Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 37 records · Page 2Linked to original sources

PubMed2001

Bladder reconstruction with autotransplanted ileum in the dog: better functional results than standard enterocystoplasty.

OBJECTIVE: To compare, in a dog model, the properties of a reconstructed bladder (peristalsis, histological changes and absorption) using an autotransplanted ileal segment with standard enterocystoplasty. MATERIALS AND METHODS: Female beagle dogs were divided into two groups. In group 1 (autotransplantation, six dogs), a Heineke-Mikulicz-type pouch was constructed using autotransplanted terminal ileum. The artery and vein of the terminal ileum were anastomosed to the iliac artery and vein, respectively. The pouch was anastomosed to the bladder remnant immediately above the vesical triangle. In group 2 (control, five dogs) the same type of bladder reconstruction using terminal ileum was undertaken but with no vessel anastomosis. Bladder function in these two groups was then compared for peristalsis (by monitoring intravesical pressure), histological changes (by microscopy) and glucose reabsorption (by measuring the amount of glucose remaining in the reconstructed bladder). The mean (range) follow-up was 11 (7-18) months for group 1 and 9.2 (7-12) months for group 2; the recovery time before examination was 4.6 (2-7) months for group 1 and 4.0 (2-6) months for group 2. RESULTS: In group 1, there were no major complications in five dogs after the procedure and they survived for > 7 months; the autotransplant became necrotic in one dog where the arterial diameter was < 1 mm. In the control group, all five dogs survived for > or = 7 months after surgery. Intestinal peristalsis was inhibited in group 1 but not in group 2. The bladder was oval/spherical in group 1 and elongated in group 2, with a thinner epithelium and fewer goblet cells in the latter. Glucose reabsorption was greater in group 2 than in group 1. CONCLUSION: Bladder reconstruction using autotransplanted terminal ileum in dogs is technically feasible. For bowel peristalsis and reabsorption of glucose, autotransplanted ileum may have functional advantages over a standard enterocystoplasty.

Absorption↗

PubMed2001

Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer.

OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.

Aged↗

PubMed2001

Versatility and donor site morbidity of the lateral upper arm flap in intraoral reconstruction.

OBJECTIVE: The lateral upper arm flap is not widely used yet for intraoral defect reconstruction. Investigation of its morphologic and functional outcome was the objective of this study. STUDY DESIGN: The morphologic and functional results of recipient (swallowing, flap survival, dehiscence of margins, cutaneous fistulas, intraoral hairs) and donor sites (wound healing, scar width and length, sensory and motor disturbance) (n = 44) were checked clinically. Postoperative swallowing was investigated via videofluorography (n = 11). RESULTS: The lateral upper arm flap showed low donor site morbidity, primary closure was achieved in all but one case. Sensory deficit at the proximal forearm (n = 27) occurred without any case of compromise of radial nerve function. Videofluorography allows for objective evaluation of swallowing function. CONCLUSIONS: The lateral upper arm flap is the reconstruction of first choice for intraoral defects due to its low donor site morbidity.

Adult↗

PubMed2001

Renal cell carcinoma with extension of tumor thrombus into the vena cava: surgical strategy and prognosis.

PURPOSE: The outcome of patients who underwent radical resection of renal cell carcinoma extending into the vena cava was retrospectively analyzed, and risk factors for long-term survival were investigated. METHODS: From 1983 to 1999, 33 patients who had renal cell carcinoma with inferior vena caval tumor extension underwent 34 surgical procedures. There were 27 men and six women with an average age of 60.1 years. Twenty-two cases (64.7%) were classified as stage III (T1-2 N1 M0 or T3 N0-1 M0), and 12 cases (35.3%) as stage IV (T4 or N2-3 or M1). Coexistent lung metastasis was found in seven cases (20.6%). The tumor thrombi invaded into the inferior vena cava below the hepatic hilum in 19 cases, below the orifice of hepatic veins in 12, and above the diaphragm in 3. Cardiopulmonary bypass graft was applied in 13 cases (38.2%). Inferior vena cava was reconstructed by direct suture (n = 19), polytetrafluoroethylene patch angioplasty (n = 13), or graft replacement (n = 2). RESULTS: Two patients died during the early postoperative period because of retrohepatic caval injury and intraoperative pulmonary embolism. Late death occurred in 16 patients; the causes of death were tumor recurrence in 15 and acute pulmonary embolism as a result of graft thrombosis in 1. Overall 1-, 5-, and 10-year survival rates were 70%, 44%, and 26.4%, respectively. One- and 5-year survival rates were 81.3% and 52.9% for stage III and 50% and 31.2% for stage IV; a statistically significant correlation was found between surgical staging and survival (P =.049). Patients without lymph node metastasis had a significant survival advantage over those with lymph node metastasis (P =.022). There was no significant difference in survival on the basis of the presence or absence of synchronous lung metastasis (P =.291). The degree of local extension of the tumor or the level of tumor thrombus did not tend to influence survival. CONCLUSIONS: Surgical prognosis in patients with renal cell carcinoma extending into the vena cava was determined by the staging of the tumor, especially lymph node status, and not by the level of tumor thrombus or the presence of concurrent lung metastasis. The use of cardiopulmonary bypass graft is recommended for the resection of tumor thrombus extending over the diaphragm.

Adult↗

PubMed2001

Usefulness of Ureteropyeloscopy for diagnosis of upper urinary tract tumors.

BACKGROUND: Upper urinary tract tumors have historically been diagnosed using urinary cytology examination and radiography. As the technique and instrumentation of ureteroscopic inspection and biopsy have advanced, ureteroscopic examination has become more routine. We studied the applicability and safety of using ureteropyeloscopy to diagnose upper urinary tract tumors. PATIENTS AND METHODS: Between January 1994 and October 1999, 50 patients at Kobe University Hospital underwent ureteropyeloscopy for suspected upper urinary tract tumors. RESULTS: The sensitivity values of radiography, urinary cytology, and ureteroscopy were 96%, 60%, and 92%, respectively. The specificity values of the three procedures examination were 12%, 84%, and 88%, respectively. No major complications or dissemination of malignant cells were evident. CONCLUSION: Ureteroscopic examination is a safe, sensitive, and specific means of detecting upper urinary tract tumors.

Adult↗

PubMed2001

Acquisition of resistance to Fas-mediated apoptosis by overexpression of clusterin in human renal-cell carcinoma cells.

Recent studies have shown the antiapoptotic activity of clusterin against a wide variety of stimuli; however, the functional role of clusterin in Fas-mediated apoptosis has not been well characterized. We transfected the clusterin cDNA into human renal-cell carcinoma (RCC) ACHN cells that scarcely express clusterin protein in order to examine whether overexpression of clusterin inhibits the Fas-mediated signal pathway for apoptotic cell death. No significant difference was observed in the in vitro cell growth rates between the clusterin-transfected cell line (ACHN/CL) and the vector-only-transfected control cell line (ACHN/C), whereas the colony-forming efficiency in soft agar of ACHN/CL was significantly higher than that of ACHAN/C. The anti-Fas monoclonal antibody CH11 induced apoptosis in ACHAN/C cells in a dose-dependent manner; however, the growth-inhibitory effect of CH11 on ACHN/CL cells was markedly suppressed, with corresponding increases in p53 expression and decrease in the fraction of cells in the sub-G(1) phase of the cell cycle. Furthermore, the cytotoxic effect of CH11 on ACHN/CL cells was augmented by treatment with interferon-gamma, but a corresponding effect on ACHN/C cells was not observed. These findings suggest that overexpression of clusterin may contribute to a phenotype resistant to Fas-mediated apoptosis, and that if interferon-gamma treatment is added according to the clusterin expression level, Fas-mediated therapy could be a novel approach to RCC.

Adult↗

PubMed2001

Prognostic variables in patients who have undergone radical cystectomy for transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate whether several clinicopathological factors could be used as prognostic predictors in patients who have undergone radical cystectomy for transitional cell carcinoma (TCC) of the bladder. METHODS: Between January 1985 and June 2000, 154 patients underwent radical cystectomy and pelvic lymphadenectomy for TCC of the bladder at a single institution. Their clinicopathological findings were analyzed based on the criteria of the Japanese Urological Association. RESULTS: Histopathological examination revealed that the tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in 85 and 33 patients, respectively. The cause-specific 5-year survival rate was 64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0% for those with vascular invasion (p < 0.001); and 76.5% for patients without lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001). Multivariate analysis revealed a strong independent correlation of the pathological stage and lymph node metastasis with poor prognosis and, furthermore, the incidence of lymph node metastasis was significantly related to the increase in pathological stage. CONCLUSIONS: In this series, the pathological stage, lymph node metastasis and vascular involvement, but not tumor grade, were significantly useful prognostic factors in patients who have undergone radical cystectomy for TCC and among them only pathological stage and lymph node metastasis could be used as independent predictors for poor prognosis.

Adult↗

PubMed2001

Significance of prostate-specific antigen--alpha(1)-antichymotrypsin complex for diagnosis and staging of prostate cancer.

OBJECTIVE: To evaluate the clinical significance of measuring the prostate-specific antigen-alpha(1)-antichymotrypsin (PSA-ACT) for differentiating prostate cancer from benign prostate hypertrophy (BPH) and for the staging of prostate cancer. METHODS: Before treatment, total PSA (tPSA) and PSA-ACT were measured in 120 patients with prostate cancer and in 150 patients with BPH using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, the tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. RESULTS: tPSA, PSAD, PSA-ACT and ACTD levels in patients with prostate cancer paralleled the clinical stage and were significantly higher than those in patients with BPH. Furthermore, these four values were significantly higher in patients with pathologically extraprostatic disease than those with organ-confined disease. Receiver operating characteristics analysis among patients with PSA values of 4.1-10 ng/ml revealed that the areas under the curve for tPSA and ACTD were similar to those for PSA-ACT and ACTD, respectively and that no significant differences in the differentiation between prostate cancer and BPH were observed among these parameters. CONCLUSIONS: Measurement of PSA-ACT provides useful information for the clinical staging of prostate cancer and differential diagnosis between prostate cancer and BPH; however, compared with tPSA, PSA-ACT may not be significantly superior in the diagnosis and staging of prostate cancer.

Diagnosis, Differential↗

PubMed2001

Secreted type of modified interleukin-18 gene transduced into mouse renal cell carcinoma cells induces systemic tumor immunity.

PURPOSE: Interleukin (IL)-18 is a novel cytokine that has been identified as a strong interferon-gamma inducer. IL-18 has bioactivity similar to that of IL-12 and demonstrates antitumor effects. Since IL-18 does not have a signal sequence, we constructed the gene, consisting of the signal sequences of interferon-beta and mature IL-18 complementary (c) DNA. The modified gene was subsequently transduced into a mouse renal cell carcinoma cell line to induce IL-18 secretion from tumor cells to establish whether this IL-18 secreting tumor cell line may induce systemic tumor immunity. MATERIALS AND METHODS: Modified IL-18 cDNA consisting of the signal sequences of interferon-beta and mature type of IL-18 cDNA was constructed by the overlap extension method. The modified and original IL-18 cDNA was transduced into the RenCa mouse renal cell carcinoma cell line. Expression of IL-18 messenger RNA and concentration of IL-18 in the culture supernatant were determined. Direct antitumor and tumor vaccine effects were investigated in syngeneic Balb/c mice. To determine the mechanism of the antitumor effect immunodeficient mice were challenged with IL-18 secreting RenCa cells. RESULTS: Although the modified and original IL-18 genes transduced RenCa showed almost the same level of IL-18 messenger RNA expression, only RenCa cells transduced with modified IL-18 gene secreted IL-18 into the culture supernatant and were completely rejected when transplanted into syngeneic mice. T lymphocytes were involved in this antitumor effect. Moreover, the modified IL-18 transduced RenCa induced tumor vaccine effect against parental RenCa cells injected at a distant site. CONCLUSIONS: Immune gene therapy using modified IL-18 cDNA appears to be effective and IL-18 secreting cancer cells may be a candidate for tumor vaccine therapy.

Animals↗

PubMed2001

Introduction of clusterin gene into human renal cell carcinoma cells enhances their resistance to cytotoxic chemotherapy through inhibition of apoptosis both in vitro and in vivo.

Recent studies have revealed the powerful antiapoptotic activity of clusterin in various malignant tumors; however, the significance of clusterin expression in the acquisition of a resistant phenotype against several kinds of treatment in human renal cell carcinoma (RCC) has not been well characterized. We, therefore, transfected the clusterin cDNA into RCC ACHN cells, that scarcely express clusterin protein, to examine whether overexpression of clusterin inhibits chemotherapy-induced apoptosis both in vitro and in vivo. Although no significant differences were observed in the in vitro growth rates between clusterin-transfected ACHN (ACHN/CL) and the vector only-transfected cell line (ACHN/Co), ACHN/CL exhibited high resistance to cisplatin treatment compared with ACHN/Co, with a greater than 5-fold higher IC(50) through the inhibition of apoptotic cell death, which was demonstrated by DNA fragmentation analysis and western blotting of PARP protein. Moreover, intravenous administration of cisplatin into athymic nude mice bearing ACHN/CL tumors resulted in 2- to 3-times faster tumor growth compared with ACHN/Co tumors. These findings suggest that clusterin overexpression helps confer a chemoresistant phenotype through inhibition of apoptosis in human RCC cells.

Animals↗

PubMed2001

Voiding dysfunction of sigmoid neobladder in women: a comparative study with men.

OBJECTIVE: We compared results of urodynamic testing in male and female patients with sigmoid neobladders following radical cystectomy to determine factors important to voiding status, especially in women. METHODS: Continence status, urodynamics by pressure-flow measurements, and neocystograms were evaluated in 14 male and 9 female patients. RESULTS: Of 14 male patients, 11 (78.6%) showed acceptable urinary continence during the day, as did all of the 9 female patients. At night, 6 of the 14 men and 6 of the 9 women were continent with or without voiding at regular intervals. All 14 male patients could void volitionally during the follow-up period. In contrast, 1 of 9 female patients required clean intermittent catheterization to manage the large amount of residual urine. Her neocystourethral angle was 90 degrees and pelvic descent of the bladder (pouchocele) was observed. The intrareservoir pressure at maximal flow was significantly lower in female than in male patients (p<0.05). The ratio of abdominal pressure to intrareservoir pressure did not differ significantly between males and females. Abdominal straining generated most of the intrareservoir pressure. An increase in intrareservoir pressure was associated with urinary flow, but the magnitude of pressure did not correlate with the peak urinary flow. CONCLUSION: The location of the neobladder and avoidance of angulation at its outlet are important for obtaining good voiding after the reconstruction of neobladder in women, but the intrareservoir pressure is less critical.

Colon, Sigmoid↗

PubMed2001

Role of percutaneous image-guided biopsy in the evaluation of renal masses.

OBJECTIVE: The objective of the present study was to evaluate the indications, accuracy, complications and impact of image-guided percutaneous biopsy of renal masses. MATERIALS AND METHODS: Between 1994 and 1999, percutaneous biopsies under ultrasonography or computerized tomography guidance were performed in 33 patients with renal mass (22 men and 11 women, mean age 57.5 years, range 21-88). We retrospectively analyzed the relationship between clinical and histopathological findings, and discuss the appropriateness of the indications for image-guided percutaneous biopsy in the diagnosis of renal masses. RESULTS: The indications used in our institution were as follows: (1) clinical and radiological findings to suggest a diagnosis other than primary renal cell carcinoma (RCC) (n = 15); (2) suspicious lesions of RCC in multiple cystic renal masses (n = 7); (3) differentiation of transitional cell carcinoma of the renal pelvis from RCC (n = 7); (4) differentiation of angiomyolipoma from RCC (n = 4). Sufficient amounts of tissues were obtained from all patients for pathological diagnosis. Among 33 patients, 21 (63.6%) were diagnosed positive for malignancy, and 15 underwent surgical intervention. The histopathological findings between percutaneous biopsy and surgically resected tissue were identical in 13 cases (86.7%). No patient developed major complications requiring surgical treatment. CONCLUSION: If performed under appropriate selection of patients, percutaneous image-guided biopsy is a safe, reliable and accurate method of managing suspicious and/or indeterminate renal mass, and may contribute to the selection of appropriate clinical management by avoiding unnecessary procedures.

Adult↗

PubMed2001

Senile plaques in an aged western lowland gorilla.

Senile plaques (SPs) were found in the cerebral cortex of a 44-year-old Western lowland gorilla (Gorilla gorilla gorilla). All the SPs were obtained as dense assemblies consisting of fibrous materials by silver impregnation, but were not detected by Congo red. More SPs were detected by immunostaining for amyloid beta protein (A beta) and a half of A beta-positive-SPs were also immunoreactive for apolipoprotein E. Moreover, all SPs were immunoreactive for A beta 42 and A beta 43, but not for A beta 40. SPs also did not contain A beta precursor protein-positive structures. These findings suggested that SPs in this case were diffuse plaques. To our knowledge, this is the first report of SPs in the gorilla.

Aging↗

PubMed2001

Bcl-2 modulates Fas-mediated apoptosis in human renal cell carcinoma cell lines.

The objective of this study was to characterize the role of Bcl-2 expression in Fas-mediated apoptosis in human renal cell carcinoma (RCC) cell lines. RT-PCR analyses showed that 10 different RCC cell lines expressed Fas, but not Fas ligand. Seven of 10 cell lines expressed Fas strongly, while 3 cell lines weakly expressed Fas by flow cytometric analyses. Measurement of the LDH concentration in the culture supernatant revealed that 6 of the 7 cell lines which expressed Fas strongly were sensitive to treatment with an agonistic anti-Fas monoclonal antibody (CH11), whereas all cell lines which weakly expressed Fas did not show Fas-mediated cell death. Furthermore, Bcl-2 expression was found only in three cell lines which were all susceptible to CH11, and the downregulation of Bcl-2 protein by treatment with antisense oligodeoxynucleotide targeting Bcl-2 gene resulted in an enhancement of cell death induced by CH11. These findings suggest that strong Fas expression is necessary for Fas-mediated cell death in RCC cell lines, and Bcl-2 has a protective role against treatment with an anti-Fas monoclonal antibody, despite the fact that Bcl-2 expression was observed only in sensitive cell lines to Fas-mediated cell death.

Antibodies, Monoclonal↗

PubMed2001

Effects of retinoic acid and interferon-gamma on expression of the retinoic acid receptor in mouse renal cell carcinoma.

The clinical outcome of interferon-gamma treatment of metastatic renal cell carcinoma remains unsatisfactory. To overcome this, a reagent that has a different action on cancer cells is desired. One such candidate may be 13-cRA (cis retinoic acid), a vitamin A derivative known to markedly regulate the differentiation and proliferation of normal and neoplastic cells. Moreover, 13-cRA demonstrates a remarkable synergistic effect with IFN-gamma in certain types of cancer. We investigated the efficacy of concomitant administration of 13-cRA and IFN-gamma. The in vivo anti-tumor effects were evaluated in a lung metastasis model using a mouse renal cell carcinoma cell line (RenCa). The in vitro anti-tumor effects were also assessed by MTT assay. The presence of retinoic acid receptors (RAR)-alpha, -beta and -gamma was examined by PCR analysis. The influence of IFN-gamma on these retinoic acid receptors was evaluated by Northern blotting. IFN-gamma showed anti-tumor effects both in vivo and in vitro. This effect was enhanced synergistically with concomitant 13-cRA treatment. RenCa cells expressed RAR-alpha, and -gamma, but not -beta according to PCR analysis. IFN-gamma treatment increased the expression level of RAR-alpha and RAR-gamma according to Northern blot analysis. Combination therapy using IFN-gamma and 13-cRA showed synergistic anti-tumor effects, which exceeded those of each therapy alone. Moreover, IFN-gamma treatment increased RAR-alpha and RAR-gamma expression. Thus, the augmented anti-tumor effects of IFN-gamma and 13-cRA may be attributable to enhanced expression of RAR-alpha and RAR-gamma by IFN-gamma treatment.

Animals↗

PubMed2001

[Laparoscopic radical prostatectomy: initial 17 case report].

PURPOSE: We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer. MATERIAL AND METHOD: Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1 ng/ml, 6, respectively. We followed the operation technique from the "Montsouris technique". Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures. RESULTS: No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600 ml (range 100 to 3,135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2 ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent. CONCLUSION: Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer.

Aged↗

PubMed2001

Significance of matrix metalloproteinases and tissue inhibitors of metalloproteinase expression in the recurrence of superficial transitional cell carcinoma of the bladder.

PURPOSE: We determined whether expression levels of matrix metalloproteinase (MMP)-2, MMP-9, membrane-type MMP-1 (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 messenger (m) RNA in superficial transitional cell carcinoma of the bladder may be used as predictors of tumor recurrence. MATERIALS AND METHODS: Total RNA was extracted from 51 superficial transitional cell carcinomas of the bladder, and expression levels of MMP-2, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 messenger mRNA in these specimens were measured by Northern blot analysis. Results were evaluated in regard to tumor recurrence. RESULTS: Mean MMP-9 and TIMP-2 mRNA expression in the tumors of patients with recurrence were 2.5 and 3-fold higher, respectively, than in those of patients without recurrence despite no significant differences in MMP-2, MT1-MMP or TIMP-1 expression. The recurrence-free survival rate of patients with elevated MMP-9 and TIMP-2 mRNA expression was significantly lower than that of patients with normal MMP-9 and TIMP-2 expression, respectively. In addition, Cox's multivariate analysis revealed that elevated MMP-9 and TIMP-2 were strongly associated with a high incidence of intravesical recurrence of superficial bladder cancer. CONCLUSIONS: These results indicate that MMP-9 and TIMP-2 are strongly expressed in the tumors of patients with recurrence compared with those without recurrence and elevated MMP-9 and TIMP-2 may be used as predictors of recurrence in patients with superficial transitional cell carcinoma.

Adult↗

PubMed2001

Long-term results of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer: biochemical and pathological effects.

The objective of this study was to evaluate the long-term biochemical and pathological effects induced by neoadjuvant hormonal therapy (NHT) in patients with clinically localized disease. Between March 1993 and May 1997, 24 patients with clinically localized prostate cancer received NHT for 3 to 11 months (median: 5 months) using luteinizing hormone-releasing hormone analogue prior to radical prostatectomy and pelvic lymphadenectomy. The clinical stage was T1 in 1 patient, T2 in 17 and T3 in 6, the pretreatment serum prostate-specific antigen (PSA) value was < or = 10 ng/ml in 5 patients, 10 to 20 ng/ml in 4 and > 20 ng/ml in 15 (mean: 34.7 micrograms/l), and the Gleason score was < or = 4 in 9 patients, 5 to 7 in 11 and > 8 in 3. The mean prostate specific antigen (PSA) value 3 months after NHT had reduced below 2 ng/ml in 18 of the 24 patients (67%), and finally decreased by an average of 95% (i.e., 1.9 ng/ml) prior to surgery. The pathological stage was pT0 in 2 patients, pT2 in 10 and pT3 in 12. The incidence of organ-confined disease (OCD) was significantly higher in patients with clinical stage T1 or T2a than with T2b or T3, with pretreatment PSA values < or = 10 ng/ml than with PSA values > 10 ng/ml, and with PSA values < or = 2 than with PSA values > 2 at 3 months after NHT; in contrast, the Gleason score had no significant impact on the rate of OCD. After a median follow-up of 49 months (range 34 to 85 months), 6 patients (25%) had a recurrence evidenced by rising PSA, and the 3-year recurrence-free survival rate was 79%. These results suggest that NHT appears not to be of significant additional benefit to patients who have a higher clinical T stage, higher pretreatment PSA values and/or in patients whose PSA values do not normalize early in the treatment process.

Aged↗