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Chih-Hsin Lee, Yuan-Feng Lin, Yen-Chou Chen, Shuit-Mun Wong, Shu-Hui Juan, Huei-Mei Huang
We previously synthesized new tubulin inhibitors, MPT0B169 and MPT0B002, which induced growth inhibition and apoptosis in leukemia cells. However, their effects on solid tumor cells have not been determined. In this study, we investigated the effects of MPT0B169 and MPT0B002 on glioblastoma, breast, lung, and colorectal cancer (CRC) cell lines. A cell viability analysis showed that MPT0B169 and MPT0B002 were more effective in inhibiting the proliferation of COLO205 and HT29 CRC cells than U87MG and GBM8401 glioblastoma, MCF-7 and MDA-MB-231 breast cancer, and A549 lung cancer cells...
September 18, 2018: Pharmacology
Perla R Colunga-Pedraza, Gisela B Gomez-Cruz, Julia E Colunga-Pedraza, Guillermo J Ruiz-Argüelles
In 1963 Jean Bernard introduced the concept of "geographic hematology" and distinguished 2 branches, i.e., "ethnic hematology," which deals with differences between populations, and "environmental hematology," which considers factors such as food habits, infections, and others. Both of these branches have implications in the distribution of hematological diseases worldwide. In comparison with Caucasian populations, in Mexico a significantly higher prevalence of acute lymphoblastic, acute promyelocytic, and acute megakaryoblastic leukemias has been described...
September 18, 2018: Acta Haematologica
Fiorina Giona, Michelina Santopietro, Giuseppe Menna, Maria Caterina Putti, Concetta Micalizzi, Nicola Santoro, Ottavio Ziino, Rosamaria Mura, Saverio Ladogana, Grazia Iaria, Antonella Sau, Roberta Burnelli, Nadia Vacca, Sayla Bernasconi, Caterina Consarino, Fara Petruzziello, Maria Luisa Moleti, Andrea Biondi, Franco Locatelli, Robin Foà
BACKGROUND: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. METHODS: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed...
September 18, 2018: Acta Haematologica
Leslie Naesens, Helena Devos, Friedel Nollet, Lucienne Michaux, Dominik Selleslag
INTRODUCTION: Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, is a rare neoplastic condition defined as a tumor mass consisting of myeloblasts or immature myeloid cells occurring at an extramedullary site. Clinical presentation is diverse and determined by a tumor mass effect or local organ dysfunction. CASE REPORT: We report the case of a 25-year-old previously healthy male with rapidly progressive shortness of breath. A chest CT scan demonstrated a heterogenous anterosuperior mediastinal mass with pleural and pericardial invasion...
September 18, 2018: Acta Haematologica
Mary Lynn Savoie, Isabelle Bence-Bruckler, Lothar B Huebsch, Marc Lalancette, Chris Hillis, Irwin Walker, Jeffrey H Lipton, Donna L Forrest, Dennis Dong Hwan Kim
The majority of patients with TKI failure respond to HCT. However, the relapse risk remains high. This study has evaluated transplant outcomes in 223 CML patients with TKI failure due to resistance (n = 132) or intolerance (n = 29), as well as those that were TKI naïve/responding with advanced disease (n = 35) or with chronic phase (CP, n = 27). We studied outcomes according to post-transplant BCR-ABL transcript level within 3 months. With respect to transplant outcomes according to the post-transplant BCR/ABLtranscript level within 3 months, the group failing to achieve a 1...
September 5, 2018: Leukemia Research
Peng Zhang, Fuhong He, Jie Bai, Shohei Yamamoto, Shi Chen, Lin Zhang, Mengyao Sheng, Lei Zhang, Ying Guo, Na Man, Hui Yang, Suyun Wang, Tao Cheng, Stephen D Nimer, Yuan Zhou, Mingjiang Xu, Qian-Fei Wang, Feng-Chun Yang
ASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with other gene mutations. However, the molecular mechanisms underlying the leukemogenesis associated with ASXL1 and cooperating mutations remain to be elucidated. Here we report that Asxl1 loss cooperated with haploinsufficiency of Nf1, a negative regulator of the RAS signaling pathway, to accelerate the development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic stem and progenitor cells resulted in a gain-of-function transcriptional activation of multiple pathways critical for leukemogenesis, such as MYC, NRAS, and BRD4...
September 18, 2018: Journal of Clinical Investigation
Ruosi Yao, Yingli Wang, Danyang Han, Yuhui Ma, Musong Ma, Yaping Zhao, Jiang Tan, Jun Lu, Guiying Xu, Xiaoxue Li
Accumulating evidence has revealed that the methylation of lysines on nonhistones by histone lysine methyltransferases (HMTs) is crucial for regulating tumo-rigenesis and metastasis. However, whether the methy-lation of lysines on HMT complex components occurs and has functions in cancer progression is less well understood. WD repeat domain 5 (WDR5) is a core component of an HMT complex named mixed lineage leukemia (MLL)/Suppressor of Variegation, Enhancer of Zeste, and Trithorax 1 (SET1). In the present study, it was reported that lysines 207 and 325 (K207 and K325, respectively) of WDR5 were monomethylated by SET‑domain‑containing protein methyltransferase 6...
August 23, 2018: Oncology Reports
Hyun Jong Kim, Ji Hyun Choi, Jung-Hwan Hwang, Kyong-Shim Kim, Jung-Ran Noh, Dong-Hee Choi, Sung Je Moon, Hyun-Yong Kim, Sang-Woo Kim, Sangho Choi, Sang Mi Eum, Tran The Bach, Jaerang Rho, Ju Yong Lee, Jung Geun Park, Sei-Ryang Oh, Chul-Ho Lee, Won Keun Oh, Yong-Hoon Kim
Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5‑di‑C‑β‑D‑glucopyranosyl phloroacetophenone (βGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collagen‑induced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and micro‑computed tomography in CIA mouse paws were assessed...
August 30, 2018: International Journal of Molecular Medicine
Hien Thi Vu, Thi Xoan Hoang, Jae Young Kim
All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1...
2018: BioMed Research International
Leena T Rahmat, Anna Nguyen, Haifaa Abdulhaq, Sonam Prakash, Aaron C Logan, Gabriel N Mannis
Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine...
2018: Case Reports in Hematology
Zahra Kafi, Hamid Cheshomi, Omid Gholami
Hormesis is a new concept in dose-response relationship. Despite of traditional dose-response curves, there is a low-dose stimulation and a high-dose inhibition in this case. Hormesis effect in apoptosis induction/inhibition by natural compounds is reported previously. Here, we searched this effect for myeloid cell leukemia type-1 (Mcl-1) gene expression by phytochemicals 7-isopenthenyloxycoumarin (7-IP), arctigenin (Arg), and hesperidin (Hsp). For this purpose, first we tested the cytotoxicity of various doses of these compounds against K562 leukemia cell lines for different times by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method...
July 2018: Dose-response: a Publication of International Hormesis Society
Ke Zhang, Zhenfeng Dai, Runzhe Liu, Fang Tian, Xi Liu, Yi Sun, Xin Zhao, Xiaoping Pu
Immune thrombocytopenia (ITP) is a common acquired autoimmune disease, and thrombopoietin (TPO) is an important cytokine that regulates the production of megakaryocytes and platelets. We have identified a biologically active component, icaritin, from a Chinese herba epimedii extract. Icaritin promotes platelet production and regulates T cell polarization, but its mechanism is not clear. In this study, the BALB/c mouse model of ITP was established by injection of an antiplatelet antibody every other day for seven total times...
2018: Mediators of Inflammation
Antònia Banús-Mulet, Amaia Etxabe, Josep Maria Cornet-Masana, Miguel Ángel Torrente, María Carmen Lara-Castillo, Laura Palomo, Meritxell Nomdedeu, Marina Díaz-Beyá, Francesc Solé, Benet Nomdedeu, Jordi Esteve, Ruth M Risueño
Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to high morbimortality associated with this procedure coupled with advanced age of most patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were identified as cancer stem cell therapeutic targets in acute myeloid leukemia...
September 17, 2018: Scientific Reports
Dan Yue, Xun Sun
Idelalisib, a selective PI3Kδ inhibitor, has been approved by the FDA for chronic lymphocytic leukemia/small lymphocytic lymphoma treatment and for follicular lymphoma treatment when combined with rituximab. However, the mechanisms of effective action of idelalisib in hepatocellular carcinoma (HCC) remain unclear. In the current study, we aimed to investigate how idelalisib inhibits the growth of HCC cells and enhances the effects of other chemotherapeutic drugs. Our results show that idelalisib treatment promotes Bim induction in HCC via the FoxO3a pathway following PI3K/AKT inactivation...
September 17, 2018: Cell Death & Disease
Anahita Dastur, AHyun Choi, Carlotta Costa, Xunqin Yin, August F Williams, Joseph D McClanaghan, Max Greenberg, Justine E Roderick, Neha U Patel, Jessica L Boisvert, Ultan McDermott, Mathew J Garnett, Jorge Almenara, Steven Grant, Kathryn Rizzo, Jeffrey A Engelman, Michelle A Kelliher, Anthony C Faber, Cyril H Benes
PURPOSE: Effective targeted therapies are lacking for refractory and relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL). Suppression of the NOTCH pathway using gamma-secretase inhibitors (GSIs) is toxic and clinically not effective. The goal of this study was to identify alternative therapeutic strategies for T-ALL. EXPERIMENTAL DESIGN: We performed a comprehensive analysis of our high throughput drug screen across hundreds of human cell lines including fifteen T-ALL models...
September 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Qi Jin, Carlos A Martinez, Kelly M Arcipowski, Yixing Zhu, Blanca T Gutiérrez-Díaz, Kenneth K Wang, Megan R Johnson, Andrew Volk, Feng Wang, Jian Wu, Charles Grove, Hui Wang, Ivan Sokirniy, Paul M Thomas, Young Ah Goo, Nebiyu A Abshiru, Nobuko Hijiya, Sofie Peirs, Niels Vandamme, Geert Berx, Steven Goossens, Stacy Ann Marshall, Emily J Rendleman, Yoh-Hei Takahashi, Lu Wang, Radhika Rawat, Elizabeth T Bartom, Clayton K Collings, Pieter Van Vlierberghe, Jean-Pierre Bourquin, Beat Bornhauser, Valentina Serafin, Silvia Bresolin, Maddalena Paganin, Benedetta Accordi, Giuseppe Basso, Neil L Kelleher, Joseph Weinstock, Kumar Suresh, John D Crispino, Ali Shilatifard, Alexandros Strikoudis, Christine Mantis, Irawati Kandela, Stephen Kelly, Beatrix Ueberheide, Panagiotis Ntziachristos
PURPOSE: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Chemotherapy treatments show high response rates but have debilitating effects and carry risk of relapse. Previous work implicated NOTCH1 and other oncogenes. However, direct inhibition of these pathways affects healthy tissues and cancer alike. Our goal in this work has been to identify enzymes active in T-ALL whose activity could be targeted for therapeutic purposes. EXPERIMENTAL DESIGN: To identify and characterize new NOTCH1 druggable partners in T-ALL, we coupled studies of the NOTCH1 interactome to expression analysis and a series of functional analyses in cell lines, patient samples and xenograft models...
September 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nikhil A Huprikar, Matthew R Peterson, Jeffrey D DellaVolpe, Valerie G Sams, James H Lantry, Robert J Walter, Michael B Osswald, Kevin K Chung, Phillip E Mason
BACKGROUND: The prognosis of hematologic malignancies has improved over the past three decades. However, the prognosis in hematologic malignancies with severe acute respiratory distress syndrome has remained poor. Initial reports regarding the utility of extracorporeal membrane oxygenation in hematologic malignancies have been controversial, with limited evaluations of acute leukemia patients supported by extracorporeal membrane oxygenation. METHODS: We conducted a retrospective review of patients with acute leukemia who developed acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation support at our facility from July 2015 through August 2017...
September 17, 2018: International Journal of Artificial Organs
Fumitaka Koga, Kosuke Takemura, Hiroshi Fukushima
Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have a favorable prognosis and quality of life with a preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting the clinical outcomes of chemoradiation-based BPT...
September 15, 2018: International Journal of Molecular Sciences
Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud
Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators...
September 14, 2018: Cancers
Michaela Dostalova Merkerova, Hana Remesova, Zdenek Krejcik, Nikoleta Loudova, Andrea Hrustincova, Katarina Szikszai, Jaroslav Cermak, Anna Jonasova, Monika Belickova
The DLK1⁻DIO3 region contains a large miRNA cluster, the overexpression of which has previously been associated with myelodysplastic syndromes (MDS). To reveal whether this overexpression is epigenetically regulated, we performed an integrative analysis of miRNA/mRNA expression and DNA methylation of the regulatory sequences in the region (promoter of the MEG3 gene) in CD34+ bone marrow cells from the patients with higher-risk MDS and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), before and during hypomethylating therapy with azacytidine (AZA)...
September 14, 2018: Cells
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