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Biomedical subjects

Cheol Kwak

Publications and source records attributed to Cheol Kwak.

35 records · Page 2Linked to original sources

Initial tumor stage and grade as a predictive factor for recurrence in patients with stage T1 grade 3 bladder cancer.

PURPOSE: We evaluated whether the risk of progression and the recurrence rate were different in patients with primary and nonprimary stage T1 grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between 1983 and 1997, 75 patients were treated for stage T1 grade 3 transitional cell carcinoma of the bladder. Of these patients 68 (primary and nonprimary tumor in 58 and 14, respectively) without carcinoma in situ who had not undergone complete cystectomy immediately after diagnosis were included in the study. No maintenance regimen was used. Median followup was 100 months (range 9 to 217). RESULTS: The incidence of multiple tumors in patients with nonprimary tumors was significantly higher than in patients with primary disease (p = 0.035). However, the recurrence-free survival rate in patients with primary T1 GIII bladder tumor was significantly lower than that of patients with nonprimary T1 GIII bladder tumor (p = 0.0016). Multivariate analysis using Cox's proportional hazard regression model revealed that only initial tumor status had statistically significant effects on tumor recurrence (p = 0.007) and no other factors had a significant influence on recurrence-free survival. Progression-free and cancer specific survival rates were also significantly different between the 2 groups (p = 0.036 and 0.0307, respectively). CONCLUSIONS: Our study indicates that patients with primary stage T1 grade 3 bladder cancers have higher recurrence and progression potential than those with nonprimary disease despite the higher incidence of multiple tumors in patients with nonprimary tumors.

Adult↗

Expression of survivin, a novel inhibitor of apoptosis, in superficial transitional cell carcinoma of the bladder.

PURPOSE: We investigated whether the over expression of survivin, a new antiapoptotic protein, might provide prognostic information in patients with superficial bladder cancer. MATERIALS AND METHODS: Immunohistochemical staining of paraffin sections using a monoclonal antibody for survivin was performed in 88 cases of superficial bladder cancer using the standard avidin-biotin-peroxidase technique. The relationships between the expression of survivin, clinicopathological characteristics and clinical outcome were analyzed. RESULTS: Survivin expression was found in tumor cells but not in nonneoplastic bladder tissues. High expressions (greater than 20%) of survivin were observed in 51 cases (58.0%) and low expression in 37 cases. No statistically significant association was observed between survivin expression and tumor grade (p = 0.052) or pathological stage (p = 0.131). When clinical data such as sex, age, tumor number, size or shape were examined in conjunction with survivin status no statistically significant relationship was noted. Patients with a high expression of survivin had worse disease-free survival rates than those with low survivin expression (log rank test p = 0.0004). Multivariate Cox proportional hazards model analysis identified survivin expression as an independent prognostic factor of disease-free survival (p = 0.009, relative risk = 3.17). CONCLUSIONS: Our findings suggest that high survivin expression may be considered a new unfavorable prognostic factor in superficial bladder cancer.

Adult↗

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms.

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.

Adult↗

Effect of circumcision on urinary tract infection after successful antireflux surgery.

OBJECTIVE: To evaluate whether circumcision during antireflux surgery can reduce the incidence of urinary tract infection (UTI) after successful ureteric reimplantation in patients with primary vesico-ureteric reflux (VUR). PATIENTS AND METHODS: Children who had undergone antireflux surgery for primary VUR were divided into group 1 (27, circumcised at the time of antireflux surgery at the parents' request) and group 2 (50, those not circumcised). All antireflux operations were by the Cohen method. Regular urine samples were cultured to detect UTI, which was defined as a single species with >10(5) colony-forming units/mL in a midstream voided specimen. Numbers of UTI episodes before and after surgery were compared between the groups, with (99m)Tc-dimercaptosuccinic acid (DMSA) renal scans also taken in all patients. Each scan was blindly reviewed in terms of the size, number and zonal location of cortical defects, based on morphology. Interval changes were categorised as improved, no change, progressed, and new scar formation, and compared between the groups. Prophylactic antibiotics were maintained until the follow-up studies at 4-6 months after surgery. RESULTS: There was no significant difference between the groups in age at the time of operation (mean 42.4 vs 47.4 months), the age at the first documented UTI (mean 26.5 vs 29.3 months), reflux grade, or number of UTI episodes and renal parenchymal scarring on DMSA before surgery. There was no significant difference between the groups in the number of UTI episodes at a mean (range) follow-up of 151.3 (114-207) months after antireflux surgery. Also there was no significant morphological change on follow-up renal scans and no difference between the groups. CONCLUSION: These findings suggest that circumcision during antireflux surgery has no effect on the incidence of postoperative UTI.

Child↗

Effect of subclinical prostatic inflammation on serum PSA levels in men with clinically undetectable prostate cancer.

OBJECTIVES: To examine whether subclinical prostatic inflammation might influence serum prostate-specific antigen (PSA) levels in men with clinically undetectable prostate cancer. METHODS: A total of 461 patients who underwent prostate biopsy at our hospital were studied between January 1996 and December 1999. Of these patients, a total of 125 patients without detectable prostate cancer or a history or symptoms of prostatitis, with serum PSA levels of less than 20.0 ng/mL and other specified exclusion criteria, were included in the study. Inflammation observed at biopsy was scored for inflammation extent and inflammatory aggressiveness, and the effects of these morphologic aspects of inflammation on serum PSA levels were examined. RESULTS: The extent of inflammation tended to increase as the prostate volume increased (P = 0.006). Patients with a PSA greater than 2.5 ng/mL had a greater extent and aggressiveness of inflammation than those with PSA levels of 2.5 ng/mL or less (P = 0.004 and P = 0.050, respectively). However, no statistically significant differences were found in terms of the extent of inflammation or inflammatory aggressiveness between patients with PSA levels greater than 4.0 ng/mL and those with PSA levels of 4.0 ng/mL or less. Furthermore, the extent of inflammation did not account for PSA levels greater than 2.5 or 4.0 ng/mL by multivariate analysis. CONCLUSIONS: Our results indicate that subclinical prostatic inflammation is not the etiology of a serum PSA greater than 4.0 ng/mL in men without clinically detectable prostate cancer.

Adenocarcinoma↗

Urinary oxalate levels and the enteric bacterium Oxalobacter formigenes in patients with calcium oxalate urolithiasis.

OBJECTIVES: We performed a prospective study to evaluate the intestinal colonization of Oxalobacter formigenes and its relationship with urinary oxalate levels in patients with calcium oxalate stone disease. METHODS: One hundred and three patients with calcium oxalate urolithiasis, ranging in age from 21 to 73 years (mean age, 47 years) who were followed from August 2000 to September 2001 participated in this study. Fresh stool and 24-hour urine samples were collected. Genus specific oligonucleotide sequences corresponding to the homologous regions residing in the oxc gene were designed. In order to quantify O. formigenes in clinical specimens, a quantitative-PCR-based assay system utilizing a competitive DNA template as an internal standard was developed. Urine volume, pH, creatinine, oxalate, calcium, magnesium, phosphate, citrate and uric acid were measured. RESULTS: Intestinal Oxalobacteria were detected in 45.6% (n=47) of calcium oxalate stone patients by PCR. In stone formers who tested negative for Oxalobacteria, the average urinary oxalate level was 0.36 mmol/day, and this compared to 0.29 mmol/day for those patients that tested positive for Oxalobacteria (p<0.05). Mean colony forming units per gram of stool of all patients was 1.1 x 10(7) (0-4.1 x 10(8)), and the level of 24 hours urine oxalate significantly decreased with increasing level of colony forming units of O. formigenes (r=-0.356, p=0.021). CONCLUSION: Our results support the concept that O. formigenes is important in maintaining oxalate homeostasis and that its absence from the gut may be the risk of calcium oxalate urolithiasis.

Adult↗

Molecular epidemiology of fecal Oxalobacter formigenes in healthy adults living in Seoul, Korea.

BACKGROUND AND PURPOSE: Oxalobacter formigenes is a member of the intestinal flora that degrades oxalate. This bacterium maintains an important symbiotic relation with its hosts by regulating oxalic acid absorption in the intestine as well as oxalic acid concentrations in plasma. We tried to define the prevalence of fecal O. formigenes positivity in healthy adults. MATERIALS AND METHODS: Whole-bacterial DNA was isolated directly from fresh stool samples obtained from 233 healthy adults known to be free of urolithiasis. Genus-specific oligonucleotide sequences corresponding to homologous regions residing in the oxc gene that encodes oxalyl-coenzyme A decarboxylase were designed. A PCR-based assay was done on the stool samples. RESULTS: A PCR product of 416 bp encoding the oxc gene was detected in 197 of the 233 stool samples (76.8%). Adjusted to the Seoul population census 1995, the calibrated fecal O. formigenes-positive rate was estimated to be 76.7%: 79.2% in men and 74.2% in women, with no significance difference according to age or sex. CONCLUSION: These results suggest that O. formigenes inhabits the intestine of three fourths of the normal Korean populations. These data provide a base for further studies to uncover the relation between O. formigenes and urolithiasis.

Adult↗

Hand assisted laparoscopic radical nephrectomy: comparison with open radical nephrectomy.

PURPOSE: We compared the results of hand assisted laparoscopic and conventional open radical nephrectomy. MATERIALS AND METHODS: Clinical data on 54 hand assisted and 50 open radical nephrectomies performed at our hospital from September 1999 to October 2002 were reviewed. RESULTS: Mean operative time in the laparoscopic and open groups was similar (194.9 and 180.7 minutes, respectively, p = 0.087). However, estimated mean blood loss (182.8 vs 262.8 ml, p <0.001), mean days to oral intake (2.6 vs 3.7 days, p <0.001) mean duration of an indwelling drain (2.6 vs 3.2 days, p <0.001) and mean hospital stay (6.8 vs 8.9 days, p <0.001) were significantly less in the laparoscopic group. In the laparoscopic group no conversions or re-explorations were required and no major complications occurred. CONCLUSIONS: Our findings suggest that hand assisted laparoscopic radical nephrectomy represents an effective, minimally invasive treatment option in patients with suspected renal cell carcinoma.

Adult↗

Impact of varicocele on testicular volume in young men: significance of compensatory hypertrophy of contralateral testis.

PURPOSE: We examined the impact on ipsilateral testicular volume in young men with varicocele and determined whether compensatory hypertrophy exists. MATERIALS AND METHODS: Between April and November 2001, 2,700 men who were 20 years old and dwelling in the community were randomly selected at a 10% sampling fraction after a sampling process according to census district. A total of 2,080 men (77% response rate) agreed to participate in the study. All volunteers underwent standard evaluation, including medical history and physical examination. RESULTS: Testicular volume on the affected side in men with varicocele was significantly smaller than that of the contralateral side, while testicular volume on the contralateral side was significantly larger than that of the left side in normal men. In those with unilateral varicocele testicular volume on the affected side did not depend on varicocele grade but contralateral testicular volume in men with grade I varicocele was significantly smaller than in men with higher grades of the entity. The rate of testicular atrophy increased depending on varicocele grade. CONCLUSIONS: Varicocele negatively impacts testicular volume on the affected side in young men. Our findings suggest that men with higher grades of varicocele have a hypertrophied testis on the contralateral side.

Adult↗

Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer.

PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.

Adult↗

Prevalence and epidemiologic characteristics of urolithiasis in Seoul, Korea.

OBJECTIVES: To study the epidemiologic details of urolithiasis in Seoul, Korea. The prevalence of urolithiasis varies by different regions in the world and has been reported to be 4% to 15%. METHODS: A total of 2643 persons 40 to 79 years old living in Seoul were selected by stepwise random sampling. Questionnaires were used and completed by trained interviewers concerning whether the subjects had experienced urinary stone disease at any time in their life. RESULTS: Of 2643 persons interviewed, 65 experienced 78 episodes of urinary stone formation in their lifetime. Calibrated after the Seoul population census, the overall standardized lifetime prevalence rate was estimated to be 3.5%, 6.0% in men and 1.8% in women. The point prevalence rate was estimated to be 0.9%, 1.9% in men and 0.3% in women. Most of the urinary stone diseases were diagnosed at the fifth decade. Kidney stones in family members were present in 8.1% of patients with stones and 4.1% of stone-free control individuals. Twenty percent of the patients with stones experienced recurrences. CONCLUSIONS: In this first systematically assessed epidemiologic survey about the rate of urolithiasis in Korea, 6.0% of Korean men and 1.8% of women are expected to experience urinary stone disease during their lifetime.

Adult↗

Laparoscopic nephrectomy for tuberculous nonfunctioning kidney: comparison with laparoscopic simple nephrectomy for other diseases.

OBJECTIVES: To summarize the results of our 31 consecutive laparoscopic nephrectomies for renal tuberculosis and compare them with 45 laparoscopic nephrectomies performed for other benign etiologies. We previously reported our initial successful experiences in expanding the role of laparoscopic surgery with the introduction of laparoscopic nephrectomy for renal tuberculosis. METHODS: Thirty-one laparoscopic nephrectomies for renal tuberculosis were performed between June 1996 and December 2001. The patients consisted of 11 men and 20 women with a mean age of 44.2 years (range 29 to 64). The control group consisted of 17 men and 28 women with a mean age of 48.6 years (range 17 to 60). The two groups were comparable with regard to demographic data. Statistical analyses were used to compare the two groups in terms of various parameters, including surgical time, blood loss, analgesic requirements, resumption of oral intake, and hospital stay. RESULTS: Laparoscopic nephrectomy was successful in 30 cases of the tuberculosis group and 44 cases of the control group. The two groups showed comparable perioperative and postoperative parameters, except for mean operative time, which, at 244 minutes for the tuberculosis group, was significantly greater than the 216 minutes for the control group (P <0.05). No significant intraoperative or postoperative complications were observed in either group. CONCLUSIONS: The results of this study indicate that laparoscopic nephrectomy for renal tuberculosis is a safe, effective, and less invasive treatment modality. Therefore, we suggest that the renal tuberculous nonfunctioning kidney should be approached initially using the laparoscopic approach.

Adult↗

Suppression of clusterin expression enhanced cisplatin-induced cytotoxicity on renal cell carcinoma cells.

OBJECTIVES: To evaluate whether antisense transfection targeted against clusterin enhances the chemosensitivity in renal cell carcinoma. METHODS: Caki-1, a renal cell carcinoma cell line, and cisplatin were used as chemotherapeutic agents. Clusterin expression of Caki-1 cells after treatment with cisplatin was measured by Western blot analysis. After the construction of a clusterin suppression vector, clusterin expression was compared between Caki-1 cells transfected with the clusterin suppression vector (Caki-1/AS), Caki-1 cells transfected with control vector (Caki-1/VO), and parental Caki-1 cells. Tumor cell viability was measured with the MTT assay at 24 and 48 hours after cisplatin treatment. RESULTS: The expression of clusterin increased gradually in Caki-1 cells, peaking at 24 hours, and was reduced to an almost undetectable level at 48 hours after cisplatin treatment. Clusterin expression was suppressed, and the percentage of viable tumor cells decreased significantly more in the Caki-1/AS than in the Caki-1/VO or parental Caki-1 cells at 24 hours after cisplatin treatment. The change in chemosensitivity of the Caki-1/AS cells lost its significance at 48 hours after cisplatin treatment. CONCLUSIONS: Our results showed that clusterin expression increased transiently after treatment of cisplatin, and its suppression by antisense transfection enhanced the cisplatin-induced cytotoxicity of renal cell carcinoma cells. Clusterin suppression may be a useful modality in enhancing the effects of cytotoxic chemotherapy in renal cell carcinoma.

Blotting, Western↗

Distribution of serum prostate-specific antigen in healthy Korean men: influence of ethnicity.

OBJECTIVES: To evaluate the normal distribution of serum prostate-specific antigen (PSA) levels in healthy Korean men. The subjects included men younger than 40 years of age, because information on serum PSA levels in younger men is scarce. METHODS: Between January 1997 and December 1998, the serum PSA levels of the subjects who visited our hospital for a routine health checkup were determined. All men who were older than 50 years with abnormal digital rectal examination findings and/or an abnormal serum PSA level (greater than 4.0 ng/mL) underwent transrectal ultrasound-guided sextant biopsy. Two men who were found to have cancer were excluded from the analysis. The detection rate of prostate cancer for men with abnormal digital rectal examination findings and/or an abnormal serum PSA level was 2.0% for men 50 to 59 years old; 0.0% for men 60 to 69 years old; and 11.1% for men 70 to 79 years old. A total of 8297 men (aged 20 to 79 years) were included in the study. RESULTS: The median serum PSA level (5th to 95th percentile range) was 0.90 ng/mL (0.33 to 2.25) for men 20 to 29 years old; 0.89 ng/mL (0.30 to 2.35) for men 30 to 39 years old; 0.89 ng/mL (0.30 to 2.36) for men 40 to 49 years old; 0.96 ng/mL (0.32 to 2.96) for men 50 to 59 years old; 1.22 ng/mL (0.33 to 3.78) for men 60 to 69 years old; and 1.25 ng/mL (0.30 to 7.49) for men 70 to 79 years old. The median and 95th percentile serum PSA levels of Korean men younger than 50 years were higher, but those for men 50 years old or older were lower than in other races. In our study cohort, the serum PSA level weakly correlated with age (r = 0.088, P <0.001). The serum PSA level weakly correlated with age in men 50 years old or older (r = 0.116, P <0.001) but in men younger than 50 years, it did not correlate (r = 0.000, P = 0.987). CONCLUSIONS: These results suggest that the distribution and cutoff value of the serum PSA level in Korean men differ from those in other races. In addition, our findings raise the question of whether lowering the PSA cutoff may enhance the detection of cancer in this population with low prostate cancer rates.

Age Distribution↗

Effect of oxalate on the growth of renal tubular epithelial cells.

PURPOSE: Until recently, oxalate was considered merely as a major component of calcium oxalate stones, forming crystals in the lumen of the renal tubules. However, new evidence suggests that oxalate is not only a major constituent of calcium oxalate stones but also has effect on renal tubular epithelial cells, affecting the pathogenesis of nephrolithiasis. We tried to elucidate the effect of oxalate on the growth of renal tubular epithelial cells of different species and locations and also to interpret the possible role of the oxalate in the pathogenesis of urolithiasis. MATERIALS AND METHODS: Porcine proximal renal tubular epithelial cells (LLC-PK1) and canine distal renal tubular epithelial cells (MDCK) were incubated with different concentrations of oxalate, and the effect of oxalate on the growth of the cells was assessed by methylthiazoletetrazolium assay. RESULTS: Growth of the renal tubular epithelial cells was inhibited with increasing concentrations of oxalate in both proximal and distal lines. CONCLUSION: Oxalate may cause stone formation by affecting the growth of renal tubular epithelial cells as well as by providing a constituent of calcium oxalate stones.

Animals↗

Laparoscopy for definite localization and simultaneous treatment of ectopic ureter draining a dysplastic kidney in children.

BACKGROUND AND PURPOSE: Single-system ectopic ureter draining a dysplastic kidney is a rare urologic abnormality. In this study, we evaluated our own experience using laparoscopy for the simultaneous identification and removal of such ureterorenal units. PATIENTS AND METHODS: Between February 1999 and August 2001, four girls with a mean age of 11 years presented with urinary incontinence. After imaging studies including CT scan, MRI, or both were done, all the patients underwent laparoscopy for definitive localization and simultaneous treatment. RESULTS: In all cases, ultrasonography and intravenous urography combined to reveal a single normal kidney. Even the CT scan could not identify the dysplastic kidney or ectopic ureter in three children. Laparoscopy was performed transperitoneally in all four patients, and a small dysplastic kidney was identified. Discovery of the kidney was not difficult because we initially identified the ureter crossing over the iliac vessels. Laparoscopic nephroureterectomy was successful in all patients with a mean operative time of 102 minutes. There was no significant intraoperative or postoperative complication, and the mean postoperative hospital stay was 2.5 days. All patients have remained completely dry without any problems after surgery. CONCLUSIONS: For patients having a clinical suspicion of ectopic ureter draining a dysplastic kidney, laparoscopy may represent an alternative modality for simultaneous diagnosis and treatment.

Adolescent↗

Ultrastructural change due to acquired cisplatin resistance in human bladder cancer cells.

Cis-diaminedichloroplatinum (cisplatin) has therapeutic efficacy against advanced bladder cancer. However, the response is often limited due to appearance of drug-resistant tumor cells. Recently, we established a cisplatin-resistant human bladder cancer cell line, T24/R2, from T24 human bladder cancer cell line, which shows 18-fold resistance to cisplatin by the stepwise exposure of increasing concentrations of cisplatin. A light microscopic (LM) and transmission electron microscopic (EM) examination was performed to investigate the morphological and ultrastructural changes during induction of drug resistance. In LM, the cytoplasm of T24R2 cells showed plumper pattern than that of T24 parent cells. In EM, the chromatin pattern of T24R2 cells was finely dispersed compared to T24 cells, which were coarse and aggregated. The mitochondrial volume, rough endoplasmic reticulum, polyribosomes and ribosomes were moderately increased in T24R2 cells. The cell membrane showed ruffled border and great amount of double membrane vesicles and pinocytic vesicles were observed in the cell surface of T24R2 cells, which were seldom observed in T24 cells. With these findings, we concluded that human bladder cancer cells underwent morphological and ultrastructural changes during acquiring of resistance to cisplatin. We could suggest that these changes might be involved in the drug resistance mechanism in human bladder cancer cells.

Antineoplastic Agents↗