• Journal of Life Science
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• v.26 no.7
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• pp.826-834
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• 2016

The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.71-76
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• 2009

Benign myoepithelioma (BME) and malignant myoepithelioma (MME) of the salivary gland are very rare and its biologic behavior has not been clarified fully. Although, cases reports for BME and MME were increased in recent, their diagnostic criteria were not completely established. We describe herein a case of BME of the parotid gland and a case of MME of the palatal minor gland, respectively. Histologically, multinodular growth pattern, infiltration to adjacent tissues, and hyalinized and myxoid matrix were observed in MME, that were different histologic features compared with BME. Strong immunoreactivities for the S-100 protein and vimentin were detected in the tumor cells of BME and MME. In specimen of MME, moderately expressed p53 and strongly expressed p63 were detected. However, in specimen of BME, p53 was negatively and p63 was weakly expressed, respectively. In conclusion, the expression patterns of p53 and p63 as well as histologic aggressiveness might be used to diagnose the MME.

• 대한예방의학회:학술대회논문집
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• 2001.04a
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• pp.90-90
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• 2001

• Journal of Chest Surgery
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• v.37 no.8
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• pp.672-683
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• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.726-731
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• 1999

Background: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. Material and Method: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. Result: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). Conclusion: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.431-438
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• 2006

Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.

• Journal of Life Science
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• v.19 no.9
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• pp.1289-1293
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• 2009

Proto-oncogene human cervical cancer oncogene (HCCR) functions as a negative regulator of p53 and contributes to tumorigenesis in various human tissues. However, it is unknown how HCCR contributes to the cellular and biochemical mechanisms of human tumorigenesis. In this study, we showed how the expression of HCCR is modulated. The luciferase activity assay indicated that the HCCR 5'-flanking region at positions -370 to -406 plays an important role in the promoter activity. Computational analysis of this region identified one consensus sequence for the TG-interacting factor (TGIF) located at -390 to -366 (TG). Mobility shift assays (EMSA) revealed that nuclear proteins from K562 bind to the TG site, but not to the mutated TG site. The reporter activity assay with promoter constructs carrying mutated TGIF sequences pGL3-mTGIF significantly increased reporter activities compared to wild type constructs pGL3-$406{\sim}+30$. In this study, we characterized the HCCR promoter and found that HCCR expression was partially regulated by the transcription repressor TGIF, which bound the promoter at positions -390 to -366.

• Korean Journal of Soil Science and Fertilizer
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• v.18 no.3
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• pp.254-259
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• 1985

Variability of soil characteristics and purity were statistically summarized within mapping units and estimates were given for sample sizes required to reach predetermined levels of accuracy in mountain-foot slope soils. Total variances within mapped soil series (expressed as CV): 12-44% for pH, CEC, and particle size distribution was relatively unaffected and 56-196% for OM, ext.-cations, and available $P_2O_5$, affected by management. Means of some chemical properties were estimated on the assumption of lognormal distribution. These soils were correctly classified with regard to order at 52.2%, to great group 53.7%, and to series 39.7%. respectively. Approximate sample sizes required to detect the difference of 10 and 20% of the true mean with 0.95 confidence level were presented.

• Korean Journal of Ichthyology
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• v.1 no.1_2
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• pp.42-53
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• 1989

The geographic variations of the number and morphology of scutes of eightspine stickleback, Pungitius sinensis, in the southern half of the Korean peninsula were investigated. The two subspecies, P. sinensis sinensis and P. sinensis kaibarae, showed a bit of difference in the number of scutes but there was no geocline as a whole. In the frequencies of individuals with the different number of scutes between the left and right body side, there was also difference between the two subspecies, and the specimens from the Hyongsan River showed great variation. The populations of Kumho River had the largest scutes. But the specimens of the Hyongsan River had small and degenerated scutes different from all other populations, and some individuals showed the semiarmatus type arrangement of scute. Therefore, this population may be called the special type of P. sinensis. In the relationship between the time of landlocking and the size of scutes, it was speculated that the population of the Hyongsan River was landlocked long years ago and other populations of P. sinensis kaibarae except the Kumho River were landlocked more recently. For the population of the Kumho River, however, it seemed that there was no relation between salt tolerance or landlocking and number or developmental state of scutes as this landlocked population had well developed and large number of scutes.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.373-384
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• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.