tbuckley/cabot-search huggingface dataset:
Trilostane, an effective signal transduction inhibitor for advanced ER+ve and ER-ve post-menopausal breast cancer
Authors: R. Leonard, N. Bundred, A. Buzdar, P. Canney, D. Rea, A. Stewart, M. Verrill
Journal: Journal of Clinical Oncology (2004)

540 Background: Acquired endocrine resistance to both SERMs and AIs, is a major clinical problem and a leading cause of treatment failure in post menopausal women with advanced breast cancer. Trilostane (Modrenal) has been shown to modulate binding of estrogen to both estrogen receptor alpha (ERa) and estrogen receptor beta (ERβ) and block cell proliferation in breast cancer cells mediated through both ERE and AP1-dependent pathways. Methods: A total of 714 post-menopausal women with assessable progressing advanced breast cancer were treated with trilostane in eleven centers world-wide. All patients had received prior endocrine and/or chemotherapy. Results: Of the 714 patients, 616 (86%) were known or assumed to be ER+ and of these, 164 (27%) had an objective response (OR = CR + PR = 3 mths) and a further 65 (10%) had disease stabilisation (DS = 6 mths), giving an overall clinical benefit rate (CBR) of 37%. Within this ER+ cohort, 453 patients received trilostane for >12 weeks and achieved an OR of 36% and a CBR of 55%. In the ER- cohort (=15 fmol/mg cytosol protein), the CBR was 18% for all patients and 29% in those receiving trilostane for >12 weeks. Chemotherapy given prior to trilostane therapy affected the response rate: 42% (170/408) patients achieved a CBR with trilostane when previously exposed to other endocrine therapies only; compared to 25% (77/306) patients achieving a CBR with trilostane if previously treated with chemotherapy. Discussion: Trilostane is an effective endocrine agent in advanced breast cancer and, because of its unique mode of action, can also be used in patients with acquired endocrine resistance. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bioenvision Limited Bioenvision Limited
Urethral Metastasis from Prostatic Carcinoma as Diagnosed by Immunoperoxidase Technique using Prostate-Specific Antigen and Prostate-Specific Acid Phosphatase
Authors: E. Koh, K. Sekii, M. Namiki, H. Fujioka, K. Onoue, M. Sakurai, T. Sonoda
Journal: European Urology (1987)
Modulation of the Clonal Composition in Relapsed CLL: A Study Based on Targeted Deep-Sequencing of ATM, BIRC3, NOTCH1, POT1, SF3B1, SAMHD1 and TP53
Authors: Sabine Jeromin, Wolfgang Kern, Richard Schabath, Tamara Alpermann, Niroshan Nadarajah, Manja Meggendorfer, Susanne Schnittger, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2015)
Cadaver Exome Sequencing for Teaching First-Year Medical Students
Authors: Jon Cornwall, Andreas Winkelmann, Sabine Hildebrandt
Journal: JAMA (2016)

To the Editor Dr Gerhard and colleagues described the use of exome analysis of willed bodies to teach first-year medical students.1 Although we think the educational value of this approach is laudable, there are concerns about the ethical aspects of the method.
Splenectomy in Hemolytic Anemia
Authors: D M GROZDOV, M D PATSIORA
Journal: JAMA (1963)

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
The American Society of Clinical Oncology: change, growth, and rebirth.
Authors: R C Young
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.10.1757 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2120393 The American Society of Clinical Oncology: change, growth, and rebirth. R C YoungxR C YoungSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA 19111. https://doi.org/10.1200/JCO.1990.8.10.1757 First Page PDF © 1990 by American Society of Clinical Oncology
Abstract 4397: Preclinical development of a novel hypoxia-activated EGFR inhibitor using a cobalt(III)-based prodrug design
Authors: Petra Heffeter, Claudia Karnthaler-Benbakka, Diana Groza, Kushtrim Kryeziu, Walter Berger, Bernhard K. Keppler, Christian R. Kowol
Journal: Cancer Research (2015)

Abstract Chemotherapy and therapy with small targeted molecules are two major strategies for therapy of human cancer at the disseminated stage. During the last decades, thousands of compounds have been developed and, consequently, have improved therapy effectiveness. Especially the development of receptor tyrosine kinase inhibitors such as erlotinib or imatinib were major step forwards in cancer treatment. However, despite its success EGFR inhibitor therapy is still limited by strong side effects, resistance development and insufficient tumor accumulation. Aim of the here presented study was the development of novel EGFR inhibitors, which are specifically activated in the malignant tissue. To this end a cobalt(III)-based prodrug strategy was used, which allows targeted release of the active EGFR inhibitor triggered by hypoxic conditions of the solid tumor. As a first step, new inhibitors with bis-chelating moieties were prepared and tested for their efficacy against several cell models with differing EGFR status. The most promising lead candidate was selected based on potent kinase inhibition (confirmed by in vitro kinase assays as well as Western blotting) resulting in activity against EGFR-driven cells in the nM range (MTT assay). Subsequently, the respective cobalt complex was prepared and its activity tested in hypoxia vs. normoxia revealing that the new complex was distinctly more active under hypoxic conditions. Finally, the anticancer activity of the new complex was tested in two xenografts indicationg potent and hypoxia-dependent anticancer activity also in vivo. Summarizing, cobalt(III)-based tumor-targeting represents a promising strategy to reduce the side effects of tyrosine kinase inhibitors such as erlotinib. Acknowledgements. This work was performed in course of the research platform “Translational Cancer Therapy Research” Vienna, Austria and the COST action CM1105 and supported by “Fonds der Stadt Wien für innovative interdisziplinäre Krebsforschung”. Citation Format: Petra Heffeter, Claudia Karnthaler-Benbakka, Diana Groza, Kushtrim Kryeziu, Walter Berger, Bernhard K. Keppler, Christian R. Kowol. Preclinical development of a novel hypoxia-activated EGFR inhibitor using a cobalt(III)-based prodrug design. [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 4397. doi:10.1158/1538-7445.AM2015-4397
Case 25-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, H. Richard Tyler, Robert E. Scully
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. A 32-year-old man entered the hospital because of visual impairment.At the age of 18 years a duodenal ulcer developed, and six years later a partial gastrectomy was performed. Four years before admission hematemesis occurred. He was admitted to another hospital, where he recovered; no source of bleeding was found. Four months before admission he noticed loss of libido and impotence. During the next few months he became aware of diminished growth of facial and pubic hair and experienced intolerance of cold, increased thirst and polyuria. One month before entry there was the onset . . .
Single center experience of 90Y-Ibritumomab tiuxetan in the older population with non-hodgkin lymphoma.
Authors: Vaibhav Agrawal, Jose Isaac Castillo, Kelly Raup, Treanna Girton, Scott R. Collins, James O. Brady, Sharif S. Khan, Joseph Vadakara
Journal: Journal of Clinical Oncology (2016)

e19035 Background: 90Y-Ibritumomab tiuxetan (90Y-IT) as radioimmunotherapy in the treatment of B-cell non-Hodgkin lymphoma (NHL) has been approved for consolidation and salvage treatment of follicular and indolent lymphoma. It has also been studied in the treatment of diffuse large B-cell and mantle cell lymphoma. Toxicities primarily include myelosuppression with a risk of treatment-associated myelodysplastic syndrome (MDS). Methods: Retrospective cohort analysis of patients with B-cell NHL who received 90Y-IT from 2010 to 2015 at Geisinger Medical Center. Results: Sixty-five patients with NHL received 90Y-IT at median age of 68 years (range 32-91), 32 (49.2%) patients were male, and 36 (55.8%) were older than 65 years of age. Thirty patients (46.1%) had aggressive NHL and 37 (56.9%) had stage III/IV disease. Twenty-nine (44.6%) patients received > 1 line of treatment prior to 90Y-IT therapy and 62 (97%) received Rituximab based regimens. No patient received fludarabine based therapy. The median follow-up period was 16 months (range 4-68). The overall response rate was 89.2% with a PR-to-CR conversion rate of 36%. The response rate was 55% in the salvage setting. The median PFS and OS were 12 and 15 months, respectively. Patients on Rituximab maintenance (21.5%) had PFS and OS improvement (p < 0.0001). There was no significant difference in PFS and OS between patients younger and older than 65 years of age or between patients in CR and not in CR at the time of 90Y-IT. Patients not in CR at the time of 90Y-IT were responsive to Rituximab maintenance: PFS improved from median 10 to 48 months (p < 0.0001) and OS improved from median 14 to 53 months (p = 0.0003). Among patients with grade 3/4 hematologic toxicities, 6 patients required blood transfusion, 4 needed platelet transfusion, and 17 (26.1%) received pegfilgastrim. One patient required hospitalization for febrile neutropenia. Seven patients relapsed after 90Y-IT and one patient (1.5%) developed MDS (del 5q, del 20q). Conclusions: This is one of the largest reported single-center experience of 90Y-IT administered to a predominantly elderly population with B-NHL in the United States. This study demonstrates the safety and feasibility of 90Y-IT with manageable toxicity.
I-SPY 2 — Toward More Rapid Progress in Breast Cancer Treatment
Authors: Lisa A. Carey, Eric P. Winer
Journal: New England Journal of Medicine (2016)

Clinical trials of systemic therapy for operable breast cancer are evolving. Our understanding of breast cancer as a family of biologically distinct diseases has implications for patient selection and the optimization of drug choices. In addition, there is a growing dissatisfaction with trials of adjuvant therapy that are large, take many years to complete, and often result in very small improvements in outcome. For these reasons, we must be thoughtful and rigorous in focusing the testing of promising agents in patients who could derive a meaningful benefit. These realities are in part responsible for the explosion of "neoadjuvant," or preoperative, . . .
High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers
Authors: Michael Hettich, Friederike Braun, Mark D. Bartholomä, Reinhold Schirmbeck, Gabriele Niedermann
Journal: Theranostics (2016)

Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology.We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice.ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes).Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant.Under pathophysiological conditions, strong expression of the receptor/ligand pair was also found in non-lymphoid tissues.Both were specifically detected in malignant tumors.PD-1 was readily detected after combined immunoradiotherapy causing massive tumor infiltration by PD-1+ lymphocytes.PD-L1 tracer uptake was reduced in PD-L1 knockout tumors.Moreover, monitoring the expression changes of PD-L1 in response to its main inducer, the effector T cell cytokine IFN-γ, revealed robust upregulation in the lung.This suggests that T cell responses in the lung, a vital organ continuously exposed to a variety of antigens, are strongly restrained by the PD-1 checkpoint.In turn, this could explain the association of PD-1 checkpoint inhibition with potentially fatal immune-mediated pneumonitis and partially also its efficacy in lung cancer.
Association of Loss of Independence With Readmission and Death After Discharge in Older Patients After Surgical Procedures
Authors: Julia R. Berian, Sanjay Mohanty, Clifford Y. Ko, Ronnie A. Rosenthal, Thomas N. Robinson
Journal: JAMA Surgery (2016)

Older adults are at increased risk for adverse events after surgical procedures. Loss of independence (LOI), defined as a decline in function or mobility, increased care needs at home, or discharge to a nonhome destination, is an important patient-centered outcome measure.To evaluate LOI among older adult patients after surgical procedures and examine the association of LOI with readmission and death after discharge in this population.This retrospective cohort study examined 9972 patients 65 years and older with known baseline function, mobility, and living situation undergoing inpatient operations from January 2014 to December 2014 at 26 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program Geriatric Surgery Pilot Project. A total of 4895 patients were excluded because they were totally dependent, classified as class 5 by the American Society of Anesthesiologists, undergoing orthopedic or spinal procedures, or died prior to discharge.Loss of independence at time of discharge.Readmission and death after discharge.Of the 5077 patients included in this study, 2736 (53.9%) were female and 3876 (76.3%) were white, with a mean (SD) age of 75 (7) years. For this cohort, LOI increased with age; LOI occurred in 1386 of 2780 patients (49.9%) aged 65 to 74 years, 1162 of 1726 (67.3%) aged 75 to 84 years, and 479 of 571 (83.9%) 85 years and older (P < .001). Readmission occurred in 517 patients (10.2%). In a risk-adjusted model, LOI was strongly associated with readmission (odds ratio, 1.7; 95% CI, 1.4-2.2) and postoperative complication (odds ratio, 6.7; 95% CI, 4.9-9.0). Death after discharge occurred in 69 patients (1.4%). After risk adjustment, LOI was the strongest factor associated with death after discharge (odds ratio, 6.7; 95% CI, 2.4-19.3). Postoperative complication was not significantly associated with death after discharge.Loss of independence, a patient-centered outcome, was associated with postoperative readmissions and death after discharge. Loss of independence can feasibly be collected across multiple hospitals in a national registry. Clinical initiatives to minimize LOI will be important for improving surgical care for older adults.
Marking Time in the Global HIV/AIDS Pandemic
Authors: Gerald Friedland
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
Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low‐level summer sunlight exposures
Authors: S.J. Felton, M.S. Cooke, R. Kift, J.L. Berry, A.R. Webb, P.M.W. Lam, F.R. Gruijl, A. Vail, L.E. Rhodes
Journal: British Journal of Dermatology (2016)

The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown.This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults.Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage.Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR.Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.
165P Neutropenia as a predictive factor in patients with metastatic colorectal cancer treated with TAS-102
Authors: S. Hamauchi, K. Yamazaki, T. Masuishi, Y. Kito, A. Komori, T. Tsushima, A. Todaka, T. Yokota, N. Machida, A. Fukutomi, Y. Onozawa, K. Muro, H. Yasui, K. Mori, H. Taniguchi
Journal: Annals of Oncology (2015)
Case 46-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1982)

Presentation of Case A 42-year-old right-handed woman was admitted to the hospital because of headaches and papilledema. There was a 20-year history of bilateral frontal headaches, which radiated to the occiput. Six months before admission frontal and occasionally parietal or occipital headaches became more frequent. They began at any time of day and were occasionally present on waking. She sometimes had nausea and vomiting in the morning, without definite relation to headaches and associated at times with emotional stress. For several months before entry she noticed intermittent horizontal diplopia on watching television. She also began to experience bouts of blanking . . .
PD6-2-7: A single institutional experience of thymic epithelial tumors over 11 years: clinical features and outcome and implications for future management
Authors: Seung Tai Kim, Hee-Sung Lee, Jin Seok Ahn, Jeeyun Lee, Yong-Chan Ahn, Myung-Ju Ahn, Kwhanmmien Kim, Young Mog Shim, Jhingook Kim, Keunchil Park
Journal: Journal of Thoracic Oncology (2007)
Chickenpox and steroid cards
Authors: D. Calland, N. Scriven
Journal: BMJ (1996)

whether these compounds accumulate during low or high ozone episodes and, if they do, whether they are of clinical relevance.Jon G Ayres is concerned that there was in- sufficient adjustment for other confounding meteorological factors and critically black smoke or particulate matter.In fact, relative humidity, wind speed, barometric pressure, and sunshine hours were examined in the statistical models, but for reasons of editorial brevity these data were not included in the paper.The effect of ozone was not appreciably altered.