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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
Zhentao Liu, Zuhua Chen, Jingyuan Wang, Mengqi Zhang, Zhongwu Li, Shubin Wang, Bin Dong, Cheng Zhang, Jing Gao, Lin Shen
BACKGROUND: No approved targeted agents are available for esophageal squamous cell carcinoma (ESCC). Informative genomic analysis and mouse patient-derived xenografts (PDX) also called mouse avatar can greatly expedite drug discovery. METHODS: Six ESCC cell lines and 7 out of 25 PDX models derived from 188 biopsies with clear molecular features were employed to evaluate the sensitivity of several EGFR blockers in vitro and in vivo, as well as the underlying antitumor mechanisms of the most promising EGFR-TKI afatinib...
August 29, 2018: Journal of Hematology & Oncology
Carmen Vicente, Rocco Stirparo, Sofie Demeyer, Charles E de Bock, Olga Gielen, Mardelle Atkins, Jiekun Yan, Georg Halder, Bassem A Hassan, Jan Cools
BACKGROUND: The CNOT3 protein is a subunit of the CCR4-NOT complex, which is involved in mRNA degradation. We recently identified CNOT3 loss-of-function mutations in patients with T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Here, we use different Drosophila melanogaster eye cancer models to study the potential tumor suppressor function of Not3, the CNOT3 orthologue, and other members of the CCR4-NOT complex. RESULTS: Our data show that knockdown of Not3, the structural components Not1/Not2, and the deadenylases twin/Pop2 all result in increased tumor formation...
August 25, 2018: Journal of Hematology & Oncology
Manfei Si, Jinghe Lang
Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in metal homeostasis and protection against heavy metal toxicity, DNA damage, and oxidative stress. In humans, MTs have four main isoforms (MT1, MT2, MT3, and MT4) that are encoded by genes located on chromosome 16q13. MT1 comprises eight known functional (sub)isoforms (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X). Emerging evidence shows that MTs play a pivotal role in tumor formation, progression, and drug resistance...
August 23, 2018: Journal of Hematology & Oncology
Shuhua Cheng, Giorgio Inghirami, Shuo Cheng, Wayne Tam
BACKGROUND: Next-generation sequencing (NGS) of the rearranged immunoglobulin heavy-chain gene has emerged as a highly sensitive method to detect minimal residual disease (MRD) in B acute lymphoblastic leukemia/lymphoma (B-ALL). However, a sensitive and easily implemented NGS methodology for routine clinical laboratories is lacking and clinical utility of NGS-MRD surveillance in a post-remission setting to predict clinical relapse has not been determined. METHODS: Here we described a simple and quantitative NGS platform and assessed its performance characteristics, quantified NGS-MRD levels in 122 B-ALL samples from 30 B-ALL patients, and explored the clinical merit of NGS-based MRD surveillance...
August 22, 2018: Journal of Hematology & Oncology
Hui Sun, Zhaohui Huang, Weiqi Sheng, Mi-Die Xu
Compared with normal cells, tumor cells display distinct metabolic characteristics. Long non-coding RNAs (lncRNAs), a large class of regulatory RNA molecules with limited or no protein-coding capacity, play key roles in tumorigenesis and progression. Recent advances have revealed that lncRNAs play a vital role in cell metabolism by regulating the reprogramming of the metabolic pathways in cancer cells. LncRNAs could regulate various metabolic enzymes that integrate cell malignant transformation and metabolic reprogramming...
August 22, 2018: Journal of Hematology & Oncology
Cen Tang, Feng Chen, Danqing Kong, Qinfen Ma, Haiping Dai, Jia Yin, Zheng Li, Jia Chen, Xiaming Zhu, Xinliang Mao, Depei Wu, Xiaowen Tang
Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Current treatment strategies include the use of growth factors, CD34+ -selected stem cell boost, mesenchymal stem cell transfusion, and second allo-HSCT, but these treatments are not effective in all patients. Eltrombopag, an oral thrombopoietin receptor agonist, which showed promising results in severe aplasia anemia, may be an alternative choice for PGF patients. Therefore, we treated 12 patients who responded poorly to standard treatments for secondary PGF after allo-HSCT with eltrombopag...
August 16, 2018: Journal of Hematology & Oncology
Yang Liu, Yinping Dong, Li Kong, Fang Shi, Hui Zhu, Jinming Yu
Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of patients with malignant tumors. The abscopal effect induced by local RT, which is considered as a systemic anti-tumor immune response, reflects the regression of non-irradiated metastatic lesions at a distance from the primary site of irradiation. Since the application of immunotherapy, especially with immune checkpoint inhibitors, can enhance the systemic anti-tumor response of RT, the combination of RT and immunotherapy has drawn extensive attention by oncologists and cancer researchers...
August 16, 2018: Journal of Hematology & Oncology
Erhao Zhang, Peiwei Yang, Jieyi Gu, Heming Wu, Xiaowei Chi, Chen Liu, Ying Wang, Jianpeng Xue, Weiyan Qi, Qingbo Sun, Shengnan Zhang, Jialiang Hu, Hanmei Xu
BACKGROUND: The therapeutic application of T cells endowing with chimeric antigen receptors (CARs) is faced with "on-target, off-tumor" toxicity against solid tumors, particularly in the treatment of the pancreatic cancer. To our best knowledge, the pancreatic cancer cell line AsPC-1 often highly expressed some distinct tumor-associated antigens, such as carcino-embryonic antigen (CEA) and mesothelin (MSLN). Therefore, in this research, we have characterized dual-receptor CAR-modified T cells (dCAR-T) that exert effective and safe cytotoxicity against AsPC-1 cells...
August 13, 2018: Journal of Hematology & Oncology
Moshe Talpaz, Susan Erickson-Viitanen, Kevin Hou, Solomon Hamburg, Maria R Baer
BACKGROUND: Ruxolitinib improves splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis; however, nearly half develop grade 3/4 anemia and/or thrombocytopenia, necessitating dose reductions and/or transfusions. We report findings from an open-label phase 2 study exploring a dose-escalation strategy aimed at preserving clinical benefit while reducing hematological adverse events early in ruxolitinib treatment. METHODS: Patients with myelofibrosis received ruxolitinib 10 mg twice daily (BID), with incremental increases of 5 mg BID at weeks 12 and 18 for lack of efficacy (maximum, 20 mg BID)...
August 7, 2018: Journal of Hematology & Oncology
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