OBJECTIVE: The purpose of this study was (1) to evaluate the expressions of clusterin, bax, Ki-67, p53, and apoptotic index in epithelial ovarian tumors, borderline and malignant ovarian tumors, (2) to find out the correlation between their expressions and clinicopathological parameters, and (3) to evaluate the effect on the patient's survival according to their expressions. METHODS: The histological and clinical findings of 22 cases of ovarian cystadenomas, 44 cases of borderline tumors and 96 cases of carcinomas were evaluated. Expressions of clusterin, bax, Ki-67, p53, and apoptotic index were studied on paraffin-embedded tissue sections by immunohistochemical methods. RESULTS: The expressions of clusterin, p53, and Ki-67 were higher in ovarian carcinomas than borderline tumors. The overexpression of p53, and Ki-67 were frequent in high stage, poorly differentiated and bilateral ovarian carcinomas. The overexpressions of clusterin, bax, p53, and Ki-67 showed a statistically significant correlation with histologic type. Apoptotic index was higher in bax overexpression group, but there was no correlation with overexpression of clusterin or p53. Ki-67 was higher in p53 overexpression group, but there was no correlation with overexpression of clusterin or p53. There was no statistically significant correlation with each other between the overexpressions of clusterin, bax, p53, and Ki-67. The overexpressions of clusterin, Ki-67, p53 was associated with overall patient's survival in borderline significance. CONCLUSION: The overexpression of p53, and Ki-67 were frequent in poorly differentiated ovarian carcinomas. So the overexpression of p53, and Ki-67 can be used as prognostic factor. The overexpression of clusterin was more in epithelial ovarian carcinomas than in borderline tumors but showed no significant correlation with the overall patient's survival. Further studies are required to clarify the possibility of using clusterin for target therapy in epithelial ovarian carcinomas.
Clusterin ; Cystadenoma

OBJECTIVE: Immunohistochemistry was performed on normal and cervical cancer tissues to determine the differential expression patterns of clusterin. METHODS: Fifteen normal cervical tissues and thirty-two primary cervical cancer tissues were used. Clusterin expression was determined with immunohistochemical staining and quantified with scoring system. RESULTS: The normal cervical tissues expressed low levels of clusterin expression and their mean score was 1.35. On the contrary cervical cancer tissues showed high levels of clusterin expression with mean score, 4.08. And the difference of expression was statistically significant (P<0.05). CONCLUSION: These data suggest that clusterin expression is higher in cervical cancer tissues than normal cervical tissues.
Clusterin* ; Immunohistochemistry ; Uterine Cervical Neoplasms*

PURPOSE: This study was performed to evaluate the expressions of osteopontin (OPN) and clusterin in a transitional cell carcinoma (TCC) of the urinary bladder, and then compare their expression rates with the tumor invasiveness. MATERIALS AND METHODS: Twenty-five superficial and 25 invasive TCC were used for immunohistochemical staining. RESULTS: All 25 non-invasive TCC showed a strong positive reaction for OPN. Twenty of the invasive TCC showed a strong positive reaction for OPN, but 5 showed only a weak positive reaction. OPN expression was significantly decreased in the invasive TCC (p=0.02). Eighteen superficial TCC showed a weak positive reaction for clusterin, with 7 showing a negative reaction. Nine invasive TCC showed a strong positive reaction for clusterin, and 11 showed only a weak positive reaction. Five invasive TCC showed a negative reaction for clusterin. Clusterin expression was significantly increased in the invasive TCC (p=0.001). CONCLUSIONS: These results may suggest that OPN and clusterin could be used as markers to predict the biological behavior of a TCC.
Carcinoma, Transitional Cell* ; Clusterin* ; Osteopontin* ; Urinary Bladder*

Clusterin (CLU) is a multifunctional glycoprotein that has secretory and nuclear isoforms. The two isoforms are known to play opposite roles in cell survival/death. In this review, we summarize recent progress on the pro-apoptotic function of nuclear CLU in vitro and in vivo and discuss previous reports on the role of CLU in brain damage and neurodegeneration.
Apoptosis ; Brain ; Clusterin ; Glycoproteins ; Protein Isoforms

Cardiovascular Diseases ; metabolism ; physiopathology ; Clusterin ; metabolism ; physiology ; Humans

PURPOSE: This study examined the expression of clusterin and Ki-67 in human transitional cell carcinoma(TCC). In addition, the relationship of clusterin and Ki-67 expression with the clinicopathological factors and prognosis of human TCC was investigated. MATERIALS AND METHODS: 149 human TCC tissues were obtained from 149 patients who underwent a radical cystectomy(n=81) or transurethral resection(n=68). The expression of clusterin and Ki-67 was analyzed using immunohistochemical staining. The results were evaluated with respect to the clinicopathological factors. RESULTS: Positive clusterin expression was observed in 21.1% of the total TCC tissues. The expression of clusterin was not significantly related to age, gender, tumor stage and grade. However, recurrence-free survival rate of the patients with positive clusterin expression was significantly lower than that of patients with negative clusterin expression(p=0.02). The expression level of Ki-67 in the TCC tissues was associated with the tumor stage(p<0.001) and grade(p<0.001), but not with age and gender. Furthermore, the recurrence-free survival rate of patients with strong Ki-67 expression was significantly lower than that of patients with weak Ki-67 expression(p<0.001). The expression of clusterin was not significantly related to the level of Ki-67 expression. However, in the patients showing strong Ki-67 expression, the recurrence-free survival rate of the patients with positive clusterin expression was significantly lower than that of the patients with negative clusterin expression(p<0.001). CONCLUSIONS: These results suggest that the expression of clusterin and Ki-67 can be used as a useful predictor of the prognosis of patients with human TCC.
Carcinoma, Transitional Cell ; Clusterin ; Humans ; Prognosis ; Survival Rate

PURPOSE: This study was performed to evaluate the relationship of the expressions of clusterin with Ki-67 and the clinicopathological factors and significance of clusterin expression in human renal cell carcinoma (RCC). MATERIALS AND METHODS: Normal kidney (n=26) and RCC tissues (n=111) were obtained from 111 patients who had undergone a radical or partial nephrectomy. The expressions of clusterin and Ki-67 protein were analysed using immunohistochemical staining. The medical records of the patients were retrospectively reviewed to evaluate the clinicopathological factors. RESULTS: In contrast to the clusterin and Ki-67 expressions of 30.8 and 11.5%, respectively in the normal kidney (n=26), those in the RCC tissues were 93.7 and 28.8% (n=111), respectively (p<0.05). In contrast to the normal tissues, Ki-67 staining was significantly correlated with the expression of clusterin in the RCC tissues (p<0.05). The expression level of clusterin protein in the RCC tissues was significantly related to the tumor stage and grade (p<0.05), but not to age, gender or histological cell type (p>0.05). Furthermore, the recurrence-free survival in patients with strong clusterin expression was significantly lower than in those with weak expression (p<0.05). CONCLUSIONS: These findings suggest that clusterin may be involved in the progression of RCC and; therefore, a useful prognostic variable in patients with an RCC.
Carcinoma, Renal Cell* ; Clusterin* ; Humans* ; Ki-67 Antigen ; Kidney ; Medical Records ; Nephrectomy ; Retrospective Studies

OBJECTIVETo investigate the expression and correlation of mast cell, Clusterin/apoJ and transforming growth factor-beta (TGF-beta) in the different stages of human dermal hemangioma.

METHODSImmunohistochemical stain technique (SABC) and toluidine blue (TB) stain technique were respectively used to detect the expression level of Clusterin/apoJ and TGF-beta and the number of mast cells in the different stages of human dermal hemangioma.

RESULTSThere was remarkable statistical difference between the advanced stage of proliferative hemangioma and the other stages of proliferative hemangioma in the number of mast cell(P<0.01). There was also remarkable statistical difference between the early stage of involutional hemangioma and the other stages of involutional hemangioma in the number of mast cell (P<0.01). The expression of Clusterin/apoJ and TGF-beta in the advanced stage of proliferative hemangioma was significantly higher than the other stages in proliferative hemangioma (P<0.01). The expression of Clusterin/apoJ and TGF-beta in the early stage of involutional hemangioma was significantly higher than the other stages in involutional hemangioma (P<0.01). There was a significantly positive correlation between Clusterin/apoJ and TGF-beta in the different stages of human dermal hemangioma (P<0.01). The expression level of Clusterin/apoJ and TGF-beta was positively correlated with the number of mast cell in the different stages of human dermal hemangioma (P<0.01).

CONCLUSIONMast cell may play a promotive role of apoptosis during the spontaneous regulate the expression of Clusterin/apoJ and promote the spontaneous involution of human dermal hemangioma.

BACKGROUND: Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men. METHODS: For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period. RESULTS: Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues. CONCLUSION: These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.
Circadian Rhythm* ; Clusterin* ; Cues ; Fasting ; Female ; Glycoproteins ; Humans ; Leptin ; Lipid Metabolism ; Male ; Meals ; Neurobiology ; Obesity ; Plasma*

PURPOSE: The aim of this study was to know whether and how tamsulosin induces apoptosis of normal rat prostate cells, and the relationship between apoptosis and clusterin expression. MATERIALS AND METHODS: We used a prostate cell line, NRP-152 cells which are the basal epithelium cell originated from rat prostate. The NRP-152 cells were treated with various concentrations(50, 100, 200, 400 uM) of tamsulosin for 24 h. To evaluate apoptosis, the cultured NRP-152 cells were stained with Heochst 33258 and Propidium Iodide (PI) without fixation. We also examined DNA fragmentation analysis to confirm apoptosis. In addition, to elucidate the signal transduction pathway by which apoptosis is induced, we examined Bcl-2 family proteins such as Bcl-2, Bax, Bad, Bcl-xL, and Bim by real-time RT-PCR. RESULTS: After tamsulosin treatment, the rate of apoptosis was 25% at 100 micrometer, 50% at 200 micrometer, and 63% at 400 micrometer, whereas the rate of necrosis was 10% at 100 micrometer, 38% at 200 micrometer, and 56% at 400 micrometer. DNA fragmentation was also gradually increased and the highest at 400 micrometer, similar to apoptotic cell rates. As a result of real-time RT-PCR, there was significant difference of Bcl-2 and Bim mRNA expression among the groups. Expression of clusterin protein was significantly increased after treatment of tamsulosin, even as low as 50 micrometer concentration. CONCLUSION: These results demonstrate that tamsulosin causes the cell death of NRP-152 cells, displaying low concentration of tamsulosin induces apoptosis, but high concentration occurs necrosis. Bim, a proapoptotic factor of the Bcl-2 family, expression was increased in the cells treated with tamsulosin, whereas Bcl-2 expression was decreased. The present study suggests that clusterin may play a role in the process of apoptosis induced by tamsulosin and Bim could be involved in the apoptosis.
Animals ; Apoptosis* ; Cell Death ; Cell Line ; Clusterin* ; DNA Fragmentation ; Epithelium ; Humans ; Necrosis ; Propidium ; Prostate ; Rats ; RNA, Messenger ; Signal Transduction