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Experimental Hematology & Oncology

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https://www.readbyqxmd.com/read/29214116/compassionate-use-of-ruxolitinib-in-acute-and-chronic-graft-versus-host-disease-refractory-both-to-corticosteroids-and-extracorporeal-photopheresis
#1
Mauricio Sarmiento Maldonado, Pablo Ramírez Villanueva, Pablo Bertín Cortes-Monroy, Veronica Jara Arias, Katherine Soto Donoso, Pablo Uribe Gonzalez, Mauricio Ocqueteau Tachini, Jose Antonio Perez-Simón
Background: Ruxolitinib is a potent inhibitor of JAK1/2 with proven efficacy in myelofibrosis. In recent years, research in graft versus host disease (GVHD) has revealed the role of activation of JAK pathways in alloreactive lymphocytes. Some reports have shown significant responses in refractory GVHD patients. Cases presentation: In this report we present our experience in 8 patients with acute or chronic GVHD with refractoriness to steroids and extracorporeal photopheresis treated with ruxolitinib...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29209558/development-and-clinical-application-of-anti-her2-monoclonal-and-bispecific-antibodies-for-cancer-treatment
#2
REVIEW
Shengnan Yu, Qian Liu, Xinwei Han, Shuang Qin, Weiheng Zhao, Anping Li, Kongming Wu
HER2-targeted immunotherapy consists of monoclonal antibodies (e.g. trastuzumab, pertuzumab), bispecific antibodies (e.g. MM-111, ertumaxomab) and activated T cells armed with anti-HER2 bispecific antibody (HER2Bi-aATC). Trastuzumab is a classic drug for the treatment of HER2 positive metastatic breast cancer. The combined application of pertuzumab, trastuzumab and paclitaxel has been suggested as a standard therapy for HER2 positive advanced breast cancer. The resistance to anti-HER2 antibody has resulted in disease progression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29152412/histomorphological-responses-after-therapy-with-pegylated-interferon-%C3%AE-2a-in-patients-with-essential-thrombocythemia-et-and-polycythemia-vera-pv
#3
Lucia Masarova, C Cameron Yin, Jorge E Cortes, Marina Konopleva, Gautam Borthakur, Kate J Newberry, Hagop M Kantarjian, Carlos E Bueso-Ramos, Srdan Verstovsek
Background: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods: Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#4
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29046826/incorporation-of-functional-elements-enhances-the-antitumor-capacity-of-car-t-cells
#5
REVIEW
Le Qin, Ruocong Zhao, Peng Li
As chimeric antigen receptor (CAR) T cells have displayed an unprecedented efficacy in the treatment of CD19-positive malignances, it is believed that this cell therapy will be a milestone in the history of mankind's conquering of cancer. However, there are some issues that restrict CAR T cells from reaching their optimal anti-tumor capacity, especially in the treatment of solid tumors. Inhibitory cytokines, immune checkpoint molecules, hypoxia and other adverse factors have been reported to be involved in this process...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29026685/pharmacokinetics-of-carfilzomib-in-patients-with-advanced-malignancies-and-varying-degrees-of-hepatic-impairment-an-open-label-single-arm-phase-1-study
#6
Jennifer Brown, Ruth Plummer, Todd M Bauer, Stephen Anthony, John Sarantopoulos, Filip De Vos, Mike White, Marco Schupp, Ying Ou, Ulka Vaishampayan
BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29021921/post-transplant-lymphoproliferative-disorder-ptld-single-institutional-experience-of-141-patients
#7
Rohit Bishnoi, Ravneet Bajwa, Aaron J Franke, William Paul Skelton, Yu Wang, Niraj M Patel, William Birdsall Slayton, Fei Zou, Nam H Dang
BACKGROUND: Post-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world. METHODS: This study was performed at University of Florida which is one of the largest transplant center in South East United States...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28932626/complete-biochemical-response-after-pulmonary-metastasectomy-in-prostate-adenocarcinoma
#8
Jonathan Rush, Reet Pai, Rahul A Parikh
BACKGROUND: Prostate cancer most commonly metastasizes to bones or lymph nodes, and metastatic prostate cancer is suggestive of disseminated disease. Metastatic disease is usually not amenable to surgery. CASE PRESENTATION: The current report presents a unique case of in which the excision of a solitary pulmonary metastasis resulted in undetectable prostate-specific antigen. CONCLUSION: This case and others suggest metastasectomy could be considered in cases with solitary metastasis, and physicians should have a careful discussion regarding risks and possible benefits from surgical excision...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28808609/optimizing-peripheral-blood-stem-cells-transplantation-outcome-through-amend-relapse-and-graft-failure-a-review-of-current-literature
#9
REVIEW
Saeed Mohammadi, Amir Hossein Norooznezhad, Ashraf Malek Mohammadi, Hajar Nasiri, Mohsen Nikbakht, Najmaldin Saki, Mohammad Vaezi, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been considered as a valuable approach in treatment of numerous malignant and none malignant hematologic disorders. However, relapse and poor graft function (PGF) after allo-SCT remain to be controversial issues which may affect the transplantation outcome. Relevant articles were searched in MEDLINE database (2000-2016) using keywords and phrases: donor lymphocyte infusions, allogeneic stem cells transplantation, relapsed hematologic malignancies, booster schedules, cell dose, laboratory monitoring protocols and technical aspects of apheresis...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28804688/pivotal-regulators-of-tissue-homeostasis-and-cancer-macrophages
#10
REVIEW
Yulei Chen, Xiaobo Zhang
Macrophages are an essential component of innate immunity and play a vital role in inflammation and host defense. Based on immunological responses, the macrophages are classified into "activated" macrophage (M1 macrophages) participating in the responses of type I helper T (Th1) cells to pathogens and "alternatively activated" macrophages (M2 macrophages) in response to interleukin (IL)-4 and IL-13. In this review, we discuss the origin, classification and function of macrophages. We also discuss the mechanisms underlying polarization of different macrophage subtypes, including transcriptional, epigenetic and post-transcriptional regulation...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28794917/microfluidic-device-for-primary-tumor-spheroid-isolation
#11
Jiaojiao Zhou, Jimmy Su, Xiaotong Fu, Lei Zheng, Zhizhong Yin
BACKGROUND: Traditional two-dimensional (2-D) monolayer cell culture is vastly different from in vivo physiological conditions, which can lead to inaccurate or insufficient data in areas where response and efficacy within humans are being investigated, such as drug discovery, pathology studies, etc. Misleading results arise from two main disadvantages of monolayer cell culture. First, after several passages, cell lines lose many features from their original in vivo state. Second, the morphology of cells cultured in a monolayer is much different from the cell morphology in three-dimensional (3-D) in vivo conditions, thus resulting in altered cellular function...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28725494/apixaban-for-treatment-of-confirmed-heparin-induced-thrombocytopenia-a-case-report-and-review-of-literature
#12
Daniel E Ezekwudo, Rebecca Chacko, Bolanle Gbadamosi, Syeda Batool, Sussana Gaikazian, Theodore E Warkentin, Jo-Ann I Sheppard, Ishmael Jaiyesimi
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28725493/interferon-alpha-based-immunotherapies-in-the-treatment-of-b-cell-derived-hematologic-neoplasms-in-today-s-treat-to-target-era
#13
REVIEW
Li Zhang, Yu-Tzu Tai, Matthew Zhi Guang Ho, Lugui Qiu, Kenneth C Anderson
B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15-20%...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28670501/pten-is-a-negative-regulator-of-mitotic-checkpoint-complex-during-the-cell-cycle
#14
Byeong H Choi, Steve Xie, Wei Dai
Nuclear PTEN plays an important role during mitosis. To understand the molecular basis by which PTEN mediates mitotic progression, we examined whether PTEN regulated the formation of mitotic checkpoint complex (MCC). We observed that arsenic trioxide, a mitotic inducer, stimulated nuclear translocation of PTEN in a time-dependent manner. PTEN physically interacted with Cdc20 and Mad2, two important components of MCC. Arsenic treatment diminished the physical association of PTEN with BubR1 and Bub3 but not with Cdc20 and Mad2...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28638723/low-dose-methotrexate-in-sickle-cell-disease-a-pilot-study-with-rationale-borrowed-from-rheumatoid-arthritis
#15
Silvia R Brandalise, Rosemary Assis, Angelo B A Laranjeira, José Andrés Yunes, Pedro O de Campos-Lima
BACKGROUND: Inflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients. METHODS: Fourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28630798/the-role-of-cullin4b-in-human-cancers
#16
REVIEW
Ying Li, Xin Wang
Cullin 4B (CUL4B) is a scaffold of the Cullin4B-Ring E3 ligase complex (CRL4B) that plays an important role in proteolysis and is implicated in tumorigenesis. Aberrant expression of CUL4B has been reported in various types of human diseases. Recently, studies have shown that CUL4B was overexpressed in a multitude of solid neoplasms and affect the expression of several tumor suppressor genes. In this review, we aim to summarize the biological function of CUL4B in order to better understand its pathogenesis in human cancers...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28560070/clinical-implications-of-c-maf-expression-in-plasma-cells-from-patients-with-multiple-myeloma
#17
GuoQing Wei, LiJun Wang, HanJin Yang, XiaoYan Han, GaoFeng Zheng, WeiYan Zheng, Jie Sun, JiMin Shi, WenJun Wu, Yi Zhao, DongHua He, Bo Wang, Zhen Cai, JingSong He
BACKGROUND: Multiple myeloma (MM) is a type of hematological malignancy with significant heterogeneity in clinical features and prognosis. Cytogenetic abnormalities are the major factors affecting patient outcomes. Studies have shown that immunohistochemistry (IHC)-based detection of cancer-related genes expression could be alternative indicators for the prognosis of MM. METHODS: Nuclear expression of c-maf protein in the bone marrow plasma cells of 128 multiple myeloma patients were examined by IHC, and its association with the clinicopathological features of MM patients was analyzed as well...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28546884/in-vivo-and-in-situ-programming-of-tumor-immunity-by-combining-oncolytics-and-pd-1-immune-checkpoint-blockade
#18
Eric Bartee, Zihai Li
Blockade of the programmed cell death protein 1 (PD1) pathway is clinically effective against human cancers. Although multiple types of malignancies have been shown to respond to PD1 agents, only a small percentage of patients typically benefit from this treatment. In addition, PD1 therapy often causes serious immune-related adverse events. A recent study demonstrated that local, intra-tumoral, administration of modified oncolytic myxoma virus which expresses a truncated version of the PD1 protein resulted in both increased efficacy and reduced toxicity in a clinically relevant melanoma model...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#19
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28473943/cyclosporine-is-a-potential-curative-treatment-option-for-advanced-thymoma
#20
Yusuke Isshiki, Hiroaki Tanaka, Yoshio Suzuki, Yukihiro Yoshida
BACKGROUND: Thymectomy can effectively cure most thymoma patients; however, patients with advanced thymoma typically require chemotherapy, which is associated with limited efficacy in this context. Here we provide the first report of a patient with recurrent thymoma who achieved complete remission (CR) using cyclosporine therapy. CASE PRESENTATION: A 63-year-old woman who had undergone resection surgery for recurrent type B1 thymoma developed pure red cell aplasia (PRCA), and CT findings revealed thymoma recurrence...
2017: Experimental Hematology & Oncology
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