Searchable abstracts of presentations at key conferences on calcified tissues
Volume 1 | ECTS2013 | Next issue

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

Card image cap
European Calcified Tissue Society Congress 2013, 18 - 22 May 2013; Lisbon, Portugal

Poster Presentations

Cancer and bone: basic, translational and clinical

ba0001pp132 | Cancer and bone: basic, translational and clinical | ECTS2013

The central role of the histone demethylase JHDM1D in the regulation of tumor associated genes in bone tumor-related cells

Thaler Roman , Spitzer Silvia , Haider Florian , Karlic Heidrun , Klaushofer Klaus , Varga Franz

Tumor development occurs often by over-activation of members of the RAS-oncogene family (small GTPases (sGTPs)). By blocking the mevalonate pathway, aminobisphosphonates (BPs), and statines prevent activation of GTPs by inhibiting their post-translational prenylation. As we have shown, this induces apoptosis in U2OS osteosarcoma cells by re-activation of FAS expression via epigenetic DNA demethylation (1).The histone demethylase JHD...

ba0001pp133 | Cancer and bone: basic, translational and clinical | ECTS2013

Identification of tumorigenic sarcoma cancer stem cells based on high aldehyde dehydrogenase 1 activity

Lohberger Birgit , Rinner Beate , Stuendl Nicole , Walzer Sonja Maria , Windhager Reinhard , Leithner Andreas

Tumors contain a small population of cancer stem cells (CSC) proposed to be responsible for tumor maintenance and relapse. Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate CSCs in different cancer types. This study used the Aldefluor assay and fluorescence-activated cell sorting (FACS) analysis to isolate ALDH1high cells from five human sarcoma cell lines and one primary chordoma cell line. ALDH1high cell...

ba0001pp134 | Cancer and bone: basic, translational and clinical | ECTS2013

Isolation of ALDH1high cells by flow cytometry and investigation of the expression pattern of Wnt pathway genes in primary chordoma cell lines

Lohberger Birgit , Stuendl Nicole , Meditz Katharina , Liegl Bernadette , Leithner Andreas , Rinner Beate

Chordomas are rare, low to intermediate grade malignant bone tumors of the axial skeleton. Current treatment options are limited to surgical procedures as chordomas are largely resistant to conventional radiation and chemotherapy. Cell lines are valuable tools to explore molecular mechanisms involved in tumorigenesis and they have a fundamental impact on the development of new anticancer agents. We established a novel chordoma cell-line, MUG-Chor1, from a recurrent morphologic...

ba0001pp135 | Cancer and bone: basic, translational and clinical | ECTS2013

Anti-RANKL nanobody ALX-0141 shows sustained biomarker inhibition in a Phase I study in healthy postmenopausal Women

Schoen Pieter , Jacobs Sandy , Verschueren Katrien , Ottevaere Ingrid , Sobry Sigrid , Holz Josefin-Beate

Introduction: The interaction between RANK/RANKL is critical for the regulation of osteoclastogenesis and bone resorption. Inhibition of this interaction helps restore the balance between bone resorption and formation. ALX-0141, a novel biological agent (Nanobody) that specifically targets RANKL, was studied in a Phase I trial to assess the safety, tolerability, immunogenicity and PK after single injection.Methods: Forty-two healthy postmenopausal women ...

ba0001pp136 | Cancer and bone: basic, translational and clinical | ECTS2013

Modulation of macrophage activation status by bisphosphonates and breast cancer cells

Sousa Sofia , Monkkonen Jukka , Maatta Jorma

Tumour stromal macrophages differentiate into tumour associated macrophages (TAMs), with characteristics resembling the immunosuppressive M2 polarization instead of the pro-inflammatory M1. TAMs have a central role in promoting tumour vascularization, cancer cell dissemination and suppression of anti-cancer immune response. Cancer cell dissemination leads to metastasis formation which, e.g. in breast cancer often happens in bone marrow. We have studied the in vitro mo...

ba0001pp137 | Cancer and bone: basic, translational and clinical | ECTS2013

Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

Lamoureux Francois , Baud'huin Marc , Ory Benjamin , Gleave Martin , Heymann Dominique , Redini Francoise

Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, zoledronic acid triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), whi...

ba0001pp138 | Cancer and bone: basic, translational and clinical | ECTS2013

New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance

Monderer David , Luseau Alexandrine , Bellec Amelie , David Emmanuelle , Ponsolle Stephanie , Saiagh Soraya , Bercegeay Sylvain , Piloquet Philippe , Denis Marc , Lode Laurence , Redini Francoise , Biger Marine , Heymann Dominique , Heymann Marie-Francoise , Bot Ronan Le , Gouin Francois , Blanchard Frederic

Chondrosarcomas are cartilage-forming, poorly vascularized tumors. With an estimated annual incidence of 1 in 200 000, they represent the second malignant primary bone tumor of adults after osteosarcoma. These tumors are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. However, very few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish...

ba0001pp139 | Cancer and bone: basic, translational and clinical | ECTS2013

New PI3Kα-specific inhibitor, BYL719: therapeutic interest in osteosarcoma

Gobin Berengere , Baud'huin Marc , Charrier Celine , Hervouet Soizic , Lezot Frederic , Blanchard Frederic , Heymann Dominique

It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

ba0001pp140 | Cancer and bone: basic, translational and clinical | ECTS2013

NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation and the tumor development in vivo

Gobin Berengere , Battaglia Severine , Chesneau Julie , Heymann Dominique

Osteosarcoma is the most common primary malignant bone tumor, characterized by osteoid production and/or osteolytic lesions of bone. Despite recent improvements in chemotherapy and surgery, the problem of non-response to chemotherapy remains and constitutes a poor prognosis parameter. Consequently new therapeutic strategies aim to improve the overall rate of survival. The present work investigated the therapeutic interest of a dual phosphatidylinositol-3-kinase (PI3K)/mammalia...

ba0001pp141 | Cancer and bone: basic, translational and clinical | ECTS2013

Therapeutic interest of Imatinib Mesylate in osteosarcoma

Gobin Berengere , Moriceau Gatien , Ory Benjamin , Brion Regis , Redini Francoise , Heymann Dominique

Osteosarcoma is the most common primary malignant bone tumor, characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments points out the importance of exploring new therapeutic ways. Imatinib Mesylate (Glivec, Novartis Pharma), a tyrosine kinase inhibitor, has been originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that Imatinib Mesylate inhibits osteoclast differentiation th...

ba0001pp142 | Cancer and bone: basic, translational and clinical | ECTS2013

Over-expression of Smad7 in osteosarcoma cells inhibits primary tumor growth, the associated bone osteolysis and the development of lung metastasis in murine xenograft model

Lamora Audrey , Talbot Julie , Gobin Berengere , Leduc Marion , Taurelle Julien , Brion Regis , Heymann Dominique , Redini Francoise , Verrecchia Franck

Osteosarcoma, the main malignant primary bone tumor, affects a ‘young’ population composed of children and young adults. Current treatment consists of tumor resection associated with chemotherapy. Unfortunately in many cases, a lack of response to anti-tumor drugs is observed, leading to development of metastases and to the patient’s death. Because TGF-β promotes metastases from many solid epithelial tumors, we investigated the effect of inhibitory Smad7 ov...

ba0001pp143 | Cancer and bone: basic, translational and clinical | ECTS2013

Bone remodelling in patients with an IgM monoclonal gammopathy (Waldenstrom disease – MGUS)

Chappard Daniel , Bouvard Beatrice , Royer Mathieu , Hoppe Emmanuel , Legrand Erick , Ifrah Norbert , Audran Maurice

An IgM monoclonal gammopathy (MGUS) is often the first sign of a lymphomonocytic B-lymphoma (Waldenström macroglobulinemia-WD). Osteolytic lesions can occur in B cell malignancies (WD, hairy cell leukemia, LLC\..) but are less frequent than in myeloma. In addition, bone remodeling in WD is poorly understood. However, an osteoporosis is often observed in MGUS patients. We studied a series of bone biopsies performed in patients with an IgM gammopathy by histomorphometry, mi...

ba0001pp144 | Cancer and bone: basic, translational and clinical | ECTS2013

Selective BET bromodomains epigenetic signaling inhibition as a therapeutic strategy in primary bone tumors

Lamoureux Francois , Baud'huin Marc , Rodriguez Lidia , Jacques Camille , Berreur Martine , Bradner James E , Redini Francoise , Heymann Dominique , Ory Benjamin

Osteosarcoma is the most frequent primary bone tumor that develops mainly in young adults. The survival rate at 5 years is below 30% for patients with poor response to treatment or with metastasis.The histones modifications are of critical importance in maintaining the transcription program of both normal and tumor cells. The bromodomain and extra-terminal domain (BET) protein family is an important class of ‘histone reading protein’ capable to...

ba0001pp145 | Cancer and bone: basic, translational and clinical | ECTS2013

Synergistic anti-tumour effects on human breast cancer cells by mevalonate pathway inhibitors atorvastatin and zoledronic acid

Gobel Andy , Thiele Stefanie , Rauner Martina , Lorenz C Hofbauer , Tilman D Rachner

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

ba0001pp146 | Cancer and bone: basic, translational and clinical | ECTS2013

Metabolomics identifies plasma biomarkers of multiple myeloma development and progression

Mariani Elisabetta , Fontana Francesca , Mari Silvia , Manteiga Jose Manuel Garcia , Marcatti Magda , Napoli Nicola , Camnasio Francesco , Fraschini Gianfranco , Caneva Enrico , Sitia Roberto , Musco Giovanna , Ciceri Fabio , Cenci Simone

Multiple myeloma is an incurable neoplastic disorder of plasma cells, which invade the bone marrow, secrete monoclonal immunoglobulins, and induce bone lesions, hypercalcemia, anemia and renal failure. The development of myeloma relies on vicious interactions with the bone microenvironment, a deeper knowledge of which is needed to identify prognostic markers and potential therapeutic targets. To achieve an unbiased, comprehensive assessment of the extracellular milieu of myelo...

ba0001pp147 | Cancer and bone: basic, translational and clinical | ECTS2013

Involvement of the co-receptor RAMP2 in the progression of breast cancer-induced osteolytic lesions

Cappariello Alfredo , Rucci Nadia , Capulli Mattia , Muraca Maurizio , Teti Anna

Bone is the primary site of metastasis for breast cancer, which leads mainly to osteolytic lesions, Cancer cells can expand into the bone for their ability to ‘dialogue’ with resident cells, interfering with the physiological processes of bone turnover. In this study, a large-scale analysis comparing gene expression of biopsies of bone and visceral metastases from human breast cancer patients showed that the receptor (G protein-coupled) activity modifying protein-2 (...

ba0001pp148 | Cancer and bone: basic, translational and clinical | ECTS2013

Direct administration of zoledronate acid improves bone structure in local osteoporotic lesion of ovariectomized rats

Matsuo Yohei , Kashii Masafumi , Sugiura Tsuyoshi , Morimoto Tokimitsu , Honda Hirotsugu , Kaito Takashi , Iwasaki Motoki , Yoshikawa Hideki

Objective: To examine the efficacy and safety of direct administration of zoledronate acid (ZOL) on local osteoporotic lesion of ovariectomized rats.Methods: Six weeks later after ovariectomy, 16 6-month-old female S.D. rats were divided into the two groups with no differences of body weight and BMD of the proximal tibia. In the group L, 50 μl ZOL at a dose of 67 μg/kg were locally injected into the bone marrow between the two dr...

ba0001pp149 | Cancer and bone: basic, translational and clinical | ECTS2013

Cytotoxicity of picocyanobacteria strains of the genera Cyanobium on osteosarcoma cells

Martins Rosario , Costa Margarida , Garcia Monica , Barros Piedade , Costa-Rodrigues Joao , Vasconcelos Vitor , Fernandes Maria

Marine cyanobacteria have been recognized as an important source of bioactive compounds. The cytotoxicity on cancer cell lines has been extensively explored and several cyanobacteria metabolites are already described as potential anticancer compounds or are considered useful templates for the design of new anticancer drugs. The majority of compounds have been isolated from filamentous or colonial cyanobacteria that growth in high densities along shores. In contrast, picoplankt...

ba0001pp150 | Cancer and bone: basic, translational and clinical | ECTS2013

Inhibition of osteoclastogenesis by proton pump inhibitors on co-cultures of human osteoclasts and breast cancer cells

Reis Sara , Fernandes Maria , Costa-Rodrigues Joao

Proton pump inhibitors (PPIs) are a class of drugs particularly used in gastric disorders. They promote a decrease on gastric acid secretion by inhibiting the H+/K+ ATPases. Osteoclasts are cells specialized in bone resorption by H+ translocation to the bone surface. Thus, PPIs might be regarded as potential tools to modulate osteoclast resorption activity, particularly in conditions that are associated with a hyperactivation of osteoclasts, li...

ba0001pp151 | Cancer and bone: basic, translational and clinical | ECTS2013

Trolox inhibits breast cancer bone metastasis and bone destruction through suppression of PGE2 production

Lee Jong-Ho , Ha Hyunil , Jin Won Jong , Kim Sun-Don , Jung Jin Suk , Hong-Hee Kim , Lee Zang Hee

The skeleton is a preferred site of metastasis in patients with advanced breast cancer, and bone loss is one of the major complications of breast cancer metastasis. Therefore, prevention of bone metastasis is clinically important. Our previous observation of an anti-osteoclastic activity of Trolox, a vitamin E analogue, led us to investigate whether Trolox could inhibit bone metastasis and bone destruction induced by breast cancer. I.P. administration of Trolox markedly inhibi...

ba0001pp152 | Cancer and bone: basic, translational and clinical | ECTS2013

Carcinoid tumors and DXA assessment: a study in 222 menopausal women

Poiana Catalina , Carsote Mara , Petris Rodica , Trifanescu Raluca , Voicu Gabriela , Paun Diana

Introduction: The bone mineral density loss may be related to cancer. A specific correlation in the neuroendocrine tumors (NET) is not fully described yet.Aim: The analyze DXA in patients with or without NET.Material and method: We perfomed central DXA (spine and hip) with a GE Lunar device in post-menopausal women. None of them were previously treated with anti-osteoporotics drugs. The study groups included women with carcinoid tu...

ba0001pp153 | Cancer and bone: basic, translational and clinical | ECTS2013

The DXA results in 41 patients with neuroendocrine tumors: a transversal study

Carsote Mara , Geleriu Andreea , Dusceac Roxana , Miron Roxana , Ene Cristina , Radoi Valentin , Voicu Gabriela , Poiana Catalina

Different results might be registered in DXA assessment in patients with neuroendocrine tumors (NET) since various factors induce bone disturbances as bone metastases, vitamin D hypovitaminosis, etc.Aim: The analyze DXA in NET.Material and method: The patients (p) were evaluated between 2008 and 2013. The diagnosis of NET was histological confirmed. We also included medullar thyroid cancer (MTC) with distance metastases and carcino...

ba0001pp154 | Cancer and bone: basic, translational and clinical | ECTS2013

miR-192 impairs invasion and tumor-induced osteolysis by repressing CCL2 in bone metastatic colonization

Valencia Karmele , Luis-Ravelo Diego , Bovy Nicolas , Martinez-Canarias Susana , Ormazabal Cristina , Zandueta Carolina , Anton Iker , Struman Ingrid , Tabruyn Sebastien , Segura Victor , De Las Rivas Javier , Bandres Eva

Emerging evidence suggests that miRNAs (miR) can modulate a complex gene network in a cell-intrinsic and non-cell autonomous manner. We previously identified by transcriptomic analysis miR-192 to be heavily downregulated in different highly metastatic subpopulations (HMS) isolated from bone metastases in a lung cancer mice model, but its mechanistic contribution to the prometastatic activity remains unknown.To delineate the pleiotropic functions elicited...

ba0001pp155 | Cancer and bone: basic, translational and clinical | ECTS2013

Influence of sex steroids on sclerostin levels in patients with prostate cancer

Munoz-Torres Manuel , Reyes-Garcia Rebeca , Garcia-Fontana Beatriz , Morales-Santana Sonia , Varsavsky Mariela , Maria Dolores Aviles-Perez , Garcia-Martin Antonia

There is increasing evidence for the key role of osteocytes in the regulation of bone remodeling. One of the main products of these cells, sclerostin, inhibits bone formation and may also stimulate bone resorption. To our knowledge, there are few data in prostate cancer (PC) patients especially in patients with hypogonadism related to androgen deprivation therapy (ADT). The aim of this study was to compare serum levels of sclerostin in ADT-treated and untreated PC patients wit...

ba0001pp156 | Cancer and bone: basic, translational and clinical | ECTS2013

Vitamin D serum levels and breast cancer risk in a mediterranean population: a case–control study

Rodriguez-Sanz Maria , Garcia-Giralt Natalia , Torres Elisa , De Ramon Marta , Cano-Sanchez Antonio , Garcia-Perez Miguel Angel , Servitja Sonia , Garrigos Laia , Martinez-Garcia Maria , Tusquets Ignasi , Albanell Joan , Diez Adolfo , Prieto-Alhambra Daniel , Nogues Xavier

Background: Besides the classic actions of vitamin D on bone metabolism and calcium homeostasis, there is evidence emphasizing its antiproliferative and proapoptotic activities. Data coming mostly from Northern regions suggest an effect of 25-hydroxyvitamin D (25(OH)D) serum concentrations on breast cancer prevention. We aimed to study the association between 25(OH)D concentrations and breast cancer risk in a Mediterranean population (Spain).Methods: We ...

ba0001pp157 | Cancer and bone: basic, translational and clinical | ECTS2013

Bone metastatic prostate cancer cells regulate their growth via impairing osteoblast differentiation

van Driel Marjolein , Robbesom Iris , Koster Ruben , Boers-Sijmons Bianca , Chiba Hideki , van Leeuwen Hans

Metastases to the bone are the incurable final outcomes of cancer, reducing both length and quality of life in an aggressive way. Despite the discoveries of many factors involved, no cure has been found. Metastatic outgrow starts in interaction with the bone micro-environment. The first attachment in bone is with the osteoblasts lining the endosteal surface. Our aim is to study the role of the osteoblasts in metastatic tumor spread and growth.We used an ...

ba0001pp158 | Cancer and bone: basic, translational and clinical | ECTS2013

Role of receptor activity modifying proteins in skeletal regulation

Pacharne Suruchi , Richards Gareth , Wang Ning , Skerry Timothy , Caron Kathleen

Receptor activity modifying proteins (RAMPs 1, 2 and 3) are a class of important accessory proteins that interact and regulate several G-protein coupled receptor (GPCR) activity by finely modulating ligand interaction and in some cases trafficking receptors to cell surface.Predominant roles of RAMPs include ligand selectivity in receptors for Calcitonin (CT) family of peptides that comprise calcitonin, calcitonin gene related peptide, amylin and Adrenome...

ba0001pp159 | Cancer and bone: basic, translational and clinical | ECTS2013

A novel antagonist of the canonical Wnt-signalling pathway, Sostdc1, is expressed in experimental models of myeloma and suppresses bone formation

Buckle Clive , Faraahi Zahra , Lawson Michelle , Eaton Colby , Vanderkerken Karin , Croucher Peter

Introduction: Patients with multiple myeloma (MM) commonly present with devastating bone disease mediated by increased bone resorption and suppressed bone formation. We have previously shown that blocking activity of the Wnt antagonist Dkk-1 promotes osteoblastogenesis and inhibits development of bone lesions in experimental models of MM. In the 5T murine models of MM, tumour cells home to the bone marrow. Injection of 5T2MM cells into C57BLKalwRij mice results in bone disease...

ba0001pp160 | Cancer and bone: basic, translational and clinical | ECTS2013

Glucose ceramide synthase inhibitors prevent osteoclast activation and limit myeloma-induced osteolytic lesions

Ersek Adel , Xu Ke , Karadimitris Anastasios , Horwood Nicole J

Glycosphingolipids (GSL) are essential structural components of mammalian cell membranes and lipid rafts that exert pleiotropic effects on cell survival, proliferation, and differentiation. Cancer associated GSL have been shown to promote tumor growth, angiogenesis, and metastasis; however their role in osteoclast (OC) activation and the development of osteolytic bone diseases such as multiple myeloma are not known. We investigated the hypothesis that GSL contribute to OC acti...

ba0001pp161 | Cancer and bone: basic, translational and clinical | ECTS2013

Effect of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for breast cancer: the ProBONE II Study

Hadji Peyman , Kauka Anette , Bauer Thomas , Birkholz Katrin , Baier Monika , Muth Mathias Muth , Ziller May

Introduction: Bone mineral density (BMD) evaluations have shown that adjuvant chemotherapy or endocrine therapy (ET) for early breast cancer (BC) is associated with accelerated BMD loss and increased fracture risk. In recent studies, zoledronic acid (ZOL) increased BMD in premenopausal and postmenopausal women with BC, and improved disease-free survival in some patient subsets compared with no ZOL. The purpose of the current study was to investigate the effect of adjuvant trea...

ba0001pp162 | Cancer and bone: basic, translational and clinical | ECTS2013

Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer: the ZOTECT Study

Hadji Peyman , Ziller May , Maurer Tobias , Autenrieth Michael , Muth Mathias , Ruebel Amelie , May Christoph , Birkholz Katrin , Diebel Erhardt , Gleissneer Jochen , Rothe Peter , Gschwend Juergen E

Introduction: The prospective, single-arm, open-label ZOTECT study was designed to assess the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients with bone metastases.Methods: Patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) who have not received bisphosphonates for ≥6 months were enrolled at 98 sites in Ge...