• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.253-266
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• 1995

Recently, available interests concerning the biologic significance of the extracellular matrix and proliferating cells associated with periodontal disease has been increased. The distribution or expression of cellular proliferation by PCNA, macrophage detection by ${\alpha}$-l-antichymotrypsin, fibronectin playing a important role in host defence mechanisms indirectly, and transglutaminase that cross linked to fibronectin and stimulate fibrin stabilization were studied in inflammed and healthy gingiva. The excised tissue samples were fixed neutral formalin for 24 hours, embedded with paraffin, sectioned at 4-61lffi in thickness, and immunohistochemically processed by LSAB method. The positive reaction to PCNA was localized in the suprabasal and basal layer of inflammed gingiva and an increasing reactivity was observed than healthy gingiva. ${\alpha}$-I-antichymotrypsin positive cells were localized in the basal layer of inflammed gingiva, and there was no or rare positive cells in healthy gingiva. The positive reaction to fibronectin in inflammed gingiva was more than healthy gingiva,"and shown in the connective tissue subjacent to basement membrane of epithelium and in the periphery of the collagen fiber bundles. The positive cells by transglutaminase in inflammed gingiva were noted in suprabasal, spinous, and keratin layer of epithelium, and slightly increased in the capillaries of connective tissues. But the results of this study demonstrated in vitro reaction. Therefore, the role of PCNA,${\alpha}$-l-antichyrnotrypsin, transglutaminase, fibronectin and coefficient with other growth factor and extracellular matrix were further investigated in vivo.

• Clinical and Experimental Reproductive Medicine
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• v.19 no.2
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• pp.175-179
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• 1992

The factors involved in the initial neoplastic transformation and subsquent growth of uterine fibroid are poorly understood. The reduction in uterine fibroid volume associated with the chronic administration of the mechanisms mediating the decrease in fibroid volume in GnRH-a treated patients are poorly defined. The purpose of this study was to determine the proliferating cell nuclear antigen(PCNA) in fibroid from-women pretreated with GnRH analogue(GnRH-a) compared with controls. Tissue was obtained from 16 premenopausal women with uterine fibroid who received GnRH-a(D-Trp6-GnRH) intramusculary every 28 days for four injections. The mean proliferating index(PI) in patients with uterine fibroids was $2.25{\pm}0.9$, and in controls was $8.82{\pm}1.8$(P<0.001). The proliferating index was not corrleated with the reduction of fibroid volume. In this clinical study, although hypoestrogenism may be the main factor that reduce the volume of fibroid, other factors are also considered to be involved in that process. And the regrowth of uterine fibroid may be affected by increased production of PCNA after stopping GnRH-a.

• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.23-28
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• 1993

Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.

• Animal cells and systems
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• v.2 no.4
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• pp.521-527
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• 1998

The turnover of epidermal cells after seawater adaptation of the freshwater fishwas studied in the guppy (Poecilia reticulata) by means of Proliferating cell nucleus antigen (PCNA) immunocytochemistry and transmission electron microscopy. The number of PCNA-immunoreactive cells in the epidermis of the seawater-adapted guppies, which becomes thinner than that in the fresh-water, generally increases four times as much. Degeneration of filament-containing cells by necrosis or apoptosis occurs mainly in epidermal cells. Apoptotic filament-containing cells seem to be shed into the water in the environment instead of phagocytosis by adjacent macrophages. The apoptotic chloride cell has a highly condensed cytoplasm and the lumen of tubular system is distended. The apoptotic mucous cell, which has an electron-dense cytoplasm, is characterized by the presence of a large multivesicular body of different electron densities. Macrophages contain many electron-dense lysosomal bodies and large vesicles filled with cellular debris. It is concluded that mitosis and apoptosis of epidermal cells are greatly stimulated when fish are adapting to seawater. This result reflects an increase in epidermal cell turnover by change of environmental salinity.

• Animal cells and systems
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• v.1 no.1
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• pp.151-155
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• 1997

Promoter of the Drosophila proliferating cell nuclear antigen (PCNA) gene contains DRE (Drosophila DNA replication-related element) required for the high level expression of replication-related genes. Recently, we found that promoter region of the D-raf (a Drosophila homolog of the human c-raf-1) contains two sequences homologous to the DRE and demonstrated the DRE/DREF (DRE-binding factor) involvement in regulation of the D-raf gene. In this study, using ursolic acid (UA), a pentacyclic triterpene acid reported to possess antitumor activities, we examined effects of UA on proliferation of the Drosophila cultured Kc cells and on expression of the PCNA and D-raf genes. UA showed an inhibitory effect on proliferation of the Kc cells in a concentration-dependent manner in DNA content assays and [3H]thymidine incorporation assays. The IC50 value of anti-proliferative effects of UA in DNA content assays was about 7.5uM. UA showed inhibitory effects on expression of the PCNA as well as on that of the D-raf, which were examined with the reporter plasmic p5'-168DPCNACAT or p5'-878DrafCAT, respectively. The results obtained in the present study suggest that expression of the PCNA and D-raf genes is coordinately regulated in at least UA-treated Kc cells and that down-regulation of expression of the PCNA and D-raf genes might be related with the antitumor activities of UA.

• 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.

• International Journal of Oral Biology
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• v.43 no.2
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• pp.93-100
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• 2018

The investigation of the embryonic development of the cerebellum has a long history. The postnatal normal development of the cerebellum in rodents and other animals became a popular topic for morphological investigations nearly a century ago. However, surprisingly, only a few studies are available regarding the prenatal normal development of the rodent cerebellum, especially in guinea pigs. Cell proliferation is essential for the development of the nervous system. The assessment of cell proliferation can be achieved by using various methods. In this study, we investigated the cell proliferation of the cerebellar cortex in guinea pigs at different stages of pregnancy and in postnatal life. Fetuses were obtained by cesarean section at 50 or 60 days of gestation (dg). Immunohistochemistry was performed with proliferating cell nuclear antigen (PCNA) antibody in the cerebellum. Strong PCNA immunoreactivity was observed in the external granular layer (EGL), which is a neurogenic zone in the cerebellum. The proportion of PCNA-IR cells was greater at 1 week than at 60 dg in lobule I, but not lobule VIII. After 50 dg, the width of the EGL continued to decline until 1 week, due to the maturation of the EGL cells. These results demonstrate the pattern of PCNA immunoreactivity in the developing cerebellum of guinea pigs. This serves as a guideline to study abnormal cerebellum development.

• Applied Microscopy
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• v.40 no.2
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• pp.73-80
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• 2010

Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.

• 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.