scholarly journals Cell cycling and patterned cell proliferation in the wing primordium of Drosophila.

1996 ◽  
Vol 93 (2) ◽  
pp. 640-645 ◽  
Author(s):  
M. Milan ◽  
S. Campuzano ◽  
A. Garcia-Bellido
Keyword(s):  
Cell Proliferation ◽  
Cell Cycling

Diosmetin, a Potential p53 Activator, Performs Anticancer Effect by Regulating Cell Cycling and Cell Proliferation in HepG2 Cells

2017 ◽  
Vol 24 (5) ◽  
pp. 413-418
Author(s):  
Bin Liu ◽  
Miaomiao Zhang ◽  
Shuna Liu ◽  
Jie Ying ◽  
Jingjing Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hepg2 Cells ◽  
Anticancer Effect ◽  
Cell Cycling

scholarly journals Network Pharmacology Validation of Therapeutic Mechanisms of Tanshinone IIA in Colorectal Cancer

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110042
Author(s):  
Zhiyuan Sun ◽  
Jinxiang Dong ◽  
Lijie Song ◽  
Fuqiang Li ◽  
Xue Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tanshinone Iia ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Networks ◽  
Therapeutic Mechanisms ◽  
Cell Cycling ◽  
Promising Source

Curative therapies with fewer adverse effects are required for cancer treatment. Medicinal plants represent a promising source of novel therapeutic candidates. We employed network pharmacology to predict potential molecular mechanisms of salvia root-derived tanshinone IIA (Tan IIA) in the treatment of colorectal cancer (CRC), followed by empirical validation. The Traditional Chinese Medicine System Pharmacology (TCMSP), DrugBank, and GeneCards databases were queried to identify overlapping Tan IIA (therapeutic)- and CRC (disease)-relevant protein targets. Cytoscape and STRING were used to generate component-target and protein-protein interaction (PPI) networks, respectively, and topology analysis identified highly connected nodes within the latter. Target proteins were subjected to gene ontology (GO)-based biological process annotation using DAVID, and to biological pathway enrichment analysis using the Kyoto encyclopedia and genome (KEGG) database. Enriched biological processes included cell cycling and proliferation, and enriched KEGG pathways included neuroactive ligand-receptor interaction, PI3K-Akt, and cancer. Network pharmacology results predicted that Tan IIA impacts multiple targets and pathways, but that its therapeutic effect is predominantly attributable to cell cycle regulation, inhibition of cell proliferation, and induction of apoptosis. Investigation of the in vitro impact of Tan IIA on proliferation, viability, and cell cycling of 2 hoursuman CRC cell lines (SW480 and SW620), using the CCK-8 method and flow cytometry, demonstrated that Tan IIA significantly inhibits cell proliferation via inducing cell cycle arrest in the G2/M phase. Network pharmacology-predicted hypotheses were thus empirically validated, providing a basis for in-depth study of the therapeutic mechanisms of Tan IIA in the context of CRC.

Ex vivo targeting of p21Cip1/Waf1 permits relative expansion of human hematopoietic stem cells

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1260-1266 ◽  
Author(s):  
Sebastian Stier ◽  
Tao Cheng ◽  
Randolf Forkert ◽  
Christoph Lutz ◽  
David M. Dombkowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Cell Function ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Cell Cycle Checkpoints ◽  
Hematopoietic Stem ◽  
Cell Cycling

Abstract Relative quiescence is a defining characteristic of hematopoietic stem cells. Reasoning that inhibitory tone dominates control of stem cell cycling, we previously showed that mice engineered to be deficient in the cyclin-dependent kinase inhibitor, p21Cip1/Waf1 (p21), have an increased stem cell pool under homeostatic conditions. Since p21 was necessary to maintain stem cell quiescence and its absence sufficient to permit increased murine stem cell cycling, we tested whether reduction of p21 alone in human adult–derived stem cells could affect stem cell proliferation. We demonstrate here that interrupting p21 expression ex vivo resulted in expanded stem cell number and in vivo stem cell function compared with control, manipulated cells. Further, we demonstrate full multilineage reconstitution capability in cells where p21 expression was knocked down. Therefore, lifting the brake on cell proliferation by altering cell cycle checkpoints provides an alternative paradigm for increasing hematopoietic stem cell numbers. This approach may be useful for relative ex vivo human stem cell expansion.

scholarly journals Loss of the TLE4 AML Tumor Suppressor Gene Contributes to Leukemic Cell Proliferation, Differentiation Arrest, and Chemotherapy Resistance through a COX-Dependent Inflammatory Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1241-1241
Author(s):  
Thomas H Shin ◽  
David A Sweetser
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Conflicts Of Interest ◽  
Lethal Dose ◽  
Leukemic Cell ◽  
Cell Cycle Checkpoint ◽  
Chromosome 9 ◽  
Myeloid Differentiation ◽  
Inflammatory Pathways ◽  
Cell Cycling

Abstract Associated with approximately 8-13% cases of acute myeloid leukemia (AML), t (8;21) results in the formation of the fusion oncoprotein AML1-ETO (AE), which appears to promote hematopoietic precursor expansion through aberrant regulation of canonical AML1 targets. Multiple lines of evidence indicate AE is insufficient for leukemogenesis and requires cooperative secondary mutations. Interstitial deletions of chromosome 9 are one of the more frequent associated cytogenetic abnormalities seen with t(8;21). We previously identified that knockdown of TLE1 and TLE4, members of the Groucho/TLE family of co-repressors residing in a commonly deleted region of chromosome 9 in t (8;21) del (9q) AML cooperates with AE to drive myeloblastic proliferation and cause a leukemic phenotype. In this study, we show how TLE4 loss in the context of AML1-ETO expression results in cell proliferation, decreased apoptosis, blocked differentiation, and increased resistance to chemotherapy and that these effects are mediated through an upregulation of cyclooxygenase (COX)-dependent inflammation. TLE4 knockdown via shRNA (shTLE4) in Kasumi-1 cells (derived from a patient with t (8;21) AML) resulted in increased cell cycling and decreased cell death that is concomitant with significantly lower levels of p16Ink4 and p27Kip1 expression, both major regulators of the G1/S cell cycle checkpoint. RNAseq with GSEA analysis identified enrichment of pathways related to IFN signaling and inflammation within upregulated genes in shTLE4 cells compared to control. Filtering for genes with log2 fold change greater than 0.6, we identified three genes related to inflammation (PTGER4, CEBPb, FOS). As demonstration of the relevance of these findings, we showed these expression levels were also higher in primary human del (9q) and t (8;21) del (9q) leukemia samples compared to normal CD34+ cells; revealing a potential leukemogenic role for inflammatory pathways in del (9q) and t (8;21) del (9q) AML. Using a sub-lethal dose of indomethacin (50uM INDM), we found modulating the COX-dependent inflammatory axis decreased growth of shTLE4 Kasumi-1 cells, decreased cell cycling, and increased dead populations. Concomitantly, INDM treatment was able to reverse shTLE4-induced increases in PTGER4, CEBPb, FOS, and IL1b expression to levels similar to those in control cells. Given the ability to induce myeloblastic proliferation with TLE knockdown and AE expression in zebrafish, we investigated whether shTLE4 causes changes in key myeloid differentiation regulators in Kasumi-1 cells. qPCR analysis demonstrated significantly repressed ELANE, MPO, and PU.1 expression in shTLE4-treated cells, which is relieved with the addition of INDM. TLE4 knockdown in HL60 cells (derived from t (15;17) PML/RARA leukemia) increased levels of FOS, IL1b, CEBPb, and PTGER4. At the same time, shTLE4 significantly reduced CD11b+ and CD11b+ CD14+ populations while decreasing expression of PU.1 and MYB - demonstrating a similar inflammatory gene signature associated with a myeloid differentiation block found in the Kasumi-1 model. We next wanted to examine whether inhibiting COX-dependent inflammation can be synergistic with existing therapies. INDM significantly increased the cell death and apoptosis seen in both control cells as well as cells with TLE4 knockdown treated with AraC. The loss of TLE4 conferred resistance to combination treatment with indomethacin and AraC as evidenced by increased cell proliferation and decreased cell death. However, we observed that cells with TLE4 knockdown were significantly more sensitive to the combination of sunitinib and INDM, pointing to a potentially more therapeutic and less toxic treatment regimen for this otherwise resistant cell population. In this study, we have demonstrated that loss of TLE4 appears to contribute to leukemogenesis through differentiation arrest and increased proliferation mediated through upregulation of COX-dependent inflammatory pathways. Our findings suggest that COX inhibition may serve as an effective adjuvant therapy for AML. Disclosures No relevant conflicts of interest to declare.

Roles of store-operated Ca2+ channels in regulating cell cycling and migration of human cardiac c-kit+ progenitor cells

2015 ◽  
Vol 309 (10) ◽  
pp. H1772-H1781 ◽  
Author(s):  
Hui Che ◽  
Gang Li ◽  
Hai-Ying Sun ◽  
Guo-Sheng Xiao ◽  
Yan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
Progenitor Cells ◽  
Cyclin E ◽  
The Novel ◽  
Myocardial Repair ◽  
Cell Proliferation And Migration ◽  
Cell Cycling ◽  
And Migration ◽  
Proliferation And Migration

Cardiac c-kit+ progenitor cells are important for maintaining cardiac homeostasis and can potentially contribute to myocardial repair. However, cellular physiology of human cardiac c-kit+ progenitor cells is not well understood. The present study investigates the functional store-operated Ca2+ entry (SOCE) channels and the potential role in regulating cell cycling and migration using confocal microscopy, RT-PCR, Western blot, coimmunoprecipitation, cell proliferation, and migration assays. We found that SOCE channels mediated Ca2+ influx, and TRPC1, STIM1, and Orai1 were involved in the formation of SOCE channels in human cardiac c-kit+ progenitor cells. Silencing TRPC1, STIM1, or Orai1 with the corresponding siRNA significantly reduced the Ca2+ signaling through SOCE channels, decreased cell proliferation and migration, and reduced expression of cyclin D1, cyclin E, and/or p-Akt. Our results demonstrate the novel information that Ca2+ signaling through SOCE channels regulates cell cycling and migration via activating cyclin D1, cyclin E, and/or p-Akt in human cardiac c-kit+ cells.

Fibroblasts During Hypertrophic Scar Formation and Resolution

1973 ◽  
Vol 31 ◽  
pp. 428-429
Author(s):  
C. W. Kischer
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Cell Proliferation ◽  
Fine Structure ◽  
Metabolic Activity ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Ground Substance ◽  
Hypertrophic Scars ◽  
Scanning Electron

The morphology of the fibroblasts changes markedly as the healing period from burn wounds progresses, through development of the hypertrophic scar, to resolution of the scar by a self-limiting process of maturation or therapeutic resolution. In addition, hypertrophic scars contain an increased cell proliferation largely made up of fibroblasts. This tremendous population of fibroblasts seems congruous with the abundance of collagen and ground substance. The fine structure of these cells should reflect some aspects of the metabolic activity necessary for production of the scar, and might presage the stage of maturation.A comparison of the fine structure of the fibroblasts from normal skin, different scar types, and granulation tissue has been made by transmission (TEM) and scanning electron microscopy (SEM).

The Effect of Androgen Depletion and Replacement on the Epithelium of the Seminal Vesicle of the Aging Rat

1975 ◽  
Vol 33 ◽  
pp. 590-591
Author(s):  
Venita F. Allison
Keyword(s):  
Cell Proliferation ◽  
Seminal Vesicle ◽  
Male Rats ◽  
Target Cells ◽  
Cell Regeneration ◽  
Secretory Function ◽  
Electron Microscopic ◽  
Aging Rat ◽  
Microscopic Studies ◽  
Androgen Depletion

In 1930, Moore, Hughes and Gallager reported that after castration seminal vesicle epithelial cell atrophy occurred and that cell regeneration could be achieved with daily injections of testis extract. Electron microscopic studies have confirmed those observations and have shown that testosterone injections restore the epithelium of the seminal vesicle in adult castrated male rats. Studies concerned with the metabolism of androgens point out that dihydrotestosterone stimulates cell proliferation and that other metabolites of testosterone probably influence secretory function in certain target cells.Although the influence of androgens on adult seminal vesicle epithelial cytology is well documented, little is known of the effect of androgen depletion and replacement on those cells in aging animals. The present study is concerned with the effect of castration and testosterone injection on the epithelium of the seminal vesicle of aging rats.

Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

1987 ◽  
Vol 45 ◽  
pp. 934-935
Author(s):  
S.S. Poolsawat ◽  
C.A. Huerta ◽  
S.TY. Lae ◽  
G.A. Miranda
Keyword(s):  
Cell Proliferation ◽  
Liver Function ◽  
Chronic Inflammation ◽  
Foam Cell ◽  
Term Effect ◽  
Short Term ◽  
Drug Induced ◽  
Experimental Induction ◽  
Tissue Alterations ◽  
Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

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