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Journal of Hematology & Oncology

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https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#1
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#2
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28514966/clinical-applications-of-pd-l1-bioassays-for-cancer-immunotherapy
#3
REVIEW
Delong Liu, Shuhang Wang, Wendy Bindeman
Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making...
May 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28511709/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-tandem-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-high-risk-neuroblastoma-results-of-the-smc-nb-2009-study
#4
Ji Won Lee, Sanghoon Lee, Hee Won Cho, Youngeun Ma, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Eun Joo Cho, Suk-Koo Lee, Do Hoon Lim
BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with (131)I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28511686/intrathymic-injection-of-hematopoietic-progenitor-cells-establishes-functional-t-cell-development-in-a-mouse-model-of-severe-combined-immunodeficiency
#5
Andrea Z Tuckett, Raymond H Thornton, Richard J O'Reilly, Marcel R M van den Brink, Johannes L Zakrzewski
BACKGROUND: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28506242/an-imprinted-non-coding-genomic-cluster-at-14q32-defines-clinically-relevant-molecular-subtypes-in-osteosarcoma-across-multiple-independent-datasets
#6
Katherine E Hill, Andrew D Kelly, Marieke L Kuijjer, William Barry, Ahmed Rattani, Cassandra C Garbutt, Haydn Kissick, Katherine Janeway, Antonio Perez-Atayde, Jeffrey Goldsmith, Mark C Gebhardt, Mohamed S Arredouani, Greg Cote, Francis Hornicek, Edwin Choy, Zhenfeng Duan, John Quackenbush, Benjamin Haibe-Kains, Dimitrios Spentzos
BACKGROUND: A microRNA (miRNA) collection on the imprinted 14q32 MEG3 region has been associated with outcome in osteosarcoma. We assessed the clinical utility of this miRNA set and their association with methylation status. METHODS: We integrated coding and non-coding RNA data from three independent annotated clinical osteosarcoma cohorts (n = 65, n = 27, and n = 25) and miRNA and methylation data from one in vitro (19 cell lines) and one clinical (NCI Therapeutically Applicable Research to Generate Effective Treatments (TARGET) osteosarcoma dataset, n = 80) dataset...
May 15, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28499452/current-status-and-perspectives-of-patient-derived-xenograft-models-in-cancer-research
#7
REVIEW
Yunxin Lai, Xinru Wei, Shouheng Lin, Le Qin, Lin Cheng, Peng Li
Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft (PDX) models are created when cancerous cells or tissues from patients' primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models...
May 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28494772/anti-claudin-18-2-antibody-as-new-targeted-therapy-for-advanced-gastric-cancer
#8
REVIEW
Prabhsimranjot Singh, Sudhamshi Toom, Yiwu Huang
Targeted therapy and immunotherapy have revolutionized treatment of various cancers in the past decade. Despite targeted therapy with trastuzumab in Her2-positive gastric cancer patients, survival has been dismal, mostly due to disease progression and toxicity related to the treatments. One area of active development is looking for ideal monoclonal antibodies (IMAB) specific to the proteins only on the tumor and hence avoiding unnecessary side effects. Claudin proteins with isoform 2 are one such protein, specific for several cancers, particularly gastric cancer and its metastases, leading to the development of anti-claudin 18...
May 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28494777/platelet-desialylation-is-a-novel-mechanism-and-a-therapeutic-target-in-thrombocytopenia-during-sepsis-an-open-label-multicenter-randomized-controlled-trial
#9
Mei-Feng Li, Xiao-Li Li, Kai-Liang Fan, Ying-Yi Yu, Jing Gong, Shu-Ying Geng, Ya-Feng Liang, Ling Huang, Ji-Hua Qiu, Xing-Han Tian, Wen-Ting Wang, Xiao-Lu Zhang, Qing-Xia Yu, Yuan-Feng Zhang, Peng Lin, Li-Na Wang, Xin Li, Ming Hou, Lu-Yi Liu, Jun Peng
BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I)...
May 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28482908/curative-or-pre-emptive-adenovirus-specific-t-cell-transfer-from-matched-unrelated-or-third-party-haploidentical-donors-after-hsct-including-ucb-transplantations-a-successful-phase-i-ii-multicenter-clinical-trial
#10
Chongsheng Qian, Arnaud Campidelli, Yingying Wang, Huili Cai, Véronique Venard, Hélène Jeulin, Jean Hugues Dalle, Cécile Pochon, Maud D'aveni, Benedicte Bruno, Catherine Paillard, Stéphane Vigouroux, Charlotte Jubert, Patrice Ceballos, Aude Marie-Cardine, Claire Galambrun, Clément Cholle, Isabelle Clerc Urmes, Nadine Petitpain, Marcelo De Carvalho Bittencourt, Véronique Decot, Loïc Reppel, Alexandra Salmon, Laurence Clement, Danièle Bensoussan
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB)...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28482851/checkpoint-inhibitors-in-hematological-malignancies
#11
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28476164/wnt-beta-catenin-pathway-modulating-anticancer-immune-response
#12
REVIEW
Sachin Gopalkrishna Pai, Benedito A Carneiro, Jose Mauricio Mota, Ricardo Costa, Caio Abner Leite, Romualdo Barroso-Sousa, Jason Benjamin Kaplan, Young Kwang Chae, Francis Joseph Giles
Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus...
May 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28472989/circulating-mutational-portrait-of-cancer-manifestation-of-aggressive-clonal-events-in-both-early-and-late-stages
#13
Meng Yang, Umit Topaloglu, W Jeffrey Petty, Matthew Pagni, Kristie L Foley, Stefan C Grant, Mac Robinson, Rhonda L Bitting, Alexandra Thomas, Angela T Alistar, Rodwige J Desnoyers, Michael Goodman, Carol Albright, Mercedes Porosnicu, Mihaela Vatca, Shadi A Qasem, Barry DeYoung, Ville Kytola, Matti Nykter, Kexin Chen, Edward A Levine, Edgar D Staren, Ralph B D'Agostino, Robin M Petro, William Blackstock, Bayard L Powell, Edward Abraham, Boris Pasche, Wei Zhang
BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins...
May 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28464892/non-driver-mutations-in-myeloproliferative-neoplasm-associated-myelofibrosis
#14
LETTER
Bing Li, Robert Peter Gale, Zefeng Xu, Tiejun Qin, Zhen Song, Peihong Zhang, Jie Bai, Lei Zhang, Yue Zhang, Jinqin Liu, Gang Huang, Zhijian Xiao
We studied non-driver mutations in 62 subjects with myeloproliferative neoplasm (MPN)-associated myelofibrosis upon diagnosis, including 45 subjects with primary myelofibrosis (PMF) and 17 with post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF). Fifty-eight subjects had ≥1 non-driver mutation upon diagnosis. Mutations in mRNA splicing genes, especially in U2AF1, were significantly more frequent in PMF than in post-PV/ET MF (33 vs. 6%; P = 0.015). There were also striking differences in clonal architecture...
May 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28454587/emerging-therapies-for-breast-cancer
#15
REVIEW
Xichun Hu, Wei Huang, Minhao Fan
HER2 and CDK4/6 are undoubted two most important biological targets for breast cancer. Anti-HER2 treatments enhance objective response and progression-free survival/disease-free survival as well as overall survival. Three CDK4/6 inhibitors consistently improve objective response and progression-free survival; however, overall survival data are waited. Optimization of chemotherapy and endocrine strategies remains an unmet need. Check point inhibitor-based immunotherapy combined with chemotherapy is a promising field, especially for triple-negative breast cancer...
April 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28438180/recent-advances-of-highly-selective-cdk4-6-inhibitors-in-breast-cancer
#16
REVIEW
Hanxiao Xu, Shengnan Yu, Qian Liu, Xun Yuan, Sridhar Mani, Richard G Pestell, Kongming Wu
Uncontrolled cell division is the hallmark of cancers. Full understanding of cell cycle regulation would contribute to promising cancer therapies. In particular, cyclin-dependent kinases 4/6 (CDK4/6), which are pivotal drivers of cell proliferation by combination with cyclin D, draw more and more attention. Subsequently, extensive studies were carried out to explore drugs inhibiting CDK4/6 and assess the efficacy and safety of these drugs in cancer, especially breast cancer. Due to the insuperable adverse events and the less activity observed in vivo, the drug development of the initial pan-CDK inhibitor flavopiridol was consequently discontinued, and then highly specific inhibitors were extensively researched and developed, including palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219)...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434404/recent-advances-in-cancer-immunotherapy
#17
EDITORIAL
Weijing Sun
No abstract text is available yet for this article.
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434403/immunotherapy-in-genitourinary-malignancies
#18
REVIEW
Kathan Mehta, Keyur Patel, Rahul A Parikh
Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434400/role-of-modern-immunotherapy-in-gastrointestinal-malignancies-a-review-of-current-clinical-progress
#19
REVIEW
Zin W Myint, Gaurav Goel
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#20
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
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