tbuckley/cabot-search huggingface dataset:
Effect of exercise on novel biomarkers of muscle damage and cancer-related fatigue: A nationwide URCC NCORP RCT in 350 patients with cancer.
Authors: Karen Michelle Mustian, Anita Roselyn Peoples, Luke Joseph Peppone, Po-Ju Lin, Michelle Christine Janelsins, Ian Kleckner, Calvin Cole, Benjamin Esparaz, Jessica Miller, Jeffrey K. Giguere
Journal: Journal of Clinical Oncology (2017)

10020 Background: Chemotherapy may lead to systemic muscle damage. Up-regulation of developmental myosin light chain 5 (MYL5) and myosin heavy chain 8 (MYH8) genes is required for normal muscle regeneration in response to damage. However, secretion of MYL5 and MYH8 proteins into the serum suggest degradation of muscle, which, in turn, may lead to cancer-related-fatigue (CRF). In this study, we investigated (1) the effect of an exercise intervention, Exercise for Cancer Patients (EXCAP) on mRNA gene expression and serum protein levels of MYL5 and MYH8 and (2) the association of these novel biomarkers with CRF. Methods: Chemotherapy naïve cancer patients (N = 350; mean age = 55.7) from 39 community oncology practices throughout the U.S. affiliated with the URCC NCORP Research Base participated in this nationwide, multicenter, phase III RCT. Patients were randomized into 2 groups: (1) chemotherapy and (2) chemotherapy plus a 6-week aerobic and resistance exercise prescription-EXCAP. Gene expression and protein levels of MYL5 and MYH8, as well as CRF were assessed pre- and post-intervention from whole blood by qPCR, from serum by Luminex assays, and from patient-report by the Multidimensional Fatigue Symptom Inventory, respectively. Results: T-tests show MYL5, but not MYH8, mRNA levels were significantly up-regulated from pre- to post-intervention in exercisers and controls (all p &lt; 0.01) with no significant group difference. Additionally, MYL5 and MYH8 serum protein levels significantly increased from pre to post in controls (all p &lt; 0.05), but remained stable in exercisers. Significant group differences in these serum proteins (p &lt; 0.01) suggest greater muscle degradation in non-exercisers. Pearson correlations revealed trends suggesting increases in MYL5 and MYH8 serum proteins are associated with increases in CRF (r = 0.09 and r = 0.11, respectively, all p &lt; 0.10). Conclusions: Results suggest EXCAP exercise is protective from chemotherapy-induced muscle damage via its effects on MYL5 and MYH8, and changes in these novel biomarkers may mediate changes in CRF. Further research is needed to confirm these findings. NCI UGCA189961, R25 CA102618. Clinical trial information: NCT00924651.
Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab
Authors: Jakub Krejcik, Kris A. Frerichs, Inger S. Nijhof, Berris van Kessel, Jeroen F. van Velzen, Andries C. Bloem, Marloes E.C. Broekmans, Sonja Zweegman, Johan van Meerloo, René J.P. Musters, Pino J. Poddighe, Richard W.J. Groen, Christopher Chiu, Torben Plesner, Henk M. Lokhorst, A. Kate Sasser, Tuna Mutis, Niels W.C.J. van de Donk
Journal: Clinical Cancer Research (2017)

Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma cells. The aim of this study was to investigate the clinical implications and the underlying mechanisms of daratumumab-mediated CD38 reduction.
The prognostic value of cytokeratin 7, 19, thyroid transcription factor-1 and CD117 expression in lung neuroendocrine tumors of various grades
Authors: L. Gurevich, N. Korsakova, I. Voronkova, I. Kazantseva, V. Ashevskaya, A. Titov, L. Kogoniya, M. Byakhova
Journal: Annals of Oncology (2017)
Diagnostic Performance of Magnetic Resonance Enterography for Detection of Active Inflammation in Children and Adolescents With Inflammatory Bowel Disease
Authors: Hee Mang Yoon, Chong Hyun Suh, Jeong Rye Kim, Jin Seong Lee, Ah Young Jung, Kyung Mo Kim, Young Ah Cho
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Magnetic resonance (MR) enterography has the advantage over other techniques of being noninvasive, lacking ionizing radiation, and demonstrating excellent soft-tissue contrast to evaluate pediatric patients with inflammatory bowel disease (IBD). <h3>Objective</h3> To evaluate the diagnostic performance of MR enterography for detection of active inflammation in children and adolescents with known or suspected IBD. <h3>Data Sources</h3> A search of MEDLINE and EMBASE up to January 2, 2017, was performed to identify studies. Search terms included<i>child</i>,<i>pediatric</i>,<i>adolescent</i>,<i>Crohn disease</i>,<i>inflammatory bowel disease</i>, and<i>magnetic resonance enterography</i>. The search was limited to English-language publications. <h3>Study Selection</h3> Studies evaluating the diagnostic performance of MR enterography for detection of active inflammation in pediatric patients with known or suspected IBD were selected. Two reviewers independently assessed the eligibility of the selected articles. <h3>Data Extraction and Synthesis</h3> The study was performed and reported in accordance with the PRISMA guidelines. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modeling. <h3>Main Outcomes and Measures</h3> The diagnostic performance of MR enterography for detection of active inflammation in pediatric patients with known or suspected IBD was the primary outcome. Subgroup analyses and meta-regression were performed. <h3>Results</h3> Eighteen original articles involving a total of 687 patients were included. The summary sensitivity was 83% (95% CI, 75%-89%), the summary specificity was 93% (95% CI, 90%-95%), and the area under the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93-0.97). The Higgins<i>I</i><sup>2</sup>statistics demonstrated substantial heterogeneity in terms of sensitivity (<i>I</i><sup>2</sup> = 84.1%) and specificity (<i>I</i><sup>2</sup> = 68.8%). Based on per-patient analysis, the summary sensitivity was 86% (95% CI, 78%-91%) and specificity was 91% (95% CI, 82%-96%). In meta-regression, among the various potential covariates, scanner manufacturer was associated with study heterogeneity. <h3>Conclusions and Relevance</h3> Magnetic resonance enterography, which is a noninvasive, radiation-free modality, demonstrates high diagnostic performance in the diagnosis of active inflammation in pediatric patients with IBD, especially at the per-patient level.
Micro-RNA profile in advanced metastatic breast cancer as a predictive tool for response to bevacizumab-paclitaxel
Authors: M. Mendiola, V. Heredia-Soto, J. Herranz, R. Martín, P. Zamora Auñón, B. Castelo, A. Pinto Marin, M. Miguel, R. Crespo, A. Ramírez de Molina, D. Hardisson, E. Espinosa, A. Redondo
Journal: Annals of Oncology (2017)
Association between biopsychosocial distress (BPSD) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)
Authors: C.D. Bergerot, K.L. Clark, K.T. Ashing, L. Almeida, P.G. Bergerot, R. Obenchain, N. Dizman, J. Hsu, M.C. Maia, E. Philip, M. Loscalzo, S.K. Pal
Journal: Annals of Oncology (2017)
AMG 655, a fully human agonistic antibody against TRAIL receptor-2, induces apoptosis via caspase activation in vitro and in vivo
Authors: Paula Kaplan-Lefko, Yongmei Gan, Justin Huard, Matt Colloton, Steve Zoog, Gloria Juan, Taska Dobson, Matt Peach, Yang Pan, Steve Kaufman, Dan Branstetter, Angela Coxon, Allison Bianchi, Sharon Wong-Madden, Ian Foltz, Brian Gliniak
Journal: Cancer Research (2007)

4867   Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL) Receptor-2 (TR-2) is a member of the tumor necrosis factor family of receptors and can transduce an apoptotic signal following TRAIL stimulation. Agonistic TR-2 antibodies can mimic the effect of TRAIL, triggering the death of ligand sensitive cells. AMG 655 is a fully human monoclonal agonistic antibody (IgG 1 ) directed against human TR-2 and is currently in clinical development. Binding of AMG 655 to TR-2 can activate intracellular caspases and induce apoptosis in a variety of transformed human cell lines in vitro. The anti-tumor potential of AMG 655 was confirmed in vivo using Colo 205 (colon), H2122 (lung), and MiaPaCa2 (pancreatic) tumor xenograft models. AMG 655 inhibited the growth of tumor xenografts in a dose-dependent manner and at higher doses induced the regression of established tumor xenografts. The mechanism of action of AMG 655 was explored in established Colo 205 tumor xenografts using immunohistochemistry (IHC) and laser scanning cytometry. Apoptosis was evaluated by IHC staining for activated caspases and cellular proliferation was evaluated by IHC staining for BrdU. Activated caspases were induced in a dose- and time-dependent manner. Activated caspase-3 was transiently induced following a single dose of AMG 655, peaking approximately 12 hours post-treatment and returning to baseline levels by approximately 96 hours. Transient induction of activated caspase-8 occurred prior to the induction of activated caspase-3 and peaked at approximately 6 hours following treatment. In addition to activation of caspases in the extrinsic pathway, activated caspase-9 was also transiently increased indicating that AMG 655 also activates the intrinsic apoptotic pathway. Tumor cell proliferation did not change in vivo following treatment with AMG 655. Concurrent with apoptotic induction in the tumor, elevated levels of activated caspase-3 and M30 (a cytokeratin 18 neoepitope generated by apoptosis) were also detected in the serum of tumor bearing mice following treatment with AMG 655. Consistent with the rapid activation of caspases in the tumor xenograft, peak levels of activated caspase-3 and M30 were detected in the serum approximately 24 hours after treatment with AMG 655. Thus AMG 655 induces rapid apoptosis in tumors followed by subsequent detection of markers of apoptosis in the serum. These data demonstrate potent anti-tumor activity of AMG 655 both in vitro and in vivo via induction of caspase-mediated apoptosis. These data support the clinical development of AMG 655.
Inhibiting PI3Kβ with AZD8186 Regulates Key Metabolic Pathways in PTEN-Null Tumors
Authors: James T. Lynch, Urszula M. Polanska, Oona Delpuech, Urs Hancox, Antonio G. Trinidad, Filippos Michopoulos, Carol Lenaghan, Robert McEwen, James Bradford, Radek Polanski, Rebecca Ellston, Alvaro Avivar-Valderas, James Pilling, Anna Staniszewska, Marie Cumberbatch, Susan E. Critchlow, Francisco Cruzalegui, Simon T. Barry
Journal: Clinical Cancer Research (2017)

Purpose: PTEN-null tumors become dependent on the PI3Kβ isoform and can be targeted by molecules such as the selective PI3Kβ inhibitor AZD8186. However, beyond the modulation of the canonical PI3K pathway, the consequences of inhibiting PI3Kβ are poorly defined.Experimental Design: To determine the broader impact of AZD8186 in PTEN-null tumors, we performed a genome-wide RNA-seq analysis of PTEN-null triple-negative breast tumor xenografts treated with AZD8186. Mechanistic consequences of AZD8186 treatment were examined across a number of PTEN-null cell lines and tumor models.Results: AZD8186 treatment resulted in modification of transcript and protein biomarkers associated with cell metabolism. We observed downregulation of cholesterol biosynthesis genes and upregulation of markers associated with metabolic stress. Downregulation of cholesterol biosynthesis proteins, such as HMGCS1, occurred in PTEN-null cell lines and tumor xenografts sensitive to AZD8186. Therapeutic inhibition of PI3Kβ also upregulated PDHK4 and increased PDH phosphorylation, indicative of reduced carbon flux into the TCA cycle. Consistent with this, metabolomic analysis revealed a number of changes in key carbon pathways, nucleotide, and amino acid biosynthesis.Conclusions: This study identifies novel mechanistic biomarkers of PI3Kβ inhibition in PTEN-null tumors supporting the concept that targeting PI3Kβ may exploit a metabolic dependency that contributes to therapeutic benefit in inducing cell stress. Considering these additional pathways will guide biomarker and combination strategies for this class of agents. Clin Cancer Res; 23(24); 7584-95. ©2017 AACR.
Low-oestrogen oral contraceptives.
Authors: B Law
Journal: BMJ (1976)

I was surprised to read in your leading article on this subject (November 20, p. 1216) the statement that''pharmaceutical companies seem to be preferring 17alpha-hydroxyprogesterone derivatives in oral contraceptives.'' The last surviving product on the British market containing 1 of this variety of progestogen (megestorl acetate) disappeared when Volidan was withdrawn in 1975. The 22 combined pills (containing 50 mcg of estrogen or less) and the 4 progestogen-only preparations currently available in this country all rely on 19-nortestosterone derivatives. Of these, norgestrel has no inherent estrogenicity and yet when as little as .15 mg is combined with only 30 mcg of ethinyl estradiol it provides the degree of reliability quoted in your article. Editors's note: Our leading article was, perhaps, misleading on this point. Certainly all the combined oral contraceptives currently available in Britain use 19-nortestosterone derivatives for their progestogen component - and there are good commercial and clinical reasons for that choice. However, a switch to 17alpha-hydroxyprogesterone derivatives would make it easier to calculate the estrogen content of contraceptives without having to make allowance for a variable amount of metabolic conversion from nortestosterone. There is, we believe, a resurgence of interest in that alternative, though no new formulations are yet on trial.
Increase in Incidence of Leukemia in Hybrid Mice Bearing Thymic Transplants from a High Leukemic Strain<xref ref-type="fn" rid="fn1"><sup>2</sup></xref>
Authors: L. W. Law
Journal: JNCI Journal of the National Cancer Institute (1952)

Journal Article Increase in Incidence of Leukemia in Hybrid Mice Bearing Thymic Transplants from a High Leukemic Strain Get access L. W. Law L. W. Law National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 4, February 1952, Pages 789–805, https://doi.org/10.1093/jnci/12.4.789 Published: 01 February 1952 Article history Received: 04 October 1951 Published: 01 February 1952
Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas
Authors: Oliver W. Press
Journal: Journal of Clinical Oncology (2008)

This issue of Journal of Clinical Oncology presents two articles that contribute substantially to the accumulating evidence documenting the important therapeutic role that radioimmunotherapy (RIT) can play in the management of B-cell lymphomas, particularly indolent lymphomas.1,2 Radiolabeled monoclonal antibodies were first shown to possess high levels of clinical activity in patients with relapsed or refractory B-cell lymphomas,3-6 including those refractory to rituximab7,8 and chemotherapy.9 More recently, several single-arm studies have demonstrated that upfront RIT administered either alone or with chemotherapy to previously untreated indolent non-Hodgkin's lymphoma (NHL) patients produces overall response rates of 90% to 100%, complete response rates of 60% to 95%, and durable remissions.10-13
Forms for Hospital Investigations
Authors: R. Law
Journal: BMJ (1972)

usually refers to the destruction of the fetus per se.But as Dr. Wilkinson points out, many doctors conscientiously consider the needs of the whole person, allowing for the possibility that these needs may conflict with the patient's immediate demands.In my view these two issues are not distinct from each other; the destruction of the fetus must rarely be compatible with the whole patient's needs.If a woman (in one way way or another) procures an abortion, this indicates that we, as doctors, relatives, or citizens, have been failing to help her.-Iam, etc.,
Studies on Transformations in Leukemic Cells of the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;
Authors: L. W. Law
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Studies on Transformations in Leukemic Cells of the Mouse Get access L. W. Law L. W. Law National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 817–836, https://doi.org/10.1093/jnci/15.3.817 Published: 01 December 1954
Commentary: Evidence on salt is consistent
Authors: M. Law
Journal: BMJ (1996)

A rise in blood pressure is not an inevitable consequence of aging. In some societies blood pressure remains at about 110/70 mm Hg throughout life.1 2 Dietary salt, low dietary potassium, alcohol, and body weight contribute to the increase in blood pressure with age in Western countries. The Intersalt study quantifies the effect of each of these factors while allowing for the others.1

The new Intersalt paper is a valuable addition to the evidence on salt and blood pressure.3 In the original Intersalt paper the different analyses on sodium and blood pressure varied, some suggesting a strong association, others a weaker one.1 Now the position has been clarified; all the Intersalt analyses confirm salt as an important determinant of blood pressure. The average increase in blood pressure with age (from 25 to 55 years) was greater in centres with higher sodium intake, by 10 mm Hg systolic for a 100 mmol/day higher …
Subclavian Vein Cannulation
Authors: David C. Law
Journal: JAMA (1967)

To the Editor:—  Drs. Schapiro and Stern's report of four complications during subclavian vein cannulation (201:327, 1967) adds to a growing list, which obviously reflects this procedure's increasing popularity. Before it is unconditionally condemned, however, certain points should be emphasized. The complications from any procedure will vary with the skill of the operator and with attention to detail and understanding of what is involved.  In this light it would be well for those who will be doing subclavian cannulations to spend an hour or so in the autopsy room with their needles and catheters, and observe exactly how much leeway they have during the procedure, especially in reference to the apex of the lung. It will be noted that once the needle begins its journey beneath the clavicale, failure to maintain a trajectory plane exactly parallel to the frontal plane of the body will indeed result in entry into
TREATMENT OF PELLAGRA WITH LACTIC ACID BACILLI
Authors: William Lamar Law
Journal: JAMA (1913)

The last five typical cases of pellagra in my practice have been treated with Bulgarian lactic acid bacilli in tablet form, each about 7½ grains. Two tablets were given half an hour before each meal and at bedtime. The improvement in the appearance and subjective symptoms of these patients warrants this preliminary report.
Book: Tacklin Inequalities: Where are we now and what can be done?
Authors: Catherine Law
Journal: BMJ (2001)

Eds C Pantazis, D Gordon 

Policy Press, £15.99, pp 250

ISBN 1 86134 146 6

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] 

Hot on the heels of evidence based medicine comes evidence based health policy, with a proliferation of articles and journals and the birth of academic centres and review facilities. Advocates of this movement cite a sizeable body of research that might inform or even determine policy and press for randomised trials of health policy interventions. Others argue that the current evidence base is wholly insufficient and that a wider range of methodologies needs to be considered. Evidence …

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Annals of the Rheumatic Diseases
Journal: Annals of the Rheumatic Diseases (2024)

to 71 years with rheumatoid arthritis (21), degenerative joint changes (30), or non-articular rheumatism (46), with "osadrin", a preparation consisting of equal parts of 1 :4-diphenyl-3 :5-dioxypyrazolidine and dimethyl- aminophenyldimethylpyrazolone with the addition of procaine hydrochloride.The average daily dose was 1 ampoule by injection or four to six tablets by mouth for 10 to 40 days.[The dose contained in each ampoule or tablet is not stated.]In a high proportion of cases a significant anti- rheumatic effect of the treatment was demonstrated locally by diminution of pain, muscular spasm, and exudation, and systemically by disappearance of fever and return to normal of the erythrocyte sedimentation rate.The preparation was well tolerated and there was no local tenderness after injection or gastric upset after oral administration.There was no water retention in spite of increased uric acid elimination.The authors state that their results confirm those of German workers who have been using osadrin for well over 5 years.Max Mayer.
Plant sterol and stanol margarines and health
Authors: M. Law
Journal: BMJ (2000)

A new polyunsaturated margarine with added plant stanols, Benecol, was introduced in several European countries last year, and a similar margarine with added plant sterols will be introduced under the Flora label later this year. These products lower serum concentrations of cholesterol, but they are expensive.1–14 In Great Britain the cost is about £2.50 ($4.00) for a 250 g tub compared with 60p for ordinary polyunsaturated margarine and 90p for butter. This article considers quantitatively the health aspects of adding plant sterols and stanols to margarines and other foods.

#### Summary points

Plant sterols and stanols reduce the absorption of cholesterol from the gut and so lower serum concentrations of cholesterol

Plant sterols or stanols that have been esterified to increase their lipid solubilitycan be incorporated into foods

The 2 g of plant sterol or stanol added to an average daily portion of margarine reduces serum concentrations of low density lipoprotein cholesterol by an average of 0.54 mmol/l in people aged 50-59, 0.43 mmol/l in those aged 40-49, and 0.33 mmol/l in those aged 30-39

A reduction in the risk of heart disease of about 25% would be expected for this reduction in low density lipoprotein cholesterol; this is larger than the effect that could be expected to be achieved by people reducing their intake of saturated fat

The added costs of £70 per person per year will limit consumption; however, if stanols and sterols become cheaper, their introduction into the food chain will make them an important innovation in the primary prevention of heart disease

Randomised trials included in this review were identified by a Medline search using the term “plant sterols.” Additional trials were identified from citations in these papers and in review articles. Other trials in children with familial hypercholesterolaemia were not included.

Sterols are an essential …
The Flexed-Tail-Anemia Gene (&lt;italic&gt;f&lt;/italic&gt;) and Induced Leukemia in Mice
Authors: L. W. Law
Journal: JNCI Journal of the National Cancer Institute (1952)

The Flexed-Tail-Anemia Gene (f) and Induced Leukemia in Mice L. W. Law L. W. Law National Cancer Institute2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar 2National Institutes of Health, Public Health Service, Federal Security Agency. Author Notes JNCI: Journal of the National Cancer Institute, Volume 12, Issue 5, April 1952, Pages 1119–1126, https://doi.org/10.1093/jnci/12.5.1119 Published: 01 April 1952 Article history Received: 23 January 1952 Published: 01 April 1952