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PubMed1977

Effect of xenogeneic immune RNA on normal human lymphocytes against human osteosarcoma cells in vitro.

New Zealand White rabbits were immunized with whole-cell suspensions of TE-85 cells (from a human osteosarcoma) maintained in tissue culture. RNA was extracted from the lymphoid tissues of the immunized animals. Normal human peripheral blood lymphocytes were pretreated with both the whole-cell immune RNA (IRNA) and the Sephadex column-eluted fractions of the whole-cell IRNA. Significant stimulation of the cytotoxic effect of the lymphocytes was observed following whole-cell IRNA pretreatment and pretreatment with peak III fractions eluted from the column. This increase in inhibition was observed whether the target cells were TE-85 (the immunizing cells), L.M. and M.Mc. (two unrelated osteosarcoma primary cell cultures), or TE-85-M-MSV cells (a cell line capable of producing a human osteosarcoma in immunosuppressed hamsters). No inhibition was observed when cells from other types of human tumors were used as target cells. The results suggested that the transferred immunity was directed against tumor-specific osteosarcoma antigens.

Antigens, Neoplasm↗
PubMed1978

FBJ osteosarcoma virus in tissue culture. III. Isolation and characterization of non-virus-producing FBJ-transformed cells.

Hamster and rat cell lines have been established that have been transformed by FBJ murine sarcoma virus (FBJ-MuSV) but that do not produce virus. The hamster cell line originated from an osteosarcoma that appeared in a hamster inoculated at birth with an extract of a CFNo1 mouse FBJ-osteosarcoma. The rat cell line was obtained by transferring the FBJ-MuSV genome to normal rat kidney cells in the absence of the FBJ type C virus (FBJ-MuLV), which, usually in high concentration, accompanies the FBJ-MuSV. Both transformed hamster and rat cell lines contain the FBJ-MuSV genome, which can be rescued by ecotropic and xenotropic murine type C viruses. This rescued genome produces characteristic FBJ-MuSV foci in tissue culture and, in appropriate animal hosts, induces osteosarcomas typical of those induced by FBJ-MuSV. FBJ-MuSV was isolated originally from a parosteal osteosarcoma that occurred naturally in a mouse. Since there was no previous history of passage of the agent through any other animal species, these non-virus-producing hamster and rat cells transformed by FBJ-MuSV should be very helpful in molecular studies examining the origin of spontaneous sarcoma genomes in mice.

Animals↗
PubMed1977

Angiographic features of osteosarcoma.

Arteriography was carried out in 64 cases of pathologically confirmed osteosarcoma to evaluate the angiographic features of this lesion. This investigation proved that a variety of angioarchitectures exist in osteosarcomas, mainly related to the histologic type of tissue as well as the degree of differentiation of a tumor. Fibroblastic and chondroblastic osteosarcomas proved to be less vascular than the osteoblastic type, while the most differentiated tumor appeared to be the least vascular. This technique proved useful in choosing the proper site, or sites, for biopsy as well as for determining the intra- and extraosseous extension of the tumor. Instances were also encountered in which it was of assistance in differentiating osteosarcoma from pathologically similar bone lesions.

Angiography↗
PubMed1978

Telangiectatic osteosarcoma.

Of the 242 cases of osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968 only one was found to represent telangiectatic osteosarcoma. Another case was recently diagnosed in our department. The characteristic morphologic features of these neoplasms were anaplastic stroma, high mitotic activity, osteoid-formation, widely anastomosing blood spaces, and alkaline phosphatase activity. The experience gathered indicates that telangiectatic osteosarcoma constitutes a histopathologic variant of genuine osteosarcoma with a serious prognosis, necessitating the same kind of treatment as for the genuine tumour.

Adolescent↗
PubMedDate not supplied

The use of naturally occurring cancer in domestic animals for research into human cancer: general considerations and a review of canine skeletal osteosarcoma.

For many years, research into human cancer has concentrated on human patients and on artificially induced neoplasms in inbred murine hosts. Cancer, however, affects a great variety of mammals, particularly those that have been domesticated. Suchf naturally occurring neoplasms are common in dogs, cats, cattle, horses, etc., and offer fertile ground for studies relating to epidemiologyf, etiology, immunobiology, and therapy. Canine osteosarcoma is described in detail. The clinicopathologic features of this canine tumor closely approximate that of human osteosarcoma and thus make canine osteosarcoma an invaluable comparative model. Canine osteosarcoma and other naturally occurring tumors lie intermediate between the mouse models and human cancer. The use of these veterinary models in the future fabric of cancer research will broaden its base and will influence our conceptual approach to research and clinical options.

Age Factors↗
PubMed1977

An animal model for human osteosarcoma.

Osteosarcomas formed in antilymphocyte serum (ALS)-treated hamsters when 2x10(6) TE-85 human osteosarcoma cells (maintained in tissue culture) infected with M-MSV (RD-114) virus were injected adjacent to the femur or the scapula; undifferentiated sarcomas formed when 1 x 10(6) cells were injected subcutaneously. Tumors were palpable 10 to 14 days after the cells were injected and grew progressively until the animals died (mean survival time was 30 days). All animals had pulmonary metastases. Neither the subcutaneous sarcomas nor the metastases contained bone or osteoid; however, the osteosarcomas adjacent ot the femur and scapula contained collagen, osteoid and calcified bone when observed by light and electron microscopy. These results indicate that the TE-85-M-MSV cell-ALS hamster system is an animal model for the study of osteosarcomas of human cell origin.

Animals↗
PubMed1977

An osteosarcoma cell and matrix retained morphogen for normal bone formation.

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.

Alkaline Phosphatase↗
PubMed1979

Alkaline phosphatase measurements of paired normal and osteosarcoma tissue culture lines obtained from the same patient.

Markedly different levels of alkaline phosphatase production have been found in paired osteosarcoma cells and normal skin fibroblasts grown in tissue culture from 12 patients with osteosarcoma. In all cases, the osteosarcoma line contains significantly more alkaline phosphatase than does the paired normal line from that same patient. These criteria may be useful in distinguishing osteosarcoma from normal fibroblast overgrowth in tissue culture.

Alkaline Phosphatase↗
PubMed1977

Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity.

Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high-dose methotrexate-leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high-dose methotrexate-leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.

Adolescent↗
PubMed1977

Metastatic osteosarcoma to lung: a clinicopathologic study of surgical biopsies and resections.

Metastatic tumor to the lungs is one of the most important factors in the poor prognosis of primary osteosarcoma of bone. Until recently, pulmonary resection alone was the only therapeutic method available to salvage these patients. Previous investigators have reviewed a number of clinical and pathologic parameters which may possibly relate to the prognosis of osteosarcoma and the occurrence of pulmonary metastases. The pathologic features of these latter lesions have received little attention other than to state that they generally are less differentiated than the primary tumor. A review of multiple pulmonary nodules resected from 15 patients has demonstrated that 66% of all lesions were essentially identical to the primary tumor. The 5-year survival from the original amputation was 33% in this series; however, it was not possible to prognosticate a favorable outcome from the metastasis, a similar type of observation which has been made by others in relation to the primary 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↗
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↗
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↗
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↗