tbuckley/cabot-search huggingface dataset:
Prognosis significance of protease as a function of ER subsets.
Authors: C. Mazouni, S. Romain, P. Bonnier, P. Martin
Journal: Journal of Clinical Oncology (2010)

e21027 Background: Estrogen receptors (ER) and invasive protease such as urokinase-type plasminogen activator (uPA), its inhibitor plasminogen activator inhibitor type 1 (PAI-1), cathepsin D (CathD), and thymidine kinase (TK) are known prognostic factors in breast cancer (BC). The advantage of using combination of these proteases to ER to identify BC subsets of differential prognosis was evaluated. Methods: Analysis of a prospective collected clinical database. uPA, PAI-1, CathD, and TK levels were prospectively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 316 patients with primary BC treated surgically. Distribution and relation between these factors and ER were analyzed. Survival outcome according to identified BC profiles were compared. Results: The levels between ER and PAI-1 were inversely correlated (r = -0.17, p = 0.003). Similar observation was made between ER levels and uPA (r = -0.14, p = 0. 01). The quantitative values of ER were not significantly correlated with TK levels (r = 0.80, p = 0.16), neither with CathD levels (r = -0.004, p = 0.94). ER subsets divided in low (n = 66), intermediate (n = 171) and high ER (n = 79) groups. Between these ER subsets, quantitative levels of uPA, PAI-1, and TK were statistically different (p < 0.001), whereas no difference was observed for CathD levels (p = 0.96). In the total population, PAI-1, TK and CathD were significant factors for OS in univariate analysis, whereas uPA was marginally significant. In contrast, TK was a factor for OS in intermediate and high group whereas PAI-1 was only significant in high ER group. Conclusions: Proteases are related to prognosis irrespectively of ER status. In contrast, analysis as function of ER subsets modify their prognosis significance. No significant financial relationships to disclose.
In Vitro and in Vivo Antiviral Activities of AB-423 a Potent Small Molecule Inhibitor of Hepatitis B Virus Capsid Assembly
Authors: N. Mani, A. Cole, J. Phelps, A. Ardzinski, K. Cobarrubias, A. Cuconati, B. Dorsey, E. Evangelista, T. Harasym, S. Kadhim, A. Lee, H. Liang, A. Li, K. McClintock, S. Majeski, S. Reid, R. Rijnbrand, S. Tang, X. Wang, M. Sofia
Journal: Journal of Hepatology (2016)
At your next conference ask where the patients are
Authors: Fiona Godlee
Journal: BMJ (2016)

It may not feel like it just now, but what we have is doctor centred care. Perhaps also institution, manager, and nurse centred care. What we don’t yet have is patient centred care, despite this being obviously what healthcare should be. But things are slowly shifting in the right direction, and The BMJ aims to help keep up the momentum.

An editorial last week summarised where we’ve got to with The BMJ ’s patient partnership strategy (doi:10.1136/bmj.i4550), and there’s good progress to report. We now have patients as peer reviewers …
Polymorphisms of HLA-DPB1 are Associated with Long-Term Clinical Outcome in a Diverse Cohort of Chronic Hepatitis B Patients
Authors: W.P. Brouwer, A.J. van der Meer, A. Boonstra, R.J. de Knegt, R.A. de Man, F.J. ten Kate, H.L. Janssen, B.E. Hansen
Journal: Journal of Hepatology (2016)
Genetically Engineering HBV-Specific CD8+ T Cells Resistant to Trail-Mediated Apoptosis
Authors: I. Otano, F. Arce, H. Singh, A. Schurich, D. Peppa, R. Gilson, G. Fusai, H. Stauss, D. Escors, M.K. Maini
Journal: Journal of Hepatology (2016)
Allopurinol is Safe and Effective to Achieve Biochemical and Histological Remission in Patients with Autoimmune Hepatitis with Incomplete Therapeutic Response
Authors: D.R. Terrabuio, L.T. De Moraes Falcao, S.K. Ono, M.A. Diniz, F.J. Carrilho, E. Cancado
Journal: Journal of Hepatology (2016)
Evaluation of Prevalence of Erectile Dysfunction and Associated Risk Factors in Patients with Liver Cirrhosis
Authors: S. Maimone, G. Oliva, A. Di Benedetto, R. Filomia, G. Caccamo, C. Saitta, I. Cacciola, G. Squadrito, G. Raimondo
Journal: Journal of Hepatology (2016)
Cardiolipins Are Biomarkers of Mitochondria-Rich Thyroid Oncocytic Tumors
Authors: Jialing Zhang, Wendong Yu, Seung Woo Ryu, John Lin, Gerardo Buentello, Robert Tibshirani, James Suliburk, Livia S. Eberlin
Journal: Cancer Research (2016)

Abstract Oncocytic tumors are characterized by an excessive eosinophilic, granular cytoplasm due to aberrant accumulation of mitochondria. Mutations in mitochondrial DNA occur in oncocytic thyroid tumors, but there is no information about their lipid composition, which might reveal candidate theranostic molecules. Here, we used desorption electrospray ionization mass spectrometry (DESI-MS) to image and chemically characterize the lipid composition of oncocytic thyroid tumors, as compared with nononcocytic thyroid tumors and normal thyroid samples. We identified a novel molecular signature of oncocytic tumors characterized by an abnormally high abundance and chemical diversity of cardiolipins (CL), including many oxidized species. DESI-MS imaging and IHC experiments confirmed that the spatial distribution of CLs overlapped with regions of accumulation of mitochondria-rich oncocytic cells. Fluorescent imaging and mitochondrial isolation showed that both mitochondrial accumulation and alteration in CL composition of mitochondria occurred in oncocytic tumors cells, thus contributing the aberrant molecular signatures detected. A total of 219 molecular ions, including CLs, other glycerophospholipids, fatty acids, and metabolites, were found at increased or decreased abundance in oncocytic, nononcocytic, or normal thyroid tissues. Our findings suggest new candidate targets for clinical and therapeutic use against oncocytic tumors. Cancer Res; 76(22); 6588–97. ©2016 AACR.
Portal Vein Thrombosis Relevance on Liver Cirrhosis: Italian Venous Thrombotic Events Registry
Authors: F. Violi, R.G. Corazza, S.H. Caldwell, F. Perticone, A. Gatta, M. Angelico, A. Farcomeni, M. Masotti, L. Napoleone, A. Vestri, V. Raparelli, S. Basili
Journal: Journal of Hepatology (2016)
Mid-Infrared Spectroscopy has a High Sensitivity and Specificity for Point-of-Care Diagnosis of Spontaneous Bacterial Peritonitis
Authors: R. Anty, M. Le Corvec, C. Renou, A. Raoult, J.-B. Nousbaum, F. Tanne, C. Triboulot, P. Hastier, C. Fissore-Magdelein, M.-L. Peritore, V. Blanc-Amrane, E. Mariné-Barjoan, J. Vibert, E. Lemichez, O. Sire, P. Gual, H. Tarie, A. Tran, O. Loréal, L. Landraud
Journal: Journal of Hepatology (2016)
Mechanism of Thrombocytopenia Induced by Anti-CD40 Ligand Immune Complexes and the Prevalence of CD40 Ligand Autoantibodies in Patients with Thrombotic Autoimmune Disorders
Authors: Ali Amirkhosravi, Todd V Meyer, Liza Robles-Carillo, Monica Davila, Florian Langer, Hina Desai, Patricia Weinstein, Mildred Amaya, Eduardo Reyes, John L Francis
Journal: Blood (2008)
C-EDGE IBLD: Efficacy and Safety of Elbasvir/Grazoprevir (EBR/GZR) in Subjects with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders
Authors: C. Hezode, M. Colombo, U. Spengler, Z. Ben-Ari, S. Strasser, W.M. Lee, L. Morgan, J. Qiu, P. Hwang, M. Robertson, B.-Y. Nguyen, E. Barr, J. Wahl, B. Haber, R. Talwani, V. Di Marco
Journal: Journal of Hepatology (2016)
P0155 : Validity and reliability of splenic volume measurement by ultrasound and its clinical implications to define splenomegaly in liver cirrhosis
Authors: S.G. Kim, H.J. Jung, Y.S. Kim, S.H. Lee, S.W. Jeong, J.Y. Jang, Y.D. Kim, G.J. Cheon, H.S. Kim, B.S. Kim
Journal: Journal of Hepatology (2015)
Characterisation of the Specificity, Functionality and Durability of Host T-Cell Responses against the Full HEV Genome
Authors: J. Halliday, A. Brown, L. Swadling, R. Madden, R. Bendall, S. Jubb, J. Hunter, J. Maggs, P. Simmonds, D. Smith, L. Vine, C. McLaughlin, J. Collier, K. Jeffery, P. Klenerman, J. Izopet, N. Kamar, H. Dalton, E. Barnes
Journal: Journal of Hepatology (2016)
A first-in-human phase I/II study of ALK inhibitor CH5424802 in patients with ALK-positive NSCLC.
Authors: Katsuyuki Kiura, Takashi Seto, Nobuyuki Yamamoto, Makoto Nishio, Kazuhiko Nakagawa, Tomohide Tamura
Journal: Journal of Clinical Oncology (2012)

7602 Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase constitutively activated in a subset of non-small cell lung cancer (NSCLC) following chromosomal gene translocation. CH5424802 was identified as a potent, selective, and oral ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against NSCLC cells expressing EML4-ALK fusion in vitro and in vivo (Cancer Cell, 2011). Our results support the potential of CH5424802 as a new therapeutic opportunity for patients (pts) with ALK-positive NSCLC. Methods: Pts with ALK-positive NSCLC received CH5424802 twice daily orally until progressive disease or toxicity was observed. In the phase I portion, dose was escalated using an accelerated titration scheme. The primary objectives were to investigate the safety, tolerability and pharmacokinetic (PK) parameters under fasting conditions, and to determine the recommended dose (RD) for use in the phase II portion. The primary objectives of the phase II portion were to investigate the efficacy and safety at the RD. The phase I portion was amended to include an investigation under non-fasting conditions in addition to fasting conditions. Results: 15 pts (M/F: 9/6) were treated with CH5424802 under fasting conditions in 6 cohorts (20 mg bid to 300 mg bid) and 9 pts (M/F: 2/7) were treated under non-fasting conditions in 2 cohorts (240 mg bid and 300 mg bid). Median age was 42.5 years. The highest dose level defined in the protocol (300 mg bid) did not reach the MTD. Thus, a DLT was not determined. Toxicities were mild to moderate. The most frequent toxicity was grade 1 myalgia. Grade 3 toxicity (cases) occurred as follows; hypophosphatemia (2), neutropenia (2), blood CPK increased (1) and hypermagnesemia (1). PK data from the fasting cohorts showed dose-dependent increases of Cmax and AUC. All pts at all dose levels achieved tumor regression. At dose levels 240 mg bid or more under fasting conditions, all 7 pts with measurable lesions achieved a partial response. So far, 11 pts have been on study treatment ≥ 6 months. Conclusions: CH5424802 was well tolerated with promising efficacy in pts with ALK-positive NSCLC. The phase II portion is ongoing.
The Clinical Role of Micrornas (miRs) in Cytogenetically Normal (CN) Acute Myeloid Leukemia (AML): miR-155 Upregulation Independently Identifies High-Risk Patients (Pts)
Authors: Guido Marcucci, Kati Maharry, Klaus H. Metzeler, Stefano Volinia, Yue-Zhong Wu, Krzysztof Mrózek, Deedra Nicolet, Jessica Kohlschimdt, Susan Whitman, Jason H. Mendler, Sebastian Schwind, Heiko Becker, Ann-Kathrin Eisfeld, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Ramiro Garzon, Michael A. Caligiuri, Richard M. Stone, Clara D Bloomfield
Journal: Blood (2012)
ABC drug transporter gene expression in neuroblastoma.
Authors: S. Cialfi, H. P. McDowell, P. Altavista, R. Boldrini, S. Bosco, A. Clerico, A. Jenkner, G. Kokai, B. Pizer, C. Dominici
Journal: Journal of Clinical Oncology (2010)

9524 Background: In advanced neuroblastoma (NB), resistance to cytotoxics is the main cause of therapeutic failure and poor outcome. A distinctive type of resistance, multidrug resistance (MDR), is associated with increased ABC drug transporter expression. ABCB1 (MDR1), ABCC1 (MRP1) and ABCC4 (MRP4) are expressed in NB, but their impact on therapeutic response and outcome is unclear. Nothing is known on ABCG2, a major player in MDR. We investigated ABCB1, ABCC1/4 and ABCG2 gene expression in NB tumors. Methods: Untreated primary NB samples were obtained from 109 pts aged 1 d to 199 mos (median, 32 mos), staged according to INSS: 36 stage 1, 2 or 4S; and 73 stage 3 or 4. MYCN amplification (MNA) was found in 18/109 NBs (17%). Stage 3/4 pts were given induction chemotherapy including cyclophosphamide, doxorubicin, vincristine, cisplatin, carboplatin or etoposide. No selection criteria were applied for study except for the availability of frozen tumor tissue. Institutional written informed consent and ethical approval were obtained. Expression of mRNA was analyzed by real-time PCR and relative quantification done according to the Ct method. The amount of mRNA was expressed as fold change (2–ΔΔCt) of each sample compared to dorsal root ganglion, and categorized as high or low using the upper quartile 2–ΔΔCt value as cut-off point. In stage 3/4 pts, clinical end points were response to induction chemotherapy (based on INRC) and overall survival (OS). Pts with CR, VGPR or PR were categorized as responsive; the others as non-responsive. Results: All 4 genes were expressed at variable levels in the 109 NBs, irrespective of age at diagnosis, primary site, stage and MNA. In the 73 stage 3/4 pts, high levels of ABCB1 (p=0.003), ABCC1 (p<0.001), ABCC4 (p=0.001) and ABCG2 (p<0.001) were associated with non response to chemotherapy. Despite a trend for a lower OS in cases with high expression of ABCB1, ABCC1/4 or ABCG2, no significant association was found, which may reflect the influence of further treatment. Conclusions: High levels of ABCB1, ABCC1/4 and ABCG2 at diagnosis were indicative of non response to induction chemotherapy, but did not impact on OS. In advanced NB, resistance mechanisms other than MDR appear to play a contributory role in adversely affecting outcome. No significant financial relationships to disclose.
Toll-Like Receptor 3: A Potential Tumor Suppressor Gene in Hepatocellular Carcinoma?
Authors: N. Fares, M. Bonnin, A. Garcia, B. Testoni, Lydie Lefrancois, B. Bancel, V. Hervieu, T. Renno, P. Merle, S. Lebecque
Journal: Journal of Hepatology (2016)
Preparation of slab-shaped lactose carrier particles for dry powder inhalers by air jet milling
Authors: Xiang Kou, Lai Wah Chan, Changquan Calvin Sun, Paul Wan Sia Heng
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e., classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm. The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.
Oral Bacterial Activity is Significantly Associated with Autoimmune Liver Diseases and it Could be Involved in their Pathogenesis Mechanisms
Authors: F. Figorilli, G. Orrù, S. Onali, C. Salustro, S. Cappellini, E. Cocco, S. Fais, M. Melis, A. Gilardi, L. Secci, S. Casu, S. Littera, L. Chessa
Journal: Journal of Hepatology (2016)
Guidelines for Tinnitus—Reply
Authors: Adam S. Cifu, David D. Walker, Michael B. Gluth
Journal: JAMA (2016)

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A Panel of 3 Markers (H4K20ME2, H4K16AC and PIVKA-II) for Prediction of Microvascular Invasion in Hepatocellular Carcinoma
Authors: N. Pote, F. Cauchy, M. Albuquerque, O. Soubrane, P. Bedossa, V. Paradis
Journal: Journal of Hepatology (2016)
Real-Life Experience of Daa-Based Regimens Plus Ribavirin in Cirrhotic Patients Coinfected with HCV and HIV-1
Authors: E. Messina, C. Uberti-Foppa, M. Merli, L. Galli, D. Barbanotti, A. Poli, S. Salpietro, G. Morsica, S. Bagaglio, A. Andolina, A. Castagna, A. Lazzarin, H. Hasson
Journal: Journal of Hepatology (2016)
Is low-dose cyclophosphamide (Cy) plus G-CSF (G) mobilization as effective as plerixafor plus G in multiple myeloma (MM) patients (pts) who are candidates for tandem autologous transplants (autoT)?
Authors: C. Karanes, A. Dagis, S. Wang, A. Y. Krishnan, F. Sahebi, L. Popplewell, P. M. Parker, S. J. Forman, J. Palmer, G. Somlo
Journal: Journal of Clinical Oncology (2010)

8142 Background: In a recently published trial, the majority of MM pts (71.6%) who were mobilized with plerixafor plus G prior to autoT, collected > 6 × 106CD34+ cells/kg in ≤ 2 apheresis procedures, vs. 34.4% of pts who were mobilized with G and placebo (DiPersio et al, Blood 113 (23):5720-5726, 2009). We set out to assess the efficacy of Cy plus G as mobilization therapy in a similar pt population, treated at the City of Hope National Medical Center. Methods: 121 MM pts were treated on sequential tandem autoT protocols. Pts received 1.5 g/m2 of Cy followed by G at 10 microgram/kg, daily through completion of their apheresis procedures. Pts underwent consecutive leukapheresis starting on day 10 and continued until a minimum of 4 × 106 CD34+ cells/kg (up to 10 × 106 CD34+ cells/kg) were collected. Results: The median age was 54.4 years (range, 29.7-66.1). Pts were mobilized within 7.4 months from their diagnosis of MM (range, 1.3-55.3), following a median of 2 prior treatment regimens (1-8). Twenty-four percent of pts received prior radiation. The median number of days to collect 4 × 106 CD34+ cells/kg, and 6 × 106 CD34+ cells/kg were 1 (1-16), and 2 (1-16). The cumulative total for CD34+ cells/kg collected was 9.98 × 106 (2.55-35.79), requiring 3 aphereses (1-16). Neutrophil engraftment was reached in 11 days (1-16) after first, and 10 days (8-43) after the second autoT. Platelet independence was achieved by day 13 (0-71) and 12 (0-44), after the first and second autoTs. Patients who have undergone apheresis < 7 months from diagnosis were 2.6 times (CI: 1.14-5.95) more likely to reach a yield of 6 × 106 CD34+ cells/kg within the first 1-2 days (p = 0.02). Sixty-seven percent of Cy-G mobilized pts reached a yield of 6 × 106 CD34+/kg in 2 days. Conclusions: CD34+ cell yield following Cy-G mobilization in this retrospective exploratory analysis is comparable to what was reported following plerixafor-G mobilization. We suggest reserving plerixafor for pts with substantial delay between diagnosis and apheresis, and for those failing Cy-G mobilization. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
The Impact of Liver Resection on Bile Salt and FGF19 Homeostasis in Humans
Authors: K.V. Koelfat, K.M. Van Mierlo, J.G. Bloemen, A.K. Groen, P.L. Jansen, C.H. Dejong, F.G. Schaap, S.W. Olde Damink
Journal: Journal of Hepatology (2016)
Health-related quality of life (HRQL) in Hodgkin lymphoma (HL): A systematic review (SR).
Authors: Nadine Linendoll, Tully Saunders, Rebecca Burns, Jonathan Nyce, Kristen Wendell, Andrew M. Evens, Susan K. Parsons
Journal: Journal of Clinical Oncology (2016)

234 Background: AlthoughHL is highly curable with well-established treatment regimens, the impact on patients' HRQL from diagnosis through survivorship is unclear. This SR aimed to: (1) describe the literature on HRQL in HL, (2) assess the quality of these studies and (3) identify gaps for future research. Methods: We performed a PRISMA-guided SR on HRQL in HL patients. Identified articles were double-screened and data extracted; quality was evaluated using a 6-point scale adapted from published HRQL SR. Results: Sixty-two articles published between 1986- 2014 met inclusion criteria. These included 50 (81%) cross-sectional studies and 12 (19%) longitudinal studies of which three were embedded in randomized trials (RTC). Only two of the RCTs followed patients from diagnosis into survivorship; three additional longitudinal studies began assessments at diagnosis. The majority (75%) of longitudinal studies were performed over the last decade. The sample size of HL patients varied considerably with only five (41%) longitudinal studies including &gt;50 patients. On average, patients in the cross sectional studies were 10-plus years off treatment. Multidimensional HRQL was assessed in 40 studies, single HRQL domains in 21 studies, and symptoms, including fatigue, in 24 studies. Quality varied by study design. Conclusions: The number and quality of studies on HRQL in HL have increased over time. To capture HRQL trajectory from diagnosis through survivorship, we recommend that future research include prospective, longitudinal randomized design across treatment and time. [Table: see text]
Application of Mass Cytometry Time of Flight (CYTOF) for Systematic Characterization of PBMC Phenotypes Associated with HBSAG Serum Levels in Chronic HBV Patients
Authors: N. Le Bert, L. Rivino, Y. Cheng, D. Tan, E. Newell, A. Arvey, P. Kennedy, S. Pflanz, A. Bertoletti
Journal: Journal of Hepatology (2016)
The T-cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated with Survival in Aggressive B-cell Lymphoma
Authors: Colm Keane, Clare Gould, Kimberley Jones, David Hamm, Dipti Talaulikar, Jonathan Ellis, Frank Vari, Simone Birch, Erica Han, Peter Wood, Kim-Anh Le-Cao, Michael R. Green, Pauline Crooks, Sanjiv Jain, Josh Tobin, Raymond J. Steptoe, Maher K. Gandhi
Journal: Clinical Cancer Research (2016)

Purpose: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo diffuse large B-cell lymphoma (DLBCL) and the impact of TCR on survival.Experimental Design: We performed high-throughput unbiased TCRβ sequencing on a population-based cohort of 92 patients with DLBCL treated with conventional (i.e., non-checkpoint blockade) frontline "R-CHOP" therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString. The primary endpoints were 4-year overall survival (OS) and progression-free survival (PFS).Results: The TCR repertoire within DLBCL nodes was abnormally narrow relative to non-diseased nodal tissues (P < 0.0001). In DLBCL, a highly dominant single T-cell clone was associated with inferior 4-year OS rate of 60.0% [95% confidence interval (CI), 31.7%-79.6%], compared with 79.8% in patients with a low dominant clone (95% CI, 66.7%-88.5%; P = 0.005). A highly dominant clone also predicted inferior 4-year PFS rate of 46.6% (95% CI, 22.5%-76.6%) versus 72.6% (95% CI, 58.8%-82.4%, P = 0.008) for a low dominant clone. In keeping, clonal expansions were most pronounced in the EBV+ DLBCL subtype that is known to express immunogenic viral antigens and is associated with particularly poor outcome. Increased T-cell diversity was associated with significantly elevated PD-1, PD-L1, and PD-L2 immune checkpoint molecules.Conclusions: Put together, these findings suggest that the TCR repertoire is a key determinant of the TME. Highly dominant T-cell clonal expansions within the TME are associated with poor outcome in DLBCL treated with conventional frontline therapy. Clin Cancer Res; 23(7); 1820-8. ©2016 AACR.