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https://www.readbyqxmd.com/read/27913513/minimal-residual-disease-in-mantle-cell-lymphoma-insights-into-biology-and-impact-on-treatment
#1
Eva Hoster, Christiane Pott
Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913510/frontline-therapy-and-role-of-high-dose-consolidation-in-mantle-cell-lymphoma
#2
Simon Rule
Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. It is predominantly a disease of older individuals, with a median age at presentation of ∼70 years. For the majority of patients, the management revolves around immuno-chemotherapy often followed by maintenance rituximab, and at relapse, a range of options are available. For the younger patient, it is possible to be more intensive with therapy, consolidate responses with high-dose procedures, and in a few there might be the prospect of a cure...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912843/the-reduced-concentration-of-citrate-in-cancer-cells-an-indicator-of-cancer-aggressiveness-and-a-possible-therapeutic-target
#3
Icard Philippe, Lincet Hubert
Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911011/fragment-based-design-synthesis-and-biological-evaluation-of-1-substituted-indole-2-carboxylic-acids-as-selective-mcl-1-inhibitors
#4
Ziqian Wang, Wenjie Xu, Ting Song, Zongwei Guo, Lu Liu, Yudan Fan, Anhui Wang, Zhichao Zhang
Based on a known selective Mcl-1 inhibitor, 6-chloro-3-(3-(4-chloro-3,5-dimethylphenoxy)propyl)-1H-indole-2-carboxylic acid, we applied a fragment-based approach to obtain new molecules that extended into the p1 pocket of the BH3 groove and then exhibited binding selectivity for the Mcl-1 over the Bcl-2 protein. After we deconstructed the 1H-indole-2-carboxylic acid from the parental molecule, a benzenesulfonyl was substituted at the 1-position to adopt a geometry preferred for accessing the p1 pocket according to the binding mode of the parental molecule identified by X-ray crystallography...
December 2, 2016: Archiv der Pharmazie
https://www.readbyqxmd.com/read/27910887/energy-metabolism-regulated-by-hdac-inhibitor-attenuates-cardiac-injury-in-hemorrhagic-rat-model
#5
Qiyuan Kuai, Chunyan Wang, Yanbing Wang, Weijing Li, Gongqing Zhang, Zhixin Qiao, Min He, Xuanlin Wang, Yu Wang, Xingwei Jiang, Lihua Su, Yuezhong He, Suping Ren, Qun Yu
A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906967/platinum-ii-iodido-complexes-of-7-azaindoles-with-significant-antiproliferative-effects-an-old-story-revisited-with-unexpected-outcomes
#6
Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Jan Hošek, Jarmila Klusáková, Zdeněk Dvořák
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin...
2016: PloS One
https://www.readbyqxmd.com/read/27906183/male-sterility-in-mcl-1-flox-mice-is-not-due-to-enhanced-mcl1-protein-stability
#7
Casey Ah-Cann, Maximilien Tailler, Andrew J Kueh, Marco J Herold, Joseph T Opferman, Marie-Liesse Asselin-Labat, Philippe Bouillet
No abstract text is available yet for this article.
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#8
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900638/bendamustine-plus-rituximab-for-previously-untreated-patients-with-indolent-b-cell-non-hodgkin-lymphoma-or-mantle-cell-lymphoma-a-multicenter-phase-ii-clinical-trial-in-japan
#9
Michinori Ogura, Kenichi Ishizawa, Dai Maruyama, Naokuni Uike, Kiyoshi Ando, Koji Izutsu, Yasuhito Terui, Yoshitaka Imaizumi, Kunihiro Tsukasaki, Kenshi Suzuki, Tohru Izumi, Kensuke Usuki, Tomohiro Kinoshita, Masafumi Taniwaki, Nobuhiko Uoshima, Junji Suzumiya, Mitsutoshi Kurosawa, Hirokazu Nagai, Toshiki Uchida, Noriko Fukuhara, Ilseung Choi, Ken Ohmachi, Go Yamamoto, Kensei Tobinai
A Phase II, multicenter clinical trial of bendamustine plus rituximab (BR) regimen was conducted in previously untreated patients with high-tumor-burden indolent B-cell non-Hodgkin lymphoma (B-NHL) and previously untreated elderly patients with mantle cell lymphoma (MCL) in Japan. Bendamustine 90 mg/m(2)/day on days 1 and 2, as well as rituximab 375 mg/m(2) on day 1 were administered intravenously up to six cycles. The primary endpoint was the complete response (CR) rate as assessed by the International Workshop Response Criteria (1999)...
November 29, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27900291/elastin-a-possible-genetic-biomarker-for-more-severe-ligament-injuries-in-elite-soccer-a-pilot-study
#10
Rosa Artells, Ricard Pruna, Alexandre Dellal, Nicola Maffulli
BACKGROUND: The study of new genetic biomarkers in genes related to connective tissue repair and regeneration may help to identify individuals with greater predisposition to injury, who may benefit from targeted preventive measures, and those who require longer recovery time following a muscle, ligament or tendon injury. The present study investigated whether single nucleotide polymorphisms of the Elastin gene could be related to MCL injury. METHODS: 60 top class football players were studied to identify single nucleotide polymorphisms for the Elastin (ELN) gene using Allelic Discrimination analysis...
April 2016: Muscles, Ligaments and Tendons Journal
https://www.readbyqxmd.com/read/27895791/nedaplatin-enhanced-apoptotic-effects-of-abt-737-in-human-cancer-cells-via-mcl-1-inhibition
#11
Chong Zhang, Yang-Ling Li, Xu Weng, Li-Yan Li, Ming-Xian Zhou, Da-Yong Zhang, Neng-Ming Lin
Platinum compounds, such as cisplatin, carboplatin, oxaliplatin and nedaplatin, are widely used to treat a number of solid malignancies. Nedaplatin is a second-generation platinum complex, based on its pronounced anti-cancer activities against several solid tumors being equivalent to that of cisplatin, but with lower nephrotoxicity. In this context, the present study aimed to investigate the potential anti-cancer effect by combining nedaplatin with ABT-737. It was found that nedaplatin greatly increased ABT-737-mediated apoptosis in A549 and 95-D cells, accompanied by enhanced cleavage of poly(ADP-ribose) polymerase and caspase-3...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894215/the-molecular-pathogenesis-of-mantle-cell-lymphoma
#12
Niklas Vogt, Beiying Dai, Tabea Erdmann, Wolfgang E Berdel, Georg Lenz
Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) leading to constitutive cyclin D1 overexpression. However, overexpression of cyclin D1 alone is insufficient to cause malignant transformation. Secondary genetic alterations and deregulated signaling pathways involved in DNA damage response, cell proliferation, and apoptosis are indispensable for MCL lymphomagenesis. Recent studies investigating the biology of MCL have revealed crucial importance of B-cell receptor (BCR), nuclear factor-kappa B (NF-κB), phosphoinositide 3-kinase (PI3K), and BCL2 signaling for the molecular pathogenesis of MCL...
November 28, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27893461/dual-modulation-of-mcl-1-and-mtor-determines-the-response-to-sunitinib
#13
Mohamed Elgendy, Amal Kamal Abdel-Aziz, Salvatore Lorenzo Renne, Viviana Bornaghi, Giuseppe Procopio, Maurizio Colecchia, Ravindran Kanesvaran, Chee Keong Toh, Daniela Bossi, Isabella Pallavicini, Jose Luis Perez-Gracia, Maria Dolores Lozano, Valeria Giandomenico, Ciro Mercurio, Luisa Lanfrancone, Nicola Fazio, Franco Nole, Bin Tean Teh, Giuseppe Renne, Saverio Minucci
Most patients who initially respond to treatment with the multi-tyrosine kinase inhibitor sunitinib eventually relapse. Therefore, developing a deeper understanding of the contribution of sunitinib's numerous targets to the clinical response or to resistance is crucial. Here, we have shown that cancer cells respond to clinically relevant doses of sunitinib by enhancing the stability of the antiapoptotic protein MCL-1 and inducing mTORC1 signaling, thus evoking little cytotoxicity. Inhibition of MCL-1 or mTORC1 signaling sensitized cells to clinically relevant doses of sunitinib in vitro and was synergistic with sunitinib in impairing tumor growth in vivo, indicating that these responses are triggered as prosurvival mechanisms that enable cells to tolerate the cytotoxic effects of sunitinib...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27892666/mantle-cell-lymphoma-a-north-indian-tertiary-care-centre-experience
#14
Chandan Krushna Das, Ajay Gogia, Lalit Kumar, Atul Sharma, Mehar Chand Sharma, Saumya Ranjan Mallick
Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin’s lymphoma, with a pathognomonic chromosomal translocation t (11;14). Prognosis is uniformly dismal but there is a paucity of information on MCL from India. Materials and methods: We retrospectively analysed clinicopathological information on all treated patients with MCL at our centre. STATA 14.0 was used for analysis. Survival was assessed by Kaplan-Meier analysis and the Cox’s proportional hazards method. Statistical significance was defined as a P value of < 0...
January 10, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27890615/egr2-is-a-gonadotropin-induced-survival-factor-that-controls-the-expression-of-ier3-in-ovarian-granulosa-cells
#15
Hanyong Jin, Miae Won, Eunkyoung Shin, Hong-Man Kim, Kangseok Lee, Jeehyeon Bae
Pituitary gonadotropins are key hormones that orchestrate the growth and development of ovarian follicles. However, limited information is available on intra-ovarian factors that mediate the actions of gonadotropins. In this study, we identified that the early growth response 2 gene (EGR2) is a gonadotropin-inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR-binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay, electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation (ChIP), and western blot analysis...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27888063/notch1-signalling-inhibits-apoptosis-of-human-dental-follicle-stem-cells-via-both-the-cytoplasmic-mitochondrial-pathway-and-nuclear-transcription-regulation
#16
Xuepeng Chen, Songying Li, Zhaobin Zeng, Zexu Gu, Yanfang Yu, Feifei Zheng, Yi Zhou, Huiming Wang
Dental follicle stem cells (DFSCs) have been considered as promising candidate cells for periodontal tissue regeneration. Understanding the signalling pathways underlying the apoptosis of DFSCs will facilitate its biomedical application. Here we showed that Notch1 signalling could inhibit DFSCs apoptosis because the constitutive overexpression of the intracellular domain of Notch1 (ICN1) promoted proliferation and suppressed apoptosis by inhibiting cytoplasmic mitochondrial membrane depolarization, cytochrome c release and activation of caspase-9 and caspase-3...
November 22, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27880968/results-of-a-new-treatment-concept-for-concomitant-lesion-of-medial-collateral-ligament-in-patients-with-rupture-of-anterior-cruciate-ligament
#17
Fabian Blanke, Jochen Paul, Maximilian Haenle, Jannes Sailer, Geert Pagenstert, Lutz von Wehren, Stephan Vogt, Martin Majewski
Anteromedial knee injury with rupture of anterior cruciate ligament (ACL) and concomitant lesion of medial collateral ligament (MCL) is common in athletes. No standardized treatment concept can be found within the literature. This study presents results of a new treatment concept for concomitant MCL lesions in patients with ACL rupture. In this study, 67 recreational athletes with ACL injury and concomitant MCL lesion were treated according to a distinct treatment concept. Patients were classified in six different types of concomitant MCL lesion depending on grade of MCL lesion and presence of anteromedial rotatory instability (AMRI)...
November 23, 2016: Journal of Knee Surgery
https://www.readbyqxmd.com/read/27878290/-oleocanthal-exerts-anti-melanoma-activities-and-inhibits-stat3-signaling-pathway
#18
Yanli Gu, Jing Wang, Lixin Peng
Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore explored the effects of (-)-oleocanthal (OC) on the three processes in melanoma and investigated underlying mechanisms. In vitro, OC suppressed proliferation, migration, invasion and induced apoptosis in melanoma cells. In addition, OC inhibited proliferation, migration, invasion and tube formation in human umbilical vascular endothelial cells. In vivo, it exhibited potent activity in suppressing tumor growth in a subcutaneous xenograft model...
November 23, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27875574/chidamide-inhibits-aerobic-metabolism-to-induce-pancreatic-cancer-cell-growth-arrest-by-promoting-mcl-1-degradation
#19
Mu He, Zhixin Qiao, Yanbing Wang, Qiyuan Kuai, Changlan Li, Yu Wang, Xingwei Jiang, Xuanlin Wang, Weijing Li, Min He, Suping Ren, Qun Yu
Pancreatic cancer is a fatal malignancy worldwide and urgently requires valid therapies. Previous research showed that the HDAC inhibitor chidamide is a promising anti-cancer agent in pancreatic cancer cell lines. In this study, we elucidate a probable underlying anti-cancer mechanism of chidamide involving the degradation of Mcl-1. Mcl-1 is frequently upregulated in human cancers, which has been demonstrated to participate in oxidative phosphorylation, in addition to its anti-apoptotic actions as a Bcl-2 family member...
2016: PloS One
https://www.readbyqxmd.com/read/27873035/dmfc-3-5-dimethyl-7-h-furo-3-2-g-chromen-7-one-regulates-bim-to-trigger-bax-and-bak-activation-to-suppress-drug-resistant-human-hepatoma
#20
Jun Xiang, Zhe Wang, Qianqian Liu, Xia Li, Jianguo Sun, Kwok-Pui Fung, Feiyan Liu
3,5-Dimethyl-(7)H-furo[3,2-g]chromen-7-one (DMFC) is a coumarin derivative with anti-cancer activity against human hepatoma cells, but the mechanisms underlying DMFC function in cancer suppression is unknown. In this study, we aimed at elucidating the molecular mechanisms underlying DMFC anti-cancer activity and determining whether DMFC is effective in suppression of drug-resistant human hepatocellular carcinoma. We show here that DMFC effectively suppresses both the parent and the multidrug-resistant hepatoma cell growth in vitro and DMFC suppresses hepatoma cell growth at least in part through inducing tumor cell apoptosis...
November 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
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