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https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#1
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27913220/mapk-erk-activity-is-required-for-the-successful-progression-of-mitosis-in-sea-urchin-embryos
#2
Mulner-Lorillon Odile, Chassé Héloïse, Morales Julia, Bellé Robert, Cormier Patrick
Using sea urchin embryos, we demonstrate that the MEK/MAPK/ERK cascade is essential for the proper progression of the cell cycle. Activation of a limited fraction of MAPK/ERK is required between S-phase and M-phase. Neither DNA replication nor CDK1 activation are impacted by the inhibition of this small active MAPK/ERK fraction. Nonetheless, the chromatin and spindle organisations are profoundly altered. Early morphological disorders induced by the absence of MAPK/ERK activation are correlated with an important inhibition of global protein synthesis and modification in the cyclin B accumulation profile...
November 29, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27909289/hyperthermia-enhances-17-dmag-efficacy-in-hepatocellular-carcinoma-cells-with-aggravated-dna-damage-and-impaired-g2-m-transition
#3
Zhizhou Huang, Xueqiong Zhou, Yangfan He, Xiangyu Ke, Ying Wen, Fei Zou, Xuemei Chen
Due to the lack of effective treatment, hepatocellular carcinoma (HCC) is one of the malignancies with low survival rates worldwide. Combination of hyperthermia and chemotherapy has shown promising results in several abdominal tumours, but high expression of HSP90 in tumours attenuated the efficacy of hyperthermia. Thus a combination of hyperthermia and inhibition of HSP90 might be a feasible therapeutic strategy for HCC. One hepatic cell line (L02) and two HCC cell lines (Huh7 and HepG2) were heated at 42 °C for 0, 0...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906621/isolation-of-a-novel-protein-p12-from-adult-drosophila-melanogaster-that-inhibits-deoxyribonucleoside-and-protein-kinase-activities-and-activates-3-5-exonuclease-activity
#4
Louise Slot Christiansen, Gabriella van Zanten, Dvora Berenstein, Marianne Lauridsen, Søren Kjærulff, Leif Søndergaard, Birgitte Munch-Petersen
We have previously found that Drosophila melanogaster only has one deoxyribonucleoside kinase, Dm-dNK, however, capable to phosphorylate all four natural deoxyribonucleosides. Dm-dNK was originally isolated from an embryonic cell line. We wanted to study the expression of Dm-dNK during development from embryonic cells to adult flies and found declining Dm-dNK activity during development and no activity in adult flies. Surprisingly, the extract from adult flies exhibited a strong inhibitory effect on deoxyribonucloside kinase activity...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27889260/two-bistable-switches-govern-m-phase-entry
#5
Satoru Mochida, Scott Rata, Hirotsugu Hino, Takeharu Nagai, Béla Novák
The abrupt and irreversible transition from interphase to M phase is essential to separate DNA replication from chromosome segregation. This transition requires the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these switch-like phosphorylations to the auto-activation of Cdk1:CycB through the removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive feedback in Cdk1 activation creates a bistable switch that makes mitotic commitment irreversible [2-4]...
November 15, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27885657/cdc25b-is-involved-in-the-centrosomal-microtubule-nucleation-in-two-cell-stage-mouse-embryos
#6
Cheng Cui, Tianxia Zang, Yu Cao, Xin Qin, Xuewei Zhang
CDC25B has been demonstrated to activate the complex of CDK1/Cyclin B and trigger mitosis. We have recently demonstrated that p-CDC25B-Ser351 is located at the centrosomes of mouse oocytes and contributes to the release of mouse oocytes from prophase I arrest. But much less is known about CDC25B function at the centrosome in two-cell stage mouse embryos. Here we investigate the effect of CDC25B regulating the microtubules nucleation. Microinjection of anti-CDC25B antibody caused aberrant microtubule nucleation...
November 25, 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27876123/blm-germline-and-somatic-pkmyt1-and-ahcy-mutations-genetic-variations-beyond-mycn-and-prognosis-in-neuroblastoma
#7
E M Novak, N S Halley, T M Gimenez, A Rangel-Santos, A M P Azambuja, M Brumatti, P L Pereira, C S C Vince, R R Giorgi, I Bendit, L M Cristofani, V Odone-Filho
Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and often lethal in childhood. Clinical and biologic characteristics that are independently prognostic of outcome in NB are currently used for risk stratification to optimally the therapy. It includes age at diagnosis, International Neuroblastoma Staging System tumor histopathology and MYCN amplification. However, even in patients with theoretically good prognosis, such as localized tumor and non-amplified MYCN, either disease progress or recurrence may occur...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27863441/sulforaphane-inhibits-proliferation-and-invasive-activity-of-everolimus-resistant-kidney-cancer-cells-in-vitro
#8
Eva Juengel, Sebastian Maxeiner, Jochen Rutz, Saira Justin, Frederik Roos, Wael Khoder, Igor Tsaur, Karen Nelson, Wolf O Bechstein, Axel Haferkamp, Roman A Blaheta
Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27857970/bora-dependent-plk1-regulation-a-new-weapon-for-cancer-therapy
#9
Luca Cirillo, Yann Thomas, Lionel Pintard, Monica Gotta
The mitotic kinase polo like kinase 1 (PLK1) is overexpressed in many cancers and its inhibition slows down proliferation and increases apoptosis in cancer cell lines. Understanding how PLK1 is activated is therefore crucial for the development of novel PLK1 inhibitors with anticancer properties. We recently identified a conserved regulatory loop leading to PLK1 activation that involves cyclin-dependent kinase 1 (CDK1).
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27856242/1-25-oh-2d3-induced-interaction-of-vitamin-d-receptor-with-p50-subunit-of-nf-%C3%AE%C2%BAb-suppresses-the-interaction-between-klf5-and-p50-contributing-to-inhibition-of-lps-induced-macrophage-proliferation
#10
Dong Ma, Ruo-Nan Zhang, Ya Wen, Wei-Na Yin, Disi Bai, Guo-Ying Zheng, Jin-Shui Li, Bin Zheng, Jin-Kun Wen
KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)2D3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27848884/understanding-the-structural-basis-for-inhibition-of-cyclin-dependent-kinases-new-pieces-in-the-molecular-puzzle
#11
Nayara M Bernhardt Levin, Val Oliveira Pintro, Maurício Boff de Ávila, Bruna Boldrini de Mattos, Walter F De Azevedo
BACKGROUND: Cyclin-dependent kinases (CDKs) comprise an important protein family for development of drugs, mostly aimed for use in treatment of cancer but there is also potential for development of drugs for neurodegenerative diseases and diabetes. Since the early 1990s, structural studies have been carried out on CDKs, in order to determine the structural basis for inhibition of this protein target. OBJECTIVE: Our goal here is to review recent structural studies focused on CDKs...
November 16, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27847202/ethyl-acetate-extract-of-peperomia-tetraphylla-induces-cytotoxicity-cell-cycle-arrest-and-apoptosis-in-lymphoma-u937-cells
#12
Dayong Yu, Xiuxiu Yang, Xuan Lu, Liying Shi, Baomin Feng
The current study evaluated the cytotoxicity and the mechanism of apoptotic induction by Peperomia tetraphylla in U937 lymphoma cells. The results showed that P. tetraphylla ethyl acetate extract (EAEPT) inhibited the cell growth in U937 cells by MTT assay. After the U937 cells were treated with EAEPT, the cells exhibited marked morphological features of apoptosis (Hoechst 33342 staining) and the number of apoptotic cell (Annexin V-FITC/PI staining) increased. The treatment of EAEPT could induce loss of mitochondrial membrane potential (MMP) and increase the ROS level...
November 12, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27846394/restoring-p53-function-in-human-melanoma-cells-by-inhibiting-mdm2-and-cyclin-b1-cdk1-phosphorylated-nuclear-iaspp
#13
Min Lu, Hilde Breyssens, Victoria Salter, Shan Zhong, Ying Hu, Caroline Baer, Indrika Ratnayaka, Alex Sullivan, Nicholas R Brown, Jane Endicott, Stefan Knapp, Benedikt M Kessler, Mark R Middleton, Christian Siebold, E Yvonne Jones, Elena V Sviderskaya, Jonathan Cebon, Thomas John, Otavia L Caballero, Colin R Goding, Xin Lu
No abstract text is available yet for this article.
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27836197/design-facile-synthesis-and-biological-evaluations-of-novel-pyrano-3-2-a-phenazine-hybrid-molecules-as-antitumor-agents
#14
Yuanyuan Lu, Yuru Yan, Linlin Wang, Xiaobing Wang, Jing Gao, Tao Xi, Zhixiang Wang, Feng Jiang
A series of novel pyrano[3,2-a]phenazine derivatives (1a-1r and 2a-2q), designed as hybrid molecules of phenazine and pyran pharmocophores, were facilely synthesized in two steps with 77-93% overall yields in this study. Cytotoxic evaluation indicates that many compounds exhibited cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compounds 1c, 1i, 2e, and 2l were found to have excellent antiproliferative activity against the HepG2 cancer cell line. Thus, inhibitory effect of subcutaneously implanted xenografted mice in vivo (H22H8D8 cells) of the four compounds as well as topoisomerase I and IIα inhibitory activities in vitro (HepG2 cells) were determined...
November 3, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27835911/prognostic-and-predictive-values-of-cdk1-and-mad2l1-in-lung-adenocarcinoma
#15
Yuan-Xiang Shi, Tao Zhu, Ting Zou, Wei Zhuo, Yi-Xin Chen, Ma-Sha Huang, Wei Zheng, Chen-Jing Wang, Xi Li, Xiao-Yuan Mao, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu
Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835685/light-tnfsf14-increases-the-survival-and-proliferation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#16
Sook-Kyoung Heo, Eui-Kyu Noh, Gi-Dong Gwon, Jeong Yi Kim, Jae-Cheol Jo, Yunsuk Choi, SuJin Koh, Jin Ho Baek, Young Joo Min, Hawk Kim
LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT...
2016: PloS One
https://www.readbyqxmd.com/read/27832629/inhibition-of-erk1-2-signaling-pathway-is-involved-in-melatonin-s-antiproliferative-effect-on-human-mg-63-osteosarcoma-cells
#17
Lifeng Liu, Ying Xu, Russel J Reiter, Yutao Pan, Di Chen, Yangzhou Liu, Xingyu Pu, Liguo Jiang, Zengchun Li
BACKGROUND: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. AIMS: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. METHODS/RESULTS: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27831832/silencing-of-cdk2-but-not-cdk1-separates-mitogenic-from-anti-apoptotic-signaling-sensitizing-p53-defective-cells-for-synthetic-lethality
#18
Tatyana S Nekova, Susanne Kneitz, Hermann Einsele, Ralf Bargou, Gernot Stuhler
Small molecule inhibitors targeting CDK1/CDK2 have been clinically proven effective against a variety of tumors, albeit at the cost of profound off target toxicities. To separate potential therapeutic from toxic effects, we selectively knocked down CDK1 or CDK2 in p53 mutated HACAT cells by siRNA silencing. Using dynamic, cell cycle wide proteome arrays, we observed minor changes in overall abundance of proteins critically involved in cell cycle transition despite profound G2/M or G1/S arrest, respectively...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27831827/mitotic-entry-the-interplay-between-cdk1-plk1-and-bora
#19
Alfonso Parrilla, Luca Cirillo, Yann Thomas, Monica Gotta, Lionel Pintard, Anna Santamaria
Polo-like kinase 1 (Plk1) is an important mitotic kinase that is crucial for entry into mitosis after recovery from DNA damage-induced cell cycle arrest. Plk1 activation is promoted by the conserved protein Bora (SPAT-1 in C. elegans), which stimulates the phosphorylation of a conserved residue in the activation loop by the Aurora A kinase. In a recent article published in Cell Reports, we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation. We identified 3 conserved Sp/Tp residues that are located in the N-terminal, most conserved part, of SPAT-1/Bora...
November 10, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27816812/a-transcriptome-based-perspective-of-cell-cycle-regulation-in-dinoflagellates
#20
David Morse, Philip Daoust, Siham Benribague
Dinoflagellates are a group of unicellular and generally marine protists, of interest to many because of their ability to form the large algal blooms commonly called "red tides". The large algal concentrations in these blooms require sustained cell replication, yet to date little is known about cell cycle regulation in these organisms. To address this issue, we have screened the transcriptomes of two dinoflagellates, Lingulodinium polyedrum and Symbiodinium sp., with budding yeast cell cycle pathway components...
October 17, 2016: Protist
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