Naotaka Sakamoto

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer

We investigated whether a new marker of bone turnover, pyridinoline cross‐linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis.

Establishment and Characterization of Doxorubicin-Resistant Human Bladder Cancer Cell Line, Kk47/adm

A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been established in vitro by exposing KK47 parent cells to progressively higher concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross-resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin, mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of the KK47/ADM cells showed a positive reaction with monoclonal antibody against P-glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated that the resistance exhibited by the KK47/ADM line was mainly due to a lower accumulation of the drug caused by an increased active efflux, and these were reversed in the presence of verapamil. Although verapamil enhanced doxorubicin sensitivity of KK47/ADM, a complete overcoming of the resistance could not be obtained. These two lines with different chemosensitivity are thus considered to be a useful model for developing new chemotherapeutic strategies against multidrug resistant bladder cancer.

Urinary bladder carcinoma with a neoplastic squamous component : a mapping study of 31 cases

A mapping study of cystectomy specimens in three cases of pure squamous cell carcinoma and 28 cases with transitional cell carcinoma with squamous differentiation is described, with an emphasis on the histogenesis of pure squamous cell carcinoma. Two of the three cases of pure squamous cell carcinoma had extensive benign keratinizing mucosa and an atypical squamous metaplastic mucosa contiguous with the tumour. These pure squamous cell carcinomas seemed to be derived from the squamous metaplasia. On the other hand, in all except one of the cases of transitional cell carcinoma with squamous differentiation, there was neither benign keratinizing nor atypical squamous metaplastic mucosa in the bladder.

Recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract.

A retrospective analysis of 53 patients with an upper urinary tract (UUT) transitional cell carcinoma, which was treated surgically, was performed in relation to the development of a subsequent bladder tumor. In 19 of the 53 patients (35.8%) bladder tumors developed following surgery of a UUT tumor. The simultaneous occurrence of a bladder tumor and more than two tumors in the UUT had a significant influence on the rate of bladder tumor recurrence. On the other hand, location, mode of growth, grade, stage and vascular invasion of the UUT tumor, and history of bladder tumors did not seem to be related to the frequency of subsequent bladder tumors. These findings suggest that the diversity of UUT tumors at the time of diagnosis is an important factor in bladder tumor recurrence. Therefore, clinical and pathological examinations should be carefully performed in patients with UUT tumors.

Metallothionein expression is correlated with cisplatin resistance in transitional cell carcinoma of the urinary tract.

Metallothioneins (MTs) are small cysteine-rich, metal-binding proteins involved in resistance to heavy-metal toxicity, and are known to bind cisplatin. Several experiments suggest possible involvement of MT in cellular resistance to cisplatin. To investigate the relationship between MT expression and cisplatin resistance in urinary tract transitional cell carcinoma (TCC), immunohistochemical staining for MT was performed in 31 untreated TCCs of the urinary tract. The results were compared with the sensitivity of the tumors to cisplatin as assessed by the microtiter succinate dehydrogenase inhibition (mSDI) test. Variable MT expression was observed in all 31 TCCs, but there was no specific correlation between histopathological parameters and MT expression. Fourteen (87.5%) of the 16 TCCs with less than 10% of their tumor cells positive for MT were sensitive to cisplatin. On the other hand, 6 (75.0%) of the 8 TCCs with MT expression by more than 30% of their tumor cells were resistant to cisplatin, and there was a significant correlation between MT expression and cisplatin resistance (p < 0.01). These results suggest the possible involvement of MT in the intrinsic cisplatin resistance of urinary tract TCC and that immunohistochemical investigation of MT may be useful for predicting the response of these tumors to cisplatin therapy.

Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: A prospective randomized study

Abstract Background: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara‐C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract.

Molecular analysis of mechanisms regulating drug sensitivity and the development of new chemotherapy strategies for genitourinary carcinomas.

A bstractThe emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

Sclerosing adenosis of the prostate : histopathologic and immunohistochemical analysis

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroraa, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35), These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.

Hand assisted laparoscopic radical nephrectomy for renal carcinoma using a new abdominal wall sealing device.

PURPOSE We report our initial experience with a hand assisted laparoscopic radical nephrectomy for patients with renal carcinoma, and compare our results to those of conventional open radical nephrectomy. MATERIALS AND METHODS The clinical data on 6 consecutive patients who underwent hand assisted laparoscopic radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal wall sealing device. We compared the results of this procedure with those of conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell carcinoma. RESULTS The hand assisted laparoscopic radical nephrectomy for renal carcinoma was successfully performed without any major or minor complications in all 6 patients. Mean operation time for the laparoscopic group was significantly longer than that for the open surgery group (303 minutes versus 224 minutes, p = 0.0042). However, no significant difference was observed in mean estimated blood loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the open surgery group). The frequency of parenteral analgesia postoperatively in the laparoscopic group was significantly lower than that in the open surgery group (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to recover more rapidly than the open surgery group. The abdominal wall sealing device was easy to attach to the abdominal wall, and allowed rapid hand removal and reinsertion. CONCLUSIONS Our preliminary results indicate that a hand assisted laparoscopic radical nephrectomy with the abdominal wall sealing device is an effective and safe surgical procedure, and is less invasive than open radical nephrectomy.

Suitability of Colchicine and Superoxide Dismutase for the Suppression of Renal Scarring following an Infection with Bacteria Showing Mannose-Sensitive Pili

Two new strains of Serratia marcescens were constructed by the gene manipulation method from the clinical isolate US 46, which has two kinds of pili--mannose-sensitive (MS) and mannose-resistant (MR) ones--on the cell surface. After cloning the genes of the MS and MR pili, either the MS or the MR gene was transferred to the nonpiliated Escherichia coli, and MS- or MR-piliated strains were obtained. In the experimental pyelonephritis model of rats, MS- or MR-piliated bacteria were inoculated directly to the renal parenchyma, and the following results were obtained. MS-piliated rather than MR-piliated strains stimulated severe scarring of the kidney, and this scarring was suppressed by treatment with colchicine or superoxide dismutase (SOD) during an early stage of the infection. These findings suggest that MS-piliated bacteria stimulated polymorphonuclear leukocytes, which released large amounts of superoxide resulting in renal scarring. SOD was hoped to be a drug capable of preventing renal scarring, and such a result was successfully obtained.