Masaru Murai

AN ESSENTIAL ROLE FOR NUCLEAR FACTOR KAPPA B IN PREVENTING TNF-alpha-INDUCED CELL DEATH IN PROSTATE CANCER CELLS

PURPOSEnAlthough tumor necrosis factor-alpha (TNF-alpha) induces a strong cytotoxic effect on cell growth, many authors have reported that various cancer cells are resistant to TNF-alpha and the basis for this sensitivity or resistance to TNF-alpha remains to be elucidated. Since nuclear factor kappa B (NF-kappaB) activation has recently been reported to inhibit TNF-alpha-induced cell death, we studied whether NF-kappaB also assumes a protective role in TNF-alpha-induced cell death in prostate cancer cells.nnnMATERIALS AND METHODSnWe used two human prostate cancer cell lines of DU145 and PC-3. We prepared two different NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC) and NF-kappaB decoy. NF-kappaB DNA binding activity was detected by electrophoretic mobility shift assay (EMSA). Cell survivals were measured by MTT assay. Induction of apoptosis was detected by nuclear staining and measured by fragmented DNA ELISA.nnnRESULTSnEMSA showed that NF-kappaB inhibitors continuously inhibited TNF-alpha-induced NF-kappaB activation. Cell growth was not inhibited by either TNF-alpha (50 ng./ml. or less) or NF-kappaB inhibitors. However, both PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors showed significant growth inhibition compared with controls (p<0.05). Nuclei of PCA cells appeared severely fragmented by this combination therapy. Furthermore, the levels of DNA fragmentation were significantly elevated in PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors compared with controls (p<0.05).nnnCONCLUSIONSnNF-kappaB activation is suggested to produce the resistance of DU145 and PC-3 to TNF-alpha and that the combination of TNF-alpha and NF-kappaB inhibitors could be constituted an effective therapy to TNF-alpha-resistant human prostate cancer cells.

Successful Diagnosis Of Orthotopic Rat Superficial Bladder Tumor Model By Ultrathin Cystoscopy

PURPOSEnIn the orthotopic animal bladder tumor model noninvasive evaluation of the tumor establishment and the therapeutic effect has been difficult. To our knowledge we present the first diagnosis of orthotopic rat superficial bladder tumor model by ultrathin cystoscopy.nnnMATERIALS AND METHODSnThe established AY-27 rat bladder carcinoma cell line was transplanted orthotopically into 22 female Fischer F344 rats. A cell suspension containing 4 x 10 AY-27 cells was instilled into the bladder, which had been conditioned with mild acid washing. To evaluate tumor growth serial cystoscopy was performed via the urethra with an ultrathin endoscope (diameter 0.75 mm.) 5 to 14 days after tumor cell inoculation. At intervals after cystoscopic tumor detection the rats were sacrificed for autopsy and histological examination.nnnRESULTSnIn all 22 rats the orthotopic bladder tumor was established 7 to 10 days after tumor cell implantation and in most it was superficial. Cystoscopy permitted inspection of the urethra and whole bladder surface. We detected all tumors as broad based papillary mass (minimal lesion 1 mm. or less) and inspected its detailed appearance and accurate location.nnnCONCLUSIONSnThe orthotopic rat superficial bladder tumor model and the diagnostic procedure by ultrathin cystoscopy would be ideal system for preclinical evaluation of new potential intravesical therapies.

Rupture of a Pyelocaliceal Diverticulum

Although numerous reports have described the complications associated with pyelocaliceal diverticula, rupture of a pyelocaliceal diverticulum is extremely rare. We present a case of spontaneous rupture of a pyelocaliceal diverticulum with ureteral calculus. After passage of the calculus, no extravasation was demonstrated without any surgical or manipulative procedure. The unusual etiopathological setting which predisposed to the occurrence of such a rare phenomenon is discussed.

Spontaneous Peripelvic Extravasation due to Squamous Cell Carcinoma of the Ureter

A case of spontaneous urinary peripelvic extravasation secondary to an obstructing squamous cell carcinoma of the ureter is presented. A review of the literature reveals that peripelvic extravasation caused by tumor obstruction of the ureter is rare and most of its underlying lesions are metastatic retroperitoneal adenopathy.

Discrimination between urinary tract tissue and urinary stones by fiber-optic-pulsed photothermal radiometry method in vivo

To minimize urotherial tissue injuries by false laser irradiation during the laser stones fragmentation, a novel fiber-optic analytical system was developed which was able to distinguish urotherial tissues from urinary stones in vivo. This system was composed of the fiber-optic pulsed photo-thermal radiometry (PPTR) system together with a thin-fiber endoscope. The ultraviolet Ar laser was employed as the excitation light source. The catheter of this system was 6F in diameter and consisted of SiO2 glass fiber (400 micrometers (phi) ) as an excitation line, an As-S glass fiber (400 micrometers (phi) ) as a detection line, and a thin-fiber endoscope (610 micrometers (phi) ). A urinary stone was introduced into the canine ureter uneter under general anesthesia. The catheter system was inserted through an opening of the ureter distal to the stone. The e-folding decay time of the PPTR waveform of which optical and/or thermal properties of the tissues and stones were characterized was measured in vivo. The e-folding decay times were significantly different between urinary stones and the canine ureter. These results suggest that the fiber-optic PPTR analysis might be significantly useful procedure to prevent urotherial tissue from false irradiation injuries in clinical laser stone fragmentation.

Basic investigation of laser therapy for the ureteral stricture using ultraviolet argon laser and multifiber catheter

In order to develop new, easy, and safe treatment for urinary tract stricture, we investigated the laser plasty using a combination of an uv Ar laser for ablation and a novel multi-fiber catheter for laser delivery. To investigate the characteristics of the uv Ar laser ablation to ureteral tissue, the experiment in vitro was performed. The ureter was clearly ablated with sufficient thin coagulation layer. The proper laser power for the tissue ablation was about 0.5 W for 0.4 mm core-diameter fiber. The multi-fiber catheter (1.6 mm in outer diameter) consisted of 13 pixels of silica glass fibers (0.2 mm in core diameter) for laser delivery and a through lumen (0.9 mm in inner diameter) for guidewire. The catheter was inserted into a canine ureter under the general anesthesia. The ureter and urinary tract were irradiated using about 0.6 W of laser power at the catheter tip with 40s duration. The irradiated urinary tract tissues were histologically investigated. The ureter was ablated up to the submucosa layer. The urinary tract endotherium was eliminated by the laser ablation without the carbonization. No perforation was found at various irradiation conditions. To investigate the ureteral tissue damage of the uv Ar laser irradiation, the serosa temperature was measured by a thermocouple. The temperature elevation of the serosa could be restricted up to 60 degree(s)C, at which the protein was not coagulated. We concluded that the combination of uv Ra laser and multi-fiber catheter offered easy, reliable therapy for coronary structure.

Infrared fiber optic radiometry analysis to prevent tissue injuries during endourological laser therapy

To prevent a false laser irradiation to an urotherial tissue during the laser stone fragmentation, we applied the fiber-optic pulsed photothermal radiometry (PPTR) to discrimination between urinary stones and urotherial tissues. The experiment was made in vitro with the various wet sample of the urinary stones and the canine urotherial tissues. Three different lasers, ultraviolet argon laser(UV Ar laser), visible argon laser(Vis. Ar laser) and carbon monoxide laser(CO laser), were used for excitation light sources of the PFTR method and compared to obtain clear discrimination between the stones and the tissue. The UV Ar laser gave the best result among them. The wet canine urotherial tissue was clearly differential from the urinary stones by the measurement of the e-folding decay time of the PPTR waveform.