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PubMedDate not supplied

Growth and hormone control mechanisms in osteosarcoma. Evidence for a new therapeutic approach.

The association between osteosarcoma and growth, including altered carbohydrate metabolism has been investigated in 5 osteosarcoma patients. Serum from an adolescent osteosarcoma patient has been noted to consistently enhance 3-H-thymidine uptake in cultured chondrocytes and tumor cells. Females survive osteosarcoma more frequently than males. In vitro serum-enhanced proliferation of osteosarcoma cells is suppressed by estradiol.

Adolescent↗
PubMed1998

Prognosis of osteosarcoma with pulmonary metastases at initial presentation is not dismal.

Prognosis of osteosarcoma has been improved markedly with the introduction of effective, intensive chemotherapy. However, there are many reports that indicate that the prognosis of osteosarcoma with pulmonary metastases at the initial presentation is poor. One hundred seventeen patients with osteosarcoma involving the extremities were treated at the Chiba Cancer Center from 1976 to 1995. Of these, nine (7.6%) patients had pulmonary metastases at initial presentation; these nine patients are the subjects of this article. There was an average of 0.9 pulmonary metastatic lesions at initial presentation seen on plain chest radiographs, an average 2.9 lesions seen on computed tomograms of the chest, and an average 12.7 lesions found at thoracotomy in these nine patients. The pulmonary metastatic lesions that could not be detected by computed tomography of the chest were resected by thoracotomy. Three patients died, and six patients are alive, with the 5-year survival being 64.8%. Intensive chemotherapy and aggressive surgical therapy were done for these patients with osteosarcoma with pulmonary metastases at initial presentation, and it is thought that this improved the prognosis of these patients. Pulmonary metastases of osteosarcoma at initial presentation do not always indicate a hopeless prognosis.

Adolescent↗
PubMed2001

Primary osteosarcoma of the distal femur in two consecutive brothers.

The following report describes two consecutive brothers from a nonimmigrant family, with no identifiable predisposing factors, who presented with osteosarcomas of their distal femurs, one at the age of 18 years and the other at the age of 21 years. Until a cost-effective program is developed to screen for osteosarcoma, a detailed family history should be obtained from every new patient with osteosarcoma and parents should be urged to schedule early evaluations of siblings with complaints of painful extremities. Increased frequency of cytogenetic studies to screen for genetic abnormalities in patients with osteosarcoma is recommended to help elucidate the cause of osteosarcoma.

Adolescent↗
PubMed2002

Expression of CD44 isoforms correlates with the metastatic potential of osteosarcoma.

CD44 is a family of cell surface glycoproteins that not only function as receptors to hyaluronan and other extracellular matrix ligands but also is implicated in the invasiveness and metastasis of malignancies. The expression of CD44 and its variant isoforms was evaluated by immunohistochemistry in primary osteosarcoma, and the metastatic significance and prognostic relevance were assessed. Fifty formalin-fixed, paraffin-embedded conventional osteosarcoma samples were immunostained with monoclonal antibodies to CD44s, CD44v5, and CD44v6. When more than 50% of the tumor cells were stained, the result was regarded as ++ (overexpression). Staining patterns of CD44 mainly were membranous with a minor cytoplasmic pattern contribution. CD44s was overexpressed in 16% (eight of 50), CD44v6 in 20% (10 of 50), and CD44v5 in 46% (23 of 50) of the osteosarcomas. Of 26 patients with metastasis, CD44s was overexpressed in six (23%), CD44v6 in four (15%), and CD44v5 in 17 (65%). Overexpression of CD44v5 correlated significantly with metastasis. The survival rate of the patients in the CD44v5-positive (overexpressed) group was significantly lower than that of the patients in the CD44v5-negative group. Overexpression of CD44v5 may play a role in the metastatic behavior of osteosarcoma and may be a prognostic parameter of osteosarcoma.

Adolescent↗
PubMed2002

Etiology of osteosarcoma.

Although the prognosis and quality of life of patients with osteosarcoma were improved significantly during the past decades, the pathogenesis and etiology of this disease remain obscure. Significant interest and effort in this cancer led to the identification of numerous etiologic agents. Several chemical agents such as beryllium, viruses such as FBJ, subsequently found to contain the src-oncogene, and radiation were shown to be potent inducers of osteosarcoma. Paget's disease, electrical burn, or trauma all are thought to be other factors that may contribute to the pathogenesis. More recently, patients with hereditary diseases such as Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were found to have an increased risk of having osteosarcoma develop. During the past few years, the molecular analysis brought a wealth of new information with numerous genes that were associated with osteosarcoma and its clinical disease progression. They can be categorized into self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue evasion and metastasis. Although the understanding of these processes in osteosarcoma still is incomplete, it may have the potential to significantly affect the patient care in the future.

Animals↗
PubMed1996

Metastatic osteosarcoma of the kidney presenting as renal hemorrhage.

PURPOSE: Renal osteosarcoma may arise as a metastasis from a primary bone osteosarcoma or as a primary renal tumor. Metastatic renal osteosarcoma has been found at autopsy in approximately 10% of patients who die of this disease. PATIENT AND METHODS: A case report of a young Chinese patient presenting with acute onset of renal infarction and hemorrhage from a renal metastasis of osteosarcoma is presented, as well as a review of the literature. RESULTS: Some patients with solitary renal metastatic osteosarcoma may have long-term disease-free survival after nephrectomy. Early diagnosis and thus increased awareness of this condition is important.

Adult↗
PubMedDate not supplied

Osteosarcoma associated with absent thumbs: a report of two cases.

An 8-year-old Hispanic boy with a hypoplastic left thumb, absent right thumb, and short stature experienced right leg pain and limp. A right tibial lesion was imaged and found to be osteosarcoma on biopsy. A 6-year-old Hispanic girl with congenitally absent thumbs experienced a pathologic fracture of her left femur after a minor sports injury. The radiologic abnormality seen was diagnosed as osteosarcoma on biopsy. Both patients continue to do well after intensive preoperative and postoperative high-dose chemotherapy and definitive reconstructive limb surgery. Osteosarcoma has been linked to several congenital syndromes in which absent thumbs are a feature. These two patients with absent thumbs and no definable syndrome experiencing osteosarcoma suggest that congenitally absent thumbs might be a risk factor for osteosarcoma in the absence of a syndrome.

Bone Neoplasms↗
PubMedDate not supplied

Thyroid carcinoma after successful treatment of osteosarcoma: a report of three patients.

We report three cases of papillary thyroid carcinoma occurring after successful treatment of osteosarcoma. Only one of the three patients received radiation therapy (to the chest) as part of the primary treatment of osteosarcoma. The onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of osteosarcoma therapy. All patients are alive and disease-free from both malignancies. Whereas the association between osteosarcoma and thyroid carcinoma has not previously been recognized, there have been five case reports of these two entities occurring in the same patient. Three of these cases occurred in patients with Werner syndrome. None of the patients reported here had physical stigmata of Werner syndrome or a family history consistent with a hereditary cancer syndrome. Thyroid carcinoma occurs infrequently in patients with osteosarcoma, but in view of the rarity of these two disorders, this association may represent an inherited predisposition to these malignancies.

Adolescent↗
PubMed2003

Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification.

The purpose of this study was to investigate whether Her-2/neu expression at diagnosis of osteosarcoma could provide biologic and prognostic information that predicts the risk of pulmonary metastases and outcome. Human epidermal growth factor (Her-2/neu) expression in 25 initial pretreatment osteosarcoma biopsies and 12 posttreatment pulmonary metastatic osteosarcoma resection specimens was assessed by standard immunohistochemical techniques on formalin-fixed paraffin-embedded tissue. As a screening analysis to determine if gene amplification may be a mechanism for increased Her-2/neu expression, FISH analysis was conducted on seven Her-2/neu immunostain-positive samples and five Her-2/neu immunostain-negative samples. Cytoplasmic Her-2/neu reactivity was identified in 11/25 (44%) of primary tumors and in 7/12 (58%) resection specimens from pulmonary metastases. Cytoplasmic Her-2/neu expression was associated with shorter overall metastasis-free survival. Her-2/neu gene amplification was identified by FISH analysis in six of the seven immunostain-positive samples but was also identified in two of the five immunostain-negative samples. Her-2/neu expression in patients with osteosarcoma is associated with an increased risk of metastasis and may define a subset of patients with a more aggressive tumor phenotype. Her-2/neu gene amplification may provide a mechanism for Her-2/neu overexpression in certain cases of osteosarcoma. Whether Her-2/neu expression influences outcome needs to be examined further in a prospective fashion. The hope is that Her-2/neu expression will identify patients who may benefit from the addition of directed biologic therapy.

Adolescent↗
PubMed2004

Simultaneous osteosarcoma lung metastasis and second primary lung cancer.

Second malignant neoplasms (SMNs) after treatment of children and adolescent cancers have been extensively studied. Lung cancer as an SMN is rare in all type of primary cancer in children and in osteosarcoma as well. The authors reviewed all cases of osteosarcomas treated at their institution from 1975 to 2000 and found 22 cases of SMN, only 1 involving lung cancer. The authors describe this latter case, a 17-year-old girl with a localized osteosarcoma of the tibia who developed simultaneously lung metastases of osteosarcoma and a primitive lung adenocarcinoma only 18 months from the diagnosis. Lung cancer is unusual in youths as a primary malignancy or as a second primary malignancy. The occurrence of a primitive lung cancer together with lung metastases from osteosarcoma is even more unusual, and examination of all new lung nodules is highly recommended.

Adenocarcinoma↗
PubMed2003

Metachronous osteosarcoma: a report of five cases.

Five patients with primary osteosarcoma who were treated effectively with chemotherapy and resective surgery and in whom a metachronous tumor subsequently developed in another site but who never had evidence of pulmonary metastases are described. The original bone scans of the five patients showed only the primary site as being involved. After diagnosis and treatment of the initial tumor, at intervals ranging from 12 to 78 months (average, 39 months) another osteosarcoma developed in the patients at a distant bony site. After diagnosis and treatment of the second osteosarcoma, followup of these patients for a mean of 77 months (range, 24-96 months) after the appearance of the metachronous tumor and for a mean of 118 months (range, 99-150 months) after the diagnosis of the primary lesion showed that none had pulmonary metastases develop. No recurrences of the local tumors have occurred and four of the patients currently are alive and free of disease. One of the patients had a fatal acute myelogenous leukemia develop 144 months after the discovery of the primary osteosarcoma and 86 months after the appearance of the metachronous disease. At the time of her death, however she had no evidence of osteosarcoma in any site.

Adolescent↗
PubMed2005

Height as a risk factor for osteosarcoma.

Previous investigations have suggested that osteosarcoma may be associated with a taller stature, but the relationship between height and osteosarcoma remains controversial. Height at diagnosis was evaluated in a continuous series of 962 osteosarcoma subjects treated between 1981 and 2001. Patients diagnosed during growth (group 1) were separated from those diagnosed in adulthood (group 2). Height (H) and final height (FH) were expressed as standard deviation scores (SDS), calculated by national reference data. Group 1 subjects were above the 50th centile and their mean H-SDS values (0.31 +/- 1.1) were significantly higher than the mean FH-SDS values (P < 0.0001) of the group 2 subjects, both in males and females. In contrast, the mean FH-SDS (0.01 +/- 1.1) of group 2 did not differ from that of the reference population. The highest incidence of osteosarcoma was at 12.5 years in females, 14.5 years in males. These data confirm previous observations of an association between osteosarcoma development and height, at least in growing individuals. The higher incidence during the pubertal spurt, in the anatomic sites of greater growth and in taller individuals, suggests that growth factors play an important role in the pathogenesis of this bone cancer.

Adolescent↗
PubMed2005

Non-myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma.

The prognosis of patients with relapsed osteosarcoma is dismal despite the use of intensive chemotherapy. We describe a patient with refractory osteosarcoma who underwent non-myeloablative peripheral blood stem cell transplantation (PBSCT) from an human leukocyte antigen (HLA)-identical sibling during a third complete remission. The patient suffered pulmonary relapse after the transplantation. Cyclosporin A withdrawal induced a graft-vs.-osteosarcoma effect and graft-vs.-host disease, but eventually the tumor progressed. Although our experience in this case suggested the presence of a graft-vs.-osteosarcoma effect during non-myeloablative allogenic PBSCT, this strategy might have limited value for refractory osteosarcoma with rapid growth kinetics.

Adolescent↗
PubMed1994

Periosteal osteosarcoma of the femur with bone marrow involvement: a case report.

Periosteal osteosarcoma is an exceedingly rare type of chondroblastic osteosarcoma, showing rather better prognosis, and secondary bone marrow involvement is unusual. A case of a 22 year old male with periosteal osteosarcoma of the right femur with an associated bone marrow lesion is presented. The juxtacortical tumor, 16 x 11 x 9 cm, was located on the bone cortex of the upper diaphysis and extended into the surrounding soft tissues. A minimal bone marrow lesion was present, although the bone cortex was quite intact. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. The bone marrow lesion, interestingly, contained both multiple nodules of well-differentiated chondrosarcomatous components and a few demarcated foci of atypical spindle cells producing a fine osteoid matrix. It was reasonable to conclude, therefore, that this tumor was a periosteal osteosarcoma with an unusual secondary bone marrow lesion rather than a conventional (central) chondroblastic osteosarcoma with soft tissue invasion. The patient's good prognosis with no tumor recurrence or metastasis during more than 7 years follow-up after surgery supports this conclusion.

Adult↗
PubMed1997

Osteosarcoma and pulmonary metastases: 15-year experience from a single institution.

BACKGROUND: The outcome of management in patients with osteosarcoma and pulmonary metastases at a Sydney teaching hospital was reviewed. METHODS: A retrospective review was undertaken of all patients diagnosed with osteosarcoma and treated by the Bone and Soft Tissue Unit and the Medical Oncology Department, Royal Prince Alfred Hospital between 1979 and January 1995. Information was collected on demographics, tumour site, tumour histology, primary management including surgery and adjuvant therapy, and the subsequent development and management of pulmonary metastases. RESULTS: A total of 56 patients with localized osteosarcoma was seen. Overall survival and survival following pulmonary metastases was assessed. There were 33 (59%) males and 23 (41%) females, with a median age of 27 years. Survival at 5 years, for patients with non-axial osteosarcoma was 60% (95% CI, 44-77%). Pulmonary metastases without other metastatic disease being apparent, developed in 22 patients, of whom 12 underwent surgical resection. The median disease-free interval of these latter patients was 20 months (95% CI, 8-32 months). Median survival among patients not undergoing surgical resection was 5 months from detection of metastases. Patients undergoing resection of pulmonary metastases had a median survival of 17 months following detection of pulmonary metastases (95% CI, 7-27 months). Actuarial 5-year survival was 16% (95% CI, 0-42%). CONCLUSIONS: A small proportion of patients with resectable pulmonary metastases from osteosarcoma achieve long-term disease-free survival following surgical resection. It is not possible to accurately identify these patients prospectively.

Actuarial Analysis↗
PubMedDate not supplied

Resection of pulmonary metastases in canine osteosarcoma: 36 cases (1983-1992).

Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both. Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.

Animals↗
PubMed2004

Examination of the signal transduction pathways leading to activation of gelatinolytic activity by interleukin-1alpha and Porphyromonas gingivalis in human osteosarcoma cells.

BACKGROUND: Recently, evidence show that matrix metalloproteinases (MMP) play an important role in the pathogenesis of periodontal diseases. However, the mechanisms and signal transduction pathways involved in the production of MMPs in human osteosarcoma cells are not fully understood. OBJECTIVES: The purpose of this study was to investigate the gelatinolytic activity in human osteosarcoma cells stimulated with interleukin-1alpha (IL-1alpha) or Porphyromonas gingivalis in the absence or presence of SB203580 (p38 inhibitor), U0126 [mitogen-activated protein kinase kinase (MEK) inhibitor], and LY294002 [phosphatidylinositaol 3-kinase (PI3K) inhibitor]. METHODS: IL-1alpha and the supernatants of P. gingivalis were used to evaluate gelatinolytic activity in human osteosarcoma cells using gelatin zymography. Furthermore, to search possible signal transduction pathways, SB203580, U0126, and LY294002 were added to test how they modulated the gelatinolytic activity. RESULTS: Gelatin zymography demonstrated that the latent proforms of gelatinases MMP-2 and MMP-9 were released by human osteosarcoma cells. Secretion of MMP-9 was time-dependent by stimulating with IL-1alpha or P. gingivalis. In addition, SB203580, U0126, and LY294002 significantly reduced the IL-1alpha or P. gingivalis-stimulated MMP-9 production, respectively (p < 0.05). However, none of the kinase inhibitors affected the MMP-2 level compared with the control during the 4-day culture period (p > 0.05). CONCLUSIONS: Our findings demonstrated that IL-1alpha and P. gingivalis enhance MMP-9 production in human osteosarcoma cells, and the signal transduction pathways p38, MEK, and PI3K are involved in the inhibition of MMP-9. SB203580, U0126, and LY294002 suppress MMP-9 production and/or activity and may therefore be valuable therapeutics in MMP-mediated periodontal destruction, and might be proved clinically useful agents, in combination with standard treatment modalities, in the treatment of periodontitis.

Culture Media, Conditioned↗
PubMed2005

Assessment of cytological criteria for diagnosing osteosarcoma in dogs.

OBJECTIVES: To evaluate the specific cytological criteria of osteosarcomas in dogs. METHODS: Significant cytological characteristics of osteosarcoma and benign mesenchymal bone proliferations were determined from imprint smears of 25 dogs with osteosarcoma (group 1) and 20 dogs admitted for removal of surgical bone implants after uncomplicated healing of bone fractures (group 2). RESULTS: Mild to moderate cellular necrosis occurred frequently in patients with osteosarcoma. The cytoplasm of osteoblasts was pale blue to blue with a more pronounced basophilia in group 2. In 48 per cent of the patients in group 1, but none in group 2, osteoblasts showed a slight to moderate eosinophilic cytoplasmic granulation. In both groups, osteoblasts contained one red to pale blue nucleus with one or two grey-red to blue nucleoli in group 2. Forty-four per cent of animals in group 1 had osteoblasts with more than two nucleoli per nucleus. The median nuclear:cytoplasmic ratio was higher in group 1 (1:2.0) than in group 2 (1:3.5). Osteoblasts in group I were frequently seen to have a clumped chromatin pattern and showed significantly more criteria of malignancy (median six criteria per patient) than those in group 2 (median two criteria per patient). In group 1, mitoses of osteoblasts were detectable in 23 of 25 dogs, whereas only one dog in group 2 had evidence of mitotic osteoblasts. CLINICAL SIGNIFICANCE: Cytological criteria can be helpful in the diagnosis of canine osteosarcoma.

Animals↗