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PubMed1975

"Skip" metastases in osteosarcoma.

Careful study of 40 cases of osteosarcoma without evidence of multifocal disease, pulmonary metastasis, or history of exposure to predisposing factors has given histologic evidence of microscopic foci of osteosarcoma separate from the primary focus of osteogenic sarcoma. These "skip" lesions are to all pathologic examination completely separate from the primary focus of osteogenic sarcoma. They are more often found proximal to the primary, both intraosseously and transarticularly. Histologically, these "skips" represent areas of osteosarcoma which in many cases are a less-differenitated form of the tumor. The natural history of such tumors with "skips" following ablative surgery is an increased incidence of local recurrence and subsequent pulmonary metastases.

Adolescent↗
PubMed1975

Investigation of carbohydrate metabolism and somatomedin in osteosarcoma patients.

Altered carbohydrate metabolism associated with fibrosarcomas and chondrosarcomas has been well-documented in past literature. This report describes abnormal carbohydrate metabolism in 2 osteosarcoma patients, and abnormalities in growth hormone and somatomedin serum levels. Experimental evidence is presented showing in vitro suppression of osteosarcoma tumor cell proliferation by 17 beta Estradiol. Estrogen inhibition of linear bone growth, cartilage proliferation, and somatomedin is discussed with reference to possible estrogen therapy in osteosarcoma.

Adolescent↗
PubMed1977

Carcinoembryonic antigen in osteosarcoma.

Plasma carcinoembryonic antigen (CEA) assay was done in 30 patients with osteosarcoma. CEA was found positive (greater 2.5 ng/ml) in 17 of 21 patients who had active evidence of disease and negative (less than 2.5 ng/ml) in all 9 patients who were in complete remission resulting from previous amputation of chemotherapy. Serial CEA determinations demonstrated a fall to normal in 7 of 9 patients following successful surgery of chemotherapy and a ruse and fall (fluctuation) of levels in 8 patients who had tumor progression while on chemotherapy. Clinical recurrence of disease in two instances preceded or coincied with CEA elevation. The CEA assay in osteosarcoma although non-specific could be used as an inportant adjunct to experienced clinical judgment, periodic x-ray examination, and laboratory study to prognosticate the course of osteosarcoma during therapy. The interpretation of a rising or falling CEA titer alone, however, must be made with caution.

Adolescent↗
PubMed1979

Childhood multifocal osteosarcoma--diagnosis by 99mtechnetium bone scan: a case report.

A 14-year-old boy with osteosarcoma presented with evidence of a solitary bone lesion by clinical and radiographic examination. A preoperative 99mtechnetium bone scan revealed multiple skeletal osteoblastic abnormalities and upon biopsy of one of these lesions, the diagnosis of multifocal osteosarcoma was established. This unusual case dramatically illustrates the value of 99mtechnetium bone scan in preoperative staging of patients with osteosarcoma.

Adolescent↗
PubMed1979

Ultrastructure of telangiectatic osteosarcoma.

Recent investigations have shown that telangiectatic osteosarcoma has a poorer prognosis than other osteosarcomas. To elucidate the histogenesis of TOS two cases were investigated on the electron microscopic level. The results show that besides anaplastic, osteoblast-like, and fibroblast-like tumor cells angiosarcomatous components can be observed in this malignant bone tumor, which are characterized by endothelial cells with pinocytotic vesicles, tight intercellular junctions, fine fibrils, and so-called Weibel-Palade bodies in their cytoplasm. From these results, it is concluded that telangiectatic osteosarcoma is derived from multipotent mesenchymal cells with potential differentiation into various directions, such as osteoblast-like cells, and fibroblast-like cells.

Adolescent↗
PubMed1976

[Juxtacortical osteosarcoma (author's transl)].

Juxtacortical osteosarcoma should be considered a very rate distinctive entity under all malignant bone tumors. The tumor has a remarkable tendency to grow from the periostal tissues peripherally with a usually marked degree of ossification without primary medullary involvement. It's different und characteristic behavior in clinical, roentgenographic and microscopic findings from that of other types of bone-forming sarkomas is discussed by means of a just treated case. In contrast to osteogenic osteosarcoma the prognosis for early well treated juxtacortical osteosarcoma is much better.

Adult↗
PubMed1977

Aneurysmal bone cyst and telangiectatic osteosarcoma. A histopathological and morphometric study.

In a series of 105 cases of aneurysmal bone cyst, 18 showed an unusually high level of mitotic activity and/or increased nuclear pleomorphism which complicated the differential diagnosis with respect to telangiectatic osteosarcoma. An attempt was made to use semi-automatized morphometric and histophotometric techniques to establish objective morphological differences between these unusual cases of aneurysmal bone cyst and 16 cases of telangiectatic osteosarcoma. Three cases (two of aneurysmal bone cyst and one of telangiectatic osteosarcoma) proved unsuitable for analysis. In 24 of the remaining 31 cases (77%) a computerized discriminant analysis permitted correct discreimination with a high degree of certainty on the basis of quantitative nuclear characteristics determined in paraffin sections. In the other 7 cases the diagnosis was less certain (3), doubtful (2) or erroneous (2). The relevant nuclear characteristics were (in ascending sequence of discrimination): the largest nuclear surface area, the mitotic index, and the percentage of nuclear sections exceeding an arbitrarily chosen limit of 60 micron2. The criterion of nuclear size for discrimination between these benign and malignant lesions could be applied for two reasons: firstly, because a group of extremely large nuclei occur in malignant cases, and secondly, because the average nuclear size is larger in malignant than in benign lesions. The extremely large nuclei occur as only a small percentage of the total nuclear population. The other variables investigated, i.e., cellularity and nuclear contour ratio, did not contribute greatly to the differentiation. In 11 cases, the average nuclear Feulgen extinction was estimated as an additional variable.

Adolescent↗
PubMed1978

Ultrastructural cytology of human osteosarcoma cells.

The cytology of 6 osteosarcomas was examined by electron microscopy. In keeping with the varied pattern of osteosarcomas seen by light microscopy several types of tumor cells could be differentiated: osteoblast-like, fibroblast-like, chondroblast-like, osteoclast-like and histiocyte-like cells. Moreover, atypical malignant mesenchymal cells and vascular spaces were present. The individual cytoplasmic organelles are not considered to be specific to particular types of cell as seen from the discussion of the significance of rough endoplasmic reticulum, microfilaments and lysosomes. Only examination of the composite pattern of subcellular organelles allows the differentiation of certain cell types. All tumor cells visible in osteosarcomas are considered as modifications of a transformed common progenitor cell. Because of the variegated cytological picture a multipotent mesenchymal cell rather than an osteoblastic cell is assumed to be the ancestor cell.

Adolescent↗
PubMed1975

Studies on a factor responsible for new bone formation from osteosarcoma in mice.

The bone inducing factor derived from BF osteosarcoma was purified in the following manner. Step 1. The sarcoma, grown in CBA mice, was excised and lyophilized. Step 2. The powder was washed with chilled acetone. Step 3. The acetone-treated powder was then homogenized with chilled distilled water. Step 4. Washing with 0.15M KCl. Step 5. The precipitate was incubated in in 0.2 N NH2OH, pH7.0, for 48 H at 25 degrees. After Step 5, the bone-forming activity showed a slight increase; however, the factor remained insoluble. The properties of the factor were as follows. The factor is relatively relatively heat stable; the osteogenic activity survived the treatment at 75 degrees for 15 min or at 55 degrees for 19 h. The activity was easily lost by mechanical shaking. Incubation with DNase, RNase, neuraminidase, chondroitinase ABC and beta-galactosidase left the osteogenic activity intact, but treatment with either pronase or collagnease destroyed this activity. The results suggest that the factor may be a protein. The activity was seen with the lyophilized BF osteosarcoma cells (without matrix), and it is probable that the factor was exclusively synthesized in the cells. The bone formation, observed across a millipore filter when living BF osteosarcoma enclosed in a millipore chamber was implanted in mice, suggests the synthesis and secretion of the factor from the cells.

Animals↗
PubMed2026

Flavones in osteosarcoma: Molecular mechanisms, antitumor activity, and translational challenges.

Osteosarcoma remains the most common primary malignant bone tumor, and survival has improved little over recent decades because of metastasis and therapeutic resistance. Flavones exhibit diverse anti-osteosarcoma activities by suppressing proliferation, inducing apoptosis, ferroptosis and autophagy, inhibiting metastasis, and modulating oncogenic signaling pathways, including PI3K-Akt, Wnt-β-catenin, STAT3, MAPK, and NF-κB. This review summarizes the cell-line-specific molecular mechanisms of representative flavones, critically evaluates current experimental limitations, and discusses strategies to improve clinical translation through nanotechnology-based delivery and combination therapy. Although clinical evidence remains lacking, flavones represent promising adjunctive candidates for overcoming chemoresistance and improving osteosarcoma treatment.

apoptosis and metastasis↗
PubMed1976

Monitoring of murine osteosarcoma by serial alkaline phosphatase determinations.

To establish that alkaline phosphatase (AP) was released by osteosarcoma cells, we measured this enzyme in C3H/HeJ mice with im-implanted osteosarcoma and in in vitro cultures of neoplastic cells subjected to short-term incubation. We found that 10(5) osteosarcoma cells synthesized a significant amount of AP in vitro in 30 minutes at 37 degrees C. A good correlation existed between pulmonary metastatic tumors and the AP values. Serum AP measurements indicated approximate sizes of disseminated and localized tumors, but could not monitor early localized tumors.

Alkaline Phosphatase↗
PubMed1977

Osteosarcoma of bone and its important recognizable varieties.

Osteosarcoma of bone is a recognizable entity if the histopathologist designates tumors as such when their malignatn cells produce osteoid substance even if only in small foci. Such definition distinguishes this lesion from other sarcomas that arise in bone, especially chondrosarcoma and fibrosarcoma. There is a general tendency to consider that osteosarcomas represent a stereotyped form of disease for which new modalities of treatment can be applied and assessed. The question of whether a given osseous lesion is actually malignant and not a benign neoplasm or even a reactive non-neoplastic condition simulating a malignant tumor may be difficult for the histopathologist. Pathologists without considerable experience in the diagnosis of bone tumors find this question especially vexing. The establishment of a valid diagnosis of osteosarcoma introduces the additional problem that the 11 varieties considered in this paper may pose significant recognizable variations in the clinical capability of the disease. It is apparent that the physician must recognize the known clinicopathologic and prognostic factors of these subtypes in his assessment of the overall problem.

Adolescent↗
PubMed1975

Pathology of osteosarcoma.

Osteosarcoma of bone is a tumor composed of malignant cells that produce osteoid. Some tumors show predominant chondroid or fibromatoid ground substance. All, however, are highly malignant and about 80 per cent produce death with metastases. The roentgenogram affords important evidence for the correct diagnosis of many of them. Differential diagnosis should include consideration of those sarcomas with many benign giant cells and the group of "telangiectatic" osteosarcomas that may contain only small diagnostic areas. Malignant fibrous histiocytoma is now considered as a possible diagnosis for some malignant bone tumors, but the exact criteria for the diagnosis of this condition are still somewhat obscure. Newer modalities of adjunctive treatment, such as resection of pulmonary metastases, chemotherapy, and immunotherapy, give promise of improving the prognosis for osteosarcoma.

Adult↗
PubMed1975

Electron microscopic observations of 20 human osteosarcomas.

Twenty primary osteosarcomas of bone and two osteosarcomas metastatic to the lung were examined by electron microscopy. The tumor cells, whether from an area exhibiting chondroid, osteoid or collagenous matrix, showed common abnormalities in configuration and fine structure. The cells tended to be spindle-shaped with centralized nuclei. The nucleus was enlarged, irregular in shape, and frequently lobulated. The choromatin was dense and arranged around the periphery of the nucleus. There was a large prominent, irregularly shaped nucleolus. Smooth membranes were sparse to absent. The rough endoplasmic reticulum was abundant, disorderly, and tended to be markedly dilated in mature cells. The mitochondria were numerous, variable in size and configuration, and were intimately surrounded by rough endoplasmic reticulum. The collagenous matrix was disorganized with the fibers and bundles randomly oriented and arranged. No structures definitely identifiable as virus-particles were seen. However, microstructures resembling unenveloped nucleocapsids of paramyxo- or related viruses were noted. All fine structure abnormalities could be associated with an increased metabolic rate and/or with abnormal protein and enzyme synthesis. No definitive diagnostic features were found. The fine structure of cell cultures derived from the osteosarcomas in this study was similar to that of the fresh tissue. No virus-like particles were seen in any of these cell lines.

Bone Matrix↗
PubMed1975

The host immune response in human osteosarcoma.

A patient's immunologic response to a malignant tumor may be a major factor in determining his ultimate prognosis. An in vitro microcytotoxicity test using cultured tritiated thymidine (3HT) labeled osteosarcoma cells and autologous fibroblasts has been developed to determine the nature of this response. The role of cell mediated and serum factors has been quantitatively evaluated and the following results obtained. Osteosarcoma patients have been demonstrated to possess a normal cellular immune response which exhibits non-specific cytotoxicity in vitro. These patients can not differentiate their tumor cells from autologous fibroblasts, even though they may significantly suppress the growth of homologous tumors or fibroblasts. Serum blocking factors capable of inhibiting lymphocyte mediated cytotoxicity are occasionally noted. A reliable quantitative microcytotoxicity technique is presented which demonstrates that: (1) osteosarcoma is not due to host immuno-incompetence, (2) a common sarcoma antigen does not exist and (3) serum blocking factors may occasionally be present.

Adolescent↗
PubMedDate not supplied

Establishment and alkaline phosphatase activity of clonal cell lines of murine osteosarcomas. A preliminary study.

Clonal cell lines of murine osteosarcomas were established and have been maintained in vitro for over a year. By implanting these cultured cells into mice, osteosarcomas, whose histological picutres were exactly the same as those of the original tumors, were easily reproduced. The cultured cells of murine osteosarcomas contain an extremely high level of alkaline phosphatase activity. The cells also secrete a great amount of extracellular alkaline phosphatase in culture media.

Alkaline Phosphatase↗
PubMed1978

Ultrastructural study of tumor cell differentiation in osteosarcoma of jaw bones.

Tw osteosarcomas of jaw bones have been studied by electron microscopy. The objectives were to examine the specific cell types in relation to functions and ultrastructural features, and to examine matrices produced by tumor cells. The osteosarcoma cells were subdivided into four cell types: anaplastic, chondroblastic, osteoblastic, and osteocytic--giant cells were not considered in the present investigation. Compared to normal bone cells, no specific sign of malignancy was found. However, tumor cells seem to lose functional abilities, i.e. a modification of matrix. Consequently, tumor matrix has altered organic and inorganic components with impairment of collagen maturation and matrix mineralization. The alteration in both processes may be related to a diminished production of proteoglycans. The cytogenic hypothesis of a tumor stem cell may be supported by the identification of anaplastic osteosarcoma cells resembling immature reticulum cells. One may speculate on transformation of this cell type as a genetically predetermined osteoprogenitor cell of malignant potential.

Adult↗
PubMed1977

The effect of immunotherapy with BCG on the development of radiostrontium (90Sr)-induced osteosarcoma.

The development of radiostrontium-induced osteosarcoma was studied in BCG-treated and in untreated control mice. Within the observation period of 420 days after the administration of radiostrontium there was a total tumour-incidence of 89.5 and 90.5 per cent for the respective groups of animals. There was no statistically significant difference between the two groups, neither with regard to the time of the first roentgenographic appearance of the osteosarcoma, nor concerning the total tumour incidence , nor with regard to the distribution of the primary sites of the tumours. The tumours of the BCG-treated animals showed a clear tendency to a slower growth rate in comparison to that of the tumours in the control animals. This effect was probably immunological in nature. The mortality in osteosarcoma following radiostrontium administration, however, showed no significant difference between the two groups. Light microscopical and ultrastructural examination did not disclose any clear structural difference between the tumours from BCG-treated and untreated control animals.

Animals↗