tbuckley/cabot-search huggingface dataset:
P0519 : Lipidomics reveals that low plasma unsaturated to saturated fat ratios are biomarkers of NAFLD and liver damage
Authors: M. Gaggini, C. Saponaro, C. Rosso, E. Buzzigoli, F. Carli, D. Ciociaro, L. Mezzabotta, E. Vanni, R. Gambino, F. Saba, S. Carenzi, G.P. Caviglia, M.L. Abate, A. Smedile, M. Rizzetto, M. Cassader, E. Bugianesi, A. Gastaldelli
Journal: Journal of Hepatology (2015)
Immunity to Tumor-Associated Antigens in Vasectomized Men&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: D J Anderson, N J Alexander, D L Fulgham, A A Vandenbark, D R Burger
Journal: JNCI Journal of the National Cancer Institute (1982)

Leukocytes from 49 vasectomized and 57 age-matched nonvasectomized men were tested in the leukocyte adherence inhibition (LAI) assay for reactivity to sperm and various 3-M KCl human tumor extracts. Forty-four percent of the vasectomized men and 15% of the control group were reactive to the sperm antigen preparation (P less than or equal to 0.03). Similarly, a significantly higher percentage of vasectomized men responded to 3 of 5 tumor extracts tested: melanoma I (34.7 vs. 15.8%, P less than or equal to 0.04), squamous cell carcinoma (48.8 vs. 26.0%, P less than or equal to 0.04), and breast carcinoma (19.5 vs. 4%, P less than or equal to 0.04). Thirty percent of vasectomized versus 4% of the control group responded to more than two tumor antigens (P less than or equal to 0.03). The degree of LAI reactivity to each tumor extract was highly correlated with degree of antisperm LAI reactivity, and the degree of LAI responsiveness to one of the melanoma extracts was significantly correlated with antisperm antibody titer as measured by the sperm-immobilization assay. Furthermore, nonresponsive leukocytes from the control population converted to tumor antigen-responsive when incubated with sera from vasectomized LaI-positive men. Data from this study indicated that a large percentage of vasectomized men with sperm immunity were responsive to tumor-associated antigens in the LAI test and that antisperm antibodies or other serum factors played a role in this response. These results and the evidence that most tumor antigen-responsive cancer patients also have serum antibodies that reacted with sperm suggested that vasectomized men and cancer patients frequently responded to immunologically cross-reactive antigenic determinants present on both sperm and tumor cells.
Reversible hexadimethrine-induced alterations in glomerular structure and permeability.
Authors: C R Bridges, H G Rennke, W M Deen, J L Troy, B M Brenner
Journal: Journal of the American Society of Nephrology (1991)

Female Munich-Wistar rats received hexadimethrine (HDM) i.v. until the onset of proteinuria (PEAK)--a period of not more than 30 min. There were four experimental groups: C (control), H (HDM only), HH (HDM and heparin), and HHD (identical to HH but with dextran clearances measured). Rats in groups HH and HHD received a heparin bolus after the PEAK period, whereas rats in group H did not. HDM led to dramatic increases in both albumin and IgG excretion. Glomerular filtration rate and renal plasma flow rate were reduced by 30 to 50% after HDM infusion. Neutral dextran clearances for radii greater than 30 A were elevated during the PEAK period, and, concurrently, there was extensive intraglomerular microthrombosis, obliteration of foot processes, and disruption of filtration slit diaphragms. One hour later, glomerular filtration rate, renal plasma flow rate, dextran clearances, and proteinuria returned to baseline in groups HH and HHD but not in group H. Recovery in heparin-treated rats was associated with reversal of HDM-associated morphological alterations. Membrane pore-size parameters calculated from the dextran clearances indicate that HDM leads to a detect in glomerular size-selectivity. The facts that maximal albuminuria tended to precede maximal excretion of IgG and that increases in albumin excretion were proportionately greater than those of dextran or IgG suggest that HDM also leads to a time-dependent defect in glomerular charge-selectivity.
Abstract A33: Combined therapy of a novel anti-NOTCH2/3 antibody with paclitaxel inhibits tumor growth in a patient-derived breast tumor xenograft
Authors: Jie Wei, Jennifer Cain, Jalpa Shah, Breanna Wallace, Tracy Tang, Min Wang, Christopher Murriel, Cancilla Belinda, Austin Gurney, Aaron Sato, John Lewicki, Ann Kapoun, Tim Hoey
Journal: Clinical Cancer Research (2015)

Abstract Cancer stem cells (CSCs) have been identified as the small subpopulation of cells in many cancers and are thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. The NOTCH pathway, comprised of ligands JAG1, JAG2, DLL1, DLL3 and DLL4 and receptors NOTCH1, NOTCH2, NOTCH3 and NOTCH4, plays a critical role in stem cell signaling, cell proliferation, survival, apoptosis, and differentiation. Because of the existing body of data that implicates aberrant NOTCH pathway activation in resistance to chemotherapeutic agents in epithelial and hematologic tumors, we hypothesized that NOTCH inhibition would enhance the anti-tumor activity of chemotherapeutic agents. We have identified a NOTCH3 activating mutation in a patient breast cancer and developed a xenograft tumor model from the primary patient sample, OMP-B37. The combination of paclitaxel and OncoMed's anti-Notch2/3 antibody, OMP-59R5, inhibited the tumor growth of OMP-B37 xenograft tumors. In addition, we found that treatment with OMP-59R5 drove changes in tumor heterogeneity as indicated by the increased expression of markers associated with a mature cellular fate. The down-regulation of tumor growth promoting genes and NOTCH pathway markers was observed with OMP-59R5 treatment. The enhanced activity of combined OMP-59R5 and paclitaxel therapy in patient-derived tumor xenografts suggests that there is therapeutic potential in combining targeted NOTCH pathway inhibition with chemotherapeutic agents. Citation Format: Jie Wei, Jennifer Cain, Jalpa Shah, Breanna Wallace, Tracy Tang, Min Wang, Christopher Murriel, Cancilla Belinda, Austin Gurney, Aaron Sato, John Lewicki, Ann Kapoun, Tim Hoey. Combined therapy of a novel anti-NOTCH2/3 antibody with paclitaxel inhibits tumor growth in a patient-derived breast tumor xenograft. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A33.
PTH-131 Umbilical hernia repair in cirrhosis: outcomes and prognostic factors in a liver transplant unit
Authors: S John, P Burnell, S Robinson, S Masson, G Sen, M Hudson, D Manas
Journal: Gut (2015)

<h3>Introduction</h3> Patients with end stage liver disease (ESLD) carry a significant risk of adverse outcome after abdominal wall hernia repair, particularly with emergent surgery. Historically, high morbidity and mortality rates have been reported in this cohort. Here, we aim to assess the main predictors for mortality in our own group of high-risk ESLD patients undergoing umbilical hernia repair <h3>Method</h3> We performed a retrospective review of a prospectively maintained database of patients with ESLD undergoing surgical repair of complicated umbilical hernias at a regional liver transplant unit over a 15-year period (1999 to 2014). Two third of the patients were operated in the last 6 years. Patient characteristics and outcomes have been analysed and p &lt; 0.05 was considered significant (SPSS vs.19). <h3>Results</h3> In total, 69 patients underwent surgical repair (M-52; F-17) at a median age of 58 years (19–88). Of these, 71% were operated on emergently due to incarceration/strangulation or rupture. The patients’ Childs-Pugh grade was A (n = 11; 16%), B (n = 32, 46%) and C (n = 26, 38%); the majority (71%) had ascites. The median MELD score was 12 (2–36) and median UKELD was 53(45–63). Postoperatively, 43% patients required ITU care with median LOS 2 days (1–13) and median hospital stay of 11 days (1–73). Postoperative decompensation occurred in 79% of patients, with 26% subsequently requiring liver transplantation in follow-up. At 120 days, the rate of mortality or transplantation was 19%. Overall mortality was 30% at a median follow-up of 35 months (1–160 months). Following univariate logistic regression analysis, Childs-Pugh Grade C, requirement for ITU care, post-operative decompensation and hepatic encephalopathy were significant for prediction of mortality or transplantation at 120 days. After multivariate analysis, only hepatic encephalopathy remained significant, with an odds ratio of 7.04 (p = 0.04). <h3>Conclusion</h3> In this series of patients with ESLD, emergent surgical repair of complicated umbilical hernias was associated with significant morbidity and mortality. In our series, development of post-operative encephalopathy was an independent predictor of mortality. This may reflect the late presentation (71% emergent surgery) and high rate of C-P C patients in this cohort. <h3>Disclosure of interest</h3> None Declared.
Evidence for a Proliferative Advantage of Human Leukemia Colony-Forming Cells In Vitro 23
Authors: Hal E. Broxmeyer, Elliot Grossbard, Niels Jacobsen, Malcolm A. S. Moore
Journal: JNCI Journal of the National Cancer Institute (1978)

Inhibitory mechanisms that might provide leukemia granulocytic stem cells with a proliferative advantage over normal granulocytic stem cells were investigated. Extracts from marrow and blood cells of patients with leukemia were assayed for inhibitory activity against the exogenously stimulated cloning of normal and leukemia granulocyte—monocyte colony-forming cells in agar (CFU-C) present in fractions of nonadherent light density bone marrow. Extracts of cells from patients who had acute leukemia not in remission and who had inhibitory activity containing cells had higher levels of inhibitory activity against normal CFU-C than did extracts from cells of patients who had chronic leukemia. Extracts from normal cells did not inhibit exogenously stimulated normal or leukemia colony formation. Leukemia CFU-C were unaffected by single or multiple additions of leukemia cell extracts containing 104-106 times as much inhibitory activity as that necessary for maximal inhibition of CFU-C from normal donors. Cells from patients with acute leukemia in remission rarely demonstrated inhibitory activity. However, CFU-C from most of these patients with acute leukemia in remission were insensitive to active leukemia cell extracts. The cell responsible for inhibitory activity against normal CFU-C was nonadherent and of light density and had a velocity sedimentation range of 2.5–6.3 mm/hour. The number and percent of cells containing inhibitory activity varied from patient to patient but appeared to be higher in patients with more aggressive disease. inhibitory cells could be partially separated from CFU-C of leukemia patients. These in vitro phenomena may have relevance to the pathogenesis of acute leukemia.
R3327 Prostate Adenocarcinoma Clonogenic Cells: Epithelial Properties and Hormone Response&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: J J Dibner, A Nakeff
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article R3327 Prostate Adenocarcinoma Clonogenic Cells: Epithelial Properties and Hormone Response Get access Julia J. Dibner, Julia J. Dibner 5Section of Cancer Biology, Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4511 Forest Park Blvd., St. Louis, Mo. 63108. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexander Nakeff Alexander Nakeff 7 5Section of Cancer Biology, Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4511 Forest Park Blvd., St. Louis, Mo. 63108. 7Address reprint requests to Dr. Nakeff. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 70, Issue 6, June 1983, Pages 1057–1058, https://doi.org/10.1093/jnci/70.6.1057 Published: 01 June 1983 Article history Received: 23 September 1980 Revision received: 22 November 1982 Accepted: 13 December 1982 Published: 01 June 1983
Complication models to predict radiation-induced cardiac toxicity in patients with breast cancer
Authors: S. K. Das, A. Baydush, S. Zhou, M. Miften, X. Yu, K. Light, T. Wong, S. Borges-Neto, L. Marks
Journal: Journal of Clinical Oncology (2004)

758 Background: Predicting the risk of radiation therapy (RT) induced normal tissue complications is important during RT field design. A widely employed formalism for predicting complication, though sparsely validated with clinical data, is the Kutcher normal tissue complication probability (NTCP) model. We herein examine the validity of the NTCP model, in comparison to other statistical models, as a predictor of left ventricle perfusion defects caused by tangential RT to the left-breast/chest wall. Methods: Since 1998, we have been conducting an IRB-approved prospective clinical trial in patients receiving left-sided tangential photon therapy (46–50 Gy at 1.8–2 Gy/fx) to assess RT-induced changes in cardiac function. Patients had pre-RT and 6-month post-RT SPECT (single photon emission computed tomography) cardiac perfusion scans. The datasets of 68 patients with normal pre-RT SPECT scans form the basis of this report. Of these patients, 19 had SPECT perfusion defects at 6 months. The left ventricle dose-volume histograms (DVH) of all patients were used to generate the NTCP model and two other statistical discriminants: generalized equivalent uniform dose (GEUD), and linear discriminant analysis (LDA). GEUD converted the nonuniform dose distribution into an equivalent uniform dose. LDA used a linear combination of step-wise selected DVH features to optimally separate the groups with and without defects. To compare the three models, we used receiver operating characteristic (ROC) curves that plot sensitivity and specificity as a function of discriminant value. A higher ROC curve, and hence higher area under the curve, implies a better model. Results: The areas under the curve for NTCP, GEUD, and LDA were 0.81, 0.81, and 0.91, respectively. The ROC curves for NTCP and GEUD were exactly coincident. LDA was a better predictor than both (p = 0.03). Conclusions: In the breast cancer patient population studied, the widely used NTCP model was a worse predictor of RT induced cardiac toxicity than the simpler linear discriminant analysis. (Supported by DOD award BC010663. Thanks to UNC for PLUNC software.) No significant financial relationships to disclose.
O-011 Characteristics and outcomes of patients enrolled in the CORRECT and CONCUR phase 3 trials of regorafenib for metastatic colorectal cancer (mCRC)
Authors: A. Grothey, E. Van Cutsem, A. Wagner, J. Kalmus, S. Qin, R. Xu, T.W. Kim, J. Li
Journal: Annals of Oncology (2015)
Cytodifferentiation in the Acute Myeloblastic Leukemias of Man2
Authors: S. Lan, E. A. McCulloch, J. E. Till
Journal: JNCI Journal of the National Cancer Institute (1978)

Correlation analysis of numbers of colony-forming progenitor cells was used as an approach to the quantitation of human pluripotent stem cells. Marrow specimens were obtained from 24 patients with untreated acute myeloblastic leukemia, 22 patients under treatment, and 29 patients with no hematologic malignant disease. Three classes of progenitor cells were assayed: burst-forming units dependent on erythropoietin (BFU-E), colony-forming units dependent on erythropoietin (CFU-E), and granulopoietic progenitors (CFU-C). Significant positive correlations between numbers of BFU-E, CFU-E, and CFU-C were found in all 3 groups of patients. In contrast, no such positive correlations were seen between marrow blasts and any of the classes of colony-forming progenitors. These results were compatible with a shared relationship of the colony-forming progenitors to a pluripotent cell of origin and raised the possibility that the immediate progenitors of the blasts may not be any of the myelopoietic progenitor cells monitored in these studies.
American Board of Psychiatry and Neurology, Inc. Report on the 2004 Examinations
Journal: American Journal of Psychiatry (2005)

Joan Setsuko R. Kagawa, M.D. Stephen Jay Kanes, M.D., Ph.D. Anthony Marwan Kassir, M.D. Joseph Kenan, M.D. Safeer Ahmed Khan, M.D. Sikandar Khan, M.D. Yasmin Farida Khan, M.D. Henry Htwe Lay Khin, M.D. Amy Jean Kieswetter, M.D. Danielle Lynne Kizer, M.D. Bradley Jay Kleinsasser, M.D. Kristine Elizabeth Klemm, M.D. Kimberly Gottlieb Klipstein, M.D. Ljudmil Kljusev, M.D. Himabindu Koneru, M.D. Maya Leba Kopell, M.D. Elizabeth Jane Kostrey, M.D. Heather V. Krell, M.D., M.P.H. Malathy Kuppuswamy, M.D.
Population-Based Patterns of Surgical Care for Stage IIIA NSCLC in the Netherlands between 2010 and 2013
Authors: Chris Dickhoff, Max Dahele, A. Joop de Langen, Marinus A. Paul, Egbert F. Smit, Suresh Senan, Koen J. Hartemink, Ronald A. Damhuis
Journal: Journal of Thoracic Oncology (2016)
Response to Letter Regarding Article, “Temporal Trends in Percutaneous Coronary Intervention Appropriateness: Insights From the Clinical Outcomes Assessment Program”
Authors: Steven M. Bradley, Chad M. Bohn, David J. Malenka, Michelle M. Graham, Chris L. Bryson, James M. McCabe, Jeptha P. Curtis, Anne Lambert-Kerzner, Charles Maynard
Journal: Circulation (2016)
Response Rate as a Regulatory End Point in Single-Arm Studies of Advanced Solid Tumors
Authors: Geoffrey R. Oxnard, Katharine H. Wilcox, Mithat Gonen, Mikhael Polotsky, Bradford R. Hirsch, Lawrence H. Schwartz
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Objective response rate (ORR) is an increasingly important end point for accelerated development of highly active anticancer therapies, yet its relationship to regulatory approval is not well characterized. <h3>Objective</h3> To identify circumstances in which a high ORR is associated with regulatory approval, and therefore might be an appropriate end point for definitive single-arm studies of anticancer therapies. <h3>Data Source</h3> A database of all oncology clinical trials registered at clinicaltrials.gov between October 1, 2007, and September 30, 2010. <h3>Study Selection</h3> Trials of palliative systemic therapies for 4 measurable solid tumor types, limited to those with trial arms of at least 20 patients reporting ORR per Response Evaluation Criteria in Solid Tumors (RECIST). <h3>Data Extraction and Synthesis</h3> A systematic search was used to identify the reported ORR for each eligible treatment arm that had been presented publicly. <h3>Main Outcomes and Measures</h3> For each treatment regimen, defined as a single-agent or unique combination of agents for 1 cancer type, the mean ORR and the maximum ORR statistically exceeded were calculated, and their association with regulatory approval was studied. A regimen was considered approved for a specific cancer type if it had received regulatory approval in any country for treatment of advanced cancer of that type. <h3>Results</h3> From 1800 trials, 874 eligible trial arms in 578 eligible trials were identified; 542 arms had ORR data available for 294 regimens. Maximum ORR and mean ORR were significantly associated with regulatory approval (τ = 0.27,<i>P</i> &lt; .001; τ = 0.12,<i>P</i> = .01); this relationship was stronger for single-agent therapies (τ = 0.49; τ = 0.41) than for combination regimens (τ = 0.28; τ = 0.17). Evaluation of ORR thresholds between 20% and 60% as potential trial end points demonstrated that ORR statistically exceeding 30% with a single agent had 98% specificity and 89% positive predictive value for identifying regimens achieving regulatory approval. <h3>Conclusions and Relevance</h3> For single-agent regimens, high ORR was associated with regulatory approval; this relationship was less strong for combination regimens. Our data suggest that high ORR (eg, statistically exceeding an ORR of 30%) is an appropriate end point for single-arm trials aiming to demonstrate breakthrough activity of a single-agent anticancer therapy.
Rational for "eight-in-one" chemotherapy.
Authors: H S Friedman
Journal: Journal of Clinical Oncology (1988)

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.1988.6.2.393 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3339400 Rational for "eight-in-one" chemotherapy. H S FriedmanxH S FriedmanSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.2.393 First Page PDF © 1988 by American Society of Clinical Oncology
Increased expression of α1-hydroxylase (CYP27B1) in IL-13-exposed primary bronchial epithelial cells (PBEC): Consequences for activation of vitamin D and expression of the antimicrobial peptide hCAP-18/LL-37
Authors: J.A. Schrumpf, R.M. Verhoosel, M.A.J.A. Sterkenburg, S. Zuyderduyn, P.S. Hiemstra
Journal: European Respiratory Journal (2011)

Vitamin D3 (25(OH)D 3 ) increases expression of hCAP-18/LL-37 in PBEC. This requires conversion of 25(OH)D3 by 1α-hydroxylase (CYP27B1) into its active metabolite 1,25(OH) 2 D 3 , that increases expression of both hCAP-18/LL-37 and the vitamin D degrading enzyme (CYP24A1). IL-13 is highly expressed in the lungs of asthmatics and low serum 25(OH)D 3  levels were associated with lower lung function in asthmatics.  The aim of the present study was to investigate the role of IL-13 in vitamin D metabolism and to assess its effect on expression of hCAP-18/LL-37.  Well-differentiated PBEC cultured at the air-liquid interface from 5 different donors were pre-incubated with IL-13 for 24 hours and subsequently exposed to 25(OH)D 3  for 48 hours to investigate CYP27B1, CYP24A1, vitamin D receptor (VDR), human β-defensin (hBD)-2 and -3 by qPCR. hCAP-18/LL-37 expression was determined by qPCR, immune fluorescence (IF) and Western blot.  Exposure of PBEC to IL-13 alone increased CYP27B1 and hBD-3 mRNA (fold increases of 5.2 and 3.13 resp.; p 3  to IL-13 treated cells resulted in higher expression (p 3  alone (fold increase: 32.6 and 13.9, resp.). These results were confirmed by IF and Western blot for hCAP-18/LL-37.  The present results show that IL-13 increases vitamin D metabolism in bronchial epithelial cells resulting in increased expression of hCAP-18/LL-37. Whether IL-13 contributes to host defence against infection through this mechanism requires further studies.