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PubMed1995

Fluoride exposure and childhood osteosarcoma: a case-control study.

OBJECTIVES: This study tests the hypothesis that fluoride exposure in a nonoccupational setting is a risk factor for childhood osteosarcoma. METHODS: A population-based case-control study was conducted among residents of New York State, excluding New York City. Case subjects (n = 130) were diagnosed with osteosarcoma between 1978 and 1988, at age 24 years or younger. Control subjects were matched to case subjects on year of birth and sex. Exposure information was obtained by a telephone interview with the subject, parent, or both. RESULTS: Based on the parents' responses, total lifetime fluoride exposure was not significantly associated with osteosarcoma among all subjects combined or among females. However, a significant protective trend was observed among males. Protective trends were observed for fluoridated toothpaste, fluoride tablets, and dental fluoride treatments among all subjects and among males. Based on the subjects' responses, no significant associations between fluoride exposure and osteosarcoma were observed. CONCLUSIONS: Fluoride exposure does not increase the risk of osteosarcoma and may be protective in males. The protective effect may not be directly due to fluoride exposure but to other factors associated with good dental hygiene. There is also biologic plausibility for a protective effect.

Adolescent↗
PubMed2006

Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985-2004).

OBJECTIVE-To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival. DESIGN-Retrospective case series. ANIMALS-90 dogs with stage III osteosarcoma. PROCEDURES-Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis. RESULTS-Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases. CONCLUSIONS AND CLINICAL RELEVANCE-Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.

Animals↗
PubMed1978

Osteosarcoma. A multifactorial clinical and histopathological study with special regard to therapy and survival.

A multifactorial analysis was performed on all 153 unequivocal cases of genuine osteosarcoma recorded in the Swedish Cancer Registry for the years 1958 through 1968. Cases of so-called parosteal osteosarcoma, soft-tissue osteosarcoma and osteosarcoma secondary to Paget's disease of bone were not included. The osteosarcomas were subclassified as follows: osteoblastic (69 per cent), chondroblastic (19 per cent) and fibroblastic (12 per cent). The overall 5-year survival rate was 22 per cent; 55 per cent for those who had undergone amputation above the joint proximal to the involved skeletal part, 22 per cent for those amputated on the involved skeletal part, 11 per cent for those treated with local extirpation of the tumor, and 1 per cent in cases in which the lesion was not radically removed. Tumors of the femur, humerus and scapula were as malignant as axial tumors. The former carried a 5-year survival rate of 13 per cent, regardless of whether the patients had been treated with exarticulation or amputation on the involved skeletal part. Patients with axial tumors showed a 5-year survival rate of 15 per cent. These survival data suggest that proximal amputation alone might suffice for lesions situated distally to the knee and elbow joints, while tumors in the humerus and femur should be treated with amputation combined with multicytostatic treatment or immunotherapy and axial tumors with local resection and multicytostatic or immunologic treatment.

Adolescent↗
PubMed1994

Periosteal osteosarcoma and parosteal chondrosarcoma evaluated by double immunohistochemical staining. Report of 2 cases.

Differentiation of periosteal osteosarcoma and parosteal (periosteal) chondrosarcoma by conventional histology may be difficult. One case each of clinically and histologically proven periosteal osteosarcoma and parosteal chondrosarcoma were evaluated by a double-immunohistochemical staining method using proliferating cell nuclear antigen (PCNA) and S-100 protein (S-100). Conventional histology showed proliferation of both osteoblastic and chondroblastic cells in the periosteal osteosarcoma, while there was a growth of only chondroblastic tumor cells in the parosteal chondrosarcoma. Immunohistochemical studies indicated that the nuclei of chondroblastic cells recognized by S-100 were PCNA-negative, while osteoblastic stromal cells were PCNA-positive in the periosteal osteosarcoma. In contrast, chondroblastic cells in the parosteal chondrosarcoma were both S-100- and PCNA-positive. Our findings suggest that periosteal osteosarcoma is characterized by the proliferation of osteoblastic stromal cells, whereas parosteal chondrosarcoma is characterized by the proliferation of chondroblastic cells. This method of double immunohistochemical staining, using PCNA and S-100, may be useful in differentiating these chondroblastic tumors.

Adolescent↗
PubMed1995

Expression of p53 protein, PCNA, and Ki-67 in osteosarcomas of bone.

Expressions of p53 protein, a product of the tumor suppressor gene were studied in osteosarcomas relating to various prognostic factors. Thirty-four osteosarcomas were investigated immunohistochemically with a monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins and another clone PAb1801, which reacts with both wild- and mutant-type p53 proteins. The results were compared with expressions of proliferating cell nuclear antigen (PCNA) and Ki-67 providing a simple method for the assessment of growth fractions of tumors. PAb240 stained nuclei and cytoplasm of tumor cells in 8 of 34 osteosarcomas (23.5%), whereas PAb1801 reacted in all 34 osteosarcomas (100%). Fifteen tumors (44.1%) showed positivity for PAb1801 in more than half of the tumor cells. Twelve patients were alive and thirteen were dead. Tumors from 9 patients (75%) who survived revealed only focal positive immunoreactions with PAb1801 and tumors from 6 patients (46.1%) who died revealed diffuse reactions. Twelve cases (35.3%) showed a high PCNA index (> 40%) and fibroblastic osteosarcomas revealed the highest PCNA positivity. Twenty-two cases (64.7%) revealed a very low Ki-67 index (less than 10%) and Ki-67 index showed a good correlation with PCNA positivity (r = 0.6247). Expressions of both wild-and mutant-type p53 protein, PCNA, and Ki-67 were not correlated with other clinical or pathological parameters.

Adolescent↗
PubMed2006

Primary osteosarcoma in patients older than 40 years of age.

Among the 665 patients who registered at our hospital, we reviewed 39 cases of high grade primary osteosarcoma in patients who were older than 40 yr of age. The aim of this study was to determine if a primary osteosarcoma in older patients has different clinical features, and a poorer prognosis than in younger patients. Two evaluations were performed. In the first, an attempt was made to determine the possible prognostic factors such as gender, location, size, alkaline phosphatase, radiological findings, chemotherapy intensity, chemotherapy-induced tumor necrosis, and surgical margin. The second evaluation involved assessment of whether there were any significant clinical differences between older patients and adolescents. According to the results, a primary osteosarcoma in older patients did not reveal any significant prognostic variables. A primary osteosarcoma in older patients showed a poorer prognosis due to relatively unusual locations, common abnormal radiological findings, and a poor response to chemotherapy. Therefore, careful attention should be paid to making an accurate diagnosis and new strategies for more effective treatment, including chemotherapy, must to be developed in order to achieve long term survival in older patients with osteosarcoma.

Adult↗
PubMed2000

Expression of the SART1 tumor-rejection antigen in human osteosarcomas.

We recently reported a tumor-rejection antigen, SART1259, possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs). This study investigated the expression of SART1259 antigen in osteosarcoma and other skeletal malignant tumors to explore for a potential molecule for use in specific immunotherapy. The SART1259 antigen was detected in the cytosol fraction of 13 of 21 (62%) osteosarcoma cell lines and 3 of 8 (38%) osteosarcoma tissues, and 3 of 10 (30%) malignant fibrous histiocytoma (MFH) tissues. The HLA-A24+ and SART1259+ osteosarcoma cells were recognized by the HLA-A24 restricted and SART1 specific CTLs. These results raise a possibility that the SART1259 would be an appropriate molecule for use in specific immunotherapy of approximately one-third of HLA-A24+ patients with osteosarcoma and MFH.

Antigens, Neoplasm↗
PubMed2004

Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.

High-grade osteosarcoma is an extremely aggressive neoplasm, where over 80% of patients present with life-threatening micrometastases at diagnosis. Systemic control of the disease is therefore critical for the treatment of these patients and neoadjuvant chemotherapy using various drugs, including doxorubicin (DXR), which has been demonstrated to be the most effective regimen. Multidrug resistance (MDR) to some anticancer agents, including DXR, mediated by the MDR1 gene product P-glycoprotein (Pgp), has been shown to be a major cause of chemotherapy failure in osteosarcoma. We analyzed the effect of a cyclosporine A derivate Valspodar (PSC 833) on MDR human osteosarcoma cells. We also evaluated Pgp expression in sporadic appendicular canine osteosarcoma. Moreover, dogs were treated with combined administration of DXR and PSC 833. Several blood samples were collected for the determination of DXR and PSC 833 levels. PSC 833 induced a complete reversal of the resistant phenotype at concentrations compatible with the clinical use. Pgp was present in 12/18 (66.6%) of the cases. At the time of DXR administration, adequate blood concentrations of PSC 833, to provide a complete MDR reversal, were obtained without clinical or laboratory findings of toxicity. Combination therapy with DXR and PSC 833 allowed a 30% decrease in DXR dose infusion with equivalent therapeutic exposure. The high incidence of Pgp expression in osteosarcoma confers to the study a rationale for an effective regimen based on down-modulation of MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1985

The significance of calcified regional lymph nodes at the time of diagnosis of osteosarcoma.

The presence of lymph node metastases from osteosarcoma was rare at diagnosis, occurring in only four of 176 patients (2.3%) at St. Jude Children's Research Hospital. An additional patient presented with calcified lymph nodes, which were demonstrated to contain no evidence of metastatic osteosarcoma. These patients did not differ in race, sex or age at diagnosis from other osteosarcoma patients. Each of the four patients with lymph node metastases of osteosarcoma had tumors composed predominantly of the osteoblastic type. Regional nodal metastases, whether alone or in conjunction with other metastatic disease were a poor prognostic factor. Despite aggressive therapy, median survival was 8 1/2 months from diagnosis, which did not differ significantly from the survival achieved by other osteosarcoma patients who had other hematogenous metastases.

Adolescent↗
PubMedDate not supplied

Proximal radial and distal humeral osteosarcoma in 12 dogs.

Twelve dogs were diagnosed with osteosarcoma of the proximal radius or distal humerus from 1990 to 2002, representing 1.0% of all dogs diagnosed with appendicular osteosarcoma. The median body weight (29.8 kg) was significantly less than that of dogs with appendicular osteosarcoma at other sites. Ten dogs were treated with amputation and chemotherapy. These dogs had a metastatic rate of 60%, a median metastasis-free interval of 356 days, and a median survival time of 824 days. There were no significant differences in metastasis-free interval or survival time between dogs with osteosarcoma of the proximal radius or distal humerus and dogs with appendicular osteosarcoma at other sites.

Amputation, Surgical↗
PubMed1999

Protease expression in dedifferentiated parosteal osteosarcoma.

BACKGROUND: Parosteal osteosarcoma with dedifferentiation provides a useful model to study tumor progression from an indolent locally aggressive neoplasm to highly lethal metastasizing malignancy. Up-regulation of the proteolytic enzymes participating in stromal degradation is known to promote invasive growth and metastasis of several human and experimental tumors. METHODS: The expression patterns of urokinasase plasminogen activator (u-PA), its cell-surface receptor (u-PAR), and cathepsin B were analyzed by immunohistochemical techniques in 11 cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal osteosarcoma. RESULTS: Both enzymes and the receptor were coexpressed in most tumor cells of parosteal and dedifferentiated parosteal osteosarcoma. Their expression was strikingly enhanced in the dedifferentiated high-grade component of the tumors. Tumor cells involved in bone production (ie, those adjacent to tumor produced bone trabeculae) exhibited equally strong expression of u-PA, u-PAR, and cathepsin B, regardless of their histologic grade. Expression of u-PA, u-PAR, and cathepsin B was undetectable in the "normalized" cells embedded in the well-developed tumor bone trabeculae. CONCLUSION: These data indicate that u-PA and its interacting molecules, such as u-PAR and cathepsin B, may have some contributory effects on the metastatic potential of tumor cells in dedifferentiated parosteal osteosarcoma.

Bone Neoplasms↗
PubMed2001

Osteosarcoma of the urinary bladder occurring simultaneously with prostate and bowel carcinomas: report of a case and review of the literature.

Osteosarcoma is a very rare tumor of the urinary bladder, with only 28 well-documented cases reported in the literature to date. The tumors have characteristically been large and polypoid and most commonly have been located in the trigone. An abdominal mass has occasionally been palpated, and rectal examination has frequently revealed a mass in the region of the bladder. The prognosis for this tumor is very poor. In this report, a 75-year-old man with hematuria was found to have a primary osteosarcoma of the urinary bladder with superficial invasion. Radical cystoprostatectomy and ileal conduit urinary diversion were performed. During surgery, a synchronous mucinous adenocarcinoma of the ascending colon was found, and a right hemicolectomy was performed. Prostatic adenocarcinoma was discovered from the histology. The patient died 7 months after surgery with systemic spread of the osteosarcoma. Osteosarcoma of the bladder should be distinguished from other bladder tumors that may be associated with bone formation, such as carcinosarcomas and transitional cell carcinomas with osseous metaplasia of their stroma, both of which have a better prognosis than osteosarcoma.

Adenocarcinoma↗
PubMed2006

Postirradiation osteosarcoma of the mandible with heterologous differentiation.

Heterologous differentiation in osteosarcoma is rare, with only 17 cases previously described in the literature. We report a case of a mandibular osteoblastic osteosarcoma with rhabdomyosarcomatous differentiation in a 45-year-old man who had a history of Hodgkin lymphoma that was treated with chemotherapy and radiation. Radiographs showed a destructive osteoblastic tumor of the mandible that was proven by biopsy to be osteosarcoma. After the patient underwent neoadjuvant chemotherapy, the tumor was resected. It contained a high-grade osteosarcoma composed of osteoblastic and chondroblastic elements that had no definitive response to therapy. Within the center of the lesion was a discrete focus of pleomorphic cells with rhabdomyosarcomatous differentiation that was confirmed by immunohistochemical stains for desmin, myogenin, and myogenic differentiation antigen 1. The patient received additional chemotherapy and radiation therapy but developed lung, brain, and spinal metastases and died 7 months after surgery. To our knowledge, this is the first report of osteosarcoma of the mandible with heterologous differentiation.

Cell Transformation, Neoplastic↗
PubMed1999

[Standards, options and recommendations (SOR) for diagnosis, treatment and follow-up of osteosarcoma. Groupe de travail SOR].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. For pediatric issues, this project is a collaboration between the FNCLCC and the French Society of Pediatric Oncology (SFOP). The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for the clinical care of osteosarcoma in children and adult. METHODS: Data have been identified by literature search using Medline (1985-december 1998) and the expert groups personal reference lists. The main criteria considered were incidence, risk factors, prognostic factors and efficacy of treatment. Once the guidelines were defined, the document was submitted for review to 27 national and international independent reviewers, and to the medical committees of the 20 French Cancer Centres and, in particular, the 4 which have particular expertise in pediatric cancer management. RESULTS: The main recommendations for osteosarcoma management are that: 1) the clinical diagnosis is based on appropriate clinical and radiological findings; 2) the final diagnosis is pathological and the biopsy should be performed by the surgeon who will subsequently perform the definitive surgery; 3) surgical biopsy must be of adequate size and performed by an experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres. Inclusion of high dose methotrexate is recommended for children, and the dose of methotrexate must be adapted for adults. Inclusion of children in SFOP protocols and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases which may be curative. Amputation is rarely appropriate. Inclusion of children in SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma is recommended; 6) at the present time, there are no clear data on which to base guidelines for timing and duration of follow-up studies in this condition.

Antineoplastic Agents↗
PubMed1998

[Cytogenetic changes in low grade central osteosarcomas].

Low grade central osteosarcomas are a group of rare bone neoplasms morphologically simulating benign bone tumors or tumor-like lesions (fibrous dysplasia, nonossifying fibroma, osteoblastoma, chondromyxoidfibroma or aneurysmal bone cyst). Because of the apparent bland histology they may be misinterpreted as benign lesions despite their primary low malignant behavior and late metastatic potential including the capability to transform into a highly malignant sarcoma. In contrast to high grade osteosarcomas cytogenetic studies of these entities are very rare. Karyotyping including FISH analysis with painting- and centromere-specific probes was done in 2 cases of low grade central osteosarcomas (fibrous dysplasia like type). One case was a primary lesion in the upper femur, the other was a recurrent lesion in the upper humerus. Additionally a static DNA cytometry using Feulgen stained imprints was carried out in both cases. In the first case clonal aberrations with a Robertsonian translocation between chromosomes #14 und #15, balanced translocations including chromosomes #5 and #21, #12 and #20, and a supernumary ring chromosome derived from chromosome #1 were detected in a near diploid karyotype. The second case displayed the development from a DNA-diploid to a DNA-peritetraploid lesion during a follow up of six years. Cytogenetic different marker chromosomes and again ring chromosomes were detected in a near tetraploid karyotype. Low grade central osteosarcomas of fibrous dysplasia like type may be characterized by chromosomal aberrations including ring chromosomes. Regarding the last feature these cytogenetic findings resemble those found in low grade parosteal osteosarcomas and other mesenchymal lesions of borderline behavior or low malignancy grade (for example dermatofibrosarcoma protuberans, low grade liposarcoma).

Adolescent↗
PubMed1975

Hormone suppression of DNA synthesis in cultured chondrocyte and osteosarcoma cell line.

Recent evidence suggests that endocrine factors play an important role in the natural history of osteosarcoma. The occurrence of this tumor in the metaphysis of rapidly growing adolescents, coupled with increased female survival led to the investigation of the effects of various hormones on cultured osteosarcoma cells. The in vitro effects of physiologic concentrations of human growth hormone, 17beta estradiol, and progesterone on cultured osteosarcoma cells and chondrocytes are presented. Growth hormone significantly enhances 3H-thymidine incorporation in osteosarcoma cells and chondrocytes, in the presence of human serum. The use of other sera, culture media, or heat inactivation of the human serum abolishes this effect. Estradiol and progesterone, alone, or in combination produce significant suppression of DNA synthesis in cultured tumor cells. Several sera contain a heat-labile factor which has the capacity to block the suppressive effect of estradiol. This factor could be overcome by increasing the concentration of hormone, or by heat-inactivation of the serum. The use of hormone therapy in the treatment of osteosarcoma has never been reported, despite its demonstrated value in certain other malignancies. In light of these observations and considering the poor prognosis in this disease it seems reasonable to initiate a study of adjunctive hormone therapy in osteosarcama.

Cartilage↗
PubMedDate not supplied

Acquisition of multidrug resistance in osteosarcomas, analyzed by doxorubicin binding assay, and histologic response to chemotherapy.

BACKGROUND: The mechanism by which multidrug resistance is acquired in human osteosarcomas remains unclear. In this study, we analyzed the changes in doxorubicin (DOX) binding ability (%DB), showing chemosensitivity before and after chemotherapy with DOX and cisplatin (CDDP), and evaluated the histologic response of human osteosarcomas to chemotherapy. MATERIALS AND METHODS: Eight osteosarcomas were analyzed. %DB by the DOX binding assay was measured in fresh tumor tissues at biopsy and at resection after preoperative chemotherapy. The histologic response to chemotherapy was also evaluated. RESULTS: Changes in %DB before and after chemotherapy were classified into 4 patterns; A: high (> 80%) to low (< 80%), B: high to high, C: low to low, D: low to high. The two tumors, classified as type A and B were responders (> 90% necrosis), whereas the 6 tumors of type C and D were classified as non-responders (< 90% necrosis). Based on these data, we speculated that the fraction of cell populations with different chemosensitivities to DOX and CDDP varied and found that type B tumors have no population of resistant cells, whereas type C tumors have a large fraction of resistant cells. CONCLUSION: We concluded that osteosarcomas are composed of mixed cell populations with different chemosensitivities to anticancer agents and also that survival of multidrug resistant cell populations may be the most important mechanism in acquisition of multidrug resistance of osteosarcomas after chemotherapy.

Adolescent↗
PubMed1997

[A primary study of the association of human leucocyte antigen and osteosarcoma].

OBJECTIVE: To study the association of human leucocyte antigen and osteosarcoma in Chinese Han nationality. METHODS: The frequencies of HLA-A,B,DR,DQ locus antigens were tested in a group of 25 osteosarcoma patients and in a control group of 250 healthy persons by using complement-dependent microlymphocytoxity technique. The members of both groups were of Chinese Han nationality. Their results were compared statistically. RESULTS: The frequency of HLA-B35 was 0.400 in patient group and 0.048 in the control group. The relative risk of suffering from osteosarcoma in persons carrying HLA-B35 was 13.220 times as high as that in those without this antigen (P < 0.01). Patients with HLA-B13 had 12.048 fold increase in relative risk with poor prognosis compared to those without this antigen (P < 0.05). A tendency of worst prognosis was seen in patients who carried both HLA-B13 and HLA-B35, but patients with HLA-B40 had 7.057 times better relative safety for good prognosis than those without that antigen (P < 0.05). CONCLUSION: HLA-B35 is in close linkage to osteosarcoma susceptible gene in Chinese Han nationality. HLA-B13 and HLA-B40 may be separately related to the malignant and resistant genes of osteosarcoma.

Adolescent↗