tbuckley/cabot-search huggingface dataset:
A phase I trial of combination immunotherapy with CTLA-4 blockade and GM-CSF in hormone-refractory prostate cancer
Authors: L. Fong, B. Kavanagh, B. I. Rini, V. Shaw, V. Weinberg, E. J. Small
Journal: Journal of Clinical Oncology (2006)

2508 Background: CTLA-4 is an costimulatory molecule expressed on activated T cells that delivers an inhibitory signal to these T cells. CTLA-4 blockade with antibody treatment augments T cell responses and anti-tumor immunity in animal models. Clinical trials with anti-CTLA-4 antibody treatment have demonstrated clinical responses in different malignancies including melanoma and hormone-refractory prostate cancer (HRPC). We have also shown that administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) can also induce PSA declines in HRPC patients, presumably through enhancing presentation of endogenous antigens. The current study examines whether combining systemic GM-CSF to CTLA-4 blockade can augment immune and/or clinical responses in HRPC patients. Methods: In a phase I trial of patients with metastatic HRPC, sequential cohorts of 3–6 patients received GM-CSF (sargramostim, Berlex) 250 mg/m 2 /d SC on days 1–14 of a 28-day cycle with escalating doses (0.5, 1.5 or 3 mg/kg) of ipilimumab (MDX-010), a fully human anti-CTLA antibody (Medarex/BMS), given IV on day 1 of each cycle x 4 cycles. Patients were monitored for toxicity as well as for T cell activation. PSA and radiographic tests were performed at baseline and through therapy to evaluate for clinical response. Results: 18 patients were accrued. Ipilimumab-related dose-limiting toxicity was limited to one patient with grade 3 rash at the 3 mg/kg priming dose level. Seven patients had &lt;50% declines in their serum PSA levels. A dose response relationship was seen between ipilimumab dose and activation of both CD4 and CD8 T cells in the blood. These effects were increased compared to effects seen with ipilimumab treatment alone in prior studies. Interferon-gamma production and lytic activity were also enhanced in circulating antigen-specific CD8+ T cells by the combination. Conclusions: GM-CSF may enhance T cell activation induced by CTLA-4 blockade. With increasing doses of anti-CTLA-4, both CD4 and CD8 T cell activation can be detected in the blood, consistent with a dose-response relationship. Supported by the UCSF Prostate SPORE NIH P50 CA89520. No significant financial relationships to disclose.
Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment
Authors: Hyunwoo Oh, Dae Won Jun, Waqar K Saeed, Mindie H Nguyen
Journal: Clinical and Molecular Hepatology (2016)

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD. Keywords: Non-alcoholic fatty liver; Diagnosis; Treatment
CCL19-CCR7–dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima
Authors: Mark Roufaiel, Eric Gracey, Allan Siu, Su-Ning Zhu, Andrew Lau, Hisham Ibrahim, Marwan Althagafi, Kelly Tai, Sharon J Hyduk, Kateryna O Cybulsky, Sherine Ensan, Angela Li, Rickvinder Besla, Henry M Becker, Haiyan Xiao, Sanjiv A Luther, Robert D Inman, Clinton S Robbins, Jenny Jongstra-Bilen, Myron I Cybulsky
Journal: Nature Immunology (2016)
Adjuvant chemoradiation after curative resection for pancreatic cancer is feasible: Results of a randomised EORTC/FFCD/GERCOR study
Authors: J. Van Laethem, Eric Van Cutsem, P. Hammel, D. Azria, F. Mornex, G. Van Tienhoven, M. Peelers, P. Vergauwen, V. Budach, L. Collette, Karin Haustermans
Journal: Annals of Oncology (2008)
Effect of ET-1, FGF-2, and HGF on intracellular steroidogenesis in prostate cancer cells.
Authors: Chrysoula Vasileiou, Eleana Hatzidaki, Athanasios Karkabounas, Eleni Maragkouli, Maria Vaiou, Konstantinos Dimas, Panagiotis Liakos, Marilena Lekka, Christos Papandreou
Journal: Journal of Clinical Oncology (2013)

e16083 Background: In the prostatic epithelium endothelin-1 (ET-1), fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell proliferation and inhibition of apoptosis. The aim of this study is to investigate whether neuropeptides such as ET-1 and growth factors such as FGF and HGF may constitute an alternate pathway to intracellular steroidogenesis. Methods: PC3 cells, an androgen independent prostate cancer cell line were cultured in RPMI 1640, fully supplemented with FBS 10% and in serum free conditions. The cells were incubated with ET-1(10nM, 3 hrs incubation), FGF-2 (10 ng/ml, 3 hrs incubation) and HGF(33 ng/ml, 3 hrs incubation), and then progesterone, 17-OH progesterone and aldosterone were measured in cell lysates by LC-MS using LTQ Orbitrap XL MS 2.5.5 SP1 (Thermo-Fisher) equipped with Accela AS 2.2.1, Accela pump. The data were analysed by Xcalibur 2.1.0 Software. Results: In baseline conditions PC3 cells produce no progesterone but high amounts of 17-OH progesterone and small amounts of aldosterone. Upon stimulation with endothelin there was a significant increase in progesterone, significant decrease in 17-OH progesterone and a very significant increase in aldosterone. Similarly stimulation with both HGF and FGF resulted in significant decreases in 17-OH progesterone and increases in aldosterone. Conclusions: Our results imply that in androgen deprivation conditions intracellular steroidogenesis can still take place by stimulation via seven membrane and tyrosine kinase receptors, contributing in part to a steroid dependent phenotype in addition to a steroid independent one, thus implying the potential for new therapeutic interventions.
Programmed cell death-Ligand 1 (PD-L1) expression and outcome in patients with squamous cell cancer of anal canal (SCCAC).
Authors: Swetha Gujja, Stephen K. Williamson, Anu Batra, Anwaar Mohammed Saeed, Keith Lai, Bradley J Fogel, Jennifer D James, Eric R Siegel, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2015)

3523 Background: PD-L1 expression has been associated with worse prognosis in a variety of cancers. In anal carcinoma, the prevalence of PD-L1 positivity in tumor tissue is unknown. To evaluate the influence of PD-L1 expression on prognosis of subjects with SCCAC, a retrospective analysis was conducted. Methods: Subjects with SCCAC were identified from tumor registry at the University of Arkansas for Medical Sciences and Kansas University between 1992 and 2011. The charts were reviewed to confirm the diagnosis, stage, treatment and outcome of the subjects. Paraffin tissue blocks of the subjects were stained for PD-L1 expression using rabbit polyclonal antibody (ab153991, ABCAM). PDL1 positivity was defined as any membranous or cytoplasmic immunoreactivity within the tumor cells. Nuclear or general blush staining only was considered negative.Kaplan-Meier curves and the Wilcoxon test were used to compare subjects positive vs. negative for PD-L1 expression for differences in Overall (OS) and Recurrence-Free (RFS) survival. Results: Samples from 41 subjects were evaluated for PD-L1 expression. Median age was 52 years (range 30-94). Males were 51%. There were 80% Caucasians, 15% African-Americans, 5% others. 22% were early stage (0, I, II), 48% late stage (III, IV) and 29% unknown. 93% were p16-positive by immunohistochemistry. 71% had chemo-radiation, 2.4% had chemotherapy, 17% had surgery and 10% had unknown treatment. PD-L1 positivity was seen in 62% of late/ unknown stage and 33% of early stage disease. PD-L1-positive vs. negative patients respectively had RFS medians of 1.5 vs. 4.9 years (p = 0.068) and OS medians of 2.2 vs. 7.6 years (p = 0.64). Conclusions: PD-L1positivity was associated with poorer RFS, with a trend towards statistical significance. OS was not significantly different between the PD-L1 positive and negative groups. However, larger sample size may show statistically significant difference in RFS and OS.
O-0026 Significant Relationship Between CA19-9 Kinetics and Overall Survival (OS) from a Phase 3 Trial in Advanced Pancreatic Cancer (APC).
Authors: Dana Nickens, Eric Van Cutsem, Tatsuya Ioka, Dirk Richel, Jaafar Bennouna, Sinil Kim, Harpreet Wasan, Alejandro Ricart
Journal: Annals of Oncology (2012)
Wearable fitness device does not help maintain weight loss, study finds
Authors: Owen Dyer
Journal: BMJ (2016)

Participants in a randomised weight loss study who used a wearable fitness device to monitor their physical activity lost less weight over two years than those who self monitored their diet and activity using a website, a US study published in JAMA has found.1

The study, led by University of Pittsburgh researchers, randomly assigned 470 overweight participants aged 18-35 with a body mass index of 25-40 either to wear a BodyMedia FIT Core armband device or to self report exercise and calorie intake.

Both arms of the study first underwent a …
Understanding the Dose Regimen for Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma (MM) after Prior Proteasome Inhibitors (PIs) and Immunomodulatory Drugs (IMiDs): A Quantitative Pharmacologic Perspective
Authors: Xu Steven Xu, Xiaoyu Yan, Thomas Puchalski, Sagar Lonial, Henk M. Lokhorst, Peter M. Voorhees, Kevin Liu, Imran Khan, Richard Jansson, Tahamtan Ahmadi, Juan Jose Perez Ruixo, Honghui Zhou, Pamela L Clemens
Journal: Blood (2015)
Vaccination contre la coqueluche en Europe: l'état des lieux fin 1999
Authors: H Therre, S Baron
Journal: Eurosurveillance (2000)

L’histoire de la coqueluche dans les pays europeens a clairement montre l’efficacite de la vaccination anti-coqueluche sur la baisse de l’incidence de la maladie. Dans certains pays, les vaccins inactives a germes entiers font partie du programme national de vaccination depuis plus de 30 ans, mais les effets secondaires associes, en particulier chez les sujets plus âges, sont devenus un reel probleme. D’importants efforts ont ete realises depuis 1970 pour identifier les principaux facteurs de virulence de Bordetella pertussis afin de developper de nouveaux vaccins acellulaires. Ces facteurs sont la toxine pertussique (TP), responsable de la plupart des effets toxiniques de la bacterie, et des facteurs d’adhesion tels que l’hemagglutinine filamenteuse (FHA), la pertactine (PRN) et les agglutinogenes (AG). Les premiers vaccins acellulaires simples ont ete mis sur le marche au Japon en 1981 pour les enfants de 2 ans et plus (1), isoles puis associes aux toxoides diphterique et tetanique (DTCoq acellulaire).
Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): MM-003 analysis of patients (pts) with moderate renal impairment (RI).
Authors: Katja C. Weisel, Meletios A. Dimopoulos, Philippe Moreau, Martha Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Anne Banos, Albert Oriol Rocafiguera, Xin Yu, Lars Sternas, Christian Jacques, Mohamed H. Zaki, Jesùs F. San-Miguel
Journal: Journal of Clinical Oncology (2013)

8527 Background: Pts who have exhausted lenalidomide (LEN) and bortezomib (BORT) treatment (Tx) have a poor prognosis. A significant proportion of pts have RI with increasing incidence during disease course. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT, including those with RI. MM-003 is an open-label, multicenter, phase 3 trial comparing POM + LoDEX vs HiDEX in RRMM pts who failed LEN and BORT and progressed on their last Tx. Methods: Pts must have failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination) and must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days). Pts with creatinine clearance (CrCl) &lt; 45 mL/min were excluded. Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged &gt; 75 y) qw; or DEX 40 mg (20 mg for pts aged &gt; 75 y) D1–4, 9–12, and 17–20 (28-D cycles). Tx continued until PD or unacceptable adverse event (AE). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and AEs. This analysis examined pts with or without moderate RI (CrCl &lt; 60 vs ≥ 60mL/min). Results: 302 pts received POM + LoDEX; 153 pts received HiDEX, 31% and 39% had moderate RI, respectively. Pts with moderate RI were more likely to be older (64% vs 36% aged &gt; 65 y) vs no RI. Median follow-up was 4 mo. Median PFS and OS were significantly longer with POM + LoDEX vs HiDEX regardless of RI (Table). Similar AE rates for POM + LoDEX as well as HiDEX Tx were seen in pts with and without moderate RI (Table). Discontinuation due to AE was 5% vs 7% (no moderate RI) and 11% vs 5% (moderate RI). Conclusions: POM + LoDEX significantly extended PFS and OS vs HiDEX in pts with or without moderate RI. Tolerability of POM + LoDEX was acceptable across subgroups, with few discontinuations due to AE. Clinical trial information: NCT01311687. [Table: see text]
Safety, Feasibility and Cost Of Hematopoietic Stem Cell Transplantation Management By Peripheral Inserted Central Catheter (PICC): A Phase II Prospective Study
Authors: Daniele Derudas, Donatella Baronciani, Cristina Depau, Federica Pilo, Clara Targhetta, Sara Veronica Usai, Giuseppe Longhitano, Daniela Ibba, Emanuele Angelucci
Journal: Blood (2013)
Validation of the patient-generated part of the PG-SGA against the malnutrition screening tool (MST).
Authors: Nelda Swinton, Goulnar Kasymjanova, Mary Grossman, Victor Cohen, Carmela Pepe, Jason Scott Agulnik, David Small
Journal: Journal of Clinical Oncology (2012)

e19626 Background: It is important to identify cancer patients (pts) who are at risk for malnutrition as many pts experience an array of nutritional problems which can impact upon their treatment plan and quality of life. This requires using an easy and reliable screening tool such as the MST or the scored PG-SGA. The scored PG-SGA is a more extensive tool consisting of a patient (pt) - generated section identifying symptoms that can impact on nutritional status. It also includes a second part consisting a pt’s physical examination. Both sections are summed to give an overall PG-SGA score. We hypothesized that the PG-SGA‘s pt-generated part alone, could be a comparable screening tool to the MST. Methods: We performed a prospective analysis from our out-patient pulmonary oncology clinic between July 1, 2010 to January 1, 2012 on non-small cell lung cancer (NSCLC) pts at various times in their cancer trajectory and used the MST as the gold standard. Pts were asked the MST’s questions by an oncology dietitian and completed the pt - generated part of the PG-SGA. Cut off points of ≥ 2 for the MST and ≥ 4 for the PG-SGA ( pt-generated part) were used to identify pts at risk for malnutrition. Results: 144 pts with NSCLC (72 male, 72 female, aged 67 ± 11 years) completed the questionnaires. Sixty-nine percent (99/144) had advanced disease. Fifty-six percent (81/144) of pts had a score ≥ 2 on the MST and 70 % (101/144) pts had a score ≥ 4 on the PG-SGA ( pt generated part). In 114 cases, the MST and PG-SGA scores were congruent: 76 were true positive and 38 were true negative. And in 30 cases the scores were discordant: 25 were false positive and 5 were false negative. The PG-SGA had a sensitivity of 94 % and a specificity of 60% in comparison to the MST. Conclusions: The pt-generated part of the PG-SGA alone had a sensitivity of 94% when compared to the MST. This tool could be used to screen for malnutrition risk in NSCLC pts attending an out-patient oncology clinic.
Advances in β cell replacement and regeneration strategies for treating diabetes
Authors: Jacqueline R. Benthuysen, Andrea C. Carrano, Maike Sander
Journal: Journal of Clinical Investigation (2016)

In the past decade, new approaches have been explored that are aimed at restoring functional β cell mass as a treatment strategy for diabetes. The two most intensely pursued strategies are β cell replacement through conversion of other cell types and β cell regeneration by enhancement of β cell replication. The approach closest to clinical implementation is the replacement of β cells with human pluripotent stem cell-derived (hPSC-derived) cells, which are currently under investigation in a clinical trial to assess their safety in humans. In addition, there has been success in reprogramming developmentally related cell types into β cells. Reprogramming approaches could find therapeutic applications by inducing β cell conversion in vivo or by reprogramming cells ex vivo followed by implantation. Finally, recent studies have revealed novel pharmacologic targets for stimulating β cell replication. Manipulating these targets or the pathways they regulate could be a strategy for promoting the expansion of residual β cells in diabetic patients. Here, we provide an overview of progress made toward β cell replacement and regeneration and discuss promises and challenges for clinical implementation of these strategies.
A new genetic subset of acute lymphoblastic leukemia in both children and adults is identified by the t(12;17)(p13;q11) and its variant t(12;22)(p13;q12)
Authors: R La Starza, A Martini, A Aventin, C Bilhou-Nabera, A Angioni, R Foa, Anne Hagemeijer-Hausman, Peter Marynen, Christina Mecucci
Journal: Blood (2002)
Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: Preliminary results of a multicentric phase II study
Authors: D. Kerob, R. Porcher, O. Verola, S. Dalle, E. Maubec, J. M. Servant, F. Calvo, P. Berthaud, A. Mathieu-Boue, F. Pedeutour, C. Lebbe
Journal: Journal of Clinical Oncology (2006)

9550 Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of intermediate malignant potential. Treatment relies on a wide local excision with negative margin with frequent need of reconstructive surgery. A translocation between chromosomes 17 and 22 that places PDGFB under the control of the collagen 1A1 promoter is present in &gt; 90% of the cases leading to an up regulation of PDGFB expression and activation of the tyrosinase kinase PDGFRβ. Anecdotal reports and a report on 8 patients suggest that Imatinib mesylate (IM) has a clinical interest in DFSP. The primary aim of this phase II multicentric study is to define the percentage of clinical responders (RECIST) to a preoperative 2 months 600mg IM daily before wide local excision. The secondary goals are to determine tolerance, imaging (ultrasound and MRI), pathological responses and to analyse PDGFRβ phosphorylation status and tumour cell apoptosis in sequential tissues specimen. Fifteen adults suffering from primary or recurrent DFSP have been included since July 2004. All tumors had a diameter ≥2cm. A flexible design with interim analysis after recruitment of 6 patients was used. 18 to 28 patients had to be enrolled to detect a 30% response rate with power 80%, using a one-sided test against 5%, at the 2.5% level. Three men and 3 women, median age 48.4 years [23; 72.5] have been evaluated. Tumour characteristics are as follows : primary (n=4), recurrence (n=2) all involved trunk, median size 5.75cm [2.5–12]. Tolerance was good apart from grade 1 facial oedema (n=6) grade 2 maculopapular rash (n=1), grade 1 asthenia (n=1), grade 1 pyrosis (n=2). Translocation t(17;22) was detected in all tumours. A partial response was achieved in 3 of 6 patients. The median relative decrease of tumor in the PR and non responder patients was of 21.9% [−3.3; 72.0]. Histological analysis revealed a global decrease of cellularity often accompanied with a CD34 loss of expression, a fibrosis and mild peripheral lymphoid infiltrates. No evidence of apoptosis on tissue specimen after surgery was observed using TUNEL. These encouraging interim results weresubmitted to an independent committee who allowed to continue the trial and to include a total of 24 patients in order to reduce the confidence interval of response rate. [Table: see text]
Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer.
Authors: Bert H. O'Neil, Calin Cainap, Eric Van Cutsem, Vera A. Gorbunova, Christos Stelios Karapetis, Jordan Berlin, Richard M. Goldberg, Qin Qin, Jiang Qian, Justin L. Ricker, Mark D. McKee, Dawn M. Carlson, Tae Won Kim
Journal: Journal of Clinical Oncology (2012)

3532 Background: Linifanib is a potent and selective inhibitor of VEGF/PDGF receptors. This trial assessed the efficacy and safety of mFOLFOX6 in combination with linifanib or bevacizumab as second-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients (pts) with measurable mCRC refractory to 1 prior regimen and ECOG PS 0–1, stratified by prior bevacizumab treatment and radiotherapy, were randomized to receive mFOLFOX6 with bevacizumab 10 mg/kg on day (d) 1 of 14-d cycle (Arm A), mFOLFOX6 with daily linifanib 7.5 mg (Arm B), or mFOLFOX6 with daily linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS). Severity of adverse events (AEs) was graded using NCI-CTCAE v3.0. Results: 148 pts were randomized at 45 sites in 14 countries. 32 pts (21.6%) had received prior bevacizumab. PFS and response data are shown below (Table). Median survival (OS) was not reached at median follow up 7.6 months. Palmar-plantar erythrodysesthesia (PPE) was the only Grade 3/4 AE significantly higher on linifanib (high dose, 16.3%) vs. bevacizumab (0%). Rate of any Grade 3+ AE was significantly higher on linifanib vs. bevacizumab.Hypertension rates were 41.7% (Arm A), 40.0% (Arm B), and 36.7% (Arm C). AEs dose-related to linifanib were constipation, proctalgia, stomatitis, fatigue, weight decrease, decreased appetite, and PPE. Conclusions: The addition of linifanib to mFOLFOX6, compared to mFOLFOX6 + bevacizumab, did not provide a PFS advantage for mCRC. OS results will be updated for conference presentation. [Table: see text]