• Korean Journal of Bronchoesophagology
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• v.7 no.2
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• pp.152-160
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• 2001

The presence of HPV DNA and the expression of p53 protein and proliferating cell nuclear antigen(PCNA) in head and neck squamous cell carcinoma were determined to evaluate the relationship of these factors and their association with their pathologic stages and cervical lymph node metastasis. Among 65 patients the presence of HPV DNA was found in 12 cases(18.5%), p53 was found positive in 32 cases(49.2%) and expression of PCNA was observed in 24 cases(36.9%). The expression of PCNA was more frequent in the HPV positive cancers compared with the HPV negative ones(p =0.0018), and p53 revealed its higher rate of cooccurrence with the expression of PCNA(p =0.008), which might suggest that PCNA expression has a positive relationship with HPV and p53 mutation in head and neck cancer. There might be inverse relationship between HPV and p53 mutation(p =0.063), but 3 cases showed both HPV DNA positivity and p53 expression. HPV was detected at a higher rate in the early pathologic stages than in the advanced stages of cancer, and p53 expression was more frequently found in the advanced stages(p =0.044). These results suggests that HPV and p53 mutation might have different etiologic roles in the development of head and neck cancer, or cases with p53 mutation might have more aggressive behavior. PCNA expression showed no difference between early and late stages of cancer, and between cases with and without cervical lymph node metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.2
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• pp.142-149
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• 2001

To investigate the correlation between the clinical features and the expression of p53, PCNA, and Ki-67 of the head neck squamous cell carcinoma, immunohistochemicalstaining of p53, PCNA, and Ki-67 on the paraffin embedded tissue blocks of 116 surgically removed specimens were done. The staining intensity was divided as grade 1 to grade 3 and the results were statistically analysed. 1. The positive reation rates of cell proliferation markers (PCNA and Ki-67) were higher than that of p53. There was significant correlations of the PCNA and Ki-67 expression but there was no significant correlations between p53 and PCNA or p53 and Ki-67. 2. There were no significant correlation between the expression of p53, PCNA and Ki-67 and tumor site or tumor size. 3. There was no significant differences in the positive response according to the nodal status. The node metastasis groups revealed that higher proportion of grade 3 staining of PCNA and Ki-67 than node negative group. From the above results it is concluded that p53 and cell proliferation markers PCNA and Ki-67 might have their unique mechanism involving in the growing and progression of tumor. Overexpression of p53 does not appear to represent an independent prognostic marker in head neck squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.756-765
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• 1997

Background : To study the prognosis of patients with lung cancer, many investigators have reported the methods to detect cell proliferation in tissues including PCNA, thymidine autoradiography, flow cytometry and Ki-67. PCNA, also known as cyclin, is a cell related nuclear protein with 36KD intranuclear polypeptide that is maximally elevated in S phase of proliferating cells. In this study, PCNA was identified by paraffin-embedding tissue using immunohistochemistry which has an advantage of simplicity and maintenance of tissue architecture. The variation of PCNA expression is known to be related with proliferating fraction, histologic type, anatomic(TNM) stage, degree of cell differentiation, S-phase fraction and survival rate. We analyzed the correlation between PCNA expression and S-phase fraction, survival. Method : To investigate expression of PCNA in primary lung cancer, we used immunohistochemical stain to paraffin-embedded sections of 57 resected primary non-small cell lung cancer specimen and the results were analyzed according to the cell type, cell differentiation, TNM stage, S-phase fraction and survival. Results : PCNA expression was divided into five group according to degree of staging(-, +, ++, +++, ++++). Squamous cell type showed high positivity than in adenocarcinoma. Nonsignificant difference related to TNM stage was noticed. Nonsignificant difference related to degree of cell differentiation was noticed. S-phase fraction was increased with advance of PCNA positivity, but it could not reach the statistic significance. The 2 year survival rate and median survival time were -50% 13 months, +75% 41.3 months, ++73% 33.6 months, +++67% 29.0 months, ++++25% 9 months with statistic significance (P<0.05, Kaplan-Meier, generalized Wilcox). Conclusion : From this study, PCNA expression was high positive in squamous cell cancer. And, there was no relationship between PCNA positivity and TNM stage, cellular differentiation or S-phase fraction. But, the patients with high positive PCNA staining showed poor survival rate than the patients with lower positive PCNA staining (p<0.05). It was concluded that PCNA immunostaining is a simple and useful method for survival prediction in paraffin embedded tissue of non-small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3627-3630
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• 2012

The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously. Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN). Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing doses of 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processed for histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twenty hepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferating cell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected in hepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observed in normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells, showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with co-localization. Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors and many tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-induced tumors, possibly associated with cell proliferation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.2
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• pp.85-99
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• 2004

Purpose: This study observed the changes in the telomerase activity, it's developmental regulation, PCNA expression, and their correlation in rat's upper digestive organs during growth and aging. Materials and Methods: Upper digestive organs(buccal mucosa, gingiva, palate, submandibular and parotid glands, and tongue) were aseptically removed from Sprague-Dawley rats of fetal(gestational 20 days), growing(1, 2, 3, 5, and 7 weeks after birth) and adult(12 week old). Samples for telomerase activity were frozen on liquid nitrogen immediately after sacrifice, and stored until the use at $-75^{\circ}C$ in order to measure it. Telomerase activity was measured by a PCR-based telomeric repeat amplication protoco(TRAP) assay and quantitated with Photometric Telo TAGGG Telomerase PCR ELISA plus(Roche Diagnostics GmbH. Mannheim. Germany). PCNA expression were measured immunohistochemistry with anti PCNA Ab-1, Clone PC10(NeoMark. California. USA). Results: 1. Telomerase activities in buccal mucosa, palate and gingiva were the highest in fetus and decreased gradually or rapidly after birth and then diminished, but In salivary gland and tongue were the highest in fetus and also high at 1 week and then decreased rapidly. 2. PCNA expression in buccal mucosa, gingiva, Tongue and salivary gland was the highest in fetus and decreased gradually and then diminished. but only in palate decreased rapidly after birth and then diminished. Conclusion: The highest telomerase activity of embryonic stage decreased rapidly after birth in rat's upper digestive organs. There may be a developmental regulation of telomerase activity, but not a tissue-specific. This telomerase activity seems correlated closely with PCNA expression in rat's upper digestive system.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5207-5211
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• 2012

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

• Animal cells and systems
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• v.5 no.1
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• pp.59-64
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• 2001

To understand the late gut development and differentiation, identification and characterization of target genes of homeotic genes involved in gut development are required. We have previously reported that homeodomain proteins can regulate expression of the cell proliferation-related genes. We investigated here the expression of the Drosophila proliferating cell nuclear antigen(PCNA) and E2F(dE2F) genes in larval and adult guts using transgenic flies bearing lacz reporter genes. Both PCNA and dE2F genes were expressed strongly in whole regions of the larval and adult guts including the esophagus, proventriculus, midgut and hindgut, showing higher expression in foregut and hindgut imaginal rings of larva. Nitric Oxide(NO) has been known to be involved in cell proliferation and tumor growth and also to have an antiproliferative activity. Therefore, we also investigated effects of NO on the expression of PCNA and dE2F genes in gut through analyses of lacz reporter expression level in the SNP (NO donor)-treated larval guts. Expressions of both PCNA and dE2F were greatly declined by SNP. The inhibitory effect of NO was shown in whole regions of the gut, especially in hindgut, while the internal region of proventriculus, esophagus, foregut imaginal ring and hindgut imaginal ring was resistant. Our results suggest that this inhibitory effect may be related with the antiproliferative activity of NO.

• Applied Microscopy
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• v.42 no.3
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• pp.115-123
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• 2012

Human placenta extract (hPE) has therapeutic potential against certain diseases such as burn injury, liver cirrhosis and chronic wound through stimulating tissue repair processes. However, the effects of hPE on liver regeneration in animals are unknown. This study investigated the effect of hPE on the expression of proliferating cell nuclear antigen (PCNA) during liver regeneration induced by partial hepatectomy (PH) in rats. The activities of AST, ALT and ALP increased during a few days after PH. A high level of ALP was particularly seen at day 3 in the control group. All the levels of experimental groups were normalized by day 5 after PH. On immunohistochemistry, the expression of PCNA increased at the early days, showed a peak at day 3 after PH. The PCNA staining was more obvious in the experimental group over the whole period. By western blotting, PCNA seemed to be more strongly expressed in the hPE injected group in the early stage and fell to almost undetectable levels at day 7. On immunocytochemical observations, the number of PCNA-gold particles in the nuclei at day 1 of the hPE treated groups was more than those of the untreated groups. The results suggest that hPE could accelerate liver regeneration induced by PH involving the expression of PCNA in rats.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6001-6005
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• 2013

Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

• Advances in pediatric surgery
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• v.1 no.2
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• pp.122-132
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• 1995

Teratoma contains elements derived from all three embryonic germ layers and mature teratomas are entirely composed of mature differentiated tissues, while immature types always contain additional embryonic tissues of variable degree of immaturity, especially neuroepithelial elements. Twenty cases of teratoma in infancy and childhood were reviewed and the clinical features and pathologic findings including PCNA expression were studied. Sacrococcygeal teratomas were the most common type(45%), followed by retroperitoneal and ovarian teratomas. There was a predilection of females in a ratio of 4:1 and age distribution was most prevalent below the first year of age(45%). But in ovarian teratomas, the age at diagnosis was above 4 years of age in all cases. Serum alpha-fetoprotein levels were checked in 18 cases. In all mature teratomas and 1 of 5 immature teratomas, the levels were normal. But in 4 of 5 immature teratomas, the serum levels were elevated and progressively declined to normal range after mass excision. Radiologically, calcifications in tumor were found in 60.0% of teratomas and was higher in mature teratomas(69.2%) than immature teratomas(42.9%). Immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was done in 16 cases and PCNA expression was higher in grade III immature teratomas than grade I and II. The operative modes were complete mass excisions. Five immature teratomas were treated with multiagent PEB(Bleomycin, Etoposide, Cisplatin) adjuvant chemotherapy, 3 tolerated well without significant complications, but in one case, severe bone marrow suppression was developed and died of sepsis. In conclusion, grade III immature teratoma showed higher PCNA expression than mature or lower grade immature teratoma, which suggests that chemotherapy after surgical excision may be effective modality for grade III immature teratoma. We think, however, multicenter study is necessary because of low incidence of immature teratoma.