell aggregation under conditions of cell detachment, leading to the formation of spheroids with mesothelium-clearing capacity. These phenotypes were blocked by mutant p53 reactivation and depended on the expression of the mesenchyme transcription factor TWIST1, inhibition of p63 and de novo formation of a unique cell-matrix adhesion niche supported by autocrine fibronectin production and activation of integrins in detached cells. Inhibition of fibronectin or integrin α5 in suspension blocked cell-to-cell adhesion leading to HGS-OvCa spheroid disintegration and ultimately anoikis. These results indicate the detached FTE cells-expressing GOF mutants of p53 undergo a mesenchymal transition under conditions of matrix detachment leading to autocrine production of matrix and anchorage-independent survival and proliferation, as well as mesothelial clearance activity. These findings provide important new insights into activities of mutant p53 that may play a critical role in early events in tumorigenesis of high-grade ovarian serous tumors and provide a rationale for the development of therapeutics that target ovarian cancer cells transiting through the peritoneal cavity. This abstract is also presented as Poster B03. Citation Format: Marcin P. Iwanicki, Hsing-Yu Chen, Ioannis Zervantonakis, Marian Novak, Taru Muranen, Tan A. Ince, Ronny Drapkin, Joan S. Brugge. Mutant p53 drives early events in fallopian tube tumorigenesis through mesenchyme-associated autocrine production of matrix that supports survival and mesothelial intercalation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr PR12.
Cytogenetic and cytochemical studies on progenitor cells of primary acquired sideroblastic anemia (PASA): involvement of multipotent myeloid stem cells in PASA clone and mosaicism with normal clone
Authors: T Amenomori, M Tomonaga, I Jinnai, H Soda, H Nonaka, T Matsuo, Y Yoshida, K Kuriyama, M Ichimaru, T Suematsu
Journal: Blood (1987)