Biomedical subjects

Yoichi Mizutani

Publications and source records attributed to Yoichi Mizutani.

At least 19 recordsLinked to original sources

PubMed2007

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor.

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.

Adolescent↗

PubMed2006

The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.

OBJECTIVE: To measure dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the metabolism of 5-fluorouracil (5-FU), expression in prostate cancer and determine whether 5-chloro-2,4-dihydroxypyridine (CDHP), a potent inhibitor of DPD, enhances the antitumoral activity of 5-FU against prostate cancer. PATIENTS, MATERIALS AND METHODS: In all, 44 prostate tissue specimens were obtained from men who had a radical prostatectomy alone for prostate cancer, and 38 specimens from men who had had neoadjuvant hormonal therapy. We analysed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry, and determined its prognostic significance. In cultured human prostate cancer lines (DU145 and LNCaP), we compared the cytotoxicity of 5-FU/CDHP with that of 5-FU alone. Finally, in experiments on immunodeficient mice, we studied the effect of oral administration of tegafur, a pro-drug for 5-FU, with or without CDHP on the growth of tumours introduced by injection of DU145 cells. RESULTS: The expression of DPD was significantly higher in cancerous than normal prostate tissue; 36 of 44 (82%) specimens of prostate cancer expressed DPD, whereas only 25 of 44 (57%) specimens of normal prostate tissue expressed DPD. For men with prostate cancer who had radical prostatectomy alone, men with negative DPD expression tended to have a longer recurrence-free survival than those with positive expression; there were no recurrences in men with prostate cancer and negative DPD expression in the 5-year follow-up. DPD expression was significantly lower in men with prostate cancer who received neoadjuvant hormonal therapy. In vitro treatment of human prostate cancer cell lines with 5-FU/CDHP showed more cytotoxicity than with 5-FU treatment alone. Finally, DU145 tumours in mice treated with tegafur and CDHP were significantly smaller than in mice given tegafur alone. CONCLUSION: The present study showed that DPD expression is elevated in prostate cancer, and indicate that DPD inhibitors might enhance the antitumour activity of 5-FU against prostate cancer.

Aged↗

PubMed2006

Visual analog scale questionnaire to assess quality of life specific to each symptom of the International Prostate Symptom Score.

PURPOSE: We assessed patient quality of life specific to each of the 7 items on the International Prostate Symptom Score, as evaluated with a novel visual analog scale questionnaire. MATERIALS AND METHODS: A total of 246 male patients with a chief complaint of lower urinary tract symptom were asked to complete the International Prostate Symptom Score and visual analog scale questionnaires to assess bother or satisfaction regarding patient quality of life specific to each of the 7 items on the International Prostate Symptom Score. RESULTS: An item with the maximum visual analog scale measure matched the chief complaint in 169 patients (69%). In contrast, the chief complaint failed to match to an item with the most severe International Prostate Symptom Score in 104 patients (42%) (p = 0.012). Multiple regression analysis to define the best predictor of International Prostate Symptom Score quality of life score of the 14 items, including International Prostate Symptom Score and visual analog scale, revealed that the best predictor was the visual analog scale measure for nocturia (p = 0.0003), followed by visual analog scale measures for frequency (p = 0.0004) and incomplete emptying (p = 0.01). After alpha-blocker treatment improvement in the visual analog scale measure for the chief complaint correlated better with improvement in the International Prostate Symptom Score quality of life score than the change in International Prostate Symptom Score. The overall test-retest correlation for the visual analog scale questionnaire in 55 healthy elderly men and 44 patients with lower urinary tract symptoms was 0.772 and 0.742, respectively (p <0.00001). CONCLUSIONS: The novel visual analog scale measure of quality of life specific to each of the 7 items on the International Prostate Symptom Score has a significant impact on identifying the patient chief complaint as well as on patient specific quality of life. Our study supports the concomitant use of the International Prostate Symptom Score and visual analog scale questionnaires.

Aged↗

PubMed2006

Running suture for vesicourethral anastomosis in minilaparotomy radical retropubic prostatectomy.

INTRODUCTION: We used a running suture method for vesicourethral anastomosis in patients undergoing minilaparotomy radical retropubic prostatectomy. TECHNICAL CONSIDERATIONS: The vesicourethral anastomosis using a single knot at the 6:30-o'clock position is created with two steps of semicircular running suture. A total of 21 consecutive patients underwent this running suture method using the Endostitch in the hands of a single surgeon (T.M.) between March and November 2004. The running suture procedure was completed in 15 minutes on average. After surgery, no urinary leakage at the anastomotic site was found. Satisfactory continence was achieved in the short term in 100% (0 to 1 pad per day) of cases. However, dilation at the anastomosis using a metal dilator was required in 2 patients immediately after surgery. CONCLUSIONS: The running suture method is considered a feasible alternative in minilaparotomy radical retropubic prostatectomy.

Anastomosis, Surgical↗

PubMed2006

Complexed PSA improves prostate cancer detection: results from a multicenter Japanese clinical trial.

OBJECTIVES: To compare the distribution of total and complexed prostate-specific antigen (cPSA) in men with and without prostate cancer with another studied population and to ascertain whether cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 760 men whose serum total PSA (tPSA) values ranged from 1.0 to 100 ng/mL were enrolled. Serum samples for tPSA and cPSA (ADVIA Centaur) were obtained in all cases. The area under the curve was calculated for comparison of the tPSA and cPSA values. We calculated the number of cancers missed and false-positive results at various cutoff values of cPSA compared with the conventional tPSA threshold of 4.0 ng/mL. RESULTS: Prostate cancer was detected in 268 (35.3%) of 760 patients. cPSA was greater than 8.3 ng/mL (equivalent to 10.0 ng/mL tPSA) in 46.6% of the men with cancer. The area under the curve for cPSA (0.741) was significantly better than that for tPSA (0.721, P <0.001). At a sensitivity of 85% to 95%, significant differences were found in the corresponding specificity between tPSA and cPSA. cPSA at a 3.0-ng/mL threshold detected an identical number of cancers as a tPSA cutoff of 4.0 ng/mL; however, it decreased the false-positive results by 28 cases. CONCLUSIONS: To our knowledge, this is the first report of the distribution of cPSA in Japanese men using a urologic referral population. cPSA can be an alternative to tPSA as the first screening test. A substantial number of men in Japan with prostate cancer are currently diagnosed with a tPSA value greater than 10.0 ng/mL.

Aged↗

PubMed2006

Gene therapy with TRAIL against renal cell carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells. However, TRAIL is not toxic against most normal cells. We have accordingly examined by in vivo electroporation whether TRAIL induces apoptosis in renal cell carcinoma. In addition, combination treatment with TRAIL and 5-fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65 renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into the NC65 tumors in the right flanks of severe combined immunodeficient mice. Tumors were pulsed with the CUY21 electroporator. Electroporation was done once on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene therapy using in vivo i.t. electroporation was done once only, the growth of NC65 tumors was not inhibited. However, when TRAIL gene therapy was done thrice, growth suppression of the NC65 tumors was observed. Transfection of the TRAIL gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells were treated with TRAIL gene therapy in combination with 5-FU, stronger growth suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in severe combined immunodeficient mice. This study shows that TRAIL gene therapy induced growth suppression and apoptosis in NC65 tumors without severe side effects, and that combination treatment of NC65 cells with TRAIL gene therapy and 5-FU resulted in higher antitumor activity. These findings suggest that TRAIL gene therapy and/or 5-FU may be effective against renal cell carcinoma without harmful toxic effects.

Animals↗

PubMed2006

[Progress in therapy for testicular tumors].

Approximately 80% of patients with metastatic testicular tumors are cured by cisplatin-containing chemotherapy and surgery. However, the remaining 20% of patients with advanced testicular tumors can not be cured at present. Thus, therapy for these testicular tumors infractory to treatment is the most important issue. Recently, chemotherapy for such tumors is developing, especially salvage chemotherapy using novel anticancer agents(paclitaxel, gemcitabine,irinotecan, docetaxel, oxaliplatin, etc) and high-dose anticancer drugs. Some of the new modalities are very attractive. In this article, we reviewed mainly these new forms of chemotherapy for testicular tumors.

Antineoplastic Agents↗

PubMed2006

[Salvage chemotherapy with paclitaxel, ifosphamide and nedaplatin for relapsed or refractory germ cell cancer].

PURPOSE: Only 20-30% of patients with cisplatin refractory or relapsed germ cell cancer will remain continuously disease free with salvage chemotherapy. Paclitaxel is a potent anticancer agent against a variety of solid cancers. The present study investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer. MATERIAL AND METHODS: The combination chemotherapy consisted of paclitaxel 210 mg/m2 on day 1, nedaplatin 100 mg/m2 on day 2 and ifosphamide 1.2 g/m2 on day 2-day 6 every three weeks. Fourteen patients with cisplatin refractory germ cell cancer, ranging in age from 17 to 44 years were enrolled onto the study. RESULTS: Fourteen patients were evaluated for response and toxicity. Patients received 1-14 cycles of the combination chemotherapy. The median duration of follow-up was 34 months (10-64 months). Response rate was 57.1% (CR / PR(m-):8 cases, NC:5 cases, PD:1 cases). Seven patients remain alive without disease. However, 5 patients died of the disease. All patients had grade 3 or 4 hematological toxicity. CONCLUSION: This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer.

Adolescent↗

PubMed2005

KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors.

We investigated the expression of KIT (product of c-kit oncogene), gain-of-function mutations, and activation of its downstream signal transduction in human testicular cancers. KIT was expressed in 88% (22/25) of seminomas and in 44.4% (4/9) of non-seminomas compared to adjacent normal testicular tissue. Nine of the KIT-expressing seminomas had mutations (40.9%; 9/22) in the c-kit gene; two cases in exon 11 and 7 cases in exon 17. Two of these mutations in exon 17 were novel, and the other seven mutations were identical to the already known gain-of-function mutations which cause activation of KIT without ligand stem cell factor. All of the mutant KIT and 53.8% (7/13) of wild-type KIT were phosphorylated (activated) and associated with phosphorylated phosphatidylinositol 3-kinase (PI3K). Akt was also phosphorylated in these seminomas, suggesting that the KIT-PI3K-Akt pathway is activated in seminoma. These findings suggest that the KIT-PI3K-Akt pathway is constitutively activated in testicular germ cell tumors, due to overexpression of KIT protein and/or gain-of-function mutations in the c-kit gene.

Adult↗

PubMed2005

Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation.

Treatment of several prostate cancer (CaP) cell lines (PC-3, CL-1, and DU-145) with the nitric oxide (NO) donor DETA/NONOate upregulated Fas expression and sensitized the CaP cells to the Fas ligand CH-11 agonist monoclonal antibody-induced apoptosis. Previous findings demonstrated that the transcription repressor Yin Yang 1 (YY1), which is inhibited by NO, negatively regulates Fas transcription [H.J. Garban, B. Bonavida, Nitric oxide inhibits the transcription repressor Yin-Yang 1 binding activity at the silencer region of the Fas promoter: a pivotal role for nitric oxide in the upregulation of Fas gene expression in human tumor cells, J. Immunol. 167 (2001) 75-81]. YY1 is a zinc finger protein and thus, we hypothesized that NO inhibits YY1 activity via S-nitrosation of critical cysteines residues coordinated by Zn2+. Treatment of PC-3 cells with DETA/NONOate inhibited the constitutive DNA-binding activity of YY1 as assessed by EMSA. Further, treatment with DETA/NONOate resulted in S-nitrosation of YY1 as detected by two different methods. The DAN-based method examined NO-treated tumor-derived cell lysates that were immunoprecipitated with an anti-YY1 specific antibody and the NO released was determined quantitatively by fluorometry. The second method consisted of immunoprecipitation of the tumor cell lysates by an anti-SNO cysteine antibody and the immunoprecipitate was immunoblotted with anti-YY1 antibody. Both methods revealed significant S-nitrosation of YY1 by DETA/NONOate treatment over control untreated cells. The S-nitrosation of YY1 was further corroborated by immunohistochemistry using dual color immunofluorescence. The direct role of YY1 in the negative regulation of Fas expression was demonstrated by transfection of cells with siRNA YY1. The transfectants exhibited upregulation of Fas expression in the absence of treatment with DETA/NONOate and were sensitized to CH-11-induced apoptosis. Altogether, these findings reveal that NO inhibits YY1 DNA-binding activity through S-nitrosation and consequently results in upregulation of Fas expression and tumor cell sensitization to Fas-induced apoptosis.

Apoptosis↗

PubMed2005

Tunicamycin enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human prostate cancer cells.

Death receptor 5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L). In this study, we showed that tunicamycin, a naturally occurring antibiotic, is a potent enhancer of TRAIL-induced apoptosis through up-regulation of DR5 expression. Tunicamycin significantly sensitized PC-3, androgen-independent human prostate cancer cells, to TRAIL-induced apoptosis. The tunicamycin-mediated enhancement of TRAIL-induced apoptosis was markedly blocked by a recombinant human DR5/Fc chimeric protein. Tunicamycin and TRAIL cooperatively activated caspase-8, -10, -9, and -3 and Bid cleavage and this activation was also blocked in the presence of the DR5/Fc chimera. Tunicamycin up-regulated DR5 expression at the mRNA and protein levels in a dose-dependent manner. Furthermore, the tunicamycin-mediated sensitization to TRAIL was efficiently reduced by DR5 small interfering RNA, suggesting that the sensitization was mediated through induction of DR5 expression. Tunicamycin increased DR5 promoter activity and this enhanced activity was diminished by mutation of a CHOP-binding site. In addition, suppression of CHOP expression by small interfering RNA reduced the tunicamycin-mediated induction of DR5. Of note, tunicamycin-mediated induction of CHOP and DR5 protein expression was not observed in normal human peripheral blood mononuclear cells. Moreover, tunicamycin did not sensitize the cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may be a promising candidate for prostate cancer therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein.

Combined treatment with a proteasome inhibitor and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for cancer therapy. Proteasome inhibitors induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism of DR5 up-regulation has not been elucidated. In this study, we report that CCAAT/enhancer-binding protein homologous protein (CHOP) is a regulator of DR5 induction by proteasome inhibitor MG132. MG132 induced DR5 expression at a protein and mRNA level in prostate cancer DU145 cells. Furthermore, MG132 increased DR5 promoter activity. Using a series of deletion mutant plasmids containing DR5 promoters of various sizes, we found that MG132 stimulated the promoter activity via the region of -289 to -253. This region contained a CHOP-binding site. Site-directed mutation of the site abrogated the promoter activity enhanced by MG132. An electrophoretic mobility shift assay showed that CHOP directly bound to the MG132-responsive site on the DR5 promoter. Expression of the CHOP protein was increased with MG132 along with DR5 up-regulation. Furthermore, CHOP small interfering RNA attenuated the DR5 up-regulation due to MG132. These results indicate that the proteasome inhibitor MG132 induces DR5 expression through CHOP up-regulation.

Apoptosis↗

PubMed2005

Combination therapy with alarm and drugs for monosymptomatic nocturnal enuresis not superior to alarm monotherapy.

OBJECTIVES: To evaluate the effectiveness of alarm-based combination therapy using desmopressin and imipramine for primary monosymptomatic nocturnal enuresis. METHODS: Of the 105 patients, 37 were treated with alarm monotherapy (monotherapy group), 35 were treated with desmopressin combined with an alarm (desmopressin group), and 33 were treated with imipramine combined with an alarm (imipramine group). The therapeutic effects were evaluated at 3 and 6 months. The relapse rates and predictive factors of the therapies were also studied. RESULTS: No significant differences were found in the changes in the frequency of wet nights among the three groups, although the frequencies in all three groups decreased significantly with the therapeutic duration. Although the improvement rates at 3 months did not differ among the three groups, the improvement rate of 80% in the desmopressin group and 79% in the imipramine group at 6 months were greater than the 59% rate in the monotherapy group. After cure, no patients relapsed in the monotherapy group, and 3 (43%) each did so in the desmopressin and imipramine groups. In comparing the improved cases in each group, no significant differences were found in background factors. CONCLUSIONS: Desmopressin and imipramine combined with an alarm was no more effective than alarm monotherapy. As for alarm monotherapy, other therapeutic modalities should be considered if it has not proved effective after 3 months. In such a situation, combination therapy may be effective as a second choice. No predictive factors for the therapeutic effects in the three modalities were found.

Adolescent↗

PubMed2005

Laparoscopic pyeloplasty and isthmectomy for hydronephrosis of horseshoe kidney: a pediatric case.

A 4-year-old boy suffering from hydronephrosis of a horseshoe kidney underwent laparoscopic pyeloplasty with isthmectomy. Pyeloplasty was performed by the transposition of crossing vessels and the Anderson-Hynes method. In isthmectomy, Ligasure was used for transection of the isthmus. The surgery time was 310 minutes, the estimated blood loss was 10 mL, and the patient required no analgesia postoperatively. Convalescence was complete within 14 days. The follow-up diuretic renal scan showed prompt emptying of the radioisotope from the left collecting system, with a T1/2 of 12 minutes.

Anastomosis, Surgical↗

PubMed2005

Learning curve of hand-assisted retroperitoneoscopic nephrectomy in less-experienced laparoscopic surgeons.

AIM: To evaluate the learning curve of hand-assisted retroperitoneoscopic nephrectomy (HALS) performed by less-experienced surgeons. METHODS: The operative records of 166 patients, including 103 with renal tumors and 63 with renal pelvic or ureteral tumors, who underwent HALS performed by 18 less-experienced urologists were reviewed. RESULTS: The insufflation time in the first four cases was significantly longer than that in the sixteenth and later cases. The insufflation time in cases 5-10 was 14-24 min longer than that in the cases 16 onward, although the differences were not significant. The estimated blood loss did not differ in each group of cases. The complication rate in early cases, in which the operators' experience was five cases or less, was 6% (4/71), while that in later cases was also 7% (7/95). In the analysis of the learning curve of a single surgeon who performed 57 procedures, the insufflation time in cases 1-5 was significantly longer than in cases 41-57. The insufflation times in cases 5-10 were 45 min longer than those in cases 41-57, although the difference was not significant. The estimated blood loss did not differ in each group of cases. Complications did not seem related to operation experience. CONCLUSION: In HALS, 5-10 cases were necessary for less-experienced urologists to gain average operating skills for this procedure. It may be reasonable for less-experienced surgeons to begin standard laparoscopic procedures after experiencing 10 cases of the present procedure.

Adult↗

PubMed2005

Clinical characteristics of prostate cancer in Japanese men in the eras before and after serum prostate-specific antigen testing.

BACKGROUND: We retrospectively reviewed a large series of Japanese men with histologically proven prostate cancer to assess the clinical characteristics of the cancer in three different eras of prostate cancer management since prostate-specific antigen (PSA) testing started in 1988. METHODS: The medical records of 1125 patients treated between 1975 and 2002 were reviewed with respect to age, chief complaints, clinical stage, tumor grade, treatment options at each stage, and prognosis. We classified the patients as follows: those treated in the pre-PSA era between 1975 and 1988 (n=182), those treated in the PSA era between 1988 and 1997 (n=301; PSA era phase 1) and the PSA era between 1998 and 2002 (n=642; PSA era phase 2). RESULTS: Compared with the pre-PSA era, there were significant increases in the proportion of well-differentiated adenocarcinoma with respect to the biopsy tumor grade (24 vs 35%, P<0.01), in the proportion of linically organ-confined disease (21 vs 43%, P<0.001), and in the proportion of patients who underwent radical prostatectomy (13%vs 20%, P<0.01) after PSA testing was introduced. In addition, there was a significant difference in the proportion of subjects who were 70--79 years of age between the pre-PSA era (52%, 95/182) and the PSA era phase 2 (42%, 270/642, P<0.05). There was also a significant difference in the proportion of patients who underwent surgical castration between the pre-PSA era (78%) and PSA era phase 2 (10%, P<0.001). The proportion of patients participating in prostate cancer screening increased from 3% (pre-PSA era) to 11% (PSA era phase 1 and PSA era phase 2, P<0.05). In all clinical stages, there were significant differences between the pre- and post-PSA eras in cause-specific survival rates (5-year: 74 vs 94% in stages A and B, P<0.01; 54 vs 89% in stage C, P<0.001; 32 vs 53% in stage D, P<0.001). CONCLUSIONS: Migrations in the age of patients (toward younger patients), the stage of the cancer (towards earlier stages) and the histological findings (toward favorable findings), in addition to changes in treatment options, have contributed to the prolonged survival of Japanese men with prostate cancer after the PSA testing was introduced.

Aged↗

PubMed2005

Gene cloning, overproduction, and characterization of thermolabile alkaline phosphatase from a psychrotrophic bacterium.

The gene encoding alkaline phosphatase from the psychrotrophic bacterium Shewanella sp. SIB1 was cloned, sequenced, and overexpressed in Escherichia coli. The recombinant protein was purified and its enzymatic properties were compared with those of E. coli alkaline phosphatase (APase), which shows an amino acid sequence identity of 37%. The optimum temperature of SIB1 APase was 50 degrees C, lower than that of E. coli APase by 30 degrees C. The specific activity of SIB1 APase at 50 degrees C was 3.1 fold higher than that of E. coli APase at 80 degrees C. SIB1 APase lost activity with a half-life of 3.9 min at 70 degrees C, whereas E. coli APase lost activity with a half-life of >6 h even at 80 degrees C. Thus SIB1 APase is well adapted to low temperatures. Comparison of the amino acid sequences of SIB1 and E. coli APases suggests that decreases in electrostatic interactions and number of disulfide bonds are responsible for the cold-adaptation of SIB1 APase.

Alkaline Phosphatase↗

PubMed2005

[The second-line chemotherapy for urological cancers].

This review summarizes second-line chemotherapy for testicular cancer and urothelial cancer. For testicular cancer, the combination of bleomycin (BLM), etoposide (ETP), and cisplatin (CDDP) (BEP) is commonly used as an induction therapy. The combination of vinblastine (VLB), ifosfamide (IFM) and CDDP (VeIP) or ETP, IFM, and CDDP (VIP) is used for the second-line chemotherapy. When the efficacy of VeIP and VIP is not sufficient, high-dose chemotherapy or chemotherapy with new anticancer agents has been used for the second-line chemotherapy. High-dose chemotherapy showed long-term survival rates of 30-50%, but patients with testicular cancer resistance to CDDP have poor outcomes. Although new anticancer agents, such as paclitaxel (TXL), gemcitabine (GEM) and irinotecan have been introduced, further examinations are needed to evaluate these drugs. The combination of methotrexate, VLB, adriamycin, and CDDP (MVAC) is used as the standard chemotherapy for urothelial cancer. The outcomes of MVAC are favorable, but the duration of response is short and long-term survival cannot be expected. Recently, the efficacy of new anticancer agents including TXL and GEM against urothelial cancers has been demonstrated. Although TXL and GEM combination therapy as the second-line chemotherapy has some effects, more evidence needs to be accumulated to establish it as a second-line treatment.

Antineoplastic Combined Chemotherapy Protocols↗