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PubMed1979

Circulating immune complexes in human osteosarcoma.

Sera from 8 patients with osteosarcoma and 64 normal individuals were examined by C1q and Raji cell radioimmunoassays for the presence of circulating immune complexes. Of the 8 patients with osteosarcoma, 6 had elevated levels of immune complexes in their sera. The elevated levels of immune complexes were demonstrated by both the C1q radioimmunoassay and the Raji cell radioimmunoassay. The amount of immune complexes was quantitated by Raji cell radioimmunoassay; the mean plus or minus the standard error of the amount of aggregated human IgG equivalent per milliliter of serum was 80.12+/-72.64 micrograms for patients with osteosarcoma and 23.07+/-6.2 micrograms for normal individuals. The blocking effect of sera from patients with osteosarcoma on lymphocyte cytotoxicity against cultured osteosarcoma cells (TE-85) was examined. The result indicated that sera with elevated amounts of immune complexes also had increased levels of blocking activity. Sera were fractionated to separate immune complexes from gamma-globulins. No free tumor-specific antibody could be detected in fractionated gamma-globulin fractions from 2 patients with osteosarcoma. The sera of these patients had high amounts of immune complexes and high blocking activities.

Antibodies, Neoplasm↗

PubMed1988

[Analysis of cellular oncogenes in human osteosarcomas transplanted into nude mice].

The structures and transcripts of sixteen different cellular oncogenes (c-oncs) were studied in ten human osteosarcoma lines transplanted onto nude mice by Southern and Northern blot hybridization techniques. One osteosarcoma line (WAJI) had an amplification of c-myc gene at about ten-fold normal amount. High levels of c-myc transcripts were detected in four (MINO, OZA, SU, KiKu) of ten osteosarcoma lines. High levels of c-H-ras transcripts were also detected in four (OZA, TOMO, WAJI, SU) of ten osteosarcoma lines. Gene transcripts of c-fos were detected in only one osteosarcoma line (WAJI). Osteosarcomas containing detectable c-myc transcripts grew more rapidly in nude mice than those with undetectable c-myc transcripts. Levels of c-H-ras transcripts were apparently unrelated to the tumor growth rate.

Animals↗

PubMed1978

Combination chemotherapy for osteosarcoma.

Because of the great risk for development of pulmonary metastases following amputation for osteosarcoma, 24 consecutive patients with "clinically localized" osteosarcoma of an extremity were given adjuvant combination chemotherapy with adriamycin-cyclophosphamide-high-dose methotrexate-citrovorum factor. Thirteen of these patients remain free of tumor from 11 to 48 months following amputation. The median disease-free survival is estimated to be 18 months and the median survival 27 months. No relapses have been observed in any patients surviving free of disease beyond 23 months. Combination chemotherapy was also given to 16 patients whose disease was not localized; eight with pulmonary metastases at or following diagnosis, one with nodal metastases at diagnosis, two with osteosarcoma following radiation therapy for other malignant tumors, three with osteosarcoma of flat bones, one with parosteal osteosarcoma, and one with multifocal osteosarcoma. Three of this latter group of patients are surviving free of tumor at 8, 17, and 19 months from diagnosis. Two young patients died from complications of methotrexate and adriamycin toxicity.

Adolescent↗

PubMed1983

[Detection of human osteosarcoma-associated antigens by monoclonal antibodies].

Hybrid cell lines have been derived from a fusion between mouse myeloma cell line, NS1/Ag 4-1, and spleen cells from BALB/c mice immunized with freshly resected osteosarcoma cells from an untreated patient. Of the 276 hybrids obtained, five secreted antibodies which bound to osteosarcoma tissues but not to autologous skin fibroblasts. Antibodies secreted by individual hybrids were tested for their reaction with a panel of human normal and tumor tissues in an immunofluorescence assay, and they displayed different specificities. Two of these antibodies, OST2 and OST4, bound to osteosarcoma tissues and to some other tumors and normal tissues. The antibodies from three of these five hybrids, OST6, OST7, and OST15, reacted with all of seven osteosarcoma tissues and one chondrosarcoma tissue but not with other malignant or benign tumors. Tests of various normal tissues were negative, except for weak binding to a subpopulation of chondrocytes in calcified areas of cartilage near the subchondral bone. Interestingly, none of the antibodies showed reactivity with three osteosarcoma cell lines, Te 85, Te 418, and MG 63. The experiments established the usefulness of the hybridoma technique in preparing monospecific antibodies against human osteosarcoma associated antigens. In particular, this study demonstrates that the use of freshly resected tumor tissues in preparing monoclonal antibodies would provide a necessary tool for the study of tumor associated antigens.

Adolescent↗

PubMed1996

Multidrug resistance and malignancy in human osteosarcoma.

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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

[Low grade intramedullary osteosarcoma. Apropos of 8 cases].

PURPOSE OF THE STUDY: The authors reviewed eight patients treated for Low Grade Intramedullary Osteosarcoma (LGIO). They analyzed the radiographical and histological features and evaluated the prognosis of this disease. MATERIALS: Eight cases of LGIO were studied. The mean follow-up period was 3.9 years. LGIO is defined as a Broders classification grade I osteosarcoma. The study involved 3 males and 5 females. Mean age at the time of diagnosis was 28. METHODS: Clinical records, radiographs and C.T. Scan were available and reviewed in all cases. Five patients had had MRI. In addition to the conventional histological study, ultrastructural studies were conducted in three of the cases. On their last examination, all patients received a clinical and X-ray assessment. RESULTS: The tumor was localized around the knee in six cases on the humerus and on the proximal femur in one case. The tumor was situated in the metaphysis and was most often lytic. A malignant tumor was suspected at the outset for only two of the patients. The scanner and the MRI revealed a cortical discontinuity and extraosseous involvement in five cases. Seven patients had a wide resection, which was intra-tumoral once. The histological examination of two of those resections revealed limited areas of anaplasia; complementary chemotherapy was then conducted. We did not observe any local recurrence in this group. We observed, however, an iliac metastasis, for which another wide resection was performed. This last patient remained free of disease three years later. One patient had radiotherapy and chemotherapy; he died from pulmonary metastasis after his LGIO turned into high grade osteosarcoma. DISCUSSION: LGIO are rare, they represent 1.8 per cent of all Osteosarcomas in the Cochin file. The mean age of patients contracting LGIO is higher than that of conventional osteosarcoma patients. Observation of the radiographs and histological examination could lead to think the tumor is benign, and mistake it with a fibrous displasia. The C.T. Scan and the MRI have the advantage of showing soft tissue invasion and help the histological examination. The wide resection is the only treatment able to cure the patient. Chemotherapy would be useful for LGIO cases containing limited arcas of anaplasia. CONCLUSION: LGIO is a slowly-evolving tumor. It remains localized for a long period of time. The histological diagnosis is difficult and requires a pathologist familiar with bone tumors. Its treatment requires surgery. LGIO must be distinguished from conventional osteosarcomas because of its better prognosis.

Adult↗

PubMed1996

[Extraskeletal retroperitoneal osteosarcoma. A case report and review of the literature].

Extraskeletal osteosarcomas, localized in the retroperitoneal space, are very rare neoplasms (only 200 cases have been described); the case indicated is the second one observed in Literature. The extraskeletal osteosarcomas are very malignant mesenchymal neoplasms reproducing osseous and cartilaginous tissue disconnected from the skeletal system. From a histological point of view, the extraskeletal osteosarcomas are constituted of osseous and cartilaginous tissue with osteo-fibro-chondroblastic cells: the different representation of three types of cells define the variety of extraskeletal osteosarcomas (osteoblastic, chondroblastic, fibroblastic). Histological and ultrastructural study failed to find differences between skeletal and extraskeletal osteosarcomas. In the clinical history of some patients traumas or irradiation has been referred; although extraskeletal osteosarcomas etiology is frequently unknown. Diagnosis is generally delayed because symptoms are often absent of uncertain. Prognosis of these neoplasms is always very poor, and specially in relation to the dimension and to the possibility of its radical removal. All patients died until 2-3 years after surgery.

Aged↗

PubMedDate not supplied

Chemogene therapy: osteocalcin promoter-based suicide gene therapy in combination with methotrexate in a murine osteosarcoma model.

We previously reported that the recombinant adenovirus (Ad) vector containing the thymidine kinase (TK) gene driven by the osteocalcin (OC) promoter (Ad-OC-TK), when delivered concurrently with acyclovir (ACV), is highly selective in blocking the growth of osteosarcoma in experimental models (Cancer Res. 1996;56:4614-4619). To investigate the possible additive effects of the combined treatment of gene therapy and conventional chemotherapy (chemogene therapy), we compared the effect of low dose (IC10) methotrexate (MTX) and OC promoter-based toxic gene therapy with either of these single modalities alone. We choose low dose MTX with the intent of determining whether chemosensitization of the osteosarcoma may be possible in combination with gene therapy with an overall reduced toxicity profile and enhanced therapeutic efficacy when compared to a single agent alone. In vitro, the combined treatments of MTX (3 ng/mL) and Ad-OC-TK (20 multiplicity of infection (MOI)/target cell) plus ACV (10 mg/mL) had an additive therapeutic effect over that of either MTX (P < 0.05) or Ad-OC-TK plus ACV treatment alone (P < 0.05). In vivo, nude mice with subcutaneous tumors of either human osteosarcoma (MG-63) or rat osteosarcoma (ROS) received three intratumoral injections of Ad-OC-TK (5 x 10(8) PFU) plus daily intraperitoneal ACV (40 mg/kg body weight) for 2 weeks in combination with five weekly bolus intraperitoneal MTX (87.5 mg/kg). Osteosarcoma tumor growth was inhibited more efficiently than by either Ad-OC-TK plus ACV (P < 0.05) or MTX treatment (P < 0.005) alone. At day 45 in the ROS group, 100% of the animals survived when treated with chemogene therapy, whereas 80% survived with gene therapy and no animals survived in the MTX-treated or untreated controls. In summary, we developed a novel therapeutic strategy for the treatment of osteosarcoma employing both chemotherapy and gene therapy. Chemogene therapy could potentially achieve better antitumor effects with reduced toxicity than the conventional chemotherapy or gene therapy protocols alone.

Acyclovir↗

PubMed1998

Production and characterization of canine osteosarcoma cell lines that induce transplantable tumors in nude mice.

OBJECTIVE: To produce and characterize cell lines from canine primary appendicular osteosarcomas that induce transplantable tumors in athymic nude mice. ANIMALS: 57 six- to 8-week-old female athymic nude mice. PROCEDURE: Canine primary appendicular osteosarcoma tumors were harvested and cell lines were produced. Canine osteosarcoma (COSCA)-Toby (COSCA-T; 10 mice), COSCA-Princess (COSCA-Pr; 16) or canine osteosarcoma D-17 (ATCC CCL-183; 31) cells were injected into the proximal portion of the left tibia of nude mice to evaluate tumor production from each cell line; the right tibia served as the control. Tibial measurements were taken on alternating days to evaluate tumor growth during a 6-month period. Student's t-tests were used to determine whether size of the proximal portion of the left and right tibias differed significantly during the observation period. RESULTS: 88% of mice receiving COSCA-Pr and 50% of mice receiving COSCA-T cells developed a tumor at the injection site by 9 days after implantation. The D-17 cells induced tumors in 50% of injected tibias; however, tumors were not detected for 79 days. Tumors generated from COSCA-Pr and COSCA-T cells in nude mice were histologically similar to the canine tumor from which they were developed. CONCLUSION: New osteosarcoma cell lines that can reliably and rapidly induce transplantable tumors in nude mice were developed. CLINICAL RELEVANCE: Use of cell lines will allow evaluation of new treatments of canine primary appendicular osteosarcoma in a nude mouse model.

Animals↗

PubMed1998

A Southwest Oncology Group and Cancer and Leukemia Group B phase II study of doxorubicin, dacarbazine, ifosfamide, and mesna in adults with advanced osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

BACKGROUND: Ewing's sarcomas, osteosarcomas, and rhabdomyosarcomas are significantly more responsive to chemotherapy than other sarcomas. Adjuvant chemotherapy is used routinely based on data from randomized trials. Although a percentage of children with locally advanced or metastatic tumors remain curable, few data exist regarding the tumor's natural history or response and survival in adults. METHODS: This Phase II study evaluated doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma. RESULTS: Between 1987-1991, 81 patients were entered; 69 patients were eligible. One patient died of neutropenic infection. Ten patients (14%) responded completely and 34 patients (49%) had a complete or partial response. Response rates were significantly higher for patients with Ewing's sarcoma and rhabdomyosarcoma than for those with osteosarcoma (77%, 64%, and 26%, respectively; P < 0.005). Although there were no significant differences in progression free survival by histology, survival for patients with Ewing's sarcoma was significantly longer than for patients with osteosarcoma (P = 0.004.) At the time of last follow-up, 7 patients (10%) were alive without progression: 3 with Ewing's sarcoma, 1 with osteosarcoma, and 3 with rhabdomyosarcoma. CONCLUSIONS: MAID chemotherapy is an active regimen in adults with advanced or metastatic Ewing's sarcoma and rhabdomyosarcoma. Although there was no direct comparison with a doxorubicin and cisplatin-based regimen, the response rate and survival in patients with osteosarcoma suggest that doxorubicin and cisplatin-based chemotherapy would remain the accepted initial chemotherapy regimen. For patients with rhabdomyosarcoma and Ewing's sarcoma, 10-20% of patients remained disease free at 5 years.

Adolescent↗

PubMed1998

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy.

Pulmonary metastases are the main cause of death of patients with several types of cancer, including osteosarcoma, renal cell carcinoma, malignant melanoma, and breast cancer. Previously, we demonstrated that intralesional injection of the recombinant adenovirus (Ad) vector containing the herpes simplex virus thymidine kinase (TK) gene driven by an osteocalcin (OC) promoter (Ad-OC-TK) effectively suppressed the growth of osteosarcoma cells in vitro and tumors in vivo in a tumor-specific manner when supplemented with the prodrug acyclovir (ACV). In this communication, we studied the potential efficacy of the treatment of osteosarcoma pulmonary metastases with a systemic delivery route of Ad-OC-TK supplemented with ACV. We established osteosarcoma lung metastases in nude mice by the intravenous injection of rat osteosarcoma cells, ROS 17/2.8. These cells colonized and formed tumor nodules within 1 week in the lungs of nude mice. Whereas systemic delivery of a recombinant Ad vector containing the Escherichia coli beta-galactosidase (beta-gal) gene driven by a Rous sarcoma virus universal promoter (Ad-RSV-beta-gal) resulted in the nonspecific expression of beta-gal activity in the lung parenchyma, Ad-OC-beta-gal administration resulted in specific beta-gal expression in tumor cells deposited in the lung. When nude mice bearing ROS 17/2.8 lung tumors were treated with systemic Ad-OC-TK through tail vein administration, subsequent intraperitoneal ACV treatment significantly decreased the number of tumor nodules (P < .0001) and the net lung wet weight (P = .0005) while significantly increasing (.005 < P < .01) the survival of animals, when compared with untreated and Ad-OC-TK- or ACV-treated control groups. These results suggest that Ad-OC-TK/ACV may be used as a systemic therapy for the treatment of osteosarcoma lung metastasis.

Acyclovir↗

PubMed1985

Periosteal osteosarcoma.

An analysis of 6 patients with periosteal osteosarcoma treated by the authors along with a review of 55 patients reported in the literature demonstrates that periosteal osteosarcoma is distinctly different from conventional osteosarcoma or periosteal chondrosarcoma. Periosteal osteosarcoma is a less aggressive tumor than conventional osteosarcoma. It is a relatively well-differentiated chondroblastic osteosarcoma occurring on the surface of the long bones of the extremities. Three patients demonstrated frank medullary invasion of tumor, two grossly and one microsurgically. Patients treated with marginal resection had a 70% local recurrence rate. Patients receiving wide resection or primary amputation have survived longer with less recurrence of disease. Overall, 10 of 61 patients are dead with metastatic disease with a mean reported follow-up of 6 years and 7 months. Adjunctive therapy has been of no demonstrable aid in terms of prolonging survival. Medullary extension of this tumor should not be used to exclude this diagnosis. The authors believe that the treatment of choice is wide resection without adjunctive chemotherapy.

Adolescent↗

PubMed1990

Interferons and bone. A comparison of the effects of interferon-alpha and interferon-gamma in cultures of human bone-derived cells and an osteosarcoma cell line.

Recombinant human interferon-alpha 2C and recombinant human interferon-gamma (5-1000 U/ml) inhibit the proliferation of normal human bone-derived cells and a human osteosarcoma cell line. In the bone-derived cells the inhibitory effect of interferon-gamma was significantly greater than that of interferon-alpha, whereas in the osteosarcoma cell line the inhibitory effects of both interferons were quantitatively similar. Interferon-alpha did not affect the alkaline phosphatase activity of either type of cells. In contrast, interferon-gamma affected the activity of the enzyme in both cell types: in the bone-derived cells the effect of interferon-gamma was stimulatory whereas in the osteosarcoma cells the effect was inhibitory. In both cell types interferon-gamma selectively inhibited the incorporation of radiolabelled proline into type I collagen. In the osteosarcoma cells, the effects of both interferons on collagen synthesis were quantitatively similar. In the bone-derived cells, however, interferon-alpha decreased proline incorporation into collagen and non-collagen proteins to a similar extent and thus did not affect collagen synthesis when expressed as a percentage of total protein synthesis. Two-dimensional polyacrylamide gel electrophoresis of the radiolabelled proteins of the cell layer synthesised by both cell types in the presence of either interferon demonstrated that this treatment enhanced or induced the synthesis of a total of 21 individual proteins (19 in bone cells, 14 in osteosarcoma), ranging in apparent molecular mass over 14-87 kDa. The set of proteins induced was different in all four combinations of cells and interferon. A tentative identification of several of the proteins was possible based upon estimation of molecular mass, preferential induction by interferon-alpha or interferon-gamma and differential induction in normal and transformed bone-derived cells. The results of this study demonstrate that interferons have complex effects upon the proliferative and biosynthetic activities of human bone-derived cells and demonstrate significant differences between the responses of normal cells and transformed bone-derived cell line. Further investigations will be required in order to determine whether or not these differences are unique to the osteosarcoma cell line or are a characteristic of the effects of interferons on bone-derived cells in general.

Adolescent↗

PubMed2006

Multidisciplinary approach to diagnosis and management of osteosarcoma - a review of the St Vincent's Hospital experience.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia). METHODS: Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005. RESULTS: Median age at diagnosis was 21 (range, 11-84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients. Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy). CONCLUSION: Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.

Journal Article↗

PubMed2026

Kaposi Sarcoma-Associated Herpesvirus Is Not Detected in Osteosarcoma From KSHV-Endemic African Countries and the Non-Endemic United States Populations.

Osteosarcoma is an aggressive primary malignant bone tumor of poorly defined etiology that predominantly affects adolescents and young adults. A viral cause has long been proposed, and a recent study from Xinjiang, China, reported frequent detection of Kaposi sarcoma-associated herpesvirus (KSHV) in Uyghur osteosarcoma cases, suggesting a possible association in this KSHV-endemic population. Whether this association extends to broader populations remains unknown. Our study investigated the presence of KSHV in osteosarcoma specimens from KSHV-endemic African countries (Cameroon, Kenya, South Africa, Zambia) and the non-endemic United States. A total of 356 formalin-fixed paraffin-embedded and fresh-frozen specimens were retrieved or prospectively collected. In 77 selected high-quality specimens, KSHV infection was assessed by immunohistochemistry for LANA1 and by qPCR targeting 5 viral open reading frames (ORF25, ORF26, ORF37, ORF65, and ORF73). LANA1 expression was undetectable in all tumors. Using qPCR, 75/77 specimens were negative for all targets, 1/77 excluded due to insufficient remaining DNA quantity to perform the assay, and 1/77 positive across all five targets. Additionally, we studied the KSHV seroprevalence in a separate cohort comprised of 49 sera obtained from individuals with osteosarcoma from Zambia (n = 39) and the United States (n = 10). We measured by ELISA the presence of specific antibodies against four KSHV antigens: K8.1, KCP, VCA, and LANA1. KSHV seropositivity was detected in 15/39 individuals from Zambia and none from the United States. In the absence of compelling evidence, our findings could not support an association between KSHV infection and osteosarcoma in our study population.

Humans↗

PubMedDate not supplied

The many faces of osteosarcoma.

Osteosarcoma is the most common primary malignant tumor of bone in adolescents and young adults. It accounts for approximately 15% of all primary bone tumors confirmed at biopsy. There are numerous types of primary osteosarcoma, including intramedullary (high grade, telangiectatic, low grade, small cell, osteosarcomatosis, and gnathic), surface (intracortical, parosteal, periosteal, and high-grade surface), and extraskeletal. Osteosarcoma may also occur as a secondary lesion in association with underlying benign conditions. The identification of osteoid matrix formation and aggressive characteristics usually allows prospective radiologic diagnosis of osteosarcoma. As with all bone tumors, differential diagnosis is best assessed with radiographs, whereas staging is performed with computed tomography or magnetic resonance imaging. Understanding and recognition of the variable appearances of the different varieties of osteosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment, and follow-up.

Adolescent↗

PubMed1999

Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

BACKGROUND: Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. PROCEDURE: We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). RESULTS: Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. CONCLUSIONS: We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma.

Adolescent↗