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https://www.readbyqxmd.com/read/28819011/tp53-mutations-identify-younger-mantle-cell-lymphoma-patients-who-do-not-benefit-from-intensive-chemoimmunotherapy
#1
Christian W Eskelund, Christina Dahl, Jakob W Hansen, Maj Westman, Arne Kolstad, Lone B Pedersen, Carmen P Montano-Almendras, Simon Husby, Catja Freiburghaus, Sara Ek, Anja Pedersen, Carsten Niemann, Riikka Räty, Peter Brown, Christian H Geisler, Mette K Andersen, Per Guldberg, Mats Jerkeman, Kirsten Grønbæk
Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable and we are still unable to identify patients who will not benefit from the current standard-of-care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger MCL patients from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) and CDKN2A (20%) were significantly associated with inferior outcomes (together with MIPI, MIPI-c, Blastoid morphology and Ki67>30%); however, in multivariate analyses only TP53 mutations (HR=6...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28815582/activation-of-twist1-by-col11a1-promotes-chemoresistance-and-inhibits-apoptosis-in-ovarian-cancer-cells-by-modulating-nf-%C3%AE%C2%BAb-mediated-ikk%C3%AE-expression
#2
Yi-Hui Wu, Yu-Fang Huang, Tzu-Hao Chang, Cheng-Yang Chou
We have shown that collagen type XI alpha 1 (COL11A1) promotes ovarian cancer progression and is associated with chemoresistance to cisplatin and paclitaxel in ovarian cancer cells. Here, we demonstrate how COL11A1 regulates twist family basic helix-loop-helix transcription factor 1-related protein 1 (TWIST1) to induce chemoresistance and inhibit apoptosis in ovarian cancer cells. Small interfering RNA-mediated reduction in COL11A1 protein levels increased the chemosensitivity to cisplatin and paclitaxel via downregulated TWIST1 expression...
August 17, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28812037/a-retrospective-analysis-of-concurrent-pathology-in-acl-reconstructed-knees-of-elite-alpine-ski-racers
#3
Matthew J Jordan, Patricia Doyle-Baker, Mark Heard, Per Aagaard, Walter Herzog
BACKGROUND: Anterior cruciate ligament (ACL) tear is the most frequent injury in alpine ski racing, and there is a high prevalence of ACL reinjury. Limited data exist on the concurrent pathology with primary ACL tears in elite alpine ski racers and the magnitude of injury progression after primary ACL reconstruction (ACLR). PURPOSE: To evaluate (1) the involvement of intra-articular and multiligament pathologies at the time of primary ACLR, (2) the subsequent progression in meniscal/chondral injuries, and (3) the occurrence of ACL reinjury in elite alpine ski racers...
July 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#4
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28809055/apoptotic-effect-of-astragalin-in-melanoma-skin-cancers-via-activation-of-caspases-and-inhibition-of-sry-related-hmg-box-gene-10
#5
Ok Heui You, Eun Ah Shin, Hyemin Lee, Ju-Ha Kim, Deok Yong Sim, Jung Hyo Kim, Younghwan Kim, Jae-Ho Khil, Nam-In Baek, Sung-Hoon Kim
Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner...
August 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28808298/standards-for-arsenic-in-drinking-water-implications-for-policy-in-mexico
#6
Andrew T Fisher, Lizbeth López-Carrillo, Brenda Gamboa-Loira, Mariano E Cebrián
Global concern about arsenic in drinking water and its link to numerous diseases make translation of evidence-based research into national policy a priority. Delays in establishing a maximum contaminant level (MCL) to preserve health have increased the burden of disease and caused substantial and avoidable loss of life. The current Mexican MCL for arsenic in drinking water is 25 μg/l (2.5 times higher than the World Health Organization (WHO) recommendation from 1993). Mexico's struggles to set its arsenic MCL offer a compelling example of shortcomings in environmental health policy...
August 14, 2017: Journal of Public Health Policy
https://www.readbyqxmd.com/read/28807693/safety-and-feasibility-of-rehabilitation-interventions-in-children-undergoing-hematopoietic-stem-cell-transplant-with-thrombocytopenia
#7
Katarzyna Ibanez, Noel Espiritu, Regine L Souverain, Laura Stimler, Lauren Ward, Elyn R Riedel, Rachel Lehrman, Farid Boulad, Michael Dean Stubblefield
OBJECTIVE: To analyze the relationship between platelet counts, the intensities of physical therapies (PT) and occupational therapies (OT) services received, and the frequency of bleeding complications in children undergoing hematopoietic stem cell transplants (HSCT) during a period of severe thrombocytopenia. DESIGN: Retrospective review study SETTING: Tertiary care hospital PARTICIPANTS: Children (age <18) hospitalized for HSCT in 2010 and 2011 who received PT and OT services while markedly thrombocytopenic (platelets≤50K/mcL)...
August 11, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28806703/nox4-mediated-ros-production-induces-apoptotic-cell-death-via-down-regulation-of-c-flip-and-mcl-1-expression-in-combined-treatment-with-thioridazine-and-curcumin
#8
Seung Un Seo, Tae Hwan Kim, Dong Eun Kim, Kyoung-Jin Min, Taeg Kyu Kwon
Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA...
August 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28801299/-effect-of-bortezomib-in-inducing-apoptosis-of-imatinib-resistant-k562-cells-and-the-mechanism
#9
Jia-Ye Hua, Xu-Hong Zhou, Shu-Ting Ouyang, Yong-Bin Wu
OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28800142/alcohol-mediated-missplicing-of-mcl-1-pre-mrna-is-involved-in-neurotoxicity
#10
Rahsan Sariyer, Francesca I De Simone, Martina Donadoni, Jan B Hoek, Sulie L Chang, Ilker Kudret Sariyer
BACKGROUND: Heavy and chronic ethanol (EtOH) exposure can cause significant structural and functional damage to the adult brain. The most devastating consequence of EtOH exposure is the neurotoxicity associated with the depletion of neurons. Regulation of splice variants in the brain can modulate protein functions, which may ultimately affect behaviors associated with alcohol dependence and EtOH-mediated neurotoxicity. Since alcohol consumption is associated with neurotoxicity, it is possible that altered splicing of survival and pro-survival factors during the development of alcoholism may contribute to the neurotoxicity...
August 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28800129/the-combination-of-reduced-mcl-1-and-standard-chemotherapeutics-is-tolerable-in-mice
#11
Kerstin Brinkmann, Stephanie Grabow, Craig D Hyland, Charis E Teh, Warren S Alexander, Marco J Herold, Andreas Strasser
A common therapeutic strategy to combat human cancer is the use of combinations of drugs, each targeting different cellular processes or vulnerabilities. Recent studies suggest that addition of an MCL-1 inhibitor to such anticancer drug treatments could be an attractive therapeutic strategy. Thus, it is of great interest to understand whether combinations of conventional anticancer drugs with an MCL-1 inhibitor will be tolerable and efficacious. In order to mimic the combination of MCL-1 inhibition with other cancer therapeutics, we treated Mcl-1(+/-) heterozygous mice, which have a ~50% reduction in MCL-1 protein in their cells, with a broad range of chemotherapeutic drugs...
August 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28797244/a-lowered-26s-proteasome-activity-correlates-with-mantle-lymphoma-cell-lines-resistance-to-genotoxic-stress
#12
Khaoula Ben Younes, Simon Body, Élodie Costé, Pierre-Julien Viailly, Hadjer Miloudi, Clémence Coudre, Fabrice Jardin, Fatma Ben Aissa-Fennira, Brigitte Sola
BACKGROUND: Mantle cell lymphoma (MCL) is a B-cell hemopathy characterized by the t(11;14) translocation and the aberrant overexpression of cyclin D1. This results in an unrestrained cell proliferation. Other genetic alterations are common in MCL cells such as SOX11 expression, mutations of ATM and/or TP53 genes, activation of the NF-κB signaling pathway and NOTCH receptors. These alterations lead to the deregulation of the apoptotic machinery and resistance to drugs. We observed that among a panel of MCL cell lines, REC1 cells were resistant towards genotoxic stress...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28797213/surveillance-imaging-in-mantle-cell-lymphoma-in-first-remission-lacks-clinical-utility
#13
Daniel M Guidot, Jeffrey M Switchenko, Loretta J Nastoupil, Jean L Koff, Kristie A Blum, Joseph Maly, Christopher R Flowers, Jonathon B Cohen
Mantle cell lymphoma (MCL) is a heterogeneous disease with high relapse rates. Limited data guide the use of surveillance imaging following treatment. We constructed a retrospective cohort from two academic institutions of patients with MCL who completed first-line therapy and underwent follow-up for relapse, analyzing the effect of surveillance imaging on survival. Of 217 patients, 102 had documented relapse, with 38 (37%) diagnosed by surveillance imaging and 64 (63%) by other methods. Relapse diagnosis by surveillance imaging had no significant advantage in overall survival from diagnosis date (hazard ratio [HR] = 0...
August 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28797193/exposure-response-evaluations-of-venetoclax-efficacy-and-safety-in-patients-with-non-hodgkin-lymphoma
#14
Apurvasena Parikh, Sathej Gopalakrishnan, Kevin J Freise, Maria E Verdugo, Rajeev M Menon, Sven Mensing, Ahmed Hamed Salem
Exposure-response analyses were performed for a venetoclax monotherapy study in 106 patients with varying subtypes of non-Hodgkin lymphoma (NHL) (NCT01328626). Logistic regression, time-to-event, and progression-free survival (PFS) analyses were used to evaluate the relationship between venetoclax exposure, NHL subtype and response, PFS, or occurrence of serious adverse events. Trends for small increases in the probability of response with increasing venetoclax exposures were identified, and became more evident when assessed by NHL subtype...
August 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28791403/complex-analysis-of-the-tp53-tumor-suppressor-in-mantle-cell-and-diffuse-large-b-cell-lymphomas
#15
Lenka Zlamalikova, Mojmir Moulis, Barbora Ravcukova, Kvetoslava Liskova, Jitka Malcikova, David Salek, Jiri Jarkovsky, Miluse Svitakova, Renata Hrabalkova, Jan Smarda, Jana Smardova
Mutations and deletions of the tumor suppressor TP53 gene are the most frequent genetic alterations detected in human tumors, though they are rather less frequent in lymphomas. However, acquisition of the TP53 mutation was demonstrated to be one of the characteristic markers in mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) and prognostic value of the TP53 status has been recognized for these diseases. We present the complex analysis of the TP53 aberrations in 57 cases of MCL and 131 cases of DLBCL...
August 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791387/atelocollagen-mediated-in-vivo-sirna-transfection-in-ovarian-carcinoma-is-influenced-by-tumor-site-sirna-target-and-administration-route
#16
Matthieu Meryet-Figuière, Charlotte Lecerf, Emilie Varin, Jean-Luc Coll, Marie-Hélène Louis, Soizic Dutoit, Florence Giffard, Cécile Blanc-Fournier, Siham Hedir, Nicolas Vigneron, Emilie Brotin, Laurent Pelletier, Véronique Josserand, Christophe Denoyelle, Laurent Poulain
Ovarian cancer is the leading cause of death from gynecological malignancies worldwide, and innate or acquired chemoresistance of ovarian cancer cells is the major cause of therapeutic failure. It has been demonstrated that the concomitant inhibition of Bcl-xL and Mcl-1 anti-apoptotic activities is able to trigger apoptosis in chemoresistant ovarian cancer cells. In this context, siRNA-mediated Bcl‑xL and Mcl-1 inhibition constitutes an appealing strategy by which to eliminate chemoresistant cancer cells...
August 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28791187/ibrutinib-treatment-of-mantle-cell-lymphoma-relapsing-at-central-nervous-system-a-case-report-and-literature-review
#17
Donato Mannina, Barbara Loteta
Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD)...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28784565/mechanical-analysis-of-extra-articular-knee-ligaments-part-one-native-knee-ligaments
#18
Kristof Smeets, Joshua Slane, Lennart Scheys, Steven Claes, Johan Bellemans
BACKGROUND: The aim of this study was to provide a characterization of the tensile properties of the medial collateral ligament (MCL), lateral collateral ligament (LCL), anterolateral ligament (ALL) and medial patellofemoral ligament (MPFL). Our hypothesis was that extra-articular knee ligaments are heterogeneous in nature and possess distinct material properties. METHODS: MCL (n=12), LCL (n=11), MPFL (n=12) and ALL (n=19) samples from fresh frozen human cadaveric knees were subjected to uniaxial tensile testing to failure and analyzed for their material properties...
August 4, 2017: Knee
https://www.readbyqxmd.com/read/28782060/impacts-of-interleukin-17-neutralization-on-the-inflammatory-response-in-a-healing-ligament
#19
Anna Eb Clements, Connie S Chamberlain, Ellen M Leiferman, William L Murphy, Ray Vanderby
In this study, we sought to improve ligament healing by modulating the inflammatory response after acute injury through the neutralization of Interleukin-17 (IL-17), which we hypothesized would decrease inflammatory cell infiltration and cytokine production. Administration of an Interleukin-17 neutralizing antibody (IL-17 NA) immediately following a rat medial collateral ligament (MCL) transection resulted in alterations in inflammatory cell populations and cytokine expression within the healing ligament, but did not reduce inflammation...
May 2017: J Cytokine Biol
https://www.readbyqxmd.com/read/28776569/fbxo4-inhibits-lung-cancer-cell-survival-by-targeting-mcl-1-for-degradation
#20
C Feng, F Yang, J Wang
Mcl-1 (myeloid cell leukemia 1) is a prosurvival member of the Bcl-2 family and plays a critical role in cell survival by suppressing apoptosis through inhibiting the activity of proapoptotic proteins. It has been reported that Mcl-1 is frequently overexpressed in lung cancer. However, the exact molecular mechanism underlying Mcl-1 elevation in lung cancer is largely unknown. Here, we reported that Mcl-1 protein levels inversely correlate with FBXO4 expression, but not other F-box proteins examined, in lung cancer cell lines and lung cancer patient samples...
August 4, 2017: Cancer Gene Therapy
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