tbuckley/cabot-search huggingface dataset:
Effect of mannitol and magnesium on cisplatin-induced nephrotoxicity: A retrospective evaluation.
Authors: Robert K. Sylvester, Kyle LaPorte, Paul A. Thompson, John M. Leitch
Journal: Journal of Clinical Oncology (2015)

e20706 Background: Evidence documenting the effectiveness of mannitol and magnesium (Mg) to ↓cisplatin (CDDP) nephrotoxicity is limited. This study was conducted to evaluate the effect of mannitol and Mg on the incidence of CDDP nephrotoxicity. Methods: Data collected included age, sex, cancer diagnosis, CDDP cumulative dose, pre-CDDP serum creatinine (SCr), post-CDDP SCr, and administration of mannitol and Mg. Charts of 100 patients administered mannitol and 99 patients not administered mannitol were reviewed. The incidence of nephrotoxicity was determined for four groups (mannitol alone: n=35, mannitol + Mg: n=64, Mg alone: n=46, neither mannitol nor Mg: n=54). Nephrotoxicity was defined as increase in SCr exceeding normal range. Analysis was performed using PROC GLIMMIX in SAS 9.4. Results: Patient age, baseline SCr and administration of normal saline were similar between groups. Hydration with mannitol was associated with a lower incidence of renal impairment (p< 0.004) and greater length of time before renal impairment developed (p< 0.01). See Table. Cumulative CDDP doses and magnitude of renal impairment revealed no significant differences. Conclusions: Mannitol resulted in a statistically significant reduction in incidence and delayed the onset of CDDP nephrotoxicity. The administration of Mg with mannitol did not result in further reduction of toxicity. These data dispute the 2008 European Society of Clinical Pharmacy SIG on Cancer Care recommendation that mannitol does not attenuate CDDP-induced nephrotoxicity. Larger randomized prospective trials are needed to establish the effectiveness of mannitol and Mg to attenuate CDDP-induced nephrotoxicity. Incidence of CDDP nephrotoxicity. Group # ↑ S Cr (Prop, 95% CI) Days B4 ↑ S Cr (95% CI) Mannitol alone 2/35 = 0.057 (0.014, 0.203) 122.5 (54.2, 190.8) Mannitol + Mg 9/64 = 0.141 (0.075, 0.250) 43.3 (11.2, 75.5) Mg alone 12/46 = 0.261 (0.154, 0.406) 34.4 (6.5, 62.3) Neither 16/54 = 0.296 (0.190, 0.431) 23.6 (-0.5, 47.8)
A Phase Ib Study of Isatuximab in Combination with Bortezomib, Cyclophosphamide, and Dexamethasone (VCDI) in Patients with Newly Diagnosed Multiple Myeloma Non-Eligible for Transplantation
Authors: Enrique M. Ocio, Sara Bringhen, Stefania Oliva, Paula Rodriguez-Otero, Dheepak Kanagavel, Corina Oprea, Vivian Wei, Severine Doroumian, Joaquin Martinez-Lopez
Journal: Blood (2017)
Cholangiocyte‐Derived Exosomal Long Noncoding RNA H19 Promotes Hepatic Stellate Cell Activation and Cholestatic Liver Fibrosis
Authors: Runping Liu, Xiaojiaoyang Li, Weiwei Zhu, Yanyan Wang, Derrick Zhao, Xuan Wang, Emily C. Gurley, Guang Liang, Weidong Chen, Guanhua Lai, William M. Pandak, H. Robert Lippman, Jasmohan S. Bajaj, Phillip B. Hylemon, Huiping Zhou
Journal: Hepatology (2019)

Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte-derived exosomal long noncoding RNA-H19 (lncRNA-H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte-derived lncRNA-H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2-/- ) mouse models were used. Wild-type and H19maternalΔExon1/+ (H19KO) mice were subjected to BDL. Mdr2-/- H19maternalΔExon1/+ (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for in vivo transplantation and in vitro studies. Fluorescence-labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal-H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)/primary biliary cholangitis (PBC) liver samples were analyzed by real-time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC. H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2-/- mice. Transplanted cholangiocyte-derived H19-enriched exosomes were rapidly and preferentially taken up by HSCs and HSC-derived fibroblasts, and promoted liver fibrosis in BDL-H19KO mice and DKO mice. H19-enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC-derived fibroblasts. Conclusion: Cholangiocyte-derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies.
Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer
Authors: Seong Hye Park, Min Jee Jo, Bo Ram Kim, Yoon A Jeong, Yoo Jin Na, Jung Lim Kim, Soyeon Jeong, Hye Kyeong Yun, Dae Yeong Kim, Bu Gyeom Kim, Sang Hee Kang, Sang Cheul Oh, Dae-Hee Lee
Journal: Theranostics (2019)

A major problem of colorectal cancer (CRC) targeted therapies is relapse caused by drug resistance.In most cases of CRC, patients develop resistance to anticancer drugs.Cetuximab does not show many of the side effects of other anticancer drugs and improves the survival of patients with metastatic CRC.However, the molecular mechanism of cetuximab resistance is not fully understood.Methods: EPHB3-mediated cetuximab resistance was confirmed by in vitro western blotting, colony-forming assays, WST-1 colorimetric assay, and in vivo xenograft models (n = 7 per group).RNA-seq analysis and receptor tyrosine kinase assays were performed to identify the cetuximab resistance mechanism of EPHB3.All statistical tests were two-sided.Results: The expression of EFNB3, which upregulates the EPHB3 receptor, was shown to be increased via microarray analysis.When resistance to cetuximab was acquired, EPHB3 protein levels increased.Hedgehog signaling, cancer stemness, and epithelial-mesenchymal transition signaling proteins were also increased in the cetuximab-resistant human colon cancer cell line SW48R.Despite cells acquiring resistance to cetuximab, STAT3 was still responsive to EGF and cetuximab treatment.Moreover, inhibition of EPHB3 was associated with decreased STAT3 activity.Co-immunoprecipitation confirmed that EGFR and EPHB3 bind to each other and this binding increases upon resistance acquisition, suggesting that STAT3 is activated by the binding between EGFR and EPHB3.Protein levels of GLI-1, SOX2, and Vimentin, which are affected by STAT3, also increased.Similar results were obtained in samples from patients with CRC.Conclusion: EPHB3 expression is associated with anticancer drug resistance.
FRI-187-Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and liver-related events in patients with chronic hepatitis B: A propensity score analysis
Authors: Sung Won Lee, Jung Hyun Kwon, Hae Lim Lee, Sun Hong Yoo, Hee Chul Nam, Pil Soo Sung, SoonWoo Nam, Si Hyun Bae, Jong Young Choi, Seung KewYoon, Nam Ik Han, Jeong Won Jang
Journal: Journal of Hepatology (2019)
Bone mineral density of the left femoral neck in lymphoma survivors treated with high dose therapy with autologous stem cell support.
Authors: Mette Seland, Knut Halvor B Smeland, Harald Holte, Trine Bjoero, Kristin Godang, Jens Bollerslev, Sophie D. Fossa, Cecilie E Kiserud
Journal: Journal of Clinical Oncology (2015)

e20612 Background: As we hypothesized high dose therapy with autologous stem cell support (HDT) to increase the risk for low bone mineral density (BMD), aims of this study were to assess BMD of the left femoral neck in lymphoma survivors treated with HDT and to analyze for associations. Methods: Eligible survivors were age 18 and older at HDT at Oslo University Hospital between 1987 and 2008. Participants (n = 179) responded to questionnaires and underwent a BMD examination using a dual-energy X-ray absorptiometry (DXA) densitometer (GE Healthcare Lunar Prodigy). Low BMD was defined as Z-score more than 1 standard deviation (SD) below the mean value of the sex, age, and BMI matched DXA reference database. Logistic regression analysis was performed with low BMD as the dependent variable and clinical (subgroup of lymphoma, treatment lines, conditioning regimen, infradiaphragmatic radiotherapy, relapse, and gonadal hormone dysfunction) and lifestyle (smoking, alcohol consumption, and physical activity) parameters as independent variables. A p-value < 0.05 was considered statistically significant. Results: Age at survey was 56 years (median) and observation time from HDT was 103 months (median). BMD scores are shown in the table below. Due to group size univariate regression analysis was not performed for women. In males there were no associations between clinical and lifestyle variables and low BMD. Conclusions: Mean Z-scores for BMD of the femoral neck in long-term lymphoma survivors were close to normal. However, males had slightly reduced BMD and 21% had Z-scores below -1 SD. Clinical impacts and contributing factors of these findings need further investigation. Males (n = 116) Females (n = 63) Hodgkin lymphoma, n (%) Non-Hodgkin lymphoma, n (%) 20 (17) 96 (83) 17 (27) 46 (73) BMD (g/cm2), mean (SD) Z-score: Mean (CIa) Median (range) 0.956 (0.145) -0.3 (-0.4 to -0.1)(p = 0.007b) -0.3 (-2.5 to 2.0) 0.892 (0.126) -0.005 (-0.2 to 0.2)(p = 0.963b) -0.1 (-1.4 to 2.1) Normal BMD, n (%) Low BMDc, n (%) 92 (79) 24 (21) 59 (94) 4 (6) a95% confidence interval for mean. bDeviation from the DXA reference population was estimated by one-sample t-test. cMales versus females: p= 0.02 (chi-square test).
FRI-335-Lect2, a new hepatokine regulating cholesterol metabolism in liver during non-alcoholic fatty liver disease
Authors: Sandrine Pham, Mathilde Cadoux, Fadila Rayah, Stéphanie Bonnafous, Nesrine Mabrouk, Valentin Derangere, Philippe Gual, TRAN Albert, Catherine Postic, Chantal Desdouets, Catherine Paul, Jean-Pierre Couty
Journal: Journal of Hepatology (2019)
The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case–control and Mendelian randomization study in the European prospective investigation into cancer and nutrition
Authors: K. Smith Byrne, P.N. Appleby, T.J. Key, M.V. Holmes, G.K. Fensom, A. Agudo, E. Ardanaz, H. Boeing, H.B. Bueno-de-Mesquita, M.D. Chirlaque, R. Kaaks, N. Larrañaga, D. Palli, A. Perez-Cornago, J.R. Quirós, F. Ricceri, M.J. Sánchez, G. Tagliabue, K.K. Tsilidis, R. Tumino, R.T. Fortner, P. Ferrari, E. Riboli, H. Lilja, R.C. Travis
Journal: Annals of Oncology (2019)

BackgroundMicroseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods.Patients and methodsA nested case–control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method.ResultsPlasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51–0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56–6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95–0.97 versus EPIC observational: 0.98, 95% CI 0.97–0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP.ConclusionsIn this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.
Synergistic effect of daphnetin with tamoxifen in the inhibition of MCF-7 cell proliferation
Authors: Fausto Jimenez-Orozco, Luis Barcenas-Ochoa, Rosa Fernandez-Ramirez, Maria Garcia-Mondragon, Amelia Maldonado-Espinoza, Nicandro Mendoza-Patino, Juan Mandoki
Journal: Cancer Research (2008)

2602  Daphnetin (7,8-dihydroxycoumarin) is the most active dihydroxicoumarin in inhibiting in vitro the proliferation of several epithelial tumor cells. This compound also inhibits DNA synthesis and the activity of some protein kinases. Daphnetin is not mutagenic and is not a substrate for glycoprotein P, thus, its antiproliferative effect is not affected by the phenotype of multiple drug resistance. Daphnetin, at high concentrations, inhibits ERK1 and ERK2 phosphorylations, reduces the expression of cyclin D1 and produces arrest in phase G1 of the cell cycle; at low concentrations it activates p38 which induces cellular differentiation. Recently we have studied the association of daphnetin with other conventional antitumor agents that act in different phases of the cell cycle. Daphnetin produces summation of the antiproliferative effect only with simultaneous exposures with agents that act in S phase of the cell cycle, like cisplatin, or in G2 phase, like etoposide (no changes were observed with antimitotic agents). In contrast, sequential administrations (48 h of pre-exposure of daphnetin followed by other agents), low concentrations of daphnetin antagonized the antiproliferative effect of the three antitumor agents. Only the two higher concentrations of daphnetin increased their effect. The purpose of this work was to evaluate the antiproliferative effects produced by simultaneous and sequential associations of daphnetin with tamoxifen, that acts in G1 and S phases of the cell cycle. The MCF-7 cells were exposed to the compounds for five days in concentration proportional to the CI50 of each compound (Talalay 1984). The proliferation of the cells was estimated by the microculture tetrazolium assay (MTT) and the results were analyzed statistically (Dunnett9s test) and by isobolograms. The antiproliferative effect of daphnetin with tamoxifen was increased synergistically in the simultaneous and sequential exposures. The estrogens are necessary for the synthesis of cyclin D1; some selective estrogen receptors modulators (SERM) like tamoxifen reduce the expression of this cyclin, as well as daphnetin. The observed synergy could be a consequence of the inhibition cyclin D1 by different mechanism. These results suggest that daphnetin might be useful as a co-adjuvant of tamoxifen in the treatment of breast cancer.
Retraction: Transactivation of the <i>EGR1</i> Gene Contributes to Mutant p53 Gain of Function
Authors: Lilach Weisz, Amir Zalcenstein, Perry Stambolsky, Yehudit Cohen, Naomi Goldfinger, Moshe Oren, Varda Rotter
Journal: Cancer Research (2019)

[This article][1] ([1][2]) has been retracted at the request of the authors. The editors were made aware of concerns regarding potential manipulation of Western blot data in Fig. 2B. An internal review by the editors determined that lanes 2–8 of the vinculin panel of Fig. 3B were horizontally
FRI-256-Procoagulant imbalance in chronic hepatitis C and its relationship with cardiovascular and liver damage
Authors: Giordano Sigon, Giuseppina Pisano, Roberta D’ambrosio, Mariagrazia Clerici, Veena Chantarangkul, Pietro Lampertico, Roberta Sollazzi, Flora Peyvandi, Armando Tripodi, Silvia Fargion, Anna Ludovica Fracanzani
Journal: Journal of Hepatology (2019)
Gender specific mortality in diffuse large B cell lymphoma patients receiving R-CHOP.
Authors: Mahender Yellu, Gunjan Guha, Ayham Deeb, Tahir Latif
Journal: Journal of Clinical Oncology (2015)

e19523 Gender specific mortality in diffuse large B cell lymphoma patients receiving R-CHOP Background: Significant gender specific mortality differences were observed in diffuse large B cell lymphoma (DLBCL) patients undergoing chemo-immunotherapy, with males having worse outcome compared to females. This difference was attributed to the imprecise dosing of rituximab (male patients had lower area under the curve than female patients). We report our single institution experience evaluating gender specific mortality treated with R-CHOP at University of Cincinnati from January 2004 through October 2014.Methods: We retrospectively identified all the patients with DLBCL at our institute. Patients with incomplete data and those who has not received immunotherapy (rituximab) were considered ineligible for the study. Patients were divided into two arms based on age and sex. Statistically significant differences among groups for age, sex and race-specific mortalities were determined by two-tailed one-way ANOVA and unpaired t test.Results: A total of 122 patients with DLBCL receiving R-CHOP were found to be eligible for this study. Significant mortality difference was noted between males and females with the former 26.67% and the later 19.05% (P < 0.0001). Age was also associated with significant difference in mortality. In male patients mortality was significantly higher 41.86% (±2.4) for 60 years or older patients, whereas in those with age ≤ 60 years, the mortality was 16.53% (±0.71) (P < 0.0001). Similarly among female patients, mortality was 35.12% (±3.31) in patients above 60 years compared to 5.04% (±1.58) in patients ≤ 60 years (P < 0.0001). When relative risk analysis was performed, male patients above 60 years are about 1.19 times more susceptible than their female counterparts in the same age group. In patients with age ≤ 60 years, males are 3.28 times more likely to die than their female counterparts in the same age group. Conclusions: This single institution experience confirms significant age and gender specific mortality difference in DLBCL patients receiving rituximab-based therapy. Prospective study designs should consider alternate dosing methods to improve outcomes of patients with diffuse large B cell lymphoma.
PS-056-Higher relapse and retreatment rates in patients who started as HBeAg positive than negative after stopping long-term nucleos (t) ide analogue therapy: results from the randomized controlled STOP study
Authors: Seng Liem, Scott Fung, David Wong, Colina Yim, Jenny Chen, Seham Noureldin, Jordan Feld, Bettina Hansen, Harry Janssen
Journal: Journal of Hepatology (2019)
A 17‐Beta‐Hydroxysteroid Dehydrogenase 13 Variant Protects From Hepatocellular Carcinoma Development in Alcoholic Liver Disease
Authors: Jie Yang, Eric Trépo, Pierre Nahon, Qian Cao, Christophe Moreno, Eric Letouzé, Sandrine Imbeaud, Quentin Bayard, Thierry Gustot, Jacques Deviere, Paulette Bioulac‐Sage, Julien Calderaro, Nathalie Ganne‐Carrié, Alexis Laurent, Jean Frédéric Blanc, Erwan Guyot, Angela Sutton, Marianne Ziol, Jessica Zucman‐Rossi, Jean‐Charles Nault
Journal: Hepatology (2019)

Recently, a loss of function variant (rs72613567) in 17‐beta‐hydroxysteroid dehydrogenase 13 ( HSD17B13 ) has been identified as protective of nonalcoholic (NAFLD) and alcoholic liver disease (ALD). However, the role of this single‐nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) is currently unknown. A total of 3,315 European patients with HCC (n = 1,109) or without HCC, but with chronic liver disease (CLD; n = 2,206), from four centers were analyzed either by whole‐exome sequencing (WES; exploratory cohort, 285 HCC) or genotyped for HSD17B13 rs72613567 (validation cohort, 824 HCC and all CLD). We included a control group of 33,337 healthy European individuals from the Exome Aggregation Consortium. We compared distribution of genotype using the chi‐square test and logistic regression. In the exploratory cohort analyzed by WES, frequency of the TA allele of HSD17B13 rs72613567 was significantly decreased in HCC patients compared to healthy controls ( P = 1.52 × 10 −06 ). In the validation cohort, frequency of TA allele carriers was also decreased in patients with CLD and without HCC (39%) compared to healthy individuals (47%; P &lt; 0.0001). The protective effect of the TA allele of HSD17B13 rs72613567 was identified in patients with ALD (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.65‐0.82; P &lt; 0.0001), NAFLD (OR = 0.64; 95% CI, 0.49‐0.83; P = 0.0007), and hepatitis C (OR = 0.71; 95% CI, 0.60‐0.85; P = 0.0002). In patients with ALD, the proportion of TA allele carriers with HCC was significantly lower (32%) than in CLD patients without HCC (40%), even after adjustment for age, sex, and fibrosis (OR = 0.64; 95% CI, 0.46‐0.87; P = 0.005). Conclusion: The HSD17B13 rs72613567 loss of function variant is protective of HCC development in patients with ALD.
THU-140-Characteristics of patients and effectiveness of chronic hepatitis C treatment during the initial 4 years of access to interferon-free therapy
Authors: Robert Flisiak, Beata Lorenc, Klapaczynski Jakub, Ewa Janczewska, Wlodzimierz Mazur, Dorota Zarebska-Michaluk, Magdalena Tudrujek, Krzysztof Tomasiewicz, Dorota Dybowska, Waldemar Halota, Marek Sitko, Iwona Orłowska, Simon Krzysztof, Agnieszka Czauz-Andrzejuk, Teresa Belica-Wdowik, Hanna Berak, Jerzy Jaroszewicz, Rafal Krygier, Piekarska Anna, Łukasz Socha, Jolanta Citko, Dobracka Beata, Tronina Olga, Deron Zbigniew, Łukasz Laurans, Jolanta Bialkowska-Warzecha, Matgorzata Pawłowska
Journal: Journal of Hepatology (2019)
FRI-473-Safety and effectiveness of regorafenib in recurrent HCC after liver transplantation and progression on sorafenib: A real-life multicentre study
Authors: Massimo Lavarone, Federica Invernizzi, Carolin Czauderna, Marco Sanduzzi Zamparelli, Sherrie Bhoori, Giuliana Amaddeo, Matteo Angelo Manini, Miguel Fraile, Maria Margarita Anders, Matthias Pinter, Maria Jose Blanco Rodriguez, Mario Romero, Aballay Soteras Gabriel Alejandro, Federico Pinero, Gerda Elisabeth Villadsen, Arndt Weinmann, Gonzalo Crespo, Vincenzo Mazzaferro, Helene Regnault, Massimo De Giorgio, Maria Luisa Gonzalez Dieguez, Maria Francesca Donato, Maria Varela, Wörns Marcus, Jordi Bruix, Pietro Lampertico, María Reig
Journal: Journal of Hepatology (2019)
THU-478-CXCL5 induced by transforming growth factor-beta and Axl signalling causes neutrophil extracellular trap formation in hepatocellular carcinoma
Authors: Elisa Holstein, Eva Řezníčková, Teresita Flores, Huber Heidemarie, Gerhard Weber, Thomas Mohr, Gerald Timelthaler, Wolfgang Mikulits
Journal: Journal of Hepatology (2019)