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https://www.readbyqxmd.com/read/28106939/maximizing-output-in-rna-programmed-peptidyl-transfer-reactions
#1
Margherita Di Pisa, Anett Hauser, Oliver Seitz
A chemical reaction that is triggered by specific RNA molecules may provide opportunities for the design of artificial feedback loops. We envision a peptidyl transfer reaction, in which mRNA encoding for antiapoptotic protein would instruct the synthesis of apoptosis-inducing peptides. In this study, we tackled the RNA-programmed synthesis of a 16mer peptide derived from the Bak-BH3 protein which inhibits the antiapoptotic protein Bcl-xL. The reaction involves the transfer of a thioester-linked donor peptide fragment from one PNA conjugate onto an acceptor peptide-PNA conjugate...
January 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28103725/a-phase-1-study-of-bortezomib-and-romidepsin-in-patients-with-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-indolent-b-cell-lymphoma-peripheral-t-cell-lymphoma-or-cutaneous-t-cell-lymphoma
#2
Beata Holkova, Victor Yazbeck, Maciej Kmieciak, Prithviraj Bose, Shuo Ma, Amy Kimball, Mary Beth Tombes, Ellen Shrader, Wen Wan, Caryn Weir-Wiggins, Amanda Singh, Kevin T Hogan, Sarah Conine, Heidi Sankala, John D Roberts, Thomas C Shea, Steven Grant
A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m(2) bortezomib and 10 mg/m(2) romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease...
January 19, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28094768/bcl-w-has-a-fundamental-role-in-b-cell-survival-and-lymphomagenesis
#3
Clare M Adams, Annette S Kim, Ramkrishna Mitra, John K Choi, Jerald Z Gong, Christine M Eischen
Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28092085/evidence-that-nf-%C3%AE%C2%BAb-and-mapk-signaling-promotes-nlrp-inflammasome-activation-in-neurons-following-ischemic-stroke
#4
David Yang-Wei Fann, Yun-An Lim, Yi-Lin Cheng, Ker-Zhing Lok, Prasad Chunduri, Sang-Ha Baik, Grant R Drummond, S Thameem Dheen, Christopher G Sobey, Dong-Gyu Jo, Christopher Li-Hsian Chen, Thiruma V Arumugam
Multi-protein complexes, termed "inflammasomes," are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#5
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28088782/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-sorafenib
#6
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug combination reduced the activities of AKT, mTOR and STAT transcription factors; increased the activities of eIF2α and ULK-1; lowered the expression of MCL-1, BCL-XL, thioredoxin and SOD2; and increased the expression of Beclin1...
January 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088578/the-effect-of-long-term-hindlimb-unloading-on-the-expression-of-risk-neurogenes-encoding-elements-of-serotonin-dopaminergic-systems-and-apoptosis-comparison-with-the-effect-of-actual-spaceflight-on-mouse-brain
#7
E A Kulikova, V A Kulikov, N A Sinyakova, A V Kulikov, N K Popova
The study of spaceflight effects on the brain is technically complex concern; complicated by the problem of applying an adequate ground model. The most-widely used experimental model to study the effect of microgravity is the tail-suspension hindlimb unloading model; however, its compliance with the effect of actual spaceflight on the brain is still unclear. We evaluated the effect of one month hindlimb unloading on the expression of genes related to the brain neuroplasticity - brain neutotrophic factors (Gdnf, Cdnf), apoptotic factors (Bcl-xl, Bax), serotonin- and dopaminergic systems (5-HT2A, Maoa, Maob, Th, D1r, Comt), and compared the results with the data obtained on mice that spent one month in spaceflight on Russian biosatellite Bion-M1...
January 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#8
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28086831/evaluation-of-the-cytotoxicity-of-the-bithionol-cisplatin-combination-in-a-panel-of-human-ovarian-cancer-cell-lines
#9
Vijayalakshmi N Ayyagari, Tsung-Han Jeff Hsieh, Paula L Diaz-Sylvester, Laurent Brard
BACKGROUND: Combination drug therapy appears a promising approach to overcome drug resistance and reduce drug-related toxicities in ovarian cancer treatments. In this in vitro study, we evaluated the antitumor efficacy of cisplatin in combination with Bithionol (BT) against a panel of ovarian cancer cell lines with special focus on cisplatin-sensitive and cisplatin-resistant cell lines. The primary objectives of this study are to determine the nature of the interactions between BT and cisplatin and to understand the mechanism(s) of action of BT-cisplatin combination...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28086800/relevance-of-fxr-p62-sqstm1-pathway-for-survival-and-protection-of-mouse-hepatocytes-and-liver-especially-with-steatosis
#10
Sanae Haga, Yimin, Michitaka Ozaki
BACKGROUND: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological conditions. Surgically, severe liver injury after surgical resection often leads to fatal liver failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the injury of hepatocytes and liver is a serious concern in various clinical settings. METHODS: We studied the effects of the farnesoid X receptor (FXR) on cell survival and steatosis in mouse hepatocytes (AML12 mouse liver cells) and investigated their molecular mechanisms...
January 13, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#11
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28076833/7-o-geranylquercetin-induces-apoptosis-in-gastric-cancer-cells-via-ros-mapk-mediated-mitochondrial-signaling-pathway-activation
#12
Yanyan Zhu, Yameng Jiang, Lei Shi, Linying Du, Xiaodong Xu, Enxia Wang, Yong Sun, Xin Guo, Boyang Zou, Huaxin Wang, Changyuan Wang, Lidan Sun, Yuhong Zhen
7-O-Geranylquercetin (GQ) is a novel O-alkylated derivate of quercetin. In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase...
January 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28073911/a-truncated-g-csfr-inhibits-apoptosis-induced-by-neutrophil-elastase-g185r-mutant-implication-for-understanding-csf3r-mutations-in-severe-congenital-neutropenia
#13
Yaling Qiu, Yangyang Zhang, Nan Hu, Fan Dong
Mutations in ELANE encoding neutrophil elastase (NE) have been identified in the majority of patients with severe congenital neutropenia (SCN). The NE mutants have been shown to activate unfolded protein response (UPR) and induce premature apoptosis in myeloid cells. Patients with SCN are predisposed to acute myeloid leukemia (AML), and progression from SCN to AML is accompanied by mutations in CSF3R encoding the G-CSF receptor (G-CSFR) in approximately 80% patients. The mutations result in the expression of C-terminally truncated G-CSFRs that promote strong cell proliferation and survival...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069801/aurora-a-and-nf-%C3%AE%C2%BAb-survival-pathway-drive-chemoresistance-in-acute-myeloid-leukemia-via-the-traf-interacting-protein-tifa
#14
Tong-You Wade Wei, Pei-Yu Wu, Ting-Jung Wu, Hsin-An Hou, Wen-Chien Chou, Chieh-Lin Jerry Teng, Chih-Ru Lin, Jo-Mei Maureen Chen, Ting-Yang Lin, Hsiang-Chun Su, Chia-Chi Flora Huang, Chang-Tze Ricky Yu, Shih-Lan Hsu, Hwei-Fang Tien, Ming-Daw Tsai
Aurora A-dependent NF-κB signaling portends poor prognosis in acute myeloid leukemia (AML) and other cancers, but the functional basis underlying this association is unclear. Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML. TIFA protein was overexpressed concurrently with Aurora A and NF-κB signaling factors in patients with de novo AML relative to healthy individuals and also correlated with poor prognosis...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28069035/fbw7-regulates-apoptosis-in-activated-b-cell-like-diffuse-large-b-cell-lymphoma-by-targeting-stat3-for-ubiquitylation-and-degradation
#15
Su Yao, Fangping Xu, Yu Chen, Yan Ge, Fen Zhang, Huijie Huang, Li Li, Danyi Lin, Xinlan Luo, Jie Xu, Donglan Luo, Xiaolan Zhu, Yanhui Liu
BACKGROUND: The ubiquitin-ligase Fbw7 acts as a tumor suppressor, targeting lots of proto-oncogenes for proteolysis. However, the exact role of Fbw7 in diffuse large B-cell lymphoma (DLBCL) development remains unclear. METHODS: We evaluated Fbw7 expression in patient samples of DLBCL using immunohistochemical staining. The effect of Fbw7 overexpression on cell viability and apoptosis was investigated using activated B-cell (ABC) like DLBCL cell lines. The mechanism of Fbw7 activity in DLBCL was investigated using immunoprecipitation, ubiquitination, western blot and qualitative analyses...
January 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28064468/the-membrane-activity-of-bok-involves-formation-of-large-stable-toroidal-pores-and-is-promoted-by-cbid
#16
Yuniel Fernández-Marrero, Stephanie Bleicken, Kushal Kumar Das, Daniel Bachmann, Thomas Kaufmann, Ana J Garcia-Saez
The BCL-2 family members are key regulators of the intrinsic apoptotic pathway, which is defined by permeabilisation of the mitochondrial outer membrane by members of the BAX-like subfamily. BOK is classified as a BAX-like protein; however, its (patho-)physiological role remains largely unclear. We therefore assessed the membrane permeabilisation potential of C-terminally truncated recombinant BOK, BOK(∆C) . We show that BOK(∆C) can permeabilize liposomes mimicking the composition of mitochondrial outer membrane, but not of endoplasmic reticulum, forming large and stable pores over time...
January 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28063408/creb-knockdown-inhibits-growth-and-induces-apoptosis-in-human-pre-b-acute-lymphoblastic-leukemia-cells-through-inhibition-of-prosurvival-signals
#17
Rima Manafi Shabestari, Majid Safa, Fatemeh Alikarami, Mehdi Banan, Ahmad Kazemi
A majority of acute lymphoblastic leukemia patients overexpress CREB in the bone marrow. However, the functional significance of this up-regulation and the detailed molecular mechanism behind the regulatory effect of CREB on the growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells has not been elucidated. We demonstrated here that CREB knockdown induced apoptosis and impaired growth of BCP-ALL NALM-6 cells which was associated with caspase activation. The gene expression levels of prosurvival signals Bcl-2, Mcl-1, Bcl-xL, survivin and XIAP were down-regulated upon CREB suppression...
January 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28063218/cyclic-glycine-proline-accelerates-mammary-involution-by-promoting-apoptosis-and-inhibiting-igf-1-function
#18
Gagandeep Singh-Mallah, Christopher D McMahon, Jian Guan, Kuljeet Singh
In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28059436/the-bet-bromodomain-inhibitor-jq1-suppresses-chondrosarcoma-cell-growth-via-regulation-of-yap-p21-c-myc-signaling
#19
Huan-Tian Zhang, Tao Gui, Yuan Sang, Jie Yang, Yu-Hang Li, Gui-Hong Liang, Thomas Li, Qing-Yu He, Zhen-Gang Zha
Chondrosarcoma, the second-most frequent primary bone malignancy, is generally more resistant to conventional chemotherapy and radiotherapy. Therefore, the development of an effective adjuvant therapy is necessary. Recently, targeting the epigenetic regulator such as bromodomain and extraterminal domain (BET) proteins has achieved great success. For instance, the bromodomain inhibitor JQ1 has been shown to inhibit the growth of several cancer cells both in vitro and in vivo. Herein we demonstrated that JQ1 significantly inhibited chondrosarcoma cell growth and colony formation...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28053098/the-viral-bcl-2-homologs-of-kaposi-s-sarcoma-associated-herpesvirus-and-rhesus-rhadinovirus-share-an-essential-role-for-viral-replication
#20
Antonio Gallo, Melanie Lampe, Thomas Günther, Wolfram Brune
: KS-Bcl-2 is a Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral Bcl-2 homolog (vBcl-2), which has apoptosis and autophagy inhibiting activity when expressed in transfected cells. However, little is known about its function during viral infection. As KS-Bcl-2 is expressed during the lytic replication cycle, we used constitutively lytic and inducible-lytic KSHV mutants to investigate the role of KS-Bcl-2 during the lytic cycle. We show that KSHV cannot complete the lytic replication cycle and produce infectious progeny in the absence of KS-Bcl-2, indicating that the protein is essential for KSHV replication...
January 4, 2017: Journal of Virology
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