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https://www.readbyqxmd.com/read/28638452/targeting-tpx2-suppresses-the-tumorigenesis-of-hepatocellular-carcinoma-cells-resulting-in-arrested-mitotic-phase-progression-and-increased-genomic-instability
#1
Chao-Wen Hsu, Yu-Chia Chen, Hsing-Hao Su, Guan-Jin Huang, Chih-Wen Shu, Tony Tong-Lin Wu, Hung-Wei Pan
Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28622684/the-association-between-mad2-and-prognosis-in-cancer-a%C3%A2-systematic-review-and-meta-analyses
#2
Tara Byrne, Helen G Coleman, Janine A Cooper, W Glenn McCluggage, Amanda McCann, Fiona Furlong
This systematic review and meta-analyses investigates the expression of the cell checkpoint regulator, mitotic arrest deficiency protein 2 (MAD2) in cancerous tissue and examines whether an association exists between MAD2 levels and cancer survival and recurrence. Studies investigating MAD2 expression in cancer tissue utilising immunohistochemistry (IHC) were identified by systematic literature searches of Medline, Embase and Web of Science databases by October 2015. Random effects meta-analyses were performed to generate pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of overall and progression-free survival according to MAD2 expression...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619818/antagonistic-regulation-of-the-second-mitotic-wave-by-eyes-absent-sine-oculis-and-combgap-coordinates-proliferation-and-specification-in-the-drosophila-retina
#3
Trevor L Davis, Ilaria Rebay
The transition from proliferation to specification is fundamental to the development of appropriately patterned tissues. In the developing Drosophila eye, Eyes absent (Eya) and Sine oculis (So) orchestrate the progression of progenitor cells from asynchronous cell division to G1 arrest and neuronal specification at the morphogenetic furrow. Here, we uncover a novel role for Eya and So in promoting cell cycle exit in the Second Mitotic Wave (SMW), a synchronized, terminal cell division that occurs several hours after passage of the furrow...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28609167/hdr-brachytherapy-decreases-proliferation-rate-and-cellular-progression-of-a-radioresistant-human-squamous-cell-carcinoma-in-vitro
#4
Jony M Geraldo, Sérgio Scalzo, Daniela S Reis, Thiago L Leão, Silvia Guatimosim, Luiz O Ladeira, Lídia M Andrade
PURPOSE: To investigate the effects of HDR brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters. MATERIALS AND METHODS: An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated two times up to 1100cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay...
June 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28607478/precocious-centriole-disengagement-and-centrosome-fragmentation-induced-by-mitotic-delay
#5
Menuka Karki, Neda Keyhaninejad, Charles B Shuster
The spindle assembly checkpoint (SAC) delays mitotic progression until all sister chromatid pairs achieve bi-orientation, and while the SAC can maintain mitotic arrest for extended periods, moderate delays in mitotic progression have significant effects on the resulting daughter cells. Here we show that when retinal-pigmented epithelial (RPE1) cells experience mitotic delay, there is a time-dependent increase in centrosome fragmentation and centriole disengagement. While most cells with disengaged centrioles maintain spindle bipolarity, clustering of disengaged centrioles requires the kinesin-14, HSET...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28605876/e2f8-confers-cisplatin-resistance-to-er-breast-cancer-cells-via-transcriptionally-activating-mastl
#6
Jianjun Tian, Yuting Lin, Jianhua Yu
MASTL (microtubule-associated serine/threonine kinase-like) is a critical kinase modulating mitotic entry. In this study, we investigated the mechanism of its dysregulation in breast cancer and its involvement in cisplatin resistance in ER+ breast cancer cells. Data mining in Kaplan-Meier Plotter showed that high MASTL expression was associated with worse distant metastasis free survival (DMFS) and relapse free survival (RFS) in ER+ breast cancer patients. In TCGA breast cancer cohort (TCGA-BRCA), MASTL was strongly co-upregulated with E2F8...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28602975/the-small-molecule-inhibitor-yk-4-279-disrupts-mitotic-progression-of-neuroblastoma-cells-overcomes-drug-resistance-and-synergizes-with-inhibitors-of-mitosis
#7
Madhu Kollareddy, Alice Sherrard, Ji Hyun Park, Marianna Szemes, Kelli Gallacher, Zsombor Melegh, Sebastian Oltean, Martin Michaelis, Jindrich Cinatl, Abderrahmane Kaidi, Karim Malik
Neuroblastoma is a biologically and clinically heterogeneous pediatric malignancy that includes a high-risk subset for which new therapeutic agents are urgently required. As well as MYCN amplification, activating point mutations of ALK and NRAS are associated with high-risk and relapsing neuroblastoma. As both ALK and RAS signal through the MEK/ERK pathway, we sought to evaluate two previously reported inhibitors of ETS-related transcription factors, which are transcriptional mediators of the Ras-MEK/ERK pathway in other cancers...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28596487/znf131-suppresses-centrosome-fragmentation-in-glioblastoma-stem-like-cells-through-regulation-of-haus5
#8
Yu Ding, Jacob A Herman, Chad M Toledo, Jackie M Lang, Philip Corrin, Emily J Girard, Ryan Basom, Jeffrey J Delrow, James M Olson, Patrick J Paddison
Zinc finger domain genes comprise ~3% of the human genome, yet many of their functions remain unknown. Here we investigated roles for the vertebrate-specific BTB domain zinc finger gene ZNF131 in the context of human brain tumors. We report that ZNF131 is broadly required for Glioblastoma stem-like cell (GSC) viability, but dispensable for neural progenitor cell (NPC) viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591718/riluzole-exerts-distinct-antitumor-effects-from-a-metabotropic-glutamate-receptor-1-specific-inhibitor-on-breast-cancer-cells
#9
Sonia C Dolfi, Daniel J Medina, Aparna Kareddula, Bhavna Paratala, Ashley Rose, Jatinder Dhami, Suzie Chen, Shridar Ganesan, Gillian Mackay, Alexei Vazquez, Kim M Hirshfield
Recent evidence suggests that glutamate signaling plays an important role in cancer. Riluzole is a glutamate release inhibitor and FDA-approved drug for the treatment of amyotrophic lateral sclerosis. It has been investigated as an inhibitor of cancer cell growth and tumorigenesis with the intention of repurposing it for the treatment of cancer. Riluzole is thought to act by indirectly inhibiting glutamate signaling. However, the specific effects of riluzole in breast cancer cells are not well understood. In this study, the anti-cancer effects of riluzole were explored in a panel of breast cancer cell lines in comparison to the metabotropic glutamate receptor 1-specific inhibitor BAY 36-7620...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591504/-cellular-senescence-as-a-common-denominator-in-age-related-diseases
#10
Luis Ángel Maciel-Barón, Viviana I Pérez, Carmen Torres, Viridiana Y González-Puertos, Mina Konigsberg, Norma Edith López-Diazguerrero
Cellular senescence has been traditionally characterized by cell cycle arrest of pot-mitotic cells as a response to a cellular damage. Now is known that senescent cells secret a diverse array of cytokines, chemokines, growth factors and other that altogether are called senescence associates secretory phenotype (SASP), which might have beneficial or deleterious effects on neighbor cells. This review describes those effects as well as the relationship between the SASP and several age related diseases. We also analyze the direction that recent investigations are turning in order to modulate or avoid the effect of the SASP in those pathologies...
July 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28588720/synergistic-activity-of-the-histone-deacetylase-inhibitor-trichostatin-a-and-the-proteasome-inhibitor-ps-341-against-taxane-resistant-ovarian-cancer-cell-lines
#11
Xin Jin, Yong Fang, Yi Hu, Jing Chen, Wei Liu, Gang Chen, Mei Gong, Peng Wu, Tao Zhu, Shixuan Wang, Jianfeng Zhou, Hui Wang, Ding Ma, Kezhen Li
Although a combination of platinum- and taxane-based chemotherapy is recommended for at least 70% patients with ovarian cancer as treatment subsequent to surgery, the initial response to the chemotherapy is not durable and tumors become resistant. Histone deacetylase and proteasome inhibitors are novel therapeutic agents. However, the moderate antitumoral effect of the inhibitors has restricted their clinical use when used as single agents. The aim of the present study was to investigate the synergistic activity of trichostatin A (TSA) and PS-341 in ovarian cancer cells, along with the investigation of the molecular mechanisms of taxane resistance...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28584704/cucurbitacins-elucidation-of-their-interactions-with-the-cytoskeleton
#12
Xiaojuan Wang, Mine Tanaka, Herbenya Silva Peixoto, Michael Wink
Cucurbitacins, a class of toxic tetracyclic triterpenoids in Cucurbitaceae, modulate many molecular targets. Here we investigated the interactions of cucurbitacin B, E and I with cytoskeletal proteins such as microtubule and actin filaments. The effects of cucurbitacin B, E and I on microtubules and actin filaments were studied in living cells (Hela and U2OS) and in vitro using GFP markers, immunofluorescence staining and in vitro tubulin polymerization assay. Cucurbitacin B, E and I apparently affected microtubule structures in living cells and cucurbitacin E inhibited tubulin polymerization in vitro with IC50 value of 566...
2017: PeerJ
https://www.readbyqxmd.com/read/28580168/caml-mediates-survival-of-myc-induced-lymphoma-cells-independent-of-tail-anchored-protein-insertion
#13
Jennifer C Shing, Lonn D Lindquist, Nica Borgese, Richard J Bram
Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28576750/bzml-a-novel-colchicine-binding-site-inhibitor-overcomes-multidrug-resistance-in-a549-taxol-cells-by-inhibiting-p-gp-function-and-inducing-mitotic-catastrophe
#14
Zhaoshi Bai, Meiqi Gao, Huijuan Zhang, Qi Guan, Jingwen Xu, Yao Li, Huan Qi, Zhengqiang Li, Daiying Zuo, Weige Zhang, Yingliang Wu
Multidrug resistance (MDR) interferes with the efficiency of chemotherapy. Therefore, developing novel anti-cancer agents that can overcome MDR is necessary. Here, we screened a series of colchicine binding site inhibitors (CBSIs) and found that 5-(3, 4, 5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl) imidazol (BZML) displayed potent cytotoxic activity against both A549 and A549/Taxol cells. We further explored the underlying mechanisms and found that BZML caused mitosis phase arrest by inhibiting tubulin polymerization in A549 and A549/Taxol cells...
May 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28567478/%C3%AE-iii-tubulin-enhances-efficacy-of-cabazitaxel-as-compared-with-docetaxel
#15
Gregoriy Smiyun, Olga Azarenko, Herbert Miller, Alexander Rifkind, Nichole E LaPointe, Leslie Wilson, Mary Ann Jordan
Cabazitaxel is a novel taxane approved for treatment of metastatic hormone-refractory prostate cancer in patients pretreated with docetaxel. Cabazitaxel, docetaxel, and paclitaxel bind specifically to tubulin in microtubules, disrupting functions essential to tumor growth. High levels of βIII-tubulin isotype expression are associated with tumor aggressivity and drug resistance. To understand cabazitaxel's increased efficacy, we examined binding of radio-labeled cabazitaxel and docetaxel to microtubules and the drugs' suppression of microtubule dynamic instability in vitro in microtubules assembled from purified bovine brain tubulin containing or devoid of βIII-tubulin...
May 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28562324/prolonged-mitotic-arrest-induced-by-wee1-inhibition-sensitizes-breast-cancer-cells-to-paclitaxel
#16
Cody W Lewis, Zhigang Jin, Dawn Macdonald, Wenya Wei, Xu Jing Qian, Won Shik Choi, Ruicen He, Xuejun Sun, Gordon Chan
Wee1 kinase is a crucial negative regulator of Cdk1/cyclin B1 activity and is required for normal entry into and exit from mitosis. Wee1 activity can be chemically inhibited by the small molecule MK-1775, which is currently being tested in phase I/II clinical trials in combination with other anti-cancer drugs. MK-1775 promotes cancer cells to bypass the cell-cycle checkpoints and prematurely enter mitosis. In our study, we show premature mitotic cells that arise from MK-1775 treatment exhibited centromere fragmentation, a morphological feature of mitotic catastrophe that is characterized by centromeres and kinetochore proteins that co-cluster away from the condensed chromosomes...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28562161/pp2a-b56%C3%AE-is-required-for-an-efficient-spindle-assembly-checkpoint
#17
Prajakta Varadkar, Fatima Abbasi, Kazuyo Takeda, Jade J Dyson, Brent McCright
The Spindle Assembly Checkpoint (SAC) is part of a complex feedback system designed to ensure that cells do not proceed through mitosis unless all chromosomal kinetochores have attached to spindle microtubules. The formation of the kinetochore complex and the implementation of the SAC are regulated by multiple kinases and phosphatases. BubR1 is a phosphoprotein that is part of the Cdc20 containing mitotic checkpoint complex that inhibits the APC/C so that Cyclin B1 and Securin are not degraded, thus preventing cells going into anaphase...
May 31, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28554018/in%C3%A2-vitro-evaluation-of-the-cytotoxic-and-bactericidal-mechanism-of-the-commonly-used-pesticide-triphenyltin-hydroxide
#18
Susobhan Mahanty, Darpan Raghav, Krishnan Rathinasamy
Triphenyltin hydroxide (TPTH) is a widely used pesticide that is highly toxic to a variety of organisms including humans and a potential contender for the environmental pollutant. In the present study, the cytotoxic mechanism of TPTH on mammalian cells was analyzed using HeLa cells and the antibacterial activity was analyzed using B. subtilis and E. coli cells. TPTH inhibited the growth of HeLa cells with a half-maximal inhibitory concentration of 0.25 μM and induced mitotic arrest. Immunofluorescence microscopy analysis showed that TPTH caused strong depolymerization of interphase microtubules and spindle abnormality with the appearance of colchicine type mitosis and condensed chromosome...
May 20, 2017: Chemosphere
https://www.readbyqxmd.com/read/28550050/loss-of-hippo-signaling-promotes-polyploidy-and-tumorigenesis
#19
(no author information available yet)
YAP activates AKT signaling to promote mitotic arrest, polyploidy, and hepatocellular carcinoma.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28542137/dt-13-synergistically-enhanced-vinorelbine-mediated-mitotic-arrest-through-inhibition-of-foxm1-bicd2-axis-in-non-small-cell-lung-cancer-cells
#20
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed malignant disease with the leading cause of cancer-related death. Combination treatment remains the major strategy in the clinical therapy of NSCLC. Vinorelbine (NVB), a semi-synthetic vinca alkaloid, is used for advanced and metastatic NSCLC by destabilizing microtubule formation to induce mitotic arrest and cell death. However, the side effect of NVB heavily affected its effectiveness in clinical therapy. Hence, it is of great significance to develop new agents to synergize with NVB and decrease the adverse effect...
May 25, 2017: Cell Death & Disease
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