• Journal of Chest Surgery
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• v.38 no.12 s.257
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• pp.835-843
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• 2005

Background: Cancer of the esophagus is one of the most malignant tumors with poor prognosis. The p53 gene alteration, over expression of Cyclin D1, and Ki67 index were thought to be the prognostic factors. However, their clinical significances in esophageal squamous cell carcinoma are controversial and p53 accumulation may not correlate with genetic mutation. The current study investigates their prognostic significance in squamous cell carcinoma of the esophagus. Material and Method: The Subjects studied were 124 esophageal squamous cell carcinoma patients who underwent esophagectomy. The mutation of p53, over expression of Cyclin D1, Ki67 labelling index, mitotic index were examined by using an immunohistochemical staining. We compared the results and investigated the correlation with the mutation of p53, overexpression of Cyclin D1, Ki67 labelling index, mitotic index and tumor size, and duration of survival. Result: There was no correlation between the results in immunohistochemical staining according to age, sex, tumor size, Iymph node status, and clinical stage of the disease. Mutant p53 protein was found in 69 cases (55.6$\%$). Median survival time was 21 months in cases with negative for mutant p53 protein and 22 months in positive cases. There was no significant difference in survival (p=0.46). Median survival time was 22 months in cases with negative for Cyclin D1 and 16 months in positive cases (p=0.18). Median and mean survival time was 22 months and 36 months when Ki67 labeling index was 40 or less (102 cases). Median and mean survival was 16 months and 23 months, when Ki67 labeling index was more than 40 (22 cases). There was significant difference in survival rate (p=0.011). Conciusion: Positivity of p53 and cyclin D1 was not useful in predicting the prognosis in our study. There was no significant correlation among mutant p53 protein accumulation, Cyclin D1 over expression, and Ki67 labeling index. However, in several studies, PCR single strand conformational polymorphism analysis of p53 showed a correlation to the prognosis. We thought that there was a significant discordance between p53 gene mutation and mutant p53 protein accumulation. When Ki67 labeling index was more than 40, prognosis was poorer, Ki67 seems to be a prognostic factor in our study. Therefore, we confirmed the possibility of using molecular markers as prognostic factors.

• Journal of Microbiology and Biotechnology
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• v.30 no.7
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• pp.1044-1050
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• 2020

Abelmoschus manihot (Linn.) is a medicinal herbal plant that is commonly used to treat chronic kidney disease and hepatitis. However, its effect on cell proliferation has not been clearly revealed. In this report, we sought to determine the effect of the flower extract of A. manihot (FA) on cell proliferation. Based on our findings, FA increased the proliferation of human diploid fibroblast (HDF) and HEK293 cells. Through cell cycle analysis, FA was found to increase the number of HDF cells in the S phase and G2/M phase. FA also increased the expression of cyclin D1 and enhanced the migration of HDF cells. By administering FA to HDF cells with ≥30 passages, a decrease in the number of senescence-associated β galactosidase-positive cells was observed, thereby indicating that FA can ameliorate cellular senescence. Collectively, our findings indicate that FA increases cyclin D1 expression and regulates cell proliferation.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.159-165
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• 2006

To determine the anticancer effect of D-amygdalin (D-mandelinitrole-${\beta}$-D-gentiobioside) in human chronic myeloid leukemia cells K562, we profiled the gene expression between amygdalin treatment and control groups. Through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of D-amygdalin was $57.79{\pm}1.83%$ at the concentration of 5 mg/mL for 24 h. We performed cDNA microarray analysis and compared the gene expression profiles between D-amygdalin (5 mg/mL, 24 h) treatment and control groups. Among the genes changed by D-amygdalin, we paid attention to cell cycle-related genes, and particularly cell cycle regulator genes; because arrest of cell cycle processing was ideal tactic in remedy for cancer. In our data, expressions of cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B), ataxia telangiectasia mutated (includes complementation groups A, C, and D) (ATM), cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), and CHK1 checkpoint homolog (CHEK1, formally known as CHK1) were increased, while expressions of cyclin-dependent kinase 2 (CDK2), cell division cycle 25A (CDC25A), and cyclin E1 (CCNE1) were decreased. The pattern of these gene expressions were confirmed through RT-PCR. Our results showed that D-amygdalin might control cell cycle regulator genes and arrest S phase of cell cycle in K562 cells as the useful anticancer drug.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• Journal of Plant Biotechnology
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• v.32 no.1
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• pp.15-21
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• 2005

The expression patterns of cyclin genes, which play a crucial role on cell cycle control, were analyzed with rice calli and leaf blades from seedlings. When callus was transferred from media containing the combinations of 2,4-D and kinetin under the dark conditions to medium supplemented with cytokinin-only on 7 days after the cultures, the expression levels of A-, B- and C-type cyclins from callus were increased significantly. Despite the fact that cyclin genes were well expressed on leaf blades rather than other organs in rice seedlings, rice leaf blades grown on the medium containing various combinations and concentrations of cytokinin for 24 hours had no major effect on the expression patterns of cyclins except zeatin. The relation between cytokinin regulation and the expression of cyclins of rice is discussed.

• Biomedical Science Letters
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• v.20 no.2
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.108-108
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• 2018

In this study, we evaluated the anti-cancer effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in human colorectal cancer cells. ST-L and ST-B significantly inhibited the proliferation of human colorectal cancer cells, SW480. ST-L and ST-B decreased cyclin D1 protein level through the induction of cyclin D1 proteasomal degradation via $GSK3{\beta}$-dependent threonine-286 phosphorylation of cyclin D1. In addition, ST-L and ST-B increased HO-1 protein through p38, ROS and $GSK3{\beta}$-dependent Nrf2 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-cancer drug to treat human colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4127-4130
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• 2013

MicroRNA-16 (miR-16) has been demonstrated to regulate proliferation and apoptosis in many types of cancers, but its biological function in bladder cancer remains unknown. Here, we found expression of miR-16 to be downregulated in bladder cancer in comparison with the adjacent normal tissues. Enforced expression of miR-16 was able to inhibit cell proliferation in TCHu-1 cells, in line with results for miR-16 antisense oligonucleotides (antisense miR-16). At the molecular level, our results further revealed that cyclin D1 expression was negatively regulated by miR-16. Therefore, the data reported here demonstrate that miR-16 is an important regulator in bladder cancer, which will contribute to better understanding of important mis-regulated miRNAs.

• Environmental Mutagens and Carcinogens
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• v.24 no.2
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• pp.51-66
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• 2004

Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS). Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and west-ern bolt. In MCF-10A cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose- and time- dependent. T47-D cells treated with 1.0 $\muM$ tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 $\muM$ tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyelin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

• Journal of Applied Biological Chemistry
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• v.53 no.2
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• pp.108-111
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• 2010

New salens (3) and their Cobalt complexes (4) were prepared from meso-1,2-bis(ortho-hydroxyphenyl)-1,2-diaminoethane (1) and substituted salicylic aldehydes (2). In contrast to symmetric structure of salen ligand (3), salen-Co(III) complexes (4) showed dissymmetric molecular structure due to participation of three hydroxyl groups in complex formation. One of the salens (3b) revealed decrease in Cyclin D1 expression, which represents anti-cancer property.