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Experimental Hematology & Oncology

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https://www.readbyqxmd.com/read/28670501/pten-is-a-negative-regulator-of-mitotic-checkpoint-complex-during-the-cell-cycle
#1
Byeong H Choi, Steve Xie, Wei Dai
Nuclear PTEN plays an important role during mitosis. To understand the molecular basis by which PTEN mediates mitotic progression, we examined whether PTEN regulated the formation of mitotic checkpoint complex (MCC). We observed that arsenic trioxide, a mitotic inducer, stimulated nuclear translocation of PTEN in a time-dependent manner. PTEN physically interacted with Cdc20 and Mad2, two important components of MCC. Arsenic treatment diminished the physical association of PTEN with BubR1 and Bub3 but not with Cdc20 and Mad2...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28638723/low-dose-methotrexate-in-sickle-cell-disease-a-pilot-study-with-rationale-borrowed-from-rheumatoid-arthritis
#2
Silvia R Brandalise, Rosemary Assis, Angelo B A Laranjeira, José Andrés Yunes, Pedro O de Campos-Lima
BACKGROUND: Inflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients. METHODS: Fourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28630798/the-role-of-cullin4b-in-human-cancers
#3
REVIEW
Ying Li, Xin Wang
Cullin 4B (CUL4B) is a scaffold of the Cullin4B-Ring E3 ligase complex (CRL4B) that plays an important role in proteolysis and is implicated in tumorigenesis. Aberrant expression of CUL4B has been reported in various types of human diseases. Recently, studies have shown that CUL4B was overexpressed in a multitude of solid neoplasms and affect the expression of several tumor suppressor genes. In this review, we aim to summarize the biological function of CUL4B in order to better understand its pathogenesis in human cancers...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28560070/clinical-implications-of-c-maf-expression-in-plasma-cells-from-patients-with-multiple-myeloma
#4
GuoQing Wei, LiJun Wang, HanJin Yang, XiaoYan Han, GaoFeng Zheng, WeiYan Zheng, Jie Sun, JiMin Shi, WenJun Wu, Yi Zhao, DongHua He, Bo Wang, Zhen Cai, JingSong He
BACKGROUND: Multiple myeloma (MM) is a type of hematological malignancy with significant heterogeneity in clinical features and prognosis. Cytogenetic abnormalities are the major factors affecting patient outcomes. Studies have shown that immunohistochemistry (IHC)-based detection of cancer-related genes expression could be alternative indicators for the prognosis of MM. METHODS: Nuclear expression of c-maf protein in the bone marrow plasma cells of 128 multiple myeloma patients were examined by IHC, and its association with the clinicopathological features of MM patients was analyzed as well...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28546884/in-vivo-and-in-situ-programming-of-tumor-immunity-by-combining-oncolytics-and-pd-1-immune-checkpoint-blockade
#5
Eric Bartee, Zihai Li
Blockade of the programmed cell death protein 1 (PD1) pathway is clinically effective against human cancers. Although multiple types of malignancies have been shown to respond to PD1 agents, only a small percentage of patients typically benefit from this treatment. In addition, PD1 therapy often causes serious immune-related adverse events. A recent study demonstrated that local, intra-tumoral, administration of modified oncolytic myxoma virus which expresses a truncated version of the PD1 protein resulted in both increased efficacy and reduced toxicity in a clinically relevant melanoma model...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#6
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28473943/cyclosporine-is-a-potential-curative-treatment-option-for-advanced-thymoma
#7
Yusuke Isshiki, Hiroaki Tanaka, Yoshio Suzuki, Yukihiro Yoshida
BACKGROUND: Thymectomy can effectively cure most thymoma patients; however, patients with advanced thymoma typically require chemotherapy, which is associated with limited efficacy in this context. Here we provide the first report of a patient with recurrent thymoma who achieved complete remission (CR) using cyclosporine therapy. CASE PRESENTATION: A 63-year-old woman who had undergone resection surgery for recurrent type B1 thymoma developed pure red cell aplasia (PRCA), and CT findings revealed thymoma recurrence...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28469973/the-development-of-bispecific-antibodies-and-their-applications-in-tumor-immune-escape
#8
REVIEW
Xiaolong Zhang, Yuanyuan Yang, Dongmei Fan, Dongsheng Xiong
During the past two decades, a great evolution of bispecific antibodies (BsAbs) for therapeutic applications has been made. BsAbs can bind simultaneously two different antigens or epitopes, which leads to a wide range of applications including redirecting T cells or NK cells to tumor cells, blocking two different signaling pathways, dual targeting of different disease mediators, and delivering payloads to targeted sites. Aside from approved catumaxomab (anti-CD3 and anti-EpCAM) and blinatumomab (anti-CD3 and anti-CD19), many more BsAbs are now in various phases of clinical development...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28428908/metastatic-squamous-cell-carcinoma-of-colon-from-esophageal-cancer
#9
Natasha Garg, Constance Stoehr, Yan Shi Zhao, Heather Rojas, Chung-Tsen Hsueh
BACKGROUND: Esophageal cancer including squamous cell carcinoma (SCC) and adenocarcinoma represents 4% of all cancers in the United States. Patients with esophageal cancer frequently present with locally advanced disease, and about 40% of patients have evidence of metastatic disease on presentation. Common sites of metastasis include liver, lung and bone. Here, we present a rare case of colonic metastasis from primary esophageal SCC. CASE PRESENTATION: A 60-year-old Caucasian male with a history of 20-pack-year cigarette smoking received surgery and adjuvant chemoradiotherapy for locally advanced SCC of larynx...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28413717/advances-of-cd19-directed-chimeric-antigen-receptor-modified-t-cells-in-refractory-relapsed-acute-lymphoblastic-leukemia
#10
REVIEW
Guoqing Wei, Lijuan Ding, Jiasheng Wang, Yongxian Hu, He Huang
Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28401025/adult-acute-precursor-b-cell-lymphoblastic-leukemia-presenting-as-hypercalcemia-and-osteolytic-bone-lesions
#11
Nikki Charlotta Paul Granacher, Zwi N Berneman, Wilfried Schroyens, Ann L R Van de Velde, Anke Verlinden, Alain P A Gadisseur
BACKGROUND: Osteolytic bone lesions and hypercalcemia without peripheral blasts B-cell acute lymphoblastic leukemia (B-ALL) is reported in children but rarely seen in adults. CASE PRESENTATION: We describe the case of a 34-year old man presenting with hypercalcemia and symptomatic osteolytic bone lesions of vertebrae and ribs who was initially suspected as having a solid malignancy. Diagnostic work-up including peripheral blood examination, radiographic and nuclear studies could, however, not detect a primary tumor...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28352491/acquired-factor-viii-deficiency-two-case-reports-and-a-review-of-literature
#12
Lan Mo, George C Bao
BACKGROUND: Acquired factor VIII (FVIII) deficiency, or acquired hemophilia A (AHA), is a rare autoimmune disorder involving antibody-mediated depletion of coagulation FVIII, leading to severe, life-threatening bleeding. The condition is often associated with other autoimmune disorders, and its treatment involves replacement of FVIII and various modes of immunosuppression. Recently, a few noteworthy therapeutic advances have been made. We present two cases of severe AHA in Chinese women...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28344858/nab-paclitaxel-for-the-treatment-of-breast-cancer-an-update-across-treatment-settings
#13
REVIEW
Adam Brufsky
PURPOSE: The purpose of this systematic review is to discuss recent studies and ongoing trials of nab-paclitaxel in breast cancer and to examine the potential role of nab-paclitaxel as a backbone for immuno-oncology therapies. METHODS: PubMed and selected congress proceedings were searched for studies of nab-paclitaxel in breast cancer published between 2013 and 2015. All phase II and III clinical trials, retrospective analyses, and institutional studies were included...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28344857/metastatic-braf-k601e-mutated-melanoma-reaches-complete-response-to-mek-inhibitor-trametinib-administered-for-over-36%C3%A2-months
#14
Riccardo Marconcini, Luca Galli, Andrea Antonuzzo, Simona Bursi, Claudia Roncella, Gabriella Fontanini, Elisa Sensi, Alfredo Falcone
BACKGROUND: The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs. CASE PRESENTATION: A female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28194306/a-randomized-exploratory-phase-2-study-in-patients-with-chemotherapy-related-peripheral-neuropathy-evaluating-whole-body-vibration-training-as-adjunct-to-an-integrated-program-including-massage-passive-mobilization-and-physical-exercises
#15
Stefan S Schönsteiner, Heidi Bauder Mißbach, Axel Benner, Silja Mack, Thomas Hamel, Michael Orth, Bernhard Landwehrmeyer, Sigurd D Süßmuth, Carolin Geitner, Regine Mayer-Steinacker, Anneliese Riester, Andrea Prokein, Elfriede Erhardt, Jelena Kunecki, Anna M Eisenschink, Rainer Rawer, Hartmut Döhner, Elisabeth Kirchner, Richard F Schlenk
BACKGROUND: Chemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN. PATIENTS AND METHODS: In an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard)...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28101432/atypical-hemolytic-uremic-syndrome-in-first-trimester-pregnancy-successfully-treated-with-eculizumab
#16
Gabriela Andries, Michael Karass, Srikanth Yandrapalli, Katherine Linder, Delong Liu, John Nelson, Rahul Pawar, Savneek Chugh
BACKGROUND: Atypical hemolytic uremic syndrome is a rare disorder which is known to cause acute thrombotic microangiopathy during pregnancy with poor maternal and fetal outcomes. Atypical hemolytic uremic syndrome is caused mostly by dysregulation of alternative complement pathway secondary to genetic mutations. Most of the cases reported have been in the post-partum period. We report a rare case of a patient who presents with thrombotic microangiopathy in the first trimester of her eleventh pregnancy and was successfully treated with eculizumab...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28097046/molecular-classification-of-tissue-from-a-transformed-non-hogkin-s-lymphoma-case-with-unexpected-long-time-remission
#17
Julie Støve Bødker, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Rasmus Froberg Brøndum, Maria Bach Laursen, Steffen Falgreen, Mette Nyegaard, Alexander Schmitz, Lasse Hjort Jakobsen, Anna Amanda Schönherz, Hanne Due, Linn Reinholdt, Martin Bøgsted, Karen Dybkær, Hans Erik Johnsen
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28078190/loss-of-quiescence-and-self-renewal-capacity-of-hematopoietic-stem-cell-in-an-in-vitro-leukemic-niche
#18
Natalia-Del Pilar Vanegas, Jean-Paul Vernot
BACKGROUND: Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. METHODS: A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28078189/dabrafenib-and-trametinib-activity-in-a-patient-with-braf-v600e-mutated-and-microsatellite-instability-high-msi-h-metastatic-endometrial-cancer
#19
Michele Moschetta, Gabriel Mak, Joana Hauser, Catriona Davies, Mario Uccello, Hendrik-Tobias Arkenau
BACKGROUND: Targeting BRAF V600E mutation has been proven effective in the treatment of several types of cancer. In endometrial adenocarcinoma, the BRAF V600E mutation has been rarely reported. Whether targeting BRAF oncogene may represent a plausible therapeutic strategy for the rare patients with BRAF-mutated endometrial cancer remains to be ascertained in prospective studies. CASE PRESENTATION: We report herein the case of a heavily pre-treated patient with recurrent microsatellite instability high (MSI-H) BRAF V600E mutated endometrial adenocarcinoma, which was successfully treated with the V600E targeting agent dabrafenib...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28042518/pim1-kinase-regulates-c-kit-gene-translation
#20
Ningfei An, Bo Cen, Houjian Cai, Jin H Song, Andrew Kraft, Yubin Kang
BACKGROUND: Receptor tyrosine kinase, c-Kit (CD117) plays a pivotal role in the maintenance and expansion of hematopoietic stem/progenitor cells (HSPCs). Additionally, over-expression and/or mutational activation of c-Kit have been implicated in numerous malignant diseases including acute myeloid leukemia. However, the translational regulation of c-Kit expression remains largely unknown. METHODS AND RESULTS: We demonstrated that loss of Pim1 led to specific down-regulation of c-Kit expression in HSPCs of Pim1(-/-) mice and Pim1(-/-)2(-/-)3(-/-) triple knockout (TKO) mice, and resulted in attenuated ERK and STAT3 signaling in response to stimulation with stem cell factor...
2016: Experimental Hematology & Oncology
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