Biomedical subjects

S Fukushima

Publications and source records attributed to S Fukushima.

At least 325 records · Page 18Linked to original sources

PubMed1990

Various urinary properties in bladder tumor patients.

Urinary electrolytes, pH, urea nitrogen, creatinine, uric acid and osmolarity were measured in patients with bladder tumors and compared with those of a control group. There were 41 bladder tumor patients ranging in age from 29 to 87 (average 64) years with a male:female ratio of 32:9. According to histopathological classification of the bladder tumors, there were 34 transitional cell carcinomas (TCC) (21 G1, 10 G2, 3 G3), four squamous cell carcinomas, two adenocarcinomas and one inverted papilloma. The control group comprised 29 patients ranging in age from 35 to 80 (average 63) years with a male:female ratio of 26:3. Four urine samples were collected from each patient: early morning on the day of admission, just after admission, early morning on the day of return to hospital after temporary discharge, immediately after return to hospital after temporary discharge. The results indicated that the urinary Ca2+ and uric acid values were significantly lower in the bladder tumor group than in the control group. The urinary pH tended to be somewhat higher than in the control group, and the pH values tended to be especially high in the TCC G3 patients. There were differences in the various urinary properties between the TCC G1 and G2 and the TCC G3 patients.

Adult↗

PubMed1990

Stomach carcinogenicity of caffeic acid, sesamol and catechol in rats and mice.

The carcinogenic potential of caffeic acid, sesamol and catechol was examined in male and female F344 rats and B6C3F1 mice, groups of 30 animals being treated with diets containing 2% caffeic acid, 2% sesamol or 0.8% catechol for 104 weeks (rats) or 96 weeks (mice). Histological examination revealed that caffeic acid induced forestomach squamous cell carcinoma in 57% (P less than 0.001 vs. controls) and 50% (P less than 0.001) of male and female rats, respectively, whereas sesamol was associated with squamous cell carcinoma at incidences of 31% (P less than 0.001) in male rats, and 38% (P less than 0.001) and 17% (P less than 0.05) in male and female mice, respectively. Catechol induced glandular stomach adenocarcinomas in 54% (P less than 0.001) and 43% (P less than 0.001) of male and female rats, respectively. The results thus clearly demonstrated that all three antioxidants are carcinogenic in rodent stomach epithelia.

Animals↗

PubMed1990

Selective induction of prostate carcinomas in F344 rats treated with intraperitoneal injections of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl.

Groups of F344 and Wistar rats were given an intraperitoneal injection of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMAB) at a dose of 5 mg/kg body weight with a 1-week dietary pretreatment with ethinyl estradiol (EE), and this regimen was repeated 10 times at one-week intervals. Additional groups were given N-OH-DMAB 10 times without the dietary EE pretreatment. The total experimental period was 60 weeks. Carcinomas and atypical hyperplasias of the prostate developed in 8 (42%) and 16 (84%) of 19 F344 rats without the dietary EE treatment and in 1 (6%) and 7 (39%) of 18 rats with the EE diet, respectively. No prostatic tumors were found in Wistar rats, although atypical hyperplasias were observed in 6 of 18 rats with and 4 of 8 rats without the EE supplementation. Tumor yields in other organs were extremely low, resulting in good survival of the animals. A comparison of the results with those obtained for DMAB suggests that intraperitoneal administration of N-OH-DMAB in F344 provides a better induction method for models of prostate carcinogenesis.

Aminobiphenyl Compounds↗

PubMed1990

Structure-activity relations in promotion of rat urinary bladder carcinogenesis by phenolic antioxidants.

The urinary bladder tumor-promoting potentials of the phenolic antioxidants, 2-tert-butyl-4-methylphenol (TBMP), propylparaben, catechol, resorcinol and hydroquinone, which are structurally related to butylated hydroxyanisole (BHA), were investigated in 170 male F344 rats. The animals were initially given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator in their drinking water for 4 weeks. Three days later, groups of 20 rats received diet containing 1.0% TBMP, 3% propylparaben, 0.8% catechol, 0.8% resorcinol, 0.8% hydroquinone or basal diet alone until the end of week 36. Significant increases in the incidences and average numbers of the putative preneoplastic lesions, papillary or nodular (PN) hyperplasia, and papillomas of the urinary bladder were only observed in the group given TBMP after BBN. Development of these lesions was not enhanced by diet containing the other test compounds and no induction was associated with any of the test chemicals alone. The results thus clearly showed that TBMP, which most closely resembles BHA, promoted urinary bladder carcinogenesis. The similar effects of TBMP and BHA on urinary bladder carcinogenesis suggest a direct link between chemical structure and biological potency.

Animals↗

PubMed1990

Cellular differentiation and histogenesis of rat glandular stomach cancers.

The gastric and intestinal phenotypic expressions of tumor cells in 18 adenomatous hyperplasias, 33 well-differentiated adenocarcinomas, and 16 undifferentiated adenocarcinomas (4 poorly differentiated adenocarcinomas, 10 signet-ring cell carcinomas and 2 mucinous adenocarcinomas) induced by N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide in the rat glandular stomach were studied by histochemical stainings for mucin and immunohistochemical staining for pepsinogen isozyme 1 (Pg 1). By histochemical staining for mucin [by the paradoxical concanavalin A method, the modified method with labeled peanut lectin, the galactose oxidase-Schiff (GOS) reaction, and the sialidase-GOS reaction] and immunohistochemical staining of Pg 1, gastric cancer cells of each histological group could be clearly classified into a gastric type, including mucous neck cell pyloric gland cell, and surface mucous cell subtypes, and an intestinal type, including goblet-cell, and intestinal absorptive cell subtypes. All tumors examined in this work consisted mainly of gastric-type cells but intestinal-type tumor cells were occasionally found among the gastric-type tumor cells. The incidences of intestinal-type cells in adenomatous hyperplasias (11.1%) and small well-differentiated adenocarcinomas (28.6%) were significantly less (P less than 0.05) than that in large well-differentiated adenocarcinomas (68.4%). The incidence of intestinal-type cells in small undifferentiated adenocarcinomas (25.0%) was also less than that in large ones (58.3%). The present results suggest the occurrence of change of phenotypic expression of tumor cells from the gastric type to the intestinal type during growth of tumors.

Adenocarcinoma↗

PubMed1990

Effects of sodium nitrite and catechol or 3-methoxycatechol in combination on rat stomach epithelium.

The effects of sodium nitrite (NaNO2) and catechol or 3-methoxycatechol in combination were examined in male F344 rats. Animals were treated with 0.3% NaNO2 in the drinking water and 0.8% catechol or 2% 3-methoxycatechol in powdered diet for 24 weeks. While catechol or 3-methoxycatechol alone induced low incidences of mild or moderate hyperplasia, simultaneous administration of NaNO2 markedly enhanced the degree of hyperplasia and papilloma formation. In contrast, induction of submucosal hyperplasia and adenomas in the glandular epithelium was reduced. Thus, the results indicate that NaNO2 can modulate the metabolism of antioxidants, so that, possibly via production of new active moieties, targeting of forestomach epithelium is enhanced.

Adenoma↗

PubMed1990

Promoting effect of the peroxisome proliferator, clofibrate, but not di(2-ethylhexyl)phthalate, on urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The modifying potential of clofibrate and di(2-ethylhexyl)phthalate (DEHP) on second stage, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary bladder carcinogenesis was investigated in male F344 rats, using a uracil-accelerated transitional cell proliferation model. Six-week-old animals received 0.05% BBN in their drinking water for 4 weeks and then clofibrate (1.0, 0.5, and 0.25%) and DEHP (1.2, 0.6, and 0.3%) were given during experimental weeks 5-8 and weeks 12-20. Uracil was administered during weeks 9-11 at a dietary level of 3.0%. Control rats were treated with BBN and uracil without peroxisome proliferator. Surviving animals were killed at the end of week 20 of the experiment, when the densities of putative preneoplastic, papillary or nodular (PN) hyperplasias (numbers per 10 cm of basement membrane) were significantly increased in all clofibrate-treated, but not the DEHP groups. The incidences of PN hyperplasia were similar in both treated animals and controls. In a second experiment, rats fed diets containing 1.0% clofibrate or 1.2% DEHP were assessed for levels of DNA synthesis in urinary bladder epithelium by 5-bromo-2-deoxyuridine immunohistochemistry. Numbers of labeled nuclei remained within normal levels, and no proliferative changes were evident. Thus, the present experiments indicated that while clofibrate, but not DEHP, exerts weak enhancing effects on BBN-initiated urinary bladder carcinogenesis in rats this is not associated with increased levels of DNA synthesis in the affected epithelium.

Animals↗

PubMed1990

Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas.

Expression of the product of the c-erbB-2 gene, a proto-oncogene related to, but distinct from c-erbB-1 encoding the epidermal growth factor receptor (EGF-R), was investigated in human urinary bladder carcinomas. In addition, levels of EGF-R and transferrin receptor were also analyzed using an immunohistochemical approach, and the results compared with histological pattern and grading, and tumor staging. Increased expression of c-erb B-2 product was found in 32% of cases (7/22), a positive reaction being observed in 60% of transitional cell carcinoma (TCC) Grade 3 lesions (3/5), 20% of Grade 2 TCCs (2/10) and 100% of adenocarcinomas (AC) (2/2), but in none of the cases of squamous cell carcinoma (SCC). Although no statistical correlation with staging was evident, TCCs or SCCs of high grade and stage often showed EGF-R-positive staining, whereas other well differentiated lesions and normal bladder epithelium were generally negative. Most cases of urinary bladder carcinoma were positive for the transferrin receptor, which was not detected in normal bladder. The results thus suggested that a positive reaction for c-erbB-2 product is correlated with TCC histological grading or AC morphology. A high intensity of EGF-R staining in human bladder carcinomas may be associated with poor differentiation and invasion, whereas transferrin receptor expression might reflect tumor growth.

Adenocarcinoma↗

PubMed1990

Anticancer activity of free gamma-linolenic acid on AH-109A rat hepatoma cells and the effect of serum albumin on anticancer activity of gamma-linolenic acid in vitro.

The cytotoxicity of gamma-linolenic acid (C18:3n-6) against rat hepatoma AH-109A cells and the effect of bovine serum albumin (BSA) on its toxicity were examined in culture. The proliferation of AH-109A cells, evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, was significantly suppressed by gamma-linolenic acid above 5 micrograms/ml concentration in serum-free culture medium. However, its toxicity was reduced by supplement of BSA. Similar observation of reduced toxicity by BSA was shown by the method of trypan blue dye exclusion and a colony formation assay. The cytotoxicity of gamma-linolenic acid was correlated closely with the concentration of unbound (free) gamma-linolenic acid. Production of thiobarbituric acid reactive material, one of the indicators of lipid peroxidation, was stimulated by gamma-linolenic acid and inhibited by BSA. These results suggested that the presence of albumin suppressed the cytotoxicity of the free fatty acid.

Animals↗

PubMed1990

Release characteristics of a free polyunsaturated fatty acid from an oily lymphographic agent.

The release profiles of a free polyunsaturated fatty acid, alpha-linolenic acid, from solutions in an oily lymphographic agent Lipiodol-Ultra-Fluid (Lipiodol), to rabbit and human plasma, phosphate buffer solution (PBS), and PBS containing bovine serum albumin (BSA) were examined in vitro. The times required for 50% release of alpha-linolenic acid from Lipiodol were about 1 and 1.5 h in the rabbit and human plasma, respectively. Although only a slight amount of alpha-linolenic acid was released from Lipiodol to PBS after 24 h incubation at 37 degrees C, release was markedly enhanced by the addition of BSA to PBS. The amount of alpha-linolenic acid released from Lipiodol into PBS containing 5% BSA increased as the alpha-linolenic acid content in Lipiodol was increased. In all experiments, the release had stopped before all alpha-linolenic acid had been released. The prolongation of alpha-linolenic acid release from Lipiodol is considered a requisite for a selective anticancer effect of Lipiodol containing a free fatty acid on liver cancer.

Animals↗

PubMed1989

[Eel calcitonin treatment on patients with urogenital carcinoma for relief of pain from metastatic bone lesions].

Forty-seven patients of advanced urogenital carcinoma with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were 45 males and 2 females with a mean age of 72.9. CT was administered intravenously at a daily dose of 160 units for 10 days. The efficacy of CT on relief of pain was estimated using a mark sheets filled by each patient and his or her doctor. And also the amount of analgesics given to patients before and after the administration of CT were checked. CT was effective on 77% of patients to reduce severe bone pain, especially on osteoblastic lesions metastasized from prostatic carcinoma. CT administration decreased the amount of analgesics in 37% of the cases. As toxicity, nausea and vomiting which stopped the CT administration were observed in only one From these results, we conclude that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with urogenital carcinoma.

Aged↗

PubMed1989

Intraarterial infusion of 5-fluoro-2-deoxyuridine-C8 dissolved in a lymphographic agent in malignant liver tumors. A preliminary report.

The drug 5-fluoro-2-deoxyuridine-C8 (FUdR-C8), one of the lipophilic prodrugs of FUdR, was dissolved in an oily lymphographic agent (Lipiodol Ultra Fluid, Andre Gelbe Laboratory, Paris, France; Ethiodol, Savage Laboratories, Melville, NY) and used for the intraarterial treatment of malignant liver tumors. From August 1985 to June 1988, 33 patients with hepatocellular carcinoma and 13 patients with metastatic liver tumors were treated with this agent at the Kumamoto University Hospital and its affiliated hospitals. The response rate (complete remission [CR] and partial remission [PR]) was 27.6% for hepatocellular carcinomas and 46.1% for metastatic liver tumors. The cumulative 1-year survival rate was 55.1% for hepatocellular carcinomas and 70.0% for metastatic liver tumors. More than a 50% decrease in the tumor marker level was observed in ten of 21 patients with hepatocellular carcinoma and in two of eight patients with metastatic liver tumors. The side effects, which were transient and controlled with conservative treatment, included fever, abdominal pain, nausea, vomiting, and acute gastritis.

Adult↗

PubMed1989

Proliferative response of renal pelvic epithelium in rats to oral administration of ortho-phenylphenol, sodium ortho-phenylphenate and diphenyl.

Changes in DNA synthesis levels and morphology as observed by scanning electron microscopy (SEM) and light microscopy in rat renal papilla and pelvis following oral administration of ortho-phenylphenol (OPP), sodium ortho-phenylphenate (OPP-Na) and diphenyl, were investigated in F344 rats. OPP and OPP-Na treatment for 4 weeks was associated with elevated DNA synthesis in both renal papilla and pelvis, in addition to distinct morphological cell surface alterations. Sequential light microscope observation revealed induction of renal papillary necrosis from week 4, followed by regeneration hyperplasia at weeks 16 and 24, but no changes in the renal pelvis in the OPP case. OPP-Na not only similarly affected the renal papilla, but also brought about development of hyperplasia in the renal pelvis. No proliferative response of the kidney was apparent in rats fed diphenyl. The present study indicated that the proliferative responses in the renal pelvic epithelium following OPP-Na are similar to those induced by this chemical in the urinary bladder, and that in both cases they are indicative of promoting or carcinogenic potential.

Administration, Oral↗

PubMed1989

Modification by catechol and resorcinol of upper digestive tract carcinogenesis in rats treated with methyl-N-amylnitrosamine.

Modifying effects of the environmental contaminant catechol, and its isomers resorcinol and hydroquinone, on methyl-N-amylnitrosamine (MNAN)-induced carcinogenesis were studied in male F344 rats. Groups of 15 rats were given three i.p. injections of 25 mg/kg of body weight of MNAN within the initial 2-wk period, and commencing 1 wk thereafter they were administered 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone in powdered basal diet or were given basal diet alone for 49 wk. Additional groups of 10 to 15 rats were similarly treated without prior carcinogen exposure. Histological examination after sacrifice at wk 52 revealed that the incidences of tongue papillomas and esophageal squamous cell carcinomas in the groups given MNAN followed by catechol (57.1% and 64.3%) or resorcinol (50% and 58.8%) were significantly higher than those in the carcinogen only controls (9.1, and 0%, respectively). Hydroquinone also enhanced the development of esophageal squamous cell carcinomas but was less active than catechol or resorcinol. The incidence of alveolar hyperplasia in the lungs of the group given MNAN followed by catechol (0%) was, in contrast, significantly reduced as compared to the control value (54.5%). Hydroquinone and resorcinol showed a similar but non-significant tendency. These results indicated that the environmental contaminant, catechol and its isomers, may play a role in the development of human upper gastrointestinal cancer, in addition to exerting modifying effects in other organs.

Animals↗

PubMed1989

Hepatic arterial injection chemotherapy with cisplatin suspended in an oily lymphographic agent for hepatocellular carcinoma.

A method to prepare cisplatin suspended in an oily lymphographic agent, Lipiodol (LPS), has been established to deliver cisplatin to hepatocellular carcinoma (HCC) by the hepatic artery. Seventy-one patients, one Stage I, 16 Stage II, 16 Stage III, and 38 Stage IV, were treated with LPS therapy. A partial response was obtained in 33 cases (46.5%), a minor response in 20 cases (28.2%), and no change in 18 cases (25.3%). In 34 patients whose serum alpha-fetoprotein (AFP) levels were greater than 400 ng/ml, the serum AFP levels decreased in 31 patients (91.2%). The AFP decreased by more than 50% in 25 cases (73.5%) and more than 75% in 19 cases (55.9%). The plasma des-gamma-carboxy prothrombin (DCP) levels decreased in all of the 26 DCP-positive patients. The survival rate was 77% at 6 months and the 1-year survival rate was estimated to be 55%. The patients treated with LPS therapy survived longer compared with patients given Lipiodol containing neocarzinostatin by the hepatic artery. Complications such as acute gastroduodenal mucosal lesions (24%), cholecystitis (2.8%), pancreatitis (7%), delayed jaundice (7%), and hepatic encephalopathy (4.2%) were observed after therapy. The peak plasma platinum (Pt) concentrations determined as ultrafilterable Pt occurred 5 to 20 minutes, and 5 to 60 minutes as total Pt after the end of LPS injection. The Pt concentrations in the tumor tissues were 42 times higher in four operated cases and 7.1 times higher in six autopsy cases than those in the nontumorous tissue. These results suggest that LPS selectively accumulates in the HCC, is long-lasting and gradually releases the drug. In addition it is effective as a new anti-cancer therapy for hepatocellular carcinoma.

Adult↗

PubMed1989

Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine-induced F344 rat forestomach and glandular stomach carcinogenesis.

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol, 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrifice at Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P less than 0.001) or MNNG followed by PMC (100%, P less than 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P less than 0.05) or PMC (100%, P less than 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P less than 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity.

Adenocarcinoma↗

PubMed1989

Changes in urine composition, bladder epithelial morphology, and DNA synthesis in male F344 rats in response to ingestion of bladder tumor promoters.

An investigation of changes in urine composition, morphology of bladder epithelium, and levels of DNA synthesis following 4 or 8 weeks oral administration of bladder tumor promoters or analogs without promotion potential was performed. The sodium salts of L-ascorbate, o-phenylphenate, and bicarbonate increased the pH value, sodium content, volume, and MgNH4PO4 crystalluria of the urine, while the parent compounds, L-ascorbic acid and o-phenylphenol, which in contrast are not tumor promoters, did not induce these changes. Sodium chloride ingestion caused natriuresis without increasing urinary pH. Diphenyl administration produced only microcalculi consisting of p-phenylphenol. Treatment with the antioxidants butylated hydroxytoluene, butylated hydroxyanisole, and ethoxyquin was also not associated with any changes in urinary pH or Na ions. However, tert-butylhydroquinone did cause an increase in pH. Administration of the strong bladder carcinogens N-butyl-N-(4-hydroxybutyl)nitrosamine and N-ethyl-N-(4-hydroxybutyl)nitrosamine did not result in alteration of urine composition, with the exception of a decrease in phosphorus concentration. However, all the bladder promoters and carcinogens, without exception, brought about an elevation of DNA synthesis in the urothelium and produced morphologic surface alterations such as formation of pleomorphic or short, uniform microvilli and ropy or leafy microridges. Thus, an ability to induce proliferation and cell surface alteration was characteristic of the complete range of bladder promoters investigated. The results suggest that considerable variation in the mechanisms underlying these changes may be involved for different individuals or groups of agents.

Animals↗

PubMed1989

Cell proliferation induced by uracil-calculi and subsequent development of reversible papillomatosis in the rat urinary bladder.

The sequence of cellular alterations in urinary bladder epithelium associated with uracil-induced reversible urolithiasis was investigated in male F344 rats. Initial changes were submucosal edema with occasional mucosal erosion or ulceration which appeared on Day 2 of uracil administration. Simple hyperplasia of bladder epithelium was already evident at this time and calculus formation was noted as early as Day 4. Labeling indices in the bladder epithelium assessed by bromodeoxyuridine incorporation were about 32% on Day 4 and then gradually decreased to 6% at Week 8 and 4% at Week 25 of chronic treatment. Histologically, a direct progression from simple hyperplasias, through papillary hyperplasias to papillomatosis, accomplished by Week 5, was evident. Dysplastic lesions were also apparent by Week 25. Topographically, papillomatosis was composed of marked interconnecting mucosal ridges of relatively uniform width. No polyp-like protrusions were present and the vascular pattern revealed by resin perfusion casting demonstrated that these mucosal lesions were supported by a uniform plexus of capillary vessels. After withdrawal of uracil from the diet the labeling index dropped dramatically to 0.002% after 1 week and urolithiasis and papillomatosis had disappeared by Weeks 2 and 3, respectively. The findings suggest that papillomatosis associated with uracil-calculi is a hyperplastic rather than a neoplastic response and that induction of putative neoplastic lesions is directly related to prolonged vigorous cell proliferation.

Animals↗