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Biomedical subjects

N Takeichi

Publications and source records attributed to N Takeichi.

At least 145 records · Page 8Linked to original sources

Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogeneic class I major histocompatibility complex gene (H-2Ld).

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld-negative, and two Neor clones were selected by means of a 125I-protein A binding assay using an anti-H-2Ld monoclonal antibody. The antigenic expression of the H-2Ld gene products was only 20-40% on the Ld-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 X 10(6) in the Ld-positive clones, but only 1.3 X 10(5) in the 3LL/3 parent clone, 1.2 X 10(5) in the Neor clones, and 2.2 X 10(5) in the Ld-negative clones. The tumorigenicity of the Ld-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the Ld-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable Ld-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between Ld-positive, Ld-negative, Neor, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity.

Animals↗

Differentiation therapy of a myelomonocytic leukemia (c-WRT-7) in rats by injection of lipopolysaccharide and daunomycin.

We examined the therapeutic effect of lipopolysaccharide (LPS), a differentiation inducer, in combination with daunomycin, an antileukemia drug possessing differentiation-inducing potential, on a rat myelomonocytic leukemia (c-WRT-7). c-WRT-7 cells were found to differentiate into macrophage-like cells and to lose their growth capacity both in vitro and in vivo after incubation with LPS. Morphological differentiation of c-WRT-7 cells was observed in diffusion chambers which had been inserted into the abdominal cavity of syngeneic WKA rats given injections of LPS. A series of i.p. injections of LPS resulted in the complete inhibition of the leukemia development in about 60% of the rats while the remaining rats showed a significant prolongation of survival time when they were given i.p. injections of LPS-sensitive c-WRT-7 cells. The effect of LPS was minimal, however, in those rats which had been given i.p. injections of LPS-hyporesponsive c-WRT-7 cells. Although an i.v. injection of 100 untreated c-WRT-7 cells was enough to kill the syngeneic rats, combination treatment with LPS and daunomycin was able to inhibit completely the development of leukemia in those rats which had been given i.v. injections of LPS-sensitive c-WRT-7 cells, whereas the same treatments were only partially effective in the prolongation of survival among those rats which had been given i.v. injections of LPS-hyporesponsive c-WRT-7 cells. Our studies show that LPS was capable of curing a proportion of rats and that it significantly prolonged the survival of the remainder who had received a transplantation of the differentiation-sensitive leukemia cells; this action was significantly enhanced by the associated administration of daunomycin.

Animals↗

Inverse correlation between the metastatic capacity of cell clones derived from a rat mammary carcinoma and their intercellular communication with normal fibroblasts.

We used three highly and two weakly metastatic clones obtained from a rat mammary carcinoma cell line (c-SST-2) to examine the relationship between the metastatic capacity of tumor cells and their intercellular communication with normal fibroblasts. By employing the dye-transfer method, we found that the frequency of intercellular communication between weakly metastatic clone cells and fibroblasts was significantly higher than that between highly metastatic clone cells and fibroblasts. These results suggest that normal fibroblasts may regulate the metastatic capacity of tumor cells by intercellular communication.

Animals↗

Regulatory roles of burst-promoting activity (BPA) from bone marrow cells during human regenerating hemopoiesis.

To clarify the regulatory roles of burst-promoting activity (BPA) in cases of in vivo erythropoiesis, we examined erythroid progenitors and BPA in 18 patients with a regenerating hemopoiesis following intensive chemotherapy. Marrow erythroid progenitors increased remarkably in these patients. Bone marrow-conditioned medium (BMCM) and sera obtained from these patients revealed high levels of BPA. Serial examination of a typical case showed that BPA in BMCM and sera increased during regenerating hemopoiesis, but decreased when the hemopoiesis stabilized. Adherent cell depletion and treatment with monoclonal antibody (OKM1) reduced BPA production from the bone marrow cells, thereby suggesting that bone marrow macrophages are responsible for the BPA production. Fractionation of pooled BMCM with Amicon Diaflo membranes showed that the BPA was mainly present in the 30,000- to 50,000-dalton fraction. BPA in BMCM was heat labile, inactivated by trypsin and protease, but was not inactivated by neuraminidase. Pooled BMCM did not influence the growth of CFU-E-derived colonies. Our results suggest that to repair disturbed erythropoiesis, bone marrow macrophages produce BPA during regenerating hemopoiesis.

Adult↗

[Cancer metastasis and intercellular communication].

Three highly metastatic and two weakly metastatic clones were obtained from a spontaneously arising mammary adenocarcinoma in an SHR rat. The difference in their capacity to generate metastatic activity was recognized only when the cancer cells were inoculated s.c. but not when they were inoculated i.v. This evidence possibly indicates that the difference in the metastatic capacity of these clones is caused by different potential for detachment from the primary site and for intravasation during the various steps of metastasis. The motility of cancer cells, which is one of the most important factors in these steps of metastasis, showed no difference between the highly and weakly metastatic clones. However, the motility of cancer cells was decreased after coculture with fibroblasts, and the motility of weakly metastatic clones was more strongly decreased than that of highly metastatic clones. On the other hand, using a dye transfer method to examine the relationship between the metastatic capacity of cancer cells and the capacity of cancer cells to form junctional communications with normal fibroblasts, it was demonstrated that the communication between highly metastatic clone cells and fibroblasts was poorer in comparison to that between weakly metastatic clone cells and fibroblasts. These results suggest that the motility of cancer cells is inhibited by interaction with normal fibroblasts, and that one of these forms of interaction may be mediated by intercellular communication.

Adenocarcinoma↗

Breast cancer in a man treated effectively with a large dose of tamoxifen citrate.

Breast cancer in males is comparatively rare. A 41-year-old man visited our hospital with a complaint of left breast tumor. Initial examination showed remarkably diffuse metastatic lesions in the lung field and small metastatic lesions in the surrounding skin. Modified radical mastectomy, including the surrounding metastatic skin lesions, and incisional biopsy of the lung were performed. Estrogen receptor was positive in both the primary breast cancer and metastatic cancer lesions in the lung. Postoperative medication of tamoxifen citrate, an estrogen receptor blocking agent, in a dose of 30 mg/day, was given together with fluorouracil, BCG, cyclophosphamide, and methotrexate. No evident change could be seen in the lung field six months after the operation. The metastatic lesions in the lung disappeared two years after the operation when the dose of tamoxifen citrate was increased to 60 mg/day. At this writing, thirty months after the operation, the patient is in good health.

Adenocarcinoma↗

Aspiration biopsy cytology a highly diagnostic procedure for assessing neck masses, excluding thyroid tumors.

Aspiration biopsy cytology (ABC) was done on one hundred and forty-five patients with cervical tumors, excluding primary tumors of the thyroid and local metastasis of thyroid cancer, during the period of 44 months from 1981-85. Surgery was done on a total of fifty-five patients with lesions evaluated to be malignant and requiring resection. A correlation was determined between the histological diagnosis based on permanent paraffin sections and the diagnosis made by aspiration biology cytology in order to evaluate ABC in terms of accuracy together with its complications and limitations. The false positive rate was 6.6 per cent and the false negative rate was 8.3 per cent. Histologic diagnosis was predictable by ABC in eighty per cent of cases, but difficulty was experienced in predicting the histologic diagnosis in cases of a poorly differentiated malignancy. A few cases of slight subcutaneous bleeding occurred, but seeding implantation of cancer cells was nil. It was confirmed that ABC is a highly diagnostic procedure for assessing cervical tumors. The method is simple, safe and economical.

Biopsy, Needle↗

Metastatic ability and expression of c-fos oncogene in cell clones of a spontaneous rat mammary tumor.

It was found that cell clones c1-2, cl-2r, c1-3, c1-4 and c1-6 of a spontaneous rat mammary tumor, c-SST-2, exhibit different degrees of metastatic ability: c1-2, c1-3, c1-6 were highly metastatic, while c1-2r and c1-4 were weakly metastatic. The expression of several oncogenes in these clones was examined. The amounts of myc mRNA in the clones were nearly the same. Expression of N-ras mRNA was higher in c1-2r and c1-4 than in c1-2, c1-3 and c1-6. On the other hand, the amounts of fos mRNA in the weakly metastatic clones were markedly lower than those in the highly metastatic clones. These results suggest that fos oncogene plays a role in the high metastatic ability of c-SST-2.

Animals↗

Recognition by a natural cytotoxic antibody of lactoneotetraglycosyl ceramide as an antigenic molecule in a syngeneic rat fibrosarcoma.

Conventionally bred rats possess in their sera an NA which has a cytotoxic effect on a tumor cell line (KMT-17) derived from a fibrosarcoma induced by 3-methylcholanthrene and which can be absorbed by normal rat tissues. We have succeeded in purifying a glycosphingolipid as an antigen reactive to NA. GSLs isolated from the tumor cells were separated into neutral and acidic fractions. The former fraction was judged to be antigenic as detected by its capacity to absorb NA. The antigenic fraction was further separated into 7 fractions (Frs. A to G) by silicic acid chromatography. The antigenic activity was detected in only Frs.D and E, although Fr.D was a more potent antigen than Fr.E. Chemical and immunochemical analyses showed that both fractions are composed of lactoneotetraglycosyl ceramide (paragloboside), Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc(beta 1-1)ceramide, and that the more active GSL, Fr.D, contains larger amounts of long fatty-acid chains. Inhibition studies using disaccharides and monosaccharides indicated that a N-acetyllactosamine moiety, Gal(beta 1-4)GlcNAc, of the GSL is a specific site of NA. These results suggest that paragloboside is an NA antigen and that a sugar chain portion of this GSL is required for defining specificity while the ceramide portion plays a role in potentiating the antigenicity of this GSL antigen for NA.

Amino Sugars↗

Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.

Adenocarcinoma↗

Topical immunology of nasal allergy and mucosal IgE antibodies.

In the present study, the in vitro tissue-radioallergosorbent test (t-RAST) was performed in two groups of patients: one with perennial attacks of sneezing, serous hypersecretion and nasal congestion, the other with nasal congestion only. The results obtained were compared with those obtained by a series of conventional allergy tests. We then found that t-RAST provided objective data comparable to those obtained with serum-RAST and that the t-RAST is a reliable means of quantitatively detecting specific IgE antibodies in the nasal mucosa. t-RAST is of special value to diagnosticians because it is able to discern unequivocally and easily those patients with localized nasal allergy.

Humans↗

Survival of human normal thyroid cells after X-ray irradiation.

Normal thyroid cells from 25 individuals treated surgically for malignant or benign thyroid tumour were cultured in vitro and radiation induced cytotoxicity was studied. The mean lethal dose (Do), quasi-threshold (Dq), and extrapolation number (n) of survival curves of actively dividing thyroid cells assayed by colony formation were estimated to be 92.9 +/- 2.8 cGy (rad), 58.1 +/- 6.9 cGy and 2.0 +/- 0.1, respectively (average for 25 individuals +/- standard error). These results suggest that proliferating human thyroid cells are more sensitive to X-rays than most other nonhaematologic mammalian cells in similar assays. Cell survival was not significantly affected by sex, age, disease or exposure to atomic bomb radiation of the cell donor. However, the number of samples currently available is too small for definite conclusions in this regard.

Adolescent↗