Bartosz Puła, Monika Długosz-Danecka, Aleksander Salomon-Perzyński, Agnieszka Szymczyk, Edyta Subocz, Bożena Katarzyna Budziszewska, Justyna Rybka, Lidia Gil, Anna Waszczuk-Gajda, Elżbieta Iskierka-Jażdżewska, Jan M Zaucha, Michał Osowiecki, Weronika Piszczek, Paweł Steckiewicz, Łukasz Szukalski, Marek Hus, Ewa Lech-Marańda, Wojciech Jurczak, Krzysztof Jamroziak
PURPOSE: High-dose methylprednisolone (HDMP) with or without anti-CD20 antibody treatment in the pre B-cell receptor inhibitor (BCRi) era was used as potential salvage therapy for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) patients bearing the 17p deletion. PATIENTS AND METHODS: Outcomes were compared in retrospect between r/r patients treated with HDMP (n = 20), ibrutinib (n = 39) and idelalisib with rituximab (n = 14)...
July 10, 2020: Advances in Medical Sciences
Nuha Mahmoud, Mohamed E M Saeed, Yoshikazu Sugimoto, Anette Klinger, Edmond Fleischer, Thomas Efferth
BACKGROUND: Carnosic acid (CA) is one of the main constituents in rosemary extract. It possesses valuable pharmacological properties, including anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer activities. Numerous in vitro and in vivo studies investigated the anticancer profile of CA and emphasized its potentiality for cancer treatment. Nevertheless, the role of multidrug-resistance (MDR) related mechanisms for CA's anticancer effect is not yet known. PURPOSE: We investigated the cytotoxicity of CA against known mechanisms of anticancer drug resistance (P-gp, ABCB5, BCRP, EGFR and p53) and determined novel putative molecular factors associated with cellular response towards CA...
June 29, 2020: Phytomedicine
Annamaria Martorana, Antonino Lauria
An important challenge, in the medicinal chemistry field, is the research of novel forceful drugs to overcome tumor-acquired resistance. The c-Kit tyrosine kinase receptor (TKR) represents a suitable target for the carcinogenesis control of gastro-intestinal stromal (GIST), leukemia, and mastocytosis tumors; nevertheless, several hotspot mutations of the protein limit the efficacy of a few clinical administered TKRs inhibitors. In this study, a new in silico protocol based on ligand and structure-based combined method is proposed, with the aim to identify a set of new c-Kit inhibitors able to complex c-Kit mutated proteins...
July 8, 2020: Journal of Molecular Graphics & Modelling
Xinyuan Li, George Luo, Ting Li, Honghong Sun, Wei Wang, Emily Eiler, Jason R Goldsmith, Youhai H Chen
Genome-wide association studies have established that human REL is a susceptibility gene for lymphoid cancers and inflammatory diseases. REL is the hematopoietic member of the nuclear factor-κB (NF-κB) family and is frequently amplified in human lymphomas. However, the mechanism through which REL and its encoded protein c-Rel affect human lymphoma is largely unknown. Using both loss-of-function and gain-of-function approaches, we studied the roles of REL gene in human Jurkat leukemia cells. Compared with control Jurkat cells, REL knockout cells exhibited significant defects in cell growth and mitochondrial respiration...
July 10, 2020: Molecular Immunology
Amira A Helwa, Nehad M El-Dydamony, Rasha A Radwan, Sahar M Abdelraouf, Rana M Abdelnaby
Two series of novel morpholinopyrimidine derivatives were synthesized and screened for their in-vitro cytotoxic activity against 60 tumor cell line by the National Cancer Institute, USA. The in-vitro cytotoxic IC50 values for the most active compounds 6e, 6g, and 6l against the most sensitive cell line leukemia SR were estimated (IC50  = 0.76, 13.59, and 4.37 uM, respectively). To investigate their PI3K enzyme inhibition activity, the assay was done on Class IA (α, β, & δ) isoforms. The IC50 values were very promising: compound [6e = 11...
June 30, 2020: Bioorganic Chemistry
Silvia Park, Gi June Min, Sung Soo Park, Seung-Ah Yahng, Young-Woo Jeon, Seung-Hwan Shin, Jae-Ho Yoon, Sung-Eun Lee, Byung Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Hee-Je Kim
Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 acute myeloid leukemia (AML) patients who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate or poor-risk disease by NCCN guidelines (2017.Version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; BuCy or CyTBI) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms' tumour gene 1 (WT1) expression results before transplant...
July 10, 2020: Biology of Blood and Marrow Transplantation
Mona Dawood, Edmond Fleischer, Anette Klinger, Gerhard Bringmann, Letian Shan, Thomas Efferth
Epigenetic modifiers provide a new target for the development of anti-cancer drugs. The eraser histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that targets various non-histone proteins such as transcription factors, nuclear receptors, cytoskeletal proteins, DNA repair proteins, and molecular chaperones. Therefore, it became an attractive target for cancer treatment. In this study, virtual screening was applied to the MicroCombiChem database with 1,162 drug-like compounds to identify new HDAC6 inhibitors...
July 10, 2020: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
M Prasad, T B Balci, C Prasad, J D Andrews, R Lee, M T Jurkiewicz, M P Napier, S Colaiacovo, M J Guillen Sacoto, N Karp
The product of the BCL11B (B-Cell Leukemia 11) gene is a bi-functional transcriptional regulator that can act as either a repressor or an activator. It plays an important role in the development of the nervous, immune, and cutaneous systems, and is also involved in dental and craniofacial development. BCL11B-Related Disorder (BCL11BRD) is a novel rare neurodevelopmental disorder associated with mutations in BCL11B. A total of 17 patients have been described in the literature thus far. The main symptoms of BCL11BRD include global developmental delay, speech impairment, dental anomalies, feeding difficulties, refractive errors, dysmorphic features, and immunological abnormalities...
July 10, 2020: European Journal of Medical Genetics
Angana Biswas, Yetirajam Rajesh, Pralay Mitra, Mahitosh Mandal
ETV6 (translocation-Ets-leukemia virus) gene is a transcriptional repressor mainly involved in haematopoiesis and maintenance of vascular networks and has developed to be a major oncogene with the potential ability of forming fusion partners with many other genes with carcinogenic consequences. ETV6 fusions function primarily by constitutive activation of kinase activity of the fusion partners, modifications in the normal functions of ETV6 transcription factor, loss of function of ETV6 or the partner gene and activation of a proto-oncogene near the site of translocation...
July 10, 2020: Biochimica et Biophysica Acta. Reviews on Cancer
Yue Zhong, Run-Ze Qiu, Shan-Liang Sun, Chao Zhao, Tianyuan Fan, Min Chen, Nianguang Li, Zhi-Hao Shi
Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interests of pharmaceutical chemists and is expected to bring new hope for AML therapy...
July 13, 2020: Journal of Medicinal Chemistry
Kayleigh M Gallagher, Justine E Roderick, Shi Hao Tan, Tze King Tan, Leonard Murphy, Jun Yu, Rui Li, Kevin W O'Connor, Julie Zhu, Michael R Green, Takaomi Sanda, Michelle A Kelliher
Synthetic glucocorticoids (GCs), such as dexamethasone and prednisone, remain key components of therapy for patients with lymphoid malignancies. For pediatric patients with acute lymphoblastic leukemia (ALL), response to GCs remains the most reliable prognostic indicator; failure to respond to GC correlates with poor event-free survival. To uncover GC resistance mechanisms, we performed a genome-wide, survival-based short hairpin RNA screen and identified the orphan nuclear receptor estrogen-related receptor-β (ESRRB) as a critical transcription factor that cooperates with the GC receptor (GR) to mediate the GC gene expression signature in mouse and human ALL cells...
July 14, 2020: Blood Advances
Vanessa Collin, Annie Gravel, Benedikt B Kaufer, Louis Flamand
Human herpesvirus 6B (HHV-6B) is a betaherpesvirus capable of integrating its genome into the telomeres of host chromosomes. Until now, the cellular and/or viral proteins facilitating HHV-6B integration have remained elusive. Here we show that a cellular protein, the promyelocytic leukemia protein (PML) that forms nuclear bodies (PML-NBs), associates with the HHV-6B immediate early 1 (IE1) protein at telomeres. We report enhanced levels of SUMOylated IE1 in the presence of PML and have identified a putative SUMO Interacting Motif (SIM) within IE1, essential for its nuclear distribution, overall SUMOylation and association with PML to nuclear bodies...
July 13, 2020: PLoS Pathogens
Linlin Yang, Bowen Wu, Zhaoxing Wu, Ying Xu, Ping Wang, Mengyuan Li, Rongzhen Xu, Yun Liang
Aberrant activation of CAMKIIγ has been linked to leukemia and T-cell lymphoma, but not multiple myeloma (MM). The purpose of this study was to explore the role of CaMKIIγ in the pathogenesis and therapy of MM. In this study, we found that CaMKIIγ was aberrantly activated in human MM and its expression level was positively correlated with malignant progression and poor prognosis. Ectopic expression of CaMKIIγ promoted cell growth, colony formation, cell cycle progress and inhibited apoptosis of MM cell lines, whereas, knockdown of CAMKIIγ expression suppressed MM cell growth in vitro and in vivo...
July 13, 2020: Aging
Lei Wang, Qiong Wu, Rui Qi Wang, Run Ze Wang, Jianwen Wang
PURPOSE: In the study, we aimed to explore the mechanism of leukaemia inhibitory factor (LIF) affects hyperglycaemic induced retinopathy by regulating CaMKII-CREB pathway. METHODS: Human retinal endothelial cell (HRECs) induced by high glucose to simulate one of the pathogenesis in the diabetic retinopathy (DR) model. After LIF treatment, cell viability was detected by CCK-8 and apoptosis was detected by flow cytometry. Angiogenesis was detected by in vitro tube formation...
July 13, 2020: Archives of Physiology and Biochemistry
Reo Etani, Mitsuaki Ojima, Kentaro Ariyoshi, Yohei Fujishima, Michiaki Kai
PURPOSE: Acute myeloid leukemia (AML) is a major cancer in the human population exposed to ionizing radiation. Several past studies using a mouse model of radiation-induced AML (rAML) have shown that hemizygous deletion of the Sfpi1 gene ( HDSG ) is an initiating event for development of rAML. Although HDSG can occur in hematopoietic stem cells (HSCs) soon after radiation exposure, the cellular kinetics of HSCs carrying HDSG in various hematopoietic tissues after X-irradiation is unclear...
July 13, 2020: International Journal of Radiation Biology
Yingying Sun, Chengcheng Wu, Chunyan Liu, Zonghong Shao
BACKGROUND: Elderly patients with acute leukemia have high mutation frequency and are often accompanied by various underlying diseases, so treatment is difficult and mortality is high. METHODS: We report an elderly acute myeloid leukemia patient with a complex karyotype who received a reduced dose of decitabine in induction chemotherapy due to a combination of severe heart disease. RESULTS: After a course of induction chemotherapy, the patient achieved complete cytogenetic remission...
July 1, 2020: Clinical Laboratory
Francisco Ribeiro-Carvalho, Manuel Gonçalves-Pinho, Rui Bergantim, Alberto Freitas, Lia Fernandes
OBJECTIVE: Patients hospitalized with multiple myeloma (MM) are particularly vulnerable to depression. The present study aims to determine the frequency of depression among MM hospitalized patients, in order to assess the possible differences between those with and without depression in relation to sociodemographic and clinical variables and to measure the impact of depression on hospitalization outcomes. METHODS: An observational retrospective study was performed using an administrative data set of all hospitalizations with a primary diagnosis of MM between 2000 and 2015 in Portuguese mainland public hospitals...
July 13, 2020: Psycho-oncology
Fabian Freitag, Marius Maucher, Zeno Riester, Michael Hudecek
PURPOSE OF REVIEW: Immunotherapy with gene-engineered chimeric antigen receptor (CAR)-T cells has curative potential in advanced malignancies and undergoes a surging preclinical and clinical development. Here, we present a selection of new targets and technologies that illustrate the progress that is being made with the aspiration to make CAR-T cell therapy a universally applicable and effective treatment in cancer medicine. RECENT FINDINGS: There is a rich pipeline of new target antigens for CAR-T cells in hematology and oncology that are rated based on uniformity but also stability of expression on tumor cells under therapeutic pressure...
July 9, 2020: Current Opinion in Oncology
Hossein Khadem Haghighian, Neda Ketabchi, Maria Kavianpour
Acute lymphoblastic leukemia (ALL) is a hematological malignancy of lymphoid progenitor cells associated with excessive proliferation of lymphocytes. Curcumin, a polyphenolic compound, is known to possess anticancer activity. However, the mechanism of apoptosis induction differs in cancers. In this study, we discuss the potential apoptosis and anticancer effect of curcumin on the ALL. After choosing Medical Subject Headings (MeSH) keywords, including "Curcumin", "acute lymphoblastic leukemia", "apoptosis", as well as searching Medline/PubMed, Scopus, Sciencedirect...
July 13, 2020: Nutrition and Cancer
Xiaoyang Ji, Wenting Tan, Chunming Zhang, Yubo Zhai, Yiching Hsueh, Zhonghai Zhang, Chunli Zhang, Yanqiu Lu, Bo Duan, Guangming Tan, Renhua Na, Guohong Deng, Gang Niu
Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the "SARS-CoV-2" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying viruses and hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly if our scientific understanding is also limited, which further lowers the information processing efficiency...
July 13, 2020: Drug Development Research
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