tbuckley/cabot-search huggingface dataset:
Evaluation of Adrenocortical Function with Intramuscular Injection of ACTH Gel
Authors: Vito DeFilippis, Irving I. Young
Journal: New England Journal of Medicine (1957)

THE response of the adrenal cortex to intensive stimulation with exogenous ACTH provides an excellent guide to the functional status of the adrenal cortex under most circumstances. Tests based on this principle have recently been improved and made more reliable by the development of fairly specific methods for the measurement of hydrocortisone and some of its metabolites in the blood and urine. Jenkins et al.1 have clearly demonstrated that the determination of 17-hydroxycorticosteroids in urine after ACTH stimulation is a more sensitive index of adrenocortical responsiveness than urinary 17-ketosteroids, and is a more direct and specific index than changes in . . .
ATNT-20A PHASE I-II TRIAL EVEROLIMUS AND SORAFENIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS: BRAIN TUMOR TREATMENT COLLABORATIVE TRIAL 09-01
Authors: Jeffrey Raizer, Sean Grimm, Marta Penas-Prado, Ivo Tremont-Lukats, Alfred Yung, Nicholas Avgeropoulos, Tobias Walbert, Monica Loghin, Mark Gilbert
Journal: Neuro-Oncology (2015)

BACKGROUND: Limited treatment options exist for patients with recurrent Malignant Gliomas (rMG), especially after Bevacizumab (BEV). Everolimus targets mTOR and sorafenib targets Raf, VEGF and PDFG. Combining these agents can block two parallel pathways simultaneously. We performed a phase I trial of Everolimus and Sorafenib in patients with rMG in preparation for a phase II study. METHODS: Patients with rMG > 18 yrs, KPS ≥ 60, normal laboratory data and no history of HIV or hepatitis were eligible. No limit on prior relapses and BEV exposure was allowed. Enzyme inducing seizure drugs were not allowed. A 3 + 3 dose escalation was used to determine the MTD. The starting dose was Everolimus 5 mg a day + Sorafenib 400 mg twice a day with a dose de-escalation level of Everolimus 5 mg/day + Sorafenib 400 mg twice a day for 7 days on and 7 days off. RESULTS: 11 men and 2 women were enrolled with a median age of 50 years (19-66) and median KPS of 80 (70-100). All patients had a GBM with 7 receiving prior BEV. In cohort 1, 3 of 6 patients experienced a DLT which were grade 3: fatigue, chest pain, HTN, elevated ALT, hypercholesterolemia and hyperglycemia and one grade 4 hypertriglyceridemia. Dose de-escalation occurred with 1 of 7patients having a DLT of myositis, nausea, fatigue, hypertension and hypercholesterolemia-all grade 3. All patients died due to disease progression with a median PFS of 4 weeks and OS of 20.9 weeks. CONCLUSION: This phase I study determined a phase II dose of Everolimus at 5 mg daily and Sorafenib at 400 mg BID 7 days on and 7 days off. A phase II trial is on-going for Bev naive recurrent anaplastic gliomas and GBMs as well as recurrent GBM who failed BEV.
Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice
Authors: Yang Luo, Xiaotong Wu, Zhuang Ma, Weifeng Tan, Lanlan Wang, Daxiang Na, Guoying Zhang, Ang Yin, He Huang, Dan Xia, Yingmei Zhang, Xueying Shi, Lu Wang
Journal: Cellular and Molecular Immunology (2016)
Tumor Latency in Avian Lymphoid Leukosis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A M Fadly, H G Purchase, D G Gilmour
Journal: JNCI Journal of the National Cancer Institute (1981)

Transfer of bursa cells from older chicken infected with lymphoid leukosis (LL) virus into young recipient chicks depleted of bursal lymphocytes by cyclophosphamide shortened the latency period for lymphoma development in recipient chickens by an amount equivalent to the age of the donor. Chickens were crosses between males of the Regional Poultry Research Laboratory, East Lansing, Michigan, inbred line 151, subline 5, and females of inbred line 7, subline 2. In a further experiment with intact infected chicks, artificial metastasis at various ages by surgical bursectomy and inoculation of bursa cells into the bloodstream of the host did not shorten the latency period. These results suggest that latency in avian LL is a property of target B-cells and is unrelated to maturational events of the host physiology.
Circulating Angiogenic Factors As Biomarkers of Acute Gvhd Onset and Response to Therapy: Repair and Regeneration Versus Endothelial Damage and Inflammation
Authors: Shernan G. Holtan, Michael R. Verneris, Kirk R. Schultz, Laura Newell, Gabrielle Meyers, Fiona C. He, Todd E. DeFor, Margaret L. MacMillan, Sarah A. Cooley, Angela Panoskaltsis-Mortari, Daniel J. Weisdorf
Journal: Blood (2014)
A Reappraisal of the Results of Stopping Therapy in Childhood Leukemia
Authors: Stephen L. George, Rhomes J. A. Aur, Alvin M. Mauer, Joseph V. Simone
Journal: New England Journal of Medicine (1979)

We examined the results of stopping therapy in children with acute lymphocytic leukemia. Of 639 patients in eight consecutive "total therapy" studies, 278 (44 per cent) had all treatment stopped, usually after 2 1/2 years of complete remission. About one fifth (55 of 278) of this group have relapsed, mainly in the bone marrow. The relapse rate for the first year off therapy was higher than that for the next three years (0.16 vs. 0.04, P<0.01). The life-table estimates of the four-year relapse rates were 0.24 for all patients and 0.22 for patients receiving adequate Central-nervous-system prophylaxis. Boys had a higher relapse rate than girls (0.33 vs. 0.15, P<0.01). None of the 79 patients who remained in complete remission for at least four years off therapy have yet relapsed. Acute lymphocytic leukemia appears curable in over one third of all newly diagnosed patients who receive treatment for approximately 2 1/2 years. (N Engl J Med 300:269–273, 1979)
Restoration of normal hematopoiesis by bone marrow ablation and allogeneic marrow transplantation in a case of Hodgkin's disease therapy-related preleukemia
Authors: M Gyger, C Perreault, J Boileau, JP Aymard, Y Bonny, M Lacombe, R Lavallee, G d'Angelo, E Tawil
Journal: Blood (1983)
Study evaluating different methods of tumor volume estimation on PET-CT in carcinoma lung.
Authors: H. Kunhiparambath, R. Prabhakar, G. K. Rath, P. K. Julka, D. Sharma, H. Puthiyeduthu, N. Joshi
Journal: Journal of Clinical Oncology (2010)

e17528 Background: PET-CT has got a very vital role in present day oncology for diagnosis, staging, radiation planning, and response evaluation of tumors. We have even started talking about PET Response Criteria in Solid Tumors (PERCIST). Unfortunately, target delineation with PET currently remains a largely unaddressed problem. PET is a functional modality and the FDG concentrations within the tumor are variable. PET may either underestimate or overestimate the actual target volume. Various thresholding techniques have been developed where we take a certain percentage of the maximum SUV for edge definition. Many studies take from 15 to 40 % of Maximum SUV. The purpose of this study is to determine the performance of different edge detection methods for tumor volume estimation. Methods: Ten cases of newly diagnosed untreated Non Small cell lung cancer that underwent diagnostic PET, which had a measurable tumor on the images, were enrolled. The PET Images were transferred to the radiotherapy treatment planning system and PET and CT images were co-registered by pixel data matching. Gross Tumor was contoured on CT scan slice by slice manually by an oncologist (GTV-CT). Tumor volume was determined by summation of manually drawn regions of interest. Tumor volume was determined on FDG-PET with a semi automated method. The PET-GTV was delineated automatically by use of various percentages of the SUVmax. GTV-50, GTV-40, GTV-30, GTV-20 and GTV-15, based on the volume covered by respective percentage of maximum SUV were estimated. These volumes were compared with CT-GTV. Results: The mean maximum SUV was 7±3. The average volume of the GTV-CT was 125 cc. A significant impact of PET-derived contours on tumor volume estimation has been shown in 7 of the 10 patients with respect to the CT-GTV. PET defined GTV- 50 and GTV-40, were less than GTV-CT. Whereas GTV-30, GTV-20 and GTV-15 overestimated the GTV volume in majority of the cases. Even though GTV 40 underestimated the GTV, it was the closest match. Conclusions: Whereas the different thresholding methods either overestimated or underestimated the target volume, GTV 40 is the closest method for tumor delineation in NSCLC in our study. Further large studies needed. No significant financial relationships to disclose.
OP0189 High Grade Salivary Gland Involvement, Assessed by Histology or Ultrasonography, Is Associated with a Poor Response to Rituximab in Primary Sjögren's Syndrome Patients
Authors: D. Cornec, S. Jousse-Joulin, S. Costa, T. Marhadour, P. Marcorelles, J.-M. Berthelot, E. Hachulla, P.-Y. Hatron, V. Goeb, O. Vittecoq, E. Nowak, J.-O. Pers, V. Devauchelle-Pensec, A. Saraux
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To determine whether the extent of salivary gland involvement, assessed using unstimulated whole salivary flow (UWSF), histological focus score or salivary gland ultrasonography (SGUS), is associated with the response to rituximab in patients with primary Sjögren9s syndrome (pSS). <h3>Methods</h3> 35 pSS patients form the randomized TEARS study, which compared rituximab to placebo, had either centralized salivary gland biopsy or SGUS, at inclusion. Among rituximab-treated patients, 50% were considered responders according to the Sjögren9s Syndrome Responder Index (SSRI)-30 definition of the response at week 24. <h3>Results</h3> SGUS score was positively correlated to the focus score (r=0.61) and inversely correlated to UWSF (r=-0.68). Conversely, the focus score was not correlated with UWSF. No patients with grade 4 SGUS score responded to rituximab, compared to 88% of patients with SGUS score ≤3. The median focus score at inclusion was 0.3 (0.0-1.3) in the responders versus 4.0 (2.7-5.3) in the non-responders (p=0.02). Conversely, baseline UWSF was not associated with the response. <h3>Conclusions</h3> pSS patients with the highest histologic or morphologic salivary gland involvement do not respond to rituximab after 6 months, suggesting that a single 1gX2 rituximab course could be an unsufficient treatment for patients with the highest salivary gland B cell activity. <h3>Disclosure of Interest</h3> None declared
K-<i>ras</i>Oncogene Activation as a Prognostic Marker in Adenocarcinoma of the Lung
Authors: Robert J.C. Slebos, Robert E. Kibbelaar, Otilia Dalesio, Anko Kooistra, Jacob Stam, Chris J.L.M. Meijer, Sjoerd S. Wagenaar, Ronald G.J.R.A. Vanderschueren, Nico van Zandwijk, Wolter J. Mooi, Johannes L. Bos, Sjoerd Rodenhuis
Journal: New England Journal of Medicine (1990)

The capability of activated oncogenes to induce malignant transformation of immortalized cells in vitro has suggested that they have a similar role in the pathogenesis of human tumors. We previously found that activation of the K-ras oncogene by a point mutation in codon 12 occurs in about one third of human lung adenocarcinomas.
Case 10-2006
Authors: Norman S. Nishioka, Gregory Y. Lauwers
Journal: New England Journal of Medicine (2006)

A 66-year-old woman was found to have Barrett's esophagus with high-grade dysplasia and focal intramucosal adenocarcinoma. Her morbid obesity made her a poor candidate for esophagectomy. A pathologist and a gastroenterologist discuss the pathophysiology and management of Barrett's esophagus.
Positive Direct Antiglobulin Tests and Immune Hemolytic Anemia in Patients Receiving Procainamide
Authors: Steven Kleinman, Richard Nelson, Louise Smith, Dennis Goldfinger
Journal: New England Journal of Medicine (1984)

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.
Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and carboplatin/paclitaxel (CP) for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: G. Blumenschein, A. Sandler, T. O’Rourke, M. Eschenberg, Y. Sun, G. Gladish, R. Salgia, C. Alden, R. S. Herbst, K. Reckamp
Journal: Journal of Clinical Oncology (2006)

7119 Introduction: AMG 706 is an investigational, oral, multi-kinase inhibitor with both antiangiogenic and direct antitumor activity targeting VEGF, PDGF, and Kit receptors. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFr), has shown antitumor activity and acceptable safety in pts with solid tumors. Methods: This is an ongoing, multicenter, dose finding, phase 1b study of AMG 706 with panitumumab and CP in pts with advanced NSCLC. Primary objectives were to assess the safety and PK of AMG 706; secondary objectives included drug exposure and objective response rates. Pts had stage IIIB/IV NSCLC, ECOG score of 0–1, no symptomatic or untreated CNS metastases, and no prior chemotherapy for NSCLC (segments A&amp;C) or ≤ 1 regimen for NSCLC (segment B). AMG 706 was given orally either QD (50 mg or 125 mg) or BID (75 mg) with CP Q3W (P:200 mg/m 2 ; C: AUC = 6 mg/mL · min; Segment A), with panitumumab (9.0 mg/kg Q3W; Segment B), or with CP+ panitumumab (Segment C). AMG 706 was dosed continuously in 21-day cycles (days 3–21 in cycle 1; days 1–21 in cycle 2 and beyond); pts were sequentially enrolled into escalating AMG 706 dose cohorts. Results: As of 9/05, 22 pts were enrolled (10 in A, 12 in B) into AMG 706 dose cohorts of 50 mg and 125 mg QD. In A and B, respectively, 7 and 6 pts were men; median (range) age was 60.5 (60, 74) and 60.5 (55.7, 71.0). One pt in the 125 mg QD cohort in Segment B had grade (gr) 5 pneumonia. Treatment-related adverse events occurring in &gt;5% of all patients are summarized ( table ). Preliminary data showed that AMG 706 PK profiles were similar when administered with CP either 30 min or 48 hrs apart. At 50 mg QD, there was no effect of AMG 706 on the PK of P. Conclusions: Preliminary data indicate that AMG 706 can be combined safely with CP or panitumumab in pts with advanced NSCLC and that there is no effect on the PK of AMG 706 or P. Updated data will be presented. [Table: see text] [Table: see text]
The smartphone app ‘Rotator Cuff Injury/Strain’ by Medical iRehab
Authors: Osman Hassan Ahmed
Journal: British Journal of Sports Medicine (2015)

Injury Prevention/Rehabilitation.

iOS (3.0 and above), Android (V.1.6 and above).

£1.84.

Medical iRehab has a number of injury-specific apps available, including one targeted towards rotator cuff injury. The set-up of this app, in keeping with their other apps, is simple and straightforward. The app gives a general overview of the injury, and provides information on aspects such as pain control and self-management. A general information section contains some brief discussions of the signs and symptoms of rotator cuff injuries. The app is focused towards rehabilitation and as such there is a focus towards conservative treatment, with no mention of surgical options1 for this injury. There are a wide range of exercises included in this app (figure 1), with examples shown for mobility, strengthening …
New Approaches to Understanding Lesch–Nyhan Disease
Authors: William L. Nyhan, Dean F. Wong
Journal: New England Journal of Medicine (1996)

Since first described 32 years ago, Lesch–Nyhan disease has caught the imagination of clinicians and scientists,1 largely because of the intriguing fact that a precise metabolic error produces a complex set of clinical manifestations. Particularly intriguing are the behavioral and neurologic manifestations of the disease, which are unaccompanied by anatomical abnormalities in the brain, indicating that their pathogenesis must be chemical. Some of the clinical features of the disease, which are also present in gout, are the direct consequences of hyperuricemia and can be readily understood from the nature of the metabolic abnormality. However, the pathogenesis of the abnormalities of . . .
Phase II study of antiangiogenic (metronomic) chemotherapy for recurrent malignant gliomas
Authors: S. Kesari, D. Schiff, L. Doherty, D. Gigas, T. Batchelor, A. Muzikansky, A. O’Neill, J. Drappatz, M. Kieran, P. Y. Wen
Journal: Journal of Clinical Oncology (2006)

1569 Background: There is preclinical evidence that continuous low-dose chemotherapy may inhibit tumor endothelial proliferation and prevent tumor growth (Browder et al Cancer Res 2000;60:1878). Methods: We conducted a phase II study of continuous low-dose etoposide (VP-16), alternating with cyclophosphamide (CP), in combination with thalidomide (T) and celecoxib (C) in adult patients with recurrent malignant gliomas. There was no limit on the number of prior therapies. Patients received VP-16 [35 mg/m 2 (maximum 100 mg) daily for 21 days] alternating with CP [2 mg/kg (maximum 100 mg/day) for 21 days]. Thalidomide was started at 200 mg daily and increased by 100 mg weekly to a maximum of 1200 mg/day, as tolerated. Celecoxib was started at 200 mg twice daily and increased to 400 mg twice daily. MRIs were performed every 6 weeks. Patients were treated until tumor progression or development of unacceptable toxicity. Serum was collected for measurement of angiogenic peptides. Results: 48 patients were enrolled (15 female, 33 male). 28 had glioblastomas (GBM); 20 had anaplastic gliomas (AG). Median age was 53 years (range 33–74); median KPS was 70 (range 60–100). Patients had average of 2.1 prior chemotherapies; 33% had 3 or more prior chemotherapies. Toxicities included neutropenia (8 G3, 8 G4), leukopenia (13 G3, 8 G4), lymphopenia (26 G3), anemia (1 G3), thrombocytopenia (1 G3); nausea (1 G3), vomiting (3 G3), constipation (5 G3; 2 G4), colitis (2 G4), rash (1 G3), dizziness (1 G3); hypoxia (1 G3), and infection (2 G3). 2 patients had DVT and 6 had pulmonary emboli. There were no treatment related deaths. Fatigue was common but usually mild. 12% of patients had PR, 59% had SD, 29% progressed at their first scan. For GBM patients, median progression-free survival (PFS) was 11 weeks, 6 month-PFS was 9% and median survival was 21 weeks. For AG patients, median PFS was 14 weeks; 6 month-PFS was 26% and median survival was 41.5 weeks. Correlation of angiogenic peptide levels and response will be reported. Conclusions: Although there were some responders this regimen did not significantly improve survival in this heavily pretreated group of patients. However, further studies combining metronomic chemotherapy with more potent angiogenesis inhibitors such as lenalidomide or VEGFR inhibitors may be warranted. [Table: see text]
The L. E.-Cell Phenomenon in Chronic Hepatic Disease
Authors: Paul Heller, Hyman J. Zimmerman, Simon Rozengvaig, Karl Singer
Journal: New England Journal of Medicine (1956)

THE L. E.-cell phenomenon has been considered to be specific for systemic lupus erythematosus.1 2 3 4 5 6 Several large surveys have not revealed any false-positive L. E. tests.1 2 3 4 5 6 Nevertheless, its occurrence has been reported in other pathologic states such as multiple myeloma, pernicious anemia and moniliasis,7 8 9 10 in hypersensitivity reactions11 , 12 and in the rheumatoid syndrome after treatment with hydralazine.13 , 14 It has been emphasized that in patients with drug hypersensitivity, cells undergoing nucleophagocytosis may simulate the L. E. cell.15 16 17 18 In other cases of hypersensitivity reactions, and in the syndrome that follows hydralazine therapy, cells indistinguishable from classic L. E. cells have been found.11 12 13 14 The demonstration . . .
Prediction of pathological response to preoperative chemoradiotherapy with cetuximab in rectal cancer
Authors: J. H. Machiels, A. Debucquoy, O. Gevaert, A. Daemen, C. Sempoux, W. McBride, C. Stroh, S. Vlassak, K. Haustermans
Journal: Journal of Clinical Oncology (2008)

4095 Background: The addition of cetuximab to preoperative chemoradiation (CRT) in rectal cancer (RC) does not seem to improve the complete pathological response rate. These data outline the importance of a better understanding of the molecular mechanisms involved to allow optimal patient selection. The aims of this study were to characterize the molecular pathways activated or inhibited by cetuximab in vivo and to identify molecular profiles for response prediction to CRT. Methods: Forty patients with RC (T3-T4 and/or N+) received preoperative RT (1.8 Gy, 5 days/wk, 45 Gy) in combination with capecitabine and cetuximab (initial dose 400 mg/m2, one week before CRT followed by 250 mg/m2/wk for 5 wks). Biopsies and plasma samples were taken at baseline, after the loading dose of cetuximab but before the start of CRT, and at surgery (performed six weeks after the end of CRT). Proteomics included 96 cancer- related proteins. Baseline samples were used to search profiles for response prediction and comparison between baseline and on-treatment samples to monitor the molecular response to cetuximab. Results: The initial dose of cetuximab led to a downregulation of invasion and proliferation pathways and an upregulation of inflammatory pathways and EGFR ligands as evaluated by microarray-gene expression analysis and proteomics. The decrease in proliferation and the upregulation of the EGFR ligands were confirmed by immunohistochemistry for Ki67 (p=0.01) and ELISA for TGF-alpha (p<0.001). An expression signature of 10 genes was found to be predictive for margin invasion. The proteomics predicted the Wheeler regression grade (expression of 5 proteins). The expression of Ki67 (p=0.05) as well as TGF-alpha (p=0.01) correlated with T downstaging. Regarding K-Ras mutations, no significant correlation with pathological response was found. A trend (p=0.06) for better response according to Wheeler was observed for patients with wild-type K-Ras. Conclusions: One single dose of cetuximab given in monotherapy has a significant impact on inflammation, proliferation and invasion pathways in RC. Some molecular profiles were correlated with some pathological endpoints related to CRT efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck nv/sa Belgium, Merck Serono, Merck KGaA Merck Serono, Merck KGaA
AIDS-related Kaposi's sarcoma.
Authors: M R van den Brink, B J Dezube
Journal: Journal of Clinical Oncology (1997)

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.1997.15.3.1283 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9060573 AIDS-related Kaposi's sarcoma. M R van den BrinkxM R van den BrinkSearch for articles by this author , B J DezubexB J DezubeSearch for articles by this author Show More AIDS Malignancy Research and Treatment Center, Beth Israel Deaconess Medical Center, Boston, MA, USA. https://doi.org/10.1200/JCO.1997.15.3.1283 PDF "AIDS-related Kaposi's sarcoma.." Journal of Clinical Oncology, 15(3), pp. 1283–1284© 1997 by American Society of Clinical Oncology