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https://www.readbyqxmd.com/read/29789652/small-hypoxia-primed-mesenchymal-stem-cells-attenuate-graft-versus-host-disease
#1
YongHwan Kim, Hye Jin Jin, Jinbeom Heo, Hyein Ju, Hye-Yeon Lee, Sujin Kim, Seungun Lee, Jisun Lim, Sang Young Jeong, JiHye Kwon, Miyeon Kim, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Hyun Ho Hwang, Hwan Yeul Yu, Chae-Min Ryu, Hong Bae Jeon, Dong-Myung Shin
Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation...
May 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29780443/separase-inhibitor-sepin-1-inhibits-foxm1-expression-and-breast-cancer-cell-growth
#2
Nenggang Zhang, Debananda Pati
Sepin-1, a potent non-competitive inhibitor of separase, inhibits cancer cell growth, but the mechanisms of Sepin-1-mediated growth inhibition are not fully understood. Here we report that Sepin-1 hinders growth of breast cancer cells, cell migration, and wound healing. Inhibition of cell growth induced by Sepin-1 in vitro doesn't appear to be through apoptosis but rather due to growth inhibition. Following Sepin-1 treatment caspases 3 and 7 are not activated and Poly (ADP-ribose) polymerase (Parp) is not cleaved...
2018: Journal of Cancer Science & Therapy
https://www.readbyqxmd.com/read/29774081/g9a-stimulates-crc-growth-by-inducing-p53-lys373-dimethylation-dependent-activation-of-plk1
#3
Jie Zhang, Yafang Wang, Yanyan Shen, Pengxing He, Jian Ding, Yi Chen
Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a...
2018: Theranostics
https://www.readbyqxmd.com/read/29773584/mechanisms-in-endocrinology-cell-cycle-regulation-in-adrenocortical-carcinoma
#4
Sofia Pereira, Mariana P Monteiro, Isabelle Bourdeau, Andre Lacroix, Duarte Pignatelli
Adrenocortical carcinomas are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers...
May 17, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29771424/knockdown-of-plk1-inhibits-invasion-and-promotes-apoptosis-in-glioma-cells-through-regulating-autophagy
#5
Z-Y Wu, N Wei
OBJECTIVE: Polo like kinase 1 (PLK1), an oncogene, is a ubiquitously expressed serine/threonine protein kinase. We aimed at investigating the role of PLK1 in glioma. PATIENTS AND METHODS: Clinical glioma specimens were obtained from Zhejiang Hospital (Hangzhou, Zhejiang, China). The mRNA and protein levels of PLK1 in glioma tissues and different glioma cells were analyzed by Real-time PCR and Western blot, respectively. The expression of PLK1 protein in glioma tissues was also determined by immunohistochemistry staining...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29767505/tuned-density-of-anti-tissue-factor-antibody-fragment-onto-sirna-loaded-polyion-complex-micelle-for-optimizing-targetability-into-pancreatic-cancer-cells
#6
Hyun Su Min, Hyun Jin Kim, Jooyeon Ahn, Mitsuru Naito, Kotaro Hayashi, Kazuko Toh, Beob Soo Kim, Yasuhiro Matsumura, Ick Chan Kwon, Kanjiro Miyata, Kazunori Kataoka
Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) (PEG) and poly(L-lysine) (PLL), and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified anti-human tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic (FCS) analysis revealed that 1, 2, or 3 molecule(s) of Fab'(s) were installed onto one micellar nanoparticle according to the feeding ratio of Fab' (or DBCO) to micelle (or azide)...
May 16, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29765534/bi2536-induces-mitotic-catastrophe-and-radiosensitization-in-human-oral-cancer-cells
#7
Chieh-Yuan Cheng, Chung-Ji Liu, Yu-Chuen Huang, Shu-Hua Wu, Hsu-Wei Fang, Yu-Jen Chen
BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764989/global-assessment-of-its-network-dynamics-reveals-that-the-kinase-plk1-inhibits-the-phosphatase-pp6-to-promote-aurora-a-activity
#8
Arminja N Kettenbach, Kate A Schlosser, Scott P Lyons, Isha Nasa, Jiang Gui, Mark E Adamo, Scott A Gerber
Polo-like kinase 1 (Plk1) is an essential protein kinase that promotes faithful mitotic progression in eukaryotes. The subcellular localization and substrate interactions of Plk1 are tightly controlled and require its binding to phosphorylated residues. To identify phosphorylation-dependent interactions within the Plk1 network in human mitotic cells, we performed quantitative proteomics on HeLa cells cultured with kinase inhibitors or expressing a Plk1 mutant that was deficient in phosphorylation-dependent substrate binding...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29755309/targeted-delivery-of-crispr-cas9-mediated-cancer-gene-therapy-via-liposome-templated-hydrogel-nanoparticles
#9
Zeming Chen, Fuyao Liu, Yanke Chen, Jun Liu, Xiaoying Wang, Ann T Chen, Gang Deng, Hongyi Zhang, Jie Liu, Zhangyong Hong, Jiangbing Zhou
Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core-shell nanostructure, liposome-templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported...
December 8, 2017: Advanced Functional Materials
https://www.readbyqxmd.com/read/29753186/combination-of-pi3k-akt-pathway-inhibition-and-plk1-depletion-can-enhance-chemosensitivity-to-gemcitabine-in-pancreatic-carcinoma
#10
Yonghuan Mao, Ling Xi, Quan Li, Sheng Wang, Zeling Cai, Xinhua Zhang, Chunzhao Yu
The prognosis of pancreatic cancer (PC) remains pessimistic because of the difficulty in early diagnosis as well as the little advance in chemotherapy. Although being the first-line chemotherapy drug for PC at present, gemcitabine still has some disadvantages, such as low drug sensitivity and significant side effects. Thus, how to further improve the sensitivity of PC cells to gemcitabine is still a difficult subject in the field of pancreatic cancer-treatment. Polo-like kinase 1 (Plk1) is closely related to poor outcome in many malignant tumors and its high expression is linked to chemoresistance in PC...
May 9, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29743530/iaspp-pp1-complex-is-required-for-cytokinetic-abscission-by-controlling-cep55-dephosphorylation
#11
Kun Gao, Yuanyuan Zhang, Qing Shi, Jianong Zhang, Liang Zhang, Huiru Sun, Dongyue Jiao, Xiayin Zhao, Hongru Tao, Youheng Wei, Yuqi Wang, Hexige Saiyin, Shi-Min Zhao, Yao Li, Pingzhao Zhang, Chenji Wang
Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the apoptosis-stimulating proteins of p53 (ASPP) family, is required for proper cell division. iASPP depletion results in abnormal midbody structure and failed cytokinesis. We used protein affinity purification methods to identify the functional partners of iASPP...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29728556/expression-of-the-long-intergenic-non-protein-coding-rna-665-linc00665-gene-and-the-cell-cycle-in-hepatocellular-carcinoma-using-the-cancer-genome-atlas-the-gene-expression-omnibus-and-quantitative-real-time-polymerase-chain-reaction
#12
Dong-Yue Wen, Peng Lin, Yu-Yan Pang, Gang Chen, Yun He, Yi-Wu Dang, Hong Yang
BACKGROUND Long non-coding RNAs (lncRNAs) have a role in physiological and pathological processes, including cancer. The aim of this study was to investigate the expression of the long intergenic non-protein coding RNA 665 (LINC00665) gene and the cell cycle in hepatocellular carcinoma (HCC) using database analysis including The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and quantitative real-time polymerase chain reaction (qPCR). MATERIAL AND METHODS Expression levels of LINC00665 were compared between human tissue samples of HCC and adjacent normal liver, clinicopathological correlations were made using TCGA and the GEO, and qPCR was performed to validate the findings...
May 5, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29716963/plk1-inhibition-enhances-the-efficacy-of-bet-epigenetic-reader-blockade-in-castration-resistant-prostate-cancer
#13
Fengyi Mao, Jie Li, Qian Luo, Ruixin Wang, Yifan Kong, Colin Carlock, Zian Liu, Bennett D Elzey, Xiaoqi Liu
Polo-like kinase 1 (Plk1), a crucial regulator of cell cycle progression, is overexpressed in multiple types of cancers, and has been proven to be a potent and promising target for cancer treatment. In case of prostate cancer, we once showed that anti-neoplastic activity of Plk1 inhibitor is largely due to inhibition of androgen receptor (AR) signaling. However, we also discovered that Plk1 inhibition causes activation of the β-catenin pathway and increased ex-pression of c-Myc, eventually resulting in resistance to Plk1 inhibition...
May 1, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29710485/stimulation-of-klf14-plk1-pathway-by-thrombin-signaling-potentiates-endothelial-dysfunction-in-type-2-diabetes-mellitus
#14
Jun-Sheng Hao, Chao-Juan Zhu, Bin-Yuan Yan, Chang-You Yan, Rui Ling
Type 2 diabetes mellitus (T2DM) promotes a high oxidative stress and hypercoagulable state that drives microvascular injury and multiple-organ abnormality. Elevated thrombin activity underlies T2DM-linked endothelial dysfunction, but the mechanistic links between T2DM/oxidative stress axis and thrombin-associated endothelial pathologies are incompletely understood. In this work, immunohistochemical studies and quantitative analysis using isolated endothelial cells (ECs) identified accumulated Kru¨ppel-like family of transcription factor 14 (KLF14) deposits in ECs from multiple organs as distinct features of T2DM mice...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29687822/probing-the-nanoparticle-ago2-interaction-for-enhanced-gene-knockdown
#15
Sonal Deshpande, Neetu Singh
RNAi is emerging as a promising technology for treatment of various diseases due to its ability to silence specific target genes. To date, a number of nanoparticle based formulations have been reported for the delivery of small interfering RNA (siRNA), with continuous modifications in the nanoparticle design for enhancing their efficiency. While majority of the design aspects are focused on avoiding or overcoming endosomal entrapment, limited studies are available that address the role of interaction of nanoparticles with the RNA induced silencing complex (RISC) machinery, which is a crucial aspect deciding the outcome...
April 24, 2018: Soft Matter
https://www.readbyqxmd.com/read/29686087/nonviral-gene-editing-via-crispr-cas9-delivery-by-membrane-disruptive-and-endosomolytic-helical-polypeptide
#16
Hong-Xia Wang, Ziyuan Song, Yeh-Hsing Lao, Xin Xu, Jing Gong, Du Cheng, Syandan Chakraborty, Ji Sun Park, Mingqiang Li, Dantong Huang, Lichen Yin, Jianjun Cheng, Kam W Leong
Effective and safe delivery of the CRISPR/Cas9 gene-editing elements remains a challenge. Here we report the development of PEGylated nanoparticles (named P-HNPs) based on the cationic α-helical polypeptide poly(γ-4-((2-(piperidin-1-yl)ethyl)aminomethyl)benzyl-l-glutamate) for the delivery of Cas9 expression plasmid and sgRNA to various cell types and gene-editing scenarios. The cell-penetrating α-helical polypeptide enhanced cellular uptake and promoted escape of pCas9 and/or sgRNA from the endosome and transport into the nucleus...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29682766/non-cell-cycle-functions-of-the-cdk-network-in-ciliogenesis-recycling-the-cell-cycle-oscillator
#17
REVIEW
Liliana Krasinska, Daniel Fisher
Cyclin-dependent kinases are Ser/Thr protein kinases best known for their cell cycle roles, where CDK1 triggers mitotic onset in all eukaryotes. CDKs are also involved in various other cellular processes, some of which, such as transcription and centrosome duplication, are coupled to cell cycle progression. A new study suggests that the mitotic CDK network is active at low levels in non-dividing, differentiating precursors of multiciliated cells, and that it drives ciliogenesis. Manipulating the activity of CDK1 or PLK1 altered transitions between the amplification, growth, and disengagement phases, in a manner analogous to the control of passage through different phases of mitosis...
April 23, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29679654/the-vanillin-derivative-6-bromine-5-hydroxy-4-methoxybenzaldehyde-induces-aberrant-mitotic-progression-and-enhances-radio-sensitivity-accompanying-suppression-the-expression-of-plk1-in-esophageal-squamous-cell-carcinoma
#18
Meng-Meng Gu, Ming Li, Dexuan Gao, Lang-Huan Liu, Yue Lang, Si-Ming Yang, Hongling Ou, Bo Huang, Ping-Kun Zhou, Zeng-Fu Shang
Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase...
April 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#19
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29658607/key-signaling-pathways-genes-and-transcription-factors-associated-with-hepatocellular-carcinoma
#20
Jingcheng Wang, Yang Tian, Hui Chen, Hui Li, Shusen Zheng
The purpose of the present study was to investigate the underlying molecular mechanism of hepatocellular carcinoma (HCC) using bioinformatics approaches. The microarray dataset GSE64041 was downloaded from the Gene Expression Omnibus database, which included 60 tumor liver samples and 60 matched control samples. Differentially expressed genes (DEGs) between HCC and control groups were identified. Then functional enrichment analyses, protein‑protein interaction (PPI) network, sub‑network and integrated transcription factor (TF)‑microRNA (miRNA)‑target network analyses were performed for these DEGs...
April 12, 2018: Molecular Medicine Reports
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