Biomedical subjects

M Fukumoto

Publications and source records attributed to M Fukumoto.

At least 199 records · Page 11Linked to original sources

PubMed1991

Combining independently effective anticancer agents may not augment the independent antitumor effects: a study using human digestive organ cancer xenograft lines in nude mice.

Five human digestive organ cancer xenograft lines were subcutaneously transplanted in nude mice, and 7 anticancer agents (ACAs) were intravenously administered singly or in combinations at 4 times the standard clinical doses. Cisplatin (P) was effective in 4 lines and 5-fluorouracil (F) was effective in 3 lines. A total of 8 combinations with 2 effective ACAs were assessed in 4 lines and only 1 combination (FP) resulted in an augmented antitumor effect in a single line. A total of 11 combinations with 1 effective ACA plus 1 ineffective ACA were assessed in 2 lines, and only 1 combination (F + carboquone [CQ; Esquinon]) resulted in an augmented effect in a single line. A total of 5 combinations with independently ineffective ACAs were assessed in 1 line, and 1 combination (FP) resulted in augmented antitumor activity. No 2-ACA combinations showed enhanced side effects. Two combinations with 3 effective ACAs were assessed in 2 lines and 1 combination (FP + mitomycin C) resulted in an augmented effect with a greater mortality rate. A total of 12 combinations with both effective plus ineffective ACAs were assessed in 2 lines, and 3 combinations (FP + Adriamycin or FP + CQ or FP + etoposide) resulted in an augmented effect in 1 line with enhanced side effects. These results indicate that the combination of independently effective ACAs does not always cause an augmented antitumor effect, and may sometimes result in augmented side effects. According to this study, the 3-ACA combinations with FP + 1 effective agent appear to be the best regimens for digestive organ cancer.

Animals↗

PubMed1991

In vivo effects of human recombinant tumor necrosis factor alone and in combination with other biological response modifiers on human digestive organ cancer xenografts transplanted in nude mice.

The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers. Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 10(3), 5 x 10(3), or 10(4)U/head directly into the tumor 3 times a week for 2 weeks. EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 10(3) U/head caused tumor regression. PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 x 10(3) U/head, however, the tumors regrew after treatment. Li-7 and BDC-SN were resistant to rTNF. The effects of rTNF in combination with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 x 10(3) U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-gamma or rTNF and OK-432. However in all cases, the combination of rTNF at 10(3) U/head and any other BRM did not improve the effect. Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone. TNF may still be a useful cytokine, because it can induce the regression of tumors. However, for its clinical application, a method should be developed to reduce its side effects.

Animals↗

PubMed1991

Estimation of interleukin 6 production by reverse transcriptase-polymerase chain reaction in four human myeloma cell lines.

Although an autocrine growth mechanism through interleukin 6 has been advocated in human myeloma cells, reports of IL-6 production by cells from established myeloma cell lines are rare. In the present study, we examined whether or not a minute amount of interleukin 6 is produced in 4 human myeloma cell lines. IL-6 production was not detected in any of the 4 lines by enzyme immunoassay, bioassay with two interleukin 6-dependent murine hybridoma cell lines and Northern hybridization. However, we detected interleukin 6 mRNA in one (U266) of the 4 lines by the reverse transcriptase-polymerase chain reaction. Nevertheless, the proliferation of all 4 lines was not inhibited by an anti-interleukin 6 antibody. These results suggest that autocrine stimulation by interleukin 6 is not involved in the majority of human myeloma cell lines.

Base Sequence↗

PubMed1991

Relationships between serum thyroid stimulating hormone levels and development of thyroid tumors in rats treated with N-bis-(2-hydroxypropyl)nitrosamine.

Relationships between serum thyroid stimulating hormone (TSH) levels, carcinogen dose and development of thyroid tumors were studied in Wistar rats of both sexes treated with N-bis-(2-hydroxypropyl)nitrosamine (DHPN). DHPN (210 mg/100 g body wt) was injected i.p. weekly. Wistar rats were used, divided into five groups of males (M1-M5) and five groups of females (F1-F5). M1 and F1 received one injection of DHPN, M2 and F2 two injections of DHPN, M3 and F3 three injections of DHPN, M4 and F4 four injections, and M5 and F5 as control rats received saline vehicle. The resultant incidences of total thyroid tumors were 4% in group M1, 24% in M2, 80% in M3, 76% in M4, 0% in F1, 4% in F2, 20% in F3, 17% in F4 and 0% in M5 and F5. Thus dose dependence for DHPN carcinogenesis was found in both sexes for up to at least three injections of DHPN and in all cases males proved more susceptible than females. Similar results were gained for carcinomas treated separately. A sex difference in DHPN induction of thyroid tumor was thus shown for Wistar rats opposite to that reported to exist in humans. However, no clear relationship between dose of DHPN or incidence of thyroid tumors and serum TSH concentration was evident at the end of the experiment (week 30).

Adenoma↗

PubMed1991

Comparative study on various combination chemotherapies against human gastric cancer xenograft lines of well- and poorly-differentiated adenocarcinomas transplanted in nude mice.

Two human gastric cancer xenograft lines (GC-YN and GC-SF) transplanted in nude mice were employed to evaluate and compare the anticancer effect of seven single anticancer agents and their various combinations. Mitomycin C, cisplatin (Briplatin) (CDDP) and 5-fluorouracil (5-FU) were screened out to be effective against GC-YN and only epirubicin (Farmorubicin) (EPIR) was effective against GC-SF. Combinations of two of these 'effective' agents revealed that FP (5-FU + CDDP) is the most effective two-agent combination regimen against both lines, and some of those 'ineffective' single agents showed synergistic effects against both lines when combined with 5-FU. Moreover, three-agent combinations composed of FP and one of the other five agents were also evaluated to select out the most effective regimen. All the combinations showed higher inhibition on the tumor growth of GC-YN than FP regimen, and FP + adriamycin (Adriacin) (ADR) and FP + EPIR were more effective against GC-SF than FP. However, taking toxic effects into consideration, the results suggest that CDDP + 5-FU + EPIR (FPEPIR) may be the regimen most worthy of clinical trial in the chemotherapy against human gastric cancer.

Adenocarcinoma↗

PubMed1991

Co-production of interleukin-1 and interleukin-6 in tumor cell lines elaborating colony-stimulating factors.

Six carcinoma cell lines elaborating colony-stimulating factors (CSFs) were examined by enzyme-linked immunosorbent assay and Northern blotting to determine whether or not they co-produced interleukin-1 alpha (IL-1 alpha), IL-1 beta and IL-6. All 6 cell lines were co-producers; IL-1 alpha was produced in all 6, IL-6 in 5 and IL-1 beta in 3 of them. These results indicate that IL-1 and IL-6 are commonly co-produced in CSF-producing tumors.

Colony-Stimulating Factors↗

PubMed1991

Low uracil concentration in the liver might be responsible for the decreased antineoplastic activity of fluoropyrimidines in mice with CCl4-induced chronic liver dysfunction.

Some fluoropyrimidines are considered to be metabolized in liver microsomes. The present study was designed to assess the effect of chronic liver dysfunction on the antineoplastic activity of fluoropyrimidines. Chronic liver dysfunction was induced in BALB/c mice by 8 weeks of CCl4 injections. The 5-fluorouracil (5-FU)-sensitive MOPC-104E and 5-FU-resistant Meth-A cells were inoculated subcutaneously into the mice and then various fluoropyrimidines were administered intragastrically. The antitumor activity of the fluoropyrimidines decreased in mice with chronic liver dysfunction, although the concentration of 5-FU in the tumor of normal mice did not differ from that of mice with liver dysfunction. However, the concentration of uracil in the liver was decreased in mice with chronic liver dysfunction. On the other hand, the percent conversion of Tegafur [1-(2-tetrahydrofuryl)-5-FU] to 5-FU in the normal liver did not differ from that in the dysfunctional liver. These results suggest that low uracil concentrations in the liver may result from chronic liver dysfunction and lead to decreased antitumor efficacy of fluoropyrimidines.

Animals↗

PubMed1991

Maternal feeding behavior and child acceptance of food during diarrhea, convalescence, and health in the central Sierra of Peru.

Feeding patterns by mothers and child acceptance of food were measured in a Peruvian village to determine changes on days when children had diarrhea as compared to days of convalescence and health. Morbidity surveillance identified 40 children, aged 4-36 months, with diarrhea. Children were followed using twelve-hour in-home structured observations during two to four days each of diarrhea, convalescence, and health. Using scales of maternal encouragement to eat and child acceptance of food and cumulative logistic regression analyses, maternal encouragement to eat decreased significantly during convalescence compared to diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results illustrate the importance of carefully examining the behavioral aspects of nutritional intake. Decreases in intake during diarrhea are due to anorexia and not withdrawal of food by mothers. In response to reductions in child appetite during illness, mothers are more likely to encourage children to eat, while they tend to become more passive feeders after the diarrhea has stopped. Program efforts should focus on messages to feed children more actively especially after diarrhea episodes, when appetite levels increase.

Adult↗

PubMed1991

Pure red cell aplasia associated with non-Hodgkin's lymphoma and hemolytic anemia.

Pure red cell aplasia (PRCA) rarely occurs in non-thymic lymphoproliferative disorders. The present article describes a patient with non-Hodgkin's lymphoma (follicular, mixed type), who concurrently developed PRCA and warm type autoimmune hemolytic anemia during the clinical course. The PRCA and hemolytic anemia were successfully treated with prednisolone (60 mg/day). The patient died two years later, however, from advanced lymphoma without any recurrence of the PRCA or hemolytic anemia. To our knowledge, only 20 cases of PRCA associated with malignant lymphoma have been reported. The pathogeneses of the PRCA and hemolytic anemia in our patient are discussed.

Anemia, Hemolytic, Autoimmune↗

PubMed1991

[Protein-free culture of esophageal cancer cell lines].

We have established 13 esophageal cancer cell lines capable of growing in a protein-free environment. The growth of these cells was not affected by conditioned medium, but the growth of NIH3T3 cells and human fibroblasts was stimulated by conditioned medium. On the other hand, conditioned medium inhibited the growth of human endothelial cells. Amplified int-2 oncogene correlated well with the growth of cells in a protein-free environment but the number of EGF receptors and growth effect of EGF did not relate to such growth. Esophageal cancer cells grow automatically, possibly involving mesenchymal cells via the paracrine system. This results in a poor prognosis in patients.

Cell Division↗

PubMed1991

Tensile strength and collagen content of amniotic membrane do not change after the second trimester or during delivery.

We studied the tensile strength and collagen content of the amniotic membrane in the early and late second trimester and at term in specimens obtained after spontaneous, cesarean, and prostaglandin- and stretch-induced deliveries. No significant difference in either tensile strength or collagen content was found among any group of samples. Collagenous tissue of the amnion seems to differ constitutionally from that of the cervix and vagina and to be modulated by different mechanisms during pregnancy and delivery. It also seems to resist strong physiologic tension until it is mechanically ruptured during delivery.

Amnion↗

PubMed1991

Establishment and characterization of four myeloma cell lines which are responsive to interleukin-6 for their growth.

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.

Adult↗

PubMed1990

Sinus histiocytosis with massive lymphadenopathy in a Japanese male with symptoms of dyspnea and visual disturbance.

A case study of sinus histiocytosis with massive lymphadenopathy is reported. A Japanese male developed lymphadenopathy in the nasal cavity 10 years ago. Biopsy specimens demonstrated massive histiocytosis with phagocytosis of lymphocytes, plasmacytes, and erythrocytes. During the course of his illness, the patient experienced an episode of massive nasal bleeding, and a tracheotomy was performed because of dyspnea. He had also an operation by Killian's approach to relieve a visual disturbance. The patient has been treated with cyclophosphamide and prednisolone for 6 months.

Adult↗

PubMed1990

Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues.

The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was significant. In contrast, transforming growth factor type beta 1 was expressed in all the samples investigated. The mRNA for basic FGF and its peptide were localized in tumor cells in vivo by in situ hybridization and immunohistochemistry, showing that basic FGF is actually produced in tumor cells. Our results suggest that tumor-derived basic FGF is involved in the progression of gliomas and meningiomas in vivo, whereas acidic FGF is expressed in a tumor origin-specific manner, suggesting that acidic FGF works in tandem with basic FGF in glioma tumorigenesis.

Blotting, Northern↗

PubMed1990

Sweet's syndrome associated with immunoblastic lymphadenopathy.

Sweet's syndrome arose in a 54-year-old Japanese man who had suffered from general malaise, episodic fever, and lymphadenopathy for ten months. Skin symptoms subsided rapidly, but he died three months later with a postmortem diagnosis of immunoblastic lymphadenopathy.

Humans↗

PubMed1990

A clinicopathological study of so-called denture fibroma.

We investigated 60 cases of so-called denture fibroma, most of which occurred in women in their 50s to 70s. The most commonly affected areas were the upper alveolar ridge and the bottom of the alveolabial sulcus, and most of the prostheses responsible were complete dentures. Elevated and tumor-like lesions were most frequent. Histopathologically, about 60% of the lesions were of the fibromatous type. Degeneration and inflammation of the salivary glands were identified in one third of cases.

Adult↗

PubMed1990

Increased number of suppressor T-cells and impaired IL-2 mediated T-cell function in peripheral blood of gastric cancer patients.

The present study was designed to investigate the mechanisms responsible for suppressed T-cell immunity in gastric cancer patients. The peripheral blood T-cell functions in gastric cancer patients were evaluated by measuring responses to PHA and IL-2, and T-cell subpopulations were assessed by flow cytometry. Both the PHA and IL-2 responses decreased in patients with gastric cancer, although the proportions of CD3+ and CD25+ cells were the same for gastric cancer patients and healthy volunteers. The PHA response, but not that of IL-2, was lower in patients with liver metastasis or peritoneal dissemination than in patients without these conditions. Single regression analysis showed that with lymph node involvement in the disease the IL-2 response was more strongly suppressed than PHA response. The serum level of IAP did not correlate with the response to either PHA or IL-2. The proportion of CD4+ cells was not affected by any factor related to gastric cancer, although CD4+/CD8+ and CD8+11b-/CD8+11b+ ratios did decrease in patients with distant lymph node involvement. These changes may be due to a comparative increase in suppressor cells. These results suggest that gastric cancer patients exhibit impaired IL-2 mediated T-cell function and that the number of suppressor cells may increase with progressive lymph node involvement. These two serial effects may be indeed responsible for the impaired blood T-cell function in patients with gastric cancer.

Adult↗

PubMed1989

Greater inhibitory effects for testosterone than castration in rat thyroid tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine.

The effects of testosterone and castration on thyroid tumorigenesis subsequent to initiation by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were investigated in male Wistar rats. Following 2 weekly i.p. injections of DHPN at the dose of 210 mg/100 g body weight, testosterone was administered in the diet at concentrations of 0.15% or 0.03% for 28 weeks. Castration was performed on a separate group of animals 1 week after the final injection of DHPN. The incidence of thyroid adenomas and carcinomas were 69% (9/13) and 15% (2/13), respectively, in rats treated with DHPN alone, 0% (0/15) and 6% (1/15) in rats treated with DHPN and 0.15% testosterone, 13% (2/15) and 13% (2/15) in rats treated with DHPN and 0.03% testosterone and 33% (5/15) and 33% (5/15) in the castrated animals initiated by DHPN. The reduction in adenoma development associated with testosterone treatment was significant at both concentrations. In contrast, only a tendency for decrease of thyroid tumor incidence was observed in rats castrated.

Animals↗