Types Of Osteosarcoma Research Articles

Cancer characterization using light backscattering spectroscopy and quantitative ultrasound: an ex vivo study on sarcoma subtypes

Histological analysis is the gold standard method for cancer diagnosis. However, it is prone to subjectivity and sampling bias. In response to these limitations, we introduce a quantitative bimodal approach that aims to provide non-invasive guidance towards suspicious regions. Light backscattering spectroscopy and quantitative ultrasound techniques were combined to characterize two different bone tumor types from animal models: chondrosarcomas and osteosarcomas. Two different cell lines were used to induce osteosarcoma growth. Histological analyses were conducted to serve as references. Three ultrasound parameters and intensities of the light reflectance profiles showed significant differences between chondrosarcomas and osteosarcomas at the 5% level. Likewise, variations in the same biomarkers were reported for the two types of osteosarcoma, despite their similar morphology observed in the histological examinations. These observations show the sensitivity of our techniques in probing fine tissue properties. Secondly, the ultrasound spectral-based technique identified the mean size of chondrosarcoma cells and nuclei with relative errors of about 22% and 9% respectively. The optical equivalent technique correctly extracted scatterer size distributions that encompass nuclei and cells for chondrosarcomas and osteosarcomas (R^2 = 0.80 and R^2 = 0.73 respectively). The optical scattering contributions of nuclei were estimated at 52% for the chondrosarcomas and 69% for the osteosarcomas, probably indicating the abundant and the absent extracellular matrix respectively. Thus, the ultrasound and the optical methods brought complementary parameters. They successfully estimated morphological parameters at the cellular and the nuclear scales, making our bimodal technique promising for tumor characterization.

Synergistic Antitumor Interaction of Risedronate Sodium and Standard Anticancer Agents in Canine (D-17) and Human Osteosarcoma (U-2 OS) Cell Lines.

Simple SummaryThe study investigated canine (D-17) and human (U-2 OS) osteosarcoma exposition to risedronate sodium and chosen standard anticancer drugs concurrently used in vitro. Risedronate sodium is frequently used in the therapy of bone tissue disorders. Our study demonstrated increased efficiency of cytostatic drugs in the presence of risedronate. During the incubation, testing and evaluation the standard protocols were used. MTT and TUNEL assays were employed to estimate changes in cell viability and percentage of apoptosis. We found that a combination of doxorubicin and cisplatin with risedronate sodium produced the strongest cytotoxic effects in both cell cultures. The cytotoxicity against both types of osteosarcoma was concentration-dependent and the cytostatic drugs and risedronate sodium were found to act synergistically.The study discusses in vitro cytotoxicity of a combination of cytostatic drugs (doxorubicin, cisplatin, carboplatin, etoposide) and risedronate sodium against canine and human osteosarcoma (D-17 and U-2 OS). Standard protocols were used for the preparation of cell cultures and evaluation of their viability and apoptosis. MTT assay assessed the culture viability and EC50, while the apoptotic effect of the drugs was checked with a TUNEL assay. Doxorubicin alone showed the strongest cytotoxicity against D-17 (0.056 ± 0.019 µg/mL) and U-2 OS (0.051 ± 0.003 µg/mL), while the lowest cytotoxicity was observed for carboplatin (D-17, 6.45 ± 0.2 µg/mL and U2-OS, 27.5 ± 2.3 µg/mL). Risedronate sodium at 100, 10 and 1 µg/mL lowered viability in OS cell lines by 53.38 ± 1.46 and 49.56 ± 0.7%, 97.08 ± 3.32 and 74.92 ± 4.01%, and 102.67 ± 3.56 and 94.56 ± 3.52%, respectively. In all analyzed drug combinations, risedronate sodium significantly (* p < 0.05) increased the cytotoxicity against tested osteosarcoma cell lines. The decrease in cell viability caused by the studied compound combinations was weaker in canine than in human cell cultures. A combination of doxorubicin (all concentrations), cisplatin (1 µg/mL) and etoposide (1 µg/mL) with 100 µg/mL of risedronate sodium significantly improved the cytotoxicity of the drugs against canine and human osteosarcoma. Administration of carboplatin (1 µg/mL) and risedronate sodium (100 µg/mL), compared to carboplatin per se, produced no significant differences in cytotoxicity against the D-17 cell culture but significantly enhanced cytotoxicity in the U-2 OS line. The strongest apoptosis in both lines was detected for 0.01 µg/mL doxorubicin combined with 100 µg/mL risedronate sodium or 1 µg/mL cisplatin and 100 µg/mL risedronate sodium. In all combinations, the tested compounds revealed a synergistic mechanism of action.

Antitumor Effect of Sclerostin against Osteosarcoma.

Simple SummaryOsteosarcoma is highly variable and heterogeneous, which is one of the reasons for its resistance to treatment. Because osteosarcoma is defined by abnormal bone formation, we hypothesize its suppression could lead to effective treatment for all types of osteosarcomas. Sclerostin is secreted by osteocytes and inhibits the canonical pathway by binding to LRP5/6, thereby suppressing bone formation. The resulting suppression of bone formation leads to bone loss and osteoporosis. Here, we investigated the antitumor effect of sclerostin against osteosarcoma and found that sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells.Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan–Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.

Measuring and Optimizing MG-63 Osteosarcoma Osseointegration and Proliferation on Laser Ablated Medical-Grade Titanium

We will modify pieces of Ti64AlV medical-grade titanium, commonly used in dental and orthopedic industries, through laser ablation, to optimize osseointegration, the growth of bone that anchors a surgical implant. Such conditions would indicate that this modification of the titanium will lead to a shorter time for recovery and higher bone to implant contact rate for titanium implants. The MG-63 cell line, a type of osteosarcoma, was chosen to measure cell adhesion to a surface that is altered using the Nd:YVO4 picosecond pulsed laser.

Acute respiratory failure as initial manifestation of conventional osteosarcoma rich in giant cells: a\xa0case report

BackgroundOsteosarcoma is a malignant tumor of the bone. The giant cell-rich osteosarcoma (GCRO) is a rare histological variant of the conventional osteosarcoma, accounting for 3% of all osteosarcomas. It has a variable clinical presentation, ranging from asymptomatic to multiple pathological fractures, mainly involving long bones, and less frequently the axial skeleton and soft tissues.Case presentationWe present the case of a 25-year-old Hispanic woman, previously healthy, with a 1-month history of dyspnea on exertion, intermittent dry cough, hyporexia, and intermittent unquantified fever. She presented to the emergency department with a sudden increase in dyspnea during which she quickly entered ventilatory failure and cardiorespiratory arrest with pulseless electrical activity. Resuscitation maneuvers and orotracheal intubation were initiated, but effective ventilation was not achieved despite intubation and she was transferred to the intensive care unit of our institution. The chest radiograph showed a mediastinal mass that occluded and displaced the airway. The chest tomography showed a large mediastinal mass that involved the pleura and vertebral bodies. A thoracoscopic biopsy was performed that documented a conventional giant cell-rich osteosarcoma. The patient was considered to be inoperable due to the size and extent of the tumor and subsequently died.ConclusionsThe giant cell-rich osteosarcoma is a very rare histological variant of conventional osteosarcoma. Few cases of this type of osteosarcoma originating from the spine have been reported in the literature, and to our knowledge none of the reported cases included invasion to the chest cavity with airway compression and fatal acute respiratory failure that was present our case. Radiological and histological features of the GCRO must be taken into account to make a prompt diagnosis.

Screening of disorders associated with osteosarcoma by integrated network analysis.

Osteosarcoma is a common malignant bone tumor in children and adolescents under the age of 20. However, research on the pathogenesis and treatment of osteosarcoma is still insufficient. In the present study, based on gene-phenotype correlation network, an analysis was performed to screen disorders related to osteosarcoma. First, we analyzed the differential expression of osteosarcoma in two groups according to different types of osteosarcoma and screened the differentially expressed genes (DEGs) related to osteosarcoma. Further, these DEG coexpression modules were obtained. Finally, we identified a series of regulatory factors, such as endogenous genes, transcription factors (TFs), and ncRNAs, which have potential regulatory effects on osteosarcoma, based on the prediction analysis of related network of gene phenotypes. A total of 3767 DEGs of osteosarcoma were identified and clustered them into 20 osteosarcoma-related dysfunction modules. And there were 38 endogenous genes (including ARF1, HSP90AB1, and TUBA1B), 53 TFs (including E2F1, NFKB1, and EGR1), and 858 ncRNAs (including MALAT1, miR-590-3p, and TUG1) were considered as key regulators of osteosarcoma through a series of function enrichment analysis and network analysis. Based on the results of the present study, we can show a new way for biologists and pharmacists to reveal the potential molecular mechanism of osteosarcoma typing, and provide valuable reference for different follow-up treatment options.

Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma?

Long-term survival for all patients with osteosarcoma using current aggressive adjuvant chemotherapy and surgical resection is between 60% and 70%. In patients who present with nonmetastatic, high-grade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over amputation to preserve the limb, because limb salvage may lead to a superior quality of life compared with amputation. However, concern remains that in the attempt to preserve the limb, close or microscopically positive surgical margins may have an adverse effect on event-free survival. (1) Does a positive or close surgical margin increase the likelihood of a local recurrence? (2) Does a positive or close surgical margin adversely affect the development of metastatic disease? (3) What is the relationship of surgical margin on overall survival? With institutional review board approval, we retrospectively evaluated 241 patients treated at our institution between 1999 and 2011. Exclusion criteria included nonextremity locations, metastatic disease at initial presentation, low- or intermediate-grade osteosarcoma, treatment regimens that did not follow National Comprehensive Cancer Network (NCCN) guidelines, incomplete medical records, and any part of treatment performed outside of Moffitt Cancer Center or All Children's Hospital. Fifty-one patients were included in the final analysis, of whom 31 (61%) had followup data at a minimum of 2 years or whose clinical status was known but had died before 2 years of followup. Margin status was defined as (1) microscopically positive; (2) negative ≤ 1 mm; and (3) negative > 1 mm. Margin status, histologic response (tumor percent necrosis), type of osteosarcoma, type of surgery, presence of local recurrence, metastatic disease, and overall survival were recorded for each patient. The mean age was 22 years (range, 12-74 years) and the mean followup was 3 years (range, 0.1-14 years). Margin status was positive in 10% (five of 51), negative ≤ 1 mm 26% (13 of 51), and negative > 1 mm 65% (33 of 51). Local recurrence was noted to be 14% (seven of 51) at 3.4 years. After controlling for relevant confounding variables, the presence of a positive margin compared with a negative margin > 1 mm was the only independent predictor of local recurrence (hazard ratio [HR], 8.006; 95% confidence interval [CI], 1.314-48.781; p = 0.0241). At a mean of 3.4 years, 29% (15 of 51) of the patients developed metastatic disease with no difference with the numbers available in the probability of developing metastatic disease among the three margin groups (p = 0.614). Overall survival at 3.8 years was 75% (38 of 51). After controlling for relevant confounding variables, we found that patients with positive margins were more likely to die from disease than those with negative margins (HR, 6.26; 95% CI, 1.50-26.14; p = 0.0119); no other independent predictors of survival were identified. With the numbers of patients we had, we observed that patients with extremity, nonmetastatic, high-grade osteosarcoma who had positive margins showed a higher probability of local recurrence in comparison to those with negative surgical margins. Given that positive margins appear to be associated with poorer survival in patients with high-grade osteosarcoma of the extremities, surgeons should strive to achieve negative margins, but larger studies are needed to confirm these findings. Level III, therapeutic study.

The Time of the Insult/Triggering Event in Primary Osteosarcoma and Ewing’s Sarcoma of Bone as Determined by Incubation Period Modeling and Age Distribution of Such Malignancies

The time for the triggering event in neoplasms can be estimated using incubation period modeling techniques. We applied these techniques to primary osteosarcoma and Ewing’s sarcoma of bone using the Surveillance Epidemiology and End Results database for all cases of osteosarcoma or Ewing’s sarcoma of bone from 1993 through 2010. Secondary neoplasms were excluded. The age at diagnosis, gender, ethnicity, and anatomic location were collected. The time (xt) of the insult/triggering event was calculated using the best fit frequency distribution of age at diagnosis. There were 4,356 patients with osteosarcoma and 1,832 patients with Ewing’s sarcoma. The Pearson IV distribution was the best fit for both osteosarcoma (r2=0.987) and Ewing’s sarcoma (r2=0.99). For these distributions xt is −0.7 years of age (4 weeks after conception) for Ewing’s sarcoma, 0.45 years for long bone osteosarcoma, and 10.4 years for parosteal osteosarcoma. This confirms the genetic etiology of Ewing’s sarcoma since an xt is 4 weeks after conception. Long bone osteosarcoma is not entirely genetic, as xt was 0.4 years for conventional osteosarcoma and 10.4 years for parosteal osteosarcoma. The etiologies for those two different types of osteosarcoma are thus different.

Many faces of osteosarcoma on plain radiographs.

Osteosarcoma is the most common primary malignancy of bone. It is a very rare form of cancer with an annual incidence of 3:1,000,000 and so will not be seen by many surgeons. Coupled with this are the many different subtypes of this cancer that can have different appearances on imaging ranging from densely sclerotic to lytic or even cystic. They can be medullary, cortically or periosteally based. This article demonstrates the various different appearances associated with the different types of osteosarcoma which will assist surgeons in diagnosing this rare cancer.

Abstract B59: Zhangfei/CREBZF arrests the growth of osteosarcoma cells by displacing Mdm2 and stabilizing p53.

Abstract Osteosarcomas (OS) are the most common malignant bone tumors in humans and dogs. Although there has been dramatic progress in treating OS in both species by surgery and chemotherapy, these therapies often fail, leading to recurrence of the tumor and metastatic spread. Our previous studies showed that Zhangfei/CREBZF, a basic region-leucine zipper (bLZip) transcription factor, is a potent suppressor of growth in some cancer cell lines, including the canine osteosarcoma cell line D-17. However, the mechanisms underlying the suppressive effects of Zhangfei have not been fully elucidated. Furthermore, the effects of Zhangfei are not universal and it has no obvious effects on untransformed cells and some cancer cell lines, suggesting that Zhangfei may act through an intermediary that is either not induced or is defective in cells that it does not affect. The objective of this study was to identify such an intermediary and to determine how Zhangfei exerts its effect. By monitoring the mRNA levels, protein, localization, and transcription activity of tumor suppressor protein p53 and its target genes in D-17 cells infected with adenovirus vectors expressing Zhangfei, we found Zhangfei stabilizes p53 and co-localizes with it in cellular nuclei and that the basic-leucine zipper domain of Zhangfei is required for its profound effects on cell growth and interaction with p53. Suppression of p53 by siRNA at least partially inhibited the effects of Zhangfei on the growth of cells. The effects of Zhangfei on dog osteosarcoma cells (D-17 cells) is mirrored by its effects on the p53 expressing human osteosarcoma cell line U2OS while Zhangfei has no effect on the p53-null osteosarcoma cell line MG63. In U2OS cells Zhangfei displaces the ubiquitin ligase, MDM2, from its association with p53 suggesting a mechanism for the effects of Zhangfei on p53. Overall, we identified that Zhangfei suppressed cell growth in osteosarcoma cells through direct interaction with tumor suppressor protein p53. We demonstrated that Zhangfei stabilized p53 and promoted its nuclear retention by displacing the E3 ubiquitin ligase, Mdm2. Our findings reveal a novel mechanism by which Zhangfei may inhibit tumor growth and metastasis. This may provide a potential application to gene therapy of certain types of osteosarcoma, and perhaps other tumors containing functional p53. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B59. Citation Format: Rui Zhang, Vikram Misra. Zhangfei/CREBZF arrests the growth of osteosarcoma cells by displacing Mdm2 and stabilizing p53. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B59.

Local recurrence of a parosteal osteosarcoma 21 years after incomplete resection

Parosteal osteosarcoma (POS) is the most common form of surface osteosarcoma. Its symptoms are insidious and its duration prior to diagnosis is considerably longer than that of other types of osteosarcoma. We report a case of POS with a growing mass but no evidence of metastasis. This tumor, which was diagnosed as calcified hematoma with benign characteristics, was incompletely resected in our hospital 21 years before the diagnosis of recurrence. The patient underwent a wide en bloc resection in our hospital and was free of symptoms, with no signs of tumor recurrence or metastasis during a 53-month follow-up.

Outcomes of stage IIB osteosarcoma treated by limb salvage surgery using extracorporeally irradiated (ECI) autograft

Background: Extracorporeally irradiated (ECI) technique is an alternative of limb salvage procedure in treating osteosarcoma regarding limitation of endoprosthesis and allograft. This study evaluated the outcomes of limb salvage surgery using extracorporeally irradiated (ECI) autograft and its correlation with patient’s characteristics.Methods: Retrospective cohort design was performed to study 20 patients with stage IIB osteosarcoma treated by ECI autograft from 1995 to 2008. Survival, local recurrence, metastases, complications, union time and functional score based on Musculoskeletal Tumor Society scoring system-(MSTS) were evaluated. Kaplan-Meier method was used to describe survival, local recurrence free survival, and metastases free survival. The correlation among patient’s characteristics that were age, gender, duration, site of tumor size, type of osteosarcoma, SAP (serum alkaline phosphatase) level, type of biopsy, and type of Huvos were analyzed by Log rank test. Chi-square test was used to analyze the correlation between MSTS score and patient’s characteristics, local recurrence, metastases, complications.Results: Five-year survival was 54.97 ± 9.8 %, five-year local recurrence free survival was 66.5 ± 7.6%, and five year metastasis-free survival was 57.13 ± 10.04%. Six patients died, five were due to lung metastases and one due to complication of chemotherapy. Three underwent amputation after local recurrence. Kaplan-Meier curve showed that a good type of Huvos (III, IV) always gave better survival, local recurrence free survival, and metastases free survival than poor type of Huvos (I,II). Normal SAP level gave better local recurrence free survival compare to increased level of SAP. Mean of union rate was 8.13 months. MSTS mean score was good (70.63%) in patients with no evidence of disease. MSTS score was poor in patients with local recurrence (p = 0.025), metastases (p = 0.01), complications (p = 0.03), and the combined of those three outcomes (p = 0.001).Conclusions: Functional outcome was poor in patients with local recurrence, metastases, and complications. SAP level and type of Huvos could be studied further as predictive factors for the outcomes (survival, local recurrence, metastases). (Med J Indones 2011; 20:131-7)Keywords: extracorporeally irradiated autograft (ECI), osteosarcoma stage IIB, outcomes

Abstract 4310: Gene expression analysis of axial and appendicular osteosarcoma in the canine model

Abstract Spontaneously occurring canine osteosarcoma (OSA) is considered an excellent model of the human disease. Canine axial and appendicular osteosarcoma appear histopathologically identical. The clinical course of the two forms, however, seems to diverge. Following surgery, the axial form may be associated with a lower metastatic rate and longer survival than the appendicular form. Identifying gene expression profiles associated with decreased metastatic potential may be crucial for the development of targeted therapies for the human disease. We hypothesized that there are distinct gene expression patterns for canine axial and appendicular OSA. Six axial osteosarcoma tumor samples and six age, breed, and weight matched appendicular osteosarcoma clinical tumor samples were selected from the Center for Comparative Oncology, Michigan State University tissue bank. RNA extraction, amplification and labeling were performed using standard techniques. Raw gene expression values were obtained using the Affymetrix GeneChip Canine Genome 2.0 Array. Background correction, normalization, PM correction, summarization, and expression analysis were performed using the R software with the affy/limma/sva packages. Gene set enrichment analysis was performed using GSEA software. All RNA samples passed quality control and were included in the data set. The expression analysis took into account RNA degradation, which was similar in all tumor samples. A total of 184 genes were differentially expressed by &amp;gt;16-fold, between the two groups. Surrogate variable analysis did not result in any statistically significant differences in gene expression. Gene set enrichment analysis resulted in 9 gene sets enriched in axial, and 4 gene sets enriched in appendicular osteosarcoma samples at FDR &amp;lt; 25%. Gene ranking was similar between the two methods of analysis, with MMP1, ATP6AP1, SLC6A8, and dysadherin expression increased in axial tumor samples, while ICAM2 expression increased in appendicular samples. Expression analysis indicates no statistically significant differences in gene expression between the axial and appendicular OSA. Gene set enrichment analysis indicates potential differences in gene set enrichment between the two types of osteosarcoma. Further quantitative RT-PCR analysis is required to confirm our results. These data will guide hypothesis-driven translational studies, which may have direct clinical implications on the treatment of osteosarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4310. doi:10.1158/1538-7445.AM2011-4310

Overexpression of BMI-1 Promotes Cell Growth and Resistance to Cisplatin Treatment in Osteosarcoma

BackgroundBMI-1 is a member of the polycomb group of genes (PcGs), and it has been implicated in the development and progression of several malignancies, but its role in osteosarcoma remains to be elucidated.Methodology/Principal FindingsIn the present study, we found that BMI-1 was overexpressed in different types of osteosarcomas. Downregulation of BMI-1 by lentivirus mediated RNA interference (RNAi) significantly impaired cell viability and colony formation in vitro and tumorigenesis in vivo of osteosarcoma cells. BMI-1 knockdown sensitized cells to cisplatin-induced apoptosis through inhibition of PI3K/AKT pathway. Moreover, BMI-1-depletion-induced phenotype could be rescued by forced expression of BMI-1 wobble mutant which is resistant to inhibition by the small interfering RNA (siRNA).Conclusions/SignificanceThese findings suggest a crucial role for BMI-1 in osteosarcoma pathogenesis.

Characterization of chondroid matrix-forming sarcomas: gadolinium-enhanced and diffusion weighted MR imaging

Objective To study the Gadolinium-enhanced MRI and diffusion weighted imaging (DWI) characteristics of the chondroid matrix-forming sarcomas.Methods Contrast-enhanced MRI and DWI were performed in 14 eases of chondroid matrix-forming sarcomas (10 chondrosarcomas,4 chondroblastic esteosarcomas) and 13 cases of other types of osteosarcomas.DWI was obtained with a single-shot echo-planar imaging (EPI) sequence using a 1.5 T MR imager with two different b values of 0 and 700 s/mm2.The apparent diffusion coefficient (ADC) values were obtained in GE Functiontool software.The contrast-enhancement pattern was evaluated and the ADC values of ehondroid matrix-forming sarcomas was compared with that of other types of asteosarcoma.Independent sample t-test was performed to evaluate the difference of ADC values between the group of chondroid matrix-forming sarcoma and the group of other types of osteosarcoma.In addition, nonparametrie test was used to assess the difference of ADC values between the chondrosareoma and the chondroblastic osteosarcoma.P value less than 0.05 was considered to represent a statistical significance.Results For 14 eases of ehondroid matrix-forming sarcomas, peripheral enhancement was found in all cases, septonodular enhancement was identified in 12 cases.While 13 eases of other types of osteosarcowas demonstrated heterogeneous enhancement.The mean ADC value of chondroid matrix-forming sarcomas [(2.56 ±0.35) × 10 -3 mm2/s] was significantly higher than that of other types of osteosarcoma [( 1.16±0.20) × 10-3 mm2/s] (t = 12.704,P <0.O1 ).There was no significant difference in the ADC value between the chondrosarcoma and the chondroblastie osteesarcama(Z =0.507 ,P =0.959).Conclusion Contrast-enhanced MRI and DWI can improve differentiation between chondroid matrix-forming sarcomas and other types of osteosarcomas. Key words: Chondrosarcoma; Osteesareoma; Magnetic resonance imaging; Diffusion magnetic resonance imaging

Characterization of chondroblastic osteosarcoma: Gadolinium‐enhanced versus diffusion‐weighted MR imaging

To detect differences in magnetic resonance imaging (MRI) between chondroblastic osteosarcoma and the other types of osteosarcomas or chondrosarcomas using gadolinium-enhanced versus diffusion-weighted sequences. Contrast-enhanced MRI and diffusion-weighted imaging (DWI) were performed in five chondroblastic osteosarcoma (CO) cases, 17 other types of osteosarcomas (OS), and 18 chondrosarcomas (CS). DWI was obtained with a single-shot echo-planar imaging (EPI) sequence using a 1.5 T MR imager. The apparent diffusion coefficients (ADCs) of the minimum and maximum values were also obtained. The contrast-enhancement pattern was evaluated and minimum-maximum ADC value of CO was compared with other types of OS and CS. Both CO and CS showed a similar enhancement pattern; both showed septonodular and peripheral rim enhancement. The minimum ADC value of CO (1.24 +/- 0.10 x 10(-3)mm(2)/sec) was significantly higher than that of other types of OS (0.84 +/- 0.15 x 10(-3)mm(2)/sec) and was significantly lower than that of CS (1.64 +/- 0.20 x 10(-3)mm(2)/sec). In addition, the maximum ADC value of CO (2.28 +/- 0.20 x 10(-3)mm(2)/sec) was significantly higher than that of other types of OS (1.33 +/- 0.26 x 10(-3)mm(2)/sec). DWI appears to be more useful for differentiating between chondroblastic osteosarcoma and chondrosarcoma or other types of osteosarcoma than Gd-enhanced MRI.

Surface osteosarcoma: 2 case reports

Surface osteosarcoma of the jaw bone is extremely rare, and it differs from the central type in its clinicopathologic features. This type of osteosarcoma generally shows low-grade malignancy, grows slowly, metastasizes less often, and the prognosis is better than that of the central type. We report 2 cases of surface osteosarcoma of the jaw bone, and discuss some clinical important issues.

Diffuse Calcification of Metastases after Intensive Multiagent Chemotherapy in Widespread Osteosarcoma Leading to Death in a 18-Year-Old Male: Report of a Case and Literature Review

Multifocal osteosarcoma represents a rare and aggressive type of osteosarcoma in which multiple bone lesions are detected simultaneously in the absence of pulmonary or any other visceral organ involvement. Despite a multidisciplinary approach, overall survival remains poor and disease progresses, leading to death within 1 yr of diagnosis. Here we report a case of an 18-yr-old patient with extensively metastatic osteosarcoma developing diffuse calcification in lung, pleural, diaphragm, pericardial, subcutaneous metastases, and mediastinal lymph nodes after intensive multiagent chemotherapy. We provide an extensive review of the literature together with presentation of different aspects regarding the debate on the multicentric versus metastatic hypotheses for multifocal osteosarcoma. An update on the current understanding of the molecular features of this disease is also included.

Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas.

Amplification of genes in the 12q13-15 region occurs frequently in several malignancies including osteosarcoma. The products of these amplified genes are thought to provide cancer cells with a selective growth advantage; however, the specific gene(s) driving this amplicon is unknown. We have previously shown that the SAS gene is amplified in most parosteal osteosarcomas. In this study we analysed additional putative growth regulatory genes in this chromosomal region in 24 primary osteosarcoma specimens. CDK4 and SAS were coamplified in 6/6 parosteal tumors, and MDM2 was also amplified in 4/5 parosteal cases. In comparison, amplification occurred in only 2/16 classical intramedullary osteosarcomas and involved the SAS gene. Each amplified gene had a correspondingly elevated mRNA level. Four high grade intramedullary tumors had elevated mRNA expression of SAS, but did not exhibit gene amplification. Gene amplification/overexpression was not associated with metastatic disease and did not change markedly with tumor progression, as evidenced by analysis of sequential tumor specimens from eight patients. Three other genes in the 12q13-15 region (CDK2, WNT1 and WNT10b) were not amplified in any of the tumors. The different patterns of gene amplification and overexpression of CDK4, SAS and MDM2 in parosteal and intramedullary osteosarcomas may help explain the disparity in the biological behaviour of these two types of osteosarcoma.

Juxtacortical osteosarcoma of the jaws

Osteosarcoma is a highly malignant tumour which despite modern surgery and chemotherapy still retains a relatively poor prognosis. This prognosis is, however, much better in the rare variant known as juxtacortical osteosarcoma. Both types of osteosarcoma mainly affect the long bones but the juxtacortical variant may be treated less aggressively and has a much better survival rate. The authors report four cases of juxtacortical osteosarcoma affecting the jaws and discuss these unusual tumours and their management.