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https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#1
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29133623/immu-140-a-novel-sn-38-antibody-drug-conjugate-targeting-hla-dr-mediates-dual-cytotoxic-effects-in-hematological-cancers-and-malignant-melanoma
#2
Thomas M Cardillo, Serengulam V Govindan, Maria B Zalath, Diane L Rossi, Yang Wang, Chien-Hsing Chang, David M Goldenberg
HLA-DR is a member of the MHC class II antigen family expressed on hematological and solid tumors.  Antibodies directed against HLA-DR have demonstrated some clinical success, but toxicities limited development.  IMMU-140 is an anti-HLA-DR antibody-drug conjugate comprised of the active metabolite of irinotecan, SN-38, conjugated to a humanized anti-HLA-DR IgG4 antibody (IMMU-114); the IgG4 naked antibody is devoid of immune functions. Our aim was to determine if SN-38, the metabolite of a drug not commonly used in hematopoietic cancers, would be effective and safe when targeted to HLA-DR-expressing tumors...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29131027/microrna-194-regulates-lipopolysaccharide-induced-cell-viability-by-inactivation-of-nuclear-factor-%C3%AE%C2%BA-b-pathway
#3
Fei Xie, Lei Yang, Lili Han, Bin Yue
The present study explored the functional role of microRNA (miR)-194 in lipopolysaccharide (LPS) induced lung cell injury, along with the underlying mechanisms and to reveal the potential role in infantile pneumonia. Human fibroblasts WI38 cells were transfected with miR-194 mimic or miR-194 inhibitor, and the transfection efficiency was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, the cells were treated with or without LPS, and then cell viability, cell apoptosis and mRNA and protein expressions of key proteins of nuclear factor kappa B (NF-κB) pathway including inhibitor of NF-κB (IκB) α, p-65, and B-cell CLL/lymphoma (Bcl) 3 were analyzed...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29125235/comparison-of-the-mrna-expression-profile-of-b-cell-receptor-components-in-normal-cd5-high-b-lymphocytes-and-chronic-lymphocytic-leukemia-a-key-role-of-zap70
#4
Aleena A Gladkikh, Daria M Potashnikova, Victor Tatarskiy, Margarita Yastrebova, Alvina Khamidullina, Natasha Barteneva, Ivan Vorobjev
The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29039493/actein-induces-apoptosis-in-leukemia-cells-through-suppressing-rhoa-rock1-signaling-pathway
#5
Wen-Di Zhou, Xiang Wang, Xing-Zhen Sun, Jian Hu, Rong-Rong Zhang, Ze Hong
Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of Cimicifuga foetida, exhibiting anticancer activities as previously reported. However, the effects of actein on human leukemia have not been explored before. In this study, the role of actein in regulating apoptosis induction in human leukemia cells was investigated. Actein administration significantly enhanced apoptosis, especially in human leukemia cell line of U937 and the primary human leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039465/essential-role-of-microrna-650-in-the-regulation-of-b-cell-cll-lymphoma-11b-gene-expression-following-transplantation-a-novel-mechanism-behind-the-acute-rejection-of-renal-allografts
#6
Peng Jin, Hongxi Chen, Jinliang Xie, Cheng Zhou, Xiangrong Zhu
Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection...
October 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29036643/glass-assisted-and-standardized-assessment-of-gene-variations-from-sanger-sequence-trace-data
#7
Karol Pal, Vojtech Bystry, Tomas Reigl, Martin Demko, Adam Krejci, Tasoula Touloumenidou, Evangelia Stalika, Boris Tichy, Paolo Ghia, Kostas Stamatopoulos, Sarka Pospisilova, Jitka Malcikova, Nikos Darzentas
Motivation: Sanger sequencing is still being employed for sequence variant detection by many laboratories, especially in a clinical setting. However, chromatogram interpretation often requires manual inspection and in some cases, considerable expertise. Results: We present GLASS, a web-based Sanger sequence trace viewer, editor, aligner and variant caller, built to assist with the assessment of variations in 'curated' or user-provided genes. Critically, it produces a standardized variant output as recommended by the Human Genome Variation Society...
July 13, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-lymphocytic-leukemia
#8
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the sole known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29022890/elevated-microrna-34a-contributes-to-trophoblast-cell-apoptosis-in-preeclampsia-by-targeting-bcl-2
#9
M Guo, X Zhao, X Yuan, P Li
Preeclampsia (PE) is one of the most common pregnancy-specific pathologic complications, and is characterised by onset of hypertension and proteinuria. Placental trophoblast cell apoptosis is generally accepted as a major cause of PE. However, the details of the mechanism underlying the condition remain unclear. Here, we aimed to investigate a possible association between microRNA (miR)-34a and human trophoblast cell apoptosis during PE. We evaluated miR-34a expression in placentas from patients with PE compared with those from healthy pregnant individuals...
December 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28989655/precision-spherical-nucleic-acids-for-delivery-of-anticancer-drugs
#10
Danny Bousmail, Lilian Amrein, Johans J Fakhoury, Hassan H Fakih, John C C Hsu, Lawrence Panasci, Hanadi F Sleiman
We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood-brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28983465/myc-immunohistochemistry-predicts-myc-rearrangements-by-fish
#11
Julum Nwanze, Momin T Siddiqui, Keith A Stevens, Debra Saxe, Cynthia Cohen
MYC is the proto-oncogene classically associated with Burkitt lymphoma (BL) located at chromosomal locus 8q24. Rearrangements of MYC are seen in nearly 100% of BL but have been reported in 3-16% of diffuse large B-cell lymphomas (DLBCLs). Rearrangements of MYC are tested for by flourescence in situ hybridization (FISH). In this study, we compared immunohistochemistry (IHC) using a monoclonal antibody directed against the human Myc protein to the current method, FISH. 31 cases were identified that had been tested for MYC rearrangements by FISH over 27 months with heterogeneity in the diagnoses: 5 BL; 10 DLBCL; 3 B-cell lymphoma unclassifiable between DLBCL and BL; 5 B-cell lymphoma not otherwise specified; 1 EBV-related B-cell lymphoma; 1 composite CLL/SLL-large cell lymphoma; and 6 designated as high-grade or aggressive B-cell lymphoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#12
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916317/presence-of-human-herpesvirus-8-hhv-8-dna-sequences-in-patients-with-lymphoproliferative-diseases-and-chronic-blood-disorders
#13
Hossein Keyvani, Mohammad Hadi Karbalaie Niya, Maryam Esghaei, Farah Bokharaei-Salim, Seyed Hamid Reza Monavari
OBJECTIVE: Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma (KS), but it has also been associated with different hematologic malignancies, including plasmablastic lymphoma, Multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and various atypical lymphoproliferative disorders. Patients with underlying lymphoproliferative diseases and chronic blood disorders who become infected with this virus are at risk for human malignancies. This small study reported the frequency of human herpesvirus 8 in 81 Iranian patients with lymphoproliferative disorders for estimation of possible factors affecting malignancy...
October 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28902633/ginkgetin-inhibits-proliferation-of-human-leukemia-cells-via-the-tnf-%C3%AE-signaling-pathway
#14
Ling-Ling Pan, Wen-Jun Wu, Gao-Feng Zheng, Xiao-Yan Han, Jing-Song He, Zhen Cai
Ginkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic lymphoblastic leukemia (CLL) remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis...
October 26, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28867658/identification-and-characterization-of-a-potent-and-biologically-active-pde4-7-inhibitor-via-fission-yeast-based-assays
#15
Ana Santos de Medeiros, Arlene R Wyman, Manal A Alaamery, Christina Allain, F Douglas Ivey, Lili Wang, Hai Le, James P Morken, Alawi Habara, Cuong Le, Shuaiying Cui, Adam Lerner, Charles S Hoffman
We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28865368/sweroside-eradicated-leukemia-cells-and-attenuated-pathogenic-processes-in-mice-by-inducing-apoptosis
#16
Xiao-Lin Han, Jing-Dong Li, Wan-Ling Wang, Cui Yang, Zhi-Ying Li
Acute myeloid leukemia (AML), characterized by extremely heterogeneous molecular and biologic abnormalities, is an aggressive hematologic malignancy, hampering the research and development of effective targeted treatment modalities. Sweroside (SWE), an iridoid glycoside, is isolated from Lonicera japonIca. It has diverse biological activities, but little is known in human leukemia. Here, our study showed the potential of sweroside as an effective agent against human leukemia using in vitro and in vivo approaches...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28845710/combination-therapy-with-the-type-ii-anti-cd20-antibody-obinutuzumab
#17
REVIEW
Christian Klein, Marina Bacac, Pablo Umana, Günter Fingerle-Rowson
Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab...
October 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28835371/b-cell-receptor-signaling-regulates-metabolism-in-chronic-lymphocytic-leukemia
#18
Hima Vangapandu, Ondrej Havranek, Mary Ayres, Benny A Kaipparettu, Kumudha Balakrishnan, William Wierda, Michael J Keating, R Eric Davis, Christine M Stellrecht, Varsha Gandhi
Chronic lymphocytic leukemia (CLL) cells are quiescent but have active transcription and translation processes, suggesting that these lymphocytes are metabolically active. Based on this premise, the metabolic phenotype of CLL lymphocytes was investigated by evaluating the two intracellular ATP generating pathways. Metabolic flux was assessed by measuring glycolysis as extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation as oxygen consumption rate (OCR) and then correlated with prognostic factors...
August 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28833722/killing-two-birds-with-one-stone-response-to-pembrolizumab-in-a-patient-with-metastatic-melanoma-and-b-cell-chronic-lymphocytic-leukemia
#19
M Arenbergerova, A Fialova, P Arenberger, S Gkalpakiotis, T Jirasek, A Srp, A Novotna, H Frankova
Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1). An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5)...
August 22, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28783166/anti-leukemic-activity-of-microrna-26a-in-a-chronic-lymphocytic-leukemia-mouse-model
#20
L D'Abundo, E Callegari, A Bresin, A Chillemi, B K Elamin, P Guerriero, X Huang, E Saccenti, E M A A Hussein, F Casciano, P Secchiero, G Zauli, G A Calin, G Russo, L J Lee, C M Croce, G Marcucci, S Sabbioni, F Malavasi, M Negrini
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eμ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody...
August 7, 2017: Oncogene
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