tbuckley/cabot-search huggingface dataset:
Higher occurrence of childhood cancer in families with germline mutations in BRCA2, MMR, and CDKN2A genes
Authors: H. Olsson, S. Magnusson, Å. Borg, M. Nilberth, T. Wiebe, U. Kristoffersson
Journal: Journal of Clinical Oncology (2008)

11043 Background: The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast/ovarian cancer, DNA-mismatch repair (MMR) genes associated hereditary non polyposis colorectal cancer and CDKN2A associated familial malignant melanoma are very little studied. Herein we report the prevalence of childhood tumors (diagnosed ≤ 18 years of age) in families identified with mutation in the BRCA1/2, MMR and CDKN2A genes. Methods: Using pedigrees at the Regional Oncogenetic Clinic at Lund University Hospital, the prevalence of childhood cancer was estimated in families with mutations in the BRCA1 (n=98), BRCA2 (n=43) MMR (MLH1, MSH2 MSH6) (n=31) and CDKN2A (n=15) genes in comparison with population based control families (n=854). Family trees were expanded and data were matched to population based census, cancer and mortality registries. Results: Compared with the control group, a significantly higher prevalence of childhood cancer was found in families with mutations in BRCA2 (9.3 % vs. 0.8 % p=0.001), MMR genes (19.4 % vs. 0.8 % p <0.001) and CDKN2A (20.0 % vs. 0.8 % p <0.001), but not in families with BRCA1 mutations (1.0 % vs. 0.8 % p=0.6). Further analyses showed an increased risk for childhood tumors in families with mutations in BRCA2 (OR 12.4; 95 % CI 3.5–44.1), MMR genes (OR 29.0; 95% CI 9.1–92.6), and CDKN2A (OR 30.2; 95 % CI 7.0–131.1). Conclusions: This study suggests that the risk for childhood tumors is increased in families with germline mutations in the BRCA2, MMR and CDKN2A genes. We are presently trying to confirm the mutation status of the children. No significant financial relationships to disclose.
Effect of Aldosterone Antagonist (Spironolactone) on Patients with Severe Congestive Heart Failure
Authors: B M CARRUTHERS, R D LEDRAY, M SERAGLIA, H W MCINTOSH, G C WALSH
Journal: JAMA (1963)

Spironolactone was evaluated as a diuretic in the therapy of six patients with chronic severe congestive heart failure, during which metabolic balance studies were performed. Two of the patients showed a clear-cut although moderate diuresis and natriuresis in response to spironolactone in the presence of other diuretics. Two patients had slight unsustained responses and two showed no response. No significant change in potassium excretion was observed. A decrease in the serum sodium level was noted in four patients, associated with a rise in serum potassium. Urinary aldosterone excretion was normal or low in all patients and showed no correlation with the diuretic response to spironolactone.It is concluded that spironolactone has definite but limited usefulness in the therapy of some but not all patients with chronic congestive heart failure.
Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas
Authors: Melinda S. Merchant, Donna Bernstein, Martha Amoako, Kristin Baird, Thomas A. Fleisher, Michel Morre, Seth M. Steinberg, Marianna Sabatino, Dave F. Stroncek, Aradhana M. Venkatasan, Bradford J. Wood, Matthew Wright, Hua Zhang, Crystal L. Mackall
Journal: Clinical Cancer Research (2016)

Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. ©2016 AACR.
Progress Toward Poliomyelitis Eradication—India
Journal: JAMA (1996)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants
Authors: Michael R. Perkin, Kirsty Logan, Anna Tseng, Bunmi Raji, Salma Ayis, Janet Peacock, Helen Brough, Tom Marrs, Suzana Radulovic, Joanna Craven, Carsten Flohr, Gideon Lack
Journal: New England Journal of Medicine (2016)

The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy.We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age.In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe.The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.).
Exploratory outcome analyses according to stage and residual disease in the ICON7 trial of front-line carboplatin/paclitaxel (CP) ± bevacizumab (BEV) for ovarian cancer (OC).
Authors: Antonio Gonzalez-Martin, Amit M. Oza, Andrew C. Embleton, Jacobus Pfisterer, Jonathan A. Ledermann, Eric Pujade-Lauraine, Gunnar Kristensen, Monique A Bertrand, Philip James Beale, Andres Cervantes-Ruiperez, Emma Kent, Richard S. Kaplan, Mahesh M K Parmar, Nana Scotto, Lada Mitchell, Timothy Perren
Journal: Journal of Clinical Oncology (2015)

5548 Background: In ICON7, progression-free survival (PFS) was significantly improved in patients (pts) receiving BEV with front-line CP and continued as a single agent [Perren 2011] but no overall survival (OS) difference was detected in the intent-to-treat (ITT) population. Front-line BEV-containing therapy is approved in Europe for pts with stage IIIB–IV OC. Methods: In ICON7, pts with advanced (stage IIB–IV) or high-risk early-stage (stage I–IIA and clear cell/grade 3) OC were randomized to receive 6 cycles of CP either alone or with BEV 7.5 mg/kg q3w followed by single-agent BEV for a further 12 cycles (total duration 12 months). The primary endpoint was PFS; OS was a secondary endpoint. A post hoc exploratory analysis of subgroups defined by stage and extent of residual disease at diagnosis within the label population was performed. Results: The PFS benefit from BEV observed in the ITT population was seen consistently in all subgroups explored. As in the ITT population, no OS difference was seen in any subgroup except the previously defined 'high-risk' subgroup. Safety results in subgroups were in line with the overall population. Conclusions: Adding BEV to CP improves PFS irrespective of stage/residual disease. In pts with stage III >1 cm/IV OC this translates into an OS benefit. No OS difference (benefit or detriment) was seen in other subgroups explored. Clinical trial information: NCT00483782. PFSa OSb CP CP + BEV CP CP + BEV 'High-risk' subgroup (stage III >1 cm/IV) (N=502) No. of events/pts (%) 214/254 (84) 204/248 (82) 174/254 (69) 158/248 (64) HR (95% CI) 0.71 (0.58–0.86) 0.78 (0.63–0.97) Stage IIIB–IV, 0 cm residuum (N=411) No. of events/pts (%) 118/203 (58) 110/208 (53) 74/203 (36) 80/208 (38) HR (95% CI) 0.77 (0.59–0.99) 1.03 (0.75–1.41) Stage IIIB–IV, visible residuum (N=749) No. of events/pts (%) 295/370 (80) 310/379 (82) 246/370 (66) 242/379 (64) HR (95% CI) 0.81 (0.69–0.95) 0.87 (0.73–1.04) All stage IIIB–IV (N=1160) No. of events/pts (%) 413/573 (72) 420/587 (72) 320/573 (56) 322/587 (55) HR (95% CI) 0.81 (0.70–0.92) 0.92 (0.79–1.08) HR = hazard ratio, unstratified aData cutoff 30 Nov 2010 (median follow-up 28 months) bData cutoff 31 Mar 2013 (median follow-up 49 months)
Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk
Authors: Jonathan C. Hsu, Thomas M. Maddox, Kevin F. Kennedy, David F. Katz, Lucas N. Marzec, Steven A. Lubitz, Anil K. Gehi, Mintu P. Turakhia, Gregory M. Marcus
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. <h3>Objective</h3> To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. <h3>Design, Setting, and Participants</h3> Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS<sub>2</sub>score and the CHA<sub>2</sub>DS<sub>2</sub>-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. <h3>Main Outcomes and Measures</h3> The primary outcome was prescription of an OAC with warfarin sodium or a non–vitamin K antagonist OAC. <h3>Results</h3> The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS<sub>2</sub>score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172;<i>P</i> &lt; .001) and the CHA<sub>2</sub>DS<sub>2</sub>-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169;<i>P</i> &lt; .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS<sub>2</sub>score exceeding 3 or a CHA<sub>2</sub>DS<sub>2</sub>-VASc score exceeding 4. <h3>Conclusions and Relevance</h3> In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS<sub>2</sub>score and CHA<sub>2</sub>DS<sub>2</sub>-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription.
Ribosomal DNA Spacer Variation in the Cactophilic Yeast Clavispora opuntiae
Authors: Marc-Andre Lachance
Journal: Molecular Biology and Evolution (1990)

The rDNAs of 125 isolates of the haploid, heterothallic, cactophilic yeast Clavispora opuntiae collected worldwide were mapped with 12 restriction endonucleases.Thirty distinct repetypes were identified, and, with the exception of a single strain which had a unique restriction site in its large subunit coding region, the variation was confined to the intergenic spacer.The majority of the restriction sites were randomly assorted with respect to the mating-type alleles, indicating that sexual exchange within that facultatively outbreeding yeast species has been significant over evolutionary time.The restriction sites were also generally free of associations among one another, suggesting that rDNA homogenization has been intense and has favored the fixation of recombinant repetypes.Occasional associations or exclusions among sites or between sites and the mating types were attributed either to sampling bias or to recent introductions, in which the effects of random mating are overshadowed by founder effects.One intergenic spacer repetype was broadly dominant in yeasts isolated from cacti with a recent history of deliberate infestation with the moth Cactoblastis cactorum for biological control purposes.Human activity can thus be held accountable for a worldwide redistribution of yeast genotypes in this case.1.
On Wasted Radiation and the Interpretation of Experiments With Chronic Irradiation&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: R. H. Mole
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article On Wasted Radiation and the Interpretation of Experiments With Chronic Irradiation Get access R. H. Mole R. H. Mole Medical Research Council's Radiobiological Research Unit, Atomic Research Establishment, Harwell, Berks, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 907–914, https://doi.org/10.1093/jnci/15.4.907 Published: 01 February 1955 Article history Received: 18 October 1954 Published: 01 February 1955
Breast MRI after mammography detects additional aggressive cancers, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Magnetic resonance imaging (MRI) of the breast detects larger and potentially more aggressive cancers than those found on mammography, shows a study of women with newly diagnosed breast cancer.1

Breast MRI is the most sensitive imaging technique for detecting breast cancer and is used in screening high risk patients and for presurgical planning. But its role in looking for additional disease in women with diagnosed breast cancer is unclear because of uncertainty about the clinical significance of multicentric cancers …
Abstract 4781: A comprehensive screen for protein kinases involved in histone phosphorylation using a biochemical in-vitro approach
Authors: Daniel Mueller, Frank Totzke, Constance Ketterer, Christian Beisenherz-Huss, Diane Krämer, Thomas Weber, Carolin Heidemann-Dinger, Michael H.G. Kubbutat
Journal: Cancer Research (2015)

Abstract Gene expression is regulated by multiple mechanisms. The structure of the chromatin has been identified as one major regulator of gene expression. Histone proteins constitute the core of the nucleosomal particles, which are essential for structuring the DNA into chromatin. Various post-translational modifications of histones mainly in the N-terminal region of these proteins will compact or loosen the chromatin which in turn changes the accessibility of the DNA. Such histone modifications like methylation, acetylation and phosphorylation can therefore result either in activation or in repression of the transcription of the respective genes, depending on the specific amino acid residues modified. While histone-acetylases and histone-methyl-transferases as well as their corresponding counterparts, histone-deacetylases and histone-demethylases, are currently in the focus of epigenetic research, it is also well documented that histones are extensively modified and regulated by phosphorylation. In order to identify protein kinases able to phosphorylate histones we have generated a series of N-terminal peptides of human histone proteins H1, H2A, H2B, H3 and H4 as well as recombinant histone proteins. In a biochemical in-vitro activity assay (“KinaseFinder”) we tested these peptides and proteins as potential substrates against a panel of 339 recombinant human serine-threonine- and tyrosine-kinases. The results of the screens will be presented showing different protein kinases able to phosphorylate various histones in vitro. Additional data of approaches to verify and to characterize hit kinases, e.g. with respect to the specific target amino acid sequences, will be shown. Citation Format: Daniel Mueller, Frank Totzke, Constance Ketterer, Christian Beisenherz-Huss, Diane Krämer, Thomas Weber, Carolin Heidemann-Dinger, Michael H.G. Kubbutat. A comprehensive screen for protein kinases involved in histone phosphorylation using a biochemical in-vitro approach. [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 4781. doi:10.1158/1538-7445.AM2015-4781
Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial
Authors: Sameer A Pathan, Biswadev Mitra, Lahn D Straney, Muhammad Shuaib Afzal, Shahzad Anjum, Dharmesh Shukla, Kostantinos Morley, Shatha A Al Hilli, Khalid Al Rumaihi, Stephen H Thomas, Peter A Cameron
Journal: The Lancet (2016)
Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring
Authors: Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2016)

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL1 fusion oncogene, which in turn translates into a BCR-ABL oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib are approved by the United States Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second-line options include second and third generation TKIs. Although second and third generation TKIs are potent and selective TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR-ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP who have failed at least two TKIs, and for all patients in advanced phase disease.
Diethylnitrosamine-Induced Pancreatic Neoplasms in the Fish &lt;italic&gt;Rivulus ocellatus marmoratus&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A Thiyagarajah, J M Grizzle
Journal: JNCI Journal of the National Cancer Institute (1986)

Diethylnitrosamine [(DEN) CAS: 55-18-5] caused neoplasms of the exocrine pancreas in rivulus, Rivulus ocellatus marmoratus, a self-fertilizing hermaphroditic fish, after a single exposure to 810, 270, or 130 mg DEN/liter or after a continuous exposure to 50, 17, or 9 mg DEN/liter. Rivulus developed pancreatic adenomas after a single exposure. After continuous exposure, pancreatic adenomas, cystadenomas, and adenocarcinomas developed. Adenocarcinoma developed in fish first exposed as larvae but not in those first exposed as juveniles. Adenocarcinoma of pancreatic or biliary origin invaded the intestinal muscularis layer and mucosa. Dedifferentiation of acinar cells preceded the formation of adenomas, and atypical acinar cells formed parts of some of the ductlike structures in the pancreatic neoplasms.
Studies of a Melanoma Tumor-Associated Antigen Detected in the Spent Culture Medium of a Human Melanoma Cell Line by Allogeneic Antibody. III. Physicochemical Properties23
Authors: Rishab K. Gupta, Donald L. Morton
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Studies of a Melanoma Tumor-Associated Antigen Detected in the Spent Culture Medium of a Human Melanoma Cell Line by Allogeneic Antibody. III. Physicochemical Properties Get access Rishab K. Gupta, Rishab K. Gupta Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald L. Morton Donald L. Morton Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 72, Issue 1, January 1984, Pages 83–92, https://doi.org/10.1093/jnci/72.1.83 Published: 01 January 1984 Article history Received: 14 March 1983 Accepted: 26 July 1983 Published: 01 January 1984