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      Three cases of bone metastases in patients with gastrointestinal stromal tumors

      case-report

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          Abstract

          Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib) are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age), and one man (62 years of age). Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.

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          Most cited references19

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          Diagnosis of gastrointestinal stromal tumors: A consensus approach.

          As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time. Copyright 2002, Elsevier Science (USA). All rights reserved.
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            Antitumor effects of bisphosphonates.

            Bisphosphonates are widely used to treat skeletal complications of malignancy. These drugs accumulate in bone where they inhibit osteoclastic bone resorption and reduce the local release of factors that stimulate tumor growth. The mechanism of action of bisphosphonates is dependent on chemical structure: Nonnitrogen-containing compounds (e.g., etidronate, clodronate) are metabolized into cytotoxic analogues of ATP, whereas the more potent nitrogen-containing compounds (N-BPs; e.g., pamidronate, ibandronate, zoledronic acid) inhibit protein prenylation, thus affecting cell function and survival. Because protein prenylation is required by all cells, not just osteoclasts, the possibility arises that N-BPs could also affect the viability of tumor cells. Several groups have investigated the in vitro effects of bisphosphonates, either alone or in combination with other antineoplastic agents, on the viability and metastatic properties of many tumor cell types. Similarly, the effect of bisphosphonate treatment on osteolysis and tumor burden has been studied in a variety of animal tumor models. In vitro, submicromolar concentrations of N-BPs inhibited tumor cell adhesion and reduced invasion through extracellular matrix. At higher concentrations, antiproliferative and proapoptotic effects have been reported. In animal models of bone metastases, bisphosphonate treatment markedly reduced osteolytic lesions. There is also evidence of a reduction in tumor burden in bone and occasionally in other organs. Survival may be prolonged, but bisphosphonates do not appear to inhibit the growth of primary soft tissue tumors or orthotopic xenografts. The cell culture data clearly demonstrated that N-BPs exert antitumor properties and interact synergistically with other antineoplastic agents. As bisphosphonates accumulate in bone, they can also exert cytostatic effects on tumor cells in bone metastases, either directly or indirectly via osteoclast inhibition and alterations in the bone microenvironment. Further in vivo research is now required to optimize the dosing regimen of N-BPs to exploit fully their antitumor potential. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11128
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              Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line.

              Although emerging data suggest that zoledronic acid (Zol) may have different anti-tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti-tumoural and anti-angiogenetic effect of zoledronic acid in non-small-cell lung cancer (NSCLC) cells. We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti-angiogenic activity and apoptotic responses to it. We observed that highest Zol concentration (100μm) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P=0.0001). Zol concentration from 5 to 100μm for 2 days induced significant concentration-dependent cell death in adherent cells. Furthermore, Zol (10-100μm) induced dose-dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium. Taken together, these results support a possible anti-cancer and anti-angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti-cancer agent in non-small-cell lung cancer. © 2011 Blackwell Publishing Ltd.
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                Author and article information

                Journal
                Rare Tumors
                RT
                RT
                Rare Tumors
                PAGEPress Publications (Pavia, Italy )
                2036-3605
                2036-3613
                4 April 2011
                4 April 2011
                : 3
                : 2
                : e17
                Affiliations
                [1 ]Department of Radiology, Sant’Orsola Malpighi Hospital, Bologna University, Bologna, Italy
                [2 ]Department of Hematology and Oncologic Science “L. & A. Seragnoli”, Sant’Orsola Malpighi Hospital, Bologna University, Bologna, Italy
                Author notes
                Correspondence: Valerio Di Scioscio, Policlinico Sant’ Orsola Malpighi Bologna University Via Massarenti 9, 40138, Bologna, Italy. Tel. +39.051.6364026 - Fax. +39.051.6364223. E-mail: valerio.discioscio@ 123456aosp.bo.it

                Contributions: VDS, manuscript design, data acquisition and interpretation, manuscript critical revision, manuscript final approval; LG, data acquisition and interpretation, manuscript final approval; MCP, manuscript design, data acquisition and interpretation, manuscript final approval; MAP, manuscript design, manuscript critical revision, manuscript final approval; AM, contributions to conception and design, final approval of the version to be published; MN, contributions to conception and design, final approval of the version to be published; AB, acquisition and interpretation of data, final approval of the version to be published; MDB, critical revision for important intellectual content, final approval of the version to be published; AM, CL, MS, manuscript design, manuscript final approval; GG, data acquisition and interpretation, manuscript final approval; GB, critical revision for important intellectual content, final approval of the version to be published; MZ, manuscript critical revision, manuscript final approval.

                Conflict of interest: the authors report no conflicts of interest.

                Article
                rt.2011.e17
                10.4081/rt.2011.e17
                3132121
                21769316
                081ea49d-b20b-48c6-9145-4ed3b82113a2
                ©Copyright Di Scioscio et al., 2011

                This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0).

                Licensee PAGEPress, Italy

                History
                : 8 February 2011
                : 13 April 2011
                : 15 April 2011
                Categories
                Case Report

                Oncology & Radiotherapy
                computerezed tomografy,scan,bone metastases,imatinib.,gastrointestinal stromal tumors

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