tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study”
Authors: James M. Shikany, Monika M. Safford, P. K. Newby, Raegan W. Durant, Todd M. Brown, Suzanne E. Judd
Journal: Circulation (2016)
Brief Communication: High Resolution Proton Magnetic Resonance Spectral Characteristics of Water, Lipid, and Protein Signals From Three Mouse Cell Populations2
Authors: Ronald E. Block, Gayle P. Maxwell, David L. Prudhomme, Jerry L. Hudson
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Brief Communication: High Resolution Proton Magnetic Resonance Spectral Characteristics of Water, Lipid, and Protein Signals From Three Mouse Cell Populations Get access Ronald E. Block, Ronald E. Block Search for other works by this author on: Oxford Academic PubMed Google Scholar Gayle P. Maxwell, Gayle P. Maxwell Search for other works by this author on: Oxford Academic PubMed Google Scholar David L. Prudhomme, David L. Prudhomme Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerry L. Hudson Jerry L. Hudson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 1, January 1977, Pages 151–156, https://doi.org/10.1093/jnci/58.1.151 Published: 01 January 1977 Article history Received: 25 February 1976 Accepted: 28 May 1976 Published: 01 January 1977
Delayed Cutaneous Hypersensitivity Reactions to Extracts of Breast Cancer and Melanoma Tissue in Cancer Patients&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Giuseppe Fossati, Silvana Canevari, Marco A. Pierotti, Paolo Vezzoni, Giuseppe Della Porta, Maurizio Vaglini
Journal: JNCI Journal of the National Cancer Institute (1979)

Crude soluble extracts from breast cancer and malignant melanoma surgical specimens were obtained by the 3 m KCl method and assayed in cancer patients for a delayed cutaneous hypersensitivity reaction. The breast cancer extract was derived from a pool of 9 primary cancer specimens, whereas 8 melanoma extracts were prepared from single tumors; as controls, normal mammary and muscle tissues were employed. Positive response to the breast cancer extract was observed in 18 of 26 (69%) breast cancer patients and in 2 of 12 (17%) patients with other types of neoplasms. Reactivity to the individual melanoma extracts was varied: Positive reactions were observed in no patients with 1 extract, in 20–33% of the patients with 3 extracts, and in 75–93% with 4 extracts. By pooling the results obtained with the 8 melanoma extracts, we observed reactivity in 22 of 39 (56%) melanoma patients and in 12 of 23 (52%) patients with other tumors. Of 26 breast cancer patients, 5 (19%) reacted to normal mammary extract, and 5 of 28 (18%) melanoma patients reacted to muscle extracts; 20% and 25% of the patients with other types of tumors reacted to these extracts, respectively. The overall incidence of positive reactions to control extracts was 18 of 85 tests (21%). Ten of the 26 patients with breast cancer and 7 of the 39 patients with melanoma received simultaneous injections of extracts from breast cancer and melanoma. Most breast cancer patients reacted both to the breast cancer extract (70%) and to the melanoma extracts (90%), whereas all the melanoma patients reacted to the melanoma extracts and 2 (28%) reacted to the breast cancer extract. No correlation was found between positive response and clinical parameters, e.g., histologic diagnosis, stage of disease, age, sex, blood group, history of pregnancy, and time of surgery.
Analysis of P2Y12 receptor responsiveness to cysteinyl leukotrienes
Authors: Holly Foster, Elisabeth Stafflinger, Tak Lee, Grzegorz Woszczek
Journal: European Respiratory Journal (2011)

Leukotriene E 4  (LTE 4 ), the most stable of the cysteinyl leukotrienes (cysLT), binds poorly to classical type 1 and 2 cysLT receptors although it may potently induce bronchial constriction, airway hyperresponsiveness and inflammatory cell influx to the lungs of asthmatic individuals. Evidence of the presence of a previously unidentified LTE 4  receptor has also been provided in CysLT 1  - /CysLT 2  -  double knock out mice. A recent study has suggested that purinergic receptor P2Y 12  is required for LTE 4  mediated pulmonary inflammation in a mouse model of asthma. The aim of the study was to characterise the responsiveness of human P2Y 12  to cysteinyl leukotrienes. A model of human CysLT 1 , CysLT 2  and P2Y 12  transiently overexpressed in HEK293 cells was used and responsiveness to different agonists was measured using intracellular calcium and cAMP assays. The responsiveness of human P2Y 12  stably overexpressed in CHO cells was also analysed using a β-arrestin recruitment assay. CysLTs induced concentration dependent calcium mobilisation in cells overexpressing CysLT 1  and CysLT 2  but failed to induce any calcium response in cells expressing P2Y 12  or P2Y 12 +G α 16. In contrast, a selective P2Y 12  agonist 2-MeSADP, induced specific calcium flux in cell expressing P2Y 12 +G α 16. Similarly, specific response to 2-MeSADP, but not to cysLTs was also observed in cells expressing P2Y 12  when intracellular cAMP and β-arrestin signalling was analysed. These results suggest that LTE 4  as well as other cysLTs may not activate intracellular signalling acting through human P2Y 12  and another LTE 4  specific receptor has yet to be identified.
Rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) for patients with relapsed indolent B-cell lymphoma (RIL).
Authors: G. E. Manoukian, F. B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, A. Goy, J. E. Romaguera, B. Pro, F. Cabanillas, M. A. Rodriguez
Journal: Journal of Clinical Oncology (2010)

8078 Background: Optimal therapy for RIL remains controversial, although treatment options often include rituximab (R). Based on phase I-II studies of FND (fludarabine 25 mg/m2, d1-3; mitoxantrone 10 mg/m2, d1; dexamethasone 20 mg, d1-5) for RIL in which we observed 48% complete remission (CR), we studied the combination of R (375 mg/m2 d1) and FND for RIL. Methods: Patients did not receive maintenance rituximab. Patients could not have received prior fludarabine, and could have previously received R if they had a response lasting at least 6 months to prior R. All patients underwent biopsy prior to relapse therapy. Results: Of the 39 eligible and evaluable patients, 30 patients had follicular lymphoma, 7 had small lymphocytic lymphoma and 2 had marginal zone lymphoma. Twenty six patients entered CR/CRu (67%) and 12 partial remission (PR) (31%) for an overall response rate (ORR) of 97%. One patient had stable disease (SD). Nine patients underwent stem cell transplant (SCT) while in first remission. The median follow-up for living patients was 82 months. For all 39 patients, the 5 and 9 year overall survival (OS) rates were 84% and 57%; corresponding failure free survival (FFS) rates were 61% and 58%. When we recalculated these results, censoring the 9 patients who underwent SCT consolidation, the 5 and 9 year OS rates were 81% and 53%; corresponding FFS rates were 51% and 48%. For the 9 patients after SCT, the FFS was 100%, with no patient developing recurrence following SCT. 17 patients (44%) relapsed, and 10 patients (26%) died, only 2 of lymphoma relapse. Grade 4 neutropenia occurred in 25 patients, grade 3-4 thrombocytopenia in 5 patients, and grade 3 anemia in 1 patient. No patients died of acute toxicity while receiving R-FND; one developed treatment-related myelodysplastic syndrome. Conclusions: We conclude R-FND is a very active and well tolerated regimen for RIL. Results appear very favorable compared to prior studies with FND. In this population, patients who received R-FND were able to undergo SCT, and had very favorable outcomes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Biogen Idec, Genentech Bayer
Study confounded by lack of correction for social class
Authors: S. Westin
Journal: BMJ (1995)

consisting of non-drinkers, beer drinkers, spirits drinkers, and beer and spirits drinkers.The drinkers, again, could have ranged from those who drank beer or spirits only once a month to those who had more than five drinks a day.This would falsely increase the risk among those who did not drink wine and give a falsely low risk for those who did drink wine.Indeed, it is difficult to believe that a drink of wine only once a month can reduce the risk of cardiovascular death by 31%.If this is true it supports the premise that drinking wine may be associated with other favourable traits that influence cardiovascular risk.
Nonaqueous, Mini-Dose Glucagon for Treatment of Mild Hypoglycemia in Adults With Type 1 Diabetes: A Dose-Seeking Study
Authors: Morey W. Haymond, Maria J. Redondo, Siripoom McKay, Martin J. Cummins, Brett Newswanger, John Kinzell, Steven Prestrelski
Journal: Diabetes Care (2016)

To evaluate mini-dose glucagon in adults with type 1 diabetes using a stable, liquid, ready-to-use preparation.
Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease
Authors: M J J Rose-Zerilli, J Gibson, J Wang, W Tapper, Z Davis, H Parker, M Larrayoz, H McCarthy, R Walewska, J Forster, A Gardiner, A J Steele, C Chelala, S Ennis, A Collins, C C Oakes, D G Oscier, J C Strefford
Journal: Leukemia (2016)

The biological features of IGHV-M chronic lymphocytic leukemia responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in 13 patients presenting with cMBL or Stage A disease and good-risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom 10 have required therapy. Using cytogenetics, fluorescence in situ hybridisation, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing at diagnosis, we identified mutations in established chronic lymphocytic leukemia driver genes in nine patients (69%), non-coding mutations (PAX5 enhancer region) in three patients and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition before therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low-risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good-risk disease.
Liposomal doxorubicin-liposomal doxorubicin-rituximab for the treatment of elderly patients with diffuse large B-cell lymphoma
Authors: F. Zaja, V. Tomadini, A. Zaccaria, F. Lauria, A. L. Molinari, A. Fabbri, R. Battista, E. Angelucci, A. Gallamini, M. Battista, R. Fanin
Journal: Journal of Clinical Oncology (2005)

6687 Background: At present CHOP plus rituximab (CHOP-R) appears to be the golden standard treatment for elderly patients with diffuse large B-cell lymphoma (B-DLCL). Treatment related toxicity, in particular infectious complications and cardiac toxicity, however, still represent a major cause of morbidity and mortality. Here we report the preliminary results of a pilot study performed to evaluate the efficacy and tolerability of a Caelyx-modified CHOP-R regimen (COP-Caelyx-R). Methods: Thirty consecutive untreated patients, 60 years or older, with CD20 positive B-DLCL, stage II-IV or bulky stage I, were enrolled in the study. Caelyx 30 mg/m2 was given on day 1 in combination with standard dosage of prednisone, vincristine, cyclophosphamide (according to CHOP regimen) and rituximab every 21 days for 6 courses. G-CSF was administered as appropriate. Patients with initial bulky disease or localized residual disease received consolidation-involved field radiotherapy. The procedures planned for cardiac toxicity evaluation were echography with ejection fraction (EF) and serum troponin dosage. Hematological and extra-hematological toxic effects were graded according to the WHO classification. Results: Patients’ median age was 69 (range 60–75 years); the distribution according to International Prognostic Index (IPI) was: low 13.3%, low-intermediate 20%, high-intermediate 43.3%, high 23.3%. Twenty-nine patients are valuable for response and toxicity. Overall response (OR) and CR rate are 75.8% and 58.6%. The projected one year EFS and OS are 65% and 79%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3.5%. Extra-hematological WHO III-IV toxicity was represented by a single case of infection, mucositis and bleeding. None of the patients had clinical, instrumental and laboratory signs of cardiac toxicity; none developed hand-foot syndrome. Conclusions: COP-Caelyx-R regimen is an active regimen for the treatment of elderly B-DLCL. The replacement of conventional doxorubicin with Caelyx seems to reduce the incidence of extra-hematological toxicity, in particular cardiac and infectious complications. No significant financial relationships to disclose.
Novel phase I clinical trials in sarcoma patients: The M. D. Anderson Cancer Center experience.
Authors: V. Subbiah, R. S. Benjamin, A. Naing, J. C. Trent, D. S. Hong, P. Pinnamaneni, I. Garrido-Laguna, C. E. Herzog, E. Kleinerman, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

e13111 Background: Sarcomas represent a diverse class of molecularly distinct bone and soft-tissue mesenchymal neoplasms of more than 50 subtypes. Despite decades of multi-institutional clinical trials the prognosis of relapsed or recurrent sarcoma patients remains grim. Patients with advanced sarcomas are eligible for phase I trials. We assessed prognostic factors, and clinical outcomes for patients with diverse sarcomas in a phase I clinic focused on targeted agents. Methods: We reviewed the medical records of sequential patients with sarcomas who presented to our phase I clinic from September 2004 to May 2009. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics using both univariate and multivariate (Cox proportional hazard model) analyses. Results: Seventy-three patients with sarcomas were identified with median age 49 years (range 3 to 78 years). Forty-one were males and 32 females. Fifteen different sarcoma subtypes were seen with the common diagnoses being leiomyosarcoma (n= 12), liposarcoma (n=11), and Ewing's sarcoma (n=9). The median overall survival was 10.3 months (95% CI: 6.9-13.7). The prognostic factors analyzed were absolute lymphocyte count (ALC) < 500 (vs. > 500), ECOG performance status 2-3 (vs. 0-1), albumin < 3.5 g/dL (vs. > 3.5g/dL), hemoglobin < 9.5 (vs. > 9.5), platelets < 150 (vs. >150), BMI >25 (vs. <25), and LDH < 600 (vs. >600). In univariate analysis LDH >600 (p=0.0009) and hemoglobin < 9.5 (p=0.02) predicted shorter survival. In multivariate analysis only LDH > 600 predicted shorter survival. Median survival time of pts with LDH > 600 was 5 months (95% CI: 2.2-8.6) vs. LDH < 600 was 13.8 months (95% CI: 8.2- 19.4). Conclusions: Patients with advanced sarcomas referred for our phase I studies had a median survival of 10.3 months. In this preliminary analysis, independent factors predicting shorter survival were higher LDH (>600) and lower hemoglobin (<9.5). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Centocor, Johnson & Johnson, Maxygen, Merck Amgen, AstraZeneca, Center for Biomedical Continuing Education, Enzon, Genentech, ICSC, ImClone Systems, Johnson & Johnson, Maxygen, Merck, Pharmion, Roche Abraxis, Amgen, AmpliMed, Antigenics, AstraZeneca, Bayer, Bristol-Myers Squibb, Callisto, Centocor, Concordia, Curagen, Eisai, Enzon, Exelixis, Genentech, GlaxoSmithKline, Globomax, Kinex, Lilly, Merck, Metastatix, MGI Pharmaceuticals, Myriad, Nereus, Novartis, Pfizer, Pharmacyclics, Pharmion, Phoenix Biotech, Reata, Roche, Taiho Pharmaceutical, Vioquest, Ziopharm Oncology
P1046 : A one year retrospective review of new patient attendances at a tertiary hepatology centre highlighting the increasing challenge of NAFLD and the need to develop clinical pathways
Authors: A. Srivastava, R. Gailer, S. Tanwar, P. Trembling, A. Warner, S. Morgan, K. Sennett, D. Thorburn, E. Tsochatzis, W. Rosenberg
Journal: Journal of Hepatology (2015)
A three schedule phase I trial of CP-4055, weekly and q2 weeks in patients with advanced or metastatic solid tumors
Authors: T. Delaunoit, E. Raymond, A. Awada, F. Savinelli, S. Culine, W. Rasch, A. Yovine, N. Houédé
Journal: Journal of Clinical Oncology (2006)

2067 Background: CP-4055 (ELACYT, ara-C 5’-elaidic acid ester) is a novel cytotoxic agent with broad preclinical antitumor activity in solid tumors. CP-4055 is based on Lipid Vector Technology and has a different cellular uptake compared to ara-C. An initial phase I trial of a day 1–5 q4 weeks (w) schedule (sch) determined a recommended dose of 200 mg/m 2 /day and showed clinical activity (Aamdal et al, AACR 2005). We report a multiple sch, parallel, dose intensity-guided dose escalation phase I trial, with pharmacokinetic (PK) assessment, intended to determine Maximum Tolerated Dose (MTD). Methods: Patients (pts) with refractory solid tumors received i.v. CP-4055 over 2 hours according to 3 sch: days 1, 8 q3w (Sch 1); days 1, 15 q4w (Sch 2); days 1, 8, 15 q4w (Sch 3). Dose escalation: dose level (DL) 1: 80 mg/m 2 /w, DL2: 160; DL3: 240; DL4: 320; DL5: 400; DL6: 440; DL7: 520, with standard definitions of dose limiting toxicity (DLT). Results: Since June 2004, 45 pts have been treated in 4 European centers; 3 are still ongoing, 37 discontinued for progressive disease, 3 for refusal, 2 for AE (1 treatment-related grade [gr] 3 paresthesia), trial is ongoing. Demographics: male/female: 27/18; median age 54 (range 35–79); ECOG PS 0/1/2: 19/24/2. Main tumor types: colorectal 6, breast 5, head &amp; neck 5; median 3 lines prior chemotherapy (range 0–5). Exposure: 128 cycles administered, including 5 pts with ≥ 6 cycles. MTD: No DLT has been observed and dose escalation is ongoing. Safety (NCI-CTCAE v3): 45 pts assessable. Principal toxicities by pt (gr 1–2/3): anemia 34/1; nausea and vomiting 29/3; asthenia 24/1; neutropenia 12/2; headache 8/0; thrombocytopenia 3/0. No clear association with sch or DL was observed for this mild/moderate toxicity. There were no dose reductions. PK: ara-U/ara-C AUC ratio exceeds by 3-fold the standard ara-U/ara-C AUC ratio. Efficacy: 41 pts were assessable, 10 pts had stable disease (lasting &gt; 6 months in 4 pts: 2 NSCLC, 1 colorectal, 1 kidney). Conclusions: CP-4055 shows preliminary evidence of activity and is well tolerated up to a dose of 440 mg/m 2 /w. PK results indicate that a majority of ara-U in plasma originates from intracellular deamination of ara-C from CP-4055, confirming intracellular retention of CP-4055. Accrual is ongoing at the DI of 520 mg/m 2 /w. [Table: see text]
KLF4-Mediated Suppression of CD44 Signaling Negatively Impacts Pancreatic Cancer Stemness and Metastasis
Authors: Yongmin Yan, Zhiwei LI, Xiangyu Kong, Zhiliang Jia, Xiangsheng Zuo, Mihai Gagea, Suyun Huang, Daoyan Wei, Keping Xie
Journal: Cancer Research (2016)

Abstract KLF4 and CD44 regulate cancer cell stemness, but their precise functions and roles in metastatic progression are not well understood. In this study, we used both inducible and genetic engineering approaches to assess whether the activities of these two factors intersect in pancreatic cancer. We found that genetic ablation of Klf4 in pancreatic cancer cells isolated from Klf4flox/flox mice drastically increased CD44 expression and promoted the acquisition of stem-like properties, whereas tetracycline-inducible expression of KLF4 suppressed these properties in vitro and in vivo. Further mechanistic investigation revealed that KLF4 bound to the CD44 promoter to negatively regulate transcription and also the expression of the CD44 variant. Moreover, in human pancreatic ductal adenocarcinoma (PDAC) tissues, the expression patterns of KLF4 and CD44 were mutually exclusive, and this inverse relationship was particularly striking in human metastatic pancreatic tumors and in autochthonous mouse models of PDAC. Taken together, our findings demonstrate that KLF4 acts as a tumor suppressor in PDAC cells that restricts metastatic behaviors through direct negative regulation of CD44, providing support for the clinical investigation of therapeutic approaches focusing on targeted KLF4 activation in advanced tumors. Cancer Res; 76(8); 2419–31. ©2016 AACR.
A prospective study evaluating <sup>18</sup>F-Fluorodeoxyglucose (<sup>18</sup>FDG) positron emission tomography (PET) in the assessment of axillary nodal spread in women undergoing sentinel lymph node biopsy (SLNB) for breast cancer
Authors: K. I. Pritchard, J. Julian, D. McCready, C. Holloway, K. Gulenchyn, N. Hodgson, P. Lovrics, N. Down, R. George, M. N. Levine
Journal: Journal of Clinical Oncology (2008)

533 Background: In women with operable breast cancer, SLNB is often used to assess the axilla. 18FDG PET imaging is potentially useful because of preferential uptake of 18FDG by metabolically active tumor cells. Prior studies of PET in breast cancer have not included many women undergoing SLNB. Methods: Women with operable breast cancer diagnosed within the previous 3 months underwent 18FDG PET followed by SLNB. Axillary node assessment (ANA) consisted of SLNB alone if negative, SLNB with axillary lymph node dissection (ALND) if the SLNB or preoperative PET scan was positive or ALND alone if sentinel nodes were not identified. We considered that PET would be useful if the specificity was 95% or better. Based on a 30% prevalence of women with positive axillary nodes, 320 women were needed so that the lower boundary of the 95% CI for specificity would exclude 91%. Patients were scanned at one of 5 study centers in Ontario, using either a PET scanner or PET/CT instrumentation. Results: Between January 2005 and March 2007, 336 women were entered; 11 were not analyzable. Sentinel nodes were found for 312/325 women (96%) and were positive for tumor by H&E stain in 92 (30%). ALND was performed in 177 (54%) and was positive for tumor in 43 cases (25%): Using logistic regression, age, BMI, number of nodes, and tumor size were assessed as predictors of prevalence, positive PET, and sensitivity. Only tumor size was predictive (p<0.05) for prevalence (OR=1.6), PET positivity (OR=1.7) and PET sensitivity (OR=1.4). Conclusions: 18FDG PET is not sufficiently sensitive to detect positive axillary lymph nodes. However, the very high positive predictive value (96%) in our trial suggests that PET could be used in women with large primary tumors to identify those in whom SLNB may be avoided prior to therapeutic ALND. Parameter Estimate 95% CI Sensitivity 23.0% 15.2% - 32.5% Specificity 99.6% 97.6% - 99.9% Positive Predictive Value 95.8% 78.9% - 99.9% Negative Predictive Value 74.4% 69.1% - 79.3% Prevalence 30.8% 25.8% - 36.1% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis, Biomera, Ortho Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Pfizer, Pharmacia AstraZeneca, Aventis