Mouse Prkar1a Haploinsufficiency Leads to an Increase in Tumors in the Trp53+/- or Rb1+/- Backgrounds and Chemically-Induced Skin Papillomas by Dysregulation of the Cell Cycle and Wnt Signaling.

2010 ◽  
pp. OR20-3-OR20-3
Author(s):  
MQ Almeida ◽  
M Muchow ◽  
S Boikos ◽  
AJ Bauer ◽  
KJ Griffin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Chemically Induced ◽  
Skin Papillomas

scholarly journals Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/− or Rb1+/− backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling

2010 ◽  
Vol 19 (8) ◽  
pp. 1387-1398 ◽  
Author(s):  
Madson Q. Almeida ◽  
Michael Muchow ◽  
Sosipatros Boikos ◽  
Andrew J. Bauer ◽  
Kurt J. Griffin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Chemically Induced ◽  
Skin Papillomas

S1271 Plantago Ovata Husk Regulates Cell Cycle Progression and Wnt Signaling Pathway, Crucial Elements Implicated in Colorectal Carcinogenesis

2009 ◽  
Vol 136 (5) ◽  
pp. A-226
Author(s):  
Vanessa R. Sapoznik ◽  
Michael N. Grzybowski ◽  
Rosa M. Xicola ◽  
Brian J. Doyle ◽  
Jessica Grzybowski ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Wnt Signaling Pathway ◽  
Colorectal Carcinogenesis ◽  
Plantago Ovata ◽  
Cycle Progression

scholarly journals The Wnt Signaling Inhibitor Dickkopf-1 Is Required for Reentry into the Cell Cycle of Human Adult Stem Cells from Bone Marrow

2003 ◽  
Vol 278 (30) ◽  
pp. 28067-28078 ◽  
Author(s):  
Carl A. Gregory ◽  
Harpreet Singh ◽  
Anthony S. Perry ◽  
Darwin J. Prockop
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Wnt Signaling ◽  
Adult Stem Cells ◽  
Human Adult ◽  
Dickkopf 1

scholarly journals Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling

2011 ◽  
Vol 18 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Marina Shkreli ◽  
Kavita Y Sarin ◽  
Matthew F Pech ◽  
Natalia Papeta ◽  
Woody Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Cycle Entry ◽  
Adult Kidney

Chemically Induced Cell Cycle Arrest in Perfusion Cell Culture

2016 ◽  
pp. 161-176 ◽  
Author(s):  
Gabor Nagy ◽  
Bence Tanczos ◽  
Eszter Fidrus ◽  
Laszlo Talas ◽  
Gaspar Banfalvi
Keyword(s):  
Cell Cycle ◽  
Cell Culture ◽  
Cell Cycle Arrest ◽  
Perfusion Cell Culture ◽  
Cycle Arrest ◽  
Chemically Induced

scholarly journals Preclinical Perspectives on Garlic and Cancer

2006 ◽  
Vol 136 (3) ◽  
pp. 827S-831S ◽  
Author(s):  
John A. Milner
Keyword(s):  
Cell Cycle ◽  
Redox Status ◽  
Sulfur Compounds ◽  
Specific Cell ◽  
Organosulfur Compounds ◽  
Anticancer Properties ◽  
Cellular Events ◽  
Histone Hyperacetylation ◽  
Chemically Induced ◽  
Cycle Regulation

ABSTRACT Evidence continues to point to the anticancer properties of fresh garlic extracts, aged garlic, garlic oil, and a number of specific organosulfur compounds generated by processing garlic. These anticarcinogenic and antitumorigenic characteristics appear to arise through both dose- and temporal-related changes in a number of cellular events involved with the cancer process, including those involving drug metabolism, immunocompetence, cell cycle regulation, apoptosis, and angiogenesis. The ability of garlic and related allyl sulfur compounds to block tumors in the colon, lung, breast, and liver suggests general mechanisms that are not tissue specific. Whereas relatively few studies have compared the relative efficacy of water- and lipid-soluble allyl sulfur compounds, those that have when using chemically induced carcinogen models suggest little difference in response, whereas tumor proliferation/apoptosis is highly dependent on the species provided. A shift in sulfhydryl groups, alterations in glutathione:oxidized glutathione ratios, and resultant changes in cellular redox status may be involved in some of the phenotypic changes caused by allyl sulfur compounds. Such changes in thiols by allyl sulfurs may also account for the observed hyperphosphorylation of specific cell cycle proteins and the histone hyperacetylation that has been correlated with suppressed tumor cell proliferation. Whereas the anticarcinogenic and antitumorigenic data to date are impressive, additional studies are needed with more modest exposure to allyl sulfur compounds over prolonged periods. Likewise, additional studies are needed that incorporate transgenic and knockout models to assist in the identification of molecular targets for garlic and its associated allyl sulfur components.

Valproic Acid Accelerates Cell Cycle Progression of Hematopoietic Stem Cells Via the Activation of GSK3beta-Dependent Signaling Pathways.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1708-1708
Author(s):  
Gesine Bug ◽  
Hilal Gul ◽  
Kerstin Schwarz ◽  
Manuela Kampfmann ◽  
Xiaomin Zheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Valproic Acid ◽  
Wnt Signaling ◽  
Cell Cycle Progression ◽  
Beta Catenin ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Colony Assays

Abstract Histone deacetylase inhibitors (HDI) have attracted considerable attention because of their ability to overcome the differentiation block in leukemic blasts either alone, or in combination with differentiating agents such as all-trans retinoic acid (ATRA). We have previously reported favorable effects of the potent HDI valproic acid (VPA) in combination with ATRA in a small subset of patients with advanced acute myeloid leukemia (AML) leading to blast cell reduction and improvement of hemoglobin. This effect was accompanied by hypergranulocytosis most likely due to an enhancement of non-leukemic myelopoiesis and suppression of malignant hematopoiesis rather than enforced differentiation of leukemic cells. These data prompted us to investigate the impact of VPA on normal hematopoietic stem cells (HSC). Differentiation of cord blood-derived, purified CD34+ cells was assessed by FACS analysis after a 7-days suspension culture in presence of early acting cytokines and 30–150μg/mL VPA. VPA prevented differentation of CD34+ cells in a dose-dependent manner: concomitant with an increase of CD34+ cells from 17 to 47%, the proportion of monocytic CD14+ cells decreased from 27 to 3% (n=3). In addition, VPA induced a 30-fold amplification of CD34+ bone marrow (BM) cells within 10 days as determined by colony assays (n=3). To evaluate the functional capacity of VPA-treated HSC, murine Sca1+/lin−s cells were harvested from colony assays and replated. VPA treatment allowed up to four cycles of replating in contrast to VPA-naïve control cells. Further analysis demonstrated that the stimulatory effect of VPA on the in vitro growth and colony formation capacity of HSC was mainly due to accelerated cell cycle progression. VPA strongly increased the proportion of cells in S phase compared to untreated controls (38 vs. 17%, resp.), as detected by propidium iodid staining and BRDU incorporation as well as reduced expression of the CDK-inhibitor p21cip-1/waf using murine HSC after 7 days of culture. Downregulation of p21cip-1/waf was confirmed in CD34+ BM cells showing maximum inhibition after 48 hours of VPA treatment and no recovery thereafter. Recent results indicate that VPA exerts inhibitory activity on GSK3beta by phosphorylation on Ser-9 and stimulates Akt in human neuroblastoma cells. GSK3beta is an effector of the Wnt-signaling pathway located upstream of beta-catenin. Wnt-signaling can directly stimulate the proliferation of HSC, expand the HSC pool and lead to upregulation of HoxB4. Here we show that VPA increased the inhibition-associated phosphorylation of GSK3beta on Ser-9 in human CD34+ BM cells after 48 hours as well as in murine Sca1+/lin− cells after 7 days. Exposure to VPA enhanced beta-catenin and Akt activity not only in CD34+ HSC but also in KG-1 and TF-1 cells with maximum activation after 48 hours of VPA stimulation. Moreover, VPA lead to an 8-fold increase of the HoxB4 level in CD34+ BM cells as determined by real time PCR at 48 hours. In conclusion, we show that VPA i.) expands HSC as assesed by phenotype and function; ii.) accelerates cell cycle progression of HSC accompanied by the down-regulation of p21cip-1waf; iii.) activates the GSK3beta depending beta-catenin pathway and Akt and iv.) up-regulates HoxB4. Our data strongly suggest that VPA is able to influence some of the signaling pathway considered relevant for proliferation and self-renewal which might request reconsideration of their employment for the treatment of AML.

Genomic landscape of HBV-related hepatocellular carcinoma in south China patients with high mutational frequency of TP53 and TERT promoter.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15670-e15670
Author(s):  
Jiazhou Ye ◽  
Yinguang Wang ◽  
Rong Liang ◽  
Xue Wu ◽  
Yang Shao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
South China ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Biological Effects ◽  
Cell Cycle Control ◽  
Tert Promoter ◽  
Genomic Landscape

e15670 Background: Development of hepatocellular carcinoma (HCC) is a complex process with accumulations of polygene abnormalities and multi-pathway misregulation. Hepatitis B virus (HBV) exposure can cause liver damage and promote hepatocarcinogenesis via various biological effects. We aimed to investigate the molecular mechanisms underlying the etiology of HBV-related HCC development, and provide new insights into novel molecular targets. Methods: 84 HBV-positive HCC patients from Guangxi Province, South China, who underwent hepatic resection, were enrolled in this study. Genomic alterations were analyzed in pair-matched tumor and adjacent normal tissue using a hybridization capture-based next-generation sequencing (NGS) assay targeting 422 cancer-relevant genes. Results: In total, 691 somatic mutations, 166 copy number variations and 10 gene fusions were detected in 81 (96.4%) of 84 tumor samples. The most commonly mutated gene is TP53 in this cohort (84% of the patients), which is much higher than its frequency in the reported overall HCC patients. TERT promoter has somatic mutations in 32% of the patients, reactivation of which has been implicated in multiple cancer types. Dysfunction in the cell cycle control pathway (TP53, RB1, CCND1, CDKN2A and CCNE1) was dominant, followed by PI3K/AKT cascade (PIK3CA, AKT3, MTOR, TSC1 and TSC2), while genes of WNT signaling pathway (CTNNB1, APC and AXIN2) were mutated at a lower frequency. In addition, 69 variants in 25 DNA damage repair (DDR) genes were identified in 37 (45.7%) patients. Patients with DDR mutations had a higher tumor mutation burden (TMB) than those without DDR mutations. Conclusions: This study revealed a unique genomic landscape of HBV-related HCC. Besides TP53 being the highest mutated gene, a significant fraction of patients was identified with TERT promoter mutations, suggesting that TERT may play a role in HBV-related hepatocarcinogenesis as a novel molecular marker. Furthermore, the most common biological processes affected by HBV status in HCC were cell cycle control, PI3K/AKT and WNT signaling pathways. The possible synergistic effects of HBV in hepatocarcinogenesis warrant further investigations.

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