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Journal of Hematology & Oncology

Jun Guo, Jie Jin, Mototsugu Oya, Hirotsugu Uemura, Shunji Takahashi, Katsunori Tatsugami, Sun Young Rha, Jae-Lyun Lee, Jinsoo Chung, Ho Yeong Lim, Hsi Chin Wu, Yen Hwa Chang, Arun Azad, Ian D Davis, Marlene J Carrasco-Alfonso, Bhupinder Nanua, Jackie Han, Qasim Ahmad, Robert Motzer
BACKGROUND: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations. METHODS: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off)...
May 22, 2018: Journal of Hematology & Oncology
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
Rachel E Piddock, Christopher R Marlein, Amina Abdul-Aziz, Manar S Shafat, Martin J Auger, Kristian M Bowles, Stuart A Rushworth
Multiple myeloma (MM) remains an incurable malignancy despite the recent advancements in its treatment. The protective effects of the niche in which it develops has been well documented; however, little has been done to investigate the MM cell's ability to 're-program' cells within its environment to benefit disease progression. Here, we show that MM-derived macrophage migratory inhibitory factor (MIF) stimulates bone marrow stromal cells to produce the disease critical cytokines IL-6 and IL-8, prior to any cell-cell contact...
May 16, 2018: Journal of Hematology & Oncology
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
Chen Chen, Shujie Zhao, Anand Karnad, James W Freeman
CD44, a non-kinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in cancer development and progression. Hyaluronan, the main ligand for CD44, binds to and activates CD44 resulting in activation of cell signaling pathways that induces cell proliferation, increases cell survival, modulates cytoskeletal changes, and enhances cellular motility. The different functional roles of CD44 standard (CD44s) and specific CD44 variant (CD44v) isoforms are not fully understood...
May 10, 2018: Journal of Hematology & Oncology
Nicola Amodio, Lavinia Raimondi, Giada Juli, Maria Angelica Stamato, Daniele Caracciolo, Pierosandro Tagliaferri, Pierfrancesco Tassone
The deeper understanding of non-coding RNAs has recently changed the dogma of molecular biology assuming protein-coding genes as unique functional biological effectors, while non-coding genes as junk material of doubtful significance. In the last decade, an exciting boom of experimental research has brought to light the pivotal biological functions of long non-coding RNAs (lncRNAs), representing more than the half of the whole non-coding transcriptome, along with their dysregulation in many diseases, including cancer...
May 8, 2018: Journal of Hematology & Oncology
C Roolf, A Richter, C Konkolefski, G Knuebel, A Sekora, S Krohn, J Stenzel, B J Krause, B Vollmar, H Murua Escobar, C Junghanss
BACKGROUND: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. METHODS: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL...
May 4, 2018: Journal of Hematology & Oncology
Weili Sun, Huaying Liu, Young Kim, Nicole Karras, Anna Pawlowska, Debbie Toomey, Wade Kyono, Paul Gaynon, Joseph Rosenthal, Anthony Stein
BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematological malignancy with extremely poor outcome. The median overall survival for adult patients is 9-13 months. Pediatric patients are exceedingly rare with an unclear clinical course. Currently, no standardized therapy has been established, although an acute lymphoblastic leukemia type of treatment appears to be more effective in those patients who are able to tolerate aggressive chemotherapy...
May 2, 2018: Journal of Hematology & Oncology
Ying Wang, Yingxi Xu, Saisai Li, Jia Liu, Yanyan Xing, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Min Wang, Jianxiang Wang
BACKGROUND: Chimeric antigen receptor-engineered T (CAR-T) cells have extraordinary effect in treating lymphoblastic leukemia. However, treatment of acute myeloid leukemia (AML) using CAR-T cells remains limited to date. Leukemogenesis always relates with the abnormalities of cytogenetics, and nearly one third of AML patients have activating mutations in Fms-like tyrosine kinase 3 (FLT3) which reminded poor prognosis. Considering the FLT3 expressed in AML patients' blast cells, it may be a new candidate target for CAR-T therapy to treat FLT3+ AML, especially patients harboring FLT3-ITD mutation...
May 2, 2018: Journal of Hematology & Oncology
Ting Li, Hu-Lin Jiang, Yun-Guang Tong, Jin-Jian Lu
Heat shock protein 90 (Hsp90) is a critical molecular chaperone protein that regulates the folding, maturation, and stability of a wide variety of proteins. In recent years, the development of Hsp90-directed inhibitors has grown rapidly, and many of these inhibitors have entered clinical trials. In parallel, the functional dissection of the Hsp90 chaperone machinery has highlighted the activity disruption of Hsp90 co-chaperone as a potential target. With the roles of Hsp90 co-chaperones being elucidated, cell division cycle 37 (Cdc37), a ubiquitous co-chaperone of Hsp90 that directs the selective client proteins into the Hsp90 chaperone cycle, shows great promise...
April 27, 2018: Journal of Hematology & Oncology
Qian Huang, Jiajia Xia, Lei Wang, Xu Wang, Xiaodong Ma, Qipan Deng, Yong Lu, Munish Kumar, Zhiyuan Zhou, Ling Li, Zhaoyang Zeng, Ken H Young, Qing Yi, Mingzhi Zhang, Yong Li
BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer...
April 23, 2018: Journal of Hematology & Oncology
Yucai Wang, Grzegorz S Nowakowski, Michael L Wang, Stephen M Ansell
CD30 and programmed cell death protein 1 (PD-1) are two ideal therapeutic targets in classical Hodgkin lymphoma (cHL). The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL. Ongoing studies are evaluating their efficacy in earlier lines of therapy and have demonstrated encouraging results. These agents are expected to further change the landscape of cHL management. Increased cure rates and reduced long-term toxicity from traditional chemotherapy and radiotherapy are likely with the emergence of these novel targeted therapies...
April 23, 2018: Journal of Hematology & Oncology
Man-Qing Cao, A-Bin You, Xiao-Dong Zhu, Wei Zhang, Yuan-Yuan Zhang, Shi-Zhe Zhang, Kei-Wei Zhang, Hao Cai, Wen-Kai Shi, Xiao-Long Li, Kang-Shuai Li, Dong-Mei Gao, De-Ning Ma, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Hui-Chan Sun, Ti Zhang, Zhao-You Tang
The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK.
April 18, 2018: Journal of Hematology & Oncology
Nicole Santoro, Myriam Labopin, Federica Giannotti, Gerard Ehninger, Dietger Niederwieser, Arne Brecht, Matthias Stelljes, Nicolaus Kröger, Herman Einsele, Matthias Eder, Michael Hallek, Bertram Glass, Jürgen Finke, Fabio Ciceri, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
BACKGROUND: Acute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need. METHODS: We retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years...
April 16, 2018: Journal of Hematology & Oncology
Shuangshuang Li, Jiping Yao, Mingjie Xie, Yanning Liu, Min Zheng
Hepatocellular carcinoma remains the sixth most lethal malignancy in the world. While HCC is often diagnosed via current biomarkers at a late stage, early detection of HCC has proven to be very difficult. Recent studies have focused on using exosomal miRNAs in clinical diagnostics and therapeutics, because they have improved stability in exosomes than as free miRNAs themselves. Exosomal miRNAs act through novel mechanisms for inducing cellular responses in a variety of biological circumstances. Dysregulated expression of miRNAs in exosomes can also accelerate HCC progression, including cell proliferation and metastasis, via alteration of a network of genes...
April 11, 2018: Journal of Hematology & Oncology
Qian Liu, Anping Li, Shengnan Yu, Shuang Qin, Na Han, Richard G Pestell, Xinwei Han, Kongming Wu
BACKGROUND: C-X-C motif ligand 8 (CXCL8), known as a proinflammatory chemokine, exerts multiple effects on the proliferation, invasion, and migration of tumor cells via the autocrine or paracrine manner. Conversely, the human Dachshund homologue 1 (DACH1) is recognized as a tumor suppressor which retards the progression of various cancers. In prostate cancer, it has been demonstrated that DACH1 was negatively correlated with the expression of CXCL8 and able to antagonize the effects of CXCL8 on cellular migration...
April 10, 2018: Journal of Hematology & Oncology
Arvind Singh Mer, Johan Lindberg, Christer Nilsson, Daniel Klevebring, Mei Wang, Henrik Grönberg, Soren Lehmann, Mattias Rantalainen
BACKGROUND: Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. METHODS: We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression...
April 7, 2018: Journal of Hematology & Oncology
Sabrina Manni, Marilena Carrino, Francesco Piazza
The original article [1] contains an inadvertent error in the following sentence in the Abstract regarding the erroneous description of Ser/Thr kinases as 'phylogenetically related'.
April 5, 2018: Journal of Hematology & Oncology
Tianxiao Yang, Yilin Wang, Wenjuan Dai, Xixi Zheng, Jing Wang, Shushu Song, Lan Fang, Jiangfan Zhou, Weicheng Wu, Jianxin Gu
BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer and the third leading cause of tumor-related death, so it is urgently needed to discover efficient markers and targets for therapy. β-1,3-N-acetylgalactosaminyltransferase II (B3GALNT2) belongs to the β-1,3-glycosyltransferases (b3GT) family and has been reported to regulate development of both normal and tumor tissues. However, studies on the functions of B3GALNT2 in cancer are quite limited. Here we investigated the potential role of B3GALNT2 in HCC progression...
April 4, 2018: Journal of Hematology & Oncology
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