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Journal of Hematology & Oncology

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https://www.readbyqxmd.com/read/28870253/early-presence-of-anti-angiogenesis-related-adverse-events-as-a-potential-biomarker-of-antitumor-efficacy-in-metastatic-gastric-cancer-patients-treated-with-apatinib-a-cohort-study
#1
Xinyang Liu, Shukui Qin, Zhichao Wang, Jianming Xu, Jianping Xiong, Yuxian Bai, Zhehai Wang, Yan Yang, Guoping Sun, Liwei Wang, Leizhen Zheng, Nong Xu, Ying Cheng, Weijian Guo, Hao Yu, Tianshu Liu, Pagona Lagiou, Jin Li
BACKGROUND: Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. PATIENTS AND METHODS: We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks...
September 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28851445/chimeric-antigen-receptors-for-adoptive-t-cell-therapy-in-acute-myeloid-leukemia
#2
REVIEW
Mingxue Fan, Minghao Li, Lipeng Gao, Sicong Geng, Jing Wang, Yiting Wang, Zhiqiang Yan, Lei Yu
Currently, conventional therapies for acute myeloid leukemia (AML) have high failure and relapse rates. Thus, developing new strategies is crucial for improving the treatment of AML. With the clinical success of anti-CD19 chimeric antigen receptor (CAR) T cell therapies against B-lineage malignancies, many studies have attempted to translate the success of CAR T cell therapy to other malignancies, including AML. This review summarizes the current advances in CAR T cell therapy against AML, including preclinical studies and clinical trials, and discusses the potential AML-associated surface markers that could be used for further CAR technology...
August 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28851416/interim-analysis-of-survival-in-a-prospective-multi-center-registry-cohort-of-cutaneous-melanoma-tested-with-a-prognostic-31-gene-expression-profile-test
#3
Eddy C Hsueh, James R DeBloom, Jonathan Lee, Jeffrey J Sussman, Kyle R Covington, Brooke Middlebrook, Clare Johnson, Robert W Cook, Craig L Slingluff, Kelly M McMasters
BACKGROUND: A 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries. METHODS: Three-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis...
August 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28821272/novel-immunotherapies-for-adult-patients-with-b-lineage-acute-lymphoblastic-leukemia
#4
REVIEW
Guoqing Wei, Jiasheng Wang, He Huang, Yanmin Zhao
The past decade witnessed the rapid development of adult B-lineage acute lymphoblastic leukemia (ALL) treatment. Beyond the development of chemotherapy regimens, immunotherapy is starting a new era with unprecedented complete remission (CR) rate. Targeting B-lineage-specific surface markers such as CD19, CD20, CD22, or CD52, immunotherapy has been demonstrating promising clinical results. Among the immunotherapeutic methods, naked monoclonal antibodies (mAbs), antibody-drug conjugate (ADC), bispecific T cell engager (BiTE), and chimeric antigen receptor (CAR) T cells are the main types...
August 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28810883/treatment-of-localized-gastric-and-gastroesophageal-adenocarcinoma-the-role-of-accurate-staging-and-preoperative-therapy
#5
REVIEW
Brian Badgwell, Prajnan Das, Jaffer Ajani
Gastric cancer is the third most common cause of cancer death worldwide, although it is not in the top 10 causes of cancer death in Northern America. Due to clear differences in incidence, screening, risk factors, tumor biology, and treatment between gastric cancers from Eastern and Western countries, our treatment is primarily guided by trials from Western countries. Patients undergo an extensive staging evaluation including high-quality CT imaging, endoscopic ultrasound, and diagnostic laparoscopy with peritoneal washings for cytology...
August 15, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28806978/transcriptome-sequencing-in-pediatric-acute-lymphoblastic-leukemia-identifies-fusion-genes-associated-with-distinct-dna-methylation-profiles
#6
Yanara Marincevic-Zuniga, Johan Dahlberg, Sara Nilsson, Amanda Raine, Sara Nystedt, Carl Mårten Lindqvist, Eva C Berglund, Jonas Abrahamsson, Lucia Cavelier, Erik Forestier, Mats Heyman, Gudmar Lönnerholm, Jessica Nordlund, Ann-Christine Syvänen
BACKGROUND: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. METHODS: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes...
August 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28784178/clinical-trials-of-tyrosine-kinase-inhibitors-for-lung-cancer-in-china-a-review
#7
REVIEW
Shan Su, Yi-Long Wu
With the development of evidence-based medicine, clinical trials have become necessary for investigating and validating the efficacy of new treatments. Over the past 10 years, several clinical trials of new anticancer agents have been designed and launched in China; this has greatly promoted the development of novel agents as well as of innovative clinical study designs. However, despite the significant advances made in clinical trials for novel agents, improvements are still required. In this mini-review, we will summarize the ongoing clinical trials of small molecular inhibitors for the treatment of lung cancer in China, aiming specifically to highlight the active involvement of China in these clinical studies...
August 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28774337/pd-1-pd-l-blockade-in-gastrointestinal-cancers-lessons-learned-and-the-road-toward-precision-immunotherapy
#8
REVIEW
Junyu Long, Jianzhen Lin, Anqiang Wang, Liangcai Wu, Yongchang Zheng, Xiaobo Yang, Xueshuai Wan, Haifeng Xu, Shuguang Chen, Haitao Zhao
Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have led to significant advances in the treatment of GI cancer patients, overall survival is still low. Therefore, alternative strategies must be identified to improve patient outcomes. In the tumor microenvironment, tumor cells can escape the host immune response through the interaction of PD-1 and PD-L, which inhibits the function of T cells and tumor-infiltrating lymphocytes while increasing the function of immunosuppressive T regulatory cells...
August 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28754125/syk-inhibitors-in-clinical-development-for-hematological-malignancies
#9
REVIEW
Delong Liu, Aleksandra Mamorska-Dyga
Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors. Several oral Syk inhibitors including fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being assessed in clinical trials. The second generation compound, entospletinib, showed promising results in clinical trials against B-cell malignancies, mainly chronic lymphoid leukemia...
July 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28750681/drug-induced-amino-acid-deprivation-as-strategy-for-cancer-therapy
#10
REVIEW
Marcus Kwong Lam Fung, Godfrey Chi-Fung Chan
Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers...
July 27, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28743264/recent-developments-in-immunotherapy-of-acute-myeloid-leukemia
#11
REVIEW
Felix S Lichtenegger, Christina Krupka, Sascha Haubner, Thomas Köhnke, Marion Subklewe
The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years...
July 25, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28738836/metabolism-associated-danger-signal-induced-immune-response-and-reverse-immune-checkpoint-activated-cd40-monocyte-differentiation
#12
REVIEW
Jin Dai, Pu Fang, Jason Saredy, Hang Xi, Cueto Ramon, William Yang, Eric T Choi, Yong Ji, Wei Mao, Xiaofeng Yang, Hong Wang
Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antigen recognition, signal 2 co-stimulation or co-inhibition, and signal 3 cytokine stimulation. In this article, we propose to term signal 2 as an immune checkpoint, which describes interactions of paired molecules leading to stimulation (stimulatory immune checkpoint) or inhibition (inhibitory immune checkpoint) of an immune response...
July 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28716051/mir-380-5p-mediated-repression-of-tep1-and-tspyl5-interferes-with-telomerase-activity-and-favours-the-emergence-of-an-alt-like-phenotype-in-diffuse-malignant-peritoneal-mesothelioma-cells
#13
Graziella Cimino-Reale, Paolo Gandellini, Francesca Santambrogio, Marta Recagni, Nadia Zaffaroni, Marco Folini
BACKGROUND: Understanding the molecular/cellular underpinnings of diffuse malignant peritoneal mesothelioma (DMPM), a fatal malignancy with limited therapeutic options, is of utmost importance for the fruitful management of the disease. In this context, we previously found that telomerase activity (TA), which accounts for the limitless proliferative potential of cancer cells, is prognostic for disease relapse and cancer-related death in DMPM patients. Consequently, the identification of factors involved in telomerase activation/regulation may pave the way towards the development of novel therapeutic interventions for the disease...
July 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28697759/the-distinct-biological-implications-of-asxl1-mutation-and-its-roles-in-leukemogenesis-revealed-by-a-knock-in-mouse-model
#14
Yueh-Chwen Hsu, Yu-Chiao Chiu, Chien-Chin Lin, Yuan-Yeh Kuo, Hsin-An Hou, Yi-Shiuan Tzeng, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Tzu-Hung Hsiao, Wen-Chien Chou, Hwei-Fang Tien
BACKGROUND: Additional sex combs-like 1 (ASXL1) is frequently mutated in myeloid malignancies. Recent studies showed that hematopoietic-specific deletion of Asxl1 or overexpression of mutant ASXL1 resulted in myelodysplasia-like disease in mice. However, actual effects of a "physiological" dose of mutant ASXL1 remain unexplored. METHODS: We established a knock-in mouse model bearing the most frequent Asxl1 mutation and studied its pathophysiological effects on mouse hematopoietic system...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28693523/inhibition-of-lin28b-impairs-leukemia-cell-growth-and-metabolism-in-acute-myeloid-leukemia
#15
Jianbiao Zhou, Chonglei Bi, Ying Qing Ching, Jing-Yuan Chooi, Xiao Lu, Jessie Yiying Quah, Sabrina Hui-Min Toh, Zit-Liang Chan, Tuan Zea Tan, Phyllis Sy Chong, Wee-Joo Chng
BACKGROUND: Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28683766/randomized-double-blind-placebo-controlled-phase-iii-study-of-ixazomib-plus-lenalidomide-dexamethasone-in-patients-with-relapsed-refractory-multiple-myeloma-china-continuation-study
#16
Jian Hou, Jie Jin, Yan Xu, Depei Wu, Xiaoyan Ke, Daobin Zhou, Jin Lu, Xin Du, Xiequn Chen, Junmin Li, Jing Liu, Neeraj Gupta, Michael J Hanley, Hongmei Li, Zhaowei Hua, Bingxia Wang, Xiaoquan Zhang, Hui Wang, Helgi van de Velde, Paul G Richardson, Philippe Moreau
BACKGROUND: The China Continuation study was a separate regional expansion of the global, double-blind, placebo-controlled, randomized phase III TOURMALINE-MM1 study of ixazomib plus lenalidomide-dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM) following one to three prior therapies. METHODS: Patients were randomized (1:1) to receive ixazomib 4.0 mg or placebo on days 1, 8, and 15, plus lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, and 22, in 28-day cycles...
July 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28679395/ongoing-clinical-trials-of-pd-1-and-pd-l1-inhibitors-for-lung-cancer-in-china
#17
REVIEW
Si-Yang Liu, Yi-Long Wu
Compared to chemotherapy, promising results have been obtained by blocking the PD-1 pathway using antibodies that inhibit programmed cell death protein 1 (PD-1) or programmed cell death protein ligand 1 (PD-L1). Furthermore, global researchers and doctors are exploring how to optimize this immunotherapy in 270 clinical studies. However, Chinese clinical trials of these agents remain in the early stages. We summarize the ongoing international and domestic clinical trials using PD-1 and PD-L1 inhibitors to treat lung cancer...
July 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28676100/superior-gvhd-free-relapse-free-survival-for-g-bm-to-g-pbsc-grafts-is-associated-with-higher-mdscs-content-in-allografting-for-patients-with-acute-leukemia
#18
Qian Fan, Hui Liu, Xinquan Liang, Ting Yang, Zhiping Fan, Fen Huang, Yiwen Ling, Xin Liao, Li Xuan, Na Xu, Xiaojun Xu, Jieyu Ye, Qifa Liu
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1)...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28676064/haploidentical-allograft-is-superior-to-matched-sibling-donor-allograft-in-eradicating-pre-transplantation-minimal-residual-disease-of-aml-patients-as-determined-by-multiparameter-flow-cytometry-a-retrospective-and-prospective-analysis
#19
Ying-Jun Chang, Yu Wang, Yan-Rong Liu, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Hua Yan, Fei-Fei Tang, Xiao-Dong Mo, Kai-Yan Liu, Xiao-Jun Huang
BACKGROUND: This study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts. METHODS: A retrospective study (n = 339) and a prospective study (n = 340) were performed. MRD was determined using multiparameter flow cytometry. RESULTS: Either after retrospective or prospective analysis, patients with negative pre-MRD (pre-MRDneg) had a lower incidence of relapse than those with positive pre-MRD (pre-MRDpos) in MSDT settings (P < 0...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28673317/the-ubiquitin-conjugating-enzyme-ube2o-modulates-c-maf-stability-and-induces-myeloma-cell-apoptosis
#20
Yujia Xu, Zubin Zhang, Jie Li, Jiefei Tong, Biyin Cao, Paul Taylor, Xiaowen Tang, Depei Wu, Michael F Moran, Yuanying Zeng, Xinliang Mao
BACKGROUND: UBE2O is proposed as a ubiquitin-conjugating enzyme, but its function was largely unknown. METHODS: Mass spectrometry was applied to identify c-Maf ubiquitination-associated proteins. Immunoprecipitation was applied for c-Maf and UBE2O interaction. Immunoblotting was used for Maf protein stability. Luciferase assay was used for c-Maf transcriptional activity. Lentiviral infections were applied for UBE2O function in multiple myeloma (MM) cells. Flow cytometry and nude mice xenografts were applied for MM cell apoptosis and tumor growth assay, respectively...
July 3, 2017: Journal of Hematology & Oncology
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