• Title/Summary/Keyword: proliferating cell nuclear antigen

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Expression of Caspase 3, Survivin, and p53 Protein in Urethane Induced Mouse Lung Carcinogenesis (Urethane으로 유발된 생쥐 폐샘암종 발생과정에서 Caspase 3, Survivin과 p53 단백 발현)

  • Shin, Jong Wook;Lee, Soo Hwan;Park, Eon Sub
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.3
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    • pp.251-260
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    • 2007
  • Purpose: An imbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis. Capase 3, survivin and p53 have been identified as important members of the apoptotic related proteins. This study evaluated the proliferating cell nuclear antigen(PCNA), apoptosis, apoptotic related protein such as capase 3, survivin and p53 using urethane-induced mouse lung carcinogenesis, which provides reproducible steps from hyperplasia to adenocarcinoma. Methods: Urethane was administered to the ICR mice through an intra-peritoneal injection, The mice were sacrificed at 5, 15, and 25 weeks after urethane intervention. The sequential morphological changes and immunohistochemical expression of PCNA, apoptosis, capase 3, survivin, and p53 were examined during mouse lung carcinogenesis. Results: During carcinogenesis, the sequential histological changes were observed from hyperplasia of type II pneumocytes, to anadenoma, and ultimately to an overt adenocarcinoma. The PCNA Labeling index (LI) was 9.6% in hyperplasia, 23.2% in adenoma, and 55.7% in adenocarcinoma, respectively. The apoptotic LI was 0.24% in hyperplasia, 1.25% in adenoma, and 5.27% in adenocarcinoma. A good correlation was observed between the PCNA LI and apoptotic LI. The expression of caspase 3 was remarkable- i.e., 46.7% in adenocarcinoma, in contrast to 15% in hyperplasia and 16% in adenoma. Survivin was detected weakly in the alveolar hyperplasia and showed an increasing expressional pattern in adenoma and adenocarcinoma. p53 expression was detected only in the adenocarcinoma lesions with an expression rate of 13.3%. The level of caspase 3 expression correlated with the increase in the apoptotic index. The positive expression of caspase 3 was associated with an increased apoptotic index. Conclusions: These results suggest that the PCNA LI and apoptotic LI might be useful markers for evaluating the risk of a malignant transformation. In addition, caspase, survivin and p53 might play a role in the early and late steges of urethane-induced mouse lung carcinogenesis.

Dietary corn resistant starch regulates intestinal morphology and barrier functions by activating the Notch signaling pathway of broilers

  • Zhang, Yingying;Liu, Yingsen;Li, Jiaolong;Xing, Tong;Jiang, Yun;Zhang, Lin;Gao, Feng
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.12
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    • pp.2008-2020
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    • 2020
  • Objective: This study was conducted to investigate the effects of dietary corn resistant starch (RS) on the intestinal morphology and barrier functions of broilers. Methods: A total of 320 one-day-old broilers were randomly allocated to 5 dietary treatments: one normal corn-soybean (NC) diet, one corn-soybean-based diet supplementation with 20% corn starch (CS), and 3 corn-soybean-based diets supplementation with 4%, 8%, and 12% corn resistant starch (RS) (identified as 4% RS, 8% RS, and 12% RS, respectively). Each group had eight replicates with eight broilers per replicate. After 21 days feeding, one bird with a body weight (BW) close to the average BW of their replicate was selected and slaughtered. The samples of duodenum, jejunum, ileum, caecum digesta, and blood were collected. Results: Birds fed 4% RS, 8% RS and 12% RS diets showed lower feed intake, BW gain, jejunal villus height (VH), duodenal crypt depth (CD), jejunal VH/CD ratio, duodenal goblet cell density as well as mucin1 mRNA expressions compared to the NC group, but showed higher concentrations of cecal acetic acid and butyric acid, percentage of jejunal proliferating cell nuclear antigen-positive cells and delta like canonical Notch ligand 4 (Dll4), and hes family bHLH transcription factor 1 mRNA expressions. However, there were no differences on the plasma diamine oxidase activity and D-lactic acid concentration among all groups. Conclusion: These findings suggested that RS could suppress intestinal morphology and barrier functions by activating Notch pathway and inhibiting the development of goblet cells, resulting in decreased mucins and tight junction mRNA expression.

Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling (양성 뇌수막종의 조직학적 아형 및 이형성 뇌수막종에서 PCNA와 Ki-67 표지지수의 비교)

  • Choi, Seung Jin;Chang, Eun Deok;Kwon, Seung Oh;Kye, Dae Kon;Park, Choon Keun;Lee, Sang Won;Kang, Joon Ki
    • Journal of Korean Neurosurgical Society
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    • v.29 no.9
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    • pp.1215-1221
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    • 2000
  • Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

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The Signal Transduction Mechanisms on the Intestinal Mucosa of Rat Following Irradiation (방사선조사후 백서소장점막에서 발생하는 신호전달체계에 관한 연구)

  • Yoo Jeong Hyun;Kim Sung Sook;Lee Kyung Ja;Rhee Chung Sik
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.79-95
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    • 1997
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

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