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PubMed2006

Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma?

The role of angiogenesis as a prognostic indicator in cancer has been extensively studied in recent times with several studies demonstrating a positive correlation for various malignant tumours. However, the role of angiogenesis in osteosarcoma remains a topic of debate. In this study, we aim to evaluate the significance of intratumoural microvessel density (MVD) and the degree of vascular epithelial growth factor (VEGF) expression as markers of angiogenesis and correlate this with disease outcome. Archival paraffin-embedded pre-treatment biopsy tissue of patients treated at St. Vincent's Hospital, Melbourne, with non-metastatic osteosarcoma at initial diagnosis was reviewed. Tissue was processed for immunofluorescent staining of the microvascular endothelial cells with antibodies directed against CD31 and CD34. The degree of angiogenesis was assessed, as determined by the microvessel density (MVD). Further histological examination was performed to assess the degree of VEGF expression. Histological observations were correlated with various clinicopathological factors and patient outcome in terms of recurrence, metastasis and death. Twenty-five cases were reviewed, 15 were male and 10 were female, and the median age was 26 years (range, 13-85). The mean follow-up was 21.5 months (range, 3-75 months). The median MVD was 43 microvessels/0.26 mm2 (range, 25-54) and 46 microvessels/0.26 mm2 (range, 30-58) for CD31 and CD34, respectively. Despite the moderate to high vascularity, there was no significant difference noted between the MVD and disease outcome factors for both CD31 and CD34. There was a trend towards a higher MVD in patients aged > 40 years compared to those < 40 years (p = 0.110 for CD31 and p = 0.097 for CD34). In terms of VEGF expression, 24 of 25 cases demonstrated either moderate or strong expression; however, no prognostic significance was determined. In this study, we were able to demonstrate that osteosarcoma is a relatively vascular tumour; however, the degree of MVD and VEGF expression does not provide prognostic information. It is likely that angiogenesis plays a key role in the pathogenesis of osteosarcoma and is, therefore, a potential target for novel anti-angiogenic therapies.

Adolescent↗
PubMed2006

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model.

In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

Aminolevulinic Acid↗
PubMed2006

Optimization of a two-step desolvation method for preparing gelatin nanoparticles and cell uptake studies in 143B osteosarcoma cancer cells.

PURPOSE: To establish a matrix of parameters to synthesize nanoparticles of different sizes and to investigate the cellular uptake of these nanoparticles by osteosarcoma cancer cells in order to investigate their potential as therapeutic drugdelivery carriers. METHODS: Gelatin A and B were used to synthesize nanoparticles by a two-step desolvation process. Different parameters were investigated, including temperature, pH, concentration of glutaraldehyde, type of desolvating agent and nature of gelatin. For cell uptake studies, Texas Red labeled nanoparticles were incubated with 143B osteosarcoma cells and then evaluated using confocal laser scanning microscopy (CLSM). RESULTS: The systematic investigation of the synthesis parameters showed that it is possible to prepare gelatin-based nanoparticles with different particle sizes and a narrow size distribution. Temperature and nature of the gelatin were the most important synthesis factors. Bioimaging using CLSM showed uptake of the nanoparticles by 143B osteosarcoma cancer cells. CONCLUSIONS: Osteosarcoma cancer cells take up gelatin nanoparticles. This might improve the clinical effectiveness of anti-cancer treatments if nanoparticles are used as a drug delivery system and has important implications for future cancer treatment strategies.

Antineoplastic Agents↗
PubMed2006

[Preliminary report of combination chemotherapy including Arsenic trioxide for stage III osteosarcoma and Ewing sarcoma].

OBJECTIVE: To determine the efficacy of Arsenic trioxide combined with other chemo agents in patients with metastatic osteosarcoma and Ewing sarcoma. METHODS: From December 2002 to June 2005, 32 patients with metastatic osteosarcoma and Ewing sarcoma were treated with chemotherapy comprised Arsenic trioxide, including 19 male and 13 female, aging from 7 to 32 years. Diagnoses included 27 cases with osteosarcomas and 5 with Ewing sarcomas. Twenty-five and 7 patients had multiple lung and skeletal metastasis respectively. All patients had received 4 to 6 cycles standard chemotherapy and surgical treatments before the metastatic lesions were found. The chemotherapy protocol consisted of Arsenic trioxide, VP-16 and paclitaxel. Twenty-eight patients accepted 2 cycles, and 4 patients accepted 3 cycles chemotherapy. RESULTS: Five patients (15.6%), whose lung focus disappeared and no new metastases proved, got complete response (CR); Six patients (18.8%) got partial response (PR); In thirteen stable disease (SD) patients (40.6%), the metastatic lesions did not reduce in evidence but completely calcified in 2 patients and partly calcified in 11 patients; Eight patients (25%) whose tumor size was even bigger after the chemotherapy were defined as progress disease (PD). The average follow-up period was 20 months (ranging from 6 months to 3 years). Three patients were eventually died; The disease was progressed in 5 patients, and the tumor growth was controlled in 24 patients. CONCLUSIONS: Arsenic trioxide is a low-toxic and effective remedy for treatment of stage III osteosarcoma and Ewing sarcoma.

Adolescent↗
PubMed2006

[In vitro screening of 32 traditional Chinese herbal extracts against U2OS human osteosarcoma cells].

OBJECTIVE: To test 32 traditional Chinese medicinal herbs with effects against osteosarcoma in vitro. METHODS: U(2)OS human osteosarcoma cell line was treated with the extracts of the Chinese herbs at various concentrations. The changes in cell proliferation in response to the treatment were examined by MTT assay, and the effects of these extracts against human osteosarcoma growth were compared. Morphological observation, flow cytometry and Annexin V were employed to detect the cell apoptosis after the treatments. RESULTS: According to the results of MTT assay, several of the 32 Chinese herbs, especially Venenum Bufonis and oxgall powder, were identified to produce growth inhibition against U(2)OS cells. Further study of the aqueous extracts of Venenum Bufonis and oxgall powder demonstrated their effects in inducing U(2)OS cell apoptosis, and Venenum Bufonis showed the strongest effect. In spite of the obvious growth inhibitory effect of oxgall powder, its extract induced cell apoptosis only at high concentrations. CONCLUSION: Several of the traditional Chinese herbs, especially Venenum Bufonis and oxgall powder, may inhibit the growth of U(2)OS cell line, and the results of this study pave the way for further identification of the effective components in the herbs that inhibit osteosarcoma growth both in vivo and in vitro.

Antineoplastic Agents, Phytogenic↗
PubMed2006

May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol.

The aim was to evaluate the clinical impact of P-glycoprotein in primary non-metastatic high-grade osteosarcoma patients, treated with neoadjuvant chemotherapy protocols. P-glycoprotein was assessed by immunohistochemistry on paraffin-embedded tissue samples collected at time of diagnosis from 94 osteosarcoma patients, treated with the Italian Sarcoma Group/Scandinavian Sarcoma Group 1 (ISG/SSG 1) protocol. P-glycoprotein-positivity at diagnosis was found in 53/94 ISG/SSG 1 cases (56%) and emerged as the single factor significantly associated with an unfavourable outcome from survival and multivariate analyses. A comparative analysis of the subgroup of 94 patients considered for P-glycoprotein evaluation and the whole series of ISG/SSG 1 patients showed that this marker retained its prognostic value also in the latter group. In osteosarcoma patients treated with doxorubicin-based chemotherapy protocols, P-glycoprotein overexpression at diagnosis is an important adverse prognostic factor for outcome. P-glycoprotein evaluation can therefore constitute the basis for stratifying, at diagnosis, osteosarcoma patients for whom alternative treatments may be considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

[Expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy resistance].

OBJECTIVE: To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance. METHODS: MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay. RESULTS: The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05). CONCLUSION: Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Osteosarcoma following radiotherapy: a case report.

The case of a patient with postirradiation osteosarcoma is presented. The 20-year-old female was diagnosed as having osteosarcoma by histological examination of an open biopsy specimen. She underwent surgery for pure dysgerminoma and received adjuvant postoperative radiotherapy, 40 Gy to the pelvis and 30 Gy to the para-aortic region, 11 years ago. This case satisfied the criteria for radiation-induced osteosarcoma proposed by Cahan et al. Radiation-induced osteosarcoma is rare, but the possibility of that must be borne in mind.

Adult↗
PubMed1991

Telangiectatic osteosarcoma.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy.

Adolescent↗
PubMed1991

Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors.

The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors.

Adolescent↗
PubMed1991

Recent developments in genetic mechanisms, assessment, and treatment of osteosarcomas.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. The tumor, which is composed of malignant spindle cells that produce osteoid, typically occurs in the diaphyseal region of long bones; about half of all osteosarcomas arise in the distal femur or proximal tibia. Clinically detectable metastases are present in about 20% of patients at diagnosis, and most patients have subclinical metastases. Effective therapy with complete surgical resection of tumor and intensive multiagent chemotherapy results in the cure of over 50% of patients with osteosarcoma. Recent developments of importance include an improved understanding of the importance of the p53 gene in the pathogenesis of osteosarcoma, the description of preclinical models, the development of improved imaging techniques for determining tumor extent and responsiveness to chemotherapy, and refinements in therapy.

Adolescent↗
PubMed1991

[A solitary metastatic osteosarcoma of the lung with thin walled cavity: report of a case].

A 13-year-old girl had a history of wide resection of the left fibula under the diagnosis of osteosarcoma three years before. Postoperatively, a thin walled cystic lesion in the right upper lung field, which enlarged gradually with thickening of the wall was found on the chest roentgenogram. The right upper lobectomy was performed after clinical evaluation. The pathologic examination confirmed that the tumor was the metastatic osteosarcoma of the lung. Although metastatic osteosarcoma is common in the lung, very rare cases demonstrate thin walled cavity formation in chest roentgenogram. We reported herein a case of a solitary metastatic osteosarcoma of the lung with thin walled cavity considering with pathogenesis of the lung.

Adolescent↗
PubMed1991

[Osteosarcoma developing after radiation and chemotherapy for primary mediastinal seminoma].

This report presented an osteosarcoma arising from the same field after radiation and chemotherapy without surgery for primary mediastinal seminoma. A 45-year-old man had received from June 1979 to August 1981 irradiation and chemotherapy for the anterior-mediastinal seminoma. Since then he was been without evidence of disease for five years. In March 1987, he had suffered from an advanced tumor extending from the neck and the mediastinum to the right anterior chest wall. Further irradiation combined with thermotherapy were performed but without improvement. He was thereafter seen and admitted July 23 1987 to our hospital with complaint of back pain. Needle biopsy specimen revealed chondrosarcoma. Despite chemotherapy with CDDP, he died four months later after admission. Pathological finding of his autopsy revealed a widely invading osteosarcoma extending to extra- and intrathorax and the neck without evidence of germ cell component. To explain the pathogenesis of the secondarily developing osteosarcoma, two hypotheses are offered; 1. Malignancy of mesenchymal component in germ cell tumor. 2. Radiation-induced osteosarcoma. The latter hypothesis appears to be the most probable pathogenesis from his autopsy. These findings suggest that a long survival patient with malignant germ cell tumor after therapy should be never considered as being free from a potential risk of secondarily developing malignancy.

Combined Modality Therapy↗
PubMed1991

Suramin inhibits growth of human osteosarcoma xenografts in nude mice.

The effect of suramin on tumor growth and morphology in two different human osteosarcoma xenografts (L-I OSM and L-II OSM) grown in BALB/cA-nu/nu mice was studied. Suramin (total dose, 720 mg/kg) given by i.p. injection (60 mg/kg/dose) for up to 9 weeks significantly inhibited osteosarcoma cell growth in both tumors, suramin-treated tumors showing only one-third or less of the volume of nontreated controls. Cell cycle distribution of tumor cells measured by DNA flow cytometry demonstrated that suramin treated caused accumulation of cells in the S and G2 phases of the cell cycle, in both L-I OSM and L-II OSM. In the aneuploid L-II OSM tumor suramin preferentially inhibited the growth of aneuploid cells, leading to a decrease in the ratio of aneuploid to diploid cells. Both osteosarcomas retained their histological appearance and the liver, spleen, heart, and kidneys of the treated animals were unaffected by suramin. These results are compatible with the view that suramin inhibits the growth of human osteosarcomas by cytostatic effects.

Animals↗
PubMed1991

[Analyses regarding estrogen and estrogen receptors in an experimental osteosarcoma].

Further therapeutical investigations are necessary to obtain a satisfactory survival rate of patients by improving the conventional methods of the treatment of osteosarcoma. Our working hypothesis is that an estrogenic hormonal influence is available for the effective treatment of osteosarcoma. An attempt was made to clarify this idea using experimentally induced hamster osteosarcoma. Male and female Syrian golden hamsters were used. Small amounts of minced tumor pieces were transplanted into hamsters subcutaneously. The levels of the circulating estradiol (E2) and alkaline phosphatase (ALPase) in blood were determined after the transplantation. An estrogen receptor (ER) on tumor cells was also demonstrated. Hamsters with an increased level of serum E2 were likely to have a smaller size of primary tumors and a smaller number of nodes in the lung metastasis. These tumor cells were successfully shown to be positive for ER stain. This suggests that E2 treatment may possibly control the osteosarcoma-condition.

Alkaline Phosphatase↗
PubMed1990

Osteosarcoma risk after simultaneous incorporation of the long-lived radionuclide 227Ac and the short-lived radionuclide 227Th.

The effect of injection of 1.85 kBq/kg of the long-lived radionuclide 227Ac on the induction of osteosarcomas in female NMRI mice by different dose levels (18.5, 74, and 185 kBq/kg) of the short-lived radionuclide 227Th was investigated. The highest absolute osteosarcoma incidence was observed with the highest doses of 227Th. Addition of 227Ac resulted in an additional osteosarcoma incidence only at the lowest dose of 227Th and did not affect the osteosarcoma incidence resulting from higher doses of 227Th. The longest times to tumor appearance were observed with 227Ac alone. The latent period in two different age groups (4 weeks and 10-12 weeks) appeared to be similar following injection with combined doses of 227Th and 227Ac but different after injection of each radionuclide alone.

Actinium↗
PubMed1990

[Adjuvant chemotherapy of osteosarcoma].

Osteosarcoma is the one of the tumors that's prognosis have been improved dramatically by the introduction of chemotherapy consisting mainly of adriamycin, high-dose methotrexate with Leucovorin rescue and cisplatinum. Now, the purpose of the treatment for osteosarcoma are assurance of their life and functional and beautiful limb-sparing. Recently, preoperative chemotherapy for limb saving is given to patients with osteosarcoma of the extremities. The five year survival rate increased to 65% and limb sparing rate became above 50%. It is generally accepted that pre- and post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation.

Adult↗
PubMed1990

[The effect of CdCl2 and ZnCl2 on Dunn osteosarcoma].

Three murine sarcoma cells (Dunn osteosarcoma, Gunma clone-4, Sarcoma 1509a) were cultured for four days at various concentrations of CdCl2 or ZnCl2 and assayed for their viability. Dunn osteosarcoma was more sensitive to CdCl2 and less sensitive to ZnCl2 than the others. CdCl2 and ZnCl2 were weekly administered to C3H/He mice intraperitoneally from three days after the inoculation of Dunn osteosarcoma. The size of the tumors was measured twice a week for five weeks. CdCl2 suppressed the growth of the tumor, whereas ZnCl2 did not. These results suggest that CdCl2 has antitumor activity, especially against osteosarcoma.

Animals↗