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1.  Diversity of angiogenesis among malignant bone tumors 
Molecular and Clinical Oncology  2012;1(1):131-136.
Several studies have demonstrated that angiogenesis assessed by microvessel density (MVD) correlates with patient prognosis in various types of cancer, whereas data regarding the relevance of angiogenesis and prognosis in malignant bone tumors are scarce and controversial. The aim of this study was to examine MVD in representative malignant bone tumors, such as osteosarcoma, chondrosarcoma and Ewing’s sarcoma, in order to clarify the role of angiogenesis in prognosis. A total of 69 patients with malignant bone tumors, including 44 osteosarcomas, 20 chondrosarcomas and 5 Ewing’s sarcomas, were reviewed retrospectively and treated at our hospital between 1980 and 2007. Biopsy or pre-chemotherapy surgical specimens were immunohistochemically stained with anti-CD34 antibody. The MVD values of osteosarcomas and Ewing’s sarcomas were significantly higher compared to chondrosarcoma. In osteosarcomas with high MVD, American Joint Committee on Cancer stage IIA, good histological response to chemotherapy was significantly correlated with better disease-free survival, while MVD was closely associated with age and chemotherapy response. In chondrosarcomas, the surgical margin (marginal and intralesional), MVD (high), tumor size (≥8) and histological grade (grades 2 and 3) significantly correlated with a shorter disease-free survival, while MVD was closely associated with age and histological grade. These findings showed that osteosarcomas and Ewing’s sarcomas were hypervascular, compared to chondrosarcomas. In osteosarcomas, hypervascularity induced good chemotherapy response, leading to better prognosis, while in chondrosarcomas, high MVD was associated with histological grade and predicted poor prognosis.
doi:10.3892/mco.2012.11
PMCID: PMC3956242  PMID: 24649135
angiogenesis; osteosarcoma; chondrosarcoma; Ewing’s sarcoma; prognosis
2.  Correlation between p38 mitogen-activated protein kinase and human telomerase reverse transcriptase in sarcomas 
Background
One of the major components of telomerase is the human telomerase reverse transcriptase (hTERT) as the catalytic protein. hTERT mRNA expression are reported to be associated with prognosis and tumor progression in several sarcomas. However, there is no clear understanding of the mechanisms of hTERT in human sarcomas. Recent studies have suggested that signals transmitted through p38 mitogen-activated protein kinase (MAPK) can increase or decrease hTERT transcription in human cells. The purpose of this study was to analyse the correlation between p38 MAPK and hTERT in sarcoma samples.
Methods
We investigated 36 soft tissue malignant fibrous histiocytomas (MFH), 24 liposarcomas (LS) and 9 bone MFH samples for hTERT and p38 MAPK expression. Quantitative detection of hTERT and p38 MAPK was performed by RT-PCR.
Results
There was a significant positive correlation between the values of hTERT and p38 MAPK in all samples (r = 0.445, p = 0.0001), soft tissue MFH (r = 0.352, p = 0.0352), LS (r = 0.704, p = 0.0001) and bone MFH samples (r = 0.802, p = 0.0093). Patients who had a higher than average expression of p38 MAPK had a significantly worse prognosis than other patients (p = 0.0036).
Conclusions
p38 MAPK may play a role in up-regulation of hTERT, and therefore, p38 MAPK may be a useful marker in the assessment of hTERT and patients' prognosis in sarcomas.
doi:10.1186/1756-9966-31-5
PMCID: PMC3296589  PMID: 22243975
p38 mitogen-activated protein kinase; human telomerase reverse transcriptase; malignant fibrous histiocytoma; liposarcoma
3.  Lipophilic Bisphosphonates as Dual Farnesyl/Geranylgeranyl Diphosphate Synthase Inhibitors: An X-ray and NMR Investigation 
Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anti-cancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth, how cell activity can be predicted based on enzyme inhibition data, and, using x-ray diffraction, solid state NMR and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS.
doi:10.1021/ja808285e
PMCID: PMC2753403  PMID: 19309137
4.  Liposarcoma Arising in the Foot: A Case Report 
Case Reports in Medicine  2009;2009:630203.
Liposarcoma is categorized as a soft tissue sarcoma and most commonly appears in the lower extremities and rarely in the foot during adulthood. We present a very rare case report of a primary well-differentiated liposarcoma arising in the foot on a 60-year-old female. Marginal resection of the tumor with metatarsal ray amputation was eventually performed. The patient's postoperative course was uneventful without recurrence 5 years after the original operation. The authors review the literature and also report on the low incidence of this tumor arising in the foot.
doi:10.1155/2009/630203
PMCID: PMC2774536  PMID: 19902014
5.  Immunohistochemical expression of promyelocytic leukemia body in soft tissue sarcomas 
Background
The function of promyelocytic leukemia (PML) bodies is not well known but plays an important role in controlling cell proliferation, apoptosis and senescence. This study was undertaken to analyze the clinical significance of PML body expression in primary tumor samples from malignant fibrous histiocytoma (MFH) and liposarcoma patients.
Methods
We studied MFH and liposarcoma samples from 55 patients for PML bodies. Fluorescent immunostaining of PML bodies was performed in the paraffin-embedded tumor sections.
Results
PML body immunostaining was identified in 63.9% of MFH and 63.2% of liposarcoma samples. PML body expression rates of all sarcoma cells were 1.5 ± 1.8% (range: 0–7.0) in MFH and 1.3 ± 1.4% (0–5.2) in liposarcoma samples. PML body expression (p = 0.0053) and a high rate of PML body expression (p = 0.0012) were significantly greater prognostic risk factors for death than the other clinical factors in MFH patients. All liposarcoma patients without expression of PML were disease free at the end of the study.
Conclusion
Our study suggests that the presence of PML bodies may indicate a poor prognosis for MFH and liposarcoma patients.
doi:10.1186/1756-9966-27-73
PMCID: PMC2611968  PMID: 19025608
6.  Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study 
BMC Cancer  2005;5:79.
Background
Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures.
Methods
Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation.
Results
With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range.
Conclusion
In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.
doi:10.1186/1471-2407-5-79
PMCID: PMC1181808  PMID: 16026629
7.  Hyperthermia using magnetite cationic liposomes for hamster osteosarcoma 
Background
We have developed magnetite cationic liposomes (MCLs) and applied them to local hyperthermia as a mediator. MCLs have a positive charge and generate heat under an alternating magnetic field (AMF) by hysteresis loss. In this study, the effect of hyperthermia using MCLs was examined in an in vivo study of hamster osteosarcoma.
Method
MCLs were injected into the osteosarcoma and then subjected to an AMF.
Results
The tumor was heated at over 42°C, but other normal tissues were not heated as much. Complete regression was observed in 100% of the treated group hamsters, whereas no regression was observed in the control group hamsters. At day 12, the average tumor volume of the treated hamsters was about 1/1000 of that of the control hamsters. In the treated hamsters, no regrowth of osteosarcomas was observed over a period of 3 months after the complete regression.
Conclusion
These results suggest that this treatment is effective for osteosarcoma.
doi:10.1186/1477-044X-2-3
PMCID: PMC400754  PMID: 15040804

Results 1-7 (7)