tbuckley/cabot-search huggingface dataset:
Cardiovascular risk and coronary artery calcium score after liver transplantation: study at fouth year
Authors: L.M. Linhares, C.P. Oliveira, M.R. Alvares-Da-Silva, J.T. Stefano, E.M. Gebrim, H.V. Barbeiro, D.F. Barbeiro, D.R. Terrabuio, E. Abdala, F.G. Soriano, F.J. Carrilho, A.Q. Farias, L. Augusto, C. D’albuquerque
Journal: Journal of Hepatology (2017)
Cytotoxicity of lipoxygenase inhibitors towards prostate cancer cells in culture
Authors: Renshu Zhang, Sheree Brown, Kris Guerrier, Alemayehu Kassa, Yanfei Zhou, Xinbin Gu, Ebrahim Ashayeri, Rajagopalan Sridhar
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5863 

Free radicals may play a prominent role in the development and progression of prostate cancer. The lipid oxidation product 12-(S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid (12-S-HETE), which disrupts normal signal transduction in cells, has been associated with hormone refractory prostate cancer. Prostate cancer cells that overproduce 12-S-HETE are relatively resistant to apoptosis. Therefore inhibitors of 12-lipoxygenase may be useful for eradicating hormone refractory cells. The cytotoxicities of non specific lipoxygenase inhibitors such as nordihydroguaiaretic acid (NDGA), coumarin and 4-hydroxycoumarin towards androgen independent human prostate cancer cell lines PC-3 and DU-145 were evaluated using the MTT assay for cell viability. The anthracycline mitoxantrone is used for treating advanced prostate cancer. Therefore the cytotoxicities of the lipoxygenase inhibitors and mitoxantrone were compared. For these studies, attached monolayers of cells were exposed to graded concentrations of NDGA (1 to 20 mM) for either 6 hours or 72 hours, and cell viability was assayed at 72 hours. Cell viability was similar for both 6 and 72 hour treatments with NDGA, suggesting that NDGA was inactivated by metabolism during prolonged exposure to cells. Mitoxantrone toxicity was studied over the micromolar range, whereas the coumarins were tested in the millimolar range. Cell viability decreased to 50, 70, 72 and 64% (relative to control) as a result of 6 hour exposure of PC-3 cells respectively to mitoxantrone (0.1μM), nordihydroguaiaretic acid (20mM), coumarin (1mM) and 4-hydroxycoumarin (1mM). All three lipoxygenase inhibitors were cytotoxic to PC-3 and DU-145 cells, albeit less so than mitoxantrone, which carries some clinical risk of cardiotoxicity. When NDGA (5 mM) was combined with mitoxantrone, it decreased the cytotoxicity of mitoxantrone. Coumarin in the 1 to 5 mM range, was less cytotoxic than 4-hydroxycoumarin towards PC-3 and DU-145 cells after a 6 or 72 hour treatment. The cytotoxicity of coumarin over the 1 to 5 mM range was enhanced when combined with 4-hydroxycoumarin (1 or 5 mM). These results suggest that lipoxygenase inhibitors may have some therapeutic potential without risk of cardiotoxicity. This work was supported in part by grant # DAMD17-03-1-0123 from USMRMC, and grant 2G12 RR003048 from the RCMI program, NCRR/NIH.
A phase II trial of first-line nab-paclitaxel/carboplatin versus gemcitabine/carboplatin in advanced squamous cell carcinoma of the lung (CTONG1002).
Authors: Jinji Yang, Cheng Huang, Yong Song, Ying Cheng, Gongyan Chen, Hong-Hong Yan, Qing Zhou, Huajun Chen, Xiao-song Ben, Yi-Long Wu
Journal: Journal of Clinical Oncology (2014)

8085 Background: The administration of nab-paxlitaxel/carboplatin (nab-PC) as first-line therapy in patients with advanced non-small-cell lung cancer was efficacious and resulted in a significantly improved objective overall response rate (ORR) versus solvent-based PC in a phase III trial. Subgroup analysis showed the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment. This phase II trial (NCT01236716; CTONG1002) compared the efficacy and safety of first-line nab-PC with gemcitabine/carboplatin (GC) in advanced squamous cell carcinoma of the lung. Methods: From November 2010 to June 2013, 127 untreated patients with locally advanced and metastatic squamous cell carcinoma of the lung were randomly assigned 1:1 to receive first-line nab-PC (nab-P, 135 mg/m2, d1, d8, q3w; C, AUC = 5, d1, q3w ) or GC (G, 1,250 mg/m2, d1, d8, q3w; C, AUC = 5, d1, q3w). The primary end point was ORR. Results: There were 110 cases evaluable for ORR (nab-PC, 54; GC, 56), 119 evaluable for survival (nab-PC, 57; GC, 62) and 124 evaluable for safety (nab-PC, 59; GC, 65), respectively. ORR was 46.3% (25/54) for the nab-PC arm and 30.4% (17/56) for the GC arm respectively, P = 0.085. There was an approximately 18.8% improvement in progression-free survival (median, 5.7 v 4.8 months; hazard ratio [HR], 0.907; 95% CI, 0.588 to 1.399; P = 0.657) in the nab-PC arm versus the GC arm. Overall survival was not mature. Significantly more grade ≥ 3 leucopenia and neutropenia occurred in the nab-PC arm. Conclusions: First-line nab-PC in advanced squamous cell carcinoma of the lung was efficacious and resulted in a marginally improved ORR versus GC, but not achieving the primary end point. nab-PC produced more leucopenia and neutropenia than GC. Clinical trial information: NCT01236716.
Establishment and characterization of Smad4- and p53-null GEM models for colorectal adenocarcinoma.
Authors: Jun Won Park, Jeffrey E. Green, Hark K. Kim
Journal: Journal of Clinical Oncology (2015)

e14697 Background: Mutations of TP53 and SMAD4 are significantly recurrent in human non-hypermutated colorectal cancers. We have established and characterized a novel genetically-engineered mouse (GEM) model for colorectal cancer by performing intestinal epithelium-specific knockout of Smad4 and p53 through cre expression directed by the villin promoter. Methods: Smad4F/F conditional knockout mice were provided by Dr. Chuxia Deng (NIDDK). Compound conditional knockout mice for Smad4 and p53 (Smad4F/F;Trp53F/F) were mated with Villin-Cre mice to produce offspring that are deficient in Smad4 and p53 in the intestinal epithelium (Villin-Cre;Smad4F/F;Trp53F/F). Results: All Villin-Cre;Smad4F/F;Trp53F/F mice died of intussusception or intestinal obstruction. At the time of necropsy, all Villin-Cre;Smad4F/F;Trp53F/F mice demonstrated multiple spontaneous tumors in the small and large intestines. The incidence of intestinal adenocarcinomas was 75.9 % in Villin-Cre;Smad4F/F;Trp53F/F mice. Villin-Cre;Smad4F/F;Trp53F/F mice demonstrated signficantly shorter adenocarcinoma-free survival than Villin-Cre;Smad4F/F mice or Villin-Cre;Trp53F/F mice [p < 0.001]. These results suggest that Smad4 and p53 cooperate to suppress intestinal adenocarcinomas. One Villin-Cre;Smad4F/F; Trp53F/F;Cdh1F/+ mouse developed the adenocarcinoma in the glandular stomach, and primary cultured cells established from this mouse tumor (designated NCC-S1M) recapitulated human diffuse type gastric adenocarcinomas in morphology when implanted into mice. In vivo efficacy of anti 4-1-BB antibody, which preferentially enhances CD8+T-cells, was tested for NCC-S1M heterotopic allografts formed in immunocompetent syngeneic mice. Anti-4-1BB mAb suppressed the growth of NCC-S1M tumors compared to the control [p < 0.0001]. Conclusions: Smad4 and p53 are bona fide tumor suppressor genes in the intestinal epithelium. Given the high penetrance and rapid onset of intestinal adenocarcinomas, Villin-Cre;Smad4F/F;Trp53F/F mice are useful preclinical tools for drug testing in syngeneic mice.
Abstract A47: A patient-derived xenograft model of pancreatic cancer in mice to develop novel adjuvant therapies
Authors: Matthew G. Mullen, Timothy E. Newhook, James M. Lindberg, Sara J. Adair, Edik M. Blais, Alex D. Michaels, Edward B. Stelow, Jason A. Papin, J. Thomas Parsons, Todd W. Bauer
Journal: Cancer Research (2016)

Abstract Background: Eighty percent of patients with pancreatic ductal adenocarcinoma (PDAC) die from their disease within five years of surgical resection, likely due to presence of occult metastases at diagnosis. We have developed a patient-derived xenograft (PDX) model in mice to investigate the behavior of occult metastatic cells in the liver microenvironment and derive novel adjuvant therapies. Methods: Five PDAC tumors (215, 366, 608, 654 and 738) were resected from patients and implanted orthotopically in mice. Tumors were harvested, cell lines generated and transduced with luciferase, then injected into spleens of mice to generate microscopic liver metastases, then primary tumors removed via splenectomy. Bioluminescence imaging of mice and histologic analysis and flow cytometry of livers were utilized to characterize each tumor's distinct pattern of cell clearance and outgrowth kinetics. Affymetrix gene expression of tumors was performed. Mice were treated with adjuvant therapy following resection of primary tumors in the spleen and time-to-progression (TTP) and overall survival (OS) were measured. Results: Each PDX cell line demonstrated unique and reproducible clearance in the liver and outgrowth kinetics as measured by bioluminescence imaging. Distinct differences in gene expression were identified in tumors exhibiting rapid vs. delayed outgrowth. The MEK inhibitor trametinib (0.3 mg/kg oral daily) prolonged TTP and OS vs. control (OS - Tumor 608: 114 vs. 43 days, p&amp;lt;0.001; Tumor 366: MS not achieved vs. 167 days, p=0.0488). In a randomized preclinical trial, sequential therapy with gemcitabine followed by trametinib provided a survival advantage and increased TTP when compared with control and single agent gemcitabine treatment. Conclusions: This PDX PDAC model of occult metastasis allows characterization of hepatic clearance of tumor cells and outgrowth kinetics. Metastatic outgrowth appears to be dependent upon distinguishable tumor cell-specific factors. Trametinib effectively inhibits KRAS-MEK-ERK signaling, delays outgrowth of occult metastases and prolongs survival of mice. Utilization of this model will help further define the complex interaction of PDAC cells and the metastatic microenvironment of the liver. Citation Format: Matthew G. Mullen, Timothy E. Newhook, James M. Lindberg, Sara J. Adair, Edik M. Blais, Alex D. Michaels, Edward B. Stelow, Jason A. Papin, J. Thomas Parsons, Todd W. Bauer. A patient-derived xenograft model of pancreatic cancer in mice to develop novel adjuvant therapies. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A47.
Liver stiffness and portal hypertension predict failure to DAA treatment in a real-life cohort of hepatitis C virus-infected patients treated with recommended regimens
Authors: C. Masetti, F. De Leonardis, P. Rossi, A. Bosa, D. Di Paolo, M. Milana, F. Santopaolo, A. Pecchioli, S. Di Nardi, S. Francioso, I. Lenci, L. Baiocchi, A. Brega, F. Antenucci, T. Marianelli, M. Angelico
Journal: Journal of Hepatology (2017)
Impact of aging on genomic abnormalities in breast cancer
Authors: Vita Fedele, Christopher C. Benz, Stefania Tommasi, Angelo Paradiso, Donna Albertson
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2540 

We have previously shown that in addition to increasing breast cancer incidence, aging can significantly alter breast cancer biology as defined by validated prognostic and predictive biomarkers. In particular, biomarkers thought to reflect breast cancer genomic instability (e.g. high nuclear grade, aneuploidy, p53 immunoreactivity) show strong inverse correlations with patient age-at-diagnosis. To more directly assess the relationship between aging and breast cancer gene copy number abnormalities, comparative genomic hybridization array (aCGH, a 1MB resolution) analyses were performed on tumor DNA samples from two age-based cohorts of breast cancer cases collected from a single geographic region (Bari) and characterized by stage and hormone receptor status (ER, PR). Using the following age-at-diagnosis cohort definitions: younger (Y) ≤ 45 and older (O) ≥ 70 years, 125 (Y = 56; O = 64) cases have been analyzed to date. Consistent with previous reports, these two age cohorts contain significantly different proportions of ER/PR breast cancer phenotypes (p = 0.003): ER+/PR+ = 56% (O) vs. 43% (Y); ER+/PR- = 30% (O) vs. 16% (Y); and ER-/PR- = 14% (O) vs. 41% (Y). Using the aCGH ERBB2 17q locus to define gene amplification and ErbB2+ status, the overall study set shows 13% ErbB2+ cases, with a significant difference between the two cohorts (p = 0.03): 6% (O) vs. 21% (Y). While PR status showed no significant relationship to ErbB2 status; the overall study set shows a significant inverse relationship between ER+ and ErbB2+ status (p = 0.001). However, this inverse relationship is only significant within the younger age cohort, where 9% of ER+ Y cases are ErbB2+ in contrast to 39% of ER- Y cases that are ErbB2+ (p = 0.02). These DNA samples are also currently being analyzed for p53 (exon 5-8) mutations. At present, the findings from this breast cancer cohort study of genomic abnormalities confirm that oncogenic mechanisms differ between younger and older aged breast cancer patients even when hormone receptor status is taken into account. In particular, ERBB2 amplification is an uncommon genomic mechanism contributing to breast tumorigenesis in older patients even within the subset of ER- tumors, yet it accounts for nearly 40% of ER- breast cancers arising in younger patients.
Predictors of sustained virological response 12 weeks after the end of treatment in hepatitis C virus GT3 infected patients receiving IFN-free antiviral treatments
Authors: A. Mangia, R. Santoro, G. Cenderello, V. Piazzolla, D. Petruzzellis, D. Potenza, M.M. Squillante, M. Cela, G. De Stefano
Journal: Journal of Hepatology (2017)
The novel hexokinase 1 antibodies are useful for the diagnosis and associated with bad prognosis in primary biliary cholangitis
Authors: A. Reig, M. Garcia, Z. Shums, J. Milo, S. Encabo, C. Bentow, M. Mahler, M.A. Romera, O. Viñas, G.L. Norman, A. Parés
Journal: Journal of Hepatology (2017)
Abstract IA23: eIF4E as anti-cancer target
Authors: Gerhard Wagner, Evangelos Papadopoulos, Tingfang Yi, Melissa Leger-Abraham, Naotaka Sekiyama
Journal: Cancer Research (2017)

Abstract The interaction of the cap-binding protein eIF4E with eIF4G is central for recruiting the small ribosomal subunit to the 5' end of mRNA. This interaction is regulated by the competitive interaction with the 4E-binding proteins (4E-BPs). Genome analyses have shown that mRNAs coding for proto-oncogenes, transcription factors, translation factors, growth factors and their receptors have statistically long 5' UTRs with large negative free energies estimated with mfold. Translation of these genes thus, depends heavily on an efficient translation-initiation machinery. This is in contrast to 5' TOP mRNAs and highly expressed genes with expression controlled at the transcription level that have small negative free estimated with mfold. Consistently, overexpression of 4E-BP1 has been shown to suppress tumor growth in mouse xenografts. In a high-throughput screen of compound libraries we discovered a small molecule that mimics the action of 4E-BP1 by displacing eIF4G from eIF4E. Surprisingly, the compound does not displace 4E-BP1 but rather stabilizes its binding both in vitro and in vivo. To understand this effect we have solved crystal structures of complexes between eIF4E and several inhibitor analogs. In addition, we determined the structure of eIF4E in complex with a long fragment of 4E-BP1. These data revealed the dual mechanism of the compound displacing the tumor promoter eIF4G while stabilizing the tumor suppressor 4E-BP1. Furthermore, we investigated the activities of 4EGI-1 aggressive breast cancer cells that have properties of cancer stem cells and find that the compound specifically suppresses the aggressive properties of these cancer cells. In addition, we discovered that eIF4E is transcriptionally upregulated in hypoxia as it promoter contains hypoxia response elements utilized by Hif1a. Finally, we tested 4EGI-1 against a panel of ~1000 cancer cell lines and tested the global impact on Jurkat cells in a proteomics approach. Citation Format: Gerhard Wagner, Evangelos Papadopoulos, Tingfang Yi, Melissa Leger-Abraham, Naotaka Sekiyama. eIF4E as anti-cancer target. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA23.
Hepatic steatosis in an adult population: stronger correlation with the presence of obesity and insulin resistance than with the dietary pattern. Results from a cross-sectional study
Authors: J. Leitão, J. Cochicho, S. Carvalhana, F. Velasco, A. Silva, I. Medeiros, A.C. Alves, M. Bourbon, B. Oliveiros, V. Rodrigues, A. Carvalho, H. Cortez-Pinto
Journal: Journal of Hepatology (2017)
Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised clinical trial
Authors: Cecilie Piene Schrøder, Øystein Skare, Olav Reikerås, Petter Mowinckel, Jens Ivar Brox
Journal: British Journal of Sports Medicine (2017)

Labral repair and biceps tenodesis are routine operations for superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their efficacy is lacking. We evaluated the effect of labral repair, biceps tenodesis and sham surgery on SLAP lesions.A double-blind, sham-controlled trial was conducted with 118 surgical candidates (mean age 40 years), with patient history, clinical symptoms and MRI arthrography indicating an isolated type II SLAP lesion. Patients were randomly assigned to either labral repair (n=40), biceps tenodesis (n=39) or sham surgery (n=39) if arthroscopy revealed an isolated SLAP II lesion. Primary outcomes at 6 and 24 months were clinical Rowe score ranging from 0 to 100 (best possible) and Western Ontario Shoulder Instability Index (WOSI) ranging from 0 (best possible) to 2100. Secondary outcomes were Oxford Instability Shoulder Score, change in main symptoms, EuroQol (EQ-5D and EQ-VAS), patient satisfaction and complications.There were no significant between-group differences at any follow-up in any outcome. Between-group differences in Rowe scores at 2 years were: biceps tenodesis versus labral repair: 1.0 (95% CI -5.4 to 7.4), p=0.76; biceps tenodesis versus sham surgery: 1.6 (95% CI -5.0 to 8.1), p=0.64; and labral repair versus sham surgery: 0.6 (95% CI -5.9 to 7.0), p=0.86. Similar results-no differences between groups-were found for WOSI scores. Postoperative stiffness occurred in five patients after labral repair and in four patients after tenodesis.Neither labral repair nor biceps tenodesis had any significant clinical benefit over sham surgery for patients with SLAP II lesions in the population studied.ClinicalTrials.gov identifier: NCT00586742.
Caspofungin efficacy in re-establishing chronic haemodialyzed and renal transplant patient phagocyte primary functions against Candida albicans and C. glabrata infections.
Authors: F Giacchino, G Banche, Allizond, N Mandras, G Garneri, D Scalas, R Patti, J Roana, C Merlino, Tullio, Am Cuffini
Journal: Journal of the American Society of Nephrology (2011)
Immune Gene Expression Profile in Hepatocellular Carcinoma and Surrounding Tissue Predicts Time to Tumor Recurrence
Authors: Chiara Carone, Andrea Olivani, Raffaele Dalla Valle, Roberta Manuguerra, Enrico Maria Silini, Tommaso Trenti, Gabriele Missale, Elisabetta Cariani
Journal: Liver Cancer (2018)

The antitumor immune response may play a major role in the clinical outcome of hepatocellular carcinoma (HCC). We characterized the liver immune microenvironment by direct hybridization of RNA extracted from HCC and nontumorous tissues.RNA was extracted from frozen liver tissue samples of HCC (T; n = 30) and nontumorous tissues (NT; n = 33) obtained from 38 patients. Matched samples were available for 25 patients. The immune gene expression profile was analyzed with the nCounter GX Human Immunology v2 system (NanoString Technologies), which detects the expression levels of 579 immune response-related genes simultaneously.Since the immune gene expression profile of T and NT tissues was significantly different, the prognostic relevance of the liver immune microenvironment was evaluated in the T and NT samples separately. Unsupervised clustering detected two main clusters of immune gene expression both in T and in NT liver samples. In both cases, the expression clusters identified groups of patients with a significantly different median time to HCC recurrence (TTR) but similar overall survival. Based on T tissue, two groups with median TTR of 19 and 127 months, respectively, were detected (p < 0.005). Expression of genes related to T-cell activation was associated with longer TTR. The analysis of NT tissue discriminated subsets of patients with median TTR of 22 and 68 months (p < 0.05). In contrast to T tissue, a predominant inflammatory immune environment was associated with shorter TTR.Immune gene expression profiles predictive of TTR could be identified both in HCC and in adjacent cirrhotic tissues. Longer TTR was associated with overexpression in T tissue and downregulation in NT tissue of the immune response and of inflammation-related genes.
Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN
Authors: John-Paul Kilday, Massimo Caldarelli, Luca Massimi, Robert Hsin-Hung Chen, Yi Yen Lee, Muh-Lii Liang, Jeanette Parkes, Thuran Naiker, Marie-Lise van Veelen, Erna Michiels, Conor Mallucci, Benedetta Pettorini, Lisethe Meijer, Christian Dorfer, Thomas Czech, Manuel Diezi, Antoinette YN Schouten-van Meeteren, Stefan Holm, Bengt Gustavsson, Martin Benesch, Hermann L Müller, Anika Hoffmann, Stefan Rutkowski, Joerg Flitsch, Gabriele Escherich, Michael Grotzer, Helen A Spoudeas, Kristian Azquikina, Michael Capra, Rolando Jiménez-Guerra, Patrick MacDonald, Donna L Johnston, Rina Dvir, Shlomi Constantini, Meng-Fai Kuo, Shih-Hung Yang, Ute Bartels
Journal: Neuro-Oncology (2017)

Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3–17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0–8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8–9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities—important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.