Biomedical subjects

Tsuneharu Miki

Publications and source records attributed to Tsuneharu Miki.

At least 19 recordsLinked to original sources

PubMed2004

Prognostic significance of orotate phosphoribosyltransferase activity in bladder carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU), an antitumor agent, is used clinically against a variety of malignancies, including bladder carcinoma. 5-FU is a prodrug, and orotate phosphoribosyltransferase (OPRT) is the principal enzyme that converts 5-FU directly into an active antitumor metabolite, 5-fluoro-2'-deoxyuridine 5'-monophosphate. In addition, OPRT is the key enzyme in the de novo DNA and RNA synthetic process. To the authors' knowledge, little is known regarding the significance of OPRT in various malignancies, including bladder carcinoma. The authors analyzed the activity levels of OPRT in 60 bladder carcinomas and evaluated the association between the level of OPRT activity and the stage and grade status of bladder carcinoma. They also examined the prognostic significance of OPRT activity in patients with bladder carcinoma and the correlation between OPRT activity levels in bladder carcinoma cells and the sensitivity of those cells to 5-FU. METHODS: OPRT activity levels in nonfixed, fresh-frozen specimens of bladder carcinoma and normal bladder were determined enzymatically using a 5-FU phosphorylation assay. The sensitivity of bladder cells to 5-FU was assessed using a microculture tetrazolium dye assay. RESULTS: The activity levels of OPRT were approximately 7.5-fold higher in bladder carcinoma specimens compared with the activity levels in normal bladder specimens. OPRT activity in muscle-invasive bladder carcinoma was 2-fold higher compared with the activity in superficial bladder carcinoma (classified as Ta and T1). In addition, the activity of OPRT in T1 bladder carcinoma was 2-fold higher compared with the activity in Ta bladder carcinoma. The level of OPRT activity in Grade 3 bladder carcinoma was 6-fold and 2-fold higher compared with the activity in Grade 1 and Grade 2 bladder carcinoma, respectively. Patients who had Ta and T1 bladder carcinoma with low OPRT activity had a longer postoperative tumor free period compared with patients who had bladder carcinoma with high OPRT activity in the 3-year follow-up. There was a positive association between the activity levels of OPRT and thymidylate synthase/thymidine kinase, which are the key enzymes in the de novo/salvage DNA synthetic process. OPRT activity in bladder carcinoma cells was correlated positively with their sensitivity to 5-FU. CONCLUSIONS: to the authors' knowledge, the current study is the first to demonstrate that OPRT activity levels in bladder carcinoma were higher compared with its activity in the normal bladder tissues and that OPRT activity levels were correlated positively with the stage and grade of bladder carcinoma. In addition, high OPRT activity levels in patients with superficial bladder carcinoma predicted early recurrence and high sensitivity to 5-FU. These results suggest that the level of OPRT activity may be used both as a prognostic parameter and as a predictive indicator for 5-FU efficacy in patients with bladder carcinoma and that OPRT may be a molecular therapeutic target in bladder carcinoma.

Adult↗

PubMed2004

Neuroselective current perception threshold evaluation of bladder mucosal sensory function.

OBJECTIVE: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders. METHODS: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three different CPTs were obtained from each test site using a constant alternating current sinusoid waveform electrical stimulus presented at 2000Hz, 250Hz and 5Hz stimulation frequencies, which could selectively reflect the functions of the large myelinated fibers (A-beta-fiber), the small myelinated fibers (A-delta-fiber), and the unmyelinated fibers (C-fiber), respectively. RESULTS: As the determination of CPT values on the finger skin, the CPT values in the bladder could be determined using the neuroselective measures in all patients but three who had no sensory response (absence of sensation) caused by complete spinal injury. In the 8 patients with detrusor hyperreflexia due to incomplete spinal cord injury (supra-sacral lesion), the bladder CPT value (4.0+/-1.9) at 5Hz was significantly lower (p<0.01) than that in the controls (26.2+/-17.7). In the neurogenic bladders determined to be underactive (n=11, including post pelvic surgery, post infra-sacral level spinal cord injury and diabetes patients), the higher CPT values of bladder mucosal sensory functions were found at 5Hz (p<0.05), 250Hz (p=0.07), and 2000Hz (p<0.05) compared to the controls. CONCLUSIONS: Quantitative neuroselective measurement of CPT values in the human bladder mucosal function was feasible. Hypersensitivity or hyposensitivity of the urinary sensory function could be determined using the CPT values in comparison to control. The quantitative neuroselective estimation of the bladder sensory functions in different types of sensory peripheral nerve fibers may contribute to the appropriate selection of therapeutic strategy in patients with urinary sensory dysfunction.

Adult↗

PubMed2004

Significance of orotate phosphoribosyltransferase activity in renal cell carcinoma.

PURPOSE: The anticancer agent 5-fluorouracil (5-FU) is clinically used against various cancers, including renal cell carcinoma (RCC). It is a prodrug and orotate phosphoribosyltransferase (OPRT) is the principal enzyme that directly converts 5-FU to the active anticancer metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate. In addition, OPRT is the key enzyme in the de novo DNA and RNA synthetic process. Little is known about the significance of OPRT in various cancers, including RCC. We investigated the activity of OPRT in 83 RCCs and evaluated the association between the level of OPRT activity and the stage/grade of RCC. The relationship between OPRT activity in RCC cells and their sensitivity to 5-FU was also examined. MATERIALS AND METHODS: OPRT activity in nonfixed, fresh frozen RCC and normal kidney was determined enzymatically by the 5-FU phosphorylation assay. The sensitivity of RCC cells to 5-FU was assessed by the microculture tetrazolium dye assay. RESULTS: The activity of OPRT was approximately 8.5-fold higher in RCC than in normal kidney. OPRT activity in stage III/IV RCC was 3-fold higher than in stage I/II RCC. The level of OPRT activity in grade 3 RCC was 3-fold higher than that in grade 1/2 cancer. Patients with RCC with low OPRT activity had longer postoperative disease specific survival than those with high activity at 5-year followup. OPRT activity in RCC cells positively correlated with their sensitivity to 5-FU. CONCLUSIONS: To our knowledge this is the first study to demonstrate that OPRT activity in RCC was higher than that in normal kidney and OPRT activity positively correlated with RCC stage/grade. In addition, higher OPRT activity in RCC predicted worse prognosis and higher sensitivity to 5-FU. These results suggest that the level of OPRT activity may be used as a prognostic parameter and predictive indicator for 5-FU efficacy in RCC and OPRT may be a molecular therapeutic target in RCC.

Adult↗

PubMed2004

Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men.

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988-90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at - 80 degrees C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of </= 10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR = 0.39, 95% CI; 0.13, 0.89, trend P = 0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose-dependently reduce prostate cancer risk.

Adult↗

PubMed2004

Retroperitoneoscopic heminephroureterectomy for children with duplex anomaly: Initial experience.

OBJECTIVES: To evaluate the feasibility of retroperitoneoscopic heminephroureterectomy for children with duplex anomaly. METHODS: Retroperitoneoscopic heminephroureterectomy was performed in five children (four girls and one boy) with complete duplication of the ureter, of whom four (age range 1-5 years; mean age 3.3 years) had upper pole ectopic megaureters and one (3 years old) had an upper pole megaureter with ureterocele. In the patient with ureterocele, distal ureterectomy and ureterocelectomy were performed by Pfannenstiel incision. RESULTS: The mean operation time was 346 min (range 270-450 min) in the four patients with ectopic megaureter and 420 min (330 min for heminephroureterectomy) in the patient with ureterocele. The mean estimated blood loss was 43 mL (range 5-100 mL) in the four patients with ectopic megaureter and 40 mL in the patient with ureterocele. No postoperative complications were observed. Postoperative intravenous pyelography showed normal pyelogram and renal function of the preserved lower pole in all cases. CONCLUSIONS: Retroperitoneoscopic heminephroureterectomy for children is feasible, safe and has good postoperative results, including cosmetic results. However, the operation time needs to be reduced.

Child, Preschool↗

PubMed2003

Factors that influence the results of salvage surgery in patients with chemorefractory germ cell carcinomas with elevated tumor markers.

BACKGROUND: A standard concept for the integration of surgery into the chemotherapy-based treatment of patients with advanced germ cell carcinoma has been that surgery should be avoided in patients with serum tumor markers (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]) that remain elevated. However, some patients may benefit from resection under such chemorefractory conditions. The objective of this retrospective study was to clarify the outcome and clinical prognostic variables of salvage surgery in patients with disseminated (AJCC Stage II or III) testicular germ cell carcinoma or extragonadal germ cell carcinoma who had elevated serum markers. METHODS: The authors reviewed the clinical records of 24 patients who underwent salvage surgery with elevated serum AFP and/or HCG levels after at least 3 courses of cisplatin-based, systemic chemotherapy between January, 1985 and December, 2000. The survival rates were compared between the subgroups with regard to preoperative and postoperative clinical parameters using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: Ten of 24 patients (41.7%) were rendered free of disease and alive without disease after the surgery with or without adjuvant therapy at a median follow-up of 74 months (range, 24-207 months). Among the preoperative parameters, high HCG levels were associated with significantly poorer survival (hazard ratio [HR], 8.321; 95% confidence interval [95% CI], 1.0753-64.553; P = 0.043 and P = 0.016, respectively; log-rank test). In addition, patients who had visceral lesions at resection had a significantly poorer prognosis compared with patients who had retroperitoneal and/or mediastinal lymph node lesions (P = 0.038; log-rank test). Among postoperative parameters, incomplete resection and persistently high HCG levels were associated significantly with poor survival, with a risk of death from disease of 12.516-fold (95% CI, 1.786-87.781) and 9.311-fold (95% CI, 1.796-48.256), respectively. CONCLUSIONS: Salvage surgery in patients with high serum tumors markers resulted in long-term disease free status in approximately 40% of patients in a small subset with advanced germ cell carcinoma. Patients with elevated AFP levels alone (i.e., normal HCG levels) or with lymph node lesions alone seem to be good candidates for such surgery. Complete resection of target lesions and normalization of HCG levels after surgery are mandatory to achieve long-term disease free status.

Adolescent↗

PubMed2003

The significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor activity in renal cell carcinoma.

BACKGROUND: Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PDECGF) and has angiogenic activity. Little is known about the significance of TP/PDECGF activity in patients with renal cell carcinoma (RCC). The authors examined the enzymatic activity of TP in 66 RCC specimens and investigated the association between the level of TP activity and the stage/grade status of patients with RCC. Furthermore, the authors examined the correlation between TP/PDECGF activity and prognosis. METHODS: TP activity levels in nonfixed, fresh-frozen RCC specimens and in specimens of normal kidney were determined using a thin-layer chromatography assay. RESULTS: The activity of TP was approximately 3.5-fold greater in RCC specimens compared with normal kidney specimens. TP activity in patients with Stage III-IV RCC was 2.6-fold greater compared with TP activity in patients with Stage I-II RCC. In addition, the level of TP activity was correlated with a higher grade of RCC. Patients who had RCC with low TP activity had a longer postoperative disease-specific survival compared with patients who had RCC with high TP activity in the 5-year follow-up. CONCLUSIONS: The current study is the first to demonstrate a correlation between levels of TP activity and both disease progression and a higher grade of RCC. It also is the first to show that elevated TP activity in patients with RCC predicts a poor prognosis. The results suggest that high TP/PDECGF activity may be associated with the malignant potential of RCC and that TP/PDECGF may be a molecular therapeutic target in patients with RCC.

Adult↗

PubMed2003

Firing of micturition center neurons in the rat mesopontine tegmentum during urinary bladder contraction.

Micturition is controlled by a network of brainstem neurons involving the Barrington's nucleus. To depict clearly the brainstem system for micturition control, the present study was designed to record single neuronal activity in the mesopontine tegmentum including the Barrington's nucleus, and to observe its precise timing in relation to bladder contraction recorded simultaneously. About 1/5 of neurons encountered had firing modulated in relation to bladder contraction. Three types of neurons were distinguished; those which fired only prior to the start of contraction (type E1), those whose firing started shortly prior to and was maintained during contraction (type E2), and those whose firing was strongly suppressed during contraction (type I). Type E2 neurons were most frequently observed in the Barrington's nucleus and its close vicinity, while the neurons of the other two types were scattered widely in the mesopontine tegmentum. The results show clearly that direct neural signals to induce bladder contraction may arise from the Barrington's nucleus, and that the nucleus may receive regulatory inputs from wide areas of the mesopontine tegmentum. In addition, the present study clarified that the noradrenergic and cholinergic neurons, which are located in nuclei adjoining the Barrington's nucleus and function to control sleep/wakefulness, may not be concerned in controlling micturition directly.

Action Potentials↗

PubMed2003

Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate.

BACKGROUND: Hippostasin is a kallikrein-like serine protease, which has two alternatively spliced isoforms, brain-type and prostate-type. We previously reported alternative expression of hippostasin in prostate cancer cell lines. METHODS: We studied the expression of a variant-form hippostasin (isoform 3) mRNA by RT-PCR. Localization of the isoform 3 protein was examined by immunohistochemistry. The enzymatic activity of the recombinant protein was measured with synthetic substrates. RESULTS: A novel isoform of hippostasin contains 25 additional amino acids in the catalytic triad of brain-type hippostasin. Its mRNA was expressed in normal prostate tissue, BPH, and prostate cancer cell lines. The protein was localized in the prostate secretory epithelium. The enzyme activity was similar to that of brain-type hippostasin, which has kallikrein-like activity. CONCLUSIONS: In this study, we have identified a third isoform of hippostasin, which was designated variant-form (isoform 3). Hippostasin isoform 3 may play a role in the prostate, including reproductive and/or tumorigenic functions.

Alternative Splicing↗

PubMed2003

Human testis specific protein: a new member of aldo-keto reductase superfamily.

Human testis specific protein, HTSP, was identified initially by the search of the Expressed Sequence Tag database, followed by the screening of human testis cDNA library. Among various organs examined, the HTSP transcripts were detected only in the testis, not in other reproductive organs such as vas deferens and prostate. No cross-hybridizing signal was detected in the testis of mouse or rat, indicating that this gene is specifically expressed in the human testis. We isolated four isoforms, HTSP1, 2, 3 and 4. Screening of the high throughput genomic sequence database indicated the localization of the HTSP gene in chromosome 10. Thus, HTSP isoforms were generated by alternative splicing of a single gene. HTSP4, the longest gene product, was composed of 307 amino acids and shared 56% identity to mouse vas deferens protein as well as human aldose reductase in amino acid levels. Bacterially expressed recombinant HTSP protein showed small but significant activity towards 9,10-phenanthrenequinone among the putative substrates so far tested. Accordingly, HTSP is a new member of the aldo-keto reductase superfamily with as yet unidentified function.

Alcohol Oxidoreductases↗

PubMed2003

Bladder capacity at the time of enuresis.

OBJECTIVES: To evaluate bladder capacity at the time of enuresis and compare the daytime capacity of enuretics with that of controls. METHODS: The functional bladder capacity (FBC), which was the maximal endurable capacity in the daytime, the ordinary bladder capacity (OBC), which was the capacity at ordinary urinary sensation in the daytime, and the enuretic bladder capacity (EBC), which was the capacity at the time of enuresis, were measured in 67 patients with monosymptomatic nocturnal enuresis. The EBC was measured using a diaper and enuresis alarm. The FBC, OBC, and nocturnal bladder capacity, which was the maximal voided volume in the nighttime, were also measured in 67 controls. RESULTS: The FBC was not significantly different between enuretics and controls. The EBC in enuretics was significantly smaller than the nocturnal bladder capacity in controls. In enuretics, the EBC was significantly smaller than the FBC and was similar to the OBC. In controls, no statistically significant differences were found between the FBC and the nocturnal bladder capacity. CONCLUSIONS: In enuretics, the bladder capacity during sleep was significantly smaller than the daytime functional capacity. In controls, on the other hand, the bladder capacity during sleep did not differ from the daytime functional capacity. Our understanding of the bladder capacity in enuretics may need to change in view of this result. The inability to hold urine during sleep may be an important cause of nocturnal enuresis.

Adolescent↗

PubMed2003

Preliminary report of association of chronic diseases and erectile dysfunction in middle-aged men in Japan.

OBJECTIVES: To investigate the effect of chronic diseases on erectile dysfunction (ED) in Japanese middle-aged men using the International Index of Erectile Function, 5-item version (IIEF-5). METHODS: The subjects consisted of 640 healthy men and 396 men with chronic disease who responded to the IIEF-5 questionnaire (mean age 43.6 +/- 8.3 years, range 30 to 59). The incidence and severity of ED were calculated in three age groups (30 to 39, 40 to 49, and 50 to 59 years). RESULTS: The incidence of hypertension, cardiac disease, diabetes mellitus, and chronic renal failure was associated with the incidence and severity of ED, as was age. In stepwise multivariate logistic regression analysis, cardiac disease was the strongest independent risk factor (odds ratio [OR] 6.5), followed by diabetes mellitus (OR 5.9), chronic renal failure (OR 3.9), hypertension (OR 2.0), and age (OR 1.8). CONCLUSIONS: The results of this study demonstrated that the risk of ED increases with the presence of cardiac disease, diabetes mellitus, chronic renal failure, and hypertension in middle-aged men in Japan.

Adult↗

PubMed2003

Vesicoureteral reflux detected among patients with nocturnal enuresis.

OBJECTIVES: To clarify the characteristics of vesicoureteral reflux detected in patients with nocturnal enuresis. METHODS: Voiding cystourethrography (VCUG) was applied in 1,088 patients who visited our outpatient clinic with the chief complaint of nocturnal enuresis. The clinical features of reflux were evaluated and the prognosis of reflux and nocturnal enuresis was analyzed. RESULTS: Reflux was detected in 86 ureters in 70 patients (6.4%) out of the 1,088 patients. The grade of reflux was 3 or less in all cases. The incidence of pyuria was 5 (7%) and that of renal scar during first examination was 1 (1%). The incidence of unstable bladder was 30 (75%) in 40 patients. The resolution rate of reflux in the cases which were followed-up for 2 years or more by conservative treatment was 50-66% for each grade of reflux. The percentage of patients who had siblings with a positive history of nocturnal enuresis and the incidence of frequency differed significantly between the enuretics with reflux and the 507 enuretics without urological abnormalities. CONCLUSIONS: Our data suggest that the incidence of reflux in patients with nocturnal enuresis was rather low in comparison with the past literature, the severity was mild and the resolution rate by conservative treatment was rather high.

Child↗

PubMed2003

Isoliquiritigenin inhibits the growth of prostate cancer.

OBJECTIVE: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro. METHODS: DU145 and LNCaP prostate cancer cell lines were used as targets. We examined the effects of isoliquiritigenin on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the effects of isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter activity. RESULTS: Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner. Fluorescence-activated cell sorting (FACS) analysis indicated that isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced the expression of GADD153 mRNA and protein associated with cell cycle arrest. Further, isoliquiritigenin stimulated transcriptional activity of GADD153 promoter dose-dependently. CONCLUSION: These findings suggest that isoliquiritigenin is a candidate agent for the treatment of prostate cancer and GADD153 may play an important role in isoliquiritigenin-induced cell cycle arrest and cell growth inhibition.

CCAAT-Enhancer-Binding Proteins↗

PubMed2003

Significant antitumor effect of intratumoral ethanol injection on renal cell carcinoma.

OBJECTIVE: The effects of intratumoral ethanol injection on renal cell carcinoma (RCC) heterotransplanted in nude rats were evaluated. MATERIALS AND METHODS: The OUR95AF human RCC cell line was inoculated subcutaneously into the backs of nude rats. Four weeks after transplantation, the size of tumors became 1.5-2.0 cm in maximal length, and 95% ethanol was injected intratumorally once a week for five weeks. The effectiveness of this treatment was evaluated by measurement of tumor volume, magnetic resonance (MR) imaging using Gadopentetate-diethylenetriaminepentaacetic acid (Gd-DTPA) and histological examinations. RESULTS: In the ethanol injected group, no increase in tumor volume was recognized. The growth of the tumors was significantly suppressed after the third injection. Non-enhanced parts in MR imaging were observed in the central region of the tumors at the second injection, and increased at the third injection. After the fifth injection, only small parts of non-enhanced regions remained. Degenerative necrosis was histologically found in the non-enhanced parts of the MR image. The signal to noise ratio (SNR) and the contrast to noise ratio (CNR) calculated from T1 weighted imaging using Gd-DTPA, and relative enhancement (RE) were thought to be good parameters for evaluating the effect of ethanol injections. CONCLUSION: Intratumoral ethanol injection was very effective against RCC. Five weekly injections of ethanol induced necrosis of the tumor. MR imaging using Gd-DTPA may be a useful method for evaluating the effect of ethanol injection.

Animals↗

PubMed2003

Laparoscopic correction of vesicoureteral reflux using the Lich-Gregoir technique: initial experience and technical aspects.

We report two female cases with vesicoureteral reflux (VUR) who underwent laparoscopic correction of VUR by the Lich-Gregoir technique. One patient was 10 years of age, with international grade III reflux of the left ureter; the other was 27 years of age, with grade II reflux of the right ureter. The respective operating times were 6 h 40 min and 6 h 10 min. There were no complications during surgery. Although post-surgical ultrasonography revealed mild hydronephrosis in the adult patient, the condition resolved spontaneously 2 months after surgery. The disappearance of reflux was confirmed in both cases by voiding cystography 6 months after surgery.

Adult↗

PubMed2003

Significance of thymidine kinase activity in renal cell carcinoma.

PURPOSE: Thymidine kinase (TK) has a key role in the complementary or alternative salvage pathway of pyrimidine synthesis. Little is known about the significance of TK activity in renal cell carcinoma. We examined the activity of TK in 66 renal cell carcinomas and investigated the association of the level of TK activity with the stage and grade of renal cell carcinoma. MATERIALS AND METHODS: TK activity in nonfixed, fresh frozen renal cell carcinoma and normal kidney was determined by the DEAE cellulose disc method. RESULTS: The activity of TK was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. The higher the stage and grade of renal cell carcinoma, the higher the TK activity. TK activity correlated positively with the activity of thymidine synthase, which is a key enzyme for pyrimidine synthesis in the de novo pathway. TK activity in renal cell carcinoma cells was inversely related to their sensitivity to 5-fluorouracil. CONCLUSIONS: To our knowledge this report represents the first study to demonstrate that the level of TK activity correlates with the stage and grade of renal cell carcinoma, and higher TK activity in renal cell carcinoma predicts lower sensitivity to 5-fluorouracil. These results suggest that high TK activity may be associated with the malignant potential of renal cell carcinoma and TK may be a molecular therapeutic target for this disease. In addition, the combination of TK and thymidylate synthase inhibitors may be beneficial for renal cell carcinoma.

Adult↗

PubMed2003

Hand assisted retroperitoneoscopic nephroureterectomy: comparison with the open procedure.

PURPOSE: We report our initial experience with hand assisted retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma and compared our results to those of a contemporary series of open nephroureterectomy. MATERIALS AND METHODS: Clinical data on 34 consecutive patients who underwent hand assisted retroperitoneoscopic nephroureterectomy were reviewed and compared with those on 34 who underwent open nephroureterectomy. All specimens were extracted intact. RESULTS: Total operative time was similar in the 2 groups (233 versus 236 minutes). Estimated blood loss was significantly less in the hand assisted laparoscopy group (236 versus 427 ml.). During convalescence the frequency of parenteral analgesia postoperatively was significantly lower in the laparoscopy group than in the open surgery group. The former patients had a significantly shorter interval to oral intake and ambulation as well as a shorter hospital stay and convalescence compared with those who underwent open surgery. In each group the complication rate was 12% (4 of 34 cases). In the hand assisted laparoscopy group 1 conversion to an open procedure was due to bleeding. There was recurrence in 4 of the 34 patients (12%) in the laparoscopy group, including 2 with bladder recurrence and 2 with metastases, at an average followup of 13.1 months. CONCLUSIONS: Hand assisted retroperitoneoscopic nephroureterectomy is an effective and safe alternative to open nephroureterectomy for upper urinary tract transitional cell carcinoma.

Adult↗