Search PubMed⌕ Search

Biomedical subjects

T Kimoto

Publications and source records attributed to T Kimoto.

At least 109 records · Page 6Linked to original sources
PubMed1988

Collagen fiber formation and proliferation as a mechanism of cancer prevention and regression induced by extract from Mycobacterium tuberculosis: correlation between clinical observation and animal experiments.

Administration of polysaccharides extracted from human Mycobacterium tuberculosis bacilli, Aoyama B strain (SSM) produced regression of breast cancer in 2 women. Biopsies of tumor nodules from these patients revealed intense proliferation of collagen fibers from the stromal cells. SSM apparently promoted the proliferation and maturation of collagen fibers from the stromal cells and matrix destroyed by tumor infiltration. Transplantation of human tumor cell lines into athymic mice resulted in the formation of collagen fibers surrounding the cancer cells. SSM promoted the proliferation and maturation of collagen fibers encasing the tumor cells. The intensity of collagen fiber formation varied with the kind of cancer cells used. The degree of proliferation of collagen fibers correlated with the antitumor effects of SSM. There was hardly any migration of lymphocytes, monocytes, and macrophages in the affected sites. It is interpreted that SSM stimulates the proliferation and maturation of collagen fibers in the host as a major mechanism of its antitumor property. When examined by circular dichroism this proliferation was found to be dependent upon changes in the molecular structure of the substances which make up the cell membrane. Fibronectin was presumed to be important among these substances.

Adenocarcinoma↗
PubMed1987

Comparison of major cytoskeletons among normal human fibroblasts, immortal human fibroblasts transformed by exposure to Co-60 gamma rays, and the latter cells made tumorigenic by treatment with Harvey murine sarcoma virus.

Immortally transformed human fibroblasts in general acquire an epithelial shape, while normal human fibroblasts demonstrate a spindle-shaped feature. In order to investigate this difference, three types of major cytoskeletal elements, namely, F-actin, tubulin, and vimentin of immortal human fibroblasts were morphologically compared with those of normal human fibroblasts. As a result, a significant difference was observed in the distribution and in the number of F-actin fibers between immortal and normal fibroblasts. The cells of three immortally transformed fibroblast lines, KMST-6, WI-38 VA-13, and SUSM-1, showed a striking reduction in the number, and an altered pattern of organization, of actin fibers. On the other hand, in the normal fibroblasts, actin fibers ran parallel to each other along the long axis of the cells. Tubulin and vimentin showed no significant difference between the immortal and normal cells. Our present data show that the morphological changes seen in the immortally transformed cells are due to the disorganization and the decrease in number of actin fibers. Interestingly, both the immortal cells (KMST-6), which were not tumorigenic, and the Harvey murine sarcoma virus-transformed KMST-6 cells, which were tumorigenic and demonstrated an enhanced expression of the ras gene, revealed an overall similarity in the organization pattern and the number of actin fibers. These findings seem to indicate that the immortally transformed cells have already acquired some cancer characteristics.

Actins↗
PubMed1987

Antitumor effects of polysaccharides of human-type Mycobacterium tuberculosis on collagenation in human cancer xenografts.

The most important activity of SSM is stimulation of collagenation from cancer-infiltrated stromal tissue which confines the cancer. In order to elucidate the proliferative responses of collagen in cancer, single and double xenografts were prepared by transplantation of human gastric cancer (HGC), human lung cancer (HLC), and NB41A3 (mouse neuroblastoma) into nude mice. The collagen responses were dependent on the type of cancer cell used, particularly the cell membranes. SSM distinctly stimulated the proliferation of collagen fibers which showed a response to these cancer cells. When examined by CD, stromal collagenation was found to be dependent upon changes in the molecular structure of the cancer cell membrane. One of the glycoproteins, fibronectin, was presumed to be the most important of the substances involved.

Animals↗
PubMed1987

Pathological studies on three cases of cancer treated with polysaccharides from human-type Mycobacterium tuberculosis. Antitumor activity through collagen fiber proliferation.

Three cases of cancer treated with SSM (Special Substance, Maruyama: a polysaccharide extract from Mycobacterium tuberculosis) for a long period were studied pathologically following biopsies and autopsies. The most significant antitumor activity resulting from SSM treatment was found to be collagenation from stromal cells and the cancer cells themselves. Another significant finding was that collagenation was promoted by macrophages which had been stimulated non-specifically. However, it was apparent that SSM-A or B had to be used efficiently and quickly in order to prevent invasion or metastasis of cancer. Collagenation due to SSM treatment was more marked in metastatic cancer lesions in the liver than those in the lung. In a case of breast cancer reported in a previous investigation of SSM treatment, remarkable calcification was found in a metastatic cancer lesion which had become confined through collagenation, thus preventing cancer cell metastasis. The collagenation of cancerous lesions through SSM treatment resembled the healing of caseous tuberculosis lesions through a similar mechanism.

Adult↗
PubMed1987

The level and stability of residual catalase in cultured acatalasemic skin fibroblasts.

In an attempt to determine the level and heat stability of residual catalase in somatic cells of acatalasemic Japanese, skin fibroblasts from an acatalasemic subject were cultured, and the catalase activity of the cultured fibroblasts was compared with that of cultured normal fibroblasts. Catalase activity was determined using an oxygen electrode. The residual catalase activity in cultured acatalasemic fibroblasts was 10% of the normal. The heat stability at 55 degrees C of residual catalase in the acatalasemic fibroblasts was similar to that of normal fibroblasts.

Acatalasia↗
PubMed1986

Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses.

As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

Animals↗
PubMed1986

In vitro and in vivo properties of the virus causing natural canine distemper encephalitis.

A group of dogs with naturally occurring canine distemper developed prodromal systemic symptoms followed by neurological disorders. The post-infection courses of these diseases lasted approximately 2 months. A varying degree of demyelination and inclusion body formation was found mostly in the cerebella of virologically confirmed cases with little or no inflammatory response. The distribution of canine distemper virus antigen coincided with the histopathological lesions. The animals had moderate to high neutralizing titres to the virus in their sera and a low level of interferon-like activity in their cerebrospinal fluids. Isolation of viruses was most successful by the cocultivation method for brain specimens, but was possible by the direct method using lung homogenates. In infected Vero cells, the isolates derived from brain caused the formation of distinct plaques consisting of multinucleate giant cells, but the isolates from lung induced a cytopathic effect mainly consisting of cell rounding which eventually spread throughout the culture. The former infection produced less extracellular virus than the latter. The synthesis of the viral surface proteins H and F, and of M, was markedly reduced compared with that of the internal viral proteins such as NP, P and L. The SDS-PAGE migration pattern of the P protein varied from case to case, but was similar when isolates from different tissues of the same case were compared. In the affected tissues, the amount of viral polypeptides decreased markedly relative to that of the NP and there was also an absolute decrease compared to their abundance in Vero cells. This decrease was more obvious in the brain than in the lung. The relevance of these results is discussed.

Animals↗
PubMed1985

[Mammography in diagnosis of breast cancer].

Radiographic features of 50 breast cancers were evaluated in comparison with 83 benign lesions and the diagnostic accuracy is discussed. Most of the usual primary and secondary findings of cancer such as spicula formation, microcalcifications, skin, thickening and nipple retraction were present in these 50 cancer lesions and all of them were recognized in the benign lesions as well, although less frequently. Because breast parenchyma was dense in 81% of the cases evaluated, and mostly due to moderate to severe dysplasia, the diagnosis of the breast lesions was difficult. Therefore, we must be cautious in calling a lesion benign. The radiographic detectability of cancer was 94%, and the diagnostic accuracy was 72%, which are comparable to the results reported from other places.

Adult↗
PubMed1985

Neoplastic transformation of human diploid fibroblasts (KMST-6) by treatment with 60Co gamma rays.

Normal fibroblasts (KMS-6) derived from a human embryo were transformed in culture into neoplastic cells (KMST-6) by repeated treatment with 60Co gamma ray irradiation. Repeated treatment was necessary to obtain transformation. Control normal cells exhibited normal karyotype (46, XX) and stopped dividing due to cellular ageing at the 40th passage. The transformed cells are presently growing indefinitely (140th passage) and exhibit prominent karyologic aberrations, both numerical and structural. These 2 characteristics, indefinite growth and abnormal karyotype, are thought to be the most important parameters for neoplastic transformation of human fibroblasts. Other indispensable parameters are the presence of active mitotic figures on confluent cell sheets and colony-type morphology. Transformed cells grow into colonies with relatively smooth edges, while normal fibroblasts form colonies with jagged edges, due to the protrusion of growing fibroblasts. Other parameters, such as elevated plating efficiency, enhanced colony formation in soft agar, low serum requirement for growth, high saturation density, and acquisition of transplantability, are not reliable in the early stages of transformation. These parameters probably appear at rather later stages of transformation following several cell divisions. Among other characteristics, the transformed KMST-6 cells exhibit a B-type isozyme pattern of glucose-6-phosphate dehydrogenase, lactate-dehydrogenase isozyme pattern of human origin, no evidence of viral infection and no production of C-type virus particles.

Cell Line↗
PubMed1985

Diffuse peripheral lung disease: evaluation by high-resolution computed tomography.

High-resolution computed tomography (HRCT) was performed on 15 patients who had diffuse peripheral lung disease, and the findings were compared with those of conventional chest radiography and histologic examination. Bullae, interstitial fibrosis with honeycombing, and small granulomas were more clearly and specifically demonstrated on HRCT scans than on conventional chest radiographs in all patients. Histologically proved mild alveolar wall thickening due to alveolitis in cases of sarcoidosis and systemic lupus erythematosus was not detected. HRCT is useful for performing detailed morphological analyses of abnormalities of the peripheral portions of the lung.

Adult↗
PubMed1984

In vitro and in vivo studies on potentiation of cytotoxic effects of anticancer drugs or cobalt 60 gamma ray by interferon on human neoplastic cells.

A possibility that interferon may potentiate the cytotoxic effects of anticancer drugs or 60Co gamma ray on human neoplastic cells was studied by in vitro and in vivo experimental procedures. The human neoplastic cells used were HeLa (uterine cervical cancer) and WI-38 CT-1 (embryonic lung fibroblasts transformed in culture by 60Co gamma ray) cells. As normal human cells, WI-38 cells were used. Interferon was a preparation of beta-type produced by human fibroblasts. The cytotoxicity was determined by colony formation for in vitro experiments and by tumor growth for animal experiments. Of 17 anticancer drugs, the cytotoxic effects of six drugs, namely, peplomycin, bleomycin, aclacinomycin, cisplatin, 5-fluorouracil (5-FU), and Adriamycin (doxorubicin) were potentiated by concomitant application of interferon. The cytolethal effects of 60Co gamma ray were also enhanced by interferon. The growth of tumor induced by transplantation of HeLa cells into a nude mouse was remarkably reduced by combination therapy of interferon and 5-FU. The current results indicate a possibility that combined therapy of certain types of anticancer drugs or 60Co gamma ray with interferon may be effective in treatment of cancer patients.

Animals↗
PubMed1984

Differential growth response of normal human diploid fibroblasts and in vitro transformed human fibroblasts in serum-free defined culture medium.

Two neoplastic human cell lines, WI-38 CT-1 and SUSM-1, which were transformed in vitro with gamma rays and 4-nitroquinoline 1-oxide, respectively, grew continuously in a serum-free defined medium. The defined medium used was a 1:1 mixture by volume of Dulbecco's modified Eagle's medium and Ham's F12 (DF) supplemented with 0.1% bovine serum albumin fraction V, 10 micrograms/ml of transferrin, 1 microgram/ml of insulin, and 5 micrograms/ml of oleic acid. In the case of SUSM-1, 100 micrograms/ml of fetuin were added to cultures when the cells were subcultured. Under these conditions the growth rates of the two transformed human cell lines were almost the same as those in a DF medium containing 10% fetal bovine serum (FBS). In addition, the defined medium permitted the cells to grow indefinitely without a lag period when they were transferred from serum-containing medium into this defined medium, indicating that no selection or adaptation of the cells had occurred. Interestingly, these cell lines did not require for their growth any polypeptide growth factors such as epidermal, platelet-derived or fibroblast growth factors. On the other hand, the control WI-38 cells stopped growing in the defined medium after about 2 divisions. Another control normal cell strain of fibroblasts derived from a human embryo showed a decreased growth rate in the defined medium as compared with that in the DF medium with 10% FBS. These results suggest that the defined medium described here is useful for the selective growth of human cells transformed in vitro after treatment with carcinogens from an untransformed cell population. In addition, the defined medium for transformed human cells should contribute to studies on their growth mechanisms.

Cell Division↗
PubMed1984

Potentiation of cytotoxic effects of 5-fluorouracil by inosiplex on cancer cells.

The antitumor effect of 5-fluorouracil (5-FU) was significantly enhanced by inosiplex which has been developed as a drug possessing antiviral activity. The enhancement of antitumor effect of 5-FU was demonstrated by experiments both in vitro and in vivo, viz. depression of the colony formation rate in cultures of HeLa cells (an established cell line of human cervical carcinoma), and prolongation of the survival of mice bearing transplanted Ehrlich ascites tumor of murine mammary carcinoma origin. The HeLa cell colony formation was synergistically decreased in the presence of 0.5-2.0 micrograms/ml of 5-FU combined with 100 micrograms/ml of inosiplex. Inosiplex did not cause any appreciable inhibition of cell growth at this concentration when added alone to the culture. The mean duration of survival of tumor-bearing mice was 18.2, 20.3, 31.9 and 47.1 days in the control group and groups receiving inosiplex, 5-FU, or a combination of 5-FU and inosiplex, respectively; hence significantly prolonged in the combined therapy regimen group as compared with the control and the 5-FU treated group (P less than 0.01).

Animals↗