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https://www.readbyqxmd.com/read/29232580/design-and-synthesis-of-novel-quinacrine-1-3-thiazinan-4-one-hybrids-for-their-anti-breast-cancer-activity
#1
V Raja Solomon, Sheetal Pundir, Hoang-Thanh Le, Hoyun Lee
In an attempt to develop effective and safe anticancer agents, we designed, synthesized and examined 23 novel quinacrine (QC) derivatives by combining the 9-aminoacridine scaffold and the [1,3]thiazinan-4-ones group. Most of these hybrids showed strong anticancer activities, among which 3-(3-(6-chloro-2-methoxyacridin-9-ylamino)propyl)-2-(thiophen-2-yl)-1,3-thiazinan-4-one (25; VR151) effectively killed many different cancer cell types, including eight breast cancer cell lines with different genetic background, two prostate cancer and two lung cancer cell lines...
December 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232554/genomic-aberrations-that-activate-d-type-cyclins-are-associated-with-enhanced-sensitivity-to-the-cdk4-and-cdk6-inhibitor-abemaciclib
#2
Xueqian Gong, Lacey M Litchfield, Yue Webster, Li-Chun Chio, Swee Seong Wong, Trent R Stewart, Michele Dowless, Jack Dempsey, Yi Zeng, Raquel Torres, Karsten Boehnke, Cecilia Mur, Carlos Marugán, Carmen Baquero, Chunping Yu, Steven M Bray, Isabella H Wulur, Chen Bi, Shaoyou Chu, Hui-Rong Qian, Philip W Iversen, Farhana F Merzoug, Xiang S Ye, Christoph Reinhard, Alfonso De Dios, Jian Du, Charles W Caldwell, María José Lallena, Richard P Beckmann, Sean G Buchanan
Most cancers preserve functional retinoblastoma (Rb) and may, therefore, respond to inhibition of D-cyclin-dependent Rb kinases, CDK4 and CDK6. To date, CDK4/6 inhibitors have shown promising clinical activity in breast cancer and lymphomas, but it is not clear which additional Rb-positive cancers might benefit from these agents. No systematic survey to compare relative sensitivities across tumor types and define molecular determinants of response has been described. We report a subset of cancers highly sensitive to CDK4/6 inhibition and characterized by various genomic aberrations known to elevate D-cyclin levels and describe a recurrent CCND1 3'UTR mutation associated with increased expression in endometrial cancer...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232548/genomic-biomarkers-predicting-response-to-selective-cdk4-6-inhibition-progress-in-an-elusive-search
#3
Geoffrey I Shapiro
In this issue of Cancer Cell, Gong et al. have analyzed the sensitivity of 560 cell lines to the selective CDK4/6 inhibitor abemaciclib and have defined cancers with specific genomic "D-cyclin activating features (DCAF)" as particularly vulnerable. These findings will facilitate patient selection as development of this drug class continues.
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232009/effect-of-the-wnt-%C3%AE-catenin-signaling-pathway-on-apoptosis-migration-and-invasion-of-transplanted-hepatocellular-carcinoma-cells-after-transcatheter-arterial-chemoembolization-in-rats
#4
Bao-Ming Wang, Nuo Li
This study aims to investigate the influence of the Wnt/β-catenin signaling pathway on apoptosis, migration and invasion of transplanted hepatocellular carcinoma (HCC) cells after transcatheter arterial chemoembolization (TACE) in rat models. A total of 60 rats were grouped into sham, TACE, Wnt-C59 and TACE + Wnt-C59 groups (n = 20). Ten days after model establishment, 10 rats in each group were executed to perform pathological examination and follow-up experiment, and the remaining 10 rats in each group were reared to observe the survival condition...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29231992/hcfu-inhibits-cervical-cancer-cells-growth-and-metastasis-by-inactivating-wnt-%C3%AE-catenin-pathway
#5
Ping Liu, Shuying Ma, Hua Liu, Huazhen Han, Shanshan Wang
BACKGROUND: 1-hexylcarbamoyl-5-fluorouracil (HCFU), also known as carmofur, is an effective chemotherapeutic agent applied to several cancers. This study was aimed to explore the functional effects of HCFU on cervical cancer cells and tried to uncover its possible mechanism. METHODS: Two immortalized cervical cancer cell lines (HeLa and Caski) and primary cervical cancer cells prepared from two cervical cancer patients were used in this study. Cell viability, apoptosis, colony formation, migration, invasion, and the expressions of cell growth- and metastasis-associated factors were respectively assessed following 0-1 µg/mL of HCFU treatment for 0-48 h...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29230669/p21waf1-cip1-and-p27kip1-are-correlated-with-the-development-and-invasion-of-prolactinoma
#6
Wei Dong, Jianhua Li, Qian Liu, Chunhui Liu, Chuzhong Li, Guidong Song, Haibo Zhu, Hua Gao, Yazhuo Zhang
Cell cycle control can prevent excessive proliferative response in the pituitary homeostasis. Cyclin dependent kinases (Cdks) are modulated by cyclins or Cdk inhibitors, such as p21 and p27, which can regulate cell cycle progression from the G1 to S phases. This study was conducted to evaluate the levels and the promoter region methylation status of p21 and p27 in prolactinomas (PRL) and analyze their association with clinicopathologic features. We found high-p21 level cases were featured by 5/23 and H-scores 142...
December 11, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29229992/mirna-21-ablation-protects-against-liver-injury-and-necroptosis-in-cholestasis
#7
Marta B Afonso, Pedro M Rodrigues, André L Simão, Maria M Gaspar, Tânia Carvalho, Paula Borralho, Jesús M Bañales, Rui E Castro, Cecília M P Rodrigues
Inhibition of microRNA-21 (miR-21) prevents necroptosis in the mouse pancreas. Necroptosis contributes to hepatic necro-inflammation in the common bile duct ligation (BDL) murine model. We aimed to evaluate the role of miR-21 in mediating deleterious processes associated with cholestasis. Mechanistic studies established a functional link between miR-21 and necroptosis through cyclin-dependent kinase 2-associated protein 1 (CDK2AP1). miR-21 expression increased in the liver of primary biliary cholangitis (PBC) patients and BDL wild-type (WT) mice at both 3 and 14 days...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229991/bok-promotes-chemical-induced-hepatocarcinogenesis-in-mice
#8
Tatiana Rabachini, Yuniel Fernandez-Marrero, Matteo Montani, Giulio Loforese, Valentina Sladky, Zhaoyue He, Daniel Bachmann, Simone Wicki, Andreas Villunger, Deborah Stroka, Thomas Kaufmann
BCL-2-related ovarian killer (BOK) is a conserved and widely expressed BCL-2 family member with sequence homology to pro-apoptotic BAX and BAK, but with poorly understood pathophysiological function. Since several members of the BCL-2 family are critically involved in the regulation of hepatocellular apoptosis and carcinogenesis we aimed to establish whether loss of BOK affects diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Short-term exposure to DEN lead to upregulation of BOK mRNA and protein in the liver...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229926/cell-cycle-dependent-phosphorylation-regulates-recql4-pathway-choice-and-ubiquitination-in-dna-double-strand-break-repair
#9
Huiming Lu, Raghavendra A Shamanna, Jessica K de Freitas, Mustafa Okur, Prabhat Khadka, Tomasz Kulikowicz, Priscella P Holland, Jane Tian, Deborah L Croteau, Anthony J Davis, Vilhelm A Bohr
Pathway choice within DNA double-strand break (DSB) repair is a tightly regulated process to maintain genome integrity. RECQL4, deficient in Rothmund-Thomson Syndrome, promotes the two major DSB repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). Here we report that RECQL4 promotes and coordinates NHEJ and HR in different cell cycle phases. RECQL4 interacts with Ku70 to promote NHEJ in G1 when overall cyclin-dependent kinase (CDK) activity is low. During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29228681/cyclophosphamide-causes-osteoporosis-in-c57bl-6-male-mice-suppressive-effects-of-cyclophosphamide-on-osteoblastogenesis-and-osteoclastogenesis
#10
Dongfeng Zhao, Chenglong Wang, Yongjian Zhao, Bing Shu, Youji Jia, Shufen Liu, Hongshen Wang, Junli Chang, Weiwei Dai, Sheng Lu, Qi Shi, Yanping Yang, Yan Zhang, Yongjun Wang
The clinical evidence indicated that cyclophosphamide (CPD), one of the chemotherapy drugs, caused severe deteriorations in bones of cancer patients. However, the exact mechanisms by which CPD exerts effects on bone remodeling is not yet fully elucidated. Therefore, this study was performed to investigate the role and potential mechanism of CPD in osteoblastogenesis and osteoclastogenesis. Here it was found that CPD treatment (100mg/kg/day) for 7 days led to osteoporosis phenotype in male mice. CPD inhibited osteoblastogenesis as shown by decreasing the number and differentiation of bone mesenchymal stem cells (MSCs) and reducing the formation and activity of osteoblasts...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228647/timing-of-transcription-during-the-cell-cycle-protein-complexes-binding-to-e2f-e2f-cle-cde-chr-or-chr-promoter-elements-define-early-and-late-cell-cycle-gene-expression
#11
Gerd A Müller, Konstanze Stangner, Thomas Schmitt, Axel Wintsche, Kurt Engeland
A central question in cell cycle control is how differential gene expression is regulated. Timing of expression is important for correct progression through the cell cycle. E2F, CDE, and CHR promoter sites have been linked to transcriptional repression in resting cells and activation during the cell cycle. Further, the DREAM complex binds CHR or CDE/CHR elements of G2/M genes resulting in repression during G0/G1. Here, we show that DREAM also binds to E2F sites of S phase genes in quiescence and upon p53 activation...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228561/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#12
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228549/er%C3%AE-inhibits-cyclin-dependent-kinases-1-and-7-in-triple-negative-breast-cancer
#13
Jordan M Reese, Elizabeth S Bruinsma, David G Monroe, Vivian Negron, Vera J Suman, James N Ingle, Matthew P Goetz, John R Hawse
Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228085/immunolocalization-of-cd163-tumor-associated-macrophages-and-symmetric-proliferation-of-ki-67-as-biomarkers-to-differentiate-new-different-grades-of-laryngeal-dysplasia
#14
Caili Su, Shuangshuang Jia, Honggang Liu
Objectives: To evaluate CD163+ tumor-associated macrophages (TAMs), Ki-67, and cyclin D1 to differentiate laryngeal dysplasia in the 2017 World Health Organization classification. Methods: Immunohistochemistry for CD163, Ki-67, and cyclin D1 was performed using paraffin-embedded specimens. CD163+ TAMs infiltrating the epithelium were estimated. Ki-67 and cyclin D1 were evaluated in four parts of the epithelium-basal, parabasal, middle third, and upper third layers...
December 7, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29227548/resistance-of-oral-cancer-cells-to-5-ala-mediated-photodynamic-therapy
#15
Flávia Cristina Perillo Rosin, Marina Gabriela Teixeira, Cibele Pelissari, Luciana Corrêa
Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio-resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti-apoptotic proteins and those related to Akt/mTOR pathway. Sub-lethal doses of PDT were applied, consisting of a constant concentration of 5-aminolevulinic acid (5-ALA) (1 mM, 4-hour incubation) and increasing irradiation dose with LED (from 5...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29227343/golgi-fragmentation-induced-by-overactivated-cyclin-dependent-kinase-5-is-associated-with-isoflurane-induced-neurotoxicity
#16
Fang-Fang Miao, Cui-Cui Kong, Yan Wu, Long Fan, Tian-Long Wang
Overactivated cyclin-dependent kinase 5 (Cdk5) induces Golgi fragmentation, which interrupts the processing and trafficking of secretory cargo and subsequently synaptic plasticity and synaptogenesis, and even leads to neuronal cell death. Cdk5 overactivation and subsequent Golgi fragmentation are involved in many neurodegenerative diseases. However, whether isoflurane-induced neurotoxicity is relevant to aberrant Cdk5 activation and subsequent Golgi fragmentation remains unknown. In the present study, we explored the underlying molecular mechanisms of isoflurane-induced neurotoxicity in primary cultured hippocampal neurons...
December 8, 2017: Neuroreport
https://www.readbyqxmd.com/read/29227283/sharpin-mediated-regulation-of-protein-arginine-methyltransferase-5-controls-melanoma-growth
#17
Hironari Tamiya, Hyungsoo Kim, Oleksiy Klymenko, Heejung Kim, Yongmei Feng, Tongwu Zhang, Ji Yun Han, Ayako Murao, Scott J Snipas, Lucia Jilaveanu, Kevin Brown, Harriet Kluger, Hao Zhang, Kazuhiro Iwai, Ze'ev A Ronai
SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC), plays important roles in NF-κB signaling and inflammation. Here, we have demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth. We observed that SHARPIN interacted with PRMT5, a type II protein arginine methyltransferase, and increased its multiprotein complex and methyltransferase activity. Activated PRMT5 controlled the expression of the transcription factors SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the transcriptional corepressor SKI...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29226963/effect-of-cdk1-shrna-on-proliferation-migration-cell-cycle-and-apoptosis-in-non-small-cell-lung-cancer
#18
Shenglan Pu, Yan Zhao, Guoqi Zhou, Honglan Zhu, Ling Gong, Wei Zhang, Guichuan Huang, Daoxin Wang, Daishun Liu
OBJECTIVE: In this study, we aimed to investigate the effect of CDK1 shRNA on proliferation, migration, cell cycle and apoptosis in non-small cell lung cancer. METHODS: Protein expressions of CDK1 in HCC827 cells were measured by western blot. CCK-8 and clone formation assay was used to detect the growth and proliferation of cells. Wound healing assay was carried out to determine the migration ability of HCC cells in shRNA group, followed by flow cytometry, detecting the variation of HCC827 cell cycle and apoptosis...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29226311/emerging-innovative-therapeutic-approaches-leveraging-cyclin-dependent-kinase-inhibitors-to-treat-advanced-breast-cancer
#19
REVIEW
Marcelo Cruz, Tomás Reinert, Massimo Cristofanilli
No abstract text is available yet for this article.
December 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29225069/stimulation-of-b-raf-increases-c-jun-and-c-fos-expression-and-upregulates-ap-1-regulated-gene-transcription-in-insulinoma-cells
#20
Daniel S Langfermann, Oliver G Rössler, Gerald Thiel
Stimulation of pancreatic β-cells with glucose activates the protein kinases B-Raf and extracellular signal-regulated protein kinase that participate in glucose sensing. Inhibition of both kinases results in impairment of glucose-regulated gene transcription. To analyze the signaling pathway controlled by B-Raf, we expressed a conditionally active form of B-Raf in INS-1 insulinoma cells. Here, we show that stimulation of B-Raf strongly activated the transcription factor AP-1 which is accompanied by increased c-Jun and c-Fos promoter activities, an upregulation of c-Jun and c-Fos biosynthesis, and elevated transcriptional activation potentials of c-Jun and c-Fos...
December 7, 2017: Molecular and Cellular Endocrinology
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