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Journal of Hematology & Oncology

Cathy Zhou, Zilong Yuan, Weijie Ma, Lihong Qi, Angelique Mahavongtrakul, Ying Li, Hong Li, Jay Gong, Reggie R Fan, Jin Li, Michael Molmen, Travis A Clark, Dean Pavlick, Garrett M Frampton, Brady Forcier, Elizabeth H Moore, David K Shelton, Matthew Cooke, Siraj M Ali, Vincent A Miller, Jeffrey P Gregg, Philip J Stephens, Tianhong Li
BACKGROUND: This retrospective study was undertaken to determine if the plasma circulating tumor DNA (ctDNA) level and tumor biological features in patients with advanced solid tumors affected the detection of genomic alterations (GAs) by a plasma ctDNA assay. METHOD: Cell-free DNA (cfDNA) extracted from frozen plasma (N = 35) or fresh whole blood (N = 90) samples were subjected to a 62-gene hybrid capture-based next-generation sequencing assay FoundationACT...
November 6, 2018: Journal of Hematology & Oncology
Jinhuan Xu, Qiuxiang Wang, Hao Xu, Chaojiang Gu, Lijun Jiang, Jue Wang, Di Wang, Bin Xu, Xia Mao, Jin Wang, Zhiqiong Wang, Yi Xiao, Yicheng Zhang, Chunrui Li, Jianfeng Zhou
BACKGROUND: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome still has no standard treatment. On the basis that both POEMS syndrome and myeloma have an underlying plasma cell dyscrasia, anti-myeloma therapy can be expected to be useful for POEMS syndrome. Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) has been used in the treatment of relapsed and refractory multiple myeloma (RRMM). No POEMS syndrome cases treated with anti-BCMA CAR-T cells have been reported...
October 22, 2018: Journal of Hematology & Oncology
Florent Malard, Myriam Labopin, Christina Cho, Didier Blaise, Esperanza B Papadopoulos, Jakob Passweg, Richard O'Reilly, Edouard Forcade, Molly Maloy, Liisa Volin, Hugo Castro-Malaspina, Yosr Hicheri, Ann A Jakubowski, Corentin Orvain, Sergio Giralt, Mohamad Mohty, Arnon Nagler, Miguel-Angel Perales
BACKGROUND: Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT). METHODS: We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included...
October 20, 2018: Journal of Hematology & Oncology
Feifei Liu, Yanning Liu, Zhi Chen
Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and its mortality is still on the rise. Limited treatments and low chemotherapy sensitivity of HCC make new therapeutic strategies urgently needed. With the rise of immune checkpoint blockade, anti-CTLA-4 antibodies and anti-PD-1 antibodies have shown therapeutic effects in various tumors. T cell immunoglobulin mucin-3 (Tim-3), a newly discovered immune checkpoint molecule, plays a major role in the development of HCC. Tim-3 can be used to evaluate the prognosis and therapeutic effects in HCC, and Tim-3 intervention has shown anti-tumor effects in preclinical experiments...
October 11, 2018: Journal of Hematology & Oncology
Martin Schlesinger
The interaction of tumor cells with platelets is a prerequisite for successful hematogenous metastatic dissemination. Upon tumor cell arrival in the blood, tumor cells immediately activate platelets to form a permissive microenvironment. Platelets protect tumor cells from shear forces and assault of NK cells, recruit myeloid cells by secretion of chemokines, and mediate an arrest of the tumor cell platelet embolus at the vascular wall. Subsequently, platelet-derived growth factors confer a mesenchymal-like phenotype to tumor cells and open the capillary endothelium to expedite extravasation in distant organs...
October 11, 2018: Journal of Hematology & Oncology
Xu Liang, Adrien Briaux, Véronique Becette, Camille Benoist, Anais Boulai, Walid Chemlali, Anne Schnitzler, Sylvain Baulande, Sofia Rivera, Marie-Ange Mouret-Reynier, Laurence Venat Bouvet, Thibaut De La Motte Rouge, Jérôme Lemonnier, Florence Lerebours, Céline Callens
BACKGROUND: Postmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis. METHODS: Gene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients...
October 11, 2018: Journal of Hematology & Oncology
Daniela N Petrusca, Denise Toscani, Feng-Ming Wang, Cheolkyu Park, Colin D Crean, Judith L Anderson, Silvia Marino, Khalid S Mohammad, Dan Zhou, Rebecca Silbermann, Quanhong Sun, Noriyoshi Kurihara, Deborah L Galson, Nicola Giuliani, G David Roodman
BACKGROUND: In spite of major advances in treatment, multiple myeloma (MM) is currently an incurable malignancy due to the emergence of drug-resistant clones. We previously showed that MM cells upregulate the transcriptional repressor, growth factor independence 1 (Gfi1), in bone marrow stromal cells (BMSCs) that induces prolonged inhibition of osteoblast differentiation. However, the role of Gfi1 in MM cells is unknown. METHODS: Human primary CD138+ and BMSC were purified from normal donors and MM patients' bone marrow aspirates...
October 4, 2018: Journal of Hematology & Oncology
Stephen Couban, Giulia Benevolo, William Donnellan, Jennifer Cultrera, Steffen Koschmieder, Srdan Verstovsek, Gregory Hooper, Christian Hertig, Maneesh Tandon, Natalie Dimier, Vikram Malhi, Francesco Passamonti
BACKGROUND: The JAK inhibitor (JAKi) ruxolitinib is standard treatment for myelofibrosis (MF), but some patients are unresponsive. Pre-clinical and clinical data suggest that addition of a Hedgehog pathway inhibitor (HPI) to ruxolitinib might improve response. Vismodegib is an HPI approved for treatment of locally advanced and metastatic basal cell carcinoma. The MYLIE study assessed the safety and efficacy of combining ruxolitinib with vismodegib in ruxolitinib-naive patients with MF and characterized the pharmacokinetics (PK) of vismodegib in this setting...
September 24, 2018: Journal of Hematology & Oncology
Delong Liu, Juanjuan Zhao
Genetically modified T cells that express a chimeric antigen receptor (CAR) are opening a new frontier in cancer immunotherapy. CAR T cells currently are in clinical trials for many cancer types. Cytokine release syndrome (CRS) and neurotoxicities (CAR-related encephalopathy syndrome, CRES) are major adverse events limiting wide deployment of the CAR T cell treatment. Major efforts are ongoing to characterize the pathogenesis and etiology of CRS and CRES. Mouse models have been established to facilitate the study of pathogenesis of the major toxicities of CAR T cells...
September 24, 2018: Journal of Hematology & Oncology
Marcia Bellon, Ramona Moles, Hassiba Chaib-Mezrag, Joanna Pancewicz, Christophe Nicot
BACKGROUND: HTLV-1 is a retrovirus that infects over 20 million people worldwide and is responsible for the hematopoietic malignancy adult T cell leukemia (ATL). We previously demonstrated that Notch is constitutively activated in ATL cells. Activating genetic mutations were found in Notch; however, Notch signaling was also activated in the absence of genetic mutations suggesting the existence of other mechanisms. METHODS: We analyzed the expression of Notch receptor ligands in HTLV-I-transformed cells, ATL patient-derived cell lines, and fresh uncultured ATL samples by RT-PCR, FACS, and immunohistochemistry...
September 19, 2018: Journal of Hematology & Oncology
Guoshuang Shen, Fangchao Zheng, Dengfeng Ren, Feng Du, Qiuxia Dong, Ziyi Wang, Fuxing Zhao, Raees Ahmad, Jiuda Zhao
Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC...
September 19, 2018: Journal of Hematology & Oncology
Yingxue Qi, Wenchun Chen, Xinyu Liang, Ke Xu, Xiangyu Gu, Fengying Wu, Xuemei Fan, Shengxiang Ren, Junling Liu, Jun Zhang, Renhao Li, Jianwen Liu, Xin Liang
BACKGROUND: Platelet glycoprotein Ibα (GPIbα) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. However, the mechanism through which GPIbα participates in the metastatic process remains unclear. In addition, potential bleeding complication remains an obstacle for the clinical use of anti-platelet agents in cancer therapy. METHODS: We established a series of screening models and obtained rat anti-mouse GPIbα monoclonal antibodies (mAb) 1D12 and 2B4 that demonstrated potential value in suppressing cancer metastasis...
September 17, 2018: Journal of Hematology & Oncology
Min Su, Yuhang Xiao, Junliang Ma, Deliang Cao, Yong Zhou, Hui Wang, Qianjin Liao, Wenxiang Wang
Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers and effective prognostic indicators for metastasis and recurrence has resulted in the poor prognosis of EC. In addition, the underlying molecular mechanisms of EC development have yet to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a vital role in the pathological progression of EC. LncRNAs may regulate gene expression through the recruitment of histone-modifying complexes to the chromatin and through interactions with RNAs or proteins...
September 17, 2018: Journal of Hematology & Oncology
Hanxiao Xu, Xiaodong Lyu, Ming Yi, Weiheng Zhao, Yongping Song, Kongming Wu
During the past decade, the three-dimensional organoid technology has sprung up and become more and more popular among researchers. Organoids are the miniatures of in vivo tissues and organs, and faithfully recapitulate the architectures and distinctive functions of a specific organ.These amazing three-dimensional constructs represent a promising, near-physiological model for human cancers, and tremendously support diverse potential applications in cancer research. Up to now, highly efficient establishment of organoids can be achieved from both normal and malignant tissues of patients...
September 15, 2018: Journal of Hematology & Oncology
Zhuoyu Gu, Yixin Li, Xiaoya Yang, Meisheng Yu, Zhanru Chen, Chan Zhao, Lixin Chen, Liwei Wang
BACKGROUND: Recently, many potential prognostic biomarkers for gastric cancer (GC) have been identified, but the prognosis of advanced GC patients remains poor. Chloride channels are promising cancer biomarkers, and their family member chloride channel-3 (CLC-3) is involved in multiple biological behaviors. However, whether CLC-3 is a prognostic biomarker for GC patients is rarely reported. The molecular mechanisms by which CLC-3 is regulated in GC are unclear. METHODS: The expression of CLC-3 and XRCC5 in human specimens was analyzed using immunohistochemistry...
September 14, 2018: Journal of Hematology & Oncology
Yi Rang Kim, Jung Ki Yoo, Chang Wook Jeong, Jin Woo Choi
Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of the technical difficulty in examining the effects of CTC elimination in vivo. We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination...
September 10, 2018: Journal of Hematology & Oncology
Meng Zhang, Weiwei Weng, Qiongyan Zhang, Yong Wu, Shujuan Ni, Cong Tan, Midie Xu, Hui Sun, Chenchen Liu, Ping Wei, Xiang Du
BACKGROUND: The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. METHODS: To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression...
September 5, 2018: Journal of Hematology & Oncology
Simon Heine, Markus Kleih, Neus Giménez, Kathrin Böpple, German Ott, Dolors Colomer, Walter E Aulitzky, Heiko van der Kuip, Elisabeth Silkenstedt
BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive B-non-Hodgkin lymphoma with generally poor outcome. MCL is characterized by an aberrantly high cyclin D1-driven CDK4 activity. New molecular targeted therapies such as inhibitors of the ubiquitin-proteasome system (UPS) have shown promising results in preclinical studies and MCL patients. Our previous research revealed stabilization of the short-lived pro-apoptotic NOXA as a critical determinant for sensitivity to these inhibitors...
September 4, 2018: Journal of Hematology & Oncology
Ting Li, Chao Zhang, Shafat Hassan, Xinyue Liu, Fengju Song, Kexin Chen, Wei Zhang, Jilong Yang
Histone acetylation and deacetylation are important epigenetic mechanisms that regulate gene expression and transcription. Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family that not only participates in histone acetylation and deacetylation but also targets several nonhistone substrates, such as α-tubulin, cortactin, and heat shock protein 90 (HSP90), to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. Furthermore, HDAC6 also upregulates several critical factors in the immune system, such as program death receptor-1 (PD-1) and program death receptor ligand-1 (PD-L1) receptor, which are the main targets for cancer immunotherapy...
September 3, 2018: Journal of Hematology & Oncology
Federica Giannotti, Myriam Labopin, Roni Shouval, Jaime Sanz, William Arcese, Emanuele Angelucci, Jorge Sierra, Josep-Maria Ribera Santasusana, Stella Santarone, Bruno Benedetto, Alessandro Rambaldi, Riccardo Saccardi, Didier Blaise, Michele Angelo Carella, Vanderson Rocha, Frederic Baron, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
BACKGROUND: Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established. METHODS: This was a retrospective study based on an international European registry...
August 30, 2018: Journal of Hematology & Oncology
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