Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parameters that predict tumor aggressiveness or response to therapy are potentially useful in selecting the most appropriate treatment. In theory, the biologic aggressiveness of an untreated bone tumor may be reflected in bone scan parameters. The purpose of this study was to assess the usefulness of bone scintigraphy as a predictive indicator of subsequent metastasis in 25 dogs with primary osteosarcoma. Dogs received radiotherapy and/or intra-arterial cisplatin prior to limb-sparing surgery. Quantitative bone scintigraphy of the tumor was performed prior to treatment (25 dogs) and following treatment but prior to limb-sparing surgery (22 dogs). All dogs developed metastasis at a median time of 202 days (range, 41-444 days) after initiation of treatment. A statistically significant relationship was identified between time to metastasis and: (1) the radiographic tumor area, (2) the pretreatment ratio of mean counts per pixel in tumor-to-adjacent nontumor bone (T/NTT), and (3) the pre:post-treatment T/NTT. Larger tumor area and high pretreatment tumor activity were associated with earlier metastasis. Tumors characterized by greater decreases in scintigraphic uptake after treatment were associated with earlier metastasis. These data suggest that osteosarcomas with high pretreatment mean counts per pixel signify aggressive tumors subject to early metastasis.
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PMID:Relationship between quantitative tumor scintigraphy and time to metastasis in dogs with osteosarcoma. 163 48

The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable.
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PMID:Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. 171 20

A case of primary ovarian osteosarcoma is reported with a review of the literature. A perimenopausal woman presented with a calcific adnexal mass seen on abdominal radiography, surgical exploration revealed no gross evidence of metastatic disease. Adjuvant chemotherapy was administered due to the reported aggressiveness of this rare tumor. Following eight courses of cisplatin-doxorubicin combination chemotherapy, the patient is without evidence of disease. A differential diagnosis for extensively calcified adnexal masses is provided. Additionally, a rationale for adjuvant chemotherapy is discussed.
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PMID:Pure primary osteosarcoma of the ovary presenting as an extensively calcified adnexal mass: a case report and review of the literature. 225 67

More aggressiveness in treatment of childhood malignancies has had an evident impact on survival and rate of cure but, it has also allowed us to discover long-term effects of these treatments, and second malignant tumors of them. Between 1970 and 1993, 472 cases of malignant tumors in childhood were diagnosed in our department. Six of them (1.27%) developed a second tumor (five malignant and one benign). Relationship between first and second tumors are: seven years old boy, cervical lymphosarcoma-thyroid carcinoma; eleven years old boy, osteogenic sarcoma-vesical carcinoma: two years and six months old boy, cerebellar astrocytoma-soft tissue osteogenic sarcoma; five years old girl. Wilm's tumor-scapular osteogenic chondroma; one year and a half old girl, abdominal neuroblastoma-granulocytic sarcoma (chloroma); twelve years old boy. Hodgkin's disease-acute myeloblastic leukemia. All of them were clearly related to concogenic effect of radiation or chemotherapy.
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PMID:[Second tumors in childhood]. 776 70

The clinical, radiologic, and pathologic features of 306 osteoblastomas were analyzed. Seventy-five were Mayo Clinic cases and 231 were from consultation files. Males outnumbered females two to one. The age range was 6 months to 75 years (mean age, 20.4 years). The vertebral column including the sacrum was the most frequent site (32%). Pain was the usual complaint and neurologic findings were associated with vertebral tumors. Although most tumors were well circumscribed, cortical expansion and destruction were common radiographic findings (39%), and 12% had features suggestive of malignancy. Large, epithelioid osteoblasts were seen in 24% and were the predominant cellular element in 10%. A distinctive epithelioid multifocal pattern was recognized. Recurrence rates were 16% (Mayo Clinic cases) and 21% (consultation cases). Tumors involving the central neuraxis were associated with greater morbidity and mortality. Aggressive behavior is within the biologic spectrum of osteoblastomas, and histopathology alone does not appear to be a reliable predictor of aggressiveness. The most important differential diagnosis is osteosarcoma.
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PMID:Osteoblastoma: clinicopathologic study of 306 cases. 811 12

In osteosarcoma, resistance to chemotherapy and metastatic spread are the most important mechanisms responsible for the failure of current multimodal therapeutic programs. We have shown previously that overexpression of the MDR1 gene product P-glycoprotein is the most important predictor of an adverse clinical course in patients with osteosarcoma. treated with chemotherapy. In this study, we analyzed the relationship between P-glycoprotein expression and local aggressiveness and systemic dissemination of multidrug-resistant (MDR) human osteosarcoma cells. Compared to parental sensitive cells, MDR cells showed a decreased tumorigenicity,and metastatic ability in athymic mice, together with a reduced migratory and invasive ability and a lower homotypic adhesion ability in vitro, suggesting that P-glycoprotein overexpression is associated with a less malignant phenotype. These experimental observations were confirmed by clinical data. In fact, the time of appearance of lung metastases in a series of osteosarcoma patients treated with chemotherapy was significantly shorter in the group of cases with no expression of P-glycoprotein in the primary lesion compared to the group with P-glycoprotein overexpression. Moreover, the incidence of P-glycoprotein overexpression was found to be higher among patients with localized disease at the clinical onset than in patients with evidence of metastasis at the time of diagnosis. These data indicate that, in osteosarcoma, the MDR phenotype is not associated with a more aggressive behavior both in vitro and in clinical settings, suggesting that the previously shown association of the MDR phenotype with a worse outcome in osteosarcoma is not related to a higher metastatic ability of cells with P-glycoprotein overexpression but is more likely due to their lack of responsiveness to cytotoxic drugs.
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PMID:Multidrug resistance and malignancy in human osteosarcoma. 862 24

Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a transmembrane tyrosine kinase encoded by the met proto-oncogene, has been associated with tumor progression in different human carcinomas. More recently, the Met/HGF receptor has also been described in tumor cell lines of mesenchymal origin, suggesting the existence of an autocrine loop that may contribute to the pathogenesis of sarcomas. In this study, we analyzed the expression of Met/HGF receptor by Western blotting and immunohistochemistry in frozen samples of 87 primary tumors of bone and soft tissues. Among benign tumors, overexpression was consistently found only in giant-cell tumor, a locally aggressive lesion that may also, although rarely, spread to the lung. Among malignant lesions, the presence of the Met/HGF receptor was detected in a relevant percentage of primaries and in almost all of the recurrences. The highest levels of Met/HGF receptor were found in osteosarcoma, a highly aggressive tumor that typically permeates the host bone and rapidly expands to the soft tissues. On the contrary, only low levels of Met/HGF receptor were found in chondrosarcoma, a slowly growing tumor that usually expands without massive destruction of the surrounding structures. These data indicate an association of Met/HGF expression with local aggressiveness in human mesenchymal tumors. The finding of Met/HGF receptor overexpression in all of the osteosarcomas suggests a role for the met proto-oncogene in the pathogenesis of this tumor.
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PMID:Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors. 886 70

The introduction of aggressive chemotherapy in the treatment of osteosarcoma has improved the long-term outcome for these patients. With the increasing aggressiveness of chemotherapy protocols, hematopoietic growth factors have emerged as useful adjuncts involving, in some cases, rescue by peripheral blood stem cell (PBSC) infusion to assist faster recovery and maintain relative dose intensity. To evaluate the number of PBSCs needed, we analyzed the number of CD34+ cells and hematopoietic progenitor cells in the peripheral blood of 16 patients with osteoblastic, condroblastic and fibroblastic osteosarcoma enrolled in an Istituto Ortopedico Rizzoli-Scandinavian Sarcoma Group (IOR-SSG) pilot study, consisting of two cycles of preoperative high dose chemotherapy. The blood samples were studied at different times. The CD34+ cells were analyzed by flow cytometry and the hematopoietic progenitor cells were analyzed by tissue culture clonogenic assay. In comparing the two courses of chemotherapy, we observed that modification of the mean values of WBC, CD34+ and CFU-GM were very similar. The second course of chemotherapy seemed to induce greater hematological toxicity. All three parameters showed good correlation. The results demonstrated that the best time to collect PBSC by means of leukapheresis is post G-CSF used as rescue after ifosfamide treatment. We verified the ability of G-CSF to mobilize PBSCs in patients with osteosarcoma through cytofluorimetric analysis of CD34+ cells and their clonogenic capability. Moreover, during this preoperative treatment, we identified the best time to collect a sufficient number of PBSCs, that is after 9-10 days of G-CSF treatment following the first cycle of ifosfamide.
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PMID:Cd 34+ cells and clonogenicity of peripheral blood stem cells during chemotherapy treatment in association with granulocyte colony stimulating factor in osteosarcoma. 1046 32

Bone morphogenetic proteins, which are capable of inducing mesenchymal tissue to form bone in mammals, have been implicated as important in normal skeletal development. The expression of bone morphogenetic proteins and their receptors were studied in 36 osteosarcoma specimens, six Ewing's sarcomas, 20 synovial sarcomas, and 20 chondrosarcomas by reverse transcriptase-polymerase chain reaction, and the findings were correlated with clinical data. Bone morphogenetic protein-2, and -4 messages were detected in most sarcoma samples. Bone morphogenetic protein-6 expression was detected in 22 of 32 osteosarcomas and seven of eight chondrosarcomas. Bone morphogenetic protein-7 and receptor IB were not detected in sarcoma samples but were detected in three osteosarcoma cell lines and one malignant fibrous histiocytoma cell line. Expression of bone morphogenetic protein receptor II was found in 25 of 36 osteosarcomas, eight of 20 chondrosarcomas, four of six Ewing's sarcomas, and 15 of 20 synovial sarcoma samples. Expression of bone morphogenetic protein type II receptor was found to correlate with metastasis in osteosarcomas, which suggests that the bone morphogenetic protein pathway may participate in tumor aggressiveness or progression. The expression of bone morphogenetic protein receptor II in metastatic synovial sarcoma and dedifferentiated chondrosarcoma lesions also supports this hypothesis. The current study showed that the ligands for bone morphogenetic protein receptors, bone morphogenetic proteins-2, -4, and -6 also are expressed in osteosarcoma and other sarcoma tissues, indicating a potential for autocrine or paracrine growth stimulation in these tumors.
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PMID:Expression of bone morphogenetic proteins and receptors in sarcomas. 1062 2

Alkaline phosphatases are a family of glycoproteins that are able to hydrolize various monophosphate esters at a high pH optimum. Liver/bone/kidney (L/B/K) alkaline phosphatase (ALP) is one of the four major isoenzymes that belong to this family. Apart from its role in normal bone mineralization, other functions of L/B/K ALP remain obscure, both in physiological and in neoplastic conditions, including the bone-forming tumor osteosarcoma. In this study, we transfected the U-2 OS osteosarcoma cell line, which does not show any basal expression of this enzyme, with the full-length gene of L/B/K ALP, and analyzed the in vitro and in vivo features of four transfectants showing different expression of L/B/K ALP. A reduced in vitro ability to invade Matrigel and to grow in a semi-solid medium, together with a lower tumorigenic and metastatic ability in athymic mice, was found to be associated with a high level of cell surface L/B/K ALP activity. Moreover, L/B/K ALP transfectants showed a reduced secretion of matrix metalloproteinase-9 enzyme. These findings indicate a loss of aggressiveness of osteosarcoma cells after the expression of L/B/K ALP on their surface and suggest a new role for this enzyme.
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PMID:Reversal of malignant phenotype in human osteosarcoma cells transduced with the alkaline phosphatase gene. 1070 92


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