tbuckley/cabot-search huggingface dataset:
Abstract P3-14-11: Gene-expression analyses identify altered transcription factors and supports the antitumor activity of novel bromodomain inhibitors in triple negative breast cancer
Authors: A Ocana, J Perez-Peña, G Serrano-Heras, V Corrales-Sanchez, JC Montero, MJ Gascón-Escribano, MG Picazo, DC García-Olmo, M Martin, A Pandiella
Journal: Cancer Research (2016)

Abstract Introduction: Identification of novel therapeutic targets in triple negative breast cancer (TNBC) is a main goal. In silico evaluation of human tumors by gene expression analyses can identify functions that could be pharmacologically inhibited. BET bromodomain inhibitors are a new family of compounds that reduce activity of oncogenic transcription factors through the inhibition of bromodomains. Material and methods: We performed gene expression and functional analyses comparing triple negative tumors with normal breast samples. RT-PCR was used to evaluate genes down-regulated by treatment with the BET bromodomain inhibitors JQ1 and OTOX15 at different time points in MDA-MB231 cells. Cell proliferation and colony growth was measured by MTT uptake and 3D growth in matrigel in a panel of cell lines including HS578T, BT549, MDA-MB231 and HCC3153 treated with JQ1 and OTOX15. Evaluation of apoptosis and cell cycle was performed by flow cytometry using Annexin V and propidium iodide, respectively. Western-blot was used for evaluation of protein expression. Xenografted animals were used for the assessment of the in vivo activity of JQ1. Results: Gene expression analyses identified upregulated genes including a number of transcription factors. These genes were more expressed in MDA-MB231 compared with MCF-10A. Treatment with JQ1 reduced the expression of some transcription factors at different time points. JQ1 and OTX015 reduced proliferation and cell growth in a panel of triple negative cell lines. They also led to arrest at the G0/G1 phase in HS578T and MDA-MB231 at 12 and 24 hours; that was confirmed by the biochemical evaluation of cell cycle mediators. An induction of apoptosis was observed at 48 hours in HS578T. JQ1 at 50 mg/kg daily reduced tumor growth in MDA-MB231 xenografted in nude mice. Conclusion: Gene-expression profiling identified upregulated transcription factors in triple negative tumors compared with normal breast human samples. BET bromodomain inhibitors reduced the expression of some of these genes in cellular models. JQ1 shows clear antitumor activity in vitro and in vivo. Citation Format: Ocana A, Perez-Peña J, Serrano-Heras G, Corrales-Sanchez V, Montero JC, Gascón-Escribano MJ, Picazo MG, García-Olmo DC, Martin M, Pandiella A. Gene-expression analyses identify altered transcription factors and supports the antitumor activity of novel bromodomain inhibitors in 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 P3-14-11.
Consistent <i>TP53</i> mutations in <i>BRCA1</i> and sporadic basal-like breast tumors, while infrequent in luminal <i>BRCA1</i> tumors.
Authors: E Manié, A Vincent-Salomon, J Lehmann-Che, G Pierron, E Turpin, M Warcoin, N Gruel, I Lebigot, X Sastre-Garau, O Delattre, H de Thè, D Stoppa-Lyonnet, M Stern
Journal: Cancer Research (2009)

Abstract Abstract #4070 Breast tumors with a germline mutation of BRCA1 (BRCA1 tumors) and Basal-Like Carcinoma (BLC) have been shown to be associated with a high rate of TP53 mutations. Because it has also been shown that BRCA1 tumors frequently display a basal-like phenotype, we sought to determine whether TP53 mutations were correlated to the hereditary BRCA1 mutated status or to the particular histological type of these tumors. We first explored the status of the TP53 gene in a series of 28 BRCA1 BLCs using immunohistochemistry, direct sequencing of the coding sequence, and functional assay in yeast (FASAY), and compared it to the status of TP53 in 27 series of sporadic (non hereditary) BLCs. With this sensitive approach, TP53 was found consistently mutated in BRCA1 (28/28) and sporadic (26/27) BLCs. However, mutation spectrum was different, in particular with a much higher rate of insertion/deletion in BRCA1 BLCs (12/27) than in the sporadic group (2/25). Secondly, we analyzed the incidence of TP53 mutations in 10 BRCA1 luminal tumors, using the same strategy. Surprisingly, only 3 of these 10 tumors were mutated, a frequency similar to that found in matched sporadic luminal tumors. In conclusion, TP53 mutation is a mandatory event in BRCA1 or sporadic BLCs, but not a common feature of BRCA1 luminal tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4070.
Patterns of care and outcomes in patients with intracranial hemangiopericytomas: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: M. A. Dankwah-Quansah, P. Gutin, M. Bilsky, J. Huse, M. Rosenblum, L. E. Abrey, L. DeAngelis, A. Omuro
Journal: Journal of Clinical Oncology (2009)

e13011 Background: Intracranial hemangiopericytomas are rare primary brain tumors with a tendency to metastasize. Available literature is restricted to small series of patients, and little is known regarding optimal clinical management and disease course, particularly in the targeted therapy era. Methods: Retrospective review of all patients with intracranial hemangiopericytoma seen at MSKCC from January 1, 1990 to December 31, 2008. Patients were included if histology was reviewed at MSKCC, and if clinical information was deemed sufficient for the analysis. Results: A total of 32 patients met inclusion criteria. The median age was 43 (range 24–68), median KPS was 80 (range 70–100), 17 were women. Disease was metastatic at presentation in only one patient. Initial treatment consisted of surgical resection in all patients (gross total resection: 14 patients, partial resection: 7, equivocal/unknown extent of surgery: 11). Adjuvant radiotherapy following surgery was given to 21 patients. The median progression-free survival was 65 months; median overall survival was 153 months and the 15-year survival was 48%. Treatment for recurrence included re-resection in 19 patients, additional radiotherapy in 17, and chemotherapy in 10. Regimens used included cytotoxic chemotherapy (6 patients) and targeted therapy (sorafenib: 3 patients; sunitinib: 3; imatinib: 2; erlotinib: 1; sirolimus: 1; bevacizumab: 1). Stable disease was the best observed response to these agents. Metastatic sites throughout disease course included lungs in 7 patients, bone in 10, liver in 3 and chest wall in 2. Immunohistochemistry and molecular analyses are ongoing and updated results will be presented. Conclusions: Hemangiopericytomas can be associated with late recurrences, even in patients completely resected and irradiated. Salvage treatment with surgery and radiotherapy seems effective, although the efficacy of chemotherapy remains to be determined. Given the slow growth rates, the meaning of stable disease while on chemotherapy is uncertain. Several patients in this series received agents targeting PDGFR or VGFR pathways, but such strategies need to be investigated further. No significant financial relationships to disclose.
ATNT-19TUMOR TREATING FIELDS WITH CHEMOTHERAPY COMPARED TO CHEMOTHERAPY ALONE IN GLIOBLASTOMA PATIENTS AT FIRST RECURRENCE: A POST-HOC ANALYSIS OF THE EF-14 TRIAL
Authors: Santosh Kesari
Journal: Neuro-Oncology (2015)

BACKGROUND: Tumor Treating Fields (TTFields) are an anti-mitotic, physical treatment modality. An interim analysis of the phase 3 trial comparing TTFields with temozolomide (TTFields/TMZ) to temozolomide alone (TMZ alone) showed superior progression free and overall survival in patients with newly diagnosed GBM treated with TTFields. METHODS: After completion of radiotherapy with concomitant temozolomide, patients were randomized (2:1) to TTFields/TMZ or TMZ alone. Patients who progressed on TMZ were allowed to receive a second line chemotherapy. TTFields/TMZ patients could continue TTFields with a second line chemotherapy. We analyzed baseline characteristics, choice of chemotherapy and overall survival (OS) in patients who progressed after TMZ and tested the effect of TTFields/chemotherapy compared to chemotherapy alone on OS. RESULTS: 466 pts were randomized to TTFields/TMZ and 229 to TMZ alone. Data cutoff date was December 29, 2014 and median follow up was 12.6 months. 144 and 60 patients had progressed on TMZ or TTFields/TMZ, respectively, at the time of this analysis. Baseline characteristics between 1st recurrence patients were generally well balanced, including choice of chemotherapy. Recurrent GBM patients treated with TTFields/chemotherapy lived significantly longer than on chemotherapy alone (median OS: TTFields/chemotherapy = 11.8 months; chemotherapy alone = 9.2 months; Hazard Ratio = 0.70 (95%CI 0.48-1.00); Log Rank p = 0.049). In the 43% of patients who received bevacizumab (with or without a cytotoxic chemotherapy) as their second line treatment choice TTFields/bevacizumab led to a significantly longer OS than bevacizumab without TTFields (median OS: TTFields/bevacizumab = 11.8 months; bevacizumab alone 9.0 months; Hazard Ratio = 0.61 (95%CI 0.37-0.99) Log Rank p = 0.043). CONCLUSIONS: This post-hoc analysis suggests that recurrent GBM patients treated with combined TTFields and chemotherapy and/or bevacizumab live significantly longer than on chemotherapy and/or bevacizumab alone. Prospective trials combining TTFields with chemotherapy are warranted to validate these findings.
Effects of Estrogens and Progestins on the Biochemistry and Morphology of the Postmenopausal Endometrium
Authors: M. I. Whitehead, P. T. Townsend, J. Pryse-Davies, T. A. Ryder, R. J. B. King
Journal: New England Journal of Medicine (1981)

To study the effects of exogenous estrogens on the postmenopausal endometrium, and to determine the time course and minimum dosage of added progestins necessary to oppose estrogen stimulation, we obtained endometrial specimens from symptomatic postmenopausal women being treated with various preparations of estrogens and progestins. Morphologic changes were assessed with light and electron microscopy, and biochemical effects through measurement of DNA synthesis, estradiol and progesterone receptors, and isocitric and estradiol dehydrogenase activity. For comparison, identical studies were carried out on specimens from premenopausal women in the proliferative and secretory phases of their cycle. All the estrogens exerted stimulatory effects in the postmenopausal specimens that were comparable to those observed in the premenopausal proliferative-phase specimens. Estropipate, subcutaneous estradiol, and conjugated estrogens had some hyperphysiologic effects. Maximal progestational effects occurred in the postmenopausal specimens only after norethindrone was administered for six days, and a constant level of activity equal to that in premenopausal secretory-phase specimens was then observed until the 10th day of exposure. Similar maximal effects occurred after six days of treatment with D/L-norgestrel (150 and 5 mg daily [10 mg daily produced less complete changes]). We conclude that many estrogen preparations subject the endometrium to a potent stimulus. Norethindrone and norgestrel are protective because they counteract the proliferative effects of estrogens, but the currently recommended daily dosages of these progestins can be greatly reduced without loss of response.
P160 Bone protection in oral corticosteroid dependant asthmatics
Authors: HH Hashim, PL Molyneaux, S Regan, JH Hull, A Menzies-Gow
Journal: Thorax (2015)

<h3>Introduction</h3> Asthmatics dependant on oral corticosteroids are at risk of bone loss and significant increase in fracture risk at the hip and spine. Current guidelines recommend assessment of bone mineral density and the need for bone protection in any patient exposed to glucocorticoids for over three months. We sought to assess the usage of bone protection in steroid dependant asthmatics. <h3>Method</h3> A retrospective analysis of patients admitted for a systematic assessment of asthma over a 12 month period at the Royal Brompton hospital was performed. Steroid dependence was defined as daily maintenance oral glucocorticoid for over three months. Other Inflammatory conditions requiring corticosteroids resulted in study exclusion. <h3>Results</h3> 151 patients were admitted for a systematic assessment over a 12 month period. The mean age of subjects at assessment was 46 years of age (± 27 SD) and the majority were female (77%). Fifty four subjects (36%) were steroid dependent at the time of admission. The average daily dose of prednisolone prescribed was 12.5 mg (±5.9 SD). Two thirds of steroid dependent patients had been on corticosteroids for over 12 months (36/54). At the time of referral 11 patients were on Bisphosphonates and 34 on vitamin D replacement. The systematic assessment encompassed a DEXA scan in 49 of the steroid dependent subjects; half demonstrated normal bone density (26/54), one third had osteopenia (16/54) and seven subjects had osteoporosis. Forty Six subjects had vitamin D levels checked and the mean levels were 48 nmol/L (±27 SD). Bisphosphonates were stopped in seven patients with normal bone mineral density (13%), continued in 3 subjects and started during assessment in 4. Vitamin D supplementation was continued in 30 subjects, stopped in 2 and started in 5 subjects with osteopenia and low vitamin D levels. <h3>Conclusions</h3> In a cohort of oral glucocorticoids steroid dependant asthmatics over half have normal bone mineral density. While calcium and vitamin D supplementation occurs in the majority of subjects bisphosphonate are often used unnecessarily in a predominantly pre-menopausal and female population. Clearer guidelines for the investigation and monitoring of bone protection in steroid dependent asthmatics are required.
Bone Marrow Transplants from HLA-Identical Siblings as Compared with Chemotherapy for Children with Acute Lymphoblastic Leukemia in a Second Remission
Authors: A. John Barrett, Mary M. Horowitz, Brad H. Pollock, Mei-Jie Zhang, Mortimer M. Bortin, George R. Buchanan, Bruce M. Camitta, Judith Ochs, John Graham-Pole, Philip A. Rowlings, Alfred A. Rimm, John P. Klein, Jonathan J. Shuster, Kathleen A. Sobocinski, Robert Peter Gale
Journal: New England Journal of Medicine (1994)

It is unclear how best to treat children with acute lymphoblastic leukemia who are in a second remission after a bone marrow relapse. For those with HLA-identical siblings, the question of whether to perform a bone marrow transplantation or to continue chemotherapy has not been answered.
Carotid-Artery Dissection after a Prolonged Telephone Call
Authors: Jean-Jacques Mourad, Xavier Girerd, Michel Safar
Journal: New England Journal of Medicine (1997)

The recent report by Abenhaim et al. for the International Primary Pulmonary Hypertension Study Group (Aug.29 issue) 1 has received considerable attention in the media.Patients were excluded who had pulmonary hypertension due to many causes, but not obstructive sleep apnea.Since there were approximately twice as many case patients as controls who had body-mass indexes (the weight in kilograms divided by the square of the height in meters) of 30 or higher (35.8 percent vs. 18.3 percent), one would expect the incidence of pulmonary hypertension due to obstructive sleep apnea to be higher in the case patients. 2 The authors attempted to control for obesity by citing in their Discussion section an odds ratio of 1.0 for the interaction between obesity and the use of appetite-suppressant drugs.Yet without sleep studies to evaluate possible obstructive sleep apnea, it becomes speculative to use the term "primary" in describing the case patients with pulmonary hypertension.
The Electrocardiogram and Disturbance of Potassium Metabolism
Authors: James H. Currens, John D. Crawford
Journal: New England Journal of Medicine (1950)

A SIZABLE literature demonstrating electrocardiographic abnormalities in various disorders of potassium metabolism has developed in the last ten years. The earlier observations suggested a correlation between serum potassium levels and electrocardiographic changes.1 2 3 4 5 6 7 8 9 10 11 12 As we have observed more cases, however, it has become apparent that electrocardiographic findings and serum potassium concentrations do not always correlate.13 Since potassium is primarily an intracellular ion and presumably exerts its major physiologic effects within cells, a lack of correlation might be anticipated.The question then arises whether intracellular fluid potassium concentrations correlate better than concentrations in serum with the alterations of the electrocardiogram in patients . . .
Case 16-1968
Authors: Daniel S. Ellis, Walter G. J. Putschar
Journal: New England Journal of Medicine (1968)

Presentation of Case First admission. A forty-two-year-old woman was admitted to the hospital because of fatigue and weakness.She had been chronically fatigued for ten years. On examination ten years previously the blood pressure was 160 systolic, 100 diastolic; reserpine was administered. Seven years before admission she underwent an operation for cystic mastitis; postoperatively, there was hemorrhage from the wound, and 2 units of blood were administered, without adverse reaction. The white-cell count was 4850. A year later she entered another hospital because of increasing fatigue and headaches. The heart was normal in size; a Grade 2 apical systolic . . .
An Abundance of Options
Authors: Robert A. Kreisberg
Journal: New England Journal of Medicine (1993)

A 33-year-old rancher and outdoorsman reported four days of fever, low back pain, arthralgia, and myalgia. Two days before admission to the hospital, headache, nausea, vomiting, and fever (temperature, 39.7 °C) developed.One of the most important first steps in approaching a patient is to frame the problem -- that is, to define it in terms of either a diagnosis or a syndrome and then to think about it both pathophysiologically and probabilistically. With this patient, I would frame the problem as an acute undifferentiated fever syndrome. The chief problem is fever of a few days' duration. There . . .
Phase II trial of ixabepilone (IXA) plus cetuximab (C) as first-line therapy for advanced pancreatic carcinoma (PC).
Authors: C. S. Rocha Lima, E. H. Lin, G. P. Kim, J. K. Giguere, J. Marshall, M. Zalupski, C. N. Papageorgio, M. L. Auber, M. B. McHenry, P. A. Philip
Journal: Journal of Clinical Oncology (2010)

4086 Background: Progress in the management of PC is desperately needed. Non-gemcitabine based regimens are understudied. IXA has demonstrated activity in preclinical PC models including synergistic activity in combination with C. In a phase II cooperative group study in chemo-naïve PC patients (pts) IXA showed promising efficacy. Here we present the results of a phase II, open label trial of IXA plus C as first line therapy for metastatic PC. Methods: Previously untreated pts (KPS 70–100) witheither locallyadvanced (LA) or metastatic (M) PC, were treated with IXA (32 mg/m2) IV over 3h on day 1 every 3 weeks and C, 400 mg/m2 IV (day 1) followed by weekly 250 mg/m2 doses. Pts were treated to progression or unacceptable toxicity. The primary endpoint was six month survival rate. The study tested the null hypothesis that the true 6-month rate ≤ 50% versus the alternative that the true rate > 70%. Results: Fifty-four pts (male/female 35/19; median age 63, range 47–84; LA/M 4/50) were enrolled in the study. A median of 4 cycles (range 1–21) were administered. All enrolled pts were evaluable for toxicity and survival endpoints and 31 pts were evaluable for response. The primary endpoint of 6-month survival rate was 62% (95% CI 49–75). The 95% CI for this 6 month rate did not exclude a prespecified hurdle of 50%. Median overall survival was 7.6 months (95% CI 5.5–12.2) and the 12-month survival rate was 40% (95% CI 26.91–53.75). Objective response rate was 13% (4 PRs), 77% SD, and 6% PD. Median progression free survival was 3.9 months (95% CI 2.6–4.4). Severe neutropenia was observed in 34% of treated patients (grade 3 in 20%; grade 4 in 16%). grade 3/4 febrile neutropenia occurred in 2 (4%) patients. The most frequent nonhematologic grade 3/4 toxicities were fatigue (19%), hypomagnesemia (8%), diarrhea (6%), hypersensitivity reactions (6%), peripheral neuropathy (6%) and acneiform rash (2%). Conclusions: IXA plus C is a feasible and active regimen with an acceptable toxicity profile in chemotherapy naïve PC pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
ATPS-12RE-EVALUATION OF THE USEFULNESS OF INTRAOPERATIVE COMPUTED TOMOGRAPHY FOR NEUROSURGICAL PROCEDURES IN INTRAOPERATIVE MAGNETIC RESONANCE IMAGING ERA
Authors: Mitsuru Dan, Daisuke Yamamoto, Yu-Ichi Sato, Hiroki Kuroda, Yoshiteru Miyajima, Kimitoshi Sato, Toshihiro Kumabe
Journal: Neuro-Oncology (2015)

PURPOSE: Our hospital introduced an intraoperative computed tomography (CT) for reasons such as its broad utility, safety and economy, despite an increase in intraoperative magnetic resonance imaging (MRI). We would like to verify existence value of our intraoperative CT system for neurosurgical procedures. MATERIALS AND METHODS: We performed intraoperative CT scans for the patients with 16 gliomas and 1 anterior cerebral artery partially thrombosed large aneurysm, which was treated by A2 side to side anastomosis and proximal occlusion, using a CT with 900mm opening size, radiolucent skull clamp and three types of pin made by stainless, titan, and sapphire, respectively. We assessed the residual tumors with plain and enhanced CT scans. In the cases of non-contrast tumors, small titan clips were applied on the wall of resection cavity to clarify the residual tumors. We also use 3-dementional CT angiography (3DCTA) for evaluating the hemodynamics. The time from the preparation to take images to restarting operation, image quality including the amount of halation caused by pins, and incidence during these procedures, were evaluated. RESULT: We could obtain CT scans all of these cases, regardless of the patients' position. All the surgical instruments were just put on the table below the breast. The amount of halation with sapphire pins was minimum, however even with them, it was difficult to evaluate the detailed residual tumors just beneath the location of pins. CTA was useful, especially for demonstrating the hemodynamics after resection of insulo-opercular gliomas and bypass/clipping. Total time to take CT scans was 15–40 (mean, 27) minutes. There had occurred no incidence including anesthesia. CONCLUSION: MRI is better than CT at the point of spatial resolution, but CT can be defined as an useful system in its easy-to-use, safety, and vascular evaluation.
Effect of Buspirone on Urinary Catecholamine Assays
Authors: Fiona Jackson Cook, Donald Walt Chandler, David K. Snyder
Journal: New England Journal of Medicine (1995)

To the Editor: The article by Braveman et al. (Aug.18 issue) 1 does not mention the number of emergency room visits or any admissions in the weeks before the admission for appendicitis.This is important information, because patients with no insurance and those covered by Medicaid have a high number of emergency room visits, as the authors note, and a high number of hospital admissions during which no diagnosis is made.The patients with early signs and symptoms of appendicitis could have had one or more emergency room visits or hospital admissions for undiagnosed appendicitis, only to present later with a frankly perforated appendix.Other abdominal conditions can mimic appendicitis, and emergency ultrasound examination of the appendix has a sensitivity of 80 percent and a specificity of 54 percent for the diagnosis of appendicitis. 2