tbuckley/cabot-search huggingface dataset:
Clinical outcome of germ cell cancer patients (pts) treated with high-dose chemotherapy with stem cell support (HDC) –a single center experience
Authors: E. G. Dos Santos, F. Leal-Da-costa, N. Miranda, A. Machado, A. Guimaraes, I. Ferreira, M. Abecasis, J. L. Passos-Coelho
Journal: Journal of Clinical Oncology (2004)

4724 Background: Pts with International Germ Cell Cancer Collaborative Group (IGCCCG) “poor prognosis” disease achieve only a 41% 5-year progression-free survival (PFS) with standard chemotherapy. Pts who do not achieve a complete remission with BEP chemotherapy or who relapse after such treatment have a still worse prognosis. The clinical impact of HDC in such pts is still unclear. Methods: Pts with germ cell cancer with IGCCCCG “poor prognosis” disease at diagnosis (or, earlier, with Indiana group C) or with recurrent or refractory (i.e., less than marker negative partial remission) disease after initial BEP chemotherapy were eligible for HDC. Results: Between June 1996 and April 2003, 18 pts underwent one (13 pts) or two (5 pts) cycles of HDC with ICE (ifosfamide 10g/m2, carboplatin 1,500mg/m2 and etoposide 2,400mg/m2); 17 pts), or etoposide (1500mg/m2) plus thiotepa (900 mg/m2); 1 pt), in 6 pts as consolidation after BEP and in 12 pts for recurrent disease (7 pts) or refractoriness to BEP (5 pts). In the consolidation group (6 pts), with a median follow-up of 42 months (range 10–72 months), there are no events. Thus the PFS and overall survival (OS) at 3.5 years is 100%. In contrast, with a median follow-up of 18 months, the median PFS and OS for pts with recurrent or refractory disease subgroup are 4 months (0–40+) and 18 months (4–40+), respectively. In this subgroup, 10 pts relapsed by 8 months post-HDC and only 2 are progression-free at 20 and 40 months. Conclusions: Despite the small number of pts and short follow-up, these results compare at least as favorably to the outcome obtained with standard chemotherapy in pts with “poor prognosis” at diagnosis. In contrast the outcome of pts with recurrent or refractory disease after initial BEP chemotherapy are not better than those obtained with standard salvage chemotherapy. No significant financial relationships to disclose.
Blood Coagulation in Pregnancy
Authors: Benjamin Alexander, Lillian Meyers, John Kenny, Robert Goldstein, Victor Gurewich, Lester Grinspoon
Journal: New England Journal of Medicine (1956)

ALTHOUGH thromboembolism has frequently been attributed to abnormal blood coagulation, convincing evidence for this concept has been lacking. The disclosure of hitherto unrecognized coagulation factors and the development of methods for their assay prompted re-examination of this question. Pregnancy was selected as the initial area of study because it constitutes a common, temporary, reversible, physiologic state that is too frequently complicated by thromboembolism. This report presents data indicating that during pregnancy abnormally high levels of at least one important clotting constituent do develop, returning to normal in most cases after term. It is proposed that these changes reflect a state . . .
Spontaneous Tumors in Germ-Free Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Morris Pollard, B. A. Teah
Journal: JNCI Journal of the National Cancer Institute (1963)

Three strains of germ-free rats were examined for evidence of spontaneous neoplasms. None was observed in germ-free rats derived from Fischer and Sprague-Dawley stock. Twenty-five tumors were recorded in germ-free rodents of Wistar strain origin, the majority of which involved the mammary gland.
Abstract P4-08-07: CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer
Authors: H Wright, M Motazedi, L Nelson, J Aulmoli, L Flanagan, O Razorenova
Journal: Cancer Research (2016)

Abstract Triple negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone, and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, CUB-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1). CDCP1 is phosphorylated by Src family kinases in its full-length and cleaved states, which is important for its pro-metastatic signaling. We observed that cCDCP1, compared to flCDCP1, induced a dramatic increase in phosphorylation of the migration-associated proteins: PKCδ, ERK1/2, and p38 MAPK in HEK 293T. In addition, only cCDCP1 induced migration of HEK 293T cells and rescued migration of the TNBC cell line, MDA-MB-231, expressing shRNA against CDCP1. Importantly, we found that only cCDCP1 is capable of dimerization, which can be blocked by expression of the extracellular portion of cCDCP1 (ECC), indicating that dimerization occurs through CDCP1's ectodomain. Furthermore, we found that ECC inhibited phosphorylation of PKCδ by Src and migration of TNBC cells, indicating that the cCDCP1 dimer is an important contributor to TNBC aggressiveness. These studies have important implications for development of a therapeutic to block CDCP1 activity and TNBC metastasis. Citation Format: Wright H, Motazedi M, Nelson L, Aulmoli J, Flanagan L, Razorenova O. CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative 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 P4-08-07.
Desmosomal junctions are necessary for adult sinus node function
Authors: Valeria Mezzano, Yan Liang, Adam T. Wright, Robert C. Lyon, Emily Pfeiffer, Michael Y. Song, Yusu Gu, Nancy D. Dalton, Melvin Scheinman, Kirk L. Peterson, Sylvia M. Evans, Steven Fowler, Marina Cerrone, Andrew D. McCulloch, Farah Sheikh
Journal: Cardiovascular Research (2016)

Current mechanisms driving cardiac pacemaker function have focused on ion channel and gap junction channel function, which are essential for action potential generation and propagation between pacemaker cells. However, pacemaker cells also harbour desmosomes that structurally anchor pacemaker cells to each other in tissue, but their role in pacemaker function remains unknown. To determine the role of desmosomes in pacemaker function, we generated a novel mouse model harbouring cardiac conduction-specific ablation (csKO) of the central desmosomal protein, desmoplakin (DSP) using the Hcn4-Cre-ERT2 mouse line. Hcn4-Cre targets cells of the adult mouse sinoatrial node (SAN) and can ablate DSP expression in the adult DSP csKO SAN resulting in specific loss of desmosomal proteins and structures. Dysregulation of DSP via loss-of-function (adult DSP csKO mice) and mutation (clinical case of a patient harbouring a pathogenic DSP variant) in mice and man, respectively, revealed that desmosomal dysregulation is associated with a primary phenotype of increased sinus pauses/dysfunction in the absence of cardiomyopathy. Underlying defects in beat-to-beat regulation were also observed in DSP csKO mice in vivo and intact atria ex vivo . DSP csKO SAN exhibited migrating lead pacemaker sites associated with connexin 45 loss. In vitro studies exploiting ventricular cardiomyocytes that harbour DSP loss and concurrent early connexin loss phenocopied the loss of beat-to-beat regulation observed in DSP csKO mice and atria, extending the importance of DSP-associated mechanisms in driving beat-to-beat regulation of working cardiomyocytes. We provide evidence of a mechanism that implicates an essential role for desmosomes in cardiac pacemaker function, which has broad implications in better understanding mechanisms underlying beat-to-beat regulation as well as sinus node disease and dysfunction.
A phase II evaluation of nab-paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: A Gynecologic Oncology Group (GOG) study.
Authors: R. L. Coleman, W. Brady, D. S. McMeekin, P. G. Rose, J. T. Soper, S. S. Lentz, J. S. Hoffman, M. S. Shahin
Journal: Journal of Clinical Oncology (2010)

5010 Background: Nab-paclitaxel (Abraxane, ABX) is a novel cremophor-free nanoparticle of albumin-stabilized paclitaxel, which has favorable efficacy and toxicity characteristics relative to other solvent-based taxanes, such as paclitaxel and docetaxel, and is currently approved for recurrent breast cancer. This is the first report of weekly abraxane in patients with recurrent ovarian, fallopian tube or peritoneal cancer (OC). Methods: Eligible patients had OC, that was persistent (n = 5) or progressed within 6 months of completion (n = 42) of primary platinum and taxane-based chemotherapy. All patients were required to have measurable disease, no prior therapy for recurrent disease and GOG performance status of ≤ 2. Treatment was ABX 100 mg/m2 days 1,8,15 on a 28-day schedule. The primary endpoint was RECIST response rate (RR), evaluated in a 2-stage design (with power of 0.90 for a RR of 25% and with alpha of 0.05 for RR of 10%). Results: 51 patients were enrolled, of which 47 are evaluable; median time from frontline therapy completion to registration was just 21 days. Patient demographics include median age: 59 (34-78) years, primary site ovary: 87%, serous histology: 72%, and high-grade: 81%. All patients had measurable disease, one prior chemotherapy regimen and prior surgery. Efficacy: partial response was confirmed in 11 patients (23%); 17 patients (36%) had stable disease. The median progression-free survival (PFS) was 4.5 months (95%CI: 2.1-6.7); overall survival was 17.4 months (95%CI: 12.5, not estimable). 17 patients (36%) had PFS > 6 months. Toxicity: there were no grade 4 events; grade 3 events were neutropenia (6), anemia (3), GI (2), metabolic (2), pain (2), and leukopenia (1); neurosensory toxicity was observed as grade 2: 5; and grade 3: 1. Conclusions: ABX appears to have substantial single-agent activity and to be tolerable in this cohort of highly refractory ovarian cancer patients previously treated with paclitaxel, and further investigation is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience
Case 29-2007
Authors: Edward T. Ryan, Suzanne L. Aquino, Richard L. Kradin
Journal: New England Journal of Medicine (2007)

A 51-year-old man was admitted to this hospital because of a pulmonary nodule. Helicobacter pylori infection had been diagnosed 5 years earlier, and a subtotal gastrectomy had been performed for adenocarcinoma of the gastric antrum and pylorus 2 years earlier. In the year before admission, pleuritic chest pain developed, and multiple pulmonary nodules and cysts were seen on computed tomography (CT). Two weeks before admission, a new pulmonary nodule was seen on follow-up CT. A diagnostic procedure was performed.
Progressive Chronic Lymphocytic Leukemia After Allogeneic Hematopoietic Cell Transplantation
Authors: Potjana Jitawatanarat, Arpita Desai, Pradeep Sharda, Hong Liu, Maureen Ross, Francisco J Hernandez-Llizaliturri, Philip L McCarthy, George L Chen
Journal: Journal of the National Comprehensive Cancer Network (2012)

This case report presents a patient with poor-prognosis chronic lymphocytic leukemia (CLL) who was treated with chemotherapy and underwent allogeneic hematopoietic cell transplant (alloHCT) but ultimately progressed. The application of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL and the impact of alloHCT on secondary therapy for progressive CLL are discussed.
<i>Your Golden Hair, Margarete</i>
Authors: Carrie A. Butt
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
Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials
Authors: John W. Kitchens, Diana V. Do, David S. Boyer, Desmond Thompson, Andrea Gibson, Namrata Saroj, Robert Vitti, Alyson J. Berliner, Peter K. Kaiser
Journal: Ophthalmology (2016)
Cancer Differentiating Agent Hexamethylene Bisacetamide Inhibits BET Bromodomain Proteins
Authors: Lisa M. Nilsson, Lydia C. Green, Somsundar Veppil Muralidharan, Dağsu Demir, Martin Welin, Joydeep Bhadury, Derek T. Logan, Björn Walse, Jonas A. Nilsson
Journal: Cancer Research (2016)

Abstract Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches are not generally effective in most malignancies. Compounds such as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce differentiation in experimental systems, but their mechanisms of action and potential range of uses on that basis have not been developed. Here, we show that HMBA, a compound first tested in the oncology clinic over 25 years ago, acts as a selective bromodomain inhibitor. Biochemical and structural studies revealed an affinity of HMBA for the second bromodomain of BET proteins. Accordingly, both HMBA and the prototype BET inhibitor JQ1 induced differentiation of mouse erythroleukemia cells. As expected of a BET inhibitor, HMBA displaced BET proteins from chromatin, caused massive transcriptional changes, and triggered cell-cycle arrest and apoptosis in Myc-induced B-cell lymphoma cells. Furthermore, HMBA exerted anticancer effects in vivo in mouse models of Myc-driven B-cell lymphoma. This study illuminates the function of an early anticancer agent and suggests an intersection with ongoing clinical trials of BET inhibitor, with several implications for predicting patient selection and response rates to this therapy and starting points for generating BD2-selective BET inhibitors. Cancer Res; 76(8); 2376–83. ©2016 AACR.
Recurrent Migraine and Intravenous Immune Globulin Therapy
Authors: Cristian S. Constantinescu, Andrew P. Chang, Leo F. McCluskey
Journal: New England Journal of Medicine (1993)

To the Editor: Headache during or after intravenous immune globulin infusion is a common side effect of this increasingly frequent treatment. Headache usually occurs with initial infusions, particularly when they are administered at fast rates, but may recur even with slower subsequent infusions. Frequently, these headaches are palliated with acetaminophen and diphenhydramine. Aseptic meningitis has been associated with recurrent intravenous-immune globulin-associated headaches1–3. We report on a patient in whom migraine developed after his first intravenous immune globulin treatment. Migraine recurred after the second treatment, and propranolol prevented subsequent treatment-associated headaches. A 45-year-old man had chronic inflammatory demyelinating polyradiculoneuropathy . . .
Monitoring Women at Risk for Preterm Labor
Authors: Donald C. Dyson, Karen H. Danbe, Judith A. Bamber, Yvonne M. Crites, D. Robin Field, Jeffrey A. Maier, Lawrence A. Newman, Deborah A. Ray, David L. Walton, Mary Anne Armstrong
Journal: New England Journal of Medicine (1998)

Preterm birth is a major cause of perinatal morbidity and mortality. Whether the rate of preterm birth can be reduced by frequent contact between nurses and pregnant women or home monitoring of uterine activity is not known.
Ethel Mary Reddie
Authors: Sandy Robertson
Journal: BMJ (2016)

Ethel Mary Reddie’s fellow students at UCL included John Wing and Robin Skynner. At that time she does not seem to have considered a future in psychiatry, but she recalled having lectures in psychology from Sir Cyril Burt.

Mary’s early medical career was interrupted by marriage and domestic commitments, and she worked in a variety of settings including general practice and child health. Having moved to the West Midlands in1966 with her architect husband, Graham, who was engaged in planning Redditch new town, she took up a clinical assistant post at Rubery Hill Hospital, where her duties included the electroconvulsive therapy department; which prompted her, she later said, to consider whether there might be other approaches to mental disorder. Having worked in several units in the Birmingham area—including the Midland Nerve Hospital, the John Connolly Hospital, …
Increased Incidence of Lymphoproliferative Disorder after Immunosuppression with the Monoclonal Antibody OKT3 in Cardiac-Transplant Recipients
Authors: Lode J. Swinnen, Maria R. Costanzo-Nordin, Susan G. Fisher, E. Jeanne O'Sullivan, Maryl R. Johnson, Alain L. Heroux, George J. Dizikes, Roque Pifarre, Richard I. Fisher
Journal: New England Journal of Medicine (1990)

A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation.
RTRB-18SALVAGE FRACTIONATED STEREOTACTIC RE-IRRADIATION (FSRT) FOR PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS PROGRESSED AFTER BEVACIZUMAB TREATMENT
Authors: Wenyin Shi, Joshua Siglin, joshua Palmer, Tu Dan, Maria Werner-wasik, Jon Glass, Lyndon Kim, Voichita Bar Ad, James Evans, Kevin Judy, Christopher Farrell, David Andrews
Journal: Neuro-Oncology (2015)

PURPOSE/OBJECTIVES: Bevacizumab is a commonly used treatment for patients with recurrent high grade glioma (HGG). However, patients who progress through bevacizumab is highly refractory to salvage chemotherapy. This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. MATERIALS/METHODS: Retrospective review was conducted of HGG patients received salvage FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, 1st recurrence, and re-irradiation, were utilized as study endpoints. Date of recurrence was defined as the date to radiographic evidence of progression. Univariate and multivariate analysis were performed. RESULTS: Among the 36 patients, 30 patients had glioblastoma, and 6 patients had anaplastic astrocytoma. There were 17 males and 19 females. The median age at recurrence was 56.5 years (range 37-74). The median Karnofsky Performance Status at recurrence was 80%. The median time from initial bevacizumab treatment to FSRT was 8.6 m (range 2.5 - 32.5 m). The median plan target volume for FSRT was 27.5 cc (range 4.2 - 162.3 cc). With a median follow up of 25.7 m, the overall survival of the patients since initial diagnosis was 25 m. The median overall survival since initiation of bevacizumab was 12 months. The median overall survival from FSRT was 5.1 m. FSRT treatment was well tolerated with no grade III or higher toxicity. CONCLUSIONS: Favorable outcomes were observed in patients with recurrent HGG received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for patients with recurrent HGG failed bevacizumab treatment.
Soundings: Getting about
Authors: Trisha Greenhalgh
Journal: BMJ (1998)

The average speed of commuter traffic in central London today is two miles an hour—the same as it was in 1910. This median value obscures the increasingly frequent experience of total gridlock for minutes, and occasionally hours, at a time. My university office is situated in one of several blocks on a shrinking NHS hospital site whose car park has been taken over by industrial plant “until further notice.” The surrounding streets sport red (not yellow) lines and menacing traffic wardens.

For all these reasons, I have given up driving to work. Since my morning responsibilities include the school run, I leave the car parked in tidy suburbia, outside the house of an old lady who used to watch darkly from behind her net curtains while I unloaded my folding bicycle from the boot. Now, having apparently excluded sinister motives, she gives me a cheerful wave every morning and has even, on occasion, come to the door to get a better look at the Brompton.

“Clever, that,” she remarks, as I deftly pull full sized seat, handlebars, pedals, wheels, lights, carrier, and suspension from the impossibly small black object I have just placed on the pavement. “I expect it’s Japanese.”

It’s British, actually, and the slick unfolding manoeuvre comes with practice. On my first attempt I managed to get both saddle and handlebars facing the wrong way and a misplaced brake cable hung disjointedly from the crossbar until a passing motorist stopped to help. The three mile trip into work now follows tree lined cycle paths on Hampstead Heath and takes 15 minutes, including repackaging the bike and filing it on the bottom shelf of my cupboard.

It is an encouraging sign of our times that folding cycles are currently enjoying the status of fashion accessory to the extent that at smart city centre venues, they meet with fewer disapproving glances than mobile phones and can be handed in at the cloakroom in exchange for a raffle ticket. At a recent committee meeting at BMA House, it was heartening to see no fewer than five similar machines lined up next to the briefcases.

Why is that so significant? Because if a critical mass of our negotiators has indeed discovered the folding cycle, it will shortly become a tax deductible item for us all.