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https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#1
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28628119/differential-expression-of-mir16-in-glioblastoma-and-glioblastoma-stem-cells-their-correlation-with-proliferation-differentiation-metastasis-and-prognosis
#2
R Tian, J Wang, H Yan, J Wu, Q Xu, X Zhan, Z Gui, M Ding, J He
The function of miR16 in multiforme glioblastoma multiforme (GBM) and its stem cells (GSCs) remains elusive. To this end, we investigated the patterns of miR16 expression in these cells and their correlation with malignant behaviors and clinical outcomes. The levels of miR16 and its targeted genes in tumor tissue of GBM and GBM SGH44, U87, U251 cells as well as their stem cell counterparts were measured by qRT-PCR or western blot or immunohistochemistry. Luciferase reporter assay was used to confirm the binding of miR16 to 3'-UTR of its target genes...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#3
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#4
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
June 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28606806/bcl2-induced-by-lamtor3-mapk-is-a-druggable-target-of-chemoradioresistance-in-mesenchymal-lung-cancer
#5
Ok-Seon Kwon, Soon-Ki Hong, Soo-Jung Kwon, Young-Hyun Go, Ensel Oh, Hyuk-Jin Cha
Mesenchymal-type cancers after epithelial mesenchymal transition (EMT) were recently shown to acquire chemoresistance through expressing EMT specific transcription factors. However, druggable (or actionable) target(s) for chemoresistance in mesenchymal-type lung cancers remain unidentified. Here, we used a public clinical genomic database and mesenchymal lung cancer cells (MLCC) model derived from the A549 lung adenocarcinoma cell line to demonstrate that BCL2 expression, which is highly induced in mesenchymal-type lung cancers, as a predictor of poor prognosis in mesenchymal lung cancer patients and association with acquired chemoradioresistance...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28601699/apoptotic-induction-mediated-p53-mechanism-and-caspase-3-activity-by-novel-promising-cyanoacrylamide-derivatives-in-breast-carcinoma
#6
Magda F Mohamed, Noha Samir, Aya Ali, Nawal Ahmed, Yassmen Ali, Sarah Aref, Omnia Hossam, Mervat S Mohamed, Amr M Abdelmoniem, Ismail A Abdelhamid
New cyanoacrylamide derivatives were theoretically examined for their binding abilities to a protein model of apoptosis inhibitor proteins x-IAP and c-IAP1 using molecular modeling. The two compounds 5a and 5b proved promising IAP antagonists, where they have good binding affinity toward the selected active domains. Anticancer activity of all derivatives was performed on different human cancer cell lines (HCT116, Caco2, and MCF7) as well as normal line (HBF4). Data revealed that breast carcinoma was more sensitive to the novel compounds than other lines especially compounds 5a and 5b, but all derivatives lost their cytotoxic effect in case of Caco2 cell line and they showed low cytotoxic effect toward HCT116 cells except compound 3...
June 1, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28596293/the-uncoupling-of-autophagy-and-zinc-homeostasis-in-airway-epithelial-cells-as-a-fundamental-contributor-to-copd
#7
Eugene Roscioli, Hai Bac Tran, Hubertus Jersmann, Phan Tien Nguyen, Emily Hopkins, Susan Elizabeth Lester, Nigel Farrow, Peter D Zalewski, Paul N Reynolds, Sandra Hodge
The proper regulation of Zinc (Zn) trafficking proteins and the cellular distribution of Zn is critical for the maintenance of autophagic processes. However, there have been no studies which have examined Zn dyshomeostasis and the disease-related modulation of autophagy observed in the airways afflicted with COPD. We hypothesized that dysregulated autophagy in airway epithelial cells (AEC) is related to Zn dysregulation in cigarette smoke (CS)-induced COPD. We applied a human ex vivo air-liquid interface model, a murine model of smoke-exposure, and human lung tissues, and investigated Zn, ZIP1 and ZIP2 Zn-influx proteins, autophagy (Microtubule-associated 1A/1B-light chain-3 (LC3), Beclin-1), autophagic flux (Sequestosome), apoptosis (Bcl2; X-Linked Inhibitor of Apoptosis (XIAP), Poly (ADP)-ribose Polymerase (PARP)), and inflammation (TSLP, RANTES, and IL-1β)...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28589248/quercetin-and-tin-protoporphyrin-attenuate-hepatic-ischemia-reperfusion-injury-role-of-ho-1
#8
Yara Atef, Hassan M El-Fayoumi, Yousra Abdel-Mottaleb, Mona F Mahmoud
Ischemia reperfusion (IR) injury occurs in many clinical situations such as organ transplantation and hepatectomies resulting in oxidative stress and immune activation. Heme oxygenase-1(HO-1) is the rate-limiting step in the heme-degradation pathway and has a critical cytoprotective role. Induction of HO-1 improves liver I/R injury. Quercetin, a plant pigment (flavonoid), is an antioxidant and HO-1 inducer. Tin protoporphyrin (SnPP) is a HO-1 inhibitor. This study was designed to investigate the protective effect of quercetin in hepatic I/R injury and the role of HO-1...
June 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28579554/stat3-gain-of-function-mutations-associated-with-autoimmune-lymphoproliferative-syndrome-like-disease-deregulate-lymphocyte-apoptosis-and-can-be-targeted-by-bh3-mimetic-compounds
#9
Schafiq Nabhani, Cyrill Schipp, Hagit Miskin, Carina Levin, Sergey Postovsky, Tal Dujovny, Ariel Koren, Dan Harlev, Anne-Marie Bis, Franziska Auer, Baerbel Keller, Klaus Warnatz, Michael Gombert, Sebastian Ginzel, Arndt Borkhardt, Polina Stepensky, Ute Fischer
Autoimmune lymphoproliferative syndrome (ALPS) is typically caused by mutations in genes of the extrinsic FAS mediated apoptotic pathway, but for about 30% of ALPS-like patients the genetic diagnosis is lacking. We analyzed 30 children with ALPS-like disease of unknown cause and identified two dominant gain-of-function mutations of the Signal Transducer And Activator Of Transcription 3 (STAT3, p.R278H, p.M394T) leading to increased transcriptional activity. Hyperactivity of STAT3, a known repressor of FAS, was associated with decreased FAS-mediated apoptosis, mimicking ALPS caused by FAS mutations...
June 1, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28569785/cytoprotective-effect-of-neuropeptides-on-cancer-stem-cells-vasoactive-intestinal-peptide-induced-antiapoptotic-signaling
#10
Konduru S Sastry, Aouatef Ismail Chouchane, Ena Wang, George Kulik, Francesco M Marincola, Lotfi Chouchane
Cancer stem cells (CSCs) are increasingly considered to be responsible for tumor initiation, metastasis and drug resistance. The drug resistance mechanisms activated in CSCs have not been thoroughly investigated. Although neuropeptides such as vasoactive intestinal peptide (VIP) can promote tumor growth and activate antiapoptotic signaling in differentiated cancer cells, it is not known whether they can activate antiapoptotic mechanisms in CSCs. The objectives of this study are to unravel the cytoprotective effects of neuropeptides and identify antiapoptotic mechanisms activated by neuropeptides in response to anticancer drug treatment in CSCs...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28566733/a-benzothiazole-derivative-5g-induces-dna-damage-and-potent-g2-m-arrest-in-cancer-cells
#11
Mahesh Hegde, Supriya V Vartak, Chandagirikoppal V Kavitha, Hanumappa Ananda, Doddakunche S Prasanna, Vidya Gopalakrishnan, Bibha Choudhary, Kanchugarakoppal S Rangappa, Sathees C Raghavan
Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28551013/citrus-nomilin-down-regulates-tnf-%C3%AE-induced-proliferation-of-aortic-smooth-muscle-cells-via-apoptosis-and-inhibition-of-i%C3%AE%C2%BAb
#12
Jinhee Kim, Sanjukta Chakraborty, G K Jayaprakasha, Mariappan Muthuchamy, Bhimanagouda S Patil
Nomilin is a bitter compound present in citrus and has been demonstrated as useful for various disease preventions through anti-proliferative, anti-inflammatory, and pro-apoptotic activities. Although in vitro disease models have shown that certain limonoids in the p38 mitogen-activated protein kinase signal cascade, the downstream signaling pathways remain unclear. In this study, the effects of nomilin on the proliferation and apoptotic pathways of human aortic smooth muscle cells (HASMCs) that forms the basis of progression of atherosclerotic diseases and restenosis was tested for the first time...
May 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28525891/identification-of-precision-treatment-strategies-for-relapsed-refractory-multiple-myeloma-by-functional-drug-sensitivity-testing
#13
Muntasir Mamun Majumder, Raija Silvennoinen, Pekka Anttila, David Tamborero, Samuli Eldfors, Bhagwan Yadav, Riikka Karjalainen, Heikki Kuusanmäki, Juha Lievonen, Alun Parsons, Minna Suvela, Esa Jantunen, Kimmo Porkka, Caroline A Heckman
Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522550/suppression-of-microrna-135b-5pprotects-againstmyocardial-ischemia-reperfusion-injury-by-activatingjak2-stat3-signaling-pathway-in-mice-duringsevofluraneanesthesia
#14
Xiao-Juan Xie, Dong-Mei Fan, Kai Xi, Ya-Wei Chen, Peng-Wei Qi, Qian-Hui Li, Liang Fang, Li-Gang Ma
The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating JAK2/STAT signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by TUNEL assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, Bcl2 and Bax were detected by qRT-PCR and Western blotting...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28522442/bcl2-expression-in-dlbcl-reappraisal-of-immunohistochemistry-with-new-criteria-for-therapeutic-biomarker-evaluation
#15
Naoko Tsuyama, Seiji Sakata, Satoko Baba, Yuko Mishima, Noriko Nishimura, Kyoko Ueda, Masahiro Yokoyama, Yasuhito Terui, Kiyohiko Hatake, Masanobu Kitagawa, Naoki Ishizuka, Naoto Tomita, Kengo Takeuchi
Overexpression of the BCL2 is associated with a poor prognosis in diffuse large B-cell lymphoma (DLBCL). The assessment of MYC immunohistochemistry (IHC) is becoming optimized, whereas the criteria for BCL2 positivity are highly variable. Furthermore, data on the frequency and prognostic value of BCL2 positivity are conflicting. We aimed to evaluate BCL2 expression by IHC and assess the prognostic significance of the histopathologically-scored BCL2 expression in 456 patients with DLBCL uniformly treated with standard immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP)...
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28505327/histone-deacetylase-inhibitor-saha-is-a-novel-promising-treatment-for-cushing-s-disease
#16
Jie Lu, Grégoire P Chatain, Alejandro Bugarini, Xiang Wang, Dragan Maric, Stuart Walbridge, Zhengping Zhuang, Prashant Chittiboina
Context: Remission failure following transsphenoidal surgery in Cushing's disease (CD) from pituitary corticotroph tumors (CtT) remains clinically challenging. Histone deacetylase (HDAC) inhibitors are antitumor drugs approved for oral clinical use, with potential to affect adrenocorticotropin (ACTH) hypersecretion by inhibiting proopiomelanocortin (POMC) transcription. Objective: Testing efficacy of suberolyl hydroxamic acid (SAHA) on human and murine ACTH-secreting tumor cells...
May 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28498429/sbi0206965-a-novel-inhibitor-of-ulk1-suppresses-non-small-cell-lung-cancer-cell-growth-by-modulating-both-autophagy-and-apoptosis-pathways
#17
Fang Tang, Pengchao Hu, Zetian Yang, Chao Xue, Jun Gong, Shaoxing Sun, Liu Shi, Shimin Zhang, Zhenzhen Li, Chunxu Yang, Junhong Zhang, Conghua Xie
Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients...
May 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28493025/crnde-expression-positively-correlates-with-egfr-activation-and-modulates-glioma-cell-growth
#18
Karrie Mei-Yee Kiang, Xiao-Qin Zhang, Grace Pingde Zhang, Ning Li, Stephen Yin Cheng, Ming-Wai Poon, Jenny Kan-Suen Pu, Wai-Man Lui, Gilberto Ka-Kit Leung
BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator in carcinogenesis and cancer progression. While CRNDE has previously been found to be the most highly upregulated lncRNA in glioma, detailed information on its roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present study, we aimed at exploring the functional roles and underlying mechanisms of CRNDE in glioma. METHODS: We applied microarray data analysis to determine the prognostic significance of CRNDE in glioma patients and its correlation with epidermal growth factor receptor (EGFR) activation...
May 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28473407/clinico-pathological-features-and-outcomes-of-progression-of-cll-on-the-bcl2-inhibitor-venetoclax
#19
Mary Ann Anderson, Constantine Tam, Thomas E Lew, Surender Juneja, Manu Juneja, David Westerman, Meaghan Wall, Stephen Lade, Alexandra Gorelik, David C S Huang, John F Seymour, Andrew W Roberts
The BCL2 inhibitor venetoclax achieves responses in ~79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemo-immunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinico-pathological features of PD and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pre-treated patients on three early phase clinical trials...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28468776/vulnerability-of-small-cell-lung-cancer-to-apoptosis-induced-by-the-combination-of-bet-bromodomain-proteins-and-bcl2-inhibitors
#20
Lloyd T Lam, Xiaoyu Lin, Emily J Faivre, Ziping Yang, Xiaoli Huang, Denise M Wilcox, Richard J Bellin, Sha Jin, Stephen K Tahir, Michael Mitten, Terry Magoc, Anahita Bhathena, Warren M Kati, Daniel H Albert, Yu Shen, Tamar Uziel
10% to 15% of all lung cancers are small cell lung cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed and relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC. The BET (bromodomain and extra-terminal) proteins bind acetylated histones and recruit protein complexes to promote transcription initiation and elongation. BET proteins have been shown to regulate expression of key genes in oncogenesis such as MYC, CCND2, and BCL2L1 Here, we demonstrate that ~50% of SCLC cell lines are exquisitely sensitive to growth inhibition by the BET inhibitor, ABBV-075...
May 3, 2017: Molecular Cancer Therapeutics
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