Murine fibrosarcoma clone established in defined medium.
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Biomedical subjects
Publications and source records attributed to M Chigira.
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Wholism, known as 'homeostasis' in multicellular organisms, is fundamentally expressed in the regulation of cell proliferation and of the metabolism of individual cells. Control mechanisms represent an overriding control of the autonomy of cells in multicellular organisms. Negative regulation by suppressor genes including tumor suppressor genes is essential to maintain homeostasis in these organisms. Without wholistic regulation, the cellular society of multicellular organisms would progress from bad to worse, with eventual destruction of the whole system. The enhancement of division and differentiation of cells transduced by water-soluble factors may be considered as the controlling structure on the tumor suppressor genes. In microevolution, cell killing by the immunosurveillance systems directed at the external environments has been avoided for the 'self' cells in general, since the multicellular organism may not be considered as only a crowd of single cells.
A sclerotomic symmetry in the bony lesions was clearly demonstrated in 4 patients with osteopoikilosis. Occurrence of the lesions was highest at the C6-7 and L3-4 levels.
Levels of serum tumor markers including CEA, AFP, CA 15-3, CA 19-9, CA 125 and TPA were measured in 26 patients with bone metastases and in 9 patients with primary bone tumors. TPA was the most sensitive marker to detect skeletal metastasis being elevated in 15 of the 22 patients (68.2%). High sensitivity was observed in CEA (46.1%), CA 15-3 (40%), and CA 125 (35%), and AFP showed relatively low sensitivity (4.3%). When elevation of TPA only or elevation of more than two tumor markers including TPA was used as a screening test for skeletal metastasis, over-all sensitivity, specificity, and accuracy were 73.1%, 88.9%, and 81% respectively. No definite correlation between the markers could be seen in this study. A combination of serum tumor markers was useful in the differential diagnosis of bone metastases from primary bone lesions. However, organ specificity of the markers were relatively low.
Curettage without bone graft was performed in fifteen patients with benign bone tumors and tumor-like lesions. We studied the bone formation after curettage by plain radiography and computed tomography for six or more months. Average period before full-weight-bearing in thirteen patients of the lower extremities was three and a half months. We found no pathological fractures after curettage in any of the patients. Increases in radiodensity and reconstruction of the bone were observed in serial plain radiographs within three months. Computed tomography revealed that the center of the lesions persisted without bone formation, although thickening of cortex bone was predominant. From the data obtained here, it appears that bone grafts may not be necessary in patients, especially in younger ones, with benign bone tumors and tumor-like lesions.
Levels of serum tumor markers including tissue polypeptide antigen (TPA), CA 15-3, CA 19-9, squamous cell carcinoma antigen, carcinoembryonic antigen, alpha-fetoprotein, and PAP were measured in 26 patients with bone metastasis and in 9 patients with primary bone tumors. More than one markers was elevated in 19 of the 26 patients with bone metastasis, although there was no elevation of the markers in 3 patients with renal cell carcinoma. TPA was the most sensitive marker in the diagnosis of metastasis. CA 15-3 was also a sensitive marker in this study, since metastasis from breast carcinoma may be the most common of all metastases in the skeleton. On the other hand, alpha-fetoprotein was uniformly unresponsive except in one case of gastric cancer. Combinations of markers are valuable for metastasis screening tests. No definite correlations were found between the markers in this study. On the other hand, there was a slight elevation of the markers observed in two of the nine patients with primary bone lesions. Serum tumor markers are useful in the diagnosis of bone metastasis to differentiate it from primary bone lesions. Especially in solitary bone lesions, serum markers may be the only way to make a differential diagnosis between the two.
Tumor markers in serum should not be correlated with the prognosis of patients with malignant tumors, although the markers indicate the presence of tumors, since marker levels and prognosis are controlled independently by poly-genes. Furthermore, prognostic factors, including incidence of pulmonary metastasis, tumor growth rate, tumor drug sensitivity and host response, vary among patients. In general, tumor markers may be used to demonstrate response of tumor to treatments only when expression of the markers does not change in a time-dependent manner.
Autonomous replication of tumor cells seems to be an essential factor in the definition of the malignant tumor itself, although tumor cell proliferation is, in general, controlled by the host response including immunological reactions and microenvironment. The cause of the autonomy can hypothetically be classified into four categories as follow: (a) auto- and paracrine growth stimulation; (b) growth factor receptor abnormalities; (c) abnormal signal transduction; (d) self-incitement of 'initiator-replicon' system in DNA replication. These intracellular mechanisms may play important roles in the autonomy as shown in autocrine growth factors from the data obtained in protein-free cell culture. Hypothetically, negative regulation systems on the initiator-replicon may play roles of cell replication in multicellular organisms. Oncogene products and growth factors may affect this regulation system.
Polyacrylamide gel electrophoresis utilizing sodium dodecyl sulfate followed by specific staining for alkaline phosphatase was accomplished using sera from patients with osteosarcoma, polyostotic fibrous dysplasia, metastatic bone tumor, and idiopathic hyper-alkalinephosphatasemia. Alkaline phosphatase activity of the sera was uniformly demonstrated at a molecular weight of 60,000. L-homoarginine more strongly inhibited the alkaline phosphatase activity than did L-phenylalanine. Alkaline phosphatase activity was markedly inactivated by heating. Regarding substrate specificity, the hydrolysis of p-nitro-phenylphosphate occurred at a lower rate than did that of phenylphosphate. By contrast, the hydrolysis of alpha- and beta-glycerophosphate occurred at a higher rate than did that of phenylphosphate. As seen from the data presented here, the serum alkaline phosphatase samples obtained from these patients with skeletal disorders have several common characteristics.
Human leukocyte antigen (HLA) phenotypes were studied in twenty Japanese patients who had typical osteosarcoma. The HLA-A11 phenotype was found in ten (50 per cent) of the twenty patients, compared with 16.6 per cent of 235 control subjects (chi square = 13.248; p less than 0.0005)--an odds ratio of 5.026. These data suggest that major histocompatibility complex-linked genes may determine susceptibility to osteosarcoma.
Computed tomographical analysis of sternocostoclavicular hyperostosis was performed in 27 patients. In the earliest stage hyperostosis occurred around the cartilaginous portion of the first ribs. The sternoclavicular joint space was preserved even in the late stage III of the disorder. These findings suggest that sternocostoclavicular hyperostosis develops around the costal cartilage including periosteum, perichondrium, and the ligamentous structures, and that the sternoclavicular joint is not primarily involved. It is also suggested that perichondritis and periostitis play important roles in the etiology of this disorder.
Bone metastasis may be considered a non-stochastic process, since the blood flow in bone is lower than that in other organs and most cancers do not have a tendency to metastasize to bone in in vivo experiments. Furthermore, the experimental model of bone metastasis, based on the ligation of major venous flow, can not explain the wide-spread bone metastasis which is commonly observed in clinical cases. These observations may be explained by the hypothesis that tumor cells have a phenotype for translocating to specific tissues and that tumor cell growth is controlled by the microenvironmental factors in situ.
Roentgenological analysis of the anterior chest wall was performed in twenty six patients with sternocostoclavicular hyperostosis. Initial hyperostotic change was seen at the first costosternal junction with ventral protrusion. Hyperostosis gradually developed around the first ribs, and irregular hyperostotic changes were also seen along the costoclavicular ligaments. Even in the final stage, however, sternoclavicular joint spaces were well preserved. These findings suggest that sternocostoclavicular hyperostosis is a disorder initiated around the costal cartilage including the periosteum and perichondrium, and that arthritis is not a condition stemming from that disorder.
A patient with transient osteoporosis of the hip in her first trimester of pregnancy is reported in this study. Rapid symptomatic improvement after artificial abortion was observed. These findings exclude pressure on the obturator nerve, Sudeck's osteodystrophy, venous obstruction, and excessive demand of proteins and calcium in the etiology of this condition. Rather it is here suggested that chemical or hormonal factors related to pregnancy play an important role in the etiology.
Thirteen clones were established from a Dunn osteosarcoma by means of limiting dilution. The heterogeneity of four parameters (in vivo and in vitro growth rates, alkaline phosphatase activity and metastatic capacity) was clearly demonstrated. Statistical analysis does not reveal a high correlation between the four parameters. The highly metastatic clones 5 and 10 lost tumorigenicity at the primary site. The presence of these clones suggests that the microenvironment of the host is able to control tumor growth and that metastasis should be considered as a differentiated phenotype in tumor progression.
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Internal pressure and oxygen tension were measured in 24 patients with bone tumors and tumorous conditions. High internal pressure were observed in most of the rapidly growing lesions. The internal pressure of slowly growing and non-growing lesions were not significantly different from those of normal bone marrow. Oxygen tension was commonly higher in the rapidly growing lesions than in simultaneously obtained peripheral venous samples from the same patients. A high correlation was found between internal pressure and the growth rate of the bone lesions in this study. These data suggest that internal pressure and oxygen tension of the lesions reflect the degree of blood supply to the bone tumors and tumorous conditions.
We report a case of multiple, simple bone cysts in long tubular, short tubular, and flat bones. The internal pressure of the cysts and the oxygen tension of cyst fluid were measured simultaneously. These values were similar to those of typical solitary cysts in other patients. Curettage and bone graft onto the calcaneal cyst were effective, although steroid injection therapy into the metacarpal cyst had no effect. Piercing the ulnar and radial cysts a number of times was uniformly effective. These results may suggest that venous obstruction of the lesions play an important role in the etiology of multiple simple cysts, as shown in typical bone cysts. However, we could not exclude the possibility that simple bone cysts, solitary or multiple, represent some kind of secondary forms of other disorders, or that a simple bone cyst is a heterogeneous entity.