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Background: Drug resistance is closely related to cancer cell stemness, that is acquired along with resistance to various anticancer agents. However, this has not been investigated as a potential mechanism underlying cancer cell resistance to zoledronate, that is used to suppress bone metastasis., Materials and Methods: Zoledronate-resistant A549 lung cancer and MG63 osteosarcoma cell lines were established by repeated treatment with sub-lethal concentrations of zoledronate. Expression levels of the stem cell marker NANOG, cMYC, octamer-binding transcription factor 4, and sex-determining region Y-box 2 were evaluated and sphere formation was compared between parental and resistant cell lines. Tumourigenicity was assessed in vivo., Results: Stem cell marker expression was up-regulated and sphere formation was enhanced in resistant compared to parental cells and showed greater tumour formation capacity in mice., Conclusion: Repeated treatment of malignant tumour cell lines with zoledronate, induces the development of drug resistance and stemness., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Lipoma and well-differentiated liposarcoma (WDLS) are two representative lipogenic soft tissue tumors that have similar clinical, radiological, and pathological characteristics. Accordingly, it is difficult to distinguish these tumors preoperatively. Plasma D-dimer levels are associated with the status of tumor progression, and we hypothesized that D-dimer levels could contribute to differential diagnosis. The D-dimer levels of these two entities have not yet been reported., Patients and Methods: We investigated 43 cases of lipoma and 14 cases of WDLS. We evaluated the utility of D-dimer levels and other clinicopathological factors for preoperative differential diagnosis between the two entities., Results: Receiver operating characteristic analysis revealed that the D-dimer level may contribute to differential diagnosis (area under the curve=0.73). Univariate and multivariate models demonstrated that plasma D-dimer levels (p=0.001 (univariate), and p=0.006 (multivariate)) and lower extremity location (p=0.006 (univariate), and p=0.03 (multivariate)) were independent risk factors for WDLS., Conclusion: The D-dimer level may be a helpful marker for preoperative differential diagnosis between lipoma and WDLS., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear., Materials and Methods: Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance., Results: Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance., Conclusion: Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.

Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.

Background: Although zoledronic acid (ZOL) has been reported to show anti-tumour effects on various malignant tumours, few studies have reported the molecular mechanisms of resistance to ZOL., Materials and Methods: A drug-resistant cell line was developed by repeatedly treating human osteosarcoma cell line HOS with ZOL. Expression status of drug resistance-related molecules including ATP-binding cassette (ABC) and heat-shock protein 27 (HSP27) was confirmed in order to analyse molecular mechanisms of the drug resistance., Results: Repeated treatment with ZOL induced drug resistance with down-regulation of apoptosis in the resistant cell line. Although ABC expression was down-regulated, up-regulation of HSP27 in the resistant cell line was confirmed. The resistance was overcome by HSP27 silencing., Conclusion: Resistance to ZOL in osteosarcoma cells may be induced by a molecular mechanism different from conventional efflux pump-based resistance. Up-regulation of HSP27 expression may play a role in the development of ZOL resistance in HOS cells.

The therapeutic effect of Raloxifene (RLX) on bone turnover markers was investigated in the elderly women with osteoporosis. The mean age of the control group (< 75 years old) was 67.0 years old, similar to a large-scale clinical trial (MORE study) , and that of the elderly group ( > or =years old) was 80.7 years old. The degrees of percentage change from baseline of serum NTX, urine NTX, and BAP in the elderly group were the same as in the control group. The interval of measurement to assess the effect of RLX seems to be appropriate 3 months after treatment in serum and urine NTX, and 6 months in BAP.