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1.
Korean Journal of Urology ; : 1201-1208, 2004.
Article in Korean | WPRIM | ID: wpr-11540

ABSTRACT

PURPOSE: Promoter methylation provides an alternative pathway for the loss of tumor suppressor gene functions. This epigenetic change is a new marker for human cancers. We herein investigated the aberrant methylation profile of bladder cancer to identify the epigenetic markers that are useful for the diagnosis of bladder cancer. MATERIALS AND METHODS: Gene promoter methylation was analyzed in 50 bladder transitional cell cancer (TCC) tissues and 30 nonmalignant bladder mucosal tissues including 21 tissue samples with normal histology and 9 tissue samples with inflammation. The methylation status of 13 tumor suppressor genes was analyzed by methylation specific polymerase chain reaction and bisulfite genomic sequencing. The methylation frequency and methylation index were comparatively analyzed in each group of tissues. RESULTS: Bladder TCC showed a high frequency of promoter hypermethylation for RASSF1A(62.0%), RARbeta2(54.0%), E-cadherin(48.0%), p16INK4A(46.0%), p14ARF(34.0%) and H-cadherin(32.0%), whereas, methylation was less common for MGMT(18.0%), DAPK(14.0%) and p15INK4B(10.0%), and methylation was rare for GSTP1(4.0%), FHIT(2.0%), APC(2.0%) and MLH1(2.0%). Benign bladder mucosa rarely showed aberrant methylation except for E-cadherin (10.0%) and RARbeta2(10.0%). The methylation index of bladder TCC(0.25) was significantly higher than that of the benign bladder mucosal tissues(0.03, p<0.01). Remarkably, all of the bladder cancer tissues showed aberrant methylation of at least one of 6 genes including RASSF1A, RARbeta2, p16INK4A, p14ARF, E-cadherin and H-cadherin, whereas only 5 of 30 (16.7%) benign bladder mucosa tissues showed the same findings. CONCLUSIONS: Aberrant promoter methylation of tumor suppressor genes may be a critical step in the development of bladder TCC. Aberrant promoter methylations of RASSF1A, RARbeta2, p16INK4A, p14ARF, E-cadherin and H-cadherin may be promising epigenetic markers for the diagnosis and follow up of bladder cancer.


Subject(s)
Humans , Cadherins , Diagnosis , Epigenomics , Follow-Up Studies , Genes, Tumor Suppressor , Inflammation , Methylation , Mucous Membrane , Polymerase Chain Reaction , Tumor Suppressor Protein p14ARF , Urinary Bladder Neoplasms , Urinary Bladder
2.
Journal of Korean Society of Endocrinology ; : 140-152, 2003.
Article in Korean | WPRIM | ID: wpr-63085

ABSTRACT

BACKGROUND: Activation of the RET proto-oncogene, located on the long arms of chromosome 10, contributes to the development of thyroid cancers in two different ways. Somatic rearrangements of RET with variable genes of activation are frequently found in papillary thyroid carcinomas. And Ggerm-line point mutations are responsible for the development of medullary thyroid carcinoma and the multiple endocrine neoplasia type 2(MEN2). There are several conflicting reports on the influences of RET expression and RET/PTC rearrangements on the clinical outcome of thyroid cancer. Therefore, we performed an examination of RET expression and RET/PTC-1, -2, -3 rearrangements in papillary thyroid carcinomas and other thyroid diseases. METHODS: Twenty-six papillary thyroid carcinomas(PTCs), three follicular thyroid carcinomas (FTCs), one anaplastic thyroid carcinoma(ATC), five follicular adenomas(FAs), nineteen hyperplasias, and two normal thyroid tissues were included in this study. RT-PCR and immunohistochemistry analysis were done to identify RET gene, RET/PTC rearrangements, and ret RET protein expression. RESULTS: By RT-PCR, 89.4% of PTCs, 100% of FTCs, and 62.1% of hyperplasias expressed the RET gene, but no RET was observed in ATCs, FAs, and normal thyroid tissues. RET/PTC-1, -2,-3 rearrangements were not detected in any specimens. Immunohistochemical results revealed that 76.9% of PTCs, 50% of FAs, 52.3% of hyperplasias, and 20.6% of normal thyroid tissues expressed the RET ret protein, but FTCs and ATCs did not. Most PTCs showed strong cytoplasmic positivity in RET ret immunostaining, but the positive non- PTCs expressed weak and membranous staining. Overall, the two methods for detecting RET gene, RT-PCR and immunohistochemistry showed similar results. CONCLUSION: The RET gene was highly expressed in PTCs. In contrast to the previous reports of that theRET gene expression of RET gene is being limited to PTCs, RET was also expressed in hyperplasias, Fas, and normal thyroid tissues. However, the pattern and the degree of expression of the RET ret protein in non- PTCs were are different from those in PTCs.


Subject(s)
Adenocarcinoma, Follicular , Arm , Chromosomes, Human, Pair 10 , Cytoplasm , Gene Expression , Hyperplasia , Immunohistochemistry , Multiple Endocrine Neoplasia , Point Mutation , Proto-Oncogenes , Thyroid Diseases , Thyroid Gland , Thyroid Neoplasms
4.
Korean Journal of Urology ; : 175-186, 1999.
Article in Korean | WPRIM | ID: wpr-171952

ABSTRACT

PURPOSE: To identify antitumor effect, indication and antitumor mechanism of p21/WAF1 gene therapy in human kidney and bladder cancer. MATERIALS AND METHODS: We cloned cDNA of wild type human p21 gene by reverse transcription-polymerase chain reaction(RT-PCR) technology and constructed a mammalian expression plasmid vector carrying cDNA of wild type human p21 and CMV enhancer/promotor(pCMV-p21). pCMV-p21 was administered in vitro in complex with HDL cationic polyliposome into human kidney cancer cells(CURC-1 and CURC-2), bladder cancer cells(RT4 and T24), and liver cancer cells(Hep3B and HepG2), followed by analysis of viable cell number, cellular morphology, cell cycle distribution and development of apoptosis. RESULTS: The expression of p21 was preserved in p53-wild type cells and markedly decreased or absent in p53-mutant cells. Administration of pCMV-p21:HDL complex induced high level expression of p21 and significant suppression of growth in all of the cancer cells examined, regardless of their genetic status of p21 and p53. Transfer of p21 to cancer cells induced not only decrease of proportion of cells in G2+M/S phase but also apoptosis. CONCLUSIONS: HDL cationic polyliposome-mediated p21 gene transfer may become a promising therapeutic modality for human kidney and bladder cancer and that p21 may have a novel function to induce apoptosis to human bladder and kidney cancer cells. Further studies are necessary on in vivo antitumor effect of p21 gene transfer and molecular mechanism of p21 gene-induced apoptosis.


Subject(s)
Humans , Apoptosis , Cell Count , Cell Cycle , Cell Line , Clone Cells , DNA, Complementary , Genetic Therapy , Kidney Neoplasms , Kidney , Liver Neoplasms , Plasmids , Urinary Bladder Neoplasms , Urinary Bladder
5.
Korean Journal of Urology ; : 29-40, 1999.
Article in Korean | WPRIM | ID: wpr-44459

ABSTRACT

PURPOSE: Angiogenesis is essential for the growth and metastasis of tumors. Mechanism of angiogenesis of prostate cancer remains to be defined. Vascular endothelial growth factor(VEGF) is one of the most potent angiogenic factors and we have previously demonstrated that VEGF was expressed by rat ventral prostate in an androgen dependent manner. We herein investigated whether VEGF also plays an important role in tumor angiogenesis of prostate cancer and whether endocrine therapy inhibits expression of VEGF and angiogenesis in prostate cancer. MATERIALS AND METHODS: Frozen tumor tissues were obtained from 21 patients with prostate cancer before and 3 months after endocrine therapy and angiogenic activity was analyzed by measuring microvascular density(MVD) using immunohistochemical study for factor VIII and VEGF expression by RT-PCR -Southern blot assay and immunogistochemical study, respectively. RESULTS: Prostate cancer showed significantly increased expression of VEGF and MVD as compared with normal prostatic tissues and benign hyperplastic tissues(p<0.001). There were signficant correlations between VEGF expression and MVD of prostate cancer tissues. After endocrine therapy, both MVD and VEGF expression in prostate cancer tissues were signficantly decreased as compared with those of before endocrine therapy(p<0.001). There were no signficant differences between bilateral orchiectomy and leuprolelin therapy in inihibitory effect of VEGF expression and MVD in prostate cancer tissues. CONCLUSIONS: These results suggest that VEGF may be a major angiogenic factor in prostate cancer and one of important action mechanisms of endocrine therapy in prostate cancer may be in its inhibition of VEGF expression and tumor angiogenic activity.


Subject(s)
Animals , Humans , Rats , Angiogenesis Inducing Agents , Factor VIII , Neoplasm Metastasis , Orchiectomy , Prostate , Prostatic Neoplasms , Vascular Endothelial Growth Factor A
6.
Korean Journal of Urology ; : 1051-1060, 1998.
Article in Korean | WPRIM | ID: wpr-51029

ABSTRACT

PURPOSE: Renal oncocytoma has been a focus of interest in urologic oncology. The biologic and molecular characteristics of this disease remains ill defined due to paucity of ideal in vitro model. In this present study a new cell line of human renal oncocytoma, CURO, has been established and characterized. MATERIALS AND METHOD: The CURO cells were cultured from tissues obtained from radical nephrectomy specimen of incidentally found renal oncocytoma. The cellular and molecular biological characleristics of CURO cells were analyzed. RESULTS: CURO cells grew in monolayer with a rapid doubling time of 20 hours. The cells showed abundant mitochondria and well developed microvilli, and expressed cytokeratin, epithelial membrane antigen, and lectins of distal renal tubular and collecting duct origin. The cells showed aneuploidy with high proportion of cells in G2+M phase(27%) on flow cytometric analysis. Karyotyping study revealed clonal heterogeneity: Majority showed normal 46XX, whereas, 12% of cells showed deletion or translocation of chromosome 19, but none of the cells showed abnormality of 3p. The cells neither showed mutation of p53 gene and nor expressed two major angiogenic factors of renal cell carcinoma: vascular endothelial growth factor and basic fibroblast growth factor. The CURO cells didn't show tumorigenecity in athymic nude mouse on either subcutaneous or subrenal capsular implantation. CONCLUSIONS: The results of this study suggest that CURO may be a valuable model to study renal oncocytoma. Renal oncocytoma may be a benign tumor of distal renal tubular or collecting duct origin, but it may contain clone with high proliferative activity. Change of chromosome 19 may be a marker of development or proliferation of renal oncocytoma.


Subject(s)
Animals , Humans , Mice , Adenoma, Oxyphilic , Aneuploidy , Angiogenesis Inducing Agents , Carcinoma, Renal Cell , Cell Line , Chromosomes, Human, Pair 19 , Clone Cells , Fibroblast Growth Factor 2 , Genes, p53 , Karyotyping , Keratins , Lectins , Mice, Nude , Microvilli , Mitochondria , Mucin-1 , Nephrectomy , Population Characteristics , Vascular Endothelial Growth Factor A
7.
Korean Journal of Urology ; : 837-846, 1996.
Article in Korean | WPRIM | ID: wpr-205462

ABSTRACT

Background. p53 gene mutations are known to play an important role in the progression of bladder cancer. Immunohistochemistry (IHC) has been used routinely to analyze p53 gene mutations by identifying nuclear overexpression of p53 protein. However, the accuracy and value of IHC as a marker of p53 gene mutation has been questioned. Methods. In this study of 35 bladder transitional cell carcinoma, we compared results of IHC staining with those of polymerase chain reaction (PCR) of exons 5 to 8 of p53 gene, followed subcloning of PCR products, and DNA sequencing analysis. Results. On IHC staining, 12 bladder tumors (37.5%) showed overexpression of p53 as defined by nuclear staining of 10% or more of tumor cells. On DNA sequencing analysis, 11 out of 32 cases (34.3%) showed point mutations in one or more exons of p53 gene. The results of IHC were concordant with that of DNA sequencing in 84.3% of cases. The sensitivity and specificity of detecting p53 mutations by IHC were estimated to be 81.8% and 90.5%, respectively. Conclusion. When properly used, IHC is a highly sensitive and specific, and clinically useful method to detect p53 gene mutations in bladder cancer.


Subject(s)
Carcinoma, Transitional Cell , DNA , Exons , Genes, p53 , Immunohistochemistry , Point Mutation , Polymerase Chain Reaction , Sensitivity and Specificity , Sequence Analysis, DNA , Urinary Bladder Neoplasms , Urinary Bladder
8.
Korean Journal of Urology ; : 847-858, 1996.
Article in Korean | WPRIM | ID: wpr-205461

ABSTRACT

Background. p53 gene mutations are known to be an important prognostic factor in bladder cancer. Single strand conformation polymorphism (SSCP) analysis has been suggested to be a promising method to detect p53 gene mutation. However, the technical pitfalls associated with conventional SSCP using radioisotope precluded its wide application in clinical practice. We herein have tried non-isotopic SSCP and analyzed the value of this, new method for detecting mutation of p53 gene in bladder cancer. Methods. In this study of 32 bladder transitional cell carcinoma, we comparatively analyzed polymerase chain reaction (PCR) of exons 5 to 8 of p53 gene, followed by 1) conventional, isotopic-SSCP analysis, 2) non-isotopic SSCP analysis, and 3) DNA sequencing analysis. Results. On isotopic SSCP analysis, 9 out of 32 cases (28.1%) showed mobility shifts. On non-isotopic SSCP analysis, 10 cases (31.0%) showed mobility shifts. On DNA sequencing analysis, 11 cases (34.3%) showed point mutations. The results of isotopic SSCP analysis and non-isotopic SSCP analysis were concordant with that of DNA sequencing in 87.5% and 96.9% of cases, respectively. The sensitivity and specificity of detecting p53 mutations by isotopic and non-isotopic SSCP analysis were estimated to be 81.8% and 100%, and 91.0% and 100%, respectively. Non-isotopic SSCP significantly reduced the time and cost to analyze p53 mutation to 7.9% and 16.0% of those of isotopic SSCP, respectively (p<0.005) . Conclusions. Non-isotopic SSCP is a highly sensitive and specific, time-saving, and cost- effective method to detect p53 gene mutations in bladder cancer. This new method may be promising for the clinical application.


Subject(s)
Carcinoma, Transitional Cell , Exons , Genes, p53 , Point Mutation , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Sensitivity and Specificity , Sequence Analysis, DNA , Urinary Bladder Neoplasms , Urinary Bladder
9.
Korean Journal of Urology ; : 607-618, 1996.
Article in Korean | WPRIM | ID: wpr-175363

ABSTRACT

BACKGROUND AND PURPOSE: We had previously demonstrated by immunohistochemical study (IHS) that nm23-H1 gene may play an important role in disease prognosis as well as its participation in metastasis of urothelial cancer. The purpose of present study was 1) to reexamine the role of nm23-H1 gene in urothelial cancers at molecular level, 2) to identify the molecular mechanism of decreased immunoreactivity for nm23-H1 protein in metastatic urothelial cancers, and 3) to identify whether IHS is reliable in studying the expression of nm23-H1. MATERIALS AND METHODS: We studied expression level and mutation profiles of nm23-H1 gene in 25 fresh surgical specimens of urothelial cancer by reverse transcription polymerase chain reaction(RT-PCR)-Southern blotting analysis, and PCR of genomic DNA followed by single strand conformation polymorphism and sequencing analysis. The results of RT-PCR-Southern blotting were comparatively analyzed with those of IHS. RESULTS: mRNA transcript levels of nm23-H1 gene were significantly decreased in tumor tissues with metastasis as compared with those without metastasis. The transcript levels of nm23-H1 gene were also significantly decreased in metastatic tumor tissues as compared with primary tumor tissues. Point mutation of nm23-H1 gene was detected in only 1 of 13 urothelial cancer tissues with metastasis, whereas, mutation was observed in none of those without metastasis. The results of IHS corresponded with those of RT-PCR-Southern blotting analysis in 23 of 25 specimens. CONCLUSIONS: The nm23-H1 gene may play an important role in metastasis of urothelial cancer. Decreased transcription at mRNA level may be a major molecular mechanism of loss of immunoreactivity for nm23-H1 protein in urothelial cancer. IHS used in the present study may be a clinically useful method to study the expression of nm23-H1 and to predict metastasis potential and prognosis of urothelial cancers.


Subject(s)
DNA , Neoplasm Metastasis , Point Mutation , Polymerase Chain Reaction , Prognosis , Reverse Transcription , RNA, Messenger , Urologic Neoplasms
10.
Korean Journal of Urology ; : 521-530, 1996.
Article in Korean | WPRIM | ID: wpr-181493

ABSTRACT

BACKGROUND AND PURPOSE: Laser induced prostatectomy(LIP) has recently been considered as safe alternative to conventional transurethral resection of the prostate(TURP) in the surgical treatment of BPH. However, the value of LIP remains incompletely defined. We herein have performed a prospective study to compare TURP and LIP in treatment efficacy, safety and costs to define the value of LIP. MATERIALS AND METHODS: 113 patients with BPH who were candidates of TURP were randomized to undergo TURP or LIP and were adequately followed up for more than 1 year. There were no significant differences in preoperative clinical characteristics between 55 patients who underwent TURP and 58 patients who underwent LIP. For the LIP procedure, Nd:YAG was used in 42 patients and diode laser in 16 patients, respectively. 37 patients were treated by contact LIP only, and 21 with hybrid procedures of contact LIP and noncontact LIP using side firing laser fiber or interstitial laser fiber. Seven patients underwent LIP under local anesthesia at the outpatient department. RESULTS: International prostate symptom score(IPSS) and peak urinary flow rate(Qmax) were significantly improved at 3 months, 6 months, and 1 year after LIP as well as after TURP. There were no significant difference between TURP group(85.4%) and LIP group(87.9%) in treatment success rate as defined by improvement of IPSS and Qmax as well as patient's content for the surgical outcome. Nine(16.4%) and two(3.6%) of the patients who underwent TURP and none of the patients who LIP underwent developed ignificant bleeding and electrolyte imbalance, respectively. There were no significant difference in postoperative incidence of retrograde ejaculation, infection and urethral stricture between the two groups. Compared to TURP, the LIP procedure required significantly shorter hospitalization(6.8 vs 4.5 days) and catheterization(4.1 vs 2.6 days, all p<0.0l). There was no significant difference in total treatment cost between the two groups. CONCLUSIONS: LIP may be comparable to TURP in terms of short term treatment efficacy and cost effectiveness. LIP may be better than TURP in terms of safety and shortened hospitalization and catheterization. Further studies are necessary on long-term outcomes of LIP."


Subject(s)
Humans , Male , Anesthesia, Local , Catheterization , Catheters , Cost-Benefit Analysis , Ejaculation , Fires , Health Care Costs , Hemorrhage , Hospitalization , Incidence , Lasers, Semiconductor , Lip , Outpatients , Prospective Studies , Prostate , Prostatectomy , Transurethral Resection of Prostate , Treatment Outcome , Urethral Stricture
11.
Korean Journal of Urology ; : 507-517, 1995.
Article in Korean | WPRIM | ID: wpr-88336

ABSTRACT

No abstract available.


Subject(s)
Prostatectomy , Prostatic Hyperplasia
12.
Korean Journal of Urology ; : 135-147, 1995.
Article in Korean | WPRIM | ID: wpr-57251

ABSTRACT

No abstract available.


Subject(s)
Neoplasm Metastasis , Prognosis
13.
Korean Journal of Urology ; : 1065-1072, 1994.
Article in Korean | WPRIM | ID: wpr-209134

ABSTRACT

The clinical course of individual patient with renal cell carcinoma (RCC) is variable and difficult to predict accurately. The values of various classical prognostic factors in RCC remain ill-defined. Data on molecular analysis of oncogene and tumor suppressor genes including p53 may provide useful prognostic information for RCC. We herein investigated the prognostic value of multiple clinical and pathological parameters as well as p53 mutation in 40 patients with pathologically confirmed RCC. Mutations of p53 gene were analyzed by immunohistochemical staining using monoclonal antibody for p53 protein( M1801). On univariate analysis using log-rank test multiple parameters showed prognostic value, including clinical stage ( Robson), nuclear grade, mutation of p53, cell type, body weight loss, anemia, and increased serum level of calcium and erythrocyte sedimentation rate. However, on multivariate analysis using Cox's proportional hazard model only three parameters including stage(p <0.001 ), nuclear grade(p < 0.05), and mutation of p53(p<0.05) were found to have significant independent prognostic value. These results suggest that in RCC clinical stage and nuclear grade are two most important prognostic factors and analysis of p53 mutation may provide additional important prognostic information.


Subject(s)
Humans , Anemia , Blood Sedimentation , Calcium , Carcinoma, Renal Cell , Genes, p53 , Genes, Tumor Suppressor , Multivariate Analysis , Oncogenes , Proportional Hazards Models , Somatotypes , Weight Loss
14.
Korean Journal of Urology ; : 1309-1320, 1994.
Article in Korean | WPRIM | ID: wpr-67046

ABSTRACT

Experimental study was done to investigate the effect of combination therapy of recombinant interferon alpha-2a (IFN-alpha) and 13-cis-retinoic acid(13cRA) or all-transretinoic acid(TRA) on the in vitro and in vivo proliferation of human renal carcinoma cell line(CURC-2). 13cRA inhibited the in vitro proliferation of CURC-2 significantly at tolerable serum concentration in human(0.000001mole) and IC50 of 13cRA was found to be about 0.000003 mole. TRA did not inhibit the in vitro proliferation of CURC-2 significantly at tolerable serum concentration and IC50 of TRA was found to be too high(0.00003mole) to be administered in vivo. IFN-alpha inhibited in vitro proliferation of CURC-2 significantly with IC50 of about 500 unit/ml. Combined administration of low concentration of IFN-alpha(300 unit/ml) and 13cRA (0.000001mole) showed significant synergistic antiproliferative effect (79%, p<0.01 ) compared to single administration of IFN-alpha(29%) and 13cRA(29%). Combined administration of IFN-alpha and TRA showed underadditive effect. Combined administration of IFN-alpha(50,000 unit s.c./mouse/day) and 13cRA (0.5 mg p.o./mouse/day) to nude mouse significantly decreased the incidence(p<0.05) and tumor weight(p<0.001) of subcutaneously implanted CURC-2 cells and showed significant synergistic effect(p<0.05) compared to 13cRA or IFN-alpha single administration. 13cRA-administered animals did not show toxic sign of hypervitaminosis A. These results suggest that IFN-alpha and 13cRA show significant synergistic antiproliferative effect both in vitro and in vivo on human renal carcinoma cells and that combination therapy of IFN-alpha and 13cRA may become effective and safe adjuvant therapy for renal cell carcinoma. Based on the results of this study, clinical trials of combination therapy of IFN-alpha and 13cRA are ongoing in patients with renal cell carcinoma.


Subject(s)
Animals , Humans , Mice , Carcinoma, Renal Cell , Hypervitaminosis A , Inhibitory Concentration 50 , Interferon-alpha , Interferons , Mice, Nude , Tretinoin
15.
Korean Journal of Urology ; : 748-763, 1993.
Article in Korean | WPRIM | ID: wpr-40121

ABSTRACT

Experimental study was done to investigate the effect of suramin on the in vitro and in vivo proliferation and metastasis of penile squamous carcinoma cell line(CUPE-1), morphological changes of CUPE-1 cells induced by suramin and mechanism of action of suramin. Suramin inhibited in vitro proliferation of CUPE-1 significantly with 1C50 of 100 microgram/ml media. In vitro antiproliferative effect of suramin on CUPE-1 was reversible after stopping administration of the drug. Weekly intraperitoneal administration of 200 mg/kg of suramin to nude mouse inhibited the proliferation and metastasis of intraperitoneally implanted CUPE-1 cells significantly. but did not show significant effect on the proliferation of subcutaneously implanted CUPE-1 cells. Suramin induced senile changes on ultrastructure of CUPE-1 cells. Suramin of 300 microgram/ml inhibited the prolireration-stimulating effect of EGF significantly, whereas, suramin of 100 microgram/ml did not inhibit the effect of EGF significantly. Suramin did not show significant cytotoxicity on 3H-thymidine release assay. These results suggest that suramin is a promising drug for the treatment of advanced penile squamous cell carcinoma and blood level of suramin in clinical trial should be continuously maintained in about 300 microgram/ml, and that the main machanism of suramin against CUPE-1 is cytostatic. by antagonizing the action of EGF and inducing growth arrest and senile change.


Subject(s)
Animals , Mice , Carcinoma, Squamous Cell , Epidermal Growth Factor , Mice, Nude , Neoplasm Metastasis , Robenidine , Suramin
16.
Korean Journal of Urology ; : 391-401, 1993.
Article in Korean | WPRIM | ID: wpr-34507

ABSTRACT

Glutathione S-transferase(GST) is a family of enzymes which plays an important role in cellular detoxification by catalyzing the conjugation of electrophilic xenobiotics with glutathione and recently have been shown to be closely associated with chemical carcinogenesis and resistance to cytotoxic drugs in several types of malienancies. However, it remains ill-defined about the role of GST in bladder tumor. Herein we performed immunohistochemical study using polyclonal antibody directed against acidic(pi form) and basic GST and analyzed the intensity(0-3+) and proportion(grade 1-4) of staining in bladder specimens from 50 patients with bladder tumor and from 10 normal controls. On GST-pi immunohistochemical stain, normal bladder mucosa was stained only focally and in low intensity, whereas the staining intensity and proportion were significantly increased in transitional cell hyperplasia, dysplasia /carcinoma in situ(CIS), and overt carcinoma (p<0.05). The staining intensity and proportion of GST-pi were significantly lower in invasive and high grade (III, IV/VI) transitional cell carcinoma(TCC) compared to superficial and low grade TCC (p<0.001). There were no significant differences in the intensity and proportion of GST-pi staining between superficial bladder TCC which recurred and which did not recur after prophylactic intravesical chemotherapy. On basic GST immunohistochemical stain, normal bladder as well as preneoplastic and neoplastic lesions or the bladder showed only focal and low intensity staining. These results suggest that GST-pi may be a marker of preneoplatic lesions and low grade, superficial TCC or bladder and that invasive and high grade TCC of bladder may have another cellular deloxilication mechanism different from GST. GST may not be the major mechanism of drug resistance in superficial bladder TCC. The role or basic GST in normal bladder as well as in bladder TCC is in doubt.


Subject(s)
Humans , Carcinogenesis , Drug Resistance , Drug Therapy , Glutathione Transferase , Glutathione , Hyperplasia , Mucous Membrane , Urinary Bladder Neoplasms , Urinary Bladder , Xenobiotics
17.
Korean Journal of Urology ; : 35-50, 1993.
Article in Korean | WPRIM | ID: wpr-126884

ABSTRACT

Chung-Ang University Penile Squamous Carcinoma cell line (CUPE-1) was established from a lymph node metastasis of human penile squamous cell carcinoma (SCC). CUPE-1 grew as adherent monolayer with a defined doubling time of 24 hours. CUPE-1 showed epithelial characterization on inverted and light microscopy and showed well developed desmosomes and tonofilaments or electron microscopy. CUPE preserved cytokeratin on immunohistochemical staining. CUPE expressed the receptor of epidermal growth factor (EGF), which stimulated the proliferation of CUPE-1 CUPE-1 showed strong tumorigenecity and/or metastatic ability when subcutaneously and intraperitoneally implanted into the nude mouse. CUPE-1 produced tumor associated antigen-4 (TA-4), a tumor marker for SCC of uterine cervix, both in vitro and in vivo. In addition, the serum level-of TA-4 were specifically increased in patients with penile SCC. These results indicate that CUPE-1 retains the characteristics of human penile SCC and could provide an excellent model for the basic research and development of new therapeutic modalities of penile cancer, and that TA-4 may become a valuable tumor marker of penile SCC.


Subject(s)
Animals , Female , Humans , Male , Mice , Carcinoma, Squamous Cell , Cell Line , Cervix Uteri , Desmosomes , Epidermal Growth Factor , Intermediate Filaments , Keratins , Lymph Nodes , Mice, Nude , Microscopy , Microscopy, Electron , Neoplasm Metastasis , Penile Neoplasms
18.
Korean Journal of Urology ; : 954-960, 1992.
Article in Korean | WPRIM | ID: wpr-123243

ABSTRACT

Investigations of the anti-tumor activity of recombinant mouse TNF and etoposide(VP-16) in a nude mouse subcutaneous implantation xenograft model utilizing the CURC-1 human renal cell carcinoma cell line were performed. Recombinant mouse tumor necrosis factor-alpha(rTNF-alpha) and VP-16. both well known cytotoxic and cytostatic anticancer agents were evaluated singly and in combination against subcutaneously growing CURC-1. The results were as follows : 1. In the absence of treatment(Group I). subcutaneously growing CURC-1 tumor nodules demonstrated continued rapid growth. 2. Administration of rTNF(Group II) induced significant tumor regression in the subcutaneous nodules. 3. Administration of rTNF and Etoposide(Group III) demonstrated significant tumor growth inhibition. On histopathological findings, Group I (control) shows rare leukocyte infiltration and no tumor necrosis. In contrast, Group II shows tumor necrosis and more leukocyte infiltration than Group I . Group III demonstrates tumor necrosis. tumor cell degeneration and more leukocyte infiltration than Group II. These results suggest that TNF have antineoplastic effect against subcutaneous human renal cell carcinoma nodule but the synergistic effect of TNF with VP-l6 is uncertain.


Subject(s)
Animals , Humans , Mice , Antineoplastic Agents , Carcinoma, Renal Cell , Cell Line , Etoposide , Heterografts , Leukocytes , Mice, Nude , Necrosis , Robenidine , Tumor Necrosis Factor-alpha
19.
Journal of the Korean Cancer Association ; : 767-782, 1992.
Article in Korean | WPRIM | ID: wpr-101688

ABSTRACT

No abstract available.


Subject(s)
Carcinoma, Squamous Cell , Cell Line , Suramin
20.
Korean Journal of Urology ; : 46-55, 1991.
Article in Korean | WPRIM | ID: wpr-79548

ABSTRACT

We analyzed 39 patients with advanced prostatic cancer to define the results and prognostic factors after endocrine therapy. Patient ages ranged from 48 to 83 years (mean 66.0). Patients received immediate endocrine therapy after diagnosis. 29 patients had systemic metastasis, of whom 28 were located in bone. 20 patients received orchiectomy, 9 diethylstilbesterol (DES), 5 both orchiectomy and DES, 3 ketoconazole, and 2 detapeptyl, respectively, Response to endocrine therapy were analyzed depending on NPCP criteria. Of 32 evaluable patients. 19 (59.4% ) showed stabilization, 9 (28.1%) partial response, and 4 progression, Mean duration of partial response and stabilization were 34.9 months and 20.1 months, respectively. Post-treatment 2 and 5 year survival rate were 83.3% (20/24) and 37.5% (6/16), respectively. Number of metastatic lesion of less than 3. Gleason score of less than 8, and Karnofsky performance index of 80 or more were significant variables to predict the better response rate (p<0.025 ) and higher 2 year survival rate (p<0.05) after endocrine therapy. Age, pretreatment duration, level of serum acid phosphatase, and degree of Leydig cell atrophy on testis histology were not significantly correlated with outcomes of endocrine therapy. In conclusion, objective response to and survival after endocrine therapy in advanced prostatic cancer is limited, and only selected group of patients with intrinsically good prognosis, show good results.


Subject(s)
Humans , Acid Phosphatase , Atrophy , Diagnosis , Ketoconazole , Neoplasm Grading , Neoplasm Metastasis , Orchiectomy , Prognosis , Prostatic Neoplasms , Survival Rate , Testis
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