Biomedical subjects

S Samma

Publications and source records attributed to S Samma.

48 records · Page 3Linked to original sources

PubMed1988

[Experimental model of urinary bladder tumor in rats for evaluation of chemotherapeutic agents].

The chemotherapeutic agents were evaluated using the experimental urinary bladder tumor rat model induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Nine hundred and fourteen male rats received 0.05% BBN in drinking water for 8 weeks, and were divided into 35 groups to follow the regimens of chemotherapeutic agents. Thirty one groups received the agents after BBN treatment, and 4 groups were given the oral agents starting simultaneously with BBN treatment. All rats were killed at 20 weeks and incidence of the urinary bladder was examined histopathologically. The following 13 agents were evaluated; adriamycin (ADM), mitomycin-C (MMC), cyclophosphamide (CPM), 5-fluoro-uracil (5-Fu), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), neocarcinostatine (NCS), carbazil quinone (CQ), bleomycin (BLM), vincristine (VCR) and cis-diammine-dichloroplatinum (CDDP) were dosed intraperitoneally, and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), 1: 4 mixture of FT-207 and uracil (UFT) and 1-Hexylcarbamoyl-5-fluorouracil (HCFU) were dosed orally. Among these agents, 5-Fu, FT-207, CQ, VCR, CDDP, UFT and HCFU were effective in inhibiting the incidence of urinary bladder tumor induced by BBN. In conclusion, the experimental bladder tumor rat model induced by BBN seems to be useful in evaluating the effective chemotherapeutic agents for a superficial bladder cancer. The importance of the experimental animal model for the evaluation of chemotherapeutic agents is discussed.

Animals↗

PubMed1987

Inhibition of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat urinary bladder carcinogenesis by alpha-difluoromethylornithine.

The effect of oral administration of alpha-difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor, on N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN)-induced rat urinary bladder carcinogenesis was investigated. Four-wk-old male Fischer 344 rats, 30-38 per group, were divided into 3 groups; each group was divided into 3 subgroups. In Group A, 6-wk treatment with 0.05% BHBN in drinking water was followed by either 0.5% (A1), 0.2% (A2), or 0% (A3) DFMO in drinking water for 34 wk. In Group B, coadministration in drinking water of 0.01% BHBN and either 0.5% (B1), 0.2% (B2), or 0% (B3) DFMO was continued for 30 wk. Group C consisted of animals receiving 0.5%, 0.2%, or 0% DFMO in drinking water for 34 wk without prior or cocarcinogen treatment. Bladder tumorigenesis was clearly inhibited by DFMO; tumor incidence was 14 of 37 (38%) in A1, 16 of 38 (42%) in A2, and 31 of 35 (89%) in A3, and 7 of 35 (20%) in B1, 14 of 35 (40%) in B2, and 28 of 35 (80%) in B3 (P less than 0.01, DFMO groups as compared to the respective control A3 or B3). The average tumor volume was strikingly reduced in Group A rats given DFMO (3.0 mm3 in A1, 5.0 in A2, and 38.6 in A3). Significant suppression of tumor multiplicity (number of tumors/tumor-bearing bladder) was observed in DFMO-treated subgroups in Group B (1.1 in B1, 1.3 in B2, and 1.8 in B3). In both Groups A and B, however, DFMO failed to suppress hyperplastic changes (simple hyperplasia) or preneoplastic lesions (nodulopapillary hyperplasia). Systematic examination of all pertinent organs excluding the brain showed no adverse effects attributable to DFMO treatment except for decrease in body weight (less than 7%), which was consistently observed in the groups receiving 0.5% DFMO, and reduction in the combined weight of the prostate and seminal vesicles (less than 20%), which was noted in Group B in which exposure to DFMO was started at a younger age. These results indicate that oral administration of DFMO is quite effective in suppressing (or retarding) BHBN-induced carcinogenesis with minimal untoward effects and confirm the similar inhibitory effects demonstrated earlier with the heterotopically transplanted rat urinary bladder system.

Administration, Oral↗

PubMed1987

Induction of high-grade, high-stage carcinomas in the rat urinary bladder.

The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

Animals↗

PubMed1987

Effects of single chemotherapeutic agents on development of urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats.

Chemotherapeutic agents were evaluated for effect on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in male Wistar strain rats. Seven hundred and two rats were given 0.05% BBN in drinking water for 8 weeks. After BBN treatment, the animals were divided into 26 groups to follow regimens of single chemotherapy. All drugs were administered intraperitoneally except in one group that was treated orally. In our experimental series, 5-fluorouracil (5-FU), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), carbazilquinone (CQ), vincristine (VCR) and cis-diamminedichloroplatinum (CDDP) were effective in inhibiting the incidence of bladder tumor, however, adriamycin (ADM), mitomycin C (MMC), neocarsinostatin (NCS), cyclophosphamide (CPM) and bleomycin (BLM) were not effective.

Administration, Oral↗

PubMed1987

Rat urinary bladder denuded of urothelium. An in vivo model for the epithelial-stromal interactions in carcinogenesis.

To investigate epithelial-stromal interactions in bladder carcinogenesis, the authors developed an experimental model using a heterotopically transplanted rat urinary bladder (HTB). A rat urinary bladder which was completely denuded of epithelial cells ex vivo with hypotonic shock and a nonionic detergent was transplanted into a syngeneic recipient. No reepithelialization occurred during the 8-week posttransplant period. The basal lamina remained intact throughout this period and showed linear immunofluorescence with antibodies against laminin, Type IV collagen, and heparan sulfate-proteoglycan. When 1 X 10(5) to 5 X 10(5) dispersed normal urothelial cells were delivered into the HTB through an attached reservoir 4 days after transplantation, complete resurfacing by inoculated cells occurred within a few days. A transient hyperplasia was followed by a normal 2-3-cell-thick urothelial organization in 4 weeks. Cultured bladder carcinoma cells also resurfaced the denuded bladder basal lamina; the progressive growth of this neoplastic epithelium resulted in carcinoma in situ as well as foci of invasive carcinoma within 4 weeks following inoculation. This in vivo system has an advantage over other in vivo and in vitro models in that complete removal of epithelial cells can be achieved easily and completely; the course after reepithelialization can be modified by subsequent treatment, progression of neoplastic development can be closely observed by a change in the color of the aspirate, its cytology, and biochemical analysis of secretions; and an adequate amount of tissue can be available for subsequent examinations. The model is potentially useful not only for studying epithelial-stromal interactions during carcinogenesis, but also for examining the mechanisms of tumor invasion and metastasis.

Animals↗

PubMed1985

[Percutaneous nephrostomy].

Sixty three cases (male 32, female 31) of supravesical obstruction were treated with ultrasonically guided subcutaneous nephrostomy at our hospitals from October 1980 to October 1984. Their age ranges from 2 months to 84 years old, and median age was 52 years old. The major causes of ureteral obstruction were extended pelvic malignancies, 45 cases (71%) (gynecological 18, urological 16, gastrocolorectal 7 and others 4), and benign disease 18 cases (29%). Objectives of nephrostomy were classified in 4 categories (drainage, manipulation, irrigation and evaluation), and results of nephrostomy were discussed for each category. No major complications were observed. Only prolonged macrohematuria (over 48 hours) and fever (over 38 degrees C) were observed in 5 cases respectively. Success rate of nephrostomy placement was 97.5% of all cases. With ultrasonography and angiographic technique, percutaneous nephrostomy is an easy, safe and reliable method.

Adolescent↗

PubMed1985

[Effect of UFT on urinary bladder tumors in rats induced by N-butyl-N-(4-hydroxybutyl)nitrosamine].

The effect of combined tegafur and uracil (UFT) on the development of rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was studied. Two hundred F344 male rats were divided into 10 groups. Groups 1 to 5 were given 0.05% BBN in drinking water for the initial 8 weeks of the experiment, and Groups 6 to 10 were the controls of the prior 5 groups treated with BBN. UFT in commercial diet was administered at daily doses of 100mg (30.9 mg as FT-207) per kg of body weight in Groups 2 and 4 and 200 mg (61.7 mg as FT-207) per kg of body weight in Groups 3 and 5. Groups 2 and 3 received UFT throughout the period of the experiment, and Groups 4 and 5 for 12 weeks after 8 week treatment with BBN. All animals were sacrificed at 20 weeks, and studied histopathologically. In Groups 1 to 5, urinary bladder tumors developed in 20 of 20, 13 of 20, 6 of 20, 14 of 20 and 6 of 20, respectively. Incidences of tumors in the 4 groups treated with UFT were significantly lower than that in Group 1 treated with BBN alone. This result shows that UFT inhibits the development of urinary bladder tumors in rats induced by BBN.

Animals↗

PubMed1985

[Corticosteroid as an anti-emetic agent in cancer chemotherapy with cis-diammine-dichloroplatinum (II)].

The anti-emetic effect of corticosteroid during cancer chemotherapy with cis-diamminedichloroplatinum (II) (CDDP) is analyzed retrospectively. From November 1981 to April 1984, 23 of 50 patients receiving CDDP were given corticosteroid as an anti-emetic. Corticosteroids, methylprednisolone (80-500 mg/day) or hydrocortisone (200-480 mg/day), were administered intravenously for 1 to 3 doses. Including 4 patients who had no symptoms, 60% of patients were free from nausea and vomiting. The incidence of gastrointestinal symptoms was significantly lower than that in patients who were not given corticosteroid. Corticosteroid reduced gastrointestinal symptoms in 2 of 3 patients who had prior CDDP treatment. There were no remarkable adverse reactions except acne in 2 patients. A further controlled study is needed to determine the appropriate dose and modality of administration of corticosteroid.

Adult↗

PubMed1984

Rapid induction of carcinoma in situ in dog urinary bladder by sequential treatment with N-methyl-N'-nitrosourea and N-butyl-N-(4-hydroxybutyl)-nitrosamine.

A highly atypical intraepithelial proliferation, which was interpreted as carcinoma in situ, developed in the urinary bladder of 2 beagle dogs after repeated intravesical instillations of N-methyl-N'-nitrosourea followed by oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine. The latent period was 37 weeks. The technique may provide a useful model to study the natural history of bladder cancer, particularly carcinoma in situ.

Animals↗

PubMed1983

[Fundamental studies on intravesical instillation of carboquone for treatment of urinary bladder tumors--on the effects of intravesical instillation of carboquone in normal beagle dogs].

The effects of intravesical instillation of Carboquone at the clinically used doses of 5 and 10 mg on the normal mucosa of female beagle dogs was compared with that of 10 mg Mitomycin C used as the control drug. Intravesical instillation for 48 hours of 10 mg carboquone/20 ml phosphate buffer solution (PBS) after bilateral cutaneous uretrostomies produced severe inflammatory changes in all layers of the bladder wall. However, no secondary effects were observed in blood laboratory examinations or histological examinations of the whole organ after autopsy. Phosphate buffer solution produced no remarkable secondary effects in animals. Five milligrams carboquone per 20 ml PBS was instilled intravesically once a week for 3 weeks in normal animals. Cystoscopically , the bladder mucosa recovered normally. Blood laboratory examinations showed no abnormal results, but the bladder epithelium had regenerative epithelial hyperplasia and slightly inflammatory changes in the submucosal layers. Two of the three control animals given instillation of 10 mg of Mitomycin C/20 ml PBS had slight leucopenia at 7 days after the last intravesical instillation, but leucocyte count was normal at the end of the experiment. Cystoscopic and histological examination of the epithelium of the urinary bladder revealed severe inflammatory changes in 2 of the 3 animals.

Administration, Topical↗

PubMed1982

[Effect of carboquone (esquinone) on the development of urinary bladder tumors in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine].

The effect of carboquone (CQ) by intraperitoneal administration on the development of urinary bladder tumors in Wistar strain male rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was studied. Urinary bladder tumors were induced in 9 of 11 rats (81.8%) when they were given 0.05% BBN in drinking water for 8 weeks and then given water without BBN for 12 weeks. When CQ 0.25 mg/kg/day was administered intraperitoneally for 7 days after treatment with 0.05% BBN for 8 weeks, incidence of urinary bladder tumors was 19 of 26 rats (73.1%). When CQ 0.25 mg/kg/weekly was given for 12 weeks after treatment with BBN, incidence of urinary bladder tumors was 17 of 27 rats (63.0%). When CQ 0.5mg/kg. B.W./day was given for 7 days after treatment with BBN, tumors developed in the urinary bladder with low incidence as in 8 of 20 rats (40.0%) (P 0.1). When CQ 0.5mg/kg/weekly was given for 12 weeks after treatment of BBN, urinary bladder tumors were induced in 17 of 22 rats (77.3%). Hematotoxity was not observed in any animals treated with CQ. These results showed that CQ inhibited the development of urinary bladder tumors induced by BBN in rats.

Animals↗

PubMedDate not supplied

Immunohistochemical evaluation of estrogen receptor status in benign prostatic hypertrophy and in prostate carcinoma and the relationship to efficacy of endocrine therapy.

The levels of estrogen receptors in human benign prostatic hypertrophy and in various pathological classifications of prostate carcinoma were assessed using immunohistochemical methods. All cases of benign hypertrophy showed elevated levels of estrogen receptor, while receptor-positive cells were detected in only 48% of carcinomas, indicating a negative correlation between receptor status and malignancy. Furthermore, the prognosis for effective endocrine therapy was poor in cases where tissues demonstrated low or negative receptor levels. In addition, the estrogen receptor status was compared to cell kinetic index such as proliferating cell nuclear antigen and argyrophilic staining of the nuclear organizer region.

Aged↗