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immunity therapy for cholangiocarcinoma

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https://www.readbyqxmd.com/read/29984520/malignancy-and-mortality-in-paediatric-onset-inflammatory-bowel-disease-a-3-year-prospective-multinational-study-from-the-paediatric-ibd-porto-group-of-espghan
#1
M E Joosse, M A Aardoom, P Kemos, D Turner, D C Wilson, S Koletzko, J Martin-de-Carpi, U L Fagerberg, C Spray, C Tzivinikos, M Sladek, R Shaoul, E Roma-Giannikou, J Bronsky, D E Serban, F M Ruemmele, H Garnier-Lengline, G Veres, I Hojsak, K L Kolho, I H Davies, M Aloi, P Lionetti, S Hussey, G Veereman, C P Braegger, E Trindade, A V Wewer, A C Hauer, A C H de Vries, R Sigall Boneh, C Sarbagili Shabat, A Levine, L de Ridder
BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD...
July 8, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29893894/new-developments-in-systemic-therapy-for-advanced-biliary-tract-cancer
#2
Chigusa Morizane, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Hiroshi Ishii, Junji Furuse
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs...
August 1, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29871612/transcriptomic-analysis-and-mutational-status-of-idh1-in-paired-primary-recurrent-intrahepatic-cholangiocarcinoma
#3
C Peraldo-Neia, P Ostano, G Cavalloni, Y Pignochino, D Sangiolo, L De Cecco, E Marchesi, D Ribero, A Scarpa, A M De Rose, A Giuliani, F Calise, C Raggi, P Invernizzi, M Aglietta, G Chiorino, F Leone
BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out...
June 5, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29859792/differential-association-between-circulating-lymphocyte-populations-with-outcome-after-radiation-therapy-in-subtypes-of-liver-cancer
#4
Clemens Grassberger, Theodore S Hong, Tai Hato, Beow Y Yeap, Jennifer Y Wo, Mark Tracy, Thomas Bortfeld, John A Wolfgang, Christine E Eyler, Lipika Goyal, Jeffrey W Clark, Christopher H Crane, Eugene J Koay, Mark Cobbold, Thomas F DeLaney, Rakesh K Jain, Andrew X Zhu, Dan G Duda
PURPOSE: Irradiation may have significant immunomodulatory effects that impact tumor response and could potentiate immunotherapeutic approaches. The purposes of this study were to prospectively investigate circulating lymphoid cell population fractions during hypofractionated proton therapy (HPT) in blood samples of liver cancer patients and to explore their association with survival. METHODS AND MATERIALS: We collected serial blood samples before treatment and at days 8 and 15 of HPT from 43 patients with liver cancer-22 with hepatocellular carcinoma (HCC) and 21 with intrahepatic cholangiocarcinoma (ICC)-enrolled in a phase 2 clinical trial...
August 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29843754/immune-checkpoint-therapy-in-liver-cancer
#5
REVIEW
Feng Xu, Tianqiang Jin, Yuwen Zhu, Chaoliu Dai
Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan...
May 29, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29747443/microsatellite-instability-occurs-rarely-in-patients-with-cholangiocarcinoma-a-retrospective-study-from-a-german-tertiary-care-hospital
#6
Ria Winkelmann, Markus Schneider, Sylvia Hartmann, Andreas A Schnitzbauer, Stefan Zeuzem, Jan Peveling-Oberhag, Martin Leo Hansmann, Dirk Walter
Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29511555/impact-of-age-at-diagnosis-on-disease-progression-in-patients-with-primary-sclerosing-cholangitis
#7
Christian Rupp, Alexander Rössler, Taotao Zhou, Conrad Rauber, Kilian Friedrich, Andreas Wannhoff, Karl-Heinz Weiss, Peter Sauer, Peter Schirmacher, Caner Süsal, Wolfgang Stremmel, Daniel N Gotthardt
Background: The median age of diagnosis of primary sclerosing cholangitis (PSC) is ∼30-40 years. Objective: We aimed to analyse disease progression and liver-dependent survival in patients diagnosed with PSC after 50 years of age. Methods: Patients with PSC were analysed with regard to their age at diagnosis. Patients with a first diagnosis of PSC after the age of 50 years were considered as the late-onset group. Results: A total of 32/215 (14...
March 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29506673/desmoplastic-tumor-microenvironment-and-immunotherapy-in-cholangiocarcinoma
#8
REVIEW
Dan Høgdall, Monika Lewinska, Jesper B Andersen
Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies...
March 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29460642/novel-targeted-therapy-strategies-for-biliary-tract-cancers-and-hepatocellular-carcinoma
#9
Thomas T DeLeon, Daniel H Ahn, James M Bogenberger, Panos Z Anastasiadis, Mansi Arora, Ramesh K Ramanathan, Bashar A Aqel, George Vasmatzis, Mark J Truty, Rahmi Oklu, Tanios S Bekaii-Saab, Mitesh J Borad
Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement...
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29420117/inhibition-of-il-10-and-tgf-%C3%AE-receptors-on-dendritic-cells-enhances-activation-of-effector-t-cells-to-kill-cholangiocarcinoma-cells
#10
Chutamas Thepmalee, Aussara Panya, Mutita Junking, Thaweesak Chieochansin, Pa-Thai Yenchitsomanus
Tumor escapes host immune responses by producing immunosuppressive cytokines, such as IL-10 and TGF-β, secreted into the tumor microenvironment. These cytokines play important roles in the suppression of dendritic cell (DC) function, leading to decreased immune responses of the effector CD4+ and CD8+ T cells. To improve DC functions and enhance cytolytic activity of activated effector T-cells, we suppressed the effect of these cytokines on DCs by using specific neutralizing antibodies that inhibit IL-10 and TGF-β receptors...
June 3, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29408314/fibroblast-growth-factor-receptor-inhibition-induces-loss-of-matrix-mcl1-and-necrosis-in-cholangiocarcinoma
#11
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
June 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29138587/primary-sclerosing-cholangitis-diagnostic-and-management-challenges
#12
REVIEW
Sanjeev Sirpal, Natasha Chandok
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease affecting intra- and extrahepatic bile ducts, primarily the large biliary ducts. Clinical manifestations are broad, and the spectrum encompasses asymptomatic cholestasis, icteric cholangitis with pruritis, cirrhosis, and cholangiocarcinoma. Though rare, PSC has a propensity to affect young to middle-aged males and is strongly associated with inflammatory bowel disease. There is an unmet need for effective medical treatments for PSC, and to date, the only curative therapy is liver transplantation reserved for those with end-stage liver disease...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28844952/targeting-cholangiocarcinoma
#13
REVIEW
Joachim C Mertens, Sumera Rizvi, Gregory J Gores
Cholangiocarcinoma (CCA) represents a diverse group of epithelial cancers associated with the biliary tract, and can best be stratified anatomically into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) subsets. Molecular profiling has identified genetic aberrations associated with these anatomic subsets. For example, IDH catalytic site mutations and constitutively active FGFR2 fusion genes are predominantly identified in iCCA, whereas KRAS mutations and PRKACB fusions genes are identified in pCCA and dCCA...
April 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28567120/the-potential-role-of-comprehensive-genomic-profiling-to-guide-targeted-therapy-for-patients-with-biliary-cancer
#14
REVIEW
Hwajeong Lee, Jeffrey S Ross
Remarkable advancements in techniques of genomic profiling and bioinformatics have led to the accumulation of vast amounts of knowledge on the genomic profiles of biliary tract cancer (BTC). Recent largescale molecular profiling studies have not only highlighted genomic differences characterizing tumors of the intrahepatic and extrahepatic bile ducts and gallbladder, but have also revealed differences in genomic profiles pertaining to associated risk factors. Novel genomic alterations such as FGFR2 fusions and IDH1/2 mutations in intrahepatic cholangiocarcinoma (ICC) and ERBB2 alterations in gallbladder cancer (GBCA) are emerging as targeted therapy options capable of advancing precision medicine for the care of these patients...
June 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28218682/immune-mediated-therapies-for-liver-cancer
#15
REVIEW
Rajagopal N Aravalli, Clifford J Steer
In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/27993088/interview-with-dr-ghassan-k-abou-alfa
#16
G K Abou-Alfa
Ghassan K Abou-Alfa joined the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York back in 2001. Dr Abou-Alfa specializes in the treatment of gastrointestinal malignancies. Dr Abou-Alfa received his medical degree from the American University of Beirut, Lebanon, and completed his post-doctoral training at Yale University School of Medicine. His research is dedicated to finding novel therapies and improving the effectiveness of the current therapies for hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, while continuing to understand the basic mechanisms of the diseases and its therapy...
November 2016: Immunotherapy
https://www.readbyqxmd.com/read/27677833/parasitic-and-infectious-diseases-of-the-biliary-tract-in-migrants-and-international-travelers
#17
REVIEW
Christoph Lübbert, Sophie Schneitler
In recent years, global and regional crises have led to extraordinary worldwide migration, accompanied by an increase in long-distance travel from Western countries. Both are linked to a rising incidence of rare parasitic and infectious diseases in first world countries, including in the biliary tract. Areas covered: A selective literature research in PubMed was performed to review the most important parasitic and infectious biliary diseases, which are caused by a wide variety of pathogens and may be latent over long periods, with chronic courses leading to cholangitis, hepatic failure or development of cholangiocarcinoma...
November 2016: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27658789/genomic-profiling-of-biliary-tract-cancers-and-implications-for-clinical-practice
#18
REVIEW
Apurva Jain, Lawrence N Kwong, Milind Javle
Biliary tract cancers are relatively uncommon, have an aggressive disease course and a dismal clinical outcome. Until recently, there have been very few clinical advances in the management of these patients and gemcitabine-based chemotherapy has been the only widely accepted systemic therapy. The advent of next generation sequencing technologies can potentially change the treatment paradigm of this disease. Targeted therapy directed against actionable mutations and identification of molecular subsets with distinct prognostic significance is now feasible in clinical practice...
November 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/27618321/malignancy-after-solid-organ-transplantation-comprehensive-imaging-review
#19
REVIEW
Venkata S Katabathina, Christine O Menias, Varaha S Tammisetti, Meghan G Lubner, Ania Kielar, Akram Shaaban, Joseph Mansour, Venkateshwar R Surabhi, Amy K Hara
Life expectancies for solid organ recipients as well as graft survival rates for these patients have improved over the years because of advanced immunosuppressive therapies; however, with chronic use of these drugs, posttransplant malignancy has become one of the leading causes of morbidity for them. The risk of carcinogenesis in transplant recipients is significantly higher than for the general population and cancers tend to manifest at an advanced stage. Posttransplant malignancies are thought to develop by three mechanisms: de novo development, donor-related transmission, and recurrence of a recipient's pretransplant malignancy...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/27012989/program-death-1-immune-checkpoint-and-tumor-microenvironment-implications-for-patients-with-intrahepatic-cholangiocarcinoma
#20
Faiz Gani, Neeraja Nagarajan, Yuhree Kim, Qingfeng Zhu, Lan Luan, Feriyl Bhaijjee, Robert A Anders, Timothy M Pawlik
BACKGROUND: Program death 1 (PD-1) and its ligand (PD-L1) have been identified as potential therapeutic targets for solid and hematologic malignancies. The current study aimed to assess PD-L1 expression in intrahepatic cholangiocarcinoma (ICC) and relate clinical outcomes to its expression. METHODS: Formalin-fixed, paraffin-embedded tumor specimens were obtained for patients undergoing surgery at Johns Hopkins Hospital between 1991 and 2011. Immunohistochemistry was used to assess PD-L1 expression in tumor-associated macrophages (TAMs) and within the tumor front (TF)...
August 2016: Annals of Surgical Oncology
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