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Sample records for controls bone metastasis

  1. Pathogenesis of bone metastasis

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    Erdinc Nayir

    2016-01-01

    Full Text Available Bone metastases are more frequently seen as a complication of cancer than primary bone tumors. For example, it can be seen in as many as 70% of advanced stage breast and prostate cancer cases. Metastatic bone disease is generally categorized as osteoblastic, and osteolytic disease. However most of the cancer types demonstrate a wide spectrum between these two extremes. Paracrine interaction between parathyroid hormone–related protein (PTHrP which increases the rate of bone osteolysis, and transforming growth factor-β (TGF-β plays a role in osteolytic metastasis. Increased local bone PTHrP concentration increases expression of receptor activator of nuclear factor kappa-B ligand (RANKL with resultant activation of osteoclastogenesis. Endothelin – 1 (ET-1, and dickkopf homolog -1 (DKK-1 produced by tumor involve in osteoblastic metastasis. DKK-1 is the central regulator of osteoblastic activity, and osteoblastic bone metastasis. For the elaboration of treatment strategies against frequently seen complication, that is, bone metastases, targets involving in pathogenesis of these complications should be taken into consideration.

  2. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

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    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0408 TITLE: Macrophage Efferocytosis and Prostate Cancer Bone Metastasis PRINCIPAL INVESTIGATOR: Jacqueline D. Jones...0408 Macrophage Efferocytosis and Prostate Cancer Bone Metastasis 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...efferocytosis. The translation of this functional role during pathophysiological states such as tumor metastasis to the skeleton is unknown. The purpose of this

  3. Prostate Cancer Presenting with Parietal Bone Metastasis

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    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  4. Cellular Plasticity in Prostate Cancer Bone Metastasis

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    Dima Y. Jadaan

    2015-01-01

    Full Text Available Purpose. Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET, a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC bone metastasis. Methods. An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues. Results. The review included nineteen studies. More than 60% of the studies used ≤20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/β pathway, were highly expressed in bone metastases. Conclusions. Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity.

  5. Imaging of bone metastasis: An update

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    Gerard; J; O’Sullivan; Fiona; L; Carty; Carmel; G; Cronin

    2015-01-01

    Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques whichfuse morphological and functional data are the most sensitive and specific, and positron emission tomography(PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

  6. Therapy for bone metastasis from different cancers

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    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  7. Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

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    Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

    2014-02-01

    The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.

  8. Radiofrequency thermal ablation for pain control in patients with single painful bone metastasis from hepatocellular carcinoma

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    Carrafiello, Gianpaolo [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: gcarraf@tin.it; Lagana, Domenico [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: donlaga@gmail.com; Ianniello, Andrea [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: ianand@libero.it; Nicotera, Paolo [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: paolonicotera@virgilio.it; Fontana, Federico [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: fede.fontana@libero.it; Dizonno, Massimiliano [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: massimilianodizonno@libero.it; Cuffari, Salvatore [Service of Anaesthesiology and Palliative Care, University of Insubria, 21100 Varese (Italy)], E-mail: salvatore.cuffari@libero.it; Fugazzola, Carlo [Department of Radiology, Vascular and Interventional Radiology, University of Insubria, 21100 Varese (Italy)], E-mail: carlo.fugazzola@ospedale.varese.it

    2009-08-15

    Objective: The aim of this study was to assess the safety and the efficacy of radiofrequency thermal ablation (RFA) for pain relief and analgesics use reduction in two patients with painful bone metastases from hepatocellular carcinoma (HCC). Materials and methods: Two patients with lytic metastases from HCC located at the left superior ileo-pubic branch and at the middle arch of VII rib, performed RFA displacing a LeVeen Needle (3.5 and 4.0 cm diameter) under US (ultrasonography) and fluoroscopic guidance. Two methods were used to determine the response of both patients: the first method was to measure patient's worst pain with a Brief Pain Inventory (BPI) 1 day after the procedure, every week for 1 month, and thereafter at week 8 and 12 (total follow-up 3 months); Second method was to evaluate patient's analgesics use recorded at week 1, 4, 8 and 12. Analgesic medication use was translated into a morphine-equivalent dose. Results: The RFA were well tolerated by the patients who did not develop any complication. Both patients obtained substantial reduction of pain, which decreased from a mean score of 8 to approximately 2 in 4 weeks. In both patients we observed a reduction in the use of morphine dose-equivalent after a peak at week 1. CT (computed tomography) imaging, performed at 1 month after RFA, demonstrated that both procedures were technically successful and safe because consistent necrosis and no evidence for complications were observed. Conclusion: RFA provides a potential alternative method for palliation of painful osteolytic metastases from HCC; the procedure is safe, and the pain relief is substantial.

  9. Imaging of Pelvic Bone Metastasis from Malignant Phyllodes Breast Tumor

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    Nguyen, Ba D.

    2015-01-01

    The author reports a patient with a malignant phyllodes breast tumor, who then had a ten-year disease free interval before she developed a left pelvic bone metastasis and soft tissue invasion. Cross-sectional and radionuclide imaging of its musculoskeletal metastasis is presented. Literature concerning bone metastasis from phyllodes tumor is also briefly reviewed and discussed, along with its epidemiology.

  10. Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

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    Santini, Daniele; Procopio, Giuseppe; Porta, Camillo; Ibrahim, Toni; Barni, Sandro; Mazzara, Calogero; Fontana, Andrea; Berruti, Alfredo; Berardi, Rossana; Vincenzi, Bruno; Ortega, Cinzia; Ottaviani, Davide; Carteni, Giacomo; Lanzetta, Gaetano; Virzì, Vladimir; Santoni, Matteo; Silvestris, Nicola; Satolli, Maria Antonietta; Collovà, Elena; Russo, Antonio; Badalamenti, Giuseppe; Fedeli, Stefano Luzi; Tanca, Francesca Maria; Adamo, Vincenzo; Maiello, Evaristo; Sabbatini, Roberto; Felici, Alessandra; Cinieri, Saverio; Tonini, Giuseppe; Bracarda, Sergio

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Patients and methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). Conclusions RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk. PMID:24386138

  11. Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

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    Daniele Santini

    Full Text Available BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC as disease-related survival improves. There are few data on the natural history of bone disease in RCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs, and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL, median time to first SRE was significantly prolonged versus control (n = 186 (3 months vs 1 month for control; P<0.05. CONCLUSIONS: RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

  12. Global secretome analysis identifies novel mediators of bone metastasis

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    Mario Andres Blanco; Gary LeRoy; Zia Khan; Ma(s)a Ale(c)kovi(c); Barry M Zee; Benjamin A Garcia; Yibin Kang

    2012-01-01

    Bone is the one of the most common sites of distant metastasis of solid tumors.Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma.To comprehensively profile secreted proteins associated with bone metastasis,we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types.By comparing the secretomes of parental cells and their bone metastatic derivatives,we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines.We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis.Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1,CST2,and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1.Overall,our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

  13. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

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    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  14. The role of osteoclasts in breast cancer bone metastasis

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    François Le Pape

    2016-09-01

    Full Text Available Breast cancer frequently metastasises to the skeleton, interfering with the normal bone remodelling process and inducing bone degradation. Bone degradation is caused by osteoclasts, the normal bone-resorbing cells. Osteoclast-mediated bone degradation subsequently leads to the release of bone-derived factors that promote skeletal tumour growth. Osteoclasts themselves stimulate tumour growth. This Review describes the molecular mechanisms through which osteoclasts and breast cancer cells collaborate with each other, triggering the formation of osteolytic bone metastasis.

  15. Metastasis and bone loss: Advancing treatment and prevention

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    Coleman, Robert E.; Lipton, Allan; Roodman, G. David; Guise, Theresa A.; Boyce, Brendon F.; Brufsky, Adam M.; Clézardin, Philippe; Croucher, Peter I.; Gralow, Julie R.; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R.; Smith, Matthew R.; Suva, Larry J.

    2011-01-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy. PMID:20478658

  16. Metastasis and bone loss: advancing treatment and prevention.

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    Coleman, Robert E; Lipton, Allan; Roodman, G David; Guise, Theresa A; Boyce, Brendon F; Brufsky, Adam M; Clézardin, Philippe; Croucher, Peter I; Gralow, Julie R; Hadji, Peyman; Holen, Ingunn; Mundy, Gregory R; Smith, Matthew R; Suva, Larry J

    2010-12-01

    Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.

  17. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

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    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Gorlick, Richard; Geller, David S.

    2017-01-01

    Purpose Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. Experimental design The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. Results There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. Conclusions In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs. PMID:28264040

  18. The effect of bone morphogenetic protein-2 on osteosarcoma metastasis.

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    Gill, Jonathan; Connolly, Patrick; Roth, Michael; Chung, So Hak; Zhang, Wendong; Piperdi, Sajida; Hoang, Bang; Yang, Rui; Guzik, Hillary; Morris, Jonathan; Gorlick, Richard; Geller, David S

    2017-01-01

    Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model. The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations. There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals. In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

  19. [Encounter of cancer cells with bone. Therapy for bone metastasis from lung cancer].

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    Sugiura, Hideshi

    2011-03-01

    Bone metastasis from lung cancer requires a thorough examination of bones, including axial bones (e.g., spine, pelvis, and proximal femur) . Most patients have multiple bone metastases by the time they are initially diagnosed. In such patients, radiation therapy is often the first choice of treatment. Surgical treatment is indicated for pathological fracture and impending fracture associated with cortical bone invasion in long bone metastasis. Spinal metastasis requires accurate imaging to evaluate the extent of bone metastasis ; surgical treatment is indicated when the spinal cord is compressed. Given reports that bisphosphonates decrease the incidence of pathological fractures, prescribing bisphosphonates at an early stage is likely to be an effective therapeutic strategy for bone metastasis.

  20. Chronological study for solitary bone metastasis in the sternum from breast cancer with bone scintigraphy

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    Miyoshi, Hidenao; Otsuka, Nobuaki; Sone, Teruki; Nagai, Kiyohisa; Tamada, Tsutomu; Mimura, Hiroaki; Yanagimoto, Shinichi; Tomomitsu, Tatsushi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1999-07-01

    Since breast cancer is frequently associated with bone metastasis, bone scintigraphies have been performed to determine pre-operative staging and to survey postoperative bone metastasis. The sternum, in particular, is a site at which is difficult to differentiate between benign bone disease and bone metastasis, because of varied uptake and wide individual variations. In this study, chronological bone images were scintigraphied in six cases with solitary sternal metastasis and three cases with benign bone disease including two fracture cases and one arthritis case. On bone scintigrams in which solitary sternal metastasis appeared, increased uptake was found in five cases, and photon deficiency was observed in one case. During follow-up scintigraphies, abnormal accumulations, such as hot spots and cold lesions, increased in the bone metastasis while abnormal uptake disappeared or was unchanged in the benign bone disease cases. On CT, four cases showed osteolytic change, and one exhibited osteosclerotic change. These findings indicate that sternal metastasis usually shows osteolytic change, even if a hot lesion is recognized on bone scintigraphy. In solitary sternal metastasis, for which early diagnosis is difficult, both an integrated diagnosis using other imaging techniques and chronological bone scintigraphy are important. (author)

  1. Radiotherapy for metastasis from breast and lung cancer. Bone and Brain metastasis

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    Shigematsu, Naoyuki; Ito, Hisao; Kutsuki, Shoji; Kawada, Tetsuya; Toya, Kazuhito; Kubo, Atsushi [Keio Univ., Tokyo (Japan). School of Medicine

    1997-03-01

    Bone or brain metastasis is the common and serious condition restricting the quality of life (QOL) of the cancer patients and radiotherapy frequently plays an important role in relief of their symptoms. Because radiotherapy is given with palliative intent to the patients with limited, if variable, life expectancy, radiation schedules need to be identified which give maximum patient benefit with minimum associated morbidity and minimum disturbance of the patients` remaining life. We retrospectively analyzed 222 patients with the bone or the brain metastasis from lung or breast cancer to evaluate the effect of radiotherapy on their prognosis and QOL. The 3-year survival rates of the patients with breast and lung cancer were 21% and 3%, respectively (p<0.0001), and breast cancer patients seemed to have better prognosis than lung cancer patients for both bone metastasis (p<0.0001) and brain metastasis (p=0.09). Symptom relief by radiotherapy was obtained 84% for bone metastasis and 64% for brain metastasis and it was not affected by primary lesion (lung or breast). Sixty seven per cent of the bone and the brain metastasis was derived from adenocarcinoma and it had a tendency to give the better prognosis comparing with squamous cell carcinoma. Radiation schedules should be flexibly corresponded to the patients` tumor type (metastatic site, primary disease or histology), even if it is `just` a palliative therapy, considering their prognosis and QOL. (author)

  2. Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis

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    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0046 TITLE: Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis PRINCIPAL INVESTIGATOR: Dr...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis 5b. GRANT NUMBER W81XWH-16-1-0046 5c...14. ABSTRACT Here we report major findings for our project aimed at studying the expression of Discoidin Domain Receptors (DDRs) in breast cancer

  3. A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

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    Krishnangshu Bhanja Choudhury

    2011-01-01

    Conclusion: The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

  4. Review of Animal Models of Prostate Cancer Bone Metastasis

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    Jessica K. Simmons

    2014-06-01

    Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.

  5. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

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    Paola Bendinelli

    2016-05-01

    Full Text Available Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine, and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients.

  6. Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia

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    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2016-01-01

    Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients. PMID:27187355

  7. Mechanisms of cancer metastasis to the bone

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    Juan Juan YIN; Claire B. POLLOCK; Kathleen KELLY

    2005-01-01

    Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecular components and mechanisms that are responsible for those interactions.

  8. Multiple Metastasis-Like Bone Lesions in Scintigraphic Imaging

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    Ying Zhang

    2012-01-01

    Full Text Available Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS with technetium-99m methylene diphosphonate (Tc-99m MDP demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG, multiple myeloma (MM, disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.

  9. Incidence of bone metastasis in carcinoma buccal mucosa

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    Virendra Bhandari

    2016-01-01

    Full Text Available Introduction: Head and neck cancer is a leading health problem in India due to the habit of chewing tobacco and bad oral and dental hygiene. Carcinoma buccal mucosa is more common and is 2.5% of all malignancies at our center. Most of the patients present in stage III and IV and the survival in these cases is not very good. Bone metastasis in advanced cases of carcinoma buccal mucosa is rarely reported in the world literature. Materials and Methods: We present here cases developing bone metastasis in carcinoma buccal mucosa in last 5 years. These patients were young with loco-regionally advanced disease where bone metastasis developed within 1-year of definitive treatment. Results: The flat bones and vertebrae were mainly involved and the survival was also short after diagnosis of metastasis despite the treatment with local Radiotherapy and chemotherapy. Conclusion: The exact cause of metastasis cannot be proved, but the probability of subclinical seedling of malignant cells before the eradication of the primary tumor should be considered along with advanced local and nodal disease with high grade of tumor.

  10. Intracortical bone metastasis mimicking intracortical osteoid osteoma: a case report

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    Shin, Yu Ri; Kim, Jee Young [St. Vincent' s Hospital, The Catholic University of Korea, Suwon (Korea, Republic of)

    2007-08-15

    Cortical metastasis usually occurs in the diaphysis of the long bones with the appearance of a cookie-bite pattern; this is associated with cortical destruction extending into the soft tissue as well as into the medullary cavity, or there can be a periosteal reaction. We report here on a 66-year-old woman who was diagnosed with intracortical metastasis in the proximal metaphysis of the right femur as an initial metastatic focus from primary lung cancer. CT detected an intracortical osteolytic lesion without cortical destruction or thickening. The MR images showed extensive peritumoral edema in the surrounding soft tissue and adjacent bone marrow edema, and this all mimicked osteoid osteoma.

  11. Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

    Science.gov (United States)

    Silvestris, Nicola; Pantano, Francesco; Ibrahim, Toni; Gamucci, Teresa; De Vita, Fernando; Di Palma, Teresa; Pedrazzoli, Paolo; Barni, Sandro; Bernardo, Antonio; Febbraro, Antonio; Satolli, Maria Antonietta; Bertocchi, Paola; Catalano, Vincenzo; Giommoni, Elisa; Comandone, Alessandro; Maiello, Evaristo; Riccardi, Ferdinando; Ferrara, Raimondo; Trogu, Antonio; Berardi, Rossana; Leo, Silvana; Bertolini, Alessandro; Angelini, Francesco; Cinieri, Saverio; Russo, Antonio; Pisconti, Salvatore; Brunetti, Anna Elisabetta; Azzariti, Amalia; Santini, Daniele

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. Patients and Methods Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). Conclusions To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients. PMID:24204569

  12. Diagnosis of bone metastasis from thyroid carcinoma

    DEFF Research Database (Denmark)

    Bechsgaard, Thor; Lelkaitis, Giedrius; Jensen, Karl E

    2015-01-01

    (MRI), but histology revealed a metastasis from thyroid carcinoma, although the patient had no previous history of thyroid malignancy and resection of the thyroid gland was without malignancy. Ultrasound-guided biopsy was possible due to cortical destruction and the multidisciplinary approach with re...

  13. Characterizing the inorganic/organic interface in cancer bone metastasis

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    Wu, Fei

    Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential

  14. The unresolved role of systemic factors in bone metastasis

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    Jessalyn M. Ubellacker

    2016-09-01

    Full Text Available Systemic factors including cytokines, cell-free nucleic acids, microvesicles, and platelets are appreciated as important regulators of adenocarcinoma progression. Research findings using pre-clinical mouse models have revealed that many such systemically acting factors are either secreted by or responsive to peripheral tumors and impact bone and bone marrow (collectively referred to as the bone microenvironment to initiate processes that ultimately govern disease progression, even in the absence of detectable bone metastases. In some cases, cancer-driven modulation of the bone microenvironment involves mobilization of bone marrow hematopoietic and mesenchymal cells into the circulation that are subsequently recruited into peripheral tissues and tumors. In other cases, systemic factors alter bone marrow cell (BMC differentiation and/or gene expression to render the BMCs pro-tumorigenic even prior to their mobilization into the circulation. Given their effect on the bone microenvironment, it stands to reason that such systemic factors might also influence metastases in the bone; however, this hypothesis remains to be comprehensively tested. Here, we briefly review what is known, and not known, about systemic factors that regulate the bone microenvironment and thereby influence bone metastases. We also pose a number of currently unanswered questions in this active area of research. A better understanding of systemic processes that influence bone metastasis should aid discovery of therapeutic approaches that aim to eradicate or reduce disease burden in the bone, which is the cause of significant patient mortality and morbidity and is currently incurable.

  15. Survival in patients with breast cancer with bone metastasis

    DEFF Research Database (Denmark)

    Cetin, Karynsa; Christiansen, Christian Fynbo; Sværke, Claus;

    2015-01-01

    OBJECTIVES: Since population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis...

  16. Correlation between bone metastasis and thrombocytosis in pulmonary adenocarcinoma patients

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    ZHANG, WEI; YU, CHAO; HUANG, BIN; ZHOU, FENG-LIANG; HUANG, HAI-DONG; LI, QIANG

    2015-01-01

    Thrombocytosis is commonly observed in patients exhibiting a variety of malignancies, including pulmonary, gastrointestinal and hepatic cancer. In the present study, the correlation between distant metastasis and thrombocytosis was retrospectively reviewed in 308 cases of histopathologically confirmed pulmonary adenocarcinoma. The patients were classified as having thrombocytosis or not, based on their platelet counts upon diagnosis; thrombocytosis was documented in 82/308 patients (26.6%). A log-rank test indicated a statistically significant difference in survival between patients exhibiting thrombocytosis compared with patients not exhibiting thrombocytosis (Pthrombocytosis upon diagnosis. In descending order of frequency, metastases were documented at the following sites: Lymph nodes (218/308 patients; 70.8%), bone (138/308 patients; 44.8%), lung (93/308 patients; 30.2%), brain (67/308 patients; 21.8%), liver (46/308 patients; 4.9%), adrenal glands (11/308 patients; 3.6%) and kidneys (5/308 patients; 1.6%). Bone metastasis occurred significantly more frequently in patients exhibiting thrombocytosis (50/82 patients: 61.0%; Pthrombocytosis (88/226 patients; 38.9%). Furthermore, according to univariate analysis, thrombocytosis, weight loss, an Eastern Cooperative Oncology Group performance status score of ≥2 points, anemia, increased erythrocyte sedimentation rate, and increased alkaline phosphatase (AKP) and carcinoembryonic protein (CEA) levels were risk factors for bone metastasis. According to multivariate analysis, thrombocytosis, weight loss, and increased AKP and CEA levels were correlated with bone metastasis. Therefore, patients exhibiting pulmonary adenocarcinoma and thrombocytosis have a higher risk of bone metastasis compared with patients not exhibiting thrombocytosis. PMID:25621048

  17. Cadherin-11 in renal cell carcinoma bone metastasis.

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    Robert L Satcher

    Full Text Available Bone is one of the common sites of metastases from renal cell carcinoma (RCC, however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.

  18. Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

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    Ihsen Slim

    2012-01-01

    Full Text Available Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma. It is generally confined to the neck with or without spread to regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly include lung and bone. Metastases involving oral and maxillofacial region are extremely rare. We described a case of malar metastasis revealing a follicular variant of papillary thyroid carcinoma, presenting with pain and swelling of the left cheek in a 67-years-old female patient with an unspecified histological left lobo-isthmectomy medical history. To our knowledge, this is the first recorded instance of a malar metastasis from a follicular variant of papillary thyroid carcinoma.

  19. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

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    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  20. Regulation of Prostate Cancer Bone Metastasis by DKK1

    Science.gov (United States)

    2012-09-01

    this task would have likely identified targets and secondary effects of host-derived DKK1 in prostate cancer bone metastasis. Task 3... effects and supports a mechanism of DKK1 resistance. To test the extent to which expression of Kremen could restore DKK1-mediated Wnt signaling...9(8):607-14. 14. Nelson JB. Endothelin receptor antagonists. World Journal of Urology. 2005; 23(1):19-27. 15. Dacquin R, Starbuck M, Schinke T

  1. Targeting Neuropilin-1 in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2011-04-01

    metastasis. Prostate 2000;44: 91–103. 32. Beier F, LuValle P. The cyclin D1 and cyclin A genes are targets of activated PTH/ PTHrP receptors in Jansen’s...various stimuli, including parathyroid hormone (PTH), PTH related protein ( PTHrP ), calcitriol, tumor necrosis factor- (TNF-), glucocorticoids...Bone Cells Guise303 and Mundy304 presented the concept of a vicious cycle involving TGF produced by bone cells that promotes the production of PTHrP by

  2. The evaluation of Tracp5b as a marker for monitoring treatment results of bone metastasis in breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    Xiaoyun Huang; Yan Si; Jia Zhao; Qiang Ding

    2008-01-01

    Objective:To evaluate the sensitivity of serum tartrate-resistant acid phosphatase 5b(Tracp5b) activity in monitoring bisphosphonate treatment results of bone metastasis in breast cancer(BC) patients. Methods:The serum activities of Tracp5b, CEA, CA153 were measured in 58 BC patients, including 26 without bone metastasis, 32 with bone metastasis. The serum activities of Tracp5b, CEA, CA153 were also measured in 19 patients with bone metastasis after 3 months of bisphosphonate treatment. Eighteen healthy women with age from 34 to 70 served as control. Results:Serum Tracp5b was significantly elevated in patients with bone metastasis compared with that in all any other groups(P< 0.05). The sensitivity of TracpSb was 78.13% and the specificity was 86.36%. The sensitivity of CA153 was 37.50% and the specificity was 77.27%. The sensitivity of CEA was 21.88% and the specificity was 84.09%. The serum activity of Tracp5b decreased significantly(P < 0.05) after 3 months of bisphosphonate treatment, while the levels of CA153 and CEA were unchanged. Conclusion:Serum TracpSb activity is a useful diagnostic marker for bone metastasis in BC patients and can be used to evaluate the treatment results of bisphosphonate.

  3. Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

    Institute of Scientific and Technical Information of China (English)

    Heng-Wei Zhang; Xian-Fu Sun; Ya-Ning He; Jun-Tao Li; Xu-Hui Guo; Hui Liu

    2013-01-01

    Objective: To analyze breast cancer bone metastasis related gene-CXCR4. Methods: This research screened breast cancer bone metastasis related genes by high-flux gene chip. Results:It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. Conclusions: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.

  4. Plant-derived anticancer agents: a promising treatment for bone metastasis

    Science.gov (United States)

    Juárez, Patricia

    2014-01-01

    Bone metastasis is a very frequent complication of advanced cancer, and it remains an incurable disease. Current therapies that have been approved for the treatment of bone metastases delay the occurrence of skeletal-related events and can extend the patient's lifespan by a few years. However, they will not cure or cause the regression of established bone metastases, and new side effects are emerging after prolonged treatment. Thus, new therapies are severely needed. There are compelling evidences from in vitro and in vivo preclinical studies that support the use of compounds derived from plants to treat several forms of cancers including bone metastasis. More than 25% of the drugs used during the past 20 years were directly derived from plants, whereas another 25% are chemically altered natural products. Still, only 5–15% of the ∼250 000 higher plants have ever been investigated for bioactive compounds. There is a growing interest for the study of anticancer drugs with relatively low side effects that target specific key signaling pathways that control the establishment and progression of the cancer metastasis. Therefore, further studies are needed to identify new natural compounds with high efficiency in cancer prevention and treatment. Extensive reviews about plant-derived agents and their use in cancer have been published, but none when it comes to the treatment of bone metastases. Only a few of these compounds have been evaluated for the treatment of bone metastasis; here we describe some of the most prominent ones that are having the potential to reach the clinic soon.

  5. Orbital metastasis: A rare manifestation of scapular bone osteosarcoma

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    Mohammad Taher Rajabi

    2014-01-01

    Full Text Available Purpose: To report a case of orbital metastasis from scapular bone osteosarcoma. Case Report: A 55-year-old man who was a known case of scapular bone osteosarcoma, was referred to our clinic with ocular symptoms including acute painful decreased vision, proptosis, conjunctival injection, and chemosis. He had undergone surgical excision of the original tumor and received systemic chemotherapy 4 months before. Imaging studies and incisional biopsy were performed for the orbital lesion, the histopathological examination confirmed the diagnosis of metastatic osteosarcoma. The patient was referred to the oncologist for palliative chemotherapy and further intervention; however, he deceased 2 months later due to sepsis in the context of immunosuppression. Conclusion: Metastatic involvement of the orbit due to osteosarcoma is a rare condition manifesting with orbital mass, pain, diplopia and ocular motility disturbance. Although there is no effective treatment, the combination of modalities such as chemotherapy, radiotherapy, and surgery may delay progression of the disease.

  6. Does Cytoreductive Prostatectomy Really Have an Impact on Prognosis in Prostate Cancer Patients with Low-volume Bone Metastasis? Results from a Prospective Case-Control Study.

    Science.gov (United States)

    Steuber, Thomas; Berg, Kasper D; Røder, Martin A; Brasso, Klaus; Iversen, Peter; Huland, Hartwig; Tiebel, Anne; Schlomm, Thorsten; Haese, Alexander; Salomon, Georg; Budäus, Lars; Tilki, Derya; Heinzer, Hans; Graefen, Markus; Mandel, Philipp

    2017-07-08

    The impact of cytoreductive radical prostatectomy (CRP) on oncological outcomes in patients with prostate cancer (PCa) and distant metastases has been demonstrated by retrospective data with their potential selection bias. Using prospective institutional data, we compared the outcomes between 43 PCa patients with low-volume bone metastases (1-3 lesions) undergoing CRP (median follow-up 32.7 mo) and 40 patients receiving best systemic therapy (BST; median follow-up 82.2 mo). The inclusion criteria for both cohorts were identical. So far, no significant difference in castration resistant-free survival (p=0.92) or overall survival (p=0.25) has been detected. Compared to recent reports, the outcomes for our control group are more favorable, indicating a potential selection bias in the previous retrospective studies. Therefore, the unclear oncological effect has to be weighed against the potential risks of CRP. However, patients benefit from a significant reduction in locoregional complications (7.0% vs 35%; p<0.01) when undergoing CRP. In this study we analyzed the impact of surgery in patients with prostate cancer and bone metastases. Using prospective data, we could not show a significant benefit of surgery on survival, but the rate of locoregional complications was lower. Therefore, patients should be treated within prospective trials evaluating the role of cytoreductive prostatectomy in low-volume, bone metastatic prostate cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. The role of tumour-associated macrophages in bone metastasis

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    Sofia Sousa

    2016-09-01

    Full Text Available This overview addresses the recent research developments in the role of tumour-associated macrophages (TAM in bone metastasis biology and management of breast and prostate cancer as well as in primary and lung metastatic osteosarcoma. Immunosuppressive M2-type TAMs have been shown to associate with poor prognosis. Throughout their life cycle, macrophages (Macs can adapt to environmental cues and influence the surroundings by secreting different cytokines and enzymes crucial to matrix remodelling, infection fighting, immune regulation and/or inflammation. In general terms, there is a broad and complex spectrum of Mac polarization statuses from M1 (classically activated/inflammatory to M2 (alternatively activated/wound healing/immune regulating Macs. Often the activation status of TAMs resembles more the M2-type. Considering the physiological functions of M2 Macs, it is no surprise that TAMs appear to have a role in metastasis, participating in almost every step of the metastatic cascade, which we review and explore in selected bone tropic cancers.

  8. Coordinate regulation of microenvironmental stimuli and role of methylation in bone metastasis from breast carcinoma.

    Science.gov (United States)

    Matteucci, Emanuela; Maroni, Paola; Disanza, Andrea; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2016-01-01

    The pathogenesis of bone metastasis is unclear, and much focus in metastatic biology and therapy relays on epigenetic alterations. Since DNA-methyltransferase blockade with 5-aza-2'-deoxycytidine (dAza) counteracts tumour growth, here we utilized dAza to clarify whether molecular events undergoing epigenetic control were critical for bone metastatization. In particular, we investigated the patterns of secreted-protein acidic and rich in cysteine (SPARC) and of Endothelin 1, affected by DNA methyltransferases in tumours, with the hypothesis that in bone metastasis a coordinate function of SPARC and Endothelin 1, if any occurs, was orchestrated by DNA methylation. To this purpose, we prepared a xenograft model with the clone 1833, derived from human-MDA-MB231 cells, and dAza administration slowed-down metastasis outgrowth. This seemed consequent to the reductions of SPARC and Endothelin 1 at invasive front and in the bone marrow, mostly due to loss of Twist. In the metastasis bulk Snail, partly reduced by dAza, might sustain Endothelin 1-SPARC cooperativity. Both SPARC and Endothelin 1 underwent post-translational control by miRNAs, a molecular mechanism that might explain the in vivo data. Ectopic miR29a reduced SPARC expression also under long-term dAza exposure, while Endothelin 1 down-regulation occurred in the presence of endogenous-miR98 expression. Notably, dAza effects differed depending on in vivo and in vitro conditions. In 1833 cells exposed to 30-days dAza, SPARC-protein level was practically unaffected, while Endothelin 1 induction depended on the 3'-UTR functionality. The blockade of methyltransferases leading to SPARC reduction in vivo, might represent a promising strategy to hamper early steps of the metastatic process affecting the osteogenic niche.

  9. Potential of targeted drug delivery system for the treatment of bone metastasis.

    Science.gov (United States)

    Vinay, Raichur; KusumDevi, V

    2016-01-01

    Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis.

  10. An open cohort study of bone metastasis incidence following surgery in breast cancer patients

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    Yoshimoto Masataka

    2010-07-01

    Full Text Available Abstract Background To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year, medium risk (1-3%, and low risk ( Results Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436. Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T, nodal grade (pN, and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I Conclusions Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

  11. An Unusual Bone Metastasis Mimicking SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) Syndrome on Bone Scintigraphy.

    Science.gov (United States)

    Ni, Jianming; Tang, Ping

    2016-02-01

    The costosternoclavicular region is not a common bone metastasis site, and symmetrical involvement is even rarer. Increased tracer uptake in the manubrium and sternoclavicular joints usually gives the typical "bull-horn" appearance seen in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Herein, we report a case of a 47-year-old woman with a history of invasive ductal carcinoma who had undergone left radical mastectomy 3 years earlier and presented with typical increased tracer uptake in the bilateral sternocostoclavicular region resembling the so-called bull horn. The final diagnosis of metastasis from breast cancer was made histopathologically following biopsy.

  12. Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein.

    Science.gov (United States)

    Yan, Zhang; Jin, Su; Wei, Zhang; Huilian, Hou; Zhanhai, Yin; Yue, Teng; Juan, Li; Jing, Li; Libo, Yao; Xu, Li

    2014-09-01

    Prostate cancer frequently metastasizes to the skeleton but the underlying mechanism remains largely undefined. Discoidin domain receptor 2 (DDR2) is a member of receptor tyrosine kinase (RTK) family and is activated by collagen binding. This study aimed to investigate the function and detailed mechanism of DDR2 in prostate cancer bone dissemination. Herein we found that DDR2 was strongly expressed in bone-metastatic prostate cancer cells and tissues compared to that in normal controls. Enhanced expression of constitutively activated DDR2 led to elevation in motility and invasiveness of prostate cancer cells, whereas knockdown of DDR2 through specific shRNA caused a dramatic repression. Knockdown of DDR2 in prostate cancer cells resulted in significant decrease in the proliferation, differentiation and function of osteoblast. Over-expression of DDR2 in prostate cancer cells resulted in notable acceleration of osteoclast differentiation and bone resorption, whereas knockdown of DDR2 exhibited the opposite effects. An intrabone injection bone metastasis animal model demonstrated that DDR2 promoted osteolytic metastasis in vivo. Molecular evidence demonstrated that DDR2 regulated the expression, secretion, and promoter activity of parathyroid hormone-related protein (PTHrP), via modulating Runx2 phosphorylation and transactivity. DDR2 was responsive to TGF-β and involved in TGF-β-mediated osteoclast activation and bone resorption. In addition, DDR2 facilitated prostate cancer cells adhere to type I collagen. This study reveals for the first time that DDR2 plays an essential role in prostate cancer bone metastasis. The mechanism disclosure may provide therapeutic targets for the treatment of prostate cancer.

  13. Magnetic resonance imaging and bone scintigraphy in bone metastasis detection: A comparative study

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    Lučić Silvija

    2010-01-01

    Full Text Available Background/Aim. Bone scintigraphy is well-known method for the detection of neoplastic lesions with a high sensitivity and, at the same time, a lower specificity. On the other hand magnetic resonance imaging (MRI is previously established noninvasive imaging method regarding its diagnostic specificity. The aim of this study was to determine the possibilities and to correlate two different diagnostic methods - bone scintigraphy and MRI in the detection of bone metastasis in the spine and pelvic bones. Methods. A total of 123 patients who underwent both bone scintigraphy and spine and pelvic MRI on 1.5 T MR imager were enrolled in this study. Scans were subsequently analyzed in total and divided in regions of interest (cervical, upper, middle and lower thoracic, upper and lower lumbar and pelvic region, which includes sacral spinal segment; afterwards the total number of 585 matching regions were compared and statistically analyzed. Results. The statistical analysis demonstrated significant correlation between the findings of both methods in total. Divided by regions of interest, significant degrees of correlation were demonstrated in all of them, except in the cervical spine region where the r-value was in the range of low correlation. Conclusion. Having a high mutual correlation, bone scintigraphy and MRI are to be considered as the complementary diagnostic methods in the detection of bone metastases. Still, increased diagnostic potential of MRI may highlights negative bone scintigraphy findings in the patients with solitary metastatic lesions or diffuse vertebral infiltration. Advances in the bone scintigraphy (single photon emission tomography - SPECT, SPECTcomputed tomography - SPECT-CT and MRI (whole body MRI, diffusion MRI, make it possible the diagnostic potential of both methods will result in a further improvement in bone metastasis detection.

  14. Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

    Science.gov (United States)

    Nakajima, Kosei; Kho, Dong Hyo; Yanagawa, Takashi; Zimel, Melissa; Heath, Elisabeth; Hogan, Victor; Raz, Avraham

    2016-06-01

    The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.

  15. The Host Microenvironment Influences Prostate Cancer Invasion, Systemic Spread, Bone Colonization, and Osteoblastic Metastasis

    Science.gov (United States)

    Ganguly, Sourik S.; Li, Xiaohong; Miranti, Cindy K.

    2014-01-01

    Prostate cancer (PCa) is the second leading cause of cancer death in men worldwide. Most PCa deaths are due to osteoblastic bone metastases. What triggers PCa metastasis to the bone and what causes osteoblastic lesions remain unanswered. A major contributor to PCa metastasis is the host microenvironment. Here, we address how the primary tumor microenvironment influences PCa metastasis via integrins, extracellular proteases, and transient epithelia-mesenchymal transition (EMT) to promote PCa progression, invasion, and metastasis. We discuss how the bone-microenvironment influences metastasis; where chemotactic cytokines favor bone homing, adhesion molecules promote colonization, and bone-derived signals induce osteoblastic lesions. Animal models that fully recapitulate human PCa progression from primary tumor to bone metastasis are needed to understand the PCa pathophysiology that leads to bone metastasis. Better delineation of the specific processes involved in PCa bone metastasize is needed to prevent or treat metastatic PCa. Therapeutic regimens that focus on the tumor microenvironment could add to the PCa pharmacopeia. PMID:25566502

  16. The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

    Science.gov (United States)

    Lipton, Allan; Uzzo, Robert; Amato, Robert J.; Ellis, Georgiana K.; Hakimian, Behrooz; Roodman, G. David; Smith, Matthew R.

    2011-01-01

    Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis. PMID:19878635

  17. Establishment of Animal Model for Bone Metastasis of Walker 256 Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    PANG; Fang-fang; SHEN; Hong-tao; HE; Ming; DONG; Ke-jun; WU; Shao-yong; DOU; Liang; SHI; Yan-jun; ZHANG; Shuang; WANG; Xiao-ming; ZHAO; Qin-zhang; YANG; Xu-ran; XU; Yong-ning; LAN; Xiao-xi; CAI; Li; JIANG; Shan

    2013-01-01

    Bone metastasis is a common complication of cancer.It often occurs in lung,breast and prostate cancer,and may cause osteolytic lesions,or cause few osteoblastic lesions.It has already advanced cancer When cancer metastasis to bone,which usually cannot be cured.It is one of the important factors leading to the death of cancer patients.Studying animal model of bone

  18. Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

    Directory of Open Access Journals (Sweden)

    Daniele Santini

    Full Text Available BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC. Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs, and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%. The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis; 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%. Most of these lesions were osteolytic (82.4%; 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819. The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005, ECOG performance status (p = 0.002 and treatment with bisphosphonate (p = 0.024 were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE (p = 0.021 and OS (p = 0.001. CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

  19. Natural History of Malignant Bone Disease in Hepatocellular Carcinoma: Final Results of a Multicenter Bone Metastasis Survey

    Science.gov (United States)

    Santini, Daniele; Pantano, Francesco; Riccardi, Ferdinando; Di Costanzo, Giovan Giuseppe; Addeo, Raffaele; Guida, Francesco Maria; Ceruso, Mariella Spalato; Barni, Sandro; Bertocchi, Paola; Marinelli, Sara; Marchetti, Paolo; Russo, Antonio; Scartozzi, Mario; Faloppi, Luca; Santoni, Matteo; Cascinu, Stefano; Maiello, Evaristo; Silvestris, Franco; Tucci, Marco; Ibrahim, Toni; Masi, Gianluca; Gnoni, Antonio; Comandone, Alessandro; Fazio, Nicola; Conti, Alessandro; Imarisio, Ilaria; Pisconti, Salvatore; Giommoni, Elisa; Cinieri, Saverio; Catalano, Vincenzo; Palmieri, Vincenzo Ostilio; Infante, Giovanni; Aieta, Michele; Trogu, Antonio; Gadaleta, Cosmo Damiano; Brunetti, Anna Elisabetta; Lorusso, Vito; Silvestris, Nicola

    2014-01-01

    Background Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. Patients and Methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. Results The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). Conclusions This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life. PMID:25170882

  20. Analysis of clinicopathological factors associated with bone metastasis in breast cancer.

    Science.gov (United States)

    Chen, Jing; Zhu, Shu; Xie, Xiu-zhen; Guo, Shan-feng; Tong, Liang-qian; Zhou, Sheng; Zhao, Ming; Xianyu, Zhi-qun; Zhu, Xiao-hua; Xiong, Wei

    2013-02-01

    Breast cancer is the second leading cause of cancer death in women today. Once breast cancer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk of bone metastasis, and to find predictive factors for the occurrence of bone metastasis at an earlier stage of breast cancer. Three hundred and sixty patients with pathologically proved breast cancer visiting the Department of Nuclear Medicine for whole body bone scan from January 2006 and January 2009 were investigated in this study. Clinicopathological information was obtained, which consisted of age, menopausal status, clinical staging, lymph node stage, histological grade, the expression of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). Correlation between bone metastasis and the associated factors was tested by using the Chi-square test. A Cox multivariate analysis was used to assess the factors which independently contributed to survival after bone metastasis in breast cancer patients. Survival curves were drawn for metastasis-free interval and the independent factors which contributed to survival, using the Kaplan-Meier method. Twenty-four patients were excluded from subsequent analysis. Three hundred and thirty-six enrolled patients ranged in age from 22 to 77 years (mean, 47.8 years). ER/PR status [ER(+) vs. ER(-), χ (2)=4.328, P=0.037; ER(+)PR(+) vs. ER(+)PR(-), χ (2)=4.425, P=0.035] and histological grade (χ (2)=7.131, P=0.028) were significantly associated with bone metastasis. ER status (x (2)=8.315, P=0.004) and metastasis-free interval (χ (2)=6.863, P=0.009) were independent prognostic factors for survival in breast cancer patients with bone metastasis. Our study suggested that ER/PR status and histological grade are risk factors for the development of bone metastasis in breast cancer patients. However, ER status and metastasis-free interval are independent prognostic factors for survival in

  1. Analysis of patients surviving for six months after irradiation of a bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, Kiyoshi; Akisada, Masayoshi (Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine); Yoshida, Tsugio; Sugahara, Shinji; Okumura, Toshiyuki; Mitsuhashi, Shoichi; Kawashima, Mitsuhiko

    1989-11-01

    The effects of treatment of a bone metastasis have been studied in 49 patients who survived for more than six months after radiotherapy (RT). Relief from the symptoms reached a rate as high as 91% (85/93 irradiated sites) irrespecive of the primary site of the cancer. However, the survival rate and the rate of symptom relief maintenance were statistically higher in those with breast canser (15 patients, 38 irradiated sites) than in those with a lung cancer (15, 24). The local control rate was dose dependent (TDF). High-dose irradiation, therefore, is recommended to achieve a high local control rate for patients with a long life expectancy. (author).

  2. Wnt signaling pathway: implications for therapy in lung cancer and bone metastasis.

    Science.gov (United States)

    Xi, Yongming; Chen, Yan

    2014-10-10

    Lung cancer remains a major worldwide health problem and patients have high rate of metastasis including bone. Although pathologic characteristics of this disease are clear and well established, much remains to be understood about this tumor, particularly at the molecular signaling level. Secreted signaling molecules of the Wnt family have been widely investigated and found to play a prominent role to induce human malignant diseases, such as breast and prostate cancer. A variety of studies have also demonstrated that the Wnt signaling pathway is closely associated with bone malignancies including osteosarcoma, multiple myeloma, and breast or prostate cancer induced bone metastasis. The aim of this review is to provide a summary regarding the role of the Wnt signaling pathway in lung cancer and bone metastasis, highlighting the aberrant activation of Wnt in this malignancy. We also discuss the potential therapeutic applications for the treatment of lung cancer and cancer induced bone metastasis targeting the Wnt pathway.

  3. [Analysis of risk factors for bone metastasis after radical resection of colorectal cancer within 5 years].

    Science.gov (United States)

    Li, Ang; Tan, Zhen; Fu, Chuangang; Wang, Hao; Yuan, Jie

    2017-01-25

    To investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years. Clinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively. Of 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ(2)=4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ(2)=4.266, P=0.039), lymph node metastasis (χ(2)=13.054, P=0.000) and pulmonary metastasis(χ(2)=35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36

  4. Effect of Pamidronate on Bone Pain in Patients with Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Shahrbanoo Keihanian

    2013-06-01

    Full Text Available Background & Objectives: Bone metastases induce harmful potential complications on the life of patients. Pamidronate reduces skeletal complications in patients with bone metastases. This study evaluated the effect of Pamidronate on bone pain in cancer patients with bone metastasis.   Methods: This was quasi experimental study carried out at Imam Sajjad hospital in Ramsar on 41 patients with malignancy by convenience sampling. In this study 90 mg of Pamidronate was injected intravenously each month for 3 months. Data collection was done through demographic and clinical data questionnaire and visual analog scale . Data of before and after intervention were compared. Statistical analysis was performed using paired t tests, chi-square, Friedman and Wilcox on tests with SPSS version 11.5 and p<0.05 was considered significant.   Results: Statistical analysis showed that the most age group (36% was 50-59 years and the most patients (65.9% were female. The most common type of cancer was breast (43.9% and the most common bone metastasis point in the most of patients (65.9% was diffuse. The most common sites of pain associated with bone were sternum, ischium and T3-T4 vertebrae. Before treatment, the most patients (80.5% complained of moderate pain whereas after treatment, the majority of them (41.5% complained of low pain. The results of this study indicated that there was significant difference (p=0.032 between consumption of NSAIDs before and after treatment, but there was no significant difference between consumption of o pium before and after treatment (p=0.096.   Conclusion: Pamidronate is effective in prevention of losing bone, reduced pain and analgesic consumption . So i t can be used as primary and routine treatment .

  5. Effects of lentivirus-mediated silencing of Periostin on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer.

    Science.gov (United States)

    Che, Jing; Shen, Wen-Zhuang; Deng, Yu; Dai, Yu-Hong; Liao, Yong-De; Yuan, Xiang-Lin; Zhang, Peng

    2017-08-01

    The study aims to investigate the effects of Periostin gene silencing on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer (LC). LC patients were divided into bone metastasis and non-bone metastasis groups; Healthy volunteers were selected as normal group. ELISA was performed to detect serum Periostin levels and plasma calcium ion concentration. SBC-5 cells were assigned into blank group (without transfection), negative control (NC) group (transfected with empty plasmid), si-Periostin group (transfected with si-Periostin plasmid), si-Integrin-αvβ3 group (transfected with Integrin-αvβ3 siRNA plasmid) and si-Periostin+si-Integrin-αvβ3 group (transfected with si-Periostin and si-Integrin-αvβ3 plasmid). qRT-PCR and Western blotting were performed to determine mRNA and protein expression of Periostin, metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins. CCK-8, scratch test and transwell assay were applied to detect cell proliferation, migration and invasion respectively. Nude mouse models of LC bone metastasis were established. TRAP Staining was employed to measure the number of osteoclasts. Bone metastasis group exhibited higher levels of Periostin compared to normal and non-bone metastasis groups. Si-Periostin, si-Integrin-αvβ3 and si-Periostin+si-Integrin-αvβ3 groups showed decreased Periostin expression, proliferation rate, migration distance, invasive cells, and expressions of metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins compared to blank and NC groups. Similarly, number of osteoclasts and expression of integrin signaling pathway-related proteins were decreased, and bone injury and calcium ion concentration were reduced. The study demonstrated that down-regulation of Periostin expression modulated tumor microenvironment and inhibited bone metastasis by blocking integrin-signaling pathway in LC

  6. CORRELATION OF PARATHYROID HORMONE-1 RECEPTOR EXPRESSION TO BONE METASTASIS OF BREAST CARCINOMA PATIENTS

    Directory of Open Access Journals (Sweden)

    P. A. Tusta-Adiputra

    2014-01-01

    Full Text Available Background: Bone metastasis is a common complication of metastasis of breast cancer and it is a unique pathobiology process. The Parathyroid Hormone-related Peptide (PTHrP is a protein which has an important role in breast cancer cells to invade and infiltrate bones or bone marrow and accelerate angiogenetic process. The objective of this study is to reveal the relationship of PTHrP receptor named Parathyroid Hormone-1 Receptor (PTH1R expression to bone metastasis in breast cancer patients. Methods: This was an analytical cross-sectional study, applying a non probability consecutive sampling. Samples were divided into two groups, i.e. one group of breast cancer metastasis to bone (+others and another group with non-bone metastasis. Patients were collected from an existed data base (from medical record, cancer register, histopathology, since 2007. The specimen paraffin blocks were re-examined using IHC technique for PTHrP receptor. The data were analyzed and tested with Chi-Square (X2, otherwise it would be tested using Fisher Exact Test. Each group would be allocated minimal of 17 patients/samples. Results: The Chi-Square test failed to show the association between PTH1R expression in breast cancer patients with bone metastasis (p=0.295. The relative prevalence result for positive PTH1R expression was 1.48. There was no proof that positive PTH1R expression was an associated factor for bone metastasis (95% confidence interval. Conclusion: PTH1R expression is not a factor associated with bone metastasis in breast cancer patients. 

  7. [Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

    Science.gov (United States)

    Meng, X Y; Song, S T

    2017-03-23

    Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

  8. Intestinal-type sinonasal adenocarcinoma with bone metastasis: a case report

    Institute of Scientific and Technical Information of China (English)

    Akhavan A.; Binesh F.; Teimoori S.; Soltani H.R.

    2011-01-01

    Intestinal type adenocarcinoma is a slow growing tumor of sinonasal area, that account for 4% of malignancies of this area. In women it occurs sporadically. This tumor rarely metastasis to other organs. In this article we presented a woman with sinonasal intestinal type adenocarcinoma with optic nerve involvement and multiple bone metastasis.

  9. The Biological Effects of Dickkopf1 on Small Cell Lung Cancer Cells and Bone Metastasis.

    Science.gov (United States)

    Pang, Hailin; Ma, Ningqiang; Jiao, Mi; Shen, Weiwei; Xin, Bo; Wang, Tongfei; Zhang, Feng; Liu, Lili; Zhang, Helong

    2017-01-02

    The bone is among the most common sites of metastasis in patients with lung cancer. Over 30%-40% of lung cancers can develop bone metastasis, and no effective therapeutic methods exist in clinic cases. Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferentially metastasizes to the skeleton. However, the role of DKK1 in osteotropism of small cell lung cancer (SCLC) remains to be elucidated. This study aimed to define the role of DKK1 in SCLC bone metastasis and investigate the underlying mechanisms. Our results demonstrated that the expression level of DKK1 was dramatically higher in bone metastatic SCLC cells (SBC-5 cell line) compared with that in cells without bone metastatic ability (SBC-3 cell line). Therefore, we hypothesized that DKK1 was involved in the bone metastasis of SCLC. We then suppressed the DKK1 expression in SBC-5 cells by RNAi and found that downregulation of DKK1 can inhibit cell proliferation, colony formation, cell migration, and invasion, but increase the apoptosis rate. Downregulation of DKK1 did not affect the cell cycle progression of SBC-5 cells in vitro. In vivo, downregulated DKK1 in SBC-5 cells resulted in attenuated bone metastasis. These results indicated that DKK1 may be an important regulator in bone metastases of SCLC, and targeting DKK1 may be an effective method to prevent and treat skeleton metastases in SCLC cases.

  10. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Science.gov (United States)

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

    2015-10-01

    The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  11. Metastasis of greater wing of sphenoid bone in bronchogenic carcinoma: a unusual case report.

    Science.gov (United States)

    Gupta, Prashant K; Mital, Mukta; Dwivedi, Amit; Gupta, Kumkum

    2011-01-01

    Orbital metastasis in systemic cancer is known to occur and occurs in up to 7% of all systemic cancers. Orbital features typically present after the diagnosis of the primary tumor. In about 20% of cases, there is no known primary cancer at the time of presentation with orbital metastatic disease. Here we report a case of a 60-year-old male smoker, in whom proptosis, due to metastasis in greater wing of left sphenoid bone secondary to bronchogenic carcinoma, was the initial symptom. We could not find in literature metastasis to greater wing of sphenoid bone due to small cell carcinoma of lung.

  12. The Roles of Epithelial-to-Mesenchymal Transition (EMT and Mesenchymal-to-Epithelial Transition (MET in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Binnaz Demirkan

    2013-11-01

    Full Text Available Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK, receptor activator of nuclear kappa ligand (RANKL, vitamin D, bone sialoprotein (BSP, osteopontin (OPN, and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT and mesenchymal-epithelial transition (MET effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ, insulin-like growth factor I & II (IGF I & II, platelet-derived growth factor (PDGF, parathyroid hormone-related protein (PTH(rP, vascular endothelial growth factor (VEGF, epithelial growth factors II/I (ErbB/EGF, interleukin 6 (IL-6, IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs, catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP, and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

  13. A novel gene expression signature for bone metastasis in breast carcinomas.

    Science.gov (United States)

    Savci-Heijink, C Dilara; Halfwerk, Hans; Koster, Jan; van de Vijver, Marc J

    2016-04-01

    Metastatic cancer remains the leading cause of death for patients with breast cancer. To understand the mechanisms underlying the development of distant metastases to specific sites is therefore important and of potential clinical value. From 157 primary breast tumours of the patients with known metastatic disease, gene expression profiling data were generated and correlated to metastatic behaviour including site-specific metastasis, metastasis pattern and survival outcomes. We analysed gene expression signatures specifically associated with the development of bone metastases. As a validation cohort, we used a published dataset of 376 breast carcinomas for which gene expression data and site-specific metastasis information were available. 80.5 % of luminal-type tumours developed bone metastasis as opposed to 41.7 % of basal and 55.6 % of HER2-like tumours. A novel 15-gene signature identified 82.4 % of the tumours with bone metastasis, 85.2 % of the tumours which had bone metastasis as first site of metastasis and 100 % of the ones with bone metastasis only (p 9.99e-09), in the training set. In the independent dataset, 81.2 % of the positive tested tumours had known metastatic disease to the bone (p 4.28e-10). This 15-gene signature showed much better correlation with the development of bone metastases than previously identified signatures and was predictive in both ER-positive as well as in ER-negative tumours. Multivariate analyses revealed that together with the molecular subtype, our 15-gene expression signature was significantly correlated to bone metastasis status (p genes, APOPEC3B, ATL2, BBS1, C6orf61, C6orf167, MMS22L, KCNS1, MFAP3L, NIP7, NUP155, PALM2, PH-4, PGD5, SFT2D2 and STEAP3, encoded mainly membrane-bound molecules with molecular function of protein binding. The expression levels of the up-regulated genes (NAT1, BBS1 and PH-4) were also found to be correlated to epithelial to mesenchymal transition status of the tumour. We have identified a

  14. Searching early bone metastasis on plain radiography by using digital imaging processing

    Energy Technology Data Exchange (ETDEWEB)

    Jaramillo-Nunez, A.; Perez-Meza, M. [Instituto Nacional de Astrofisica, Optica y Electronica, Apdo. Postal 51 y 216, Pue. (Mexico); Universidad de la Sierra Sur, C. P. 70800, Miahuatlan, Oax. (Mexico)

    2012-10-23

    Some authors mention that it is not possible to detect early bone metastasis on plain radiography. In this work we use digital imaging processing to analyze three radiographs taken from a patient with bone metastasis discomfort on the right shoulder. The time period among the first and second radiography was approximately one month and between the first and the third one year. This procedure is a first approach in order to know if in this particular case it was possible to detect an early bone metastasis. The obtained results suggest that by carrying out a digital processing is possible to detect the metastasis since the radiography contains the information although visually it is not possible to observe it.

  15. Inhibitory Effects of Megakaryocytes in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2010-04-01

    10. Liao J, McCauley LK 2006 Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein ( PTHrP ). Cancer Metastasis...expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions. International Journal of Cancer 2008; Aug 26;123(10):2267-2278. 7

  16. Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Lei Jin; Yan Zhang; Hui Li; Ling Yao; Da Fu; Xuebiao Yao; Lisa X Xu; Xiaofang Hu; Guohong Hu

    2012-01-01

    Bone metastasis is a frequent complication of breast cancer and a common cause of morbidity and mortality from the disease.During metastasis secreted proteins play crucial roles in the interactions between cancer cells and host stroma.To characterize the secreted proteins that are associated with breast cancer bone metastasis,we preformed a label-free proteomic analysis to compare the secretomes of four MDA-MB-231 (MDA231) derivative cell lines with varied capacities of bone metastasis.A total of 128 proteins were found to be consistently up-/down-regulated in the conditioned medium of bone-tropic cancer cells.The enriched molecular functions of the altered proteins included receptor binding and peptidase inhibition.Through additional transcriptomic analyses of breast cancer cells,we selected cystatin E/M (CST6),a cysteine protease inhibitor down-regulated in bone-metastatic cells,for further functional studies.Our results showed that CST6 suppressed the proliferation,colony formation,migration and invasion of breast cancer cells.The suppressive function against cancer cell motility was carried out by cancer cell-derived soluble CST6.More importantly,ectopic expression of CST6 in cancer cells rescued mice from overt osteolytic metastasis and deaths in the animal study,while CST6 knockdown markedly enhanced cancer cell bone metastasis and shortened animal survival.Overall,our study provided a systemic secretome analysis of breast cancer bone tropism and established secreted CST6 as a bonafide suppressor of breast cancer osteolytic metastasis.

  17. Pelvic and lumbar metastasis detected by bone scintigraphy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C. [Hospital Clinic Universitari de Valencia (Spain). Servei de Medicina Nuclear; Garcia Garc`ia, T.; Azagra Ros, P. [Hospital Clinic Universitari de Valencia (Spain). Servei d`Oncologia; Maruenda Paulino, J.I. [Hospital Clinic Universitari de Valencia (Spain). Servei Traumatologia; Ferrer Albiach, C. [Hospital Clinic Universitari de Valencia (Spain). Servei Radioterapia

    1999-05-01

    A case of a 43-year-old man suffering from pleural mesothelioma with distant bone metastasis is reported. The results of bone scintigraphy and NMR findings allowed the diagnosis. The current case describes a hematogenous metastasis to the pelvis and vertebral column from a malignant pleural mesothelioma that was detected initally by bone scintigraphy. (orig.) [Deutsch] Fallbericht ueber einen 43jaehrigen Mann mit Pleural-Mesotheliom und Knochenmetastasen. Die Diagnose wurde durch Knochenszintigraphie und NMR gestellt. Der vorliegende Fall beschreibt die haematogene Metastasierung ins Becken und in die Wirbelsaeule, ausgehend von einem malignen Pleural-Mesotheliom, das urspruenglich durch Knochenszintigraphie diagnostiziert wurde. (orig.)

  18. Comparison of bone scan with carbohydrate antigen 15-3 for evaluation of bone metastasis of brest cancer.

    Science.gov (United States)

    Mohammadzadeh, M; Alikhah, H; Zareh, A G A

    2010-02-15

    This study aimed at comparing the bone scan and CA15-3 titer in patients with breast cancer for evaluation of bone metastasis. Thirty five patients with definite diagnosis of breast cancer were evaluated in Tabriz Imam Khomeini Hospital from 2007 to 2008. Bone scan (99 mTc-MDP) performed in all patients. The serum CA15-3 was measured by ECLIA method. The increased level was considered as >30 U mL(-1). The serum level of CA15-3 was compared between the patients with and without bone metastasis, as well as its correlation with the extent of bone involvement. Thirty five patients with the mean age of 51.69 +/- 10.77 (34-81) years were enrolled in the study. According to bone scan results, 24 (68.8%) patients revealed bone metastasis. The mean level of serum CA15-3 was significantly higher in patents with bone metastasis than patients without metastasis (26.37 +/- 4.74 U mL(-1) vs. 19.09 +/- 1.99 U mL(-1); p 21.8 U mL(-1) for the serum level of CA15-3 in our patients, with a sensitivity and specificity of 91.7 and 91%, respectively. Serum level of CA15-3 is higher in the patients with bone metastatic breast cancer; however, the recommended cut-off point might not be suitable for Iranian patients. Further studies with large sample sizes are recommended.

  19. Medical treatment of breast cancer bone metastasis: from bisphosphonates to targeted drugs.

    Science.gov (United States)

    Erdogan, Bulent; Cicin, Irfan

    2014-01-01

    Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor κB ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

  20. Beta 2-Microglobulin: A Novel Therapeutic Target for the Treatment of Human Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2009-03-14

    interaction with RANKL derived from osteoblasts, in response to tumor-derived soluble factors such as PTHrP [26, 29, 30], contributes to increased bone turnover...the view that in oste- olytic bone metastasis RANKL is osteoblast-derived and is induced by cancer cell-derived PTHrP [30, 32]. However, we have...that increased bone resorption results in elevated TGFβ, which promotes cancer cells to synthesize parathyroid hormone-related peptide ( PTHrP ) that

  1. Risk of metastasis among rib abnormalities on bone scans in breast cancer patients

    Science.gov (United States)

    Li, Qin; Chen, Zhiqiang; Zhao, Yansheng; Li, Xiuqing; Pan, Hong; Xia, Tiansong; Chen, Lin; Xu, Zhaoqiang; Zhou, Wenbin; Liu, Xiaoan

    2015-01-01

    Bone scan abnormalities, especially rib lesions, are often confusing for physicians due to a high number of false-positive lesions. This study investigated risk factors that are associated with bone metastasis in 613 breast cancer patients with bone scan abnormalities. Significantly increased rates of bone metastasis were observed in patients with multiple lesions, large tumor sizes, and lymph node involvement. In addition, patients with concurrent lesions of rib and other sites exhibited a significant higher rate of metastatic disease compared to those with other site lesions (P = 0.009). In the subset of 324 patients with rib abnormalities, the rate of metastasis was extremely low in patients with pure rib lesions (1.2%; 95% CI: 0.1%–4.1%). Concurrent lesions of rib and other sites were more likely to be rib metastasis compared to pure rib lesions (P rib lesions and lesions located on bilateral ribs were more likely to be rib metastasis (P rib abnormalities could be recommended for follow-up only. However, if concurrent lesions of rib and other sites were detected on bone scans, additional radiological examinations should be performed to patients. PMID:25939860

  2. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi (Kawasaki Medical School, Kurashiki, Okayama (Japan))

    1994-06-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of [sup 99m]Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, [gamma]-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author).

  3. ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.

    Science.gov (United States)

    Masuda, Tetsuro; Endo, Motoyoshi; Yamamoto, Yutaka; Odagiri, Haruki; Kadomatsu, Tsuyoshi; Nakamura, Takayuki; Tanoue, Hironori; Ito, Hitoshi; Yugami, Masaki; Miyata, Keishi; Morinaga, Jun; Horiguchi, Haruki; Motokawa, Ikuyo; Terada, Kazutoyo; Morioka, Masaki Suimye; Manabe, Ichiro; Iwase, Hirotaka; Mizuta, Hiroshi; Oike, Yuichi

    2015-03-16

    Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

  4. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  5. Anti-transforming growth factor ß antibody treatment rescues bone loss and prevents breast cancer metastasis to bone.

    Science.gov (United States)

    Biswas, Swati; Nyman, Jeffry S; Alvarez, JoAnn; Chakrabarti, Anwesa; Ayres, Austin; Sterling, Julie; Edwards, James; Rana, Tapasi; Johnson, Rachelle; Perrien, Daniel S; Lonning, Scott; Shyr, Yu; Matrisian, Lynn M; Mundy, Gregory R

    2011-01-01

    Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFβ. Because TGFβ favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFβ antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFβ antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFβ antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFβ treatment resulted in a twofold increase in bone volume (ptreatment with anti-TGFβ antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFβ antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFβ antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFβ treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors.

  6. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

    Science.gov (United States)

    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  7. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

    Science.gov (United States)

    Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

    2013-11-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  8. Effect of PRO-SELF Pain Control Program on Pain Score from Bone Metastasis%PRO-SELF疼痛管理项目对肿瘤骨转移患者疼痛评分的影响

    Institute of Scientific and Technical Information of China (English)

    王静; 熊永祥; 黄启静; 郑艳娟; 卢妍容

    2014-01-01

    目的:进一步了解 Pro-self 疼痛管理项目对患者疼痛评分的影响。方法已证实有肿瘤骨转移的门诊病人随机分为 Pro-self 组(n=29)和标准护理组(n=30)。针对 Pro-self 组患者,疼痛专科护士分别在第1,4周电话访问,指导如何应对癌症疼痛及止痛药使用,以及与医师沟通,从而改进疼痛控制策略。标准护理组按常规护理。4周后患者对疼痛情况进行评分。结果 Pro-self 组在疼痛评分上降低,且与标准护理组有统计学差异(P<0.05)。两组在疼痛持续时间上没有统计学差异。结论 Pro-self 疼痛管理项目能有效提高患者自我护理能力,增强了癌症疼痛的管理。%Objective to better understand the effect of the Pro-self Pain control Program on pain scores. Methods:oncology outpatients with pain from bone metastasis were randomly assigned to the Pro-self intervention group (n=29) or standard care group (n=30). Pro-self group patients were taught how to cope with cancer pain and use an analgesic drug, and were given instructions on how to communicate with their doctors about unrelieved pain, at week 1 and 4 respectively. Patients in standard care group received routine nursing. Patients scored the pain intensity after 4weeks. Results Pain intensity scores in the PRO-SELF group decreased compared with pre-intervention, significantly lower than that in the standard care group (p<0.05). no differences were observed on hours per day in cancer pain between these two groups. Conclusions the use of Pro-self Pain control Program can improve self care ability and help to manage the cancer pain.

  9. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis.

    Science.gov (United States)

    Zhu, Wei; Holmes, Benjamin; Glazer, Robert I; Zhang, Lijie Grace

    2016-01-01

    Bone is one of the most common metastatic sites of breast cancer, but the underlying mechanisms remain unclear, in part due to an absence of advanced platforms for cancer culture and study that mimic the bone microenvironment. In the present study, we integrated a novel stereolithography-based 3D printer and a unique 3D printed nano-ink consisting of hydroxyapatite nanoparticles suspended in hydrogel to create a biomimetic bone-specific environment for evaluating breast cancer bone invasion. Breast cancer cells cultured in a geometrically optimized matrix exhibited spheroid morphology and migratory characteristics. Co-culture of tumor cells with bone marrow mesenchymal stem cells increased the formation of spheroid clusters. The 3D matrix also allowed for higher drug resistance of breast cancer cells than 2D culture. These results validate that our 3D bone matrix can mimic tumor bone microenvironments, suggesting that it can serve as a tool for studying metastasis and assessing drug sensitivity. From the Clinical Editor: Cancer remains a major cause of mortality for patients in the clinical setting. For breast cancer, bone is one of the most common metastatic sites. In this intriguing article, the authors developed a bone-like environment using 3D printing technology to investigate the underlying biology of bone metastasis. Their results would also allow a new model for other researchers who work on cancer to use.

  10. MicroRNAs and Osteolytic Bone Metastasis: The Roles of MicroRNAs in Tumor-Induced Osteoclast Differentiation

    Directory of Open Access Journals (Sweden)

    Tadayoshi Kagiya

    2015-08-01

    Full Text Available Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients to suffer bone fractures, pain, and hypercalcemia. It is important to understand the mechanism of bone metastasis to establish new cancer therapies. MicroRNAs are small, noncoding RNAs that are involved in various biological processes, including cellular differentiation, proliferation, apoptosis, and tumorigenesis. MicroRNAs have significant clinical potential, including their use as new therapeutic targets and disease-specific biomarkers. Recent studies have revealed that microRNAs are involved in osteoclast differentiation and osteolytic bone metastasis. In this review focusing on microRNAs, the author discusses the roles of microRNAs in osteoclastogenesis and osteolytic bone metastasis.

  11. Detection of bone metastasis in nasopharyngeal carcinoma by bone scintigraphy: A retrospective study in perspective of limited resource settings

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Background: Nasopharyngeal carcinoma (NPC is an aggressive tumor with a significant proportion of patients presenting with distant metastasis. The skeleton is one of the most common sites of distant failure. This retrospective study was performed to analyze the incidence and patterns of skeletal metastasis in NPC detected by bone scintigraphy in resource-poor settings. Materials and Methods: We analyzed records of 301 NPC patients attending our oncology outpatient department from January 2002 to December 2012. Of these, 33 patients who presented with bony pain underwent bone scan (BS for suspect of skeletal metastasis. In patients with positive scans, histological diagnosis to confirm metastasis was attempted. Results: Bone metastasis (BM was found in 19 patients (57.6% of patients undergoing BS, 6.3% of total NPC patients. About 36.8% and 15.8% of BM cases were in the age group 20-29 and 30-39 years, respectively (P = 0.27. 63.1% of metastatic cases were of World Health Organization type-II histology (P = 0.021. Of the patients diagnosed with BM, 52.6% belonged to stage IV at presentation (P = 0.022. Spine was involved in 56% of the positive cases, followed by the pelvis (32%, and ribs (24%. On univariate analysis, histology (P < 0.001, stage at diagnosis (P = 0.007 and age group (P = 0.001 were identified as significant factors affecting BM. However, on multivariate analysis, only stage (P = 0.001 was a significant factor. Conclusion: Bone scintigraphy can be considered in limited resource settings for the evaluation of distant metastasis in the patients of advanced NPC.

  12. Chronic Osteomyelitis in Sternum Mimicking Bone Metastasis of Lung Cancer Patient

    Energy Technology Data Exchange (ETDEWEB)

    Im, Hyung Jun; Kim, Yu Keong; Lee, Sang Mi; Lee, Won Woo; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul (Korea, Republic of)

    2009-06-15

    Primary sternal osteomyelitis without predisposing factors is a rare condition, and it is hardly differentiated from metastatic bone tumor especially in patient with the history of primary malignancy because osteomyelitis shares frequently common findings with metastatic bone lesion on {sup 18}F-FDG PET and bone scan. Although there have been several publications of primary osteomyelitis mimicking bone metastasis in the spine or extremities, we report a case of primary sternal osteomyelitis in the patient with lung cancer, which has, to our knowledge, not been reported before.

  13. Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.

    Science.gov (United States)

    Valta, Maija P; Zhao, Hongjuan; Ingels, Alexandre; Thong, Alan E; Nolley, Rosalie; Saar, Matthias; Peehl, Donna M

    2014-06-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

  14. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  15. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

    Science.gov (United States)

    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

    Directory of Open Access Journals (Sweden)

    Sandra Casimiro

    2016-08-01

    Full Text Available Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors. The deep comprehension of the molecular mechanisms of bone metastases may allow the future development of specific anti-tumoral therapies, but so far the approved and effective therapies for bone metastatic disease are mostly based in bone-targeted agents, like bisphosphonates, denosumab and, for prostate cancer, radium-223. Bisphosphonates and denosumab have proven to be effective in blocking bone resorption and decreasing morbidity; furthermore, in the adjuvant setting, these agents can decrease bone relapse after breast cancer surgery in postmenopausal women. In this review, we will present and discuss some examples of applied knowledge from the bench to the bed side in the field of bone metastasis.

  17. Bone metastasis of glandular cardiac myxoma mimicking a metastatic carcinoma.

    Science.gov (United States)

    Uppin, Shantveer G; Jambhekar, Nirmala; Puri, Ajay; Kumar, Rajiv; Agarwal, Manish; Sanghvi, Darshana

    2011-01-01

    Skeletal metastasis from a cardiac myxoma is rare. We describe an extremely unusual case of a cardiac myxoma metastasing to the femur in a 46-year-old female presenting with pain in the right hip. Radiographs showed an expansile lytic lesion with pathological fracture involving the neck and proximal shaft of the right femur. Histology revealed features of cardiac myxoma with heterologous glandular elements, which was initially mistaken for a metastatic mucin-secreting adenocarcinoma.

  18. Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital

    Directory of Open Access Journals (Sweden)

    Kriti Chauhan

    2016-01-01

    Full Text Available Background: Bone marrow metastasis by a nonhematologic malignancy signifies advanced stage of disease and confers a poor prognosis. The aim of this study was to analyze clinical presentation, hematological profile, biochemical profile, radiological presentation, and patterns of bone marrow involvement in patients with metastatic nonhematologic malignancies retrospectively. Materials and Methods: Ninety bone marrow procedures were done in cases of nonhematologic malignancies for suspected involvement or as a part of staging procedure. Results: Sixteen out of 90 patients showed metastasis by nonhematologic malignancies. The most common malignancy to metastasize was malignant small round cell tumor (Ewing's sarcoma and rhabdomyosarcoma followed by carcinoma breast and prostate. The most common clinical presentation was backache, fever anorexia, and abdominal pain. The biochemical findings included raised serum calcium and lactate dehydrogenase. 62.5% had anemia and 37.5% had thrombocytopenia. Leukocytosis was seen in 37.5% of patients. Leukoerythroblastic picture was seen in 43.75% cases. Of the eleven cases where both bone marrow aspirate and biopsies were done, 10 cases showed malignant cells in both. Immunohistochemistry was conclusive in four cases. The combined procedure of aspiration and biopsy gives a higher yield and are essential in patients with suspected bone marrow metastasis in nonhematologic malignancies.

  19. Bone metastasis in hepatocellular carcinoma. A report of five cases and a review of the literature.

    Science.gov (United States)

    Maccauro, G; Muratori, E; Sgambato, A; Liuzza, F; Esposito, M; Grieco, A; Gosheger, G

    2005-01-01

    Hepatocarcinoma occurs frequently throughout the world. Bone metastases are rare although incidence has increased because of progress in diagnosis and treatment. The authors report 5 cases of bone metastases and review the literature. The spine is the most frequent localization of bone metastases. Radiotherapy is the treatment of choice for this lesion. Surgery should be used to prevent and treat complications such as nerve compression and pathologic fracture, only if the coagulative pattern and the conditions of the patient allow it. The authors recommend the use of long intramedullary nailing when localization of the disease is in the femur, with prophylactic stabilization of the neck in diaphyseal metastasis.

  20. Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhou Zhen

    2012-04-01

    Full Text Available Abstract Background This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC. Methods The model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45 and non-bone metastasis group (other visceral metastasis and those without recurrence (n = 60. Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC. Results The molecular model for predicting bone metastasis was logit (P = − 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253 demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency. Conclusion The molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.

  1. Autocrine and paracrine STIP1 signaling promote osteolytic bone metastasis in renal cell carcinoma.

    Science.gov (United States)

    Wang, Jiang; You, Hongbo; Qi, Jun; Yang, Caihong; Ren, Ye; Cheng, Hao

    2017-03-07

    Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis. We observed high levels of both intracellular and extracellular STIP1 protein in bone metastatic tissue samples. Elevated STIP1 mRNA in the primary RCC tumors remarkably correlated with worse clinical outcomes. Furthermore, both human recombinant STIP1 protein and anti-STIP1 neutralizing antibody were used in the functional studies. We found that 1) STIP1 protein on the extracellular surface of tumor cells promoted the proliferation and migration/invasion of RCC tumor cells through the autocrine STIP1-ALK2-SMAD1/5 pathway; and 2) STIP1 protein secreted into the extracellular tumor stromal area, promoted the differentiation of osteoclasts through the paracrine STIP1-PrPc-ERK1/2 pathway. Increased cathepsin K (CTSK), the key enzyme secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption was further detected in the differentiated osteoclasts. These results provide evidence of the great potential of STIP1 as a novel biomarker and therapeutic target in RCC bone metastasis.

  2. Case of thyroid cancer with bone metastasis greatly ameliorated by radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Reiko; Hara, Hisato; Hukumitsu, Masayuki; Kamisasa, Isao; Tanaka, Kiyoshi; Miyanaga, Yutaka; Ben, Morikatsu; Asahara, Akira; Hayakawa, Kinya.

    1988-01-01

    A 53-year-old woman complaining of a cervical mass and intractable lumbago was admitted to the hospital. Eight years ago she had a tumor in her left thyroid lobe enucleated and it proved to be a microfollicular adenoma. This time she underwent total thyroidectomy under the diagnosis of thyroid cancer with vertebral metastasis and this was followed by /sup 131/I therapy but severe lumbago remained unchanged. Irradiation to the lumbar vertebra was added and this greatly relieved her from pain. Pathological examination revealed poorly differentiated thyroid carcinoma. We suppose that the unusually excellent radiosensitivity of this bone metastasis was attributable to its histopathological nature.

  3. Tumor-Host Interaction in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2006-01-01

    metastasized to bone. ACKNOWLEDGMENTS We thank Dr. Corazon Bucana for her expert advice, Donna Reynolds and Joseph Douglas for their technical assistance...gratefully acknowledge the assistance of Dr. Corazon Bucana for confocal micro- scope images. References 1. Karunagaran D, Tzahar E, Beerli RR, et al

  4. Hyoid bone chondrosarcoma with cervical nodal metastasis: A case ...

    African Journals Online (AJOL)

    Hisham Mostafa Abdel-Fattah

    2015-11-18

    Nov 18, 2015 ... bone tumors in adults, second only to osteosarcoma.1 It consti- tutes around 11% of ... treated in our institute, and a review of the literature. 2. Case report ... drosarcoma in the lymph node, with large areas of hyaline material ...

  5. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

    Science.gov (United States)

    Maroni, Paola; Bendinelli, Paola; Morelli, Daniele; Drago, Lorenzo; Luzzati, Alessandro; Perrucchini, Giuseppe; Bonini, Chiara; Matteucci, Emanuela; Desiderio, Maria Alfonsina

    2015-01-01

    In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. PMID:26703564

  6. Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2017-02-01

    of DDR1 in intraosseous tumor growth. Specific Aim 3. Task 1: Evaluate role of DDRs in regulation of pro- osteolytic factors. Nothing to...report Task 2: In vitro osteoclastogenesis studies. Nothing to report 10 2) Specific objectives: The objectives during the period...within the bone in the presence of estrogen. Specific Aim 3, Task 1 and Task 2: not initiated yet. 4) Other achievements: Nothing to report

  7. MMP-8, A Breast Cancer Bone Metastasis Suppressor Gene

    Science.gov (United States)

    2006-08-01

    and connectivity density (Conn.D). Cross-sectional area was determined by outlining the periosteal surface and performing a two-dimensional analysis...diaphysis were made, and the same segmenta- tion parameters were used for analysis. The periosteal surface was outlined, and a two- dimensional analysis was...twice at 12 and 2 days before sacrifice in 6 weeks old mice. Bone histomorphometric studies were carried out with proximal tibial metaphyses, a standard

  8. Targeting Neuropilin-1 in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2010-04-01

    leukemia (Mcl-1) as a novel downstream target of NRP1 signaling in metastatic prostate cancer cells. During the third year of the supporting period...supporting period, we identified myeloid cell leukemia -1 (Mcl-1) as a novel downstream target of NRP1 signaling in bone metastatic prostate cancer cells...myeloid cell leukemia -1 expression through neuropilin-1-dependent activation of c-MET signaling in human prostate cancer cells. Molecular Cancer , 2010

  9. Lung cancer presenting as a metastasis to the carpal bones: a case report

    Directory of Open Access Journals (Sweden)

    Rinonapoli Giuseppe

    2012-11-01

    Full Text Available Abstract Introduction A first metastasis to the hand is extremely rare. Usually, an acrometastasis is a sign of very advanced disease, with the presence of previous multiple metastases elsewhere. The present paper is one of the very few case reports of first metastatic location to carpal bones. To date, only Lederer et al., in 1990, and Song and Yao in 2012, have described a metastasis to the trapezium from lung cancer. Case presentation A 74-year-old Caucasian man was submitted to several physical examinations for thumb pain. The first diagnosis was tendonitis and the second diagnosis was thumb carpometacarpal osteoarthritis. Only when the patient was admitted to an internal medicine department for deterioration of his general condition and an enormous mass on his left hand was an open biopsy performed. It revealed a metastasis from large-cell lung carcinoma. A total-body scintigraphy and total-body computed tomography scan were negative for other secondary locations. The patient underwent an amputation at the distal third of the forearm. Conclusion Less than 20 case reports are available in the literature dealing with metastases to carpal bones. Very few cases are described as carpal metastases in the absence of other previous metastases, and only two articles, before the present one, have reported a metastasis to the trapezium. This case report teaches us two things: first, patient adherence to follow-up is extremely important; and, second, a thorough examination of diagnostic findings needs to be carried out at all times.

  10. Localized experimental bone metastasis drives osteolysis and sensory hypersensitivity at distant non-tumor-bearing sites.

    Science.gov (United States)

    Abdelaziz, Dareen M; Stone, Laura S; Komarova, Svetlana V

    2015-08-01

    Patients with breast cancer metastasis to bone suffer from inadequate pain relief. Animal models provide increased understanding of cancer-induced bone and sensory alterations. The objective of this study was to investigate the measures of pain at distant non-tumor-bearing sites in animals with localized bone metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and thermal stimuli in the contralateral paw was examined. In addition to previously demonstrated development of osteolysis and hypersensitivity to mechanical and thermal stimuli in the cancer-injected tibia, these animals exhibited an increase in sensory hypersensitivity in the contralateral limb. No bone lesions were evident on radiographs of the contralateral limbs. Histomorphometry detected decreased bone volume per tissue volume and increased osteoclast number in the contralateral tibia and vertebral bones of cancer-bearing animals. Neuroplasticity was examined by immunofluorescence for calcitonin gene-related peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were significantly elevated both ipsilateral and contralateral in tumor-bearing animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression, and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced sensitivity to cold and protected against bone loss. Localized bone cancer drives hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant from the primary tumor area. Drugs targeting these mechanisms may be useful in the treatment of pain distant from the primary tumor site.

  11. Alteration of osteoblast arrangement via direct attack by cancer cells: New insights into bone metastasis

    Science.gov (United States)

    Kimura, Yumi; Matsugaki, Aira; Sekita, Aiko; Nakano, Takayoshi

    2017-01-01

    Intact bone tissue exhibits a characteristic anisotropic microstructure derived from collagen fiber alignment and the related c-axis orientation of apatite crystals, which govern the mechanical properties of bone tissue. In contrast, tumor-invaded bone exhibits a disorganized, less-aligned microstructure that results in severely disrupted mechanical function. Despite its importance both in basic principle and in therapeutic applications, the classical understanding of bone metastasis is limited to alterations in bone mass regulated by metastatic cancer cells. In this study, we demonstrate a novel mechanism underlying the disruption of bone tissue anisotropy in metastasized bone. We observed that direct attack by cancer cells on osteoblasts induces the less-organized osteoblast arrangement. Importantly, the crystallographic anisotropy of bone tissue is quantitatively determined by the level of osteoblast arrangement. Osteoblast arrangement was significantly disrupted by physical contact with cancer cells such as osteolytic melanoma B16F10, breast cancer MDA-MB-231, and osteoblastic prostate cancer MDA-PCa-2b cells. The present findings demonstrate that the abnormal arrangement of osteoblasts induced by physical contact with cancer cells facilitates the disorganized microstructure of metastasized bone. PMID:28303941

  12. Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and {sup 18}F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh [India Institute of Medical Sciences, New Delhi (India)

    2012-12-15

    Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells {sup 18}F fluorodeoxyglucose ({sup 18}F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased {sup 18}F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of {sup 18}F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with {sup 18}F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case.

  13. Myeloid-specific TGF-β signaling in bone promotes basic-FGF and breast cancer bone metastasis.

    Science.gov (United States)

    Meng, X; Vander Ark, A; Lee, P; Hostetter, G; Bhowmick, N A; Matrisian, L M; Williams, B O; Miranti, C K; Li, X

    2016-05-05

    Breast cancer (BCa) bone metastases cause osteolytic bone lesions, which result from the interactions of metastatic BCa cells with osteoclasts and osteoblasts. Osteoclasts differentiate from myeloid lineage cells. To understand the cell-specific role of transforming growth factor beta (TGF-β) in the myeloid lineage, in BCa bone metastases, MDA-MB-231 BCa cells were intra-tibially or intra-cardially injected into LysM(Cre)/Tgfbr2(floxE2/floxE2) knockout (LysM(Cre)/Tgfbr2 KO) or Tgfbr2(floxE2/floxE2) mice. Metastatic bone lesion development was compared by analysis of both lesion number and area. We found that LysM(Cre)/Tgfbr2 knockout significantly decreased MDA-MB-231 bone lesion development in both the cardiac and tibial injection models. LysM(Cre)/Tgfbr2 knockout inhibited the tumor cell proliferation, angiogenesis and osteoclastogenesis of the metastatic bones. Cytokine array analysis showed that basic fibroblast growth factor (bFGF) was downregulated in MDA-MB-231-injected tibiae from the LysM(Cre)/Tgfbr2 KO group, and intravenous injection of the recombinant bFGF to LysM(Cre)/Tgfbr2 KO mice rescued the inhibited metastatic bone lesion development. The mechanism by which bFGF rescued the bone lesion development was by promotion of tumor cell proliferation through the downstream mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)-cFos pathway after binding to the FGF receptor 1 (FGFR1). Consistent with animal studies, we found that in human BCa bone metastatic tissues, TGF-β type II receptor (TβRII) and p-Smad2 were expressed in osteoclasts and tumor cells, and were correlated with the expression of FGFR1. Our studies suggest that myeloid-specific TGF-β signaling-mediated bFGF in the bone promotes BCa bone metastasis.

  14. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  15. Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain

    Directory of Open Access Journals (Sweden)

    Koizumi Mitsuru

    2010-08-01

    Full Text Available Abstract Background Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs or survival (cause specific death, CSD, retrospectively. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis. Results Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not

  16. Study on {sup 41}Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Hongtao; Pang, Fangfang [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang [China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Pang, Yijun [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Yang, Xianlin [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); Ruan, Xiangdong [College of Physics, Guangxi University, Nanning 530004 (China); Liu, Manjun; Xia, Chunbo [Guiin Medical University, Guilin 541004 (China)

    2015-10-15

    The annual incidence of new cancer patients in China is about 2 million, 30–40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of {sup 41}Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague–Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl{sub 2} solution (containing 1.4 mg Ca and 5nCi {sup 41}Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for {sup 41}Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of {sup 41}Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that {sup 41}Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  17. Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence.

    Science.gov (United States)

    Awolaran, Olugbenga; Brooks, Susan A; Lavender, Verna

    2016-12-01

    Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised. 15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CX3CR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CX3CR1

  18. Short- term curative effects of Boning on relieving pain of bone metastasis of lung cancer%博宁缓解肺癌骨转移疼痛的近期疗效

    Institute of Scientific and Technical Information of China (English)

    岳莉; 吴红卫; 薛海鸥; 王新华

    2002-01-01

    @@ Background:23.8% patients with late stage lung cancer accompany bone metastasis, which bring about severe pain and make great influence on patients' living quality.Boning is the representation of domestic second generation Diphosphonate, which take good curative effects on bone pain caused by bone metastasis of malignant tumor.

  19. Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

    OpenAIRE

    Starup-Linde, Jakob

    2013-01-01

    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone marker...

  20. Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

    Science.gov (United States)

    Zhang, Wei-dong; Liu, Da-ren; Feng, Cheng-cheng; Zhou, Chuan-biao; Zhan, Chen-ni; Que, Ri-sheng; Chen, Li

    2014-12-01

    Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

  1. Crizotinib Treatment in a Lung Adenocarcinoma Harboring ALK Fusion Gene with Bone Marrow Metastasis: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Xiaoyan LI

    2015-02-01

    Full Text Available Background and objective Distant metastasis was common in lung cancer, especially patients with bone marrow metastasis had poor prognosis and there were few effective methods. Crizotinib had been confirmed to be used in anaplastic lymphoma kinase (ALK positive lung adenocarcinoma, but the efficacy in lung cancer with bone marrow metastasis was unknown. In the present study, we reported one case of ALK-positive lung adenocarcinoma with bone marrow matastasis given crizotinib treatment, the safety and efficacy was summarized. Methods ALK fusion was tested by fluorescence in situ hybridization (FISH. Crizotinib was given with dose of 250 mg, bid. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and bone marrow response was evaluated by bone marrow puncture and biopsy. Adeverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results The patient achieved partial response (PR after 6 weeks of crizotinib, especially the objective response of bone marrow metastasis was complete response (CR. The patient stopped crizotinib because of pneumonia. The progression free survival (PFS and overall survival (OS was 20 weeks and 22 weeks respectively. Conclusion Crizotinib could be an effective method for ALK-positive lung cancer with bone marrow metastasis and showed good tolerance.

  2. Three-dimensional microstructural analysis of human lumber vertebrae using microcomputed tomography in bone metastasis from prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tamada, Tsutomu [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2000-11-01

    Prostate cancer frequently metastasizes to bone, inducing osteosclerotic lesions. However, the morphological details of bone metastasis of prostate cancer have not been clarified. The trabecular bone structure of bone metastasis from prostate cancer was investigated in three dimensions using microcomputed tomography (micro-CT). A total of 17 cubes of the lumber spine of a 77-year-old man with prostate cancer were excised post mortem: four of them from non-metastatic and the rest from metastatic sites. The samples were measured using micro-CT with a resolution of 23.2 {mu}m and the standard structural indices and degree of anisotropy were computed. After micro-CT measurement, the samples were tested in a destructive manner for the assessment of mechanical properties. Samples from the metastatic sites showed significantly higher values than those from non-metastatic sites for bone volume (BV), bone surface (BS), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) (p<0.005). Bone surface density (BS/BV) and trabecular separation (Tb.Sp) were significantly higher in the samples from non-metastatic sites (p<0.001). Samples from metastatic sites showed a more isotropic arrangement of trabecular bone than those from non-metastatic sites. Three-dimensionally reconstructed images depicted several different patterns of sclerotic bone metastasis, and osteolytic appearance was observed in all of them. Structural parameters such as BV/TV were well correlated with the mechanical properties (r=0.899). The present study clarified the trabecular microstructure of bone metastasis from prostate cancer and suggests that both osteolysis and osteogenesis progress while interacting with each other in all phases of bone metastasis. (author)

  3. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  4. Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice.

    Science.gov (United States)

    Sakaguchi, Satoshi; Goto, Hisatsugu; Hanibuchi, Masaki; Otsuka, Shinsaku; Ogino, Hirokazu; Kakiuchi, Soji; Uehara, Hisanori; Yano, Seiji; Nishioka, Yasuhiko; Sone, Saburo

    2010-05-01

    Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment.

  5. Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions

    Energy Technology Data Exchange (ETDEWEB)

    Misaki, Takashi; Iwata, Masahiro; Kasagi, Kanji; Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-04-01

    Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from out initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal. (author)

  6. Bone metastasis versus bone marrow metastasis? Integration of diagnosis by 18F-fluorodeoxyglucose positron emission/computed tomography in advanced malignancy with super bone scan: Two case reports and literature review

    Directory of Open Access Journals (Sweden)

    Chia-Yang Lin

    2013-04-01

    Full Text Available Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle-aged woman with a history of breast cancer with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT diagnosis simultaneously. Based on imaging of 18F-FDG PET/CT, diffusely incremental 18F-FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm-related endocrine factors.

  7. Tubulocystic Carcinoma of the Kidney with Bone Metastasis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Im, Mi Hye; Jung, Yoon Young; Choi, Yun Sun; Kim, Yun Jung [Dept. of Radiology, Eulji Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of); Kim, Eun Kyung [Dept. of Pathology, Eulji Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of); Yoo, Tak Keun [Dept. of Urology, Eulji Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Tubulocystic carcinoma of the kidney is a rare neoplasm occurring predominantly in males, and has a relatively indolent disease course. Herein, we present a case of histologically proven tubulocystic renal carcinoma in a 22-year-old woman with emphasis on the imaging findings of CT, US, 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), and pathological features. Unusually, the woman had single bone metastasis in the left parasymphyseal pubic bone without any other evidence of metastatic disease on 18F-FDG PET/CT at the time of the diagnosis. A few months later, the bone metastases progressed into multiple cervical vertebrae and the skull base.

  8. {sup 68}Ga Labeling of DOTMP using Freeze-dried Kit for the Imaging of Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Dho, So Hee; Choi, Sangmu; Kim, Sooyong; Cho, Eunha; Lee, Soyoung; Jung, Sunghee; Lim, Jaecheong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Bone is a favorable site of metastasis and is invaded common primary tumors such as prostate, breast, and lung. Due to the progressive pain and mortality of the bone metastasis, effort has been focused on the detection of bone metastasis in the field of nuclear medicine (Mitterhauser, Toegel et al. 2007, Mirzaei, Jalilian et al. 2015). In designing suitable imaging agents for bone metastasis, multidentate polyaminophosphonate are regarded as the most promising candidates as carrier ligands owing to their high bone affinity, selective localization in skeletal lesions and ability to form metal chelates with high in-vivo stability (Chakraborty, Das et al. 2008). 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene. Freeze-dried DOTMP kit vial was consist of 400 μ of DOTMP, 19.27 mg of ammonium acetate and 17.62 mg of ascorbic acid. All the preparative steps were carried out under aseptic conditions, and the prepared kit vials were shown in Fig. 3(A). The easy and efficient labeling of this kit with 68Ga make them suitable for preparing 68Ga-DOTMP for imaging of bone metastasis.

  9. Clinicopathological features and treatment of extremity bone metastasis in patients with endometrial carcinoma: a case report and review

    Institute of Scientific and Technical Information of China (English)

    JIANG Guo-qing; GAO Yu-nong; GAO Min; ZHENG Hong; YAN Xin; WANG Wen; AN Na; CAO Kun

    2011-01-01

    Unlike other non-gynecologic solid tumors, such as breast cancer, lung cancer, metastasis to bone from endometrial carcinoma is rare, metastasis to extremity is extremely rare. We report a 51-year-old multiparous woman with FIGO Stage IVb Grade 2 endometrial adenocarcinoma which metastasized to left lower extremity bone. She received an amputation of left lower extremity below the knees, and a total abdominal hysterectomy and bilateral salpingo-oophorectomy, and followed by systemic chemotherapy, radiation therapy to the pelvis and progestational agent. She had a complete response to above treatments, and disease-free survival for 10 months. After recurrence, she received chemotherapy, radiotherapy and progestational agent once again. She had lived 56 months and is still alive by the time of report. Metastasis of endometrial carcinoma to extremity bone can rarely occur and should be considered when the patient with endometrial carcinoma complained of unexplained pain and swelling associated with extremity bone.

  10. Future directions for bone metastasis research - highlights from the 2015 bone and the Oncologist new updates conference (BONUS).

    Science.gov (United States)

    Fernandes, Ricardo; Siegel, Peter; Komarova, Svetlana; Hilton, John; Addison, Christina; Ibrahim, Mohammed F K; Werier, Joel; Dennis, Kristopher; Singh, Gurmit; Amir, Eitan; Jarvis, Virginia; Emmenegger, Urban; Mazzarello, Sasha; Clemons, Mark

    2016-06-01

    In an era of reduced peer-reviewed grant funding, performing academic bone oncology-related research has become increasingly challenging. Over the last 10 years we have held an annual meeting to bring together clinicians, clinician/scientists and basic biomedical researchers interested in the effects of cancer and its treatment on skeletal tissues. In the past these "Bone and the Oncologist New Updates Conference (BONUS)" meetings have served as critical catalyst for initiating productive research collaborations between attendees. The 2015 BONUS meeting format focused on potential key research themes that could form the basis of a coordinated national research strategy to tackle unmet clinical and research needs related to complications associated with cancer metastasis to bone. The three themes planned for discussion were: Is bone metastases-related pain the main issue facing patients? Are there new therapeutic targets for patients with bone metastases? How do we more firmly link basic science with clinical practice? We present a summary of lectures and commentaries from the attendees to serve as an example that other similarly motivated groups can model and share their experiences. It is our hope that these presentations will result in comments, feedback and suggestions from all those researchers interested in this important area.

  11. Future directions for bone metastasis research – highlights from the 2015 bone and the Oncologist new updates conference (BONUS

    Directory of Open Access Journals (Sweden)

    Ricardo Fernandes

    2016-06-01

    Full Text Available In an era of reduced peer-reviewed grant funding, performing academic bone oncology-related research has become increasingly challenging. Over the last 10 years we have held an annual meeting to bring together clinicians, clinician/scientists and basic biomedical researchers interested in the effects of cancer and its treatment on skeletal tissues. In the past these “Bone and the Oncologist New Updates Conference (BONUS” meetings have served as critical catalyst for initiating productive research collaborations between attendees. The 2015 BONUS meeting format focused on potential key research themes that could form the basis of a coordinated national research strategy to tackle unmet clinical and research needs related to complications associated with cancer metastasis to bone. The three themes planned for discussion were: Is bone metastases-related pain the main issue facing patients? Are there new therapeutic targets for patients with bone metastases? How do we more firmly link basic science with clinical practice? We present a summary of lectures and commentaries from the attendees to serve as an example that other similarly motivated groups can model and share their experiences. It is our hope that these presentations will result in comments, feedback and suggestions from all those researchers interested in this important area.

  12. Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Maroni, Paola [Istituto Ortopedico Galeazzi, IRCCS, Milano (Italy); Matteucci, Emanuela [Dipartiimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, Milano (Italy); Drago, Lorenzo; Banfi, Giuseppe [Istituto Ortopedico Galeazzi, IRCCS, Milano (Italy); Dipartiimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, Milano (Italy); Bendinelli, Paola [Dipartiimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, Milano (Italy); Desiderio, Maria Alfonsina, E-mail: a.desiderio@unimi.it [Dipartiimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, Milano (Italy)

    2015-01-15

    The present study deals with the molecular mechanisms involved in the regulation of E-cadherin expression under hypoxia, because the adjustment of the amount of E-cadherin due to physical stimuli of the microenvironment might influence the colonization of metastasis to skeleton. We analyzed the effect of 1% oxygen tension, that is similar to that encountered in the bone marrow by metastatic cells spreading from breast carcinoma. The purpose was to evaluate the hypoxia-orchestrated control of E-cadherin transactivation via hypoxia inducible factor-1 (HIF-1) and peroxisome proliferator activated receptor-γ (PPARγ), and the involvement of Hippo pathway members, as regulators of transcription factors. To give a translational significance to the study, we took into consideration human pair-matched ductal breast carcinoma and bone metastasis: E-cadherin and Wwox were expressed in bone metastasis but not in breast carcinoma, while HIF-1α and TAZ seemed localized principally in nuclei of metastasis and were found in all cell compartments of breast carcinoma. A close examination of the regulatory mechanisms underlying E-cadherin expression in bone metastasis was done in 1833 clone derived from MDA-MB231 cells. Hypoxia induced E-cadherin only in 1833 clone, but not in parental cells, through HIF-1 and PPARγ activities, while Wwox decreased. Since Wwox was highly expressed in bone metastasis, the effect of ectopic Wwox was evaluated, and we showed E-cadherin transactivation and enhanced invasiveness in WWOX transfected 1833 cells. Also, hypoxia was additive with ectopic Wwox remarkably enhancing HIF-1α nuclear shuttle and accumulation due to the lengthening of the half-life of HIF-1α protein; under this experimental condition HIF-1α appeared as a slower migrated band compared with control, in agreement with the phosphorylation state. The in vitro data strongly supported the almost exclusive presence of HIF-1α in nuclei of human-bone metastasis. Thus, we identified

  13. Parathyroid hormone-related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice.

    Science.gov (United States)

    Miki, Toyokazu; Yano, Seiji; Hanibuchi, Masaki; Kanematsu, Takanori; Muguruma, Hiroaki; Sone, Saburo

    2004-02-10

    We previously established an osteolytic bone metastasis model with multiorgan dissemination in natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice using human small cell lung cancer cells (SBC-5), which highly express the parathyroid hormone-related protein (PTHrP). In our present study, we evaluated the role of PTHrP on bone metastasis by SBC-5 cells using anti-PTHrP neutralizing antibody (Ab). Anti-PTHrP Ab did not affect the proliferation or cytokine production of SBC-5 cells in vitro. Repeated intravenous injection with anti-PTHrP Ab inhibited the formation of bone metastasis in a dose-dependent manner, while the same treatment had no significant effect on the metastasis to visceral organs (lung, liver, kidney and lymph node). In addition, treatment with anti-PTHrP Ab improved the elevated serum calcium level, associated with inhibition of osteolytic bone metastasis, suggesting that anti-PTHrP Ab inhibited bone metastasis via suppression of bone resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is essential for bone metastasis, but not visceral metastasis, by small cell lung cancer SBC-5 cells.

  14. Alterations of the Bone Marrow Microenvironment Contribute to Prostate Cancer Skeletal Metastasis

    Science.gov (United States)

    2012-05-01

    584–593. doi:10.1038/ nrc867 14. Roodman GD (2004) Mechanisms of bone metastasis. New Engl J Med 350(16):1655–1664. doi:10.1056/NEJMra030831 15...90. doi:10.1182/blood-2006-05-021352 39. Shiozawa Y, Havens AM, Jung Y, Ziegler AM, Pedersen EA, Wang J, Lu G, Roodman GD, Loberg RD, Pienta KJ...6 Fabiana N. Soki1, David Sadler1, Sudha Sud2, Sandra Tisdelle5, Stephanie D. Daignault4, Jeffrey A. Nemeth6, 7 Linda A. Snyder6, Thomas J. Wronski5

  15. TGF-Beta Induction of PMEPA1: Role in Bone Metastasis Due to Prostate Cancer

    Science.gov (United States)

    2009-01-01

    receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line . Cancer Sci 2007;98:127–33. 21. Stebbins ...Zylux corporation). TGF-β significantly increased PMEPA1 promoter activity in the 3 cell lines tested which was reversed by the Tgfbr1 inhibitor...or type 2 receptor(28;29). Using sqRT-PCR in multiple prostate cancer cells lines , we measured a 150-fold decrease of Tgfbr2 expression in C4-2B

  16. Does magnetic resonance imaging give value-added than bone scintigraphy in the detection of vertebral metastasis?

    Science.gov (United States)

    Chiewvit, Pipat; Danchaivijitr, Nasuda; Sirivitmaitrie, Kaewta; Chiewvit, Sunanta; Thephamongkhol, Kullatorn

    2009-06-01

    To determine the role of Magnetic Resonance (MR) imaging for the investigation ofpatients with suspected metastasis to the spine by bone scintigraphy. Retrospectively reviewed with comparison was made between Technetium-99m Methylene Diphosphonate (99(m)Tc-MDP) bone scintigraphy and corresponding spine MR images in 48 cases of vertebral metastasis at Siriraj Hospital. The intervals between bone scintigraphy and MR images did not exceed 1 month. The authors studied between January 2005 and December 2006 Bone scintigraphy were performed with planar imaging of the entire body and MR imaging was performed with the 1.5 tesla and 3.0 tesla scanner using standard techniques with T1-, T2-weighted images and fat-suppressed T1-weighted images with intravenous administration of gadopentetate dimeglumine. The MR imaging findings were studied: location (cervical or thoracic or lumbar or sacrum spine), number of lesions (solitary or multiple lesions), pattern of enhancement (homogeneous or inhomogeneous), involvement of spinal canal, compression of spinal cord, extradural extension, other incidental findings such as pulmonary metastasis, pleural effusion, lymphadenopathy The final diagnosis was confirmed clinically and followed-up for further management (radiation or surgery) or followed-up by MR imaging (1 month-16 months) and bone scintigraphy (5 months-12 months). Forty-eight cases (80 lesions) of vertebral metastasis were identified (25 men and 23 women; mean age 61 years and range 8-84 years). Primary neoplasms include breast cancer (n=11), colorectal cancer (n=7), lung cancer (n=6), prostate cancer (n=5), nasopharyngeal cancer (n=5), head and neck cancer (n=3), thyroid cancer (n=2), liver cancer (n=2), esophagus cancer (n=1), bladder cancer (n=1), retroperitoneum cancer (n=1), medulloblastoma (n=1), cervical cancer (n=1), ovarian cancer (n=1), malignant melanoma (n=1). The result of bone scintigraphy and MR imaging is used to evaluate vertebral metastasis: in 44 lesions of

  17. CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as micro-metastasis

    Institute of Scientific and Technical Information of China (English)

    Dao-Rong Wang; Guo-Yu Chen; Xun-Liang Liu; Yi Miao; Jian-Guo Xia; Lin-Hai Zhu; Dong Tang

    2006-01-01

    AIM: To detect the expression of CD44 correlated with the ability of micro-metastasis in peripheral blood and bone marrow of patients with gastric cancer and to deduce its clinical significance.METHODS: Preoperative peripheral blood and bone marrow specimens from 46 patients with gastric cancer and 6 controls were studied by semi-quantitative RTPCR amplification of CD44v6mRNA. Preoperative and postoperative peripheral blood specimens from 40patients with gastric cancer and 14 controls were studied by quantitative RT-PCR amplification of CD44v6mRNA in the corresponding period.RESULTS: Semi-quantitative RT-PCR amplification showed that CD44v6mRNA expression of peripheral blood and bone marrow was positive in 39 (84.8%)and 40 (86.9%) of 46 patients with gastric cancer,respectively. In peripheral blood, CD44v6mRNA expression was positive for diffuse type in 30 (93.8%)of 32 patients and for intestinal type in 9 (64.3%)of 14 patients. On the other hand, in bone marrow,CD44v6mRNA expression was positive for diffuse type in 31 (96.9%) of 32 patients and for intestinal type in 10 (71.4%) of 14 patients. There was a significant difference between the diffuse type and intestinal type.Quantitative RT-PCR amplification demonstrated that CD44v6mRNA was not expressed in the peripheral blood of controls and CD44v6mRNA expression was positive for preoperative peripheral blood in 40 patients with gastric cancer, the expression levels being from 4.9×102 to 3.2×105 copies/g RNA. The average expression level of CD44v6mRNA in peripheral blood was 3.9×1010copies/g RNA. The expression levels of CD44v6mRNA in peripheral blood in gastric cancer patients after curative operation increased from 5.5×100 to 7.6×10copies/g RNA (P=0.00496). After curative operation, the expression level decreased markedly.CONCLUSION: Semi-quantitative and quantitative RTPCR amplification for CD44v6mRNA is a sensitive and specific method for the detection of micro-metastasis in peripheral blood and bone

  18. Bone Metastasis

    Science.gov (United States)

    ... clinical trials with your doctor. Physical therapy A physical therapist can work with you to devise a plan ... increase your strength and improve your mobility. A physical therapist may suggest assistive devices to help you cope. ...

  19. Evaluation of the pain and local tenderness in bone metastasis treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS)

    Science.gov (United States)

    Namba, Hirofumi; Kawasaki, Motohiro; Kato, Tomonari; Tani, Toshikazu; Ushida, Takahiro; Koizumi, Norihiro

    2017-03-01

    It has been reported that MRgFUS has pain palliative effects on the local pain in patients with bone metastasis. In general, a severity of pain has been evaluated using only subjective method with numerical rating scale (NRS) or visual analogue scale (VAS). It is important to evaluate local pain-palliative effects of MRgFUS treatment with objective and quantitative method. The aim of this study is to investigate changes in the severity of local pain of bone metastasis before and after MRgFUS treatments, measuring pressure pain threshold (PPT) using pressure algometer, and pain intensity using electrical stimulation device (the Pain Vision system) at most painful site of bone metastasis. We have conducted MRgFUS for pain palliation of bone metastasis for 8 patients, and evaluated the local tenderness quantitatively for 8 patients, and evaluated local pain intensity for 7 patients. Before the treatments, PPTs were 106.3kPa [40.0-431.5] at metastatic site and 344.8 kPa [206.0-667.0] at normal control site, which showed a significant difference. The PPTs at metastatic site shows a significant increase from 106.3 kPa [40.0-431.5] at the baseline to 270.5 kPa [93.5-533.5] at 3 months after the treatment. The NRS score shows a significant decrease from 6.0 [4-8] at baseline to 1 [0-3] at 3 months after the treatment. Similarly, the pain intensity shows a significant decrease 245 [96.3-888.7] at baseline to 55.9 [2.8-292] at 3 months after the treatment. The results of our study illustrate the pain-relieving effects of MRgFUS for the treatment of painful bone metastasis. PPT might be a useful parameter not only for assessing a treatment's effect, but also for the decision of the painful area to treat with MRgFUS. Pain Vision seems to be useful for quantitative and objective evaluation of local pain of painful bone metastasis.

  20. Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients

    DEFF Research Database (Denmark)

    Klaff, Rami; Varenhorst, Eberhard; Berglund, Anders

    2016-01-01

    OBJECTIVE: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naïve prostate cancer. MATERIALS AND METHODS: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group......, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n = 319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival. RESULTS: Qo......L rating scales showed a decrease with increasing extent of bone metastasis (p prostate...

  1. Genome-wide identification of bone metastasis-related microRNAs in lung adenocarcinoma by high-throughput sequencing.

    Directory of Open Access Journals (Sweden)

    Lin Xie

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. They participate in a wide variety of biological processes, including apoptosis, proliferation and metastasis. The aberrant expression of miRNAs has been found to play an important role in many cancers. RESULTS: To understand the roles of miRNAs in the bone metastasis of lung adenocarcinoma, we constructed two small RNA libraries from blood of lung adenocarcinoma patients with and without bone metastasis. High-throughput sequencing combined with differential expression analysis identified that 7 microRNAs were down-regulated and 21 microRNAs were up-regulated in lung adenocarcinoma with bone metastasis. A total of 797 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in bone metastasis, survival of the primary origin and metastatic angiogenesis of lung adenocarcinoma. These include the MAPK, Wnt, and NF-kappaB signaling pathways, as well as pathways involving the matrix metalloproteinase, cytoskeletal protein and angiogenesis factors. CONCLUSIONS: This study provides some insights into the molecular mechanisms that underlie lung adenocarcinoma development, thereby aiding the diagnosis and treatment of the disease.

  2. Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer

    Science.gov (United States)

    Liu, Jin; Li, Defang; Dang, Lei; Liang, Chao; Guo, Baosheng; Lu, Cheng; He, Xiaojuan; Cheung, Hilda Y. S.; He, Bing; Liu, Biao; Li, Fangfei; Lu, Jun; Wang, Luyao; Shaikh, Atik Badshah; Jiang, Feng; Lu, Changwei; Peng, Songlin; Zhang, Zongkang; Zhang, Bao-Ting; Pan, Xiaohua; Xiao, Lianbo; Lu, Aiping; Zhang, Ge

    2017-01-01

    The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3′UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p. PMID:28071724

  3. A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone

    Institute of Scientific and Technical Information of China (English)

    LING Li-jun; WANG Feng; WANG Shui; LIU Xiao-an; SHEN En-chao; DING Qiang; LU Chao; XU Jian; CAO Qin-hong; ZHU Hai-qing

    2008-01-01

    Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.Methods Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1x105, 1x106 human breast cancer stem-like cells, and 1x106 parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1x106 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR). Results Our results demonstrated that cells in implanted human bones of group B, which received 1x106 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P=0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

  4. F-8 sodium fluoride position emission tomography/computed tomography for detection of thyroid cancer bone metastasis compared with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Jong; Lee, Won Woo; Park, So Yeon; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-04-15

    The aim of the study was to compare the diagnostic performances of F-18 sodium fluoride positron emission tomography/computed tomography (bone PET/CT) and bone scintigraphy (BS) for the detection of thyroid cancer bone metastasis. We retrospectively enrolled 6 thyroid cancer patients (age = 44.7 ± 9.8 years, M:F = 1:5, papillary:follicular = 2:4) with suspected bone metastatic lesions in the whole body iodine scintigraphy or BS, who subsequently underwent bone PET/CT. Pathologic diagnosis was conducted for 4 lesions of 4 patients. Of the 17 suspected bone lesions, 10 were metastatic and 7 benign. Compared to BS, bone PET/CT exhibited superior sensitivity (10/10 = 100% vs. 2/10 = 20%, p = 0.008), and accuracy (14/17 = 82.4% vs. 7/17 = 41.2%, p < 0.025). The specificity (4/7 = 57.1%) of bone PET/CT was not significantly different from that of BS (5/7 = 71.4%, p > 0.05). Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.

  5. Radiation therapy for metastatic lesions from breast cancer. Breast cancer metastasis to bone

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Shinya; Hoshi, Hiroaki [Gifu Univ. (Japan). School of Medicine

    2000-10-01

    This paper summarizes radiation therapy in the treatment of bone metastases from breast cancer. Bone metastasis occurs in approximately 70% of breast cancer patients, and the goals of radiation therapy for bone metastasis are: palliation of pain, prevention and treatment of neuropathic symptoms, and prevention of pathologic fractures. The prognosis of bone metastasis from breast cancer is known to be better than that of bone metastasis from other solid tumors. Local-field radiation, hemibody (or wide-field) radiation, and systemic radionuclide treatment are the major methods of radiation therapy for pain palliation. Although many studies have shown that breast cancer is more responsive to radiation therapy for pain palliation than other solid tumors, some studies found no significant difference. Local-field radiation therapy, which includes multi-fraction irradiation and single-fraction irradiation, is currently the most generally used method of radiotherapy for pain palliation. Pain palliation has been reported to be achieved in approximately 80% to 90% of patients treated with local-field external beam irradiation. Three types of multi-fraction irradiation therapy are administered depending on the prognosis: high-dose fraction irradiation (36-50 Gy/12-25 Fr/2.4-5 wk), short-course irradiation (20-30 Gy/10-15 Fr/2-3 wk), and ultra-short-course irradiation (15-25 Gy/2-5 Fr/1 wk). The most common irradiation schedule is 30 Gy/10 Fr/2 wk. Although many reports indicate no significant difference in pain palliation according to the dose, the percentage of patients who show a complete cure is significantly higher in those treated with doses of 30 Gy or more, and thus the total irradiation dose should be at least 30 Gy. High-dose fraction irradiation is indicated for patients with an expected survival time of 6 months or more while short-course or single-fraction irradiation is indicated for those with an expected survival time of 3 months or more. Single

  6. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    Directory of Open Access Journals (Sweden)

    Alison Gartland

    2016-09-01

    Full Text Available Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

  7. The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis

    DEFF Research Database (Denmark)

    Gartland, Alison; Erler, Janine Terra; Cox, Thomas Robert

    2016-01-01

    and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview......Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating...... of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis....

  8. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Science.gov (United States)

    Ferreira, Diêgo dos Santos; Faria, Samilla Dornelas; Lopes, Sávia Caldeira de Araújo; Teixeira, Cláudia Salviano; Malachias, Angelo; Magalhães-Paniago, Rogério; de Souza Filho, José Dias; Oliveira, Bruno Luis de Jesus Pinto; Guimarães, Alexander Ramos; Caravan, Peter; Ferreira, Lucas Antônio Miranda; Alves, Ricardo José; Oliveira, Mônica Cristina

    2016-01-01

    Background Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. Purpose To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases. Materials and methods Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals. Results Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart. Conclusion These results suggest that bone-targeted p

  9. Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis.

    Science.gov (United States)

    Angeloni, Valentina; Contessi, Nicola; De Marco, Cinzia; Bertoldi, Serena; Tanzi, Maria Cristina; Daidone, Maria Grazia; Farè, Silvia

    2017-09-18

    Breast cancer (BC) represents the most incident cancer case in women (29%), with high mortality rate. Bone metastasis occurs in 20-50% cases and, despite advances in BC research, the interactions between tumor cells and the metastatic microenvironment are still poorly understood. In vitro 3D models gained great interest in cancer research, thanks to the reproducibility, the 3D spatial cues and associated low costs, compared to in vivo and 2D in vitro models. In this study, we investigated the suitability of a poly-ether-urethane (PU) foam as 3D in vitro model to study the interactions between BC tumor-initiating cells and the bone microenvironment. PU foam open porosity (>70%) appeared suitable to mimic trabecular bone structure. The PU foam showed good mechanical properties under cyclic compression (E=69-109kPa), even if lower than human trabecular bone. The scaffold supported osteoblast SAOS-2 cell line proliferation, with no cytotoxic effects. Human adipose derived stem cells (ADSC) were cultured and differentiated into osteoblast lineage on the PU foam, as shown by alizarin red staining and RT-PCR, thus offering a bone biomimetic microenvironment to the further co-culture with BC derived tumor-initiating cells (MCFS). Tumor aggregates were observed after three weeks of co-culture by e-cadherin staining and SEM; modification in CaP distribution was identified by SEM-EDX and associated to the presence of tumor cells. In conclusion, we demonstrated the suitability of the PU foam to reproduce a bone biomimetic microenvironment, useful for the co-culture of human osteoblasts/BC tumor-initiating cells and to investigate their interaction. 3D in vitro models represent an outstanding alternative in the study of tumor metastases development, compared to traditional 2D in vitro cultures, which oversimplify the 3D tissue microenvironment, and in vivo studies, affected by low reproducibility and ethical issues. Several scaffold-based 3D in vitro models have been proposed

  10. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis.

    Science.gov (United States)

    Vashisht, Shikha; Bagler, Ganesh

    2012-01-01

    Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.

  11. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis.

    Directory of Open Access Journals (Sweden)

    Shikha Vashisht

    Full Text Available Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.

  12. Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model

    Science.gov (United States)

    Mercatali, Laura; La Manna, Federico; Groenewoud, Arwin; Casadei, Roberto; Recine, Federica; Miserocchi, Giacomo; Pieri, Federica; Liverani, Chiara; Bongiovanni, Alberto; Spadazzi, Chiara; de Vita, Alessandro; van der Pluijm, Gabri; Giorgini, Andrea; Biagini, Roberto; Amadori, Dino; Ibrahim, Toni; Snaar-Jagalska, Ewa

    2016-01-01

    Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model. PMID:27556456

  13. Cancer Patients Use Hospital-Based Care Until Death : A Further Analysis of the Dutch Bone Metastasis Study

    NARCIS (Netherlands)

    Meeuse, Jan J.; van der Linden, Yvette M.; Post, Wendy J.; Wanders, Rinus; Gans, Rijk O. B.; Leer, Jan Willem H.; Reyners, Anna K. L.

    2011-01-01

    Purpose: To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. Methods: The Dutch Bone Metastasis Study (DBMS) was a nationwide study proving

  14. Cancer patients use hospital-based care until death: a further analysis of the dutch bone metastasis study

    NARCIS (Netherlands)

    Meeuse, J.J.; Linden, Y.M. van der; Post, W.J.; Wanders, R.; Gans, R.O.; Leer, J.W.H.; Reyners, A.K.

    2011-01-01

    Abstract Purpose: To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. Methods: The Dutch Bone Metastasis Study (DBMS) was a nationwide study

  15. Development of a Patient-Derived Xenograft (PDX of Breast Cancer Bone Metastasis in a Zebrafish Model

    Directory of Open Access Journals (Sweden)

    Laura Mercatali

    2016-08-01

    Full Text Available Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231. The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT, revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.

  16. FEASIBILITY OF WHOLE BODY DIFFUSION WEIGHTED IMAGING IN DETECTING BONE METASTASIS ON 3.0T MR SCANNER

    Institute of Scientific and Technical Information of China (English)

    Xian Xu; Lin Ma; Jins-han Zhang; You-quan Cai; Bai-xuan Xu; Liu-quan Chen; Fei Sun; Xing-gao Guo

    2008-01-01

    Objective To evaluate the feasibility of whole body diffusion weighted imaging (DWI) in bone metastasis detection using bone scintigraphy as comparison.Methods Forty-five patients with malignancy history were enrolled in our study. All the patients received the whole body DWI and bone scintigraphy scan within 1 week. The magnetic resonance (MR) examination was performed on 3.0T MR scanner using embedded body coil. The images were reviewed separately by two radiologists and two nuclear medicine physicians, who were blinded to the results of the other imaging modality. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two techniques for detecting bone metastasis were analyzed.Results A total of 181 metastatic lesions in 77 regions of 34 patients were detected by whole body DWI, and 167 metastatic lesions in 76 regions of 31 patients were identified by bone scintigraphy. The patient-based sensitivity and PPV of whole body DWI and bone scintigraphy were similar (89.5% vs. 81.6%, 97.1% vs. 91.2%), whereas, the patient-basod specificity and NPV of whole body DW1 were obviously higher than those of bone scintigraphy (85.7% vs. 57.1%, 60.0% vs. 36.4%). Ten regions negative in scintigraphy but positive in whole body DWI, mainly located in spine, pelvis, and femur; nine regions only detected by scintigraphy, mainly located in skull, sternum, clavicle, and scapula. The region-based sensitivity and specificity of whole body DWI were slightly higher than those of bone scintigraphy (89.5% vs. 88.4%, 95.6% vs. 87.6%). Conclusion Whole body DWI reveals excellent concordance with bone scintigraphy regarding detection of bone metastasis, and the two techniques are complementary for each other.

  17. Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using {sup 18F} FDG PET/CT and {sup 99mT}c HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with of without soft tissue formation from HCC. of 4,151 patients with HCC, 263 patients had bone metastases. Eighty five patients with bone metastasis from HCC underwent contrast enhanced FDG PET/CT. Fifty four of the enrolled subjects had recent {sup 99mT}c HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow up studies. Forty seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft tissue formation group had more frequent bone pain (77 vs. 37%, p<0.0001), higher SUVmax (6.02 vs. 3.52, p<0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non soft tissue formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion based analysis (98 vs. 53%, p=0.0015) and in patient based analysis (100 vs. 80%, p<0.001). Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast enhanced PET/CT will be useful in finding and delineating soft tissue forming bone metastasis from HCC.

  18. [Bronchial carcinoid tumor and scintigraphy of somatostatin receptors: detection of bone metastasis].

    Science.gov (United States)

    Banzo, J; Abós, M D; Prats, E; García, F; Freile, E; Razola, P; Escalera, T

    2001-10-01

    Surgery is the treatment of choice for bronchial carcinoid tumor (BCT), whenever the staging is adequate. There is little information about the capability of the somatostatin receptor scintigraphy (SRS) to detect bone metastases in the carcinoid tumor. This work has aimed to evaluate retrospectively the diagnostic accuracy of the SRS in the detection of bone metastases in BCT. Based on their clinical indication, the patients were classified into two different groups: Group A (n = 4), staging of a known BCT; and Group B (n = 6), treatment control. The SRS results could be correlated with the CT results in all 4 patients from the group A, and in one patient from the group B, and the SRS results were compared with the clinical follow up during at least one year in the other 5 patients. The SRS scan detected the 4 BCT from the group A; in 2 of them the patient staging was superior when the SRS was used than with the CT, whereas the scan overestimated the tumor stage (BCT + sarcoidosis) in another patient. During the clinical course, one of these patients developed bone and liver metastases. The SRS was normal in 5 asymptomatic patients from group B, whereas the scan showed disseminated metastatic disease (liver, bone, spleen and lymph nodes) in another patient. In the 2 patients with bone metastases, the total number of bone metastases detected by the bone scan was 12, and by the SRS 8. The four lesions that were not detected by SRS were located in the ribs (n = 3) and 12-D (n = 1). The capability of the SRS to detect bone metastases makes it more useful in BCT staging. Over the next few years, the role of the bone scan and SRS in the detection of bone metastases in carcinoid tumors needs to be established.

  19. Genomic analysis of a spontaneous model of breast cancer metastasis to bone reveals a role for the extracellular matrix.

    Science.gov (United States)

    Eckhardt, Bedrich L; Parker, Belinda S; van Laar, Ryan K; Restall, Christina M; Natoli, Anthony L; Tavaria, Michael D; Stanley, Kym L; Sloan, Erica K; Moseley, Jane M; Anderson, Robin L

    2005-01-01

    A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.

  20. A Bone Metastasis Nude Mouse Model Created by Ultrasound Guided Intracardiac Injection of Breast Cancer Cells: the Micro-CT, MRI and Bioluminescence Imaging Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Jin; Song, Eun Hye; Kim, Seol Hwa; Song, Ho Taek; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Sang Hyun [Korean Minjok Leadership Academy, Heongsung (Korea, Republic of)

    2011-01-15

    The purpose of this study was to develop a nude mouse model of bone metastasis by performing intracardiac injection of breast cancer cells under ultrasonography guidance and we wanted to evaluate the development and the distribution of metastasis in vivo using micro-CT, MRI and bioluminescence imaging. Animal experiments were performed in 6-week-old female nude mice. The animals underwent left ventricular injection of 2x105 MDA-MB-231Bo-Luc cells. After injection of the tumor cells, serial bioluminescence imaging was performed for 7 weeks. The findings of micro-CT, MRI and the histology were correlated with the 'hot' lesions seen on the bioluminescence imaging. Metastasis was found in 62.3% of the animals. Two weeks after intracardiac injection, metastasis to the brain, spine and femur was detected with bioluminescence imaging with an increasing intensity by week 7. Micro-CT scan confirmed multiple osteolytic lesions at the femur, spine and skull. MRI and the histology were able to show metastasis in the brain and extraskeletal metastasis around the femur. The intracardiac injection of cancer cells under ultrasonography guidance is a safe and highly reproducible method to produce bone metastasis in nude mice. This bone metastasis nude mouse model will be useful to study the mechanism of bone metastasis and to validate new therapeutics

  1. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  2. Long-term survival after a favorable response to anti-EGFR antibody plus chemotherapy to treat bone marrow metastasis: a case report of KRAS-wildtype rectal cancer

    Science.gov (United States)

    Nakamura, Sho; Fukui, Tadahisa; Suzuki, Shuhei; Takeda, Hiroyuki; Watanabe, Kaname; Yoshioka, Takashi

    2017-01-01

    Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy.

  3. 胃癌骨转移的临床特点%Clinical characteristics of bone metastasis from gastric cancer

    Institute of Scientific and Technical Information of China (English)

    张高嘉; 王俊锋; 李万荣; 张云鹏; 沈志祥

    2015-01-01

    据文献报道胃癌伴有骨转移发生率为0.46%~38%,胃癌伴骨转移的高危因素包括:年轻患者、病理为低分化腺癌、BorrmannⅢ型、浸润深度T3和T4、伴多发淋巴转移和胃体部肿瘤。转移途径半数以上为非门脉系统。胃癌伴骨转移而无肝转移病例占69%,骨转移与淋巴转移区站转移有密切关联,距胃原发病灶3 cm以上存在淋巴转移者,其骨转移发生率为27%。核素扫描为骨转移提供了诊断途径和可靠的依据,HCG、CEA肿瘤标志物检测对诊断骨转移有所帮助,治疗以放化疗为主。骨转移预后较差,大多生存期<6个月。%The bone is a common site of metastasis for gastric cancer. High-risk factors of metastatic gastric cancer include young age, poorly differentiated adenocarcinoma, Borrmann type III tumors, depth of invasion at Se and Pm levels, positive lymph nodes, and gastric cancer with concomitant body of stomach cancer. More than half of the transfer pathway belongs to the non-portal system. Cases of gastric cancer with bone metastasis but without liver metastasis accounted for 69%of the total gastric cancer cases, whereas the incidence rate of bone metastasis with lymph node metastasis (≥3 cm away from the primary lesion) was 27%. In addition to the tumor markers human chorionic gonadotropin and carcinoembryonic antigen, radionuclide scan of the bone metastasis provides diagnostic pathways and reliable basis for treatment. Chemoradiation and surgery as symptomatic treatments are alternative therapies for stomach cancer. Bone metastasis confers unfavorable prognosis, and the survival time is often less than six months.

  4. A ssessment of the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Lu; Zhe Zhang; Chao Yang; Jia-Cheng Zhang; Jun-Peng Ma; Peng Du; Jian Yang; Fu-Qiang Jiang; Xin-Li Jin; Peng Xie

    2016-01-01

    Objective:To study the malignant biology and bone metabolism after transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment of vertebral metastasis from lung cancer.Methods: A total of 46 cases of patients with vertebral metastasis from lung cancer treated in our hospital between May 2012 and December 2015 were selected and divided into two groups, observation group (n=23) received transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment and control group only received transcatheter vertebral arterial chemoembolization therapy. Eight weeks after treatment, serum was collected to determine the levels of tumor markers, invasive molecules and bone transformation indicators.Results:8 weeks after treatment, serum CEA, NSE, Cyfra21-1, TK1, RCAS1, CatB, CatD, CatX, MMP7, MMP9, MMP13, N-MID, BALP, OC, PINP,β-CTX, NTX, ICTP and TRACP5b levels of observation group were significantly lower than those of control group.Conclusions:Transcatheter vertebral arterial chemoembolization combined with zoledronic acid treatment can more effectively kill the cancer cells in vertebral metastases, inhibit the secretion of protease and regulate bone metabolism balance.

  5. Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice.

    Science.gov (United States)

    Wolfe, Tobie D; Pillai, Smitha Pankajavally Somanathan; Hildreth, Blake Eason; Lanigan, Lisa G; Martin, Chelsea K; Werbeck, Jillian L; Rosol, Thomas J

    2011-04-01

    Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct chemotherapy. Therapies that inhibit bone resorption, such as the bisphosphonates, may be an effective palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that therapy with a nitrogen-containing bisphosphonate, zoledronic acid (Zol), reduced OSA-induced bone lysis; however, Zol monotherapy or in combination with amputation was not effective at inhibiting pulmonary metastasis. While not reaching statistical significance, amputation of the tumor-bearing limb reduced the average incidence of lung metastases; however, this effect was nullified when Zol was added to the treatment protocol. In untreated mice, the magnitude of proximal tibial lysis was significantly correlated with the incidence of metastasis. The data support amputation alone for the management of appendicular OSA rather than combining amputation with Zol. However, in patients that are not viable candidates for amputation, Zol may be a useful palliative therapy for OSA by reducing the magnitude of lysis and therefore bone pain, despite the risk of increased pulmonary metastasis.

  6. A transcriptome-proteome integrated network identifies endoplasmic reticulum thiol oxidoreductase (ERp57) as a hub that mediates bone metastasis.

    Science.gov (United States)

    Santana-Codina, Naiara; Carretero, Rafael; Sanz-Pamplona, Rebeca; Cabrera, Teresa; Guney, Emre; Oliva, Baldo; Clezardin, Philippe; Olarte, Omar E; Loza-Alvarez, Pablo; Méndez-Lucas, Andrés; Perales, Jose Carlos; Sierra, Angels

    2013-08-01

    Bone metastasis is the most common distant relapse in breast cancer. The identification of key proteins involved in the osteotropic phenotype would represent a major step toward the development of new prognostic markers and therapeutic improvements. The aim of this study was to characterize functional phenotypes that favor bone metastasis in human breast cancer. We used the human breast cancer cell line MDA-MB-231 and its osteotropic BO2 subclone to identify crucial proteins in bone metastatic growth. We identified 31 proteins, 15 underexpressed and 16 overexpressed, in BO2 cells compared with parental cells. We employed a network-modeling approach in which these 31 candidate proteins were prioritized with respect to their potential in metastasis formation, based on the topology of the protein-protein interaction network and differential expression. The protein-protein interaction network provided a framework to study the functional relationships between biological molecules by attributing functions to genes whose functions had not been characterized. The combination of expression profiles and protein interactions revealed an endoplasmic reticulum-thiol oxidoreductase, ERp57, functioning as a hub that retained four down-regulated nodes involved in antigen presentation associated with the human major histocompatibility complex class I molecules, including HLA-A, HLA-B, HLA-E, and HLA-F. Further analysis of the interaction network revealed an inverse correlation between ERp57 and vimentin, which influences cytoskeleton reorganization. Moreover, knockdown of ERp57 in BO2 cells confirmed its bone organ-specific prometastatic role. Altogether, ERp57 appears as a multifunctional chaperone that can regulate diverse biological processes to maintain the homeostasis of breast cancer cells and promote the development of bone metastasis.

  7. Patrolling Monocytes Control Tumor Metastasis to the Lung

    OpenAIRE

    Hanna, Richard N.; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Graham D. Thomas; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz

    2015-01-01

    The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical “patrolling” monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased ...

  8. Influence of the Different Primary Cancers and Different Types of Bone Metastasis on the Lesion-based Artificial Neural Network Value Calculated by a Computer-aided Diagnostic System,BONENAVI, on Bone Scintigraphy Images

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    TAKURO ISODA

    2017-01-01

    Full Text Available Objective(s: BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN and bone scan index (BSI values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. Methods: We analyzed 50 patients (36 males, 14 females; age range: 42–87 yrs, median age: 72.5 yrs with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer. Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic,osteolytic, and mixed components was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based among the three primary cancers and four types of bone metastasis.Results: There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer, 0.909; and lung cancer, 0.864. Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic, 0.939; mildly osteoblastic, 0.788; mixed type, 0.991; and osteolytic, 0.969. The possibility of a lesion-based ANN value below 0.5 was 10.9% for bone metastasis in prostate cancer, 12.9% for breast cancer, and 37

  9. The relationship between skeletal-related events and bone scan index for the treatment of bone metastasis with breast cancer patients.

    Science.gov (United States)

    Iwase, Toshiaki; Yamamoto, Naohito; Ichihara, Hironori; Togawa, Takashi; Nagashima, Takeshi; Miyazaki, Masaru

    2014-12-01

    The aim of the present study was to investigate the relationships between the automated bone scan index (aBSI) and skeletal-related events (SRE) in breast cancer patients with bone metastasis. A computer-aided software (BONENAVI™) that was developed using an Artificial Neural Network (Artificial Neural Network) was used for the present analysis. Forty-five patients diagnosed with bone metastasis due to breast cancer from April 2005 through March 2013 were retrospectively analyzed. Before and after the time of initial treatment, aBSI, Artificial Neural Network score, and hotspot number were calculated, and the relationships between these scores and SRE were analyzed. Twenty cases showed decreased (improved) aBSI values after initial treatment (Group A), and 25 cases showed unchanged/increased (worsened) aBSI values (Group B). Chi-square analysis revealed a significant difference in incident numbers of SRE between the two groups--one case in Group A and 12 in Group B (Pbone metabolic or tumor markers, alkaline phosphatase was significantly correlated with aBSI at the time of initial treatment (R=0.69, Pcancer patients with bone metastasis at high risk of SRE.

  10. Imaging anti-angiogenic treatment response with DCE-VCT, DCE-MRI and DWI in an animal model of breast cancer bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Baeuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: t.baeuerle@dkfz-heidelberg.de; Bartling, Soenke [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: s.bartling@dkfz-heidelberg.de; Berger, Martin [Unit of Chemotherapy and Toxicology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: m.berger@dkfz-heidelberg.de; Schmitt-Graeff, Annette [Institute of Pathology, University of Freiburg, Postfach 214, 79002 Freiburg (Germany)], E-mail: annette.schmitt-graeff@uniklinik-freiburg.de; Hilbig, Heidegard [Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103 Leipzig (Germany)], E-mail: Heidegard.Hilbig@medizin.uni-leipzig.de; Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, Radiologische Klinik, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)], E-mail: hans-ulrich.kauczor@med.uni-heidelberg.de; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail: s.delorme@dkfz-heidelberg.de; Kiessling, Fabian [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Experimental Molecular Imaging, RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen (Germany)], E-mail: fkiessling@ukaachen.de

    2010-02-15

    As current classification systems for the assessment of treatment response in bone metastasis do not meet the needs of oncologists, new imaging biomarkers are desirable. Therefore, the diagnostic impact of dynamic contrast enhanced (DCE)-volumetric computed tomography (VCT) (descriptive analysis), DCE-MRI (two-compartment model) and diffusion weighted imaging (DWI) for monitoring anti-angiogenic therapy effects of the VEGF antibody bevacizumab in breast cancer bone metastases in rats was studied. Nude rats (n = 8 animals treated with bevacizumab and n = 9 untreated control rats) with site-specific osteolytic bone metastasis of the hind leg were imaged with a 1.5 T clinical MRI-scanner in an animal coil as well as in a volumetric CT-scanner at days 30, 40, 50 and 60 after inoculation of MDA-MB-231 human breast cancer cells. From these data, osteolytic lesion size (OLS), peak enhancement (PE), area under the curve (AUC), amplitude (A), exchange rate constant (k{sub ep}) and apparent diffusion coefficient (ADC) were determined in bone metastases. Prior to changes in OLS (p {<=} 0.05 at days 50 and 60) there was already a significant decrease in PE, AUC and A (p {<=} 0.05 at days 40-60) in treated animals compared to controls. However, for k{sub ep} and ADC there were no significant differences between the groups at any time point (p > 0.05 at days 40-60). In conclusion, anti-angiogenic treatment response in osteolytic breast cancer bone metastases can be assessed early with surrogate markers of vascularization, while DWI appears to be insensitive.

  11. Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

    Science.gov (United States)

    Miki, T; Yano, S; Hanibuchi, M; Sone, S

    2000-01-01

    Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer

  12. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Directory of Open Access Journals (Sweden)

    Ferreira DS

    2016-08-01

    assessed in bone metastasis-bearing animals.Results: Liposomes presented suitable diameter (~170 nm, DOX encapsulation (~2 mg/mL, controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart.Conclusion: These results suggest that bone-targeted pH-sensitive liposomes containing DOX can be an interesting strategy for selectively delivering this drug into bone-tumor sites, increasing its activity, and reducing DOX-related toxicity. Keywords: hydroxyapatite-targeted formulations, bisphosphonates, pH-responsive nanostructures, bone-tumor treatment

  13. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  14. Obtusifolin suppresses phthalate esters-induced breast cancer bone metastasis by targeting parathyroid hormone-related protein.

    Science.gov (United States)

    Hsu, Ya-Ling; Tsai, Eing-Mei; Hou, Ming-Feng; Wang, Tsu-Nai; Hung, Jen-Yu; Kuo, Po-Lin

    2014-12-10

    This study is the first to demonstrate that parathyroid hormone-related protein (PTHrP), produced by human breast cancer cells after exposure to phthalate esters, contributes to bone metastasis by increasing osteoclastogenesis. This is also the first to reveal that obtusifolin reverses phthalate esters-mediated bone resorption. Human breast cancer cells were treated with dibutyl phthalate (DBP), harvested in conditioned medium, and cultured to osteoblasts or osteoclasts. Cultures of osteoblasts with DBP-MDA-MB-231-CM increased the osteoclastogenesis activator RANKL (receptor activator of nuclear factor κ-B ligand) and M-CSF (macrophage colony-stimulating factor). PTHrP was secreted in MDA-MB-231 cells. DBP-MDA-MB-231-CM reduced osteoblasts to produce osteoprotegerin, an osteoclastogenesis inhibitor, while DBP mediated PTHrP up-regulation, increasing IL-8 secretion in MDA-MB-231 and contributing to breast cancer-mediated osteoclast differentiation and bone resorption. Obtusifolin, a major bioactive compound present in Cassia tora L., suppressed phthalate esters-mediated bone resorption. Therefore, obtusifolin may be a novel anti-breast-cancer bone metastasis agent.

  15. MicroRNA control of invasion and metastasis pathways.

    Directory of Open Access Journals (Sweden)

    Rahul eSreekumar

    2011-09-01

    Full Text Available Abstract:Despite recent advances, cancer remains a leading cause of death worldwide. In developed countries, the incidence of colorectal and breast cancer has been stable, but no improvement in prognosis has been observed if the patient presents with metastases at diagnosis. This fact highlights the importance of therapeutic approaches targeting cellular invasion and metastasis programmes as the next step in cancer treatment. During carcinoma progression a process called Epithelial-Mesenchymal Transition (EMT results in enhanced invasion and motility which is directly linked with loss of epithelial polarity and epithelial junctions, migration permissive cytoskeleton alterations, and the acquisition of mesenchymal properties. The recent discovery of microRNAs (miRNAs controlling key cellular pathways has opened a new era in understanding how EMT pathways are modulated. In this review, we classify EMT regulating proteins according to their cellular localization (membrane, cytoplasmic and nuclear, and summarize the current knowledge on how they are controlled by miRNAs and propose potential miRNAs for the transcripts that may control their expression.

  16. The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone sarcomas (Review).

    Science.gov (United States)

    Liao, Yu-Xin; Zhou, Cheng-Hao; Zeng, Hui; Zuo, Dong-Qing; Wang, Zhuo-Ying; Yin, Fei; Hua, Ying-Qing; Cai, Zheng-Dong

    2013-12-01

    Bone sarcomas, which comprise less than 1% of all human malignancies, are a group of relatively rare mesenchymal-derived tumors. They are mainly composed of osteosarcoma, chondrosarcoma and Ewing's sarcoma. In spite of advances in adjuvant chemotherapy and wide surgical resection, prognosis remains poor due to the high propensity for lung metastasis, which is the leading cause of mortality in patients with bone sarcomas. Chemokines are a superfamily of small pro-inflammatory chemoattractant cytokines which can bind to specific G protein-coupled seven-span transmembrane receptors. Chemokine 12 (CXCL12), also designated as stromal cell-derived factor-1 (SDF-1), is able to bind to its cognate receptors, chemokine receptor 4 (CXCR4) and chemokine receptor 7 (CXCR7), with high affinity. The binding of CXCL12 to CXCR4/CXCR7 stimulates the activation of several downstream signaling pathways that regulate tumor progression and metastasis. In this review, the structure and function of CXCL12 and its receptors, CXCR4 and CXCR7, as well as many factors affecting their expression are discussed. Phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are the two most important downstream pathways regulated by the CXCL12-CXCR4/CXCR7 interaction. CXCR4 expression in bone sarcomas, including tumor cells and samples and the correlation between CXCR4/CXCR7 expression and the survival of patients with bone sarcomas are also discussed. In addition, we review the involvement of the CXCL12‑CXCR4/CXCR7 axis in the growth and metastasis of bone sarcomas and the targeting of this axis in preclinical studies.

  17. Patrolling Monocytes Control Tumor Metastasis to the Lung

    Science.gov (United States)

    Hanna, Richard N.; Cekic, Caglar; Sag, Duygu; Tacke, Robert; Thomas, Graham D.; Nowyhed, Heba; Herrley, Erica; Rasquinha, Nicole; McArdle, Sara; Wu, Runpei; Peluso, Esther; Metzger, Daniel; Ichinose, Hiroshi; Shaked, Iftach; Chodaczek, Grzegorz; Biswas, Subhra K.; Hedrick, Catherine C.

    2016-01-01

    The immune system plays an important role in regulating tumor growth and metastasis. For example, classical monocytes promote tumorigenesis and cancer metastasis; however, how nonclassical “patrolling” monocytes interact with tumors is unknown. Here we show that patrolling monocytes are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack patrolling monocytes, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient patrolling monocytes into Nr4a1-deficient mice prevented tumor invasion in lung. Patrolling monocytes established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature and promoted natural killer cell recruitment and activation. Thus, patrolling monocytes contribute to cancer immunosurveillance and may be targets for cancer immunotherapy. PMID:26494174

  18. Clinical features of bone metastasis for differentiated thyroid carcinoma: A study of 21 patients from a Tunisian center

    Directory of Open Access Journals (Sweden)

    Faouzi Kallel

    2014-01-01

    Full Text Available Introduction: The differentiated thyroid cancers have a good prognosis unless the presence of metastasis. These distant metastases, especially in bone, are a major cause of impaired quality of life and death requiring intensive management. The aim of our work was to study the patients′ data, the disease characteristics and to analyze the therapeutic management of these patients. Results: This study concerned a cohort of 21 patients treated for differentiated thyroid cancer during the period from 1995 to 2011. Eighteen of our patients were aged over 45 years. A majority of them had follicular carcinoma. Bone metastases were often multiple and located at the axial skeleton. They were associated with other types of metastases, especially lung metastasis. A majority of patients received 131I treatment, following surgery or external beam radiotherapy for a palliative purpose. Overall survival was 65% at 5 years and 49% at 10 years. A long-term survival was achieved in 10% of the patients benefiting from a multidisciplinary care adapted to each case. Conclusion: Bone metastases often have a pejorative turning in the natural history of differentiated thyroid cancers. The right selection of individuals with better prognosis, for whom more aggressive curative treatment was indicated, requires a better understanding of the features of bone involvement.

  19. Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report

    Directory of Open Access Journals (Sweden)

    Arasho Belachew

    2011-10-01

    Full Text Available Abstract Introduction Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment. Case presentation We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone. During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation, there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable. Conclusions Molecular imaging by F18 fludeoxyglucose positron emission tomography helps

  20. Late bone metastasis from an apparently benign oncocytic follicular thyroid tumor

    Science.gov (United States)

    Boronat, Mauro; Cabrera, Juan J; Perera, Carmen; Isla, Concepción; Nóvoa, Francisco J

    2013-01-01

    A man underwent total thyroidectomy for goiter when he was 62 years old. The pathology report informed on a 5.5 cm oncocytic follicular adenoma and a 3.5 mm papillary microcarcinoma. Due to the papillary tumor, he was treated with ablative radioiodine therapy and suppressive doses of levothyroxine. After uneventful follow-up for 9 years, increased levels of serum thyroglobulin were detected. Further imaging studies including a whole body scan (WBS) after an empirical dose of 200 mCi 131I were negative. Two years later, a 99mTc SestaMIBI WBS and a 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography showed a well-delimited focal uptake in the right femur. A bone biopsy of the lesion demonstrated metastasis of follicular thyroid carcinoma. Retrospective histological reexamination of available material from the primary oncocytic thyroid tumor failed to reveal definitive traits of malignancy. Learning points Oncocytic follicular thyroid tumors are a relatively uncommon variant of follicular thyroid neoplasms mostly composed of distinctive large oxyphilic cells (Hürthle cells).Criteria for the distinction between benign and malignant oncocytic neoplasms are not different from those used in the diagnosis of ordinary follicular tumors.Some cases of apparently benign oncocytic neoplasms have been found to develop malignant behavior.Search to rule out vascular and capsular invasion should be particularly exhaustive in histological assessment of oncocytic thyroid tumors.Even so, long-term surveillance remains appropriate for patients with large apparently benign oncocytic tumors. PMID:24616777

  1. {sup 177}Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Das, T.; Chakraborty, S.; Banerjee, S. [Radiopharmaceuticals Div., Bhabha Atomic Research Centre, Mumbai (India); Sarma, H.D. [Radiation Biology and Health Sciences Div., Bhabha Atomic Research Centre, Mumbai (India)

    2008-07-01

    The suitable nuclear decay characteristics [T{sub 1/2} = 6.73 d, E{sub {beta}}{sub (max)} = 497 keV, E{sub {gamma}} = 113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production with adequate specific activity and radionuclidic purity using a moderate flux reactor are important attributes towards {sup 177}Lu to be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study describes the preparation of {sup 177}Lu complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and its preliminary biological evaluation in animal models with an aim to proposing it as a viable radiopharmaceutical for bone pain palliation. The choice DOTMP as the polyaminophosphonic acid carrier ligand is based on the enhanced thermodynamic stability and kinetic inertness of the metal-ligand complexes with macrocyclic chelators. {sup 177}Lu was produced with a specific activity of {proportional_to} 12 GBq/mg ({proportional_to} 324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu{sub 2}O{sub 3} target at a thermal neutron flux of {proportional_to} 6 x 10{sup 13} n/cm{sup 2} s for 21 d. {sup 177}Lu-DOTMP complex was prepared in high yield and excellent radiochemical purity (> 99%) using DOTMP synthesized and characterized in-house. The complex exhibited excellent in-vitro stability at room temperature. Biodistribution studies in Wistar rats showed rapid skeletal accumulation of the injected activity [(1.60{+-}0.19)% per gram in femur at 3 h post-injection] with fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic studies carried out in normal Wistar rats and New Zealand white rabbits also demonstrated significant accumulation of the agent in skeleton and almost no retention in any other vital organs. (orig.)

  2. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

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    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  3. Endometrial Cancer Diagnosed by the Presence of Bone Metastasis and Treated with Zoledronic Acid: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Aiko Shigemitsu

    2010-12-01

    Full Text Available Bone metastasis from endometrial cancer is rare. We report a case of endometrial cancer which was diagnosed by the presence of bone metastasis and treated with zoledronic acid. A 57-year-old woman complaining of progressive right hip pain consulted an orthopedist. She had no gynecologic complaints. X-rays revealed an osteolytic lesion of the right ischium. Bone scintigraphy was subsequently carried out and showed isotope accumulation in the right ischium. Computed tomography revealed an enlarged uterus; the patient consequently consulted a gynecologist. Histological sections of an endometrial biopsy showed endometrioid adenocarcinoma. Hysterectomy and bilateral salpingo-oophorectomy, as well as bone biopsy of the right ischium, were therefore carried out. A moderately differentiated endometrioid adenocarcinoma was expressed in the corpus. Histopathological examination of the bone biopsy also revealed adenocarcinoma. The final diagnosis was stage IVB endometrial cancer with bone and lung metastasis. Good pain relief was achieved due to chemotherapy. However, 2 months after completion of the chemotherapy, the patient was administered zoledronic acid because her hip pain had gradually increased. Following zoledronic acid administration, the hip pain reduced. Radiotherapy was then given for the right ischial metastasis after the ninth course of zoledronic acid therapy because the metastasis site had increased and the possibility of a pathological fracture had risen. However, the patient died 21 months after the initial treatment because of disease progression.

  4. Diagnosis value of serum ALP and osteocalcin in early prostate cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Zong-Yong Cheng

    2016-01-01

    Objective:To explore the role and significance of the joint detection of serum alkaline phosphatase (ALP) and osteocalcin in prostate cancer bone metastases.Methods:A total of 87 cases of prostate cancer patients were diagnosed by radionuclide bone imaging, and 51 cases of them were included in the bone metastases group, while the other 36 cases were selected as the non-metastases group. Serum levels of ALP and osteocalcin of all patients were detected. The sensitivity, specificity, accuracy, likelihood ratio and the predictive value of patients in the two groups were analyzed. The sensitivity and specificity of the combined detection of ALP and osteocalcin and their expression levels in different bone metastases degrees were analyzed.Results:Serum ALP and osteocalcin levels of patients in metastases group were higher than those in non-metastases group and normal control group. In non-metastases group, the ALP level was higher than that in normal control group, while its osteocalcin level was lower than that in control group (P<0.05); The sensitivities of ALP and osteocalcin were 77.2% and 70.6%, respectively, and their specificities were 61.1% and 54.6%, respectively. The sensitivity and specificity became 93.3% and 82.33% in combined detection of ALP and osteocalcin, which was significantly higher than the single detection (P<0.05). The expression levels of ALP and osteocalcin increased with the increase of the metastases degrees (P<0.05). Conclusions:Combined detection of ALP and osteocalcin can be used in the early diagnosis of prostate cancer with improved diagnostic efficiency.

  5. 消化道肿瘤骨转移患者297例放射性骨显像分析%An Analysis on Radioactive Bone Imaging in 297 Patients with Bone Metastasis from Gastrointestinal Cancer

    Institute of Scientific and Technical Information of China (English)

    任媛; 张茜; 庄坤

    2013-01-01

    [Purpose] To investigate the role of radioactive bone imaging in the diagnosis for gastrointestinal cancer with bone metastasis.[Methods] Radioactive bone imaging in 605 cases with gastrointestinal cancer was analyzed.[Results] Among the 605 patients,297(49.09%) occurred bone metastasis.The frequency of multiple bone metastases(88.22%) was obviously more than that of single bone metastasis (11.78%).Cancer adjacent bone metastases were the major modality.The trunk bone metastasis was more than that of limbs and skull bone.There were 69.36% patients with bone pain symptom.[Conclusion] Radionuclide bone imaging is valuable for diagnosis gastrointestinal cancer with bone metastasis.Patients with gastrointestinal cancer should receive routinely radionuclide bone imaging during the follow-up.%[目的]探讨核素骨显像对消化道肿瘤骨转移的临床诊断价值.[方法]分析605例消化道肿瘤患者中骨转移患者的全身骨显像结果.[结果] 605例肿瘤患者中,297例(49.09%)发生骨转移.多发骨转移(88.22%)多于单发骨转移(11.78%).转移灶的分布多为邻近转移,且躯干骨多于四肢骨和颅骨.69.36%患者有骨痛症状.[结论]核素骨显像对消化道肿瘤骨转移诊断具有诊断价值.消化道肿瘤患者在随访中应常规行核素骨显像.

  6. Balloon sacroplasty as a palliative pain treatment in patients with metastasis-induced bone destruction and pathological fractures

    Energy Technology Data Exchange (ETDEWEB)

    Andresen, R.; Luedtke, C.W.; Kamusella, P.; Wissgott, C. [Westkuestenklinikum Heide, Academic Teaching Hospital of the Universities of Kiel, Luebeck and Hamburg, Heide (Germany). Inst. of Diagnostic and Interventional Radiology/Neuroradiology; Radmer, S. [Center of Orthopedics, Berlin (Germany). Orthopedic Surgery and Traumatology; Schober, H.C. [Municipal Hospital Suedstadt Rostock, Academic Teaching Hospital of the University of Rostock (Germany). Dept. of Internal Medicine

    2014-09-15

    Purpose: In the case of metastatic involvement of the sacrum with destruction and consecutive pathological fracture, intense disabling pain is one of the defining factors. The feasibility, safety and pain development with cement augmentation were to be investigated. Materials and Methods: CT-guided balloon sacroplasty was conducted in 10 patients with metastasis-induced bone destruction of the sacrum. After establishment of the entry point, a K-wire was first introduced as far as the central tumor lesion via the short, or transiliac axis. A cannula was then positioned over the wire. Under CT guidance, a balloon catheter was introduced through the cannula and inflated and deflated several times. The PMMA cement was then injected into the preformed cavity. The procedure was completed by a spiral CT control using the thin-slice technique. Pain intensity was determined using a visual analog scale (VAS) before the procedure, on the 2nd postoperative day and 6 months after the intervention. Finally, the patients were asked to state how satisfied they were. Results: Balloon sacroplasty was technically feasible in all patients. The control CT scan showed central distribution of the cement in the tumor lesion. On average 6+/-1.78 (4-10) ml of PMMA cement were introduced per treated lesion. A significant (p < 0.001) reduction in pain according to the VAS occurred in all patients from 9.3+/-0.67 (8-10) pre-operatively to 2.7+/-1.28 (1-5) on the 2nd postoperative day and 2.9+/-0.81 (2-5) 6 months after the intervention. All of the patients were re-mobilized after the procedure and underwent the further therapeutic measures as planned. Conclusion: Balloon sacroplasty is a helpful therapeutic option in the overall palliative treatment of patients with tumor-induced destruction. It is a safe and practicable procedure that markedly reduces disabling pain. (orig.)

  7. 15-deoxy-δ12,14-prostaglandin j2 inhibits osteolytic breast cancer bone metastasis and estrogen deficiency-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    Full Text Available Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL mRNA levels and normalized osteoprotegerin (OPG mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer

  8. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis.

    Science.gov (United States)

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi

    2016-08-01

    From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity.

  9. Natural killer lytic-associated molecule plays a role in controlling tumor dissemination and metastasis

    Directory of Open Access Journals (Sweden)

    Richard Glenn Hoover

    2012-12-01

    Full Text Available Natural killer lytic-associated molecule (NKLAM is an E3 ubiquitin ligase that plays a major role in the cytolytic activity of NK cells. NKLAM is rapidly synthesized and then targeted to the granule membranes of NK cells upon NK activation. Previous studies have shown an essential role for NKLAM in NK killing activity in vitro. These findings were extended to an in vivo model of NK-mediated tumor killing in which NKLAM-deficient knockout (KO mice injected with B16 melanoma cells were found to have significantly higher numbers of pulmonary tumor nodules than wild type (WT mice. To further investigate the role of NKLAM and NK function in tumor immunity in vivo, we utilized additional tumor models to compare tumor development and progression in NKLAM KO and WT mice. Primary tumor growth, dissemination, and metastasis of RMA-S lymphoma cells and E0771 breast cancer cells were evaluated. Both tumor cell lines were stably transfected with constructs that allow expression of green fluorescent protein (GFP, which serves as a tumor-specific marker. Intravenous injection of NK-sensitive RMA-S lymphoma cells resulted in greater dissemination of lymphoma cells in NKLAM KO mice than in WT mice. Lymphoma cells were found in the lymph nodes and bone marrow of NKLAM KO mice two weeks after injection; few detectable tumor cells remained in WT mice. E0771 syngeneic breast cancer cells were injected into the mammary pads of NKLAM KO and WT mice. Primary tumor growth was greater in NKLAM KO than in WT mice. More significantly, there were four to five fold more tumor cells in the blood and lungs of NKLAM KO than in WT mice two weeks after injection of tumor cells into the mammary pad. These results indicate that NKLAM plays a role in tumor development in vivo, especially in controlling tumor dissemination and metastasis to distant sites.

  10. Osteonecrosis Mimicking Bone Metastasis in Femoral Head on {sup 18F} FDG PET/CT: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyu Ho; Oh, Jin Kyoung; Kim, Sung Hoon; Yoo, Ik Dong; Choi, Eun Kyoung; Han, Eun Ji [The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2011-03-15

    A 77 year old woman underwent chemotherapy, radiotherapy, and brachytherapy for cervical cancer 9 years ago. On a follow up {sup 18F} fluorodeoxyglucose (FDG) PET/CT image, focal FDG uptake was noted in a focal osteolytic lesion in the right femoral head. During magnetic resonance imaging, this lesion showed subchondral dark signal intensity rim on T1 weighted image and double line sign on T2 weighted image, suggestive of osteonecrosis. The lesion was pathologically confirmed as osteonecrosis after surgery. This case demonstrates that osteonecrosis of the femoral head may demonstrate focal FDG uptake mimicking bone metastasis.

  11. Integrin signaling modes controlling cell migration and metastasis

    NARCIS (Netherlands)

    Truong, Hoa Hoang

    2011-01-01

    The aim of this thesis is to address how integrin-mediated signaling regulates cellular processes that have profound effects on cell morphology, motility, cancer metastasis, and FN fibrillogenesis, and how these findings can be utilized for relevant medical purposes or advancement of drug discovery.

  12. MR Imaging Findings of a Primary Cardiac Osteosarcoma and Its Bone Metastasis with Histopathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Se Jin; Choi, Jung Ah; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of); Chun, Eun Ju; Choi, Sang Il; Chung, Jin Haeng [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Choi, Ho Cheol [Gyeongsang National University Hospital, Jinju (Korea, Republic of)

    2011-02-15

    An osteosarcoma of cardiac origin is extremely rare, and a comprehensive description of MR imaging (MRI) findings of cardiac osteosarcoma and its metastasis in the femur have not been reported in the literature. We present a case of cardiac osteosarcoma in a 47-year-old woman and its metastasis to the femur, focusing on the description of MRI findings of the cardiac and metastatic bony osteosarcoma with a histopathologic correlation

  13. Acute Cavernous Sinus Syndrome from Metastasis of Lung Cancer to Sphenoid Bone

    Directory of Open Access Journals (Sweden)

    Marianna Zelenak

    2012-01-01

    Full Text Available Cavernous sinus syndrome is a rare entity in oncology reported only in occasional case reports. Optimal therapy is thus poorly defined with rapidly progressive disease dominating the picture. Management includes prompt diagnosis, attempts at stabilization of cranial nerve function, and aggressive control of central pain syndrome. Here, we report cavernous sinus syndrome secondary to the original squamous cell carcinoma of the lung. With common presenting causes of this syndrome being infection, thrombosis or tumor, it might seem that metastatic tumor would be expected in a patient with a cancer diagnosis. What was not so expected was the extremely rapid progression from mild headache and mild trigeminal neuralgia with negative-contrast head CT to a massive, destructive lesion involving several skull bones and skull base, only 3 weeks later. In addition, the patient was severely immunosuppressed at the completion of induction chemotherapy. Infectious processes, although unlikely, were considered, as aggressive cancer therapy (including high-dose steroids and radiation therapy had no impact on this disease. Despite accurate localization, the aggressive nature of this disease with massive bone destruction and dural thickening limited any chance of a durable control. We discuss the process of evaluation, diagnosis and treatment of symptoms and the importance of a team approach to best palliate these unfortunate patients.

  14. MicroRNA-33a functions as a bone metastasis suppressor in lung cancer by targeting parathyroid hormone related protein.

    Science.gov (United States)

    Kuo, Po-Lin; Liao, Szi-Hui; Hung, Jen-Yu; Huang, Ming-Shyan; Hsu, Ya-Ling

    2013-06-01

    Bone is a common site of metastasis for lung cancer, and is associated with significant morbidity and a dismal prognosis. MicroRNAs (miRNAs) are increasingly implicated in regulating the progression of malignancies. The efficacy of miR-33a or anti-miR-33a plasmid was assessed by Real-time PCR. Luciferase assays were using One-Glo Luciferase Assay System. Measurement of secreted factors was determined by ELISA kit. We have found that miR-33a, which is downregulated in lung cancer cells, directly targets PTHrP (parathyroid hormone-related protein), a potent stimulator of osteoclastic bone resorption, leading to decreased osteolytic bone metastasis. We also found that miR-33a levels are inversely correlated with PTHrP expression between human normal bronchial cell line and lung cancer cell lines. The reintroduction of miR-33a reduces the stimulatory effect of A549 on the production of osteoclastogenesis activator RANKL (receptor activator of nuclear factor kappa-B ligand) and M-CSF (macrophage colony-stimulating factor) on osteoblasts, while the expression of PTHrP is decreased in A549 cells. miR-33a overexpression also reduces the inhibitory activity of A549 on the production of OPG (osteoprotegerin), an osteoclastogenesis inhibitor. In addition, miR-33a-mediated PTHrP downregulation results in decreased IL-8 secretion in A549, which contributes to decreased lung cancer-mediated osteoclast differentiation and bone resorption. These findings have led us to conclude that miR-33a may be a potent tumor suppressor, which inhibits direct and indirect osteoclastogenesis through repression of PTHrP. miR-33a may even predict a poor prognosis for lung cancer patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Comparison of single versus multiple fractions for palliative treatment of painful bone metastasis: First study from north west India

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Background: Bone metastasis is a usual cause of pain in advanced cancer. Conventional radiation schedules require larger hospital stay and thus are not suitable for patients with poor general condition. This prospective observational study aims to compare the pain-relieving efficacy of different radiation fractionation schedules, i.e., 8 Gy administered in a single fraction versus 30 Gy administered in 10 fractions. Materials and Methods: Two hundred and fifty consecutive patients of bone metastasis were evaluated for the study, with 63 patients being excluded due to non-fulfillment of the inclusion criteria. The response to radiotherapy leading to pain relief as per the Visual Analog Scale was recorded at the end of treatment, 8 days, 15 days and 1 month during the follow-up visits. Results: Sixty-two percent of the patients received a single fraction while the remaining received 10 fractions. In the 10-fraction group, overall response was present in 60% of the patients. Stable pain was present in 23% of the patients while 9% patients had progressive pain. At 1 month of completion of treatment, 9% patients were lost to follow-up. In the single-fraction arm, overall response was seen in 58%, stable pain in 27% and progressive pain in 7% of the patients. Six percent of the patients were lost to follow-up. Conclusions: Single-fraction treatment for bony metastasis is as effective as multiple fractions to relieve bony pain and provides treatment convenience to both the patient and the caregiver.

  16. Establishment of A Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang3 and Its Real Bone Metastasis Clone CPA-Yang3BM in Immunodeficient Mice

    Directory of Open Access Journals (Sweden)

    Shunfang YANG

    2011-02-01

    Full Text Available Background and objective The recurrence and metastasis of lung cancer is a tough problem worldwide. The aim of this study is to establish a novel Chinese lung adenocarcinoma cell line and its real bone-seeking clone sub-line for exploring the molecular mechanism of lung cancer metastasis. Methods The cells came from the pleural effusion of a sixtyfive years old female patient with lung adenocarcinoma and supraclavicular lymph node metastases. The gene expression was detected by real-time quantitative PCR. Intracardiac injection of the cells into nude mice was performed and in vivo imaging was obtained by bone scintigraphy and conventional radiography. Bone metastases were determined on bone scintigraphy and then the lesions were resected under deep anesthesia for bone metastasis cancer cell culture. The process was repeated for four cycles to obtain a real bone-seeking clone. Results The tumorigenesis rate started at 4th passage in immunodeficient mice via subcutaneously and as well as later passages. Approximately 1×106 cancer cells were injected into left cardiac ventricle of immunodeficient mice resulted bone metastasis sites were successfully revealed by bone scintigraphy and pathological diagnosis, the mandible (100%, scapula (33%, humerus (50%, vertebral column (50%, femur (66.7% and accompanied invasion with other organs, the adrenal gland (17%, pulmonary (33%, liver (50%, submaxillary gland (33% in the mice after inoculation two-three weeks. The chromosome karyotype analysis of the cells was subdiploid. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR, SVIL, FN1 genes were overexpress. The novel cell was named CPA-Yang3. The femur metastasis cell was repeated in vivo-in vitro-in vivo with three cycles and harvested a real bone metastasis clone. It was named CPA-Yang3BM. Conclusion Tne characteristics of novel strain CPAYang3 is a highly metastasis cell line of

  17. Value of Bone Scan in Addition to F-18 FDG PET/CT and Characteristics of Discordant Lesions between F-18 FDG PET/CT and Bone Scan in the Spinal Bony Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Sung Min; Nam, Hyun Yeol; Kim, In Ju; Kim, Yong Ki [Pusan National University Hospital, Pusan (Korea, Republic of); Kim, Ju Sung [College of Medical Life Science, Silla University, Pusan (Korea, Republic of)

    2008-06-15

    Our purpose was to evaluate spinal bony metastasis which could be missed on an F-18 FDG PET/CT (FDG PET/CT) alone, and to characterize discordant metastatic lesions between FDG PET/CT and bone scan. FDG PET/CT and bone scans of 43 patients with spinal bony metastasis were analyzed retrospectively. A McNemar test was performed comparing the FDG PET/CT alone to the FDG PET/CT plus bone scan in the spinal bony metastases. A one-way chi-square test was performed to characterize the metastases that were missed on the FDG PET/CT alone. To evaluate discordant lesions between FDG PET/CT and bone scan, we performed logistic regression analyses. The independent variables were sites (cervical, thoracic, and lumbar), size (large and small), and maximum SUVs, and the dependant variable was bone scan uptake (positive and negative MDP uptake). A significant difference was found between the FDG PET/CT alone and the FDG PET/CT combined with the bone scan (p<0.01). Using the FDG PET/CT only, diffuse osteoblastic metastasis was missed with a significantly higher frequency (p=0.04). In the univariate analysis, cervical vertebra and small size were related to negative MDP uptake, and thoracic vertebra and large size were related to positive MDP uptake. However, in the multivariate analysis, only the large size was related to positive MDP uptake. A bone scan in addition to the FDG PET/CT increased the ability to evaluate spinal bony metastases, especially for diffuse osteoblastic metastasis. Large metastasis was related to positive bone scan uptake in spinal bony metastasis.

  18. Hepcidin蛋白与前列腺癌骨转移的相关性研究%Role of Hepcidin in prostate cancer patients with bone metastasis

    Institute of Scientific and Technical Information of China (English)

    薛冬; 何小舟; 许贤林; 周萃星; 徐宁

    2013-01-01

    Objective To detect the expression and correlation of serum Hepcidin,IL-6,sTfR,BMP6 diversity and explore the role of serum Hepcidin in prostate cancer with bone metastasis.Methods From January 2012 to March 2012,serum Hepcidin,IL-6,sTfR,BMP6 diversity were tested by ELISA in 25 prostate cancer patients with bone metastasis,30 prostate cancer patients without bone metastasis and 30 patients with BPH were used as the control group.The mean patient's age was 67 years (range from 55 to 75 years).In prostate cancers with bone metastasis group,the mean PSA base line was 138.0 μg/L (ranged from 20.0-1500 μg/L),the prostate cancers without bone metastasis group,mean PSA was 10.2 μg/L(ranged from 3.5-28.2 μg/L),and in BPH group,the mean PSA was 3.7 μg/L (ranged from 0.3-14.2 μg/L).Venous blood samples were taken in fasting mornings,then stored 3 ml in EDTA anticoagulant vacuum tube and centrifuged at4 ℃ for 10 min,the isolated serum were then preserved in-80 ℃ refrigerator.The competitive in-phase enzyme-linked immunoassay (ELISA) was used to detect serum Hepcidin,IL-6 and sTfR and BMP6 levels.Results Serum Hepcidin expressions in three groups were 67.7 ± 40.6 μg/L,37.5 ± 15.3 μg/L and 34.3 ± 10.7 μg/L,respectively.For prostate cancers with bone metastasis group,serum Hepcidin expression were higher than control group (P < 0.05),and associated with IL-6(22.5 ±22.1 μg/L),sTfR (5.7 ± 2.6 μg/L),BMP6 (429.3 ± 188.4 μg/L),correlation coefficients were 0.972,-0.987,0.971 (P < 0.05).Conclusions Increased serum Hepcidin level might be a sensitive index for diagnosis and prognosis of prostate cancers with bone metastasis.%目的 观察前列腺癌骨转移患者血清中IL-6、sTfR、BMP6等指标的变化,分析3个指标之间的相关性,探讨Hepcidin蛋白在前列腺癌骨转移中的作用.方法 选取2012年1月至2012年3月前列腺癌骨转移患者25例、前列腺癌无骨转移患者30例和BPH患者30例,年龄55~75岁,平均67

  19. Physiopathology of Spine Metastasis

    Directory of Open Access Journals (Sweden)

    Giulio Maccauro

    2011-01-01

    Full Text Available The metastasis is the spread of cancer from one part of the body to another. Two-thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour.

  20. Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT.

    Directory of Open Access Journals (Sweden)

    Hervé Nyangoga

    Full Text Available BACKGROUND: Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography. They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. CONCLUSION: This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular

  1. Samarium-153 EDTMP reduces multiple bone metastasis besides pain relieve; Reduction des metastases osseuses apres traitement au samarium 153-EDTMP en complement de son effet antalgique

    Energy Technology Data Exchange (ETDEWEB)

    Haffaf, E.M.; Oufriha, N. [Hopital Central de l' Armee, Service de Medecine Nucleaire, Alger (Algeria)

    2006-10-15

    This case report shows an almost disappearance of multiple painful bone metastases, on a {sup 99m}Tc-HMDP bone scintigraphy, about three months after administration of {sup 153}Sm-EDTMP (Quadramet in a 78 year-old man with hormone refractory prostate adenocarcinoma. One {sup 153}Sm-EDTMP reduced the PSA level in this patient by more than 70% for at least 2 months. It raises the possibility that this radiopharmaceutical could have therapeutic effect on bone metastasis in addition to its bone pain palliation effect. (authors)

  2. Research advances of the bone metastasis of the colorectal cancer%结直肠癌骨转移研究进展

    Institute of Scientific and Technical Information of China (English)

    赵亮; 苏佳灿

    2012-01-01

    As one of the most common malignant tumors, the colorectal cancer showed an increasing morbidity and mortality in recent years. Bone metastasis was the terminal manifestation of the colorectal cancer with low metastasis rate. It commonly occurred in multiple bones, leading severe pain, hypercalcemia, pathologic fracture and so on. Appropriate imaging examinations such as X-ray, CT, MRI and ECT and laboratory parameters such as CEA could provide help in the diagnose of the bone metastasis of the colorectal cancer. The mechanism of the bone metastasis of the colorectal cancer was still not clear now, however studies showed that metastasis promoting genes and metastasis suppressing genes might play important roles. The treatment of the bone metastasis included 2 aspects: the systemic treatment including radionuclide therapy, chemotherapy and bone resorption inhibitor therapy and the local treatment including operation and radiotherapy. The bone metastasis of the colorectal cancer was usually ignored in clinic and there were still a lot of problems remaining to be studied in the future.%@@ 结直肠癌是常见恶性肿瘤之一.流行病学资料刘放等[6] 分析了191例结直肠癌术后骨转移的患者,显示,2000年全世界有70万人患结直肠癌,占全部占同期治疗3454例结直肠癌的5.5%,其中结肠癌骨癌症新发病例数的9.4%;50万人死于结直肠癌,占转移率为2.9%,直肠癌转移率为7.5%,结、直肠癌癌症死亡数的7.9%[1-2] .在过去的20多年中,结直转移率差异具有显著的统计学意义.可见,结直肠肠癌的发病数和死亡数在世界大多数国家和地区都癌骨转移率虽然较低,但总体呈上升趋势,且直肠呈上升趋势.

  3. The critical role of bisphosphonates to target bone cancer metastasis: an overview.

    Science.gov (United States)

    Singh, Tejinder; Kaur, Veerpal; Kumar, Manish; Kaur, Prabhjot; Murthy, R S R; Rawal, Ravindra K

    2015-01-01

    Cancer becomes the leading cause of deaths worldwide, including breast cancer, prostate cancer and lung cancer that preferentially metastasize to bone and bone marrow. Bisphosphonates (BPs) have been used successfully for many years to reduce the skeletal complications related with the benign and malignant bone diseases that are characterized by enhanced osteoclastic bone resorption. Nitrogen-containing bisphosphonates (N-BPs) have also been demonstrated to exhibit direct anti-tumour effects. BPs binds avidly to the bone matrix, and released from matrix during bone resorption process, BPs are internalized by the osteoclasts where they interfere with biochemical pathways and induce osteoclast apoptosis. BPs also antagonizes the production of osteoclast and promotes the osteoblasts proliferation. Currently, Zoledronic acid is widely used as one of the BP having high bone specificity and potential to inhibit the osteoclast-mediated bone resorption. In addition to inhibition of cell multiplication and initiation of apoptosis in cultured cancer cells, they also interfere with adhesion of cancer cells to the bone matrix and inhibit cell migration and invasion. Pathophysiology and current target therapies like conjugate of BPs with liposomes, nanoparticle used for the treatment of bone cancer is reviewed in this article along with the use of different BPs.

  4. Bone metastasis treatment using magnetic resonance-guided high intensity focused ultrasound

    NARCIS (Netherlands)

    Yeo, Sin Yuin; Elevelt, Aaldert; Donato, Katia; van Rietbergen, Bert; ter Hoeve, Natalie D.; van Diest, Paul J.; Grüll, Holger

    2015-01-01

    Objectives: Bone pain resulting from cancer metastases reduces a patient's quality of life. Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) is a promising alternative palliative thermal treatment technique for bone metastases that has been tested in a few clinical studies. Here

  5. Comparison of (18)F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Ilhan; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo [Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Seoul (Korea, Republic of); Kong, Chang-Bae; Song, Won Seok; Cho, Wan Hyeong; Jeon, Dae-Geun; Lee, Soo-Yong [Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Orthopedic Surgery, Seoul (Korea, Republic of); Koh, Jae-Soo [Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2013-12-15

    We compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99 m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma. We retrospectively reviewed 206 patients with stage II-IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6 months. Diagnostic performances of PET/CT, BS, and their combinations were calculated. Out of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98 %, respectively, for PET/CT; 76, 97, and 96 %, respectively, for BS; and 100, 96, and 97 %, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100 %) was significantly higher than that of PET/CT (92 %) or BS (74 %) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77 %). PET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity. (orig.)

  6. Bone Marrow Microenvironmental Control of Prostate Cancer Skeletal Localization

    Science.gov (United States)

    2011-05-01

    1 Jinhui Liao,1 Janice E. Berry,1 Xin Li,1 Amy J. Koh,1 Megan N. Michalski,1 Matthew R. Eber,1 Fabiana N. Soki,1 W. David Sadler,1 Sudha Sud,2 Sandra...cancer metastases. Mol Cell Endocrinol 2009; 310: 71-81. 5. Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004; 350: 1655-64. 6. Shiozawa

  7. The Role of p53 Mutations in Metastasis of Prostate Cancer to Bone

    Science.gov (United States)

    2004-12-01

    transfectant. This implies that the bone would be less calcified and therefore weaker in patients bearing CaP bone metastases with this mutation. This has...Semi-quantitative fluorescence analysis of calcein binding as a measurement of in vitro mineralization. Calcified Tissue Internat. 67, 80-84 (2000) L...made into the skin along the lower half of the hind leg. The tendons were cut just above the ankle, allowing the large muscle to be peeled from the

  8. From aneurysmal bone cyst to telangiectatic osteosarcoma with metastasis in inguinal lymph nodes: Case report

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    Janevska Vesna

    2015-01-01

    Full Text Available Introduction. Aneurysmal bone cyst is a benign bone lesion composed of blood filled cystic cavities lined by fibrous septa. Its malignant transformation of is a rare event. Case report. We report a case of a lesion in the second metatarsal bone in a 29-year-old male, presented as a slight swelling of the right foot. After the curettage had been done, the diagnosis of aneurysmal bone cyst was made but the recurrence occurred 4 years later. The biopsy of the recurrent tumor showed compact neoplastic tissue consistent with diagnosis of giant cell tumor with malignancy. The malignant component was recognized as a high grade sarcoma with osteoid production. A tumor mass with the whole II metatarsal bone was extirpated and a resected part of fibula was transplanted. A year later, another recurrence occurred, an amputation was performed and a teleangiectatic osteosarcoma with ingvinal lymph nodes metastases was diagnosed. No other tumor mass was confirmed, either clinically or by imaging techniques at the time of his third operation. He died 4 months later with multiple pulmonary metastases. Conclusion. We emphasize the importance of team work in order to achieve the accurate diagnosis, highlighting careful radiological examinations, good sampling and awareness of unusual cases in bone tumor pathology.

  9. Reproductive hormones in breast cancer bone metastasis: The role of inhibins

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    Caroline Wilson

    2016-09-01

    Full Text Available The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine or from distant sites (endocrine. Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones. The molecular mechanism driving this differential effect has not been definitively identified, however, there is evidence that both reproductive hormones and bisphosphonates can affect similar paracrine factors and cellular components of the bone metastatic niche. This review focuses on how the ovarian endocrine hormone, inhibin, interacts with the paracrine factors activin and follistatin, abundant in the primary tumour and bone microenvironment, with subsequent effects on tumour cell survival. Inhibin also affects the cellular components of the bone microenvironment primarily the osteoblastic niche. Recent evidence has shown that bisphosphonates also alter this niche, which may represent a common mechanism by which inhibin and bisphosphonates interact to influence disease outcomes in early breast cancer. Further research is needed to fully elucidate these molecular mechanisms to enable understanding and future development of alternative bone targeted treatments with anti-tumour efficacy in premenopausal women.

  10. A New In Vitro Model of Breast Cancer Metastasis to Bone

    Science.gov (United States)

    2010-04-01

    1,25-dihydroxy vitamin D3 and 10–8 M menadione. The hFOB 1.19 line was conditionally immortalized by transfection with a gene encoding for the...2007) 24:385. Proceedings of the 11th International Congress of the Metastasis Research Society. Krishnan V1, Ravi D2 , Vogler EA1,2, and A.M...buffered medium containing various nutrients (e.g., amino acids, glucose, serum proteins, vitamins ). As cells grow, nutrients are depleted, waste

  11. Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer.

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    Xianbo Peng

    Full Text Available BACKGROUND: Human non-small cell lung cancer (NSCLC patients exhibit a high propensity to develop skeletal metastasis, resulting in excessive osteolytic activity. The RANKL/RANK/OPG system, which plays a pivotal role in bone remodeling by regulating osteoclast formation and activity, is of potential interest in this context. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, western blotting, and immunohistochemical analysis were used to examine the expression of RANKL, RANK, and OPG in human NSCLC cell lines with different metastatic potentials, as well as in 52 primary NSCLC samples and 75 NSCLC bone metastasis samples. In primary NSCLC patients, the expression of these proteins was correlated with clinicopathological parameters. Recombinant human RANKL and transfected RANKL cDNA were added to the PAa cell line to evaluate the promoter action of RANKL during the process of metastasis in vitro and in vivo. RESULTS: Up-regulated RANKL, RANK, and OPG expression and increased RANKL:OPG ratio were detected in NSCLC cell lines and in tumor tissues with bone metastasis, and were correlated with higher metastatic potential. The metastatic potential of NSCLC in vitro and in vivo, including migration and invasion ability, was significantly enhanced by recombinant human RANKL and the transfection of RANKL cDNA, and was impaired after OPG was added. The increased expression of RANKL and OPG correlated with tumor stage, lymph node metastasis, and distant metastasis. CONCLUSIONS: Differential expression of RANKL, RANK, and OPG is associated with the metastatic potential of human NSCLC to skeleton, raising the possibility that the RANKL/RANK/OPG system could be a therapeutic target for the treatment of metastatic NSCLC patients.

  12. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer

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    Santanu Pal

    2014-01-01

    Full Text Available Background: The primary aim of this prospective non-randomized study was to evaluate the effect of hemi-body irradiation (HBI on pain and quality of life in cancer patients with extensive bone metastases. The secondary aim was to evaluate side-effects and cost-effectiveness of the treatment. Materials and Methods: Between March 2008 and December 2010, a total of 23 (male = 14, female = 9, median age = 60 years diagnosed cases of metastatic cancer patients (prostate = 11, breast = 6, and lung = 6 received HBI, which was delivered as lower (n = 7 (dose = 8 Gy, upper (n = 8 (dose = 6 Gy, or sequential HBI (n = 8 with a Telecobalt unit (Theratron 780C. Among them, one lung cancer patient died at 2 months and one prostate cancer patient defaulted after the second follow-up. Thus, 21 patients (male = 13, female = 8, median age = 65 years (prostatic cancer = 10, breast cancer = 6, and lung cancer = 5 were followed up for a minimum of 6 months. Evaluations were performed before and at 2, 4, 8, 16, and 24 weeks after treatment. Pain evaluation was done by Visual Analogue Scale (VAS, Verbal Rating Scale (VRS, Percentage of Pain Relief (PRR, and Global Pain Score (GPS. Toxicity was assessed by CTC v-3 toxicity scores in the medical record. Assessment of oral morphine consumption was done before and after radiation using paired t-test, and correlation analysis was also done with decrease of morphine consumption and reduction of pain score using statistical analysis. Results: Response (control of pain was partial (PR in 67% and complete (CR in 22% of patients. For most patients, the pain control lasted throughout the follow-up period (6 months. From 66.66% patients requiring 13 or more Morphine (10 mg tablets per day prior to HBI, none of the patients required to consume 13 or more Morphine (10 mg tablets per day following HBI, which was correlated with significant reduction in various pain scores (P < 0.05. One way ANOVA with Dunnett′s Multiple Comparison

  13. A review of bone metastasis and its treatments, with a special emphasis on local and systemic radiotherapy

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    Peiman Haddad

    2014-01-01

    Treatment of bone metastases consist of analgesics, radiotherapy, surgery and bisphosphonates. Control of bone metastases is a challenging process, necessitating a multi-disciplinary approach and teamwork between the treating physicians. Radiotherapy is the most useful modality for this purpose in oncology, given both as a local and systemic therapy. We hope that this review would be able to help in choosing the best treatment option for this common palliative situation in Iranian cancer patients.

  14. 放射性核素骨显像对乳腺癌骨转移的临床应用价值%Diagnostic value of 99Tcm-MDP radionuclide bone imaging in bone metastasis of breast cancer

    Institute of Scientific and Technical Information of China (English)

    黄之杰; 霍红艳; 李正勇; 王庆旭; 孙志勇

    2011-01-01

    目的 探讨乳腺癌骨转移SPECT的影像学表现.方法 回顾性分析了168例乳腺癌患者骨转移的影像学表现,SPECT选择99Tcm -MDP作为显像剂,综合分析乳腺癌骨转移性病变的SPECT扫描特点.结果 乳腺癌SPECT扫描以多样性表现为特点;SPECT影像检出率达94.0%,但其缺乏特异性.结论 放射性核素骨显像结合临床资料,能够早期发现骨转移病灶,为临床治疗提供有力的依据.%Objective To investigate the image of bone metastasis of breast cancer scanned by single photo emission computer tomography ( SPECT ). Methods The clinical data of 168 women with confirmed bone metastasis of breast cancer were retrospectively studied. They all received SPECT using 99Tcm- MDP as an imaging agent, and then the imaging features were analyzed and compared with X - ray, CT and MRI ones. Results SPECT image of bone metastasis of breast cancer was characterized by multiformity. Its sensitivity to bone metastasis was high ( 94.0% ) compared with that of X - ray ( 28.1% ), CT ( 56.7% ) and MRI ( 82.6% ), but the specificity- was poor. Conclusion 99 Tcm- MDP radionuclide bone imaging combined with clinical data can detect and localize bone metastasis early,and therefore provide evidences for tailored management.

  15. Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

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    Shuai Huang

    2016-07-01

    Full Text Available Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR, a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β and inhibits the secretion of vascular endothelial growth factor (VEGF. The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs, and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000 by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001 and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008 were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.

  16. Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs.

    Science.gov (United States)

    Huang, Sheng; Tang, Yubo; Peng, Xinsheng; Cai, Xingdong; Wa, Qingde; Ren, Dong; Li, Qiji; Luo, Jiaquan; Li, Liangping; Zou, Xuenong; Huang, Shuai

    2016-10-01

    Bone metastasis is a main cause of cancer-related mortality in patients with advanced prostate cancer. Emerging evidence suggests that the acidic extracellular microenvironment plays significant roles in the growth and metastasis of tumors. However, the effects of acidity on bone metastasis of PCa remain undefined. In the present study, PC-3 cells were cultured in acidic medium (AM; pH 6.5) or neutral medium (NM; pH 7.4), aiming to investigate the effects and possible mechanisms of acidic extracellular microenvironment in bone metastasis of PCa. Our results showed that AM can promote spheroid and colony formations, cell viability and expression of stem cell characteristic-related markers in PC-3 cells. Moreover, AM stimulates MMP-9 secretion and promotes invasiveness of PC-3 cells, and these effects can be inhibited by blocking of MMP-9. Furthermore, AM stimulates VEGF secretion of PC-3 and AM conditioned medium (CMAM) promotes vasculogenesis of BM-EPCs by increasing cell viability, migration, tube formation, which involved activating the phosphorylation of VEGFR-2, Akt and P38, when pH of NM conditioned medium (CMNM) was modulated the same as AM conditioned medium (CMAM). Further studies have shown that CMNM induced vasculogenesis of BM-EPCs can be inhibited by the inhibition of VEGFR2 with DMH4. These findings suggest that acidic extracellular microenvironment may have the potential to modulate prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs. Improved anticancer strategies should be designed to selectively target acidic tumor microenvironment.

  17. Detection of bone metastasis of prostate cancer. Comparison of whole-body MRI and bone scintigraphy; Nachweis ossaerer Metastasen des Prostatakarzinoms. Vergleich der Leistungsfaehigkeit der Ganzkoerper-MRT und der Skelettszintigrafie

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    Ketelsen, D.; Roethke, M.; Aschoff, P.; Lichy, M.P.; Claussen, C.D.; Schlemmer, H.P. [Abt. fuer Diagnostische und Interventionelle Radiologie, Eberhard-Karls-Univ. Tuebingen (Germany); Merseburger, A.S. [Klinik fuer Urologie, Eberhard-Karls-Univ. Tuebingen (Germany); Reimold, M. [Abt. fuer Nuklearmedizin, Eberhard-Karls-Univ. Tuebingen (Germany)

    2008-08-15

    Purpose: prostate cancer continues to be the third leading cancer-related mortality of western men. Early diagnosis of bone metastasis is important for the therapy regime and for assessing the prognosis. The standard method is bone scintigraphy. Whole-body MRI proved to be more sensitive for early detection of skeletal metastasis. However, studies of homogenous tumor entities are not available. The aim of the study was to compare bone scintigraphy and whole-body MRI regarding the detection of bone metastasis of prostate cancer. Materials and methods: 14 patients with histologically confirmed prostate cancer and a bone scintigraphy as well as whole-body MRI within one month were included. The mean age was 68 years. Scintigraphy was performed using the planar whole-body technique (ventral and dorsal projections). Suspect areas were enlarged. Whole-body MRI was conducted using native T1w and STIR sequences in the coronary plane of the whole body, sagittal imaging of spine and breath-hold STIR and T1w-Flash-2D sequences of ribs and chest. Bone scintigraphy and whole-body MRI were evaluated retrospectively by experienced radiologists in a consensus reading on a lesion-based level. Results: whole-body MRI detected significantly more bone metastasis (p = 0.024). 96.4% of the demonstrated skeletal metastases in bone scintigraphy were founded in whole-body MRI while only 58.6% of the depicted metastases in MRI were able to be located in scintigraphy. There was no significant difference regarding bone metastasis greater than one centimeter (p = 0.082) in contrast to metastasis less than one centimeter (p = 0.035). Small osteoblastic metastases showed a considerably higher contrast in T1w sequences than in STIR imaging. Further advantages of whole-body MRI were additional information about extra-osseous tumor infiltration and their complications, for example stenosis of spinal canal or vertebral body fractures, found in 42.9% of patients. (orig.)

  18. SPA-1 controls the invasion and metastasis of human prostate cancer.

    Science.gov (United States)

    Shimizu, Yosuke; Hamazaki, Yoko; Hattori, Masakazu; Doi, Keiko; Terada, Naoki; Kobayashi, Takashi; Toda, Yoshinobu; Yamasaki, Toshinari; Inoue, Takahiro; Kajita, Yoichiro; Maeno, Atsushi; Kamba, Tomomi; Mikami, Yoshiki; Kamoto, Toshiyuki; Yamada, Tomomi; Kanno, Toru; Yoshikawa, Kiyotsugu; Ogawa, Osamu; Minato, Nagahiro; Nakamura, Eijiro

    2011-04-01

    Recent studies suggest that SIPA1 encoding a Rap GTPase-activating protein SPA-1 is a candidate metastasis efficiency-modifying gene in human breast cancer. In this study, we investigated the expression and function of SPA-1 in human prostate cancer (CaP). Immunohistochemical studies of tumor specimens from CaP patients revealed a positive correlation of SPA-1 expression with disease progression and metastasis. The correlation was recapitulated in human CaP cell lines; LNCaP that rarely showed metastasis in SCID mice expressed an undetectable level of SPA-1, whereas highly metastatic PC3 showed abundant SPA-1 expression. Moreover, SIPA1 transduction in LNCaP caused prominent abdominal lymph node metastasis without affecting primary tumor size, whereas shRNA-mediated SIPA1 knockdown or expression of a dominant-active Rap1 mutant (Rap1V12) in PC3 suppressed metastasis. LNCaP transduced with SPA-1 (LNCaP/SPA-1) showed attenuated adhesion to the precoated extracellular matrices (ECM) including collagens and fibronectin, due to defective ECM-medicated Rap1 activation. In addition, LNCaP/SPA-1 showed a diminished level of nuclear Brd4, which is known to bind SPA-1, resulting in reduced expression of a series of ECM-related genes. These results suggest that SPA-1 plays an important role in controlling metastasis efficiency of human CaP by regulating the expression of and interaction with ECM in the primary sites. © 2011 Japanese Cancer Association.

  19. Study the Influence of Arthritis on Breast Cancer-Associated Bone Metastasis

    Science.gov (United States)

    2008-10-01

    cytokines, chemokines, cyclooxygenases (COX), lipooxygenase (LOX), and various eicosanoids , that may attract and foster tumor cells to the inflamed...osteoclasts, causing bone resorption. PGE2 interacts with its eicosanoid receptors to induce the damage (26). IL-6 is an autocrine and paracrine growth factor

  20. Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Narjess Ayati

    2013-04-01

    Full Text Available Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. Methods: 28 patients (14 males and 14 females aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8. 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%. The lowest amount of peripheral blood cells was detected in the fourth week

  1. Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Narjess Ayati

    2013-04-01

    Full Text Available Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. Methods: 28 patients (14 males and 14 females aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8. 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%. The lowest amount of peripheral blood cells was detected in the fourth week

  2. 乳腺癌骨转移分子机制研究进展%Research progress on the molecular mechanism of breast cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    曾慧娟(综述); 王少华(审校)

    2015-01-01

    Breast cancer is one of the most common malignant tumors in women. Bone is commonly affected in the context of metastatic breast cancer.Once bone metastasis happens, patient would experience poor prognosis and impaired quality of life.However, there is a lack of approaches for more sensitive and specific diagnosis and treatments for breast cancer bone metastasis.Thus, it is im-perative to find new treatment target from molecular mechanism.In this paper, we review the current research progress on the molecular mechanism from several levels including gene profile, proteins and microRNAs.We also review the establishment of animal models of breast cancer bone metastasis.With the achievements acquired in the completed or undergoing researches on breast cancer bone metasta-sis, we hope the finding of the optimal diagnostic and therapeutic targets could lead the breast cancer research into a new era.%乳腺癌是女性最常见的恶性肿瘤之一,骨为其最易发生转移的部位。一旦发生骨转移,患者预后及生活质量明显下降,然而目前仍缺乏有力证据证实的、能够应用于临床的特异性诊疗手段。因此,迫切需要从其分子机制入手,寻找新的分子靶点。文中就乳腺癌骨转移在基因、蛋白及miRNA3个层面机制的研究进展作一综述,并阐述了乳腺癌骨转移动物模型的建立方法。

  3. Analysis of risk factors for bone metastasis in patients with prostate cancer%前列腺癌患者骨转移相关危险因素分析

    Institute of Scientific and Technical Information of China (English)

    高乃芳; 宋立敏; 庞敏; 宿超

    2016-01-01

    Objective:To analyze and investigate risk factors associated with prostate cancer with bone metastasis by gathering general information of newly diagnosed prostate cancer patients with bone metastases. Methods:120 cases with prostate cancer were selected and divided into observation group ( with bone metastases) and control group ( without bone metastases) according to bone me-tastases or not, 60 cases in each group. The Logistic regression univariate and multivariate analysis were used. Results:The capsule infiltration, pelvic lymph node hyperplasia, age, PSA value and Gleason score of observation group were significantly higher than those of control group. The age (OR=1. 301), PSA value (OR=1. 218), Gleason score (OR=7. 026), capsular infiltration (OR=333. 987) were the main risk factor for bone metastasis of the patients with prostate cancer. Conclusions: The high-risk factors for bone metastasis of prostate cancer are age, PSA, Gleason score and capsule infiltration.%目的::搜集初诊前列腺癌骨转移患者的一般资料,分析研究前列腺癌骨转移的相关危险因素。方法:选取前列腺癌患者120例,按照是否骨转移分为观察组和对照组,每组各60例。观察组患者为骨转移者;对照组患者为无骨转移者。采用Logistic回归方法对两组患者进行单因素和多因素分析。结果:观察组患者包膜浸润、盆腔淋巴结增生、年龄、PSA 值、Gleason 评分均显著高于对照组。年龄( OR=1.301)、PSA 值(OR=1.218)、Gleason 评分(OR=7.026)、有无包膜浸润(OR=333.987)为前列腺癌患者发生骨转移的主要危险因素。结论:前列腺癌患者骨转移的高危因素为年龄、PSA、Gleason 评分和包膜浸润。

  4. Multicentic primary angiosarcoma of bone mimicking metastasis on {sup 18}F-FDG PET/CT in a patient with a history of sigmoid colon cancer: A case report

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    Yoo, Min Young; Kim, Seok Ki; Park, Seog Yun; Kwon, Young Mee; Yun, Tak; Kim, Tae Sung [National Cancer Center, Goyang (Korea, Republic of); Lee, Eun Seong [Dept. of Nuclear Medicine, Chung Ang University Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Primary angiosarcoma of the bone (PAB) is a rare and fatal high-grade malignant vascular bone tumor. We report a rare case of multicentric PAB mimicking bone metastasis in a 59-year-old female patient with a history of sigmoid colon cancer. This patient complained of lower back and pelvic pain and presented with multiple osteolytic bone lesions on plain radiography and pelvic computed tomography. First, bone metastasis of sigmoid colon cancer was suspected. However, on the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) scan, the patient presented unusual multiple hypermetabolic osteolytic bone lesions involving contiguous bones of the lower half of the body. After bone biopsy, these lesions were confirmed to be multicentric PAB. To the best of our knowledge, this is the first case report of an {sup 18}F-FDG PET/CT scan in a patient with multicentric primary bone angiosarcoma.

  5. A novel 3-D mineralized tumor model to study breast cancer bone metastasis.

    Directory of Open Access Journals (Sweden)

    Siddharth P Pathi

    Full Text Available BACKGROUND: Metastatic bone disease is a frequent cause of morbidity in patients with advanced breast cancer, but the role of the bone mineral hydroxyapatite (HA in this process remains unclear. We have developed a novel mineralized 3-D tumor model and have employed this culture system to systematically investigate the pro-metastatic role of HA under physiologically relevant conditions in vitro. METHODOLOGY/PRINCIPAL FINDINGS: MDA-MB231 breast cancer cells were cultured within non-mineralized or mineralized polymeric scaffolds fabricated by a gas foaming-particulate leaching technique. Tumor cell adhesion, proliferation, and secretion of pro-osteoclastic interleukin-8 (IL-8 was increased in mineralized tumor models as compared to non-mineralized tumor models, and IL-8 secretion was more pronounced for bone-specific MDA-MB231 subpopulations relative to lung-specific breast cancer cells. These differences were pathologically significant as conditioned media collected from mineralized tumor models promoted osteoclastogenesis in an IL-8 dependent manner. Finally, drug testing and signaling studies with transforming growth factor beta (TGFbeta confirmed the clinical relevance of our culture system and revealed that breast cancer cell behavior is broadly affected by HA. CONCLUSIONS/SIGNIFICANCE: Our results indicate that HA promotes features associated with the neoplastic and metastatic growth of breast carcinoma cells in bone and that IL-8 may play an important role in this process. The developed mineralized tumor models may help to reveal the underlying cellular and molecular mechanisms that may ultimately enable more efficacious therapy of patients with advanced breast cancer.

  6. 肺癌骨转移的诊疗进展%Advances in diagnosis and treatment of lung cancer with bone metastasis

    Institute of Scientific and Technical Information of China (English)

    马姣; 李银鹏; 刘政

    2015-01-01

    Lung cancer is the leading cause of cancer-associated death.Most advanced lung cancer patients are accompanied with bone metastasis,leading to serious decline in quality of life.So it is very important for clinicians that early diagnosis and treatment of the patients who are suffering from lung cancer with bone metastasis.%在世界范围内肺癌的病死率占所有恶性肿瘤首位.大部分晚期肺癌患者伴有骨转移,由此导致患者的生活质量严重下降,因此肺癌骨转移的早期诊断、治疗对于临床医师是极其重要的.

  7. Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis.

    Science.gov (United States)

    Ooi, Li Laine; Zheng, Yu; Zhou, Hong; Trivedi, Trupti; Conigrave, Arthur D; Seibel, Markus J; Dunstan, Colin R

    2010-10-01

    Breast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice. The effects of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels. In vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)(2)D(3) inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49±0.08 mm(2) versus 1.68±0.15 mm(2), Pbone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth. Vitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these

  8. Bone balance within a cortical BMU: local controls of bone resorption and formation.

    Directory of Open Access Journals (Sweden)

    David W Smith

    Full Text Available Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the 'integration of information' occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable

  9. Bone balance within a cortical BMU: local controls of bone resorption and formation.

    Science.gov (United States)

    Smith, David W; Gardiner, Bruce S; Dunstan, Colin

    2012-01-01

    Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the 'integration of information' occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.

  10. From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging

    Science.gov (United States)

    2015-11-01

    to the date of euthanasia (Fig. 4, right panel). Normalization to the photon flux of the mammary tumors was not possible because they were resected... Humanized Mouse Model with Molecular Imaging PRINCIPAL INVESTIGATOR: Emily Powell CONTRACTING ORGANIZATION: The University of Texas MD Anderson...Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging 5b. GRANT

  11. Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis

    Directory of Open Access Journals (Sweden)

    Gabet Yankel

    2010-09-01

    Full Text Available Abstract Background Prostate cancer (PCa cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. Results We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which Doxycycline (Dox treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1, proteolytic enzymes (MMP9, CST7, cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A, intracellular signaling molecules (DUSP1, SPHK1, RASD1 and transcription factors (Sox9, SNAI2, SMAD3 functioning in epithelium to mesenchyme transition (EMT, tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is

  12. Inhibition of Embryonic Genes to Control Colorectal Cancer Metastasis

    Science.gov (United States)

    2014-09-01

    stem cells. Cell. 2005;122:947-56. 34. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell...bracket spanning across shNG-1 and shNp8-1, the P value of each compared to the corresponding shNEG control is the indicated value. Figure 4: LV

  13. Transforming growth factor-β signalling controls human breast cancer metastasis in a zebrafish xenograft model.

    Science.gov (United States)

    Drabsch, Yvette; He, Shuning; Zhang, Long; Snaar-Jagalska, B Ewa; ten Dijke, Peter

    2013-11-07

    The transforming growth factor beta (TGF-β) signalling pathway is known to control human breast cancer invasion and metastasis. We demonstrate that the zebrafish xenograft assay is a robust and dependable animal model for examining the role of pharmacological modulators and genetic perturbation of TGF-β signalling in human breast tumour cells. We injected cancer cells into the embryonic circulation (duct of cuvier) and examined their invasion and metastasis into the avascular collagenous tail. Various aspects of the TGF-β signalling pathway were blocked by chemical inhibition, small interfering RNA (siRNA), or small hairpin RNA (shRNA). Analysis was conducted using fluorescent microscopy. Breast cancer cells with different levels of malignancy, according to in vitro and in vivo mouse studies, demonstrated invasive and metastatic properties within the embryonic zebrafish model that nicely correlated with their differential tumourigenicity in mouse models. Interestingly, MCF10A M2 and M4 cells invaded into the caudal hematopoietic tissue and were visible as a cluster of cells, whereas MDA MB 231 cells invaded into the tail fin and were visible as individual cells. Pharmacological inhibition with TGF-β receptor kinase inhibitors or tumour specific Smad4 knockdown disturbed invasion and metastasis in the zebrafish xenograft model and closely mimicked the results we obtained with these cells in a mouse metastasis model. Inhibition of matrix metallo proteinases, which are induced by TGF-β in breast cancer cells, blocked invasion and metastasis of breast cancer cells. The zebrafish-embryonic breast cancer xenograft model is applicable for the mechanistic understanding, screening and development of anti-TGF-β drugs for the treatment of metastatic breast cancer in a timely and cost-effective manner.

  14. LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.

    Science.gov (United States)

    Ketscher, A; Jilg, C A; Willmann, D; Hummel, B; Imhof, A; Rüsseler, V; Hölz, S; Metzger, E; Müller, J M; Schüle, R

    2014-10-06

    Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.

  15. Systemic metabolic radiotherapy with samarium-153 EDTMP for the treatment of painful bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, A. N. [University of Miami School of Medicine, Division of Nuclear Medicine, Miami, FL (United States)

    2001-03-01

    Various radioisotopes conjugated to pyrophosphate analogues have been developed for systemic metabolic radiotherapy. Samarium-153-EDTMP is a 1:1 complex of radioactive Samarium-153 and a Tetraphosphonate (ethylenediamine-tetramethylene phosphonic acid (EDTMP)). Samarium Sm-153-EDTMP has a high affinity for skeletal tissue and concentrates by chemiabsorption in areas of enhanced metabolic activity, where it associates with the hydroxyappetite crystal. Samarium-153 Lexidronam (Quadramet (R)) has been approved for routine use by the FDA. This agent offers several advantages over other agents used for palliating bone pain. Due to its half-life of 46 hours and its beta emissions, a high dose rate can be delivered to regions adjacent to enhanced osteoblastic activity over a short period of time with little residual long term activity being left in the bone marrow. This paper summarizes both animal studies and clinical studies performed with this agent. Special emphasis will be given to the pivotal Phase-III clinical studies and subsequent studies performed since its approval by the FDA. Special considerations regarding appropriate selection of patients, preparation, follow-up of patients and adjustments to the usual recommended dose (1 mCi/Kg (35 Mbq/kg)) will be discussed. Current and future treatment options utilizing Sm-153-EDTMP with other pharmaceuticals appear promising and will substantially extend its use into new areas. In addition, because it also emits a 103 keV gamma ray which makes it suitable for imaging and assessment of biodistribution, dosimetric application are possible in the future.

  16. Systemic metabolic radiotherapy with samarium-153 EDTMP for the treatment of painful bone metastasis.

    Science.gov (United States)

    Serafini, A N

    2001-03-01

    Various radioisotopes conjugated to pyrophosphate analogues have been developed for systemic metabolic radiotherapy. Samarium-153-EDTMP is a 1:1 complex of radioactive Samarium-153 and a Tetraphosphonate [ethylenediamine-tetramethylene phosphonic acid (EDTMP)]. Samarium Sm-153-EDTMP has a high affinity for skeletal tissue and concentrates by chemiabsorption in areas of enhanced metabolic activity, where it associates with the hydroxyapatite crystal. Samarium-153 Lexidronam [Quadramet (R)] has been approved for routine use by the FDA. This agent offers several advantages over other agents used for palliating bone pain. Due to its half-life of 46 hours and its beta emissions, a high dose rate can be delivered to regions adjacent to enhanced osteoblastic activity over a short period of time with little residual long term activity being left in the bone marrow. This paper summarizes both animal studies and clinical studies performed with this agent. Special emphasis will be given to the pivotal Phase-III clinical studies and subsequent studies performed since its approval by the FDA. Special considerations regarding appropriate selection of patients, preparation, follow-up of patients and adjustments to the usual recommended dose [1 mCi/kg (35 Mbq/kg)] will be discussed. Current and future treatment options utilizing Sm-153-EDTMP with other pharmaceuticals appear promising and will substantially extend its use into new areas. In addition, because it also emits a 103 keV gamma ray which makes it suitable for imaging and assessment of biodistribution, dosimetric applications are possible in the future.

  17. Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

    2013-10-15

    The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

  18. Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, Alexei L. [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Li, Richard [Division of Radiation Oncology, Dana Farber/Boston Children' s Cancer and Blood Disorders Center, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hill-Kayser, Christine [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania (United States); Little, Anthony [Division of Oncology, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Hawkins, Randall A. [Department of Radiology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Hamilton, Jeffrey; Lau, Michael [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Tran, Hung Chi [Division of Hematology/Oncology, Children' s Hospital of Los Angeles, Los Angeles, California (United States); Strahlendorf, Caron [Division of Hematology and Oncology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia (Canada); Lemons, Richard S. [Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); Matthay, Katherine K.; DuBois, Steven G. [Department of Pediatrics, University of California at San Francisco School of Medicine and UCSF Benioff Children' s Hospital, San Francisco, California (United States); and others

    2014-07-15

    Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore

  19. Nasal Adenocarcinoma in a Horse with Metastasis to Lung, Liver, and Bone and Review of Metastasis in Nine Horses with Sinonasal Tumors

    Directory of Open Access Journals (Sweden)

    Ashley Hanna

    2015-01-01

    Full Text Available Sinonasal neoplasia metastasizing to distant organs is rare in horses. This case report describes the clinical and imaging findings of a horse with sinonasal neoplasia, which had metastasized to the lung, liver, and humerus. Additionally, the prevalence of sinonasal neoplasia and their incidence of distant metastasis among horses that presented to the Oregon State University Veterinary Teaching Hospital (OSU-VTH were estimated. Of 5,558 equine patients who presented to the OSU-VTH in the last nine years, 1.4% were diagnosed with sinonasal disease and 10.3% of these cases had sinonasal neoplasia with only one having confirmed distant metastasis. This case was an eleven-year-old quarter horse which was evaluated due to a history of a right forelimb lameness of three weeks duration. Two and a half months later he presented again, this time for unilateral epistaxis and persistent right forelimb lameness. Radiography of the right elbow noted an increasingly irregular, periosteal response and osteolytic lesion of the right distal humeral condyle. At the time of the second presentation, nasosinal endoscopy identified a lobulated mass in the region of the ethmoid turbinates. Histopathology of this mass revealed an adenocarcinoma of nasal origin with metastasis to the lung, liver, and right humerus.

  20. 全身骨显像诊断肺癌骨转移的临床价值%Clinical value of the whole body bone imaging in diagnosing bone metastasis from lung cancer

    Institute of Scientific and Technical Information of China (English)

    贾莉; 夏正武; 马世兴

    2011-01-01

    Objective: To explore clinical value of the whole body bone imaging in diagnosing bone metastasis from lung cancer, in order to guide staging and treatment of patients with lung cancer. Methods: 126 patients with pathological diagnosis of lung cancer were performed whole body bone imaging, CT and ALP, blood calcium inspection. Probability of bone metastasis from lung cancer of the different pathological type and different clinical stage were counted. The whole body bone imaging and clinical factors of suspicious bone metastasis (including bone pain, alkaline phosphatase, high calcium lev -els, arbitrary or a few) for diagnosis accuracy of bone metastases were statistical compared. Results: The incidence of bone metastasis from lung cancer was 27.8%, and the bone metastases occurrence probability of peripheral lung cancer was higher than central lung cancer (P<0.01), bone metastases occurrence probability of lung adenocarcinoma was higher than lung squamous cell carcinoma (P<0.01), bone metastases occurrence probability of period Ⅲ, IV patients was obviously higher than that of period I , II (P<0.01). The sensitivity (94.3%), specific degrees (84.6%), accuracy (87.3%) of the whole body bone imaging diagnosis of bone metastases from lung cancer were higher than the clinical factors of suspicious bone metas -tasis diagnosis of bone metastases. Conclusion: Whole body bone imaging should be a routine examination in patients with lung cancer. The clinical significance is important to determine stage and treatment of lung cancer.%目的:探讨全身骨显像在诊断肺癌骨转移的临床价值,以便更好地指导肺癌患者的分期及治疗.方法:126例病理确诊为肺癌的患者均行全身骨显像、CT及碱性磷酸酶、血钙检查.统计肺癌患者不同病理类型、不同临床分期发生骨转移的几率,将全身骨显像与可疑骨转移临床因素(包括骨痛、碱性磷酸酶升高、高钙血症中任意一项或几项)诊断骨转移

  1. Tibial bone metastasis as an initial presentation of endometrial carcinoma diagnosed by fine-needle aspiration cytology: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sarag Aboujafar Boukhar

    2015-01-01

    Full Text Available Endometrial cancer is the most common gynecologic malignancy in the United States. However, bony metastasis is infrequent and exceptionally rare as the initial presentation. We report a case of a 77-year-old female with a clinically silent endometrial carcinoma who presented with a left tibial metastasis as the first manifestation of her disease. Ours is only the third case diagnosed by fine-needle aspiration (FNA cytology, and the first to detail the cytomorphologic features of metastatic endometrial cancer to bone. These microscopic findings, including three-dimensional cohesive clusters with cellular overlapping and cuboidal to columnar cells exhibiting low nuclear: cytoplasmic ratios and partially vacuolated cytoplasm, differ significantly from those of endometrial carcinoma on a Papanicolaou test. The tumor bore similarity to the more commonly encountered metastatic colon cancer, but immunohistochemical staining enabled reliable distinction between these entities. A review of osseous metastases of endometrial cancer demonstrates a predilection for bones of the lower extremity and pelvis with a predominance of the endometrioid histologic subtype. In about a quarter of the cases, the bony metastasis was the first manifestation of the cancer. FNA was an effective diagnostic modality for this unusual presentation of a common malignancy. Awareness of this entity and its differential diagnosis is essential for accurate and timely diagnosis.

  2. Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: evidence from in vivo models.

    Science.gov (United States)

    Wang, Ning; Docherty, Freyja E; Brown, Hannah K; Reeves, Kimberley J; Fowles, Anne C M; Ottewell, Penelope D; Dear, T Neil; Holen, Ingunn; Croucher, Peter I; Eaton, Colby L

    2014-12-01

    It has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or "niche"). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by two-photon microscopy to be engrafted in the tibiae in close proximity (∼40 µm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases.

  3. Controlling Bone Graft Substitute Microstructure to Improve Bone Augmentation.

    Science.gov (United States)

    Sheikh, Zeeshan; Drager, Justin; Zhang, Yu Ling; Abdallah, Mohamed-Nur; Tamimi, Faleh; Barralet, Jake

    2016-07-01

    Vertical bone augmentation procedures are frequently carried out to allow successful placement of dental implants in otherwise atrophic ridges and represent one of the most common bone grafting procedures currently performed. Onlay autografting is one of the most prevalent and predictable techniques to achieve this; however, there are several well documented complications and drawbacks associated with it and synthetic alternatives are being sought. Monetite is a bioresorbable dicalcium phosphate with osteoconductive and osteoinductive potential that has been previously investigated for onlay bone grafting and it is routinely made by autoclaving brushite to simultaneously sterilize and phase convert. In this study, monetite disc-shaped grafts are produced by both wet and dry heating methods which alter their physical properties such as porosity, surface area, and mechanical strength. Histological observations after 12 weeks of onlay grafting on rabbit calvaria reveal higher bone volume (38%) in autoclaved monetite grafts in comparison with the dry heated monetite grafts (26%). The vertical bone height gained is similar for both the types of monetite grafts (up to 3.2 mm). However, it is observed that the augmented bone height is greater in the lateral than the medial areas of both types of monetite grafts. It is also noted that the higher porosity of autoclaved monetite grafts increases the bioresorbability, whereas the dry heated monetite grafts having lower porosity but higher surface area resorb to a significantly lesser extent. This study provides information regarding two types of monetite onlay grafts prepared with different physical properties that can be further investigated for clinical vertical bone augmentation applications.

  4. Common endocrine control of body weight, reproduction, and bone mass

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

    2003-01-01

    Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

  5. Hepatocyte Growth Factor and Interleukin-6 in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2006-06-01

    herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62, 3920-4. (2002). 10. Rutter, M.M. et al...anti-IGFBP5 were used as a negative control. 40 µg total protein or immunoprecipitated proteins were analyzed on 12% NuPAGE or 4-12% Bis-Tris Gels ...right panel) in HS27a grown in 10% FCS. A 292 base fragment with in the AR mRNA (panel A) is amplified by PCR and detected by agarose gel

  6. Radionuclide Bone Imaging Features of Bone Metastasis from 158 Patients of Esophageal Cancer%158例食管癌骨转移核素骨显像特征分析

    Institute of Scientific and Technical Information of China (English)

    丁忠旗; 张俊; 盛强; 姚圣华; 骆佩芳

    2012-01-01

    目的探讨食管癌骨转移患者的核素骨显像特征及临床应用。方法收集我院2007年1月至2011年12月接受全身骨显像的158例食管癌患者病历资料。对全身骨显像结果进行统计和分析,归纳食管癌患者骨转移显像特点。结果 158例食管癌患者骨转移发生率为17.72%(28/158),其中以脊柱及肋骨转移最为多见,发生率分别为89.29%(25/28),64.29%(18/28)。依据病理类型,鳞癌、腺癌、小细胞癌的骨转移发生率分别为13.83%(13/94),21.95%(9/41)和26.09%(6/23)。结论放射性核素骨显像对食管癌患者具有重要的临床意义,应作为治疗前后骨转移诊断和随访的常规检查手段。%Objective To investigate radionuclide bone imaging features and its clinical value in esophageal cancer patients with bone metastasis.Methods The medical records of 158 patients with esophageal cancer who accepted the whole body bone scan(WBS) from January 2007 to December 2011 in our hospital were collected.The WBS results were statistically analyzed,and the imaging features were summarized.Results The bone metastasis incidence of 158 cases of esophageal cancer patients was 17.72%(28/158).The spine and rib metastasis were the most common,the rate was 89.29%(25/28) and 64.29%(18/28),respectively.According to the pathological type,the bone metastasis incidence of squamous cell carcinoma,adenocarcinoma,small cell carcinoma was 13.83%(13/94),21.95%(9/41) and 26.09%(6/23),respectively.Conclusion Radionuclide bone imaging has important clinical value in patients with esophageal cancer.It should serve as a routine means of diagnosis and follow-up of bone metastases before or after treatment of patients.

  7. Impact of initial time to prostate-specific antigen nadir on survival in prostate cancer with bone metastasis initially treated with maximum androgen blockade therapy

    Directory of Open Access Journals (Sweden)

    Yamamoto Y

    2013-10-01

    Full Text Available Background: The objective of this study is to provide certain data on clinical outcomes and their predictors of traditional maximum androgen blockade (MAB in prostate cancer with bone metastasis. Methods: Subjects were patients with prostate adenocarcinoma with bone metastasis initiated to treat with MAB as a primary treatment without any local therapy at our hospital between January 2003 and December 2010. Time to prostate specific antigen (PSA progression, overall survival (OS time, and association of clinical factors and outcomes were retrospectively evaluated. Results: A total of 57 patients were evaluable. The median age was 70 years. The median primary PSA was 203 ng/ml. Luteinizing hormone-releasing hormone agonists had been administered in 96.5% of the patients. Bicalutamide had been chosen in 89.4 % of the patients as the initial antiandrogen. The median time to PSA progression with MAB was 11.3 months (95% confidence interval [CI], 10.4 to 13.0. The median OS was 47.3 months (95% CI, 30.7 to 81.0. Gleason score 9 or greater, decline of PSA level equal to or higher than 1.0 ng/ml with MAB, and time to PSA nadir equal to or shorter than six months after initiation of MAB were independent risk factors for time to PSA progression (P=0.010, P=0.005, and P=0.001; respectively. Time to PSA nadir longer than six months was the only independent predictor for longer OS (HR, 0.255 [95% CI, 0.109 to 0.597]; P=0.002. Conclusions: Initial time to PSA nadir should be emphasized for clinical outcome analyses in future studies on prostate cancer with bone metastasis.

  8. Study Progress on Breast Cancer Metastasis to Bone Treated with Chinese Herbs%中药抗乳腺癌骨转移实验研究进展

    Institute of Scientific and Technical Information of China (English)

    张小慧; 韩向晖; 刘胜; 王春丽

    2013-01-01

    Bone is the most common metastatic site of breast cancer . And breast cancer metastasis to bone can lead to osteoporosis , hypercalcemia , spinal cord compression and pathological fracture , which seriously impact the patientsˊ quality of life and survival . Chinese herbs have a potential advantage in the treatment of breast cancer metastasis to bone. In recent ten years, a number of studies showed that Chinese medicine monomers, traditional Chinese medicine (TCM) extracts, and Chinese herbal compound prescriptions played a role in in-hibiting breast cancer cell proliferation , invading and relieving the bone destruction and bone pain by different molecular mechanisms .%骨是乳腺癌常见的转移部位,乳腺癌骨转移可导致骨质疏松、高血钙症、脊髓压迫和病理性骨折等并发症,严重影响患者的生活和生存质量。中医中药在治疗乳腺癌骨转移方面显示出潜在的优势。近10年研究发现,许多中药单体、提取物以及中药复方能够从不同分子机制发挥抑制乳腺癌细胞增殖、侵袭,缓解乳腺癌细胞引起的骨质破坏及癌性骨痛作用。

  9. Receptor activator of NF-kB (RANK expression in primary tumors associates with bone metastasis occurrence in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Daniele Santini

    Full Text Available BACKGROUND: Receptor activator of NFkB (RANK, its ligand (RANKL and the decoy receptor of RANKL (osteoprotegerin, OPG play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. MATERIALS AND METHODS: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. RESULTS: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively and disease-free survival (P = 0.059 and 0.0402, respectively. Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023 and a shorter skeletal disease-free survival (SDFS, P = 0.037. Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4 and 58.9 months (95% CI: 34.7-68.5, respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029. CONCLUSIONS: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.

  10. Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

    Science.gov (United States)

    Vincenzi, Bruno; Gaeta, Laura; Pantano, Francesco; Russo, Antonio; Ortega, Cinzia; Porta, Camillo; Galluzzo, Sara; Armento, Grazia; La Verde, Nicla; Caroti, Cinzia; Treilleux, Isabelle; Ruggiero, Alessandro; Perrone, Giuseppe; Addeo, Raffaele; Clezardin, Philippe; Muda, Andrea Onetti; Tonini, Giuseppe

    2011-01-01

    Background Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that “RANK-negative” and “RANK-positive” patients had a SDFS of 105.7 months (95% CI: 73.9–124.4) and 58.9 months (95% CI: 34.7–68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients. PMID:21559440

  11. [THE PATIENTS QUALITY OF LIFE ESTlMATION IN PRESENCE OF METASTASIS OF A RENAL-CELL CANCER IN THE BONES ON BACKGROUND OF THE BISPHOSPHONATES APPLICATION].

    Science.gov (United States)

    Boychuk, S I; Dedkov, A G; Volkov, I B; Kovahlichuk, P A; Kostyuk, V Yu

    2016-04-01

    Results of the patients quality of life (QL) estimation, while presence of a renal-cell cancer metastasis in the bones, using questionnaire QLQ-C30 and Karnofsky index, as well as the pain visual-analogue scale on background of treatment with bisphosphonates (BPH), were adduced. After conclusion of the combined treatment the general state improvement, a trustworthy reduction of the pain syndrome severity, as well as the patients' psychoemotional and social state, were noted. Complex treatment of patients, using BPH, have promoted a positive impact on their QL as well as a reduction of a skeleton complications rate.

  12. 核素骨显像与MRI对骨转移癌的诊断比较%The comparation of skeletal scintigraphy and MRI in diasnosing bone metastasis

    Institute of Scientific and Technical Information of China (English)

    黄泽黎; 张宁; 张洋; 罗伟军; 曾晓红; 梁少强; 孙宗文

    2009-01-01

    目的 评价骨显像与MRI在诊断骨转移瘤中的价值.方法 对64例可疑骨转移的恶性肿瘤患者行核素骨显像与MRI检查(两种检查间隔时间不超过2周),凡骨显像表现为明显的放射性聚集或缺损和(或)MRI的T1加权像表现为低信号强度且T2加权像表现为高低混杂或高信号强度和(或)骨质破坏的椎体均认为是肿瘤骨转移.结果 核素骨显像能有效地检出全身骨转移癌灶;MRI对扫描范围内骨转移癌检出的病灶数高于核素骨显像;核素骨显像单发病灶有一定的假阳性(3,9),MRI单发病灶假阳性较少(0/7),但部分病例(3/7)经核素骨显像检查证实为多发骨转移;MRI能了解局部病灶的准确位置及周围软组织情况.结论 核素骨显像较MRI能更有效地检出全身骨转移癌灶,是早期诊断转移癌的首选方法 ;MRI特异性更高,解剖定位明确,并能显示软组织病灶,两种检查方法 相互结合,对骨转移的诊断和治疗有重要意义.%Objective To evaluate the values of skeletal scintigraphy and MRI in detecting osseous metastasis.Methods Skeletal scintigraphy and MRI were performed in sixty-four patients with suspicious bone metastasis malignant tumor;all patients underwent skeletal scintigrapghy and MRI examinations within two weeks.Metastatic foci were defined as lesions that showed aggravations/defections of bone tracer uptakes on serial scans,and/or low signal intensity on T1WI and/or high signal intensity on T2WI of MRI,and/or bone destruction.Results Planar skeletal scintigraphy could detect the whole body bone metastasis lesions more effectively;MRI discovered more metastasis lesions than planar skeletal scintigraphy in the range of the MRI scaned;certain amounts of false-positive cases might be present in single focal cases by skeletalscintigraphy(3/9).Relatively,MRI had less false-positive cases in single foci(0/7),but the three single foci cases detected by MRI were confirmed as multi

  13. Fusion of bone marrow-derived cells with cancer cells:metastasis as a secondary disease in cancer

    Institute of Scientific and Technical Information of China (English)

    John M. Pawelek

    2014-01-01

    This perspective article highlights the leukocyte-cancer cellhybrid theory as a mechanism for cancer metastasis. Beginning from the first proposal of the theory more than a century ago and continuing today with the first proof for this theory in a human cancer, the hybrid theory offers a unifying explanation for metastasis. In this scenario, leukocyte fusion with a cancer cellis a secondary disease superimposed upon the early tumor, giving birth to a new, malignant cellwith a leukocyte-cancer cellhybrid epigenome.

  14. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2016-03-01

    Full Text Available Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination.

  15. The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

    Science.gov (United States)

    Maroni, Paola; Bendinelli, Paola; Resnati, Massimo; Matteucci, Emanuela; Milan, Enrico; Desiderio, Maria Alfonsina

    2016-01-01

    Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. PMID:27023526

  16. [Effects of SERMs on bone health. Mechanisms of bone mass control by selective estrogen receptor modulator].

    Science.gov (United States)

    Imai, Yuuki; Kato, Shigeaki

    2010-03-01

    The bone mass, which is controlled by the balances between bone formation and bone resorption can be reduced by estrogen deficiency in post-menopausal osteoporosis. Reduced bone mass can be recovered by hormone replacement therapy (HRT) , however, HRT has various side effects. Although SERMs can rescue the bone mass with less side effect compared to HRT, the precise mechanisms of this effect is still elusive. From the results of the analyses for osteoclast specific estrogen receptor (ER) alphaknockout mice and the genome wide approach of ERalphabinding site, estrogen and SERMs can, at least in part, protect the bone mass by inducing the expression of Fas ligand and controling the life span of osteoclasts. More precise molecular mechanisms of the effect of SERM, especially in tissue/cell type specificity, may help to investigate new SERM, which is more specific and effective to treat post-menopausal osteoporosis.

  17. Prognostic analysis of non - small cell lung cancer with bone metastasis%非小细胞肺癌骨转移的预后因素分析

    Institute of Scientific and Technical Information of China (English)

    李明蔚; 邝先奎; 赵向通; 黄堃; 韩伟; 董文杰; 王丽萍

    2016-01-01

    目的:分析非小细胞肺癌(non - small cell lung cancer,NSCLC)骨转移的预后相关因素和生存情况。方法回顾性分析2013年1月至2013年6月郑州大学第一附属医院收治的78例非小细胞肺癌骨转移患者的临床资料,采用Kaplan - Meier 法估计1年和2年生存率,单因素分析采用 Log - rank 时序分析筛选预后的影响因素,多因素分析采用Cox 比例风险回归模型进一步确认独立影响因素。结果非小细胞肺癌骨转移的中位生存时间为10.5个月,Kaplan -Meier 生存分析结果显示1年和2年生存率分别为48.7%和15.4%。单因素分析显示 ECOG 评分、病理类型、骨以外的其他部位转移、化疗及分子靶向治疗与预后相关(P ﹤0.05);多因素分析显示 ECOG 评分、病理类型、骨以外的其他部位转移、化疗及分子靶向治疗为预后的独立影响因素。结论体能状况好、腺癌、单纯骨转移、接受化疗及分子靶向治疗的非小细胞骨转移患者预后更好。%Objective To investigate the prognosis - related factors of non - small cell lung cancer(NSCLC)with bone me-tastasis. Methods The clinical data of 78 NSCLC patients with bone metastasis treated in the First Affiliated Hospital of Zheng-zhou University from January of 2013 to June of 2013 were retrospectively analyzed. Kaplan - Meier method was used to estima-tethe 1 - and 2 - year survival rates of patients. Log - rank time series analysis for the univariate analysis was used to screen the factors influencing the survival of patients and Cox proportional hazard model for the multivariate analysis was used to further con-NSCLC were 48. 7% and 15. 4% . Single factor analysis showed that ECOG score,pathological type,other parts of metastasis, chemotherapy and molecular targeted therapy(MTT)were associated with the prognosis of patients(P ﹤ 0. 05). Multivariate a-nalysis showed that ECOG score,pathological type,other parts of metastasis

  18. {sup 68}Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosini, Valentina; Nanni, Cristina; Castellucci, Paolo; Allegri, Vincenzo; Montini, Giancarlo; Franchi, Roberto [S. Orsola-Malpighi University Hospital, Department of Nuclear Medicine, Bologna (Italy); Zompatori, Maurizio [S. Orsola-Malpighi University Hospital, Department of Radiology, Bologna (Italy); Campana, Davide; Tomassetti, Paola [S. Orsola-Malpighi University Hospital, Department of Internal Medicine, Bologna (Italy); Rubello, Domenico [S. Maria della Misericordia Hospital, Department of Nuclear Medicine, Rovigo (Italy); Fanti, Stefano [S. Orsola-Malpighi University Hospital, Department of Nuclear Medicine, Bologna (Italy); Azienda Ospedaliero Universitaria di Bologna, Unita Operativa di Medicina Nucleare, Padiglione 30, Policlinico S.Orsola-Malpighi, Bologna (Italy)

    2010-04-15

    To retrospectively evaluate the sensitivity, specificity and accuracy of {sup 68}Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET). From among patients with NET who underwent {sup 68}Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings. PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there

  19. A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer.

    Directory of Open Access Journals (Sweden)

    Rossitza Lazova

    Full Text Available Tumor cell fusion with motile bone marrow-derived cells (BMDCs has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically.We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT, using forensic short tandem repeat (STR length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes.All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event.Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome.

  20. Solitary Plasmacytoma of the Sternum Mimicking Bone Metastasis in a Patient with a History of Breast Cancer Evaluated by F-18-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Treglia, Giorgio; Luca, Giovanella [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Barbara, Muoio; Carmelo, Caldarella [Catholic Univ., Rome (Italy)

    2014-06-15

    A 65-year-old woman with a history of breast cancer (stage T2N0M0 treated with left breast conservative therapy 7 years previously followed by hormone therapy) underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) for restaging due to increased serum tumour markers levels (CA15-3, 37 U/ml and CEA, 8 ng/ml). The patient presented thoracic pain before performing F-18-FDG PET/CT. PET/CT demonstrated an area of increased F-18-FDG uptake corresponding to an osteolytic lesion occupying the upper sternum suspicious for bone metastasis. No other areas of abnormal F-18-FDG uptake were detected in the rest of the body. Based on this PET/CT finding, the patient performed biopsy of the sternal lesion. Histology demonstrated the presence of a sternal plasmacytoma and the patient was addressed to radiation therapy. The role of F-18-FDG PET/CT in patients with multiple myeloma is well known, whereas only some articles evaluated the usefulness of this method in patients with solitary plasmacytomas. In particular, F-18-FDG PET/CT may be useful in demonstrating the evolution of solitary plasmacytomas in multiple myeloma. In our case F-18-FDG PET/CT was useful in detecting a solitary plasmacytoma of the sternum mimicking bone metastasis in a patient with history of breast cancer, correctly addressing to further histological evaluation.

  1. Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain Associated with Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2013-07-30

    exhibited metastastatic tumor growth in hind limb bones showed considerable bone destruction, anthough no fractures were observed. Further, we performed...whole animal perfusion with fixative, and subsequently removed the femur and tibia- fibula for tissue sectioning and H&E, as well as immunostainging...metastastatic tumor growth in hind limb bones showed considerable bone destruction, anthough no fractures were observed. Further, we performed whole

  2. The Diagnostic Value of Observation of Early Lung Cancer Bone Metastasis by Tumor Markers and Radionuclide Bone Imaging%肿瘤标志物检测和核素骨显像对肺癌早期骨转移的诊断价值观察

    Institute of Scientific and Technical Information of China (English)

    殷健

    2013-01-01

    Objective To approach diagnostic result of early lung cancer bone metastasis by tumor markers and radionuclide bone imaging. Method Analyzed 50 cases clinical data of lung cancer patients from May 2010 to May 2013 in our hospital department of radiology, selected 50 cases in our hospital during the same period in healthy volunteers was control group. Result The CEA, CYFR21-1, NSE detection result of radionuclide bone imaging positive group of lung cancer patients were higher than control group and radionuclide bone imaging, CEA, CYFR21-1, NSE positive incidence of of lung cancer patients were higher than control group and radionuclide bone imaging,P<0.05, the difference were statistical significance. Conclusion The staging and treatment methods to determine clinical judgment detection of serum tumor markers and radionuclide bone imaging for early lung cancer bone metastasis were significance.%目的:探讨肿瘤标志物检测和核素骨显像对肺癌早期骨转移的诊断效果。方法分析2010年5月至2013年5月影像科诊断的肺癌患者50例临床资料,选取同期我院健康体检者50例作为对照组。结果核素骨显像阳性组肺癌患者CEA、CYFR21-1、NSE检测结果均高于对照组和核素骨显像阳性组,核素骨显像阳性组肺癌患者CEA、CYFR21-1、NSE阳性率均高于对照组和核素骨显像阳性组, P<0.05,差异均有统计学意义。结论肿瘤标志物检测和核素骨显像对于肺癌早期骨转移的临床判断、分期和确定治疗方法具有重要意义。

  3. 前列腺癌骨转移的相关因素分析%Analysis of related factors of bone metastasis of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    郑路; 张丽; 王玉杰; 张立东; 安恒庆

    2015-01-01

    目的:分析前列腺癌患者的临床资料,探讨前列腺癌骨转移的相关因素。方法以SPECT全身骨显像为诊断前列腺癌骨转移的金标准,回顾性分析235例前列腺癌患者的临床资料,采用单因素及多因素Logistic回归方法对前列腺癌骨转移的相关因素进行分析。结果单因素分析显示,两组在年龄、Gleason评分、TPSA值、FPSA值、F/T值及是否合并淋巴结转移的构成分布方面的差异具有统计学意义(P<0.05);多因素Logistic回归分析显示,合并淋巴结转移(OR=14.93)、年龄(OR=1.08)、Gleason评分(OR=2.90)、TPSA值(OR=1.05)与前列腺癌骨转移具有明显相关性,其中年龄≥70岁、Gleason评分≥8分、TPSA值≥20 ng/ml和F/T值≤0.16的前列腺癌患者发生骨转移的例数明显多于其他患者,差异均具有统计学意义(P<0.05)。结论淋巴结转移、年龄、Gleason评分及TPSA值是前列腺癌骨转移的主要预测因素。对于年龄≥70岁、TPSA值≥20 ng/ml、Gleason评分≥8、F/T值≤0.16或者合并淋巴结转移的前列腺癌患者应该行SPECT全身骨显像检查,以便为患者临床早期发现及治疗提供帮助。%Objective To analyze the clinical data of patients with prostate cancer for better understanding of the factors related to bone metastasis of prostate cancer. Method With SPECT bone scan being the golden standard for the diagnosis of prostate carcinoma with bone metastasis, the clinical data of 235 cases of prostate cancer was retro-spectively analyzed, the univariate and multivariate Logistic regression analysis was a to evaluate the risk factors for bone metastasis of prostate cancer. Result In the univariate analysis, statistically significant differences were ob-served in respect of age, Gleason score, TPSA, FPSA and F/T values and lymph node metastasis (P<0.05); While the multivariate Logistic regression analysis showed that lymph node metastasis

  4. Comparison of 99mTc-3PRGD2 integrin receptor imaging with 99mTc-MDP bone scan in diagnosis of bone metastasis in patients with lung cancer: a multicenter study.

    Directory of Open Access Journals (Sweden)

    Weibing Miao

    Full Text Available 99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT. A multi-center study was prospectively designed to evaluate the diagnostic accuracy of 99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional 99mTc-MDP bone scan.The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg 99mTc-3PRGD2. 99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the 99mTc-3PRGD2 and 99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data.A total of 44 patients (29 male, 59±10 years old with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, 99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for 99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. 99mTc-MDP bone scan had better contrast in most lesions, whereas the 99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis.99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer.ClinicalTrials.gov NCT01737112.

  5. Radionuclide Bone Scan Combined with PSA, fPSA and fPSA/tPSA Ratio for Assessment of Prostatic Cancer Patients with Bone Metastasis%放射性核素骨显像联合PSA、fPSA、fPSA/tPSA评价前列腺癌骨转移

    Institute of Scientific and Technical Information of China (English)

    赵辉; 安建平; 徐晓红; 王晶

    2011-01-01

    Objective To assess the value of radionuclide bone scan combined with PSA, fPSA and fPSA/tPSA for diagnosis prostatic cancer with hone metastasis. Methods Serum levels of PSA, fPSA and fPSA/tPSA ratio were detemined in ① 35 prostatic cancer patients with definite bone metastasis lesions shown on radionucfide bone scan, ② 35 prostatic cancer patients without bone metastasis, ③ 30 patients with benign prostatic disorders and ④ 35 controls. Results The serum tumor markers levels in patients with osseous metastasis were significantly higher than those in the other three groups ( P <0.01 ). Among them,the levels in patients with more then 2 bone lesions were significantly higher than those in patients with only one or two bone lesions ( P < 0. 01 ). The serum tumor markers levels in patients without osseous metastasis were only significantly higher than those in patients with benign prostatic disorders and controls. The sensitivity of fPSA/tPSA ratio < 0.2 was highest ( 85.7%), but specificity lower ( 45.71%). The sensitivity combining tPSA/tPSA ratio and radionuclide bone scan ( ≤2 ) was lowest ( 62. 9%), but specificity was highest ( 77.14%). Conclusion PSA, fPSA and tfSA/tPSA ratio were related with osseous metastasis from prostatic cancer. Combining them was increase on diagnosis the osseous metastasis of prostatic cancer and is a valuable scheme for early detection of skeletal metastasis of prostatic cancer, especially when the results of bone scanning is equivocal. Detemination of the serum tumor markers levels would be helpful for dynamic monitoring of the extent of metastasis.%目的:评价前列腺癌患者放射性核素骨显像与血清前列腺特异抗原测定的诊断价值.方法:随机选择前列腺癌患者骨显像示骨转移与骨显像正常患者各35例,前列腺良性病患者30例及健康体检者35例,分别测定其血清中PSA、fPSA、fPSA/tPSA的含量.结果:前列腺癌无骨转移组PSA、fPSA水平较对照

  6. 3D SPECT/CT fusion using image data projection of bone SPECT onto 3D volume-rendered CT images: feasibility and clinical impact in the diagnosis of bone metastasis.

    Science.gov (United States)

    Ogata, Yuji; Nakahara, Tadaki; Ode, Kenichi; Matsusaka, Yohji; Katagiri, Mari; Iwabuchi, Yu; Itoh, Kazunari; Ichimura, Akira; Jinzaki, Masahiro

    2017-05-01

    We developed a method of image data projection of bone SPECT into 3D volume-rendered CT images for 3D SPECT/CT fusion. The aims of our study were to evaluate its feasibility and clinical usefulness. Whole-body bone scintigraphy (WB) and SPECT/CT scans were performed in 318 cancer patients using a dedicated SPECT/CT systems. Volume data of bone SPECT and CT were fused to obtain 2D SPECT/CT images. To generate our 3D SPECT/CT images, colored voxel data of bone SPECT were projected onto the corresponding location of the volume-rendered CT data after a semi-automatic bone extraction. Then, the resultant 3D images were blended with conventional volume-rendered CT images, allowing to grasp the three-dimensional relationship between bone metabolism and anatomy. WB and SPECT (WB + SPECT), 2D SPECT/CT fusion, and 3D SPECT/CT fusion were evaluated by two independent reviewers in the diagnosis of bone metastasis. The inter-observer variability and diagnostic accuracy in these three image sets were investigated using a four-point diagnostic scale. Increased bone metabolism was found in 744 metastatic sites and 1002 benign changes. On a per-lesion basis, inter-observer agreements in the diagnosis of bone metastasis were 0.72 for WB + SPECT, 0.90 for 2D SPECT/CT, and 0.89 for 3D SPECT/CT. Receiver operating characteristic analyses for the diagnostic accuracy of bone metastasis showed that WB + SPECT, 2D SPECT/CT, and 3D SPECT/CT had an area under the curve of 0.800, 0.983, and 0.983 for reader 1, 0.865, 0.992, and 0.993 for reader 2, respectively (WB + SPECT vs. 2D or 3D SPECT/CT, p < 0.001; 2D vs. 3D SPECT/CT, n.s.). The durations of interpretation of WB + SPECT, 2D SPECT/CT, and 3D SPECT/CT images were 241 ± 75, 225 ± 73, and 182 ± 71 s for reader 1 and 207 ± 72, 190 ± 73, and 179 ± 73 s for reader 2, respectively. As a result, it took shorter time to read 3D SPECT/CT images than 2D SPECT/CT (p < 0.0001) or WB

  7. Flat-Panel Detector—Based Volume Computed Tomography: A Novel 3D Imaging Technique to Monitor Osteolytic Bone Lesions in a Mouse Tumor Metastasis Model

    Directory of Open Access Journals (Sweden)

    Jeannine Missbach-Guentner

    2007-09-01

    Full Text Available Skeletal metastasis is an important cause of mortality in patients with breast cancer. Hence, animal models, in combination with various imaging techniques, are in high demand for preclinical assessment of novel therapies. We evaluated the applicability of flat-panel volume computed tomography (fpVCT to noninvasive detection of osteolytic bone metastases that develop in severe immunodeficient mice after intracardial injection of MDA-MB-231 breast cancer cells. A single fpVCT scan at 200-wm isotropic resolution was employed to detect osteolysis within the entire skeleton. Osteolytic lesions identified by fpVCT correlated with Faxitron X-ray analysis and were subsequently confirmed by histopathological examination. Isotropic three-dimensional image data sets obtained by fpVCT were the basis for the precise visualization of the extent of the lesion within the cortical bone and for the measurement of bone loss. Furthermore, fpVCT imaging allows continuous monitoring of growth kinetics for each metastatic site and visualization of lesions in more complex regions of the skeleton, such as the skull. Our findings suggest that fpVCT is a powerful tool that can be used to monitor the occurrence and progression of osteolytic lesions in vivo and can be further developed to monitor responses to antimetastatic therapies over the course of the disease.

  8. Discordant Findings of Skeletal Metastasis Between Tc99m MDP Bone Scans and F18 FDG PET/CT Imaging for Advanced Breast and Lung Cancers—Two Case Reports and Literature Review

    Directory of Open Access Journals (Sweden)

    Yu-Wen Chen

    2007-12-01

    Full Text Available Traditionally, Tc99m methyl diphosphate (MDP bone scintigraphy provides high-sensitivity detection of skeletal metastasis from breast and lung cancers in regular follow-up. Fluorodeoxyglucose (FDG positron emission tomography/computed tomography (PET/CT, based on the glucose metabolism of malignant cells, plays a role in describing rumor growth, proliferation of neoplasm and the extent of metastasis. In general, concordant findings of skeletal metastasis are seen on both types of image, especially in cases of breast and lung cancer. However, there were extremely discordant findings of skeletal metastasis between bone scans and F18 FDG PET/CT imaging in two cases among 300 consecutive F18 FDG PET/CT follow-up exams of patients with malignancies, during the past year, in our center. Both cases, one of breast cancer and one of lung cancer, had negative bone scintigraphic findings, but a diffusely high grade of F18 FDG avid marrow infiltration in the axial spine, leading to the diagnosis of stage IV disease in both cases. Owing to variant genetic aberrance of malignance, F18 FDG PET/CT reveals direct evidence of diffuse, rapid neoplasm metabolism in the bone marrow of the spine, but not of secondary osteoblastic reactions in vivo. F18 FDG PET/CT should always be employed in the follow-up of patients with malignancies.

  9. Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

    NARCIS (Netherlands)

    Wymenga, LFA; Groenier, K; Boomsma, JHB; Elferink, RO; Mensink, HJA

    2001-01-01

    Objective To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. Patients, subjects and methods Urinary DPD, serum ALP and prostate-specific antigen (PSA) were eva

  10. 骨肿瘤的发生发展及转移%The occurrence,development and metastasis in bone neoplasms

    Institute of Scientific and Technical Information of China (English)

    杨澄; 苏宏伟; 任慧文; 李宏伟

    2014-01-01

    Bonetumorisonekindofmalignanttumorwhichthreatslifeamongchildrenandadoles-cent.Osteosarcoma (OS ) and Ewing sarcoma (ES ) have been paid much attention by medical community because of their complex occurrence,development,metastasis mechanism and poor prognosis.The research showed that activation of protooncogene and mutation of suppressor gene,absence of apoptosis signal and hypox-ia-inducible factor (HIF)all participated in the occurrence,development and metastasis of OS and ES.It is suggested that clarified pathomechanism of bone tumors could provide more effective therapeutic strategies and lower the mortality of patients.%骨肿瘤中骨肉瘤(OS)和尤文肉瘤(ES)因具有较复杂的发生、发展、转移机制和不良预后而受到医学界的广泛关注。研究表明原癌基因的激活和抑癌基因的突变、凋亡信号缺失和乏氧诱导因子等均参与OS和ES的发生、发展及转移。阐明骨肿瘤复杂的病理机制能为OS和ES提供更有效的靶向治疗手段和降低患者的死亡率。

  11. Application of Radionuclide Bone Imaging Combined with Tumor Markers in the Diagnosis of Bone Metastasis in Breast Cancer Patients%核素骨显像联合肿瘤标记物检测对乳腺癌骨转移的诊断价值

    Institute of Scientific and Technical Information of China (English)

    郭小楠; 董丽

    2016-01-01

    Objective To observe the application value of radionuclide bone imaging combined with tumor markers in the diagnosis of bone metastasis in breast cancer patients .Methods 82 breast cancer patients were divided into metastasis group with 43 cases and premetastasis group with 39 cases according to the result of radionuclide bone imaging .Then 40 healthy women were selected as the control group .The results of radionuclide bone imaging and tumor markers were observed ,and the diagnostic value were compared.Results The expression level and positive rate of serum CA 125,CA15-3 and CEA of metastasis group were obviously higher,there had statistically difference (P2,there had statistically difference (P<0.05).The serum levels of CA125,CA15-3 and CEA increased gradually as bone metastatic grading increased (P<0.05).Conclusion Radionuclide bone imaging combined with tumor markers can improve the diagnostic sensitivity ,which is an important reference in the diagnosis of bone metastasis in breast cancer patients .%目的:观察核素骨显像联合肿瘤标记物对乳腺癌骨转移的诊断价值。方法选择乳腺癌患者82例,按照核素骨显像结果分为转移组43例及未转移组39例,另选取40例健康体检女性作为对照组。观察核素骨显像以及肿瘤标记物检测结果,并对其诊断价值进行考察。结果转移组血清CA125、CA15-3及CEA表达水平及阳性率显著高于未转移组及对照组,骨转移灶数目≤2患者血清CA125、CA15-3以及CEA表达水平及阳性率均显著低于骨转移灶数目>2的患者,差异均具有统计学意义(P<0.05)。且随着骨转移分级程度的升高,患者乳腺癌相关肿瘤标记物CA125、CA15-3及CEA表达水平及阳性率均呈升高趋势,各分级间差异有统计学意义( P<0.05)。结论核素骨显像联合肿瘤标记物检测可提高诊断敏感性,对于乳腺癌骨转移的诊断具有重要的参考价值。

  12. Detection of Unknown sites of multiple enchondroma (Ollier′s Disease mimicking like metastasis using bone scintigraphy

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Ollier′s disease characterized by multiple skeletal enchondroma is a rare noninherited disease of unknown etiology. Majority of the skeletal enchondroma are present in the metaphyses and diaphysis of tubular limb bones. Ollier′s disease has a predilection for unilateral distribution. Malignant changes in Ollier′s disease may occur in adult patients. Radionuclide bone scanning is one method used to assess lesions depicted on radiographs or magnetic resonance images that are presumed to be enchondromas. Furthermore, a bone scan may give a clue to the multifocality of the disease. We report a case of right first phalangeal enchondroma in a 23-year-old male, who underwent bone scintigraphy detected multifocal asymmetric right side involvement of radius, humerus, femur, and tibia which confirm a diagnosis of Ollier′s disease.

  13. Nonspecific iodine accumulation in surgical suture material mimicking follicular thyroid cancer bone metastasis in (131)I scintigraphy.

    Science.gov (United States)

    Winkens, Thomas; Nietzsche, Sandor; Gottschaldt, Michael; Freesmeyer, Martin

    2014-02-01

    A 23-year-old man with follicular thyroid carcinoma and cervical lymph node metastases showed a clear I focus on the skull after radioiodine therapy; therefore, an osseous metastasis was suspected. I and MRI fusion suggested the I focus to be adjacent to an epicranial suture from an early childhood trepanation for epidural hematoma. Radio-guided surgery found dark brown material to be the source of the radiation and successfully removed the material. Subsequent electron microscopy revealed a thread within the dark brown material, suggesting suture material as the cause of I accumulation.

  14. Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth.

    Science.gov (United States)

    Usmani, Shirine E; Pest, Michael A; Kim, Gunwoo; Ohora, Sara N; Qin, Ling; Beier, Frank

    2012-07-01

    We have recently identified transforming growth factor alpha (TGFα) as a novel growth factor involved in the joint disease osteoarthritis. The role of TGFα in normal cartilage and bone physiology however, has not been well defined. The objective of this study was to determine the role of TGFα in bone development through investigation of the Tgfa knockout mouse. The gross skeletons as well as the cartilage growth plates of Tgfa knockout mice and their control littermates were examined during several developmental stages ranging from newborn to ten weeks old. Knockout mice experienced skeletal growth retardation and expansion of the hypertrophic zone of the growth plate. These phenotypes were transient and spontaneously resolved by ten weeks of age. Tgfa knockout growth plates also had fewer osteoclasts along the cartilage/bone interface. Furthermore, knockout mice expressed less RUNX2, RANKL, and MMP13 mRNA in their cartilage growth plates than controls did. Tgfa knockout mice experience a delay in bone development, specifically the conversion of hypertrophic cartilage to true bone. The persistence of the hypertrophic zone of the growth plate appears to be mediated by a decrease in MMP13 and RANKL expression in hypertrophic chondrocytes and a resulting reduction in osteoclast recruitment. Overall, TGFα appears to be an important growth factor regulating the conversion of cartilage to bone during the process of endochondral ossification. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Value of serum NTx and BSP in diagnosing non-small cell lung cancer with bone metastasis%血清NTx和BSP测定在非小细胞肺癌骨转移诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    谢伟国; 江莲; 谢诤; 侯昕珩; 陈建波

    2011-01-01

    Objective To investigate the clinical significance of bone sialoprotein (BSP) and serum type I collagen cross-linked N-terminal peptide ( NTx) in diagnosing non-small cell lung cancer with bone metastases. Methods 67 patients with lung cancer patients were divided into bone metastasis (n =32) and those without bone metastasis (n =35)s. BSP and serum NTx levels were detected by using ELISA. The patients with bone metastases of lung cancer were re-evaluated by imaging studies 12 months after newly diagnosed. Results Compared with the group without bone metastasis, NTX and BSP in serum was significantly increased and the group difference was statistically significant ( P < 0.01). 10 patients diagnosed as non-bone metastasis occurred new bone metastases during the follow-up. Compared with the non-bone metastases, NTx and BSP of the patients with new bone metastases and bone metastasis were significantly increased, and there was significant difference between the two groups (P <0.05). Contents of NTx and BSP were increase the patients with bone metastases, compared with the group with newly diagnosed bone metastases. Conclusion NTx and BSP in serum can be used for non-small cell lung cancer with bone metastases. The increase of its content may mean non-small cell lung cancer with bone metastasis, which thus facilitates early treatment.%目的 探讨骨唾液酸蛋白(BSP)和血清Ⅰ型胶原交联氨基末端肽(NTx)测定在非小细胞肺癌骨转移诊断中的临床意义.方法 将67例肺癌患者初诊时分为骨转移组和无骨转移组,其中骨转移组32例,非骨转移组35例,并采用ELISA法对血清中NTx和BSP水平进行检测.初诊后12个月对肺癌患者骨转移情况采用影像学检查进行再次评估.结果 与无骨转移组相比,骨转移组血清NTX和BSP含量显著升高(P<0.01).10例初诊为无骨转移者在随访过程中新发生骨转移癌.与无骨转移组相比,新发骨转移癌组和初诊骨转移

  16. Spinal uptake mimicking metastasis in SPECT/CT bone scan in a patient with superior vena cava obstruction.

    Science.gov (United States)

    Rager, Olivier; Nkoulou, René; Garibotto, Valentina; Boudabbous, Sana; Arditi, Daniel

    2013-11-01

    A 46-year-old female patient with a mediastinal neuroendocrine carcinoma complicated by superior vena cava syndrome was referred for a bone metastatic workup. Bone scan with SPECT/CT showed several vertebral fixations without alterations on the unenhanced CT, but a CT scan with injection of contrast media showed vertebral densities matched to the lesions described on the SPECT/CT. This pattern confirmed presence of collateral paths through vertebral veins due to superior vena cava syndrome. Lack of metastases was confirmed by MRI.

  17. Three-minute SPECT/CT is sufficient for the assessment of bone metastasis as add-on to planar bone scintigraphy

    DEFF Research Database (Denmark)

    Zacho, Helle D; Manresa, José A Biurrun; Aleksyniene, Ramune

    2017-01-01

    BACKGROUND: The aim of this study is to assess whether ultra-fast acquisition SPECT/CT (UF-SPECT/CT) can replace standard SPECT/CT (std-SPECT/CT) as "add-on" to whole-body bone scintigraphy (WB-BS) for the investigation of bone metastases. Consecutive cancer patients referred for WB-BS who...... diagnosis was reached by two observers for each set of images (WB-BS + standard SPECT/CT or WB-BS + UF-SPECT/CT) using a three-category evaluation scale: M0: no bone metastases; M1: bone metastases; and Me: equivocal findings. RESULTS: Among the 104 included patients, most presented with prostate cancer (n...... in observer agreement between cancer types was detected. SPECT/CT provided a definitive classification in 90 of 104 cases in which WB-BS was not entirely diagnostic. CONCLUSIONS: To investigate potential bone metastases, UF-SPECT/CT can be conducted as add-on to WB-BS to notably reduce the SPECT acquisition...

  18. Mechanism of cancer-induced bone destruction: An association of connective tissue growth factor (CTGF/CCN2 in the bone metastasis

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Shimo

    2011-02-01

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family, a novel class of extracellular signal modulators. CCN2 is composed of four conserved modules connected in tandem, each of which is rich in cysteines and highly interactive with other molecules. CCN2 has various biological functions, being active in developmental processes including angiogenesis, chondrogenesis, and osteogenesis. Recently CCN2 has gained more clinical interest due to its role in cancer-induced bone destruction. In this article, the role of CCN2 in bone-destroying events as an organizer of the microenvironmental cell society is comprehensively described, and a brief summary of the recent findings on regulatory factors involved in tumor-induced bone disease is given.

  19. Inhibition on Breast Cancer Induced Bone Pain, Metastasis and Osteolysis in Nude Mice by LOVAZA and DHA Fattty Acids

    Science.gov (United States)

    2011-10-01

    vertebrae adjacent to the spinal cord, and the overlying muscle and bone were removed. The last thoracic ganglion (T13) and the ganglion with the greatest... cervical and upper thoracic levels, and the ganglia lie closely apposed to the spinal cord. L3-L5 DRG’s were removed, and placed in cold saline

  20. Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Zhen Liu

    Full Text Available BACKGROUND: Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B, a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis. METHODOLOGY: BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT of 4T1 and primary human breast cancer cells was assayed. PRINCIPAL FINDINGS: Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells. CONCLUSIONS: Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.

  1. CA153、IL-6及IL-8与乳腺癌骨转移相关性探讨%Study on the correlation between CA153, IL-6, IL-8 levels and bone metastasis in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    杨士军; 谭维琴; 鲍艳梅

    2011-01-01

    目的 探讨糖类抗原153(CA153)及细胞因子[白细胞介素6(IL-6)、白细胞介素8(IL-8)]与乳腺癌骨转移的关系.方法 对103例乳腺癌根治手术后患者行单光子发射型(SPECT)骨显像,采用放射免疫法检测血清CA153,放射免疫分析法检测IL-6、IL-8水平,与健康对照组(36例)进行对比分析.结果 骨转移组患者血清CA153、IL-6、IL-8水平明显升高,与无骨转移组及健康对照组比较差异均有统计学意义(P0.05).结论 CA153对于预测乳腺癌骨转移、筛选行全身骨显像患者具有重要意义;IL-6、IL-8参与乳腺癌骨转移的发生和发展过程,检测IL-6、IL-8对于乳腺癌骨转移的病理研究和预防、治疗可能具有重要价值.%Objective To investigate the corelation of CA153,IL-6,IL-8 and breast cancer bone metastasis. Methods 103 breast cancer patients after radical surgery were scanned by single photon emission computer tomography(SPECT). Immunoradiometric assay(IRMA) method was used to assay the serum.level of CA153,and radioimmunoassay(RIA) method was used to assay serum level of IL-6,IL-8;At the same time,the result was analyzed against the control group of 36 normal people. Results In breast cancer patients group with bone metastasis, the serum level of CA153, IL-6, IL-8 were significantly higher than normal people(P<0.05) ,while the serum level of CA153,IL-6 and IL-8 in cancer patients group without bone metastasis and in control group were not statistically significant different(P>0.05). Conclusion CA153 has great significance in predicting breast cancer bone metastasis and screening whole body bone imaging;IL-6, IL-8 is engaging in the occurrence and development of bone metastasis, assaying the serum levels of IL-6,IL-8 are of great value to pathology research,prevention and treatment of breast cancer bone metastasis.

  2. Therapeutic Targeting of TRPV1 for the Treatment of Chronic Pain Associated with Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2012-07-01

    As the PFA enters the circulation, the muscles go into spasm and, after a few minutes, the animal should be literally "fixed" in position. This...Cut into the pelvis and surrounding muscle to separate the femur from the pelvis whilst leaving the proximal head of the femur intact. Cut into the...tibia/fibula to leave the distal head intact, removing the surrounding muscle /periosteum from the bone shaft. Place the femur into a 2 ml tube

  3. Inhibition of Breast Cancer-lnduced Bone Pain, Metastasis, and Osteolysis in Nude Mice by LOVAZA and DHA Fatty Acids

    Science.gov (United States)

    2012-10-01

    GGTGAAGGTCGGTGTGAACG/CTCGCTCCTGGAAGATGGTG (30 cycles). PCR products were separated on 2% agarose gels containing ethidium bromide and visualized...and bone were removed . The last thoracic ganglion (T13) and the ganglion with the greatest contribution to the sciatic nerve (L4) were identified...closely apposed to the spinal cord. L3-L5 DRG’s were removed , and placed in cold saline solution. DRG’s were then processed either for RT-PCR

  4. Identification of a novel TGFβ/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Sanjib Chowdhury

    Full Text Available BACKGROUND: Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival. CONCLUSION/SIGNIFICANCE: This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors.

  5. 肺癌患者血清NTx、ICTP和BAP水平与骨转移的相关性研究%Relationships between the levels of sermn NTx, ICTP, BAP and bone metastasis in patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    张世强; 陈冬波; 王保庆; 张兰胜

    2011-01-01

    Objective To study the clinical significance of serum N-telopeptide of type I collagen( NTx), carboxy-terminal collagen telopeptide( ICTP), and bone-specific alkaline phosphatase(BAP) in diagnosing bone metastasis of lung cancer. Methods A total of 106 patients with lung cancer were diagnosed by pathology in this study. Patients were divided into two groups: 61 patients with bone metastasis and 45 patients without bone metastasis. The levels of serum NTx, ICTP and BAP were measured by ELISA. Results The levels of serum NTx, ICTP and BAP in bone metastasis group were (25.36 ± 11.07) nmol/L, (29. 18 ± 10. 74) μg/L and (78. 31 ± 16. 53 ) μg/L higher than ( 12. 16 ± 7.62) nmol/L, ( 11.02 ± 5.32)μg/L and (24. 01 ± 7.98 ) μg/L in non-bone metastasis group( P < 0. 01 ). The sensitivity and specificity of serum NTx in the diagnosis of bone metastasis were 90. 16% and 84. 44%, respectively. The sensitivity and specificity of serum BAP were 80. 32% and 77.78%, respectively. The sensitivity and specificity of serum ICTP were 70.49% and 91.11%, respectively. While The levels of serum NTx, ICTP and BAP in patients with more bone metastasis were significantly higher than those in single bone metastasis (P < 0. 05 ). The levels of serum NTx, ICTP and BAP were related to the degree of pain with bone metastasis. But we could not find that there were difference of serum NTx, ICTP and BAP among sex, pathology and different bone metastasis position. Conclusion The sensitivity and specificity of the serum NTx, ICTP and BAP are higher in diagnosis of lung cancer with bone metastasis. The three markers can be regarded as important factors for bone metastasis of lung cancer.%目的 探讨联合检测骨代谢生化指标血清Ⅰ型胶原氨基末端肽(NTx)、Ⅰ型胶原羧基端肽(ICTP)及骨特异性碱性磷酸酶(BAP)对诊断肺癌骨转移的临床意义.方法 选择经细胞学和病理学确诊的肺癌患者106例,分为两组,其中骨转移组61

  6. Prognosis of hepatocellular carcinoma patients with extrahepatic metastasis and the controllability of intrahepatic lesions.

    Science.gov (United States)

    Lee, Jung Il; Kim, Ja Kyung; Kim, Do Young; Ahn, Sang Hoon; Park, Jun Yong; Kim, Seung Up; Kim, Beom Kyung; Han, Kwang Hyub; Lee, Kwan Sik

    2014-04-01

    Although advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is recommended to be treated by a systemic chemotherapeutic agent without local treatment targeting the liver, studies reported that causes of death in these patients were mostly from progression of intrahepatic lesions. Thus, this study investigated prognosis and factors predicting survival in these patients so as to evaluate the role of local treatments against intrahepatic lesions when the patients already had extrahepatic metastasis. This retrospective study evaluated medical records of 277 patients with HCC and extrahepatic metastasis. The median survival was 5.9 months, and 257 patients died during the follow up. Factors affecting survival of HCC patients with extrahepatic metastasis were poor response to treatment of hepatic lesions (HR 2.207; 95% CI; p < 0.001), applying local treatment specifically targeting intrahepatic lesions (HR 0.591; 95% CI 0.436-0.803; p = 0.001), intrahepatic tumor size larger than 3 cm (HR 2.065; 95% CI 1.444-2.954; p < 0.001), and ECOG performance status 2 or higher (HR 1.543; 95% CI 1.057-2.253; p = 0.025). The patients with either complete or partial response to the therapy had 1- and 2-year survival rate of 48.8 and 12.1% whereas patient with either stable or progressive disease had 1-year survival rate of 11.4%. These results suggest that even in the HCC patients with extrahepatic metastasis, effective local treatment may still be beneficial for the survival especially in patients with acceptable performance status.

  7. SU-E-J-162: Quality Assurance Procedures for MR Guided Focused Ultrasound Treatment of Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L; Chen, X; Wang, B; Gupta, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: The purpose of this work is to develop and verify our quality assurance (QA) procedures to ensure the safety and efficacy of MR-guided focused ultrasound (MRgFUS) treatment of bone metastases. Methods: A practical QA program was developed. Monthly and daily QA (DQA) procedures were performed. The major QA items included the checks of the machine hardware, software and patient safety features. Briefly, these checks/tests include: 1) the cooling system reservoir and treatment table; 2) power to the treatment table; 3) the MR coil; 4) the transducer position with MRI; 5) image display on the treatment work station; 6) the effective focal spot in 3 directions using MR thermometry; and 7) all the safety devices including a sonication lamp, and the emergency stop-sonication switches. In order to avoid patient skin burn, it is important to remove gas bubbles in the interfaces between the treatment table and the gel pad, and the gel pad and patients skin during the patient setup. Our QA procedures have been verified and evaluated through patient treatments. Seven patients with scapula, humeral head, sacrum, ilium, pubic ramus and acetabular bone metastases were treated using MRgFUS. Results: Our study showed that all seven patients tolerated the MRgFUS treatment well. No skin toxicity or other complications were observed. The pain score (0–10) using the visual analog scale (VAS) was significantly reduced from 8.0 ± 1.1 before treatment to 4.7 ± 3.0, 3.0 ± 1.5, 3.2 ± 2.8 and 3.4 ± 1.5 at one day, one month, two months and three months after the MRgFUS treatment, respectively. Conclusion: We demonstrated that with the appropriate QA procedures, MRgFUS is a safe, effective and noninvasive treatment modality for palliation of bone metastases.

  8. A case of bone metastasis of colon cancer that markedly responded to S-1/CPT-11 combination chemotherapy and became curable by resection

    Directory of Open Access Journals (Sweden)

    Masuda Hideki

    2006-01-01

    Full Text Available Abstract Background An oral combined fluoropyrimidine anticancer drug, tegafur/gimeracil/oteracil potassium (S-1, has recently been used alone or in combination for colon cancer. Case presentation The patient was a 42-year-old man with sigmoid colon cancer with direct invasion of the urinary bladder and multiple costal metastases. A diagnosis of T4, M1, stage IV sigmoid colon cancer was made, and curative resection was considered impossible. S-1 at 50 mg/m2 was administered by oral route from day 1 to day 14. Irinotecan (CPT-11 at 40 mg/m2 was administered by intravenous day 1 and 15. This treatment was followed by 2 weeks absent period, and repeated every 4 weeks. Six cycles of administration were performed in total. Following this treatment, the multiple costal metastases resolved. Down-staging to T3, M0, stage IIA was achieved, and curative resection was judged to be possible. Conclusion Occasional cases in which S-1/CPT-11 therapy was effective have been recently reported. The patient's tumor became resectable despite the discovery of colon cancer associated with bone metastasis at the initial examination, offering hope for cancer patients.

  9. [Biology of cancer metastasis].

    Science.gov (United States)

    Robert, Jacques

    2013-04-01

    Metastatic dissemination represents the true cause of the malignant character of cancers. Its targeting is much more difficult than that of cell proliferation, because metastasis, like angiogenesis, involves a number of complex interactions between tumour and stroma; the contribution of adhesion and motility pathways is added to that of proliferation and survival pathways. Long distance extension, discontinuous in respect to the primitive tumour, is a major feature of cancer and the main cause of patients' death. Cancer cells use two main dissemination pathways: the lymphatic pathway, leading to the invasion of the lymph nodes draining the organs where the tumour evolves; and the blood pathway, leading to the invasion of distant organs such as liver, brain, bone or lung. Metastasis is inscribed within the properties of the primitive tumour, as shown by the comparative molecular analysis of the primitive tumour and its own metastases: their similarity is always more important than what could be expected from the general activation of "metastasis genes" or the inhibition of "metastasis suppressor genes". Among the signalling pathways involved in metastasis, one can mention the integrin pathway, the transforming growth factor beta (TGFβ) pathway, the chemokine pathway, the dependence receptor pathway and many others. These pathways allow the possibility of therapeutic targeting, thanks to therapeutic antibodies or small molecules inhibiting the kinases involved in these signalling pathways, but not a single properly anti-metastatic drug has yet been proposed: the complexity and the diversity of the processes allowing metastasis emergence, as well as the fact that the activation mechanisms are more often epigenetic than genetic and are generally physiological processes misled by the malignant cell, render especially difficult the therapeutic approach of metastasis.

  10. Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis.

    Science.gov (United States)

    Hansen, Sarah A; Hart, Marcia L; Busi, Susheel; Parker, Taybor; Goerndt, Angela; Jones, Kevin; Amos-Landgraf, James M; Bryda, Elizabeth C

    2016-10-01

    Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease. We used a marker-assisted speed congenic approach to transfer a well-characterized Tp53-mutant allele from an outbred rat to the genetically inbred Fischer-344 (F344) rat to create the F344-Tp53(tm1(EGFP-Pac)Qly)/Rrrc (F344-Tp53) strain. On the F344 genetic background, the tumor spectrum shifted, with the primary tumor types being osteosarcomas and meningeal sarcomas, compared to the hepatic hemangiosarcoma and lymphoma identified in the original outbred stock model. The Fischer model is more consistent with the early onset of bone and central nervous system sarcomas found in humans with germline Tp53 mutations. The frequency of osteosarcomas in F344-Tp53 homozygous and heterozygous animals was 57% and 36%, respectively. Tumors were highly representative of human disease radiographically and histologically, with tumors found primarily on long bones with frequent pulmonary metastases. Importantly, the rapid onset of osteosarcomas in this promising new model fills a current void in animal models that recapitulate human pediatric osteosarcomas and could facilitate studies to identify therapeutic targets.

  11. Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis

    Directory of Open Access Journals (Sweden)

    Sarah A. Hansen

    2016-10-01

    Full Text Available Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease. We used a marker-assisted speed congenic approach to transfer a well-characterized Tp53-mutant allele from an outbred rat to the genetically inbred Fischer-344 (F344 rat to create the F344-Tp53tm1(EGFP-PacQly/Rrrc (F344-Tp53 strain. On the F344 genetic background, the tumor spectrum shifted, with the primary tumor types being osteosarcomas and meningeal sarcomas, compared to the hepatic hemangiosarcoma and lymphoma identified in the original outbred stock model. The Fischer model is more consistent with the early onset of bone and central nervous system sarcomas found in humans with germline Tp53 mutations. The frequency of osteosarcomas in F344-Tp53 homozygous and heterozygous animals was 57% and 36%, respectively. Tumors were highly representative of human disease radiographically and histologically, with tumors found primarily on long bones with frequent pulmonary metastases. Importantly, the rapid onset of osteosarcomas in this promising new model fills a current void in animal models that recapitulate human pediatric osteosarcomas and could facilitate studies to identify therapeutic targets.

  12. Blood flow controls bone vascular function and osteogenesis

    Science.gov (United States)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  13. Changes of trabecular bone under control of biologically mechanical mechanism

    Science.gov (United States)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  14. Diagnosis and evaluation of bone metastasis with PET/CT and bone scintigraphy in patients with malignancies%PET/CT显像与全身骨扫描诊断转移性骨肿瘤的比较研究

    Institute of Scientific and Technical Information of China (English)

    程旭; 李永军; 徐兆强; 王杰; 包丽华

    2013-01-01

    Objective:To evaluate diagnostic value of PET/CT with 18F-FDG and whole-body bone scintigraphy(BS)with Tc-MDP for metastatic bone tumor in patients with malignancies. Methods: A total of 75 patients with malignances,average of 59.85 ± 13.59 years old, were included in this study. All patients underwent PET/CT imaging with 18F-FDG and BS with Tc-MDP for two weeks. Based on the diagnostic results of patients,we calculated the sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV),and accuracy of PET/CT imaging and BS method to detect bone metastasis. Moreover,image features on different body regions were assessed and compared between two imaging methods. Results: There were 34 patients diagnosed with skeletal metastasis among all 75 patients. The sensitivity of PET/CT was 94.1% (32/34) in detecting bone metastasis. The specificity of PET/CT was 95.1% (39/41)The PPV,NPV and accuracy of PET/CT were 94.1%,95.1% and 94.7% , respectively. For BS with 99mTc-MDP, the sensitivity of detecting skeletal metastasis was 91.2%(31/34)and the specificity was 65.9%(27/41). The PPV,NPV and accuracy of BS were 68.9 %,90 % and 77.3 %,respectively. On basis of region analysis,the main abnormal uptakes of 18F-FDG were located in spine,rib and pelvis by PET/CT detection. For BS with 99mTc-MDP,the main lesions were located in rib,spine and bones of limbs. Conclusion:The specificity,accuracy and PPV of PET/CT imaging were higher than those of BS. However,there was no significant difference in sensitivity and NPV between PET/CT imaging and BS.%目的:评价正电子发射计算机断层扫描(positron emission tomography/computed tomography,PET/CT)18F标记的氟脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)全身显像与99mTc标记的亚甲基二磷酸盐(99mTc-methylene diphosphonate,99mTc-MDP)全身骨扫描(bone scintigraphy,BS)诊断转移性骨肿瘤的效能.方法:共计75例临床确诊的恶性肿瘤患者纳入本研究,平均年龄(59.85±13

  15. Nasopharyngeal carcinoma with pericardial metastasis

    Directory of Open Access Journals (Sweden)

    Shang-Wen Chen

    2011-07-01

    Full Text Available Nasopharyngeal carcinoma (NPC is prevalent in Taiwan and is characterized by a high frequency of nodal metastasis. The most common organs with distal metastases are the bones, lungs, and liver, with extremely rare cases to the pericardium. Herein, we report a rare case with NPC who presented with dyspnea and orthopnea. Serial studies, including pericardial biopsy, revealed NPC with pericardial metastasis and pericardial effusion. The tumor cells of both the original and metastatic tumors were positive for Epstein–Barr virus by in situ hybridization. This is the first histologically confirmed case of NPC with pericardial metastasis.

  16. Application of bone scintigraphy in therapy response monitoring and prognosis prediction in patients with bone metastasis from lung cancer and prostate cancer%骨扫描在肺癌和前列腺癌骨转移疗效监测及预后判断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    潘懿范; 刘建军; 黄钢; 马玉波

    2011-01-01

    目的 探讨全身骨扫描在肺癌和前列腺癌骨转移疗效监测及预后判断中的应用价值.方法 将40例肺癌患者和31例前列腺癌患者在系统治疗前1个月内及治疗≥3个月后分别行全身骨扫描,观察治疗前后骨转移灶的变化与肿瘤临床综合疗效的相关性.采用Kaplan-Meier法计算生存率,Log-rank检验及Cox回归模型分析影响肺癌或前列腺癌骨转移预后的危险因素.结果 肿瘤临床综合治疗有效者( 59.68%,37/62)的骨转移疗效明显好于无效者(40.32%,25/62)(P<0.05).肺癌骨转移患者的1年生存率为54.5%,2年生存率为22.6%;前列腺癌骨转移患者的1年生存率为87.3%,2年生存率为72.3%.单因素及Cox多因素分析均显示:肺癌和前列腺癌骨转移患者的生存率与肿瘤类型及骨转移时长相关(P<0.05).肺癌与前列腺癌分组行Cox多因素分析结果显示:肺癌骨转移的预后危险因素为病理类型、治疗前骨扫描病变范围及骨转移时长;而前列腺癌骨转移的预后与骨转移时长有关.结论 全身骨扫描为肺癌和前列腺癌骨转移的疗效监测及预后判断提供了更丰富、更准确的信息.%Objective To investigate the application of bone scintigraphy in therapy response monitoring and prognosis prediction in patients with bone metastasis from lung cancer and prostate cancer. Methods Whole-body bone scintigraphy was performed in 40 patients with lung cancer and 31 patients with prostate cancer one month before systematic therapy and no less than 3 months after treatment. The changes of bone metastasis lesions were observed before and after treatment, and the correlation of bone metastasis with therapy response was explored. Survival rates were calculated by Kaplan-Meier method, and prognostic factors for survival were analysed by Log-rank test and Cox regression model. Results The therapeutic effect of bone metastasis in clinical therapy responders in primary

  17. General Information about Osteosarcoma and Malignant Fibrous Histiocytoma of Bone

    Science.gov (United States)

    ... to the lung. Bone Metastasis or Bone with Lung Metastasis Osteosarcoma and malignant fibrous histiocytoma may spread to a distant bone and/or the lung. Treatment may include the following: Combination chemotherapy followed ...

  18. Treatment Option Overview (Osteosarcoma and Malignant Fibrous Histiocytoma of Bone)

    Science.gov (United States)

    ... to the lung. Bone Metastasis or Bone with Lung Metastasis Osteosarcoma and malignant fibrous histiocytoma may spread to a distant bone and/or the lung. Treatment may include the following: Combination chemotherapy followed ...

  19. Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

    Science.gov (United States)

    Tournis, S; Michopoulou, E; Fatouros, I G; Paspati, I; Michalopoulou, M; Raptou, P; Leontsini, D; Avloniti, A; Krekoukia, M; Zouvelou, V; Galanos, A; Aggelousis, N; Kambas, A; Douroudos, I; Lyritis, G P; Taxildaris, K; Pappaioannou, N

    2010-06-01

    Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. We conducted a cross-sectional study at a tertiary center. We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

  20. Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis.

    Science.gov (United States)

    Ge, Chunxi; Wang, Zhengyan; Zhao, Guisheng; Li, Binbin; Liao, Jinhui; Sun, Hanshi; Franceschi, Renny T

    2016-12-01

    Cell-extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis. Smallie mice (Ddr2(slie/slie) ), which contain a nonfunctional Ddr2 allele, have multiple skeletal defects. A progressive decrease in tibial trabecular bone volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2(wt/slie) , and Ddr2(slie/slie) mice were compared. These changes were associated with reduced trabecular number (Tb.N) and trabecular thickness (Tb.Th) and increased trabecular spacing (Tb.Sp) in both males and females, but reduced cortical thickness only in Ddr2(slie/slie) females. Bone changes were attributed to decreased bone formation rather than increased osteoclast activity. Significantly, marrow fat and adipocyte-specific mRNA expression were significantly elevated in Ddr2(slie/slie) animals. Additional skeletal defects include widened calvarial sutures and reduced vertebral trabecular bone. To examine the role of DDR2 signaling in cell differentiation, bone marrow stromal cells (BMSCs) were grown under osteogenic and adipogenic conditions. Ddr2(slie/slie) cells exhibited defective osteoblast differentiation and accelerated adipogenesis. Changes in differentiation were related to activity of runt-related transcription factor 2 (RUNX2) and PPARγ, transcription factors that are both controlled by MAPK-dependent phosphorylation. Specifically, the defective osteoblast differentiation in calvarial cells from Ddr2(slie/slie) mice was associated with reduced ERK/MAP kinase and RUNX2-S319 phosphorylation and could

  1. Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

    Directory of Open Access Journals (Sweden)

    Pilar Sepulveda

    2002-09-01

    Full Text Available For thirty years it has been known that certain compositions of Na2O-CaO-P2O5-SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.

  2. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

    Science.gov (United States)

    Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

    2003-01-01

    Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

  3. 建立乳腺癌骨转移动物模型方法的比较研究%A comparative study of four methods for establishing animal models of human breast cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    张帆; 姜军; 齐晓伟; 唐鹏; 陈庆秋

    2010-01-01

    Objective To investigate four methods for establishing animal models of human breast cancer bone metastasis. Methods Thirty-two female nude mice aged 4-6 weeks were divided randomly into four groups (n=8 in each group). 5×105 MDA-MB-231 cells were injected into the body via the left second mammary fat pads (group A), the tail veins (group B), the left heart ventricles (group C) and the left tibia marrow cavities (group D), respectively. Tumor formations in situ were recorded in group A. Deaths after the injection were recorded. The surviving nude mice 49 days after the injection were subjected to pathological examination to determine bone metastasis. Results The rate of tumor formation in situ of group A was87.5 %(7/8). One mouse in group C died after the injection of MDA-MB-231 cells. The bone metastasis rate in groups A, B, C and D was zero (0/8), 12.5 % (1/8), 71.4 % (5/7) and 100 % (8/8), respectively. There was statistically significant difference in the bone metastasis rate between group A and group C, group A and group D, group B and group C; and group B and group D. Conclusion Injections of tumor cells via the breast fat pads and tail veins were not suitablemethods to establish animal models of human breast cancer bone metastasis. The bone metastasis model could be established efficiently by injecting tumor cells into the left heart ventricles or the bone marrow cavity of nude mice.%目的 对四种乳腺癌骨转移动物模型的构建方法进行比较研究.方法 32只4-6周龄雌性裸鼠随机分为A、B、C、D 4组,每组8只,每只裸鼠以5×105个MDA-MB-231细胞按分组分别注射入左第二乳房脂肪垫、尾静脉、左心室和左胫骨骨髓腔.观察A组裸鼠乳腺原位成瘤情况、全组注射致死情况和全组49 d后骨转移发生情况.结果 A组乳腺原位移植瘤形成率为87.5%(7/8).仅C组注射致死裸鼠1只.各组骨转移发生率分别为:0(0/8)、12.5%(1/8)、71.4%(5/7)、100%(8/8).A组和C组、A组和D组

  4. The Role of Interleukin-6/GP130 Signaling in Prostate Cancer Progression and its Contribution to Bone Metastasis Morbidity

    Science.gov (United States)

    2008-11-01

    recipients to standardize tumor volume and growth kinetics; the isotype-matched control antibody had fungal contamination and was therefore not used...SIL-6 receptor complexes in systemic juvenile idiopathic arthritis : evidence for serum factors interfering with the binding to gp130. Clinical and

  5. 地塞米松对大鼠 Walker 256乳腺癌骨转移癌痛的作用%Effect of dexamethasone on rat bone metastasis pain induced by Walker 256 mammary gland carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    张凡; 李毅; 丁杰; 张海林

    2015-01-01

    Objective To establish a rat model of bone metastasis pain induced by Walker 256 mammary gland carcinoma cells and observe the effect of dexamethasone on bone cancer pain. Methods Ascitic tumour cells were made from Walker 256 mammary gland carcinoma cells injected to tibia of rats.Then,the withdrawal threshold to mechanical stimulus and withdrawal time in response to radiant thermal stimulus were tested before and after operation.Results The withdrawal threshold to mechanical stimulus and withdrawal time in response to radiant thermal stimulus were significantly reduced in the tibia bone inoculated with Walker 256 cells.The pathology results showed the evidence of tibia bone structure was destructed by tumor.It is suggested that the model of bone metastasis pain induced by Walker 256 mammary gland carcinoma cell was successfully established.Dexamethasone (5 mg/kg ) elevated withdrawal threshold to mechanical stimulus in rat model of bone metastasis pain induced by Walker 256 mammary gland carcinoma cell.Conclusion Dexamethasone could alleviate bone cancer pain.%目的:建立大鼠 Walker 256乳腺癌骨转移癌痛模型,观察地塞米松对骨转移癌疼痛痛阈的影响。方法制备 Walker 256乳腺癌细胞的大鼠腹腔积液瘤细胞,将其注射入大鼠胫骨,测量术前及术后机械刺痛阈和辐射热痛阈。结果接种 Walker 256乳腺癌大鼠术侧机械刺激痛觉和辐射热痛觉阈值显著降低,且病理学结果显示骨质受到肿瘤破坏,提示 Walker 256大鼠乳腺癌骨转移癌疼痛模型成功建立。地塞米松(5 mg/kg)能够显著提高骨转移癌疼痛模型刺痛痛阈。结论地塞米松能够缓解大鼠骨转移癌疼痛。

  6. Preoperative embolization of primary bone tumors: A case control study

    Science.gov (United States)

    Jha, Roushan; Sharma, Raju; Rastogi, Shishir; Khan, Shah Alam; Jayaswal, Arvind; Gamanagatti, Shivanand

    2016-01-01

    AIM: To study the safety and effectiveness of preoperative embolization of primary bone tumors in relation to intraoperative blood loss, intraoperative blood transfusion volume and surgical time. METHODS: Thirty-three patients underwent preoperative embolization of primary tumors of extremities, hip or vertebrae before resection and stabilization. The primary osseous tumors included giant cell tumors, aneurysmal bone cyst, osteoblastoma, chondroblastoma and chondrosarcoma. Twenty-six patients were included for the statistical analysis (embolization group) as they were operated within 0-48 h within preoperative embolization. A control group (non-embolization group, n = 28) with bone tumor having similar histological diagnosis and operated without embolization was retrieved from hospital record for statistical comparison. RESULTS: The mean intraoperative blood loss was 1300 mL (250-2900 mL), the mean intraoperative blood transfusion was 700 mL (0-1400 mL) and the mean surgical time was 221 ± 76.7 min for embolization group (group I, n = 26). Non-embolization group (group II, n = 28), the mean intraoperative blood loss was 1800 mL (800-6000 mL), the mean intraoperative blood transfusion was 1400 mL (700-8400 mL) and the mean surgical time was 250 ± 69.7 min. On comparison, statistically significant (P < 0.001) difference was found between embolisation group and non-embolisation group for the amount of blood loss and requirement of blood transfusion. There was no statistical difference between the two groups for the surgical time. No patients developed any angiography or embolization related complications. CONCLUSION: Preoperative embolization of bone tumors is a safe and effective adjunct to the surgical management of primary bone tumors that leads to reduction in intraoperative blood loss and blood transfusion volume. PMID:27158424

  7. Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3.

    Science.gov (United States)

    Robichaud, N; del Rincon, S V; Huor, B; Alain, T; Petruccelli, L A; Hearnden, J; Goncalves, C; Grotegut, S; Spruck, C H; Furic, L; Larsson, O; Muller, W J; Miller, W H; Sonenberg, N

    2015-04-16

    The progression of cancers from primary tumors to invasive and metastatic stages accounts for the overwhelming majority of cancer deaths. Understanding the molecular events which promote metastasis is thus critical in the clinic. Translational control is emerging as an important factor in tumorigenesis. The messenger RNA (mRNA) cap-binding protein eIF4E is an oncoprotein that has an important role in cancer initiation and progression. eIF4E must be phosphorylated to promote tumor development. However, the role of eIF4E phosphorylation in metastasis is not known. Here, we show that mice in which eukaryotic translation initiation factor 4E (eIF4E) cannot be phosphorylated are resistant to lung metastases in a mammary tumor model, and that cells isolated from these mice exhibit impaired invasion. We also demonstrate that transforming growth factor-beta (TGFβ) induces eIF4E phosphorylation to promote the translation of Snail and Mmp-3 mRNAs, and the induction of epithelial-to-mesenchymal transition (EMT). Furthermore, we describe a new model wherein EMT induced by TGFβ requires translational activation via the non-canonical TGFβ signaling branch acting through eIF4E phosphorylation.

  8. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  9. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  10. Bifunctional Bisphosphonates for Delivering Biomolecules to Bone

    Science.gov (United States)

    2012-01-13

    different when p< 0.05. RESULTS AND DISCUSSION Bone tissue is the most preferential site for cancer metastasis . Breast, lung , and prostate...skeletal diseases, such as osteoporosis, bone metastasis , Paget’s disease, hypercalcemia, osteoarthritis, etc. Similarly, there are many therapeutic...osteoporotic 19 bone fractures, other bone diseases, such as osteosarcoma and osteoarthritis, also require a surgical replacement of bone

  11. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  12. Establishment and evaluation of bone invasion/metastasis model for human neuroblastoma%人类神经母细胞瘤骨侵袭与转移模型的建立和评价

    Institute of Scientific and Technical Information of China (English)

    赵红宇; 李帅; 徐东; 马良; 蔡炜嵩

    2011-01-01

    OBJECTIVE:To establish bone invasion and metastasis animal model of neuroblastoma (NB) for longterm research and treatment. METHODS: SMS-SAN and SMS-KCNR NB cells were inoculated into bone marrow cavity and tail vein, respectively. High-resolution radiographic imaging and HE staining were utilized to observe bone invasion and metastasis features, kaplan-meier curve analysis and log-rank test were used to evaluate progression-free survival and overall survival between bone invasion and bone metastasis models. RESULTS: All of 5 animals were able to form osteolytic lesions in bone invasion models in both NB cell lines, respectively, both of NB cell lines develop metastasis in bones of part of xenograft models (SMS-SAN.. 5, SMS-KCNR: 6)injected systemically, respectively. Regardless of SMS-SAN and SMS-KCNR cells lines, between two group xenograft models there was significant difference in progression-free survival analysis, and in overall survival analysis (P<0.000 1). CONCLUSION: This model mimic human NB invasive and metastatic characteristics, will increase our understanding of the biology of bone metastases mechanism.%目的:探讨如何建立适合长期研究与治疗的人类神经母细胞瘤(NB)骨侵袭/转移的动物模型,方法:将SMS-KCNR和SMS-SAN细胞采用骨髓腔内注射和静脉注射的方法分别种植到雌性无胸腺裸鼠及Cb-17/IcrHsd-重度联合免疫缺陷(SCID)变异小鼠体内.通过观测放射影像学表现,HE染色病理组织切片,观察肿瘤细胞对骨的侵袭情况,应用Kaplan-Meier曲线分析及Log-rank检验,对实验动物进行生存状况分析.结果:SMS-SAN和SMS-KCNR细胞系细胞在骨髓内直接种植后在全部试验动物中均可以侵袭骨质形成溶骨性病变;同样,在静脉注射后2种细胞系细胞均可以在部分实验动物体内(SMS-SAN:5只;SMS-KCNR:6只)经血行转移到骨或骨髓,并进一步侵袭骨皮质.在骨侵袭模型和骨转移模型之间,2种细胞在无进展生存

  13. Calculation of the Dose of Samarium-153-Ethylene Diamine Tetramethylene Phosphonate (153Sm-EDTMP as a Radiopharmaceutical for Pain Relief of bone Metastasis

    Directory of Open Access Journals (Sweden)

    Fatemeh Razghandi

    2016-04-01

    Full Text Available Introduction One of the important applications of nuclear physics in medicine is the use of radioactive elements as radiopharmaceuticals. Metastatic bone disease is the most common form of malignant bone tumors. Samarium-153-ethylene diamine tetramethylene phosphonate (153Sm-EDTMP as a radiopharmaceutical is used for pain palliation. This radiopharmaceutical usually emits beta particles, which have a high uptake in bone tissues. The purpose of this study was to calculate the radiation dose distribution of 153Sm-EDTMP in bone and other tissues, using MCNPX Monte Carlo code in the particle transport model. Materials and Methods Dose delivery to the bone was simulated by seeking radiopharmaceuticals on the bone surface. The phantom model had a simple cylindrical geometry and included bone, bone marrow, and soft tissue. Results The simulation results showed that a significant amount of radiation dose was delivered to the bone by the use of this radiopharmaceutical. Conclusion Thebone acted as a fine protective shield against rays for the bone marrow. Therefore, the trivial absorbed dose by the bone marrow caused less damage to bone-making cells. Also, the high absorbed dose of the bone could destroy cancer cells and relieve the pain in the bone.

  14. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

    Science.gov (United States)

    Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

    2016-08-01

    Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

  15. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    Directory of Open Access Journals (Sweden)

    Quarto Rodolfo

    2010-01-01

    Full Text Available Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

  16. Apropos of a case of cutaneous metastasis from laryngeal cancer with review of literature

    Directory of Open Access Journals (Sweden)

    Romeeta Trehan

    2015-01-01

    Full Text Available Cutaneous metastasis from laryngeal carcinoma is a rare occurrence. A 55-year-old male patient with supraglottic cancer was treated with concurrent chemoradiation. Eighteen months later, he presented with ulceroproliferative growth on dorsum of the right hand. Biopsy revealed metastatic squamous cell carcinoma. Further investigations revealed underlying bone destruction with lung metastasis. In view of poor general condition and widespread dissemination of disease, palliative radiotherapy was delivered to the hand of the patient. He achieved satisfactory palliation in form of pain relief, control of bleeding, and discharge. The present report serves to emphasize the importance of properly diagnosing metastatic spread to unusual sites. Such metastasis is rare and is associated with a poor prognosis. Treatment is usually aimed at providing pain relief in these patients with limited life expectancy. Hence, we present a case of extensive cutaneous metastasis from laryngeal carcinoma with review of the literature.

  17. P62: An emerging oncotarget for osteolytic metastasis

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2016-03-01

    Full Text Available Bone metastasis occurs in the majority of late-stage tumors with poor prognosis. It is mainly classified as osteoblastic metastasis and osteolytic metastasis. The pathogenesis of osteolytic metastasis is a “vicious cycle” between tumor cells and bone cells (primarily the osteoclasts, which is mediated by secretory factors. The P62 adapter protein is a versatile multitasker between tumor cells and bone cells. The overexpression of P62 has been detected among a variety of tumors, playing positive roles in both tumorigenesis and metastasis. Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially for osteolytic metastasis. Recent research has shown that a P62 DNA vaccine triggered effective anti-tumor, anti-metastatic and anti-osteoporotic activities. Growing lines of evidence point to P62 as an emerging oncotarget for osteolytic metastasis. In this review, we outline the different roles of P62 in tumor cells and osteoclasts, focusing on the P62-related signaling pathway in key steps of osteolytic metastasis, including tumorigenesis, metastasis and osteoclastogenesis. Finally, we discuss the newest observations on P62 as an oncotarget for osteolytic metastasis treatment.

  18. Metastasis of Prostate Adenocarcinoma to the Testis

    Science.gov (United States)

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  19. Influences of coupled medicinal-Shechuangzi (Fructus Cnidii) and Buguzhi(Fructus Psoraleae)on survival time and bone injury in nude mice with breast cancer with bone metastasis%药对蛇床子—补骨脂对乳腺癌骨转移裸鼠生存时间与骨损伤的影响

    Institute of Scientific and Technical Information of China (English)

    程旭锋; 刘琦; 刘胜; 张新峰; 杨顺芳

    2012-01-01

    Objective To study the influences of coupled medicinal-Shechuangzi (Fructus Cnidii) and Buguzhi {Fructus Psorakae) on survival time, activity of osteoclast and bone injury in nude mice with breast cancer with bone metastasis, and discuss the best combination of the coupled medicinal in the treatment of breast cancer with bone metastasis. Methods The model of nude mouse was established by using left ventricle injection of MDA-MB-231BO cells. The effect of coupled medicinal-Shechuangzi and Buguzhi(2. 56 g/mouse) was observed taking zoledronic acid as a positive control medicinal. All nude mice (n =84) were randomly divided into(0.2 mg/kg) group A and group B (each n =42), and each group were randomly divided again into model group, zoledronic acid group, 4 parts Shechuangzi to 0 part Buguzhi group (4 to 0 group) , 0 part Shechuangzi to 4 parts Buguzhi group (0 to 4 group) , 1 part Shechuangzi to 3 parts Buguzhi group (1 to 3 group), 2 parts Shechuangzi to 2 parts Buguzhi group (2 to 2 group), 3 parts Shechuangzi to 1 parts Buguzhi group (3 to 1 group, each re =6). A normal group (n = 6) was additionally set into group B. The survival time was observed in group A after intervention by different proportions of medicinal. The samples were collected 6 weeks after intervention by different proportions of medicinal in group B. The changes of morphology and quantity of osteoclasts were observed after TRACP staining, and the expressions of genes and proteins of M-CSF and PTHrP were detected in bone metastasis focus. Results The survival time was significantly prolonged in all intervention groups in nude mouse model (P <0. 05, P <0. 01), and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The activity of osteoclasts was inhibited to some extent in all intervention groups (P < 0. 05, P < 0. 01 ) , and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The expressions of

  20. 核素骨扫描与MRI对肺癌脊柱骨转移癌灶的检出情况比较%Comparison of radionuclide bone scan and MRI for vertebral metastasis detection from lung cancer tumor

    Institute of Scientific and Technical Information of China (English)

    李海文; 司素梅

    2013-01-01

    Objective To compare radionuclide bone scan and MRI for vertebral metastasis detection fromlung cancer tumor.Methods 45 cases with lung cancer were collected for radionuclide bone scan and MRI scan,the scanning time within 15 days.Three deputy directors read the piece,the detection rate of two kinds of examination methods was compared.Results 35 cases were detected by radionuclide bone scan and MRI (x2 =0.135,P >0.05).It was detected 84 positive bone metastases vertebral,detected in 45 of radionuclide bone scan,MRI detected73,the difference was significant (x2 =15.300,P < 0.05).Conclusion MRI can effectively detect lung cancer spine bone vertebral metastasis loci without false positive lesions,which contribute to the diagnosis and treatment of disease,worthy of clinical promotion.%目的 比较核素骨扫描与MRI对肺癌脊柱骨转移癌灶的检出情况.方法 对45例肺癌患者均行核素骨扫描与MRI扫描,两次扫描时间在15 d内,由3名副主任医师阅片,比较两种检查方法检出情况.结果 核素骨扫描与MRI共检出阳性病例35例,两种方法检出率差异无统计学意义(x2 =0.135,P>0.05);两种方法共检出84个阳性骨转移瘤椎体,其中核素骨扫描检出45个,MRI检出73个,两种方法差异有统计学意义(x2=15.300,P <0.05).结论 MRI可有效地检出肺癌脊柱骨椎体转移癌灶且不存在假阳性病灶,有助于疾病的诊断治疗,值得临床推广.

  1. Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.

    Science.gov (United States)

    Ofo, Enyinnaya; Mandavia, Rishi; Jeannon, Jean-Pierre; Odell, Edward; Simo, Ricard

    2014-01-01

    Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treated 8 years previously for a pT3b N0 M1 clear cell carcinoma of the right kidney with a right nephrectomy, and interferon immunotherapy for 18 months. The patient had originally presented to the plastic surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of the left forearm, which was excised with histology revealing metastatic renal (clear) cell carcinoma. Renal cell carcinoma has a reputation for unpredictable patterns of metastasis, and our case highlights this, with the first description in the literature of parathyroid gland metastasis. Despite the poor prognosis associated with metastatic renal cell carcinoma, our patient is still alive 10 years following original presentation, despite having metastasis to two different extra-renal sites and a shortened course of initial adjuvant systemic therapy. In parathyroid gland metastasis, metastectomy can offer excellent local long term local control. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. [A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].

    Science.gov (United States)

    Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji; Horimasu, Yasushi; Nakashima, Taku; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Murakami, Yuji; Hamada, Hironobu; Nagata, Yasushi; Hattori, Noboru

    2017-06-01

    Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

  3. 参苓白术散加味治疗肺癌骨转移的临床研究%Clinical Study on Analgesic Effect of Shen-ling-bai-zhu Powder on Pain in Bone Metastasis of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    丰哲; 练克俭; 林宗汉; 李书振; 陈涛; 程琦

    2013-01-01

    目的:观察参苓白术散加味治疗肺癌骨转移的疗效。方法:将128例本病患者随机分为治疗组和对照组各64例。治疗组采用参苓白术散加味治疗,对照组采用帕米膦酸二钠、塞来西布结合支持疗法治疗。观察比较两组患者镇痛效果、生存质量、生存期。结果:治疗组脱落5例,对照组脱落8例;综合疗效总有效率治疗组为66.1%,对照组为44.6%,治疗组优于对照组(P<0.05);止痛效果总有效率治疗组为71.2%,对照组为42.9%,治疗组优于对照组,差异有统计学意义(P<0.05);生活质量的改善对照组提高率为28.6%,治疗组提高率为59.3%,治疗组优于对照组,差异有统计学意义(P<0.05);两组治疗前后体重变化、两组生存期比较,差异均无统计学意义(P>0.05);治疗组治疗后白细胞计数优于对照组(P<0.05);并能显著改善恶心呕吐、便秘(P<0.01)。结论:参苓白术散加味能较好地缓解肺癌骨转移疼痛,提高生存质量,而且未见明显毒副作用。%Objective: To observe the analgesic effect on pain by Shen-ling-bai-zhu powder in bone metastasis of lung cancer. Methods: 128 patients were randomly divided into treatment and control groups, 64 cases in each group. Patients were treated with Shen-ling-bai-zhu powder, and pamidronate disodium and celecoxib, combined with support therapy in control group. The analgesic effect, quality of life, survival rate was observed. Results: The displacement was 5 and 8 cases respec-tively in treatment and control group; The total comprehensive effective rate was 66.1% and 44.6% respectively in treatment and control group, the effect of treatment group was significantly better than the control group (P<0.05); The comprehensive ef-fective rate of analgesic was 71.2% and 42.9% respectively in treatment and control group, the effect of treatment group was significantly better than the

  4. The Patients with Cancer Evaluation the Relationship Between Alkaline Phosphatase Level and Number of Lesions Detected on Bone Scintigraphy

    Directory of Open Access Journals (Sweden)

    Zekiye Hasbek

    2014-09-01

    Results: Fifty three of 102 patients had breast cancer; 16 patients had lung cancer; 16 patients had prostate cancer; 3 patients had ovary carcinoma, 2 patients had testicle cancer; 2 patients had endometrium cancer; 2 patients had pancreas cancer; 2 patients had gastric cancer; patients had thyroid cancer; 2 patients had rectum cancer; 1 patient had esophagus cancer and 1 patient had bladder cancer. The mean value of serum ALP level was higher in patients with bone metastasis than in patients without bone metastasis. The mean serum level of ALP was; 92.76+/-26 IU/L in patients with single bone involvement; 106.18+/-22 IU/L in patients with two bones involvement; 302.92+/-210 IU/L in patients with more than three-bones involvement and 70.07+/-17 IU/L in patients without bone metastasis. Conclusion: In our study, while ALP levels were within normal values at patients without metastatic bone lesion and patients monitored with single metastasis, and these were above normal values at patients with 2 lesion; there was a significant increase at patients with 3 or more lesions. Consequently, it and #8217;s been thought that controlling the ALP level of patients who had bone scintigraphy for evaluation of the skeletal system metastasis increase the specificity of the bone scintigraphy. [J Contemp Med 2014; 4(3.000: 128-132

  5. SPECT全身骨显像、血清tPSA及fPSA/tPSA比值及病理分级与前列腺癌骨转移的关系探讨%Correlative Study of SPECT Bone Scan, Serum tPSA and fPSA / tPSA Ratio and the Pathological Grade of Prostate Cancer with Bone Metastasis

    Institute of Scientific and Technical Information of China (English)

    徐海青; 段俊

    2011-01-01

    fPSA/tPSA ratio and whole body bone imaging studies and pathological classification. Results 107 patients with prostate cancer: 49 patients had bone metastases; accounting for 45.8% (49/107 ); in which groups of different pathological comparison between the incidence of bone metastasis significantly; the lower the degree of differentiation; the more the incidence of bone metastases high; with elevated levels of tPSA; the incidence of bone metastasis increased significantly; serum tPSA4 ~ 40 ng / ml; the use of fPSA/tPSA ratio may improve the diagnostic specificity of prostate cancer. Conclusion Patients with bone metastases of prostate cancer incidence and degree of differentiation of prostate cancer; serum PSA levels and fPSA/tPSA ratio of a certain relationship. The lower degree of differentiation; the higher the incidence of bone metastasis.%目的:探讨SPECT全身骨显像、血清tPSA水平、fPSA/tPSA比值及前列腺癌病理分级与前列腺癌骨转移的关系,并研究其发生骨转移的规律和特点.方法:以核医学SPECT全身骨显像为金标准,回顾性分析了体外放免法测定的107例前列腺癌患者的血清PSA(前列腺特异抗原)水平、血清fPSA/tPSA比值及全身骨显像和病理分级.结果:107例前列腺癌患者:49例发生骨转移,占45.8%(49/107),其中不同病理分组之间骨转移发生率比较差异有统计学意义,分化程度越低,骨转移发生率越高;随着tPSA水平的升高,骨转移的发生率明显增加;血清tPSA(4~40)ng/ml时,采用fPSA/tPSA比值,可明显提高前列腺癌诊断特异性.结论:前列腺癌患者骨转移发生率与前列腺癌的分化程度、血清PSA水平及fPSA/tPSA比值有一定的关系.分化程度越低,骨转移发生率越高.

  6. MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies.

    Directory of Open Access Journals (Sweden)

    Yunhui Zeng

    Full Text Available To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC.Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis.A total of 18 studies (n = 3271 met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29. The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00. In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33. No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000.Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.

  7. Intramedullary metastasis.

    Science.gov (United States)

    Moffie, D; Stefanko, S Z

    1980-01-01

    Three cases of intramedullary metastases and one of a metastasis into the medulla oblongata are described. In two cases the primary tumour was a bronchial carcinoma and in one case a carcinoma of the breast. In one patient a primary tumour could not be found. The literature on this condition is reviewed and the difficulties of clinical diagnosis are discussed. The question remains unanswered as to the mechanism by which these tumour-cells reach the spinal cord and there is, as yet, no satisfactory explanation for the relative rare occurrence of these metastases.

  8. Clinical Study of Whole Body Diffusion-Weighted Imaging in Diagnosing Bone Metastasis of Malignant Tumors%全身弥散加权成像对恶性肿瘤骨转移的临床应用

    Institute of Scientific and Technical Information of China (English)

    牛磊; 朱斌; 崔文; 朱蒙蒙; 王明浩; 刘圆圆; 尤传文

    2011-01-01

    Objective To investigate the clinical value of whole body MR diffusion weighted imaging(WB-DWI) in diagnosis of bone metastases in patients with malignant tumors. Methods Totally 62 patients with malignant tumors and suspected bone metastases were enrolled. All patients underwent WB-DWI and bone scintigraphy within 2 weeks. The skeletal system included 10 regions:skull , cervical spine , thoracic spine , lumbar spine , sacrum, rib , scapula , pelvic bone and femur. Hot spots or cold spots on bone scintigraphic images and hyperintensity on WB-DWI were considered as metastatic foci. The numbers of foci detected by borh scintigraphy and MR imaging were compared. Results In 62 cases,362 and 281 pathological lesions were detected by bone scintigraphy and WB-DWI, respectively. More metastases of lymph nodes and extraskeletal organs were found with WB-DWI compared with that of scintigraphy. Conclusion WB-DWI is of significant value in diagnosing bone metastasis,it combined with skeletal scintigraphy can gain more informations in dewecting bone metastases.%目的 研究全身弥散加权成像(WBDWI)对恶性肿瘤远处骨转移的临床应用.方法 62例经病理证实的恶性肿瘤患者,均在2周内分别行WBDWI及核素骨显像.将骨骼分为10个部位分析,分别为颅骨、胸骨、颈椎、胸椎、腰椎、骶椎、肋骨、肩胛骨、骨盆、股骨.以核素骨显像见异常浓聚灶或稀疏灶,WBDWI见高信号为阳性,分析比较两者所显示的病灶数.结果 62例患者中,WBDWI显示362处病灶,核素骨显像显示281处病灶.WBDWI可以发现更多的骨外器官及淋巴结的病变.结论 WBDWI对骨转移具有很好的诊断价值,可以与核素骨显像互相补充,为临床提供更加全面的信息.

  9. Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

    Science.gov (United States)

    Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

  10. Contemporary approaches for imaging skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    David Ulmert; Lilja Solnes; Daniel LJ Thorek

    2015-01-01

    The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges.

  11. Some hot issues in the treatment of bone metastasis of breast cancer: interpretation of Expert Consensus on the Diagnosis and Treatment of Bone Metastasis and Skeletal Related Diseases in Breast Cancer (2014 version)%乳腺癌骨转移治疗的若干热点问题思考和讨论:乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2014版)解读

    Institute of Scientific and Technical Information of China (English)

    王如良; 江泽飞

    2015-01-01

    乳腺癌是女性最常见的恶性肿瘤,骨转移引起的骨痛、病理性骨折等骨相关事件可严重影响患者的生命质量.2014年中国抗癌协会乳腺癌专业委员会组织相关专家再次讨论制定了"乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2014版)",文章对其中若干热点问题进行一些思考及探讨.%Breast cancer is the most common malignant tumor in women, bone related events (SREs), such as bone pain, pathological fracture and so on, can affect seriously the quality of life.Experts in Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) discussed the Consensus on the Diagnosis and Treatment of Bone Metastasis and Skeletal Related Diseases in Breast Cancer (2014 version), here reflections on several hot issues were explored.

  12. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  13. Control of bone resorption by semaphorin 4D is dependent on ovarian function.

    Directory of Open Access Journals (Sweden)

    Romain Dacquin

    Full Text Available Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D -/- mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D -/- mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function.

  14. A Case Report of Gastric Carcinoma with Bone Marrow Metastasis and Thrombotic Thrombocytopenic Purpura%胃癌骨髓转移并血栓性血小板减少性紫癜一例报告

    Institute of Scientific and Technical Information of China (English)

    丁宁; 宋永波

    2011-01-01

    Objective To improve the recognition of thrombotic thrombocytopenic purpura(TTP)and reduce misdiagnosis rate.Methods The clinical data of a patient with gastric carcinoma and bone marrow metastasis and TTP were retrospectively analyzed.Results The patient was admitted to our hospital for unknown fever and anemia.Then he had hematemesis and was diagnosed as having gastric carcinoma by gastroscope.Manifested as having progressive consciousness disorders,thrombocytopenia, hemolytic anemia gradually during the course of disease, the patient underwent blood smear detection,which showed lobe erythrocytes, and then he was diagnosed as having gastric carcinoma with bone marrow metastasis and TTP.Conclusion We should pay attention to TTP when a patient with non-hematological system disease suffers from progressive anemia and thrombocytopenia.%目的 提高对血栓性血小板减少性紫癜(thrombotic thrombocytopenic punpura,TTP)的认识,以减少误诊.方法 回顾分析1例胃癌骨髓转移并TTP的临床资料.结果 患者以发热、贫血原因待查入院,入院后出现呕血,胃镜检查确诊为胃癌.病程中出现进行性意识障碍、血小板减少及溶血性贫血,血涂片可见裂片红细胞,确诊为胃癌骨髓转移并TTP.结论 对非血液系统恶性肿瘤患者出现进行性贫血、血小板减少等表现时,应注意合并TTP.

  15. The circadian modulation of leptin-controlled bone formation

    Science.gov (United States)

    Mice with circadian gene Period and Cryptochrome mutations develop high bone mass early in life. Such a phenotype is accompanied by an increase in osteoblast numbers in mutant bone and cannot be corrected by leptin intracerebroventricular infusion. Thus, the molecular clock plays a key role in lepti...

  16. Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell–derived ADAM9

    Science.gov (United States)

    Mammadova-Bach, Elmina; Zigrino, Paola; Brucker, Camille; Bourdon, Catherine; Freund, Monique; Abrams, Scott I.; Orend, Gertaud; Gachet, Christian

    2016-01-01

    Metastatic dissemination of cancer cells, which accounts for 90% of cancer mortality, is the ultimate hallmark of malignancy. Growing evidence suggests that blood platelets have a predominant role in tumor metastasis; however, the molecular mechanisms involved remain elusive. Here, we demonstrate that genetic deficiency of integrin α6β1 on platelets markedly decreases experimental and spontaneous lung metastasis. In vitro and in vivo assays reveal that human and mouse platelet α6β1 supports platelet adhesion to various types of cancer cells. Using a knockdown approach, we identified ADAM9 as the major counter receptor of α6β1 on both human and mouse tumor cells. Static and flow-based adhesion assays of platelets binding to DC-9, a recombinant protein covering the disintegrin-cysteine domain of ADAM9, demonstrated that this receptor directly binds to platelet α6β1. In vivo studies showed that the interplay between platelet α6β1 and tumor cell–expressed ADAM9 promotes efficient lung metastasis. The integrin α6β1–dependent platelet-tumor cell interaction induces platelet activation and favors the extravasation process of tumor cells. Finally, we demonstrate that a pharmacological approach targeting α6β1 efficiently impairs tumor metastasis through a platelet-dependent mechanism. Our study reveals a mechanism by which platelets promote tumor metastasis and suggests that integrin α6β1 represents a promising target for antimetastatic therapies. PMID:27699237

  17. Osteosarcoma relapse as pleural metastasis

    OpenAIRE

    Debabrata Saha; Kaushik Saha; Arpita Banerjee; Debraj Jash

    2013-01-01

    Osteosarcoma is the most common primary bone tumor in children and young adults arising from primitive mesenchymal bone-forming cells. The lung is the most common site of metastasis of osteosarcoma. Here, we report a case of a 14-year-old male patient having osteosarcoma of tibia presenting to us for evaluation of left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast-enhanced computed tomography thorax revealed a large, heterogeneous, calcified mass (+277 H.U) at left up...

  18. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  19. PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells.

    Science.gov (United States)

    Jilg, Cordula A; Ketscher, Anett; Metzger, Eric; Hummel, Barbara; Willmann, Dominica; Rüsseler, Vanessa; Drendel, Vanessa; Imhof, Axel; Jung, Manfred; Franz, Henriette; Hölz, Stefanie; Krönig, Malte; Müller, Judith M; Schüle, Roland

    2014-12-30

    The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation. Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). SPAG9 and PRK1 colocalize in human cancer tissue and are required for p38-phosphorylation and cell migration. Accordingly, depletion of either ETS domain-containing protein Elk-1 (ELK1), an effector of p38-signalling or p38 depletion hinders cell migration and changes expression of migration-relevant genes as observed upon PRK1-depletion. Importantly, a PRK1 inhibitor prevents metastases in mice, showing that the PRK1-pathway is a promising target to hamper prostate cancer metastases in vivo. Here we describe a novel mechanism controlling the metastatic behavior of PCa cells and identify PRK1 as a promising therapeutic target to treat androgen-independent metastatic prostate cancer.

  20. Functional Interactions Between Laminin-10, alphaV beta3 Integrin and Matrix Metalloproteinase-9 in Promoting Breast Cancer Metastasis to Bone

    Science.gov (United States)

    2005-08-01

    Slavin, J., and Anderson, R. L. (1999) Clin Exp Metastasis 17, 163-170 3. Eckhardt, B. L., Parker, B. S., van Laar, R. K., Restall , C. M., Natoli, A. L...Medecine Science, supplement no2 (99) p.36A. Meeting Presentations: 1. Pouliot N., E. Sloan, A.L. Natoli, B. Eckhardt, C.M. Restall , B. Parker, L...Australia. 2. Pouliot N., C.M. Restall , A.L. Natoli, 0. Narayan and R.L. Anderson (2003). The role of MMP-9 and its regulation by tumour/stromal

  1. IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling.

    Science.gov (United States)

    Lu, Jinchang; Song, Guohui; Tang, Qinglian; Zou, Changye; Han, Feng; Zhao, Zhiqiang; Yong, Bicheng; Yin, Junqiang; Xu, Huaiyuan; Xie, Xianbiao; Kang, Tiebang; Lam, YingLee; Yang, Huiling; Shen, Jingnan; Wang, Jin

    2015-05-01

    Osteosarcoma is a common malignant bone tumor with a propensity to metastasize to the lungs. Epigenetic abnormalities have been demonstrated to underlie osteosarcoma development; however, the epigenetic mechanisms that are involved in metastasis are not yet clear. Here, we analyzed 2 syngeneic primary human osteosarcoma cell lines that exhibit disparate metastatic potential for differences in epigenetic modifications and expression. Using methylated DNA immunoprecipitation (MeDIP) and microarray expression analysis to screen for metastasis-associated genes, we identified Iroquois homeobox 1 (IRX1). In both human osteosarcoma cell lines and clinical osteosarcoma tissues, IRX1 overexpression was strongly associated with hypomethylation of its own promoter. Furthermore, experimental modulation of IRX1 in osteosarcoma cell lines profoundly altered metastatic activity, including migration, invasion, and resistance to anoikis in vitro, and influenced lung metastasis in murine models. These prometastatic effects of IRX1 were mediated by upregulation of CXCL14/NF-κB signaling. In serum from osteosarcoma patients, the presence of IRX1 hypomethylation in circulating tumor DNA reduced lung metastasis-free survival. Together, these results identify IRX1 as a prometastatic gene, implicate IRX1 hypomethylation as a potential molecular marker for lung metastasis, and suggest that epigenetic reversion of IRX1 activation may be beneficial for controlling osteosarcoma metastasis.

  2. Evaluation of genotoxic and cytotoxic effects of {sup 153} Sm-EDTMP in peripheral blood lymphocytes of bone metastasis patients; Avaliacao dos efeitos genotoxico e citotoxico do {sup 153} Sm-EDTMP em linfocitos perifericos de pacientes com metastase ossea

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Miriam Fussae

    2003-07-01

    In this study the cellular damage in peripheral lymphocytes after exposure to {sup 153} Sm-EDTMP (Samarium-153 ethylene-diamine-tetramietylene-phosphonate) was determined using the technique of micronuclei analysis and differential coloration.{sup 153} Sm-EDTMP is a radiopharmaceutical used for pain relief in patients with bone metastases. The analysis of the frequency of micronuclei in patient blood samples obtained one hour after endovenous administration of radiopharmaceutical (41 MBq/kg) showed no statistical difference in relation to basal values in binucleated cells. However the analysis of damage distribution in mononucleated cells, showed that the patients without previous radiotherapy treatment presented a significant increase in the frequency of cells with one micronucleus and in those who had taken previous radiotherapy treatment, in cells with two or more micronuclei. The in vitro experiments conducted with the exposition of total blood to three radiation concentrations of {sup 153} Sm-EDTMP (0.370, 0.555 and 1.110 MBq/mL) during one hour showed an increase in the frequency of micronuclei and necrotic and apoptotic cells with increasing radiation dose. Dose-response curves for healthy donors and patients with bone metastasis without previous radiotherapy treatment were constructed. The comparison of the curves showed that patients presented higher radiosensitivity, either micronuclei or dead cell (necrotic or apoptotic) percentages, than healthy donors. (author)

  3. Expression of Preprotachykinin-I(PPT-I), Neurokinin-1(NK-1) and Neurokinin-2(NK-2) in Breast Cancer Cells Improves Tumor Cell Survival in Bone Marrow in the Early Stage of Metastasis

    Institute of Scientific and Technical Information of China (English)

    Huilai Zhang; Huaqing Wang; Pengfei Liu; Zhi Yao; Xishan Hao

    2009-01-01

    OBJECTIVE To study the potential relationship between the expression of PPT-I, NK-1, NK2 and the development of breast cancer cells in bone marrow stroma and to provide evidence of potential molecular mechanisms of bone metastasis in early stage of breast cancer patients.METHODS The cocultures of breast cancer cell line T-47D and marrow-derived mesenchymal stem cells (MSC) were established with equal numbers. T-47D cells were separated from the coculture system at 48 h and 96 h after coculture by MACS magnetic cell sorting (MicroBeads). The expression of PPT-I, NK-1, NK-2 in T-47D was then examined before and after coculture by real-time PCR and by Western blot. Alterations in cellular ultrastructure of T-47D cells were detected before and after coculture under electron microscope. Finally, changes in cell cycle distribution were examined by flow cytometry, and growth curves from before and after coculture were drawn and analyzed. RESULTS Following coculture of T-47D and MSC, the expression of PPT-I mRNA and protein was significantly upregulated, while the expression of NK-1 and NK-2 mRNA and protein was greatly downregulated. The analysis of cell cycle distribution by flow cytometry showed that the proportion of T-47D during S phase was increased, and the duration of the G2/M phase was sharply decreased. Under electron microscope, we observed that the synthesis of hereditary material was increased, but the hepatin granules were shown prominent stacking in T-47D cells. These results suggest that although the synthesis of DNA was increased, the proliferation of cells was inhibited after coculture. The cellgrowth curve confirmed the findings from the observation under the electron microscope and flow cytometry. CONCLUSION Tumor cells could survive through the upregulation in expression of preprotachykinin-I gene during early bone metastasis in breast cancer. The phenomenon of growth suppression in breast cancer cells after coculture in the current study could be

  4. 68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml

    DEFF Research Database (Denmark)

    Petersen, Lars J; Nielsen, Julie B; Dettmann, Katja

    2017-01-01

    /computed tomography ((68)Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on (68)Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (.../ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with (18)F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, (68)Ga-PSMA PET/CT is promising for the restaging of patients......Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography...

  5. Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article).

    Science.gov (United States)

    Xie, Guang-Lun; Guo, Da-Peng; Li, Zhi-Gang; Liu, Chang; Zhang, Wei

    2016-10-01

    This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy.This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively.Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P management as compared with that before management (all P management in nausea and vomiting, and constipation.CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application.

  6. Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article)

    Science.gov (United States)

    Xie, Guang-lun; Guo, Da-peng; Li, Zhi-gang; Liu, Chang; Zhang, Wei

    2016-01-01

    Abstract This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy. This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively. Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P management as compared with that before management (all P management in nausea and vomiting, and constipation. CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application. PMID:27749531

  7. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part.

  8. Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin-like growth factor and hypoxia.

    Science.gov (United States)

    Kuchimaru, Takahiro; Hoshino, Takuya; Aikawa, Tomoya; Yasuda, Hisataka; Kobayashi, Tatsuya; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

    2014-05-01

    Bone metastasis is a multistep process that includes cancer cell dissemination, colonization, and metastatic growth. Furthermore, this process involves complex, reciprocal interactions between cancer cells and the bone microenvironment. Bone resorption is known to be involved in both osteolytic and osteoblastic bone metastasis. However, the precise roles of the bone resorption in the multistep process of osteoblastic bone metastasis remain unidentified. In this study, we show that bone resorption plays important roles in cancer cell colonization during the initial stage of osteoblastic bone metastasis. We applied bioluminescence/X-ray computed tomography multimodal imaging that allows us to spatiotemporally analyze metastasized cancer cells and bone status in osteoblastic bone metastasis models. We found that treatment with receptor activator of factor-κB ligand (RANKL) increased osteoblastic bone metastasis when given at the same time as intracardiac injection of cancer cells, but failed to increase metastasis when given 4 days after cancer cell injection, suggesting that RANKL-induced bone resorption facilitates growth of cancer cells colonized in the bone. We show that insulin-like growth factor-1 released from the bone during bone resorption and hypoxia-inducible factor activity in cancer cells cooperatively promoted survival and proliferation of cancer cells in bone marrow. These results suggest a mechanism that bone resorption and hypoxic stress in the bone microenvironment cooperatively play an important role in establishing osteoblastic metastasis.

  9. Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover.

    Science.gov (United States)

    Metzger, Corinne E; Narayanan, Anand; Zawieja, David C; Bloomfield, Susan A

    2017-04-01

    Bone loss is a common comorbidity of inflammatory bowel disease (IBD), leading to elevated fracture risk in these patients. Inflammatory factors associated with IBD cause increased bone resorption and decreased bone formation with multiple factors implicated as instigators of these alterations. In this project, we examined the influence of IBD on osteocyte proteins in male rats (2 months old) divided into two groups: induced gut inflammation via 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, and vehicle control. We examined the prevalence of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an anti-inflammatory cytokine, interleukin-10 (IL-10), the anabolic factor insulin-like growth factor-I (IGF-I), osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin in osteocytes in three bone compartments 4 weeks after initiation of gut inflammation. Histomorphometry of the proximal tibia and fourth lumbar vertebra revealed lower bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S) with TNBS. Tibial mid-shaft periosteal BFR was also lower with TNBS. Immunohistochemical staining of the distal femur demonstrated that %TNF-α(+) , %IL-6(+) , %RANKL(+) , and %OPG(+) osteocytes were elevated in cancellous bone in TNBS animals compared to vehicle. These changes were coincident with increased bone resorption. With regression analysis, %RANKL(+) osteocytes statistically predicted the increase in cancellous Oc.S (R(2)  = 0.565). Increased %sclerostin(+) osteocytes observed in the TNBS treatment predicted declines in cancellous OS (R(2)  = 0.581) as well as BFR in cancellous and cortical bone (R(2)  = 0.674, R(2)  = 0.908, respectively). Contrary to our hypothesis, %IGF-I(+) osteocytes increased in TNBS animals. In conclusion, the IBD model produced a systemic inflammation that altered the regulatory protein profile in osteocytes that

  10. Receptor activator of NF-kB (rank) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients

    NARCIS (Netherlands)

    D. Santini (Daniele); G. Schiavon (Gaia); B. Vincenzi (Bruno); L. Gaeta (Laura); F. Pantano (Francesco); A.P. Russo (Antonio); C. Ortega (Cinzia); C. Porta (Camillo); S. Galluzzo (Sara); G. Armento (Grazia); N. La Verde (Nicla); C. Caroti (Cinzia); I. Treilleux (Isabelle); A. Ruggiero (Alessandro); G. Perrone (Giuseppe); R. Addeo (Raffaele); P. Clezardin (Philippe); A.O. Muda (Andrea Onetti); G. Tonini (Giuseppe)

    2011-01-01

    textabstractBackground: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely

  11. Effect and nursing in the treatment of bone pain related to metastasis with Strontium-89%89锶治疗恶性肿瘤骨转移性疼痛的效果和护理方法

    Institute of Scientific and Technical Information of China (English)

    冀小平; 许新华; 代文莉; 覃斌芳; 鲁明骞

    2013-01-01

    Objective To explore the effect and nursing in treatment of bone pain related to metastasis with Strontium-89. Methods The clinical data of 42 patients of malignant cancer with skeletal complications were retrospectively analyzed. Bone metastases were found by radionuclide bone imaging and proved by X-ray, CT or MRI. Strontium (Sr-89)chloride was injected and the effect and adverse effect was observed. Nursing methods were conducted by clinical nurse. Results The severity of bone pain before treatment and 12 weeks after treatment were compared, 76.2% of the 42 patients were observed pain parliament, especially those patients with mammary cancer with efficient rate of 91.7%. The general adverse reactions and hematologic toxicity after treatment were observed. The side effects were mild, 33 cases occured 1 grade reversible myelosuppression with no treatment and 1 case got 2 grade myelosuppression who was cured by treatment. Several special nursing methods were conducted by clinical nurses. Conclusion Strontium-89 are effective and safe for the management of malignant cancer related bone pain, and special nursing should be paid great attention.%目的 探讨89锶治疗骨转移癌患者疼痛的效果与护理方法.方法 42例均经病理学检查确诊的恶性肿瘤患者,经ECT及X线平片、CT、MR证实骨转移,给予氯化锶注射治疗,观察疼痛缓解效果及不良反应,并做好护理.结果 42例患者经评价疗效,患者疼痛缓解率为76.2%,其中乳腺癌效果最为明显,有效率为91.7%,不良反应主要为骨髓抑制,33例患者出现白细胞、血小板及血色素下降,占78.6%,其中1例患者出现白细胞Ⅱ度下降,其余患者均为Ⅰ度下降,无需特殊处理.结论 89锶可减轻恶性肿瘤骨转移,改善生活质量,方法简便、不良反应较少,值得临床推广应用,要注意治疗前、治疗中及治疗后的护理.

  12. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study.

    Directory of Open Access Journals (Sweden)

    Marco Atteritano

    Full Text Available OBJECTIVE: The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc. METHODOLOGY: Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. RESULTS: bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001, femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001 and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001 and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001 were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OHD3 was significantly lower. In scleroderma group the serum levels of 25(OHD3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture. CONCLUSION: Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OHD3 may play a role in the risk of osteoporosis and vertebral fractures.

  13. Comparison of Whole-body MRI and Bone Scintigraphy for Diagnosing Osseous Metastasis in Patients with Breast Cancer%全身MRI和骨扫描诊断乳腺癌骨转移比较

    Institute of Scientific and Technical Information of China (English)

    王警建; 崔尊社; 李娜

    2011-01-01

    Objective To assess the diagnostic accuracy of whole-body MR] (WB-MRI) and bone scintigraphy(BS) for osseous metastasis in patients with breast cancer. Methods Twenty-two patients with breast cancer were underwent both planar BS and WB-MRI,in order to determine whether there were osseous metastases. Results The sensitivity,specificity,diagnostic accuracy,positive and negative likehood ratio of WB-MRI were 91.7% ,90% ,90.9% ,9.17 and 0.11 and for BS those were 83.3% ,80% ,81.8% ,4.16 and 0.24,respectively. Conclusion The diagnostic efficacy of WB-MRI was superior to BS for osseous metastasis in patients with breast cancer.%目的:探讨全身MRI和骨扫描对乳腺癌患者骨转移首诊的准确性.方法:对22例乳腺癌患者行全身MRI和骨扫描检查以确定有无骨转移.结果:全身MRI和骨扫描诊断骨转移的敏感度、特异度、准确度分别为91.7%、90%、90.9%和83.3%、80%、81.8%;阳性和阴性似然比分别为9.17、0.11和4.16、0.24.结论:乳腺癌患者骨转移全身MRI效果优于骨扫描.

  14. P62: An emerging oncotarget for osteolytic metastasis

    National Research Council Canada - National Science Library

    Zhang, Jing; Yang, Zuozhang; Dong, Jian

    2016-01-01

    .... Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially...

  15. Osteosarcoma relapse as pleural metastasis

    Directory of Open Access Journals (Sweden)

    Debabrata Saha

    2013-01-01

    Full Text Available Osteosarcoma is the most common primary bone tumor in children and young adults arising from primitive mesenchymal bone-forming cells. The lung is the most common site of metastasis of osteosarcoma. Here, we report a case of a 14-year-old male patient having osteosarcoma of tibia presenting to us for evaluation of left-sided pleural effusion after 4 years of mid-thigh amputation. Contrast-enhanced computed tomography thorax revealed a large, heterogeneous, calcified mass (+277 H.U at left upper and middle lobe along with massive left-sided pleural effusion. Thoracoscopy revealed a lung metastasis in the right upper and middle lobe along with 2-cm diameter mass found on the surface of parietal pleura. Lung tumor was resected and biopsy of the pleural mass was carried out. Histopathological examination from both the masses was suggestive of metastatic osteosarcoma. The case underlines the importance of performing thoracoscopy in patients of osteosarcoma who recur with lung metastasis.

  16. Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

    Science.gov (United States)

    2011-04-01

    delivered on a collagen sponge (INFUSE Bone Graft; Medtronic) has been approved by FDA for posterior-lateral spine fusions, tibial fractures, and sinus...area was defined by drawing a quadrilateral area using the periosteal corners of the four host cortices as points of reference. The relative areas of...section of an FR +BMP scaffold in Figure 8 (the ap- proximate boundary of the implant is denoted by the box) shows a mature and fully bridged periosteal

  17. 整合素受体靶向显像诊断乳腺癌溶骨性转移%Imaging of osteolytic bone metastasis from breast cancer with new integrin αvβ3 receptor targeted radiotracer

    Institute of Scientific and Technical Information of China (English)

    邵国强; 赵有财; 崔璨; 梁凯; 孙晋; 杨瑞; 王峰

    2015-01-01

    Objective To investigate the value of integrin αvβ3 targeted micro positron emission tomography (microPET)/CT imaging with 68 Ca-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-arginine-glycine-aspartate peptide dimer (68 Ga-DOTA-RGD2) as radiotracer for the detection of breast cancer osteolytic bone metastases.Methods 68 Ga-DOTA-RGD2 was prepared via one-step method at 100 ℃ for 15 min.Animal model with parathyroid hormone (PTH)-induced osteolysis in the calvarium was established and served as PTH group (BP).Biodistribution study of 68 Ga-DOTA-RGD2 was carried out in BP.Integrin receptor block study was done with pre-injection of high dose of DOTA-RGD2.68Ga-DOTA-RGD2 and 18F-NaF micmPET/CT imaging were perfromed respectively.Breast cancer osteolyic bone metastases was established via intrcardial injection of breast cancer cells.68 Ga-DOTA-RGD2 microPET/CT imaging were perfromed for the detection of breast cancer osetolytic bone metastases.Animals were sarcrificed and bone lesions were harvested for pathological examination.Results 68 Ga-DOTA-RGD2 was stable in vitro and its radiopurity was as high as (96.4 ± 2.1) % 3 h after its preparation.Its blood elimination was fast while its uptake by the liver and kidneys were relativelylow.It was discharged soon after its intravenous injection.In the BP group,regional uptake of 68 Ga-DOTA-RGD2 in osteolytic lesion of calvarium (% ID/g) reached peak (5.14 ±0.65) 60 min after tail vein injection.It was significantly more than that in BC group (2.06 ±0.35,t =7.81,P <0.05).Bone radiotracer uptake ratio of osteolytic lesion to normal calvrium (O/N) was compared based microPET/CT imaging.Bone O/N of 68Ga-DOTA-RGD2 was (6.10 ± 0.97),significantly greater than that of 18F-NaF (1.20 ±0.33,t =10.17,P <0.05).68Ga-DOTA-RGD2 microPET/CT imaging was able to demonstrate the ostelytic bone metastasis in calvarium,thoracic vertebrae and lung metastasis.They were confirmed by pathology results.Conclusion 68 Ga

  18. PATTERN OF LUNG CANCER METASTASIS BASED ON PET CT

    Directory of Open Access Journals (Sweden)

    Harsha D. S

    2017-06-01

    Full Text Available BACKGROUND Accurate staging is the cornerstone in management of lung cancer. It helps to determine the therapeutic modality and to assess prognosis. More than half of bronchogenic carcinomas have distant metastasis at the time of diagnosis. Presence of metastasis confers stage 4 for the disease. Presence of metastasis also increases patient morbidity and mortality. So the knowledge of pattern and sites of metastasis in bronchogenic carcinoma is crucial for its detection and management. Staging of bronchogenic carcinoma is one of the important indications for Positron Emission Tomography. Combined Computed tomography and PET (PET-CT is superior to either modality alone in staging of lung cancer. It helps in identifying the site and morphology of lesion. Aims and Objectives- 1. To determine the sites of metastases in Bronchogenic carcinoma by PETCT 2. To compare sites of metastases with the histological cell type MATERIALS AND METHODS It was a hospital based retrospective study involving 78 patients with histologically proven bronchogenic carcinoma who underwent PETCT scan from June 2016-May 2017 in A J Institute of medical sciences, Mangalore. The sites of metastasis were noted. Brain metastasis was not included as MRI is a more sensitive tool. The sites of metastases as determined by PETCT were compared with histological cell type of bronchogenic carcinoma. RESULTS There were a total of 78 patients 61 male and 17 females. Majority of them were adenocarcinoma, followed by squamous cell carcinoma 38.5% and small cell carcinoma 9%. Majority had lymph node metastasis to supraclavicular nodes (61.53% followed by contralateral lung (51.28%, bone metastasis (48.71%, abdominal nodes (28.21%, pleural metastasis (25.64%, adrenals (23.1%, Liver (20.51%, pericardial effusion (3.84%, spleen (2.56%. Among cases of adenocarcinoma 65.85% had metastasis to supraclavicular nodes, 56.09% had metastasis to contralateral lung, followed by bone metastasis (53

  19. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma

    OpenAIRE

    Dirik, Yalın; Çınar, Arda; Yumrukçal, Feridun; Eralp, Levent

    2014-01-01

    INTRODUCTION: We report a case with lymph node metastasis of osteosarcoma, which is a rare entity in comparison to hematogeneous lung or bone metastasis. PRESENTATION OF CASE: Twenty-seven years old male patient referred to our clinic complaining of ongoing left knee pain and swelling since one month without a history of prior trauma. Magnetic resonance imaging (MRI) revealed a mass of malignant nature which causes more prominent expansion and destruction of the bone distally with perioste...

  20. Metástases dos ossos gnáticos: estudo retrospectivo de 10 casos Gnathic bone metastasis: a retrospective study of 10 cases

    Directory of Open Access Journals (Sweden)

    Antonio Azoubel Antunes

    2008-08-01

    Full Text Available Metástases em cavidade oral são extremamente raras, representando 1% de todas as neoplasias malignas orais. OBJETIVO: Analisar retrospectivamente a incidência de metástase nos maxilares, traçando seu perfil de comportamento epidemiológico. MATERIAL E MÉTODOS: Através de estudo retrospectivo, foram analisados o sexo, idade, localização topográfica da metástase, sítio do tumor primário e tipo histológico, no período de janeiro de 1980 a janeiro de 2000, de um total de 10 pacientes. RESULTADOS: Observou-se que 5 pacientes eram do sexo masculino (50%, 3 casos ocorreram nas 2ª e 4ª décadas de vida (30 e 30%. Concernente à localização topográfica da metástase, metade dos casos ocorreu na maxila e metade na mandíbula. A tireóide e próstata foram os sítios de tumor primário que mais metastizaram para os ossos gnáticos (3 casos cada e o adenocarcinoma foi o tipo histológico de maior ocorrência de metástase (50%. Conclusões: As metástases nos maxilares acometem igualmente faixa etária, sexo e localização topográfica. A tireóide e próstata parecem ser os sítios mais freqüentes de metástase à distância, e o adenocarcinoma o tipo histológico de maior incidência de metástase.Oral cavity metastases are extremely rare, and comprise 1% of all mouth malignant neoplasms. AIM: to retrospectively analyze the incidence of maxillary metastases, and to trace its epidemiological behavior. MATERIAL AND METHODS: A retrospective study was done of the period between January 1980 and January 2000;the following indicators were reviewed: sex, age, site of the metastasis, site of the primary tumor, and the histological type of tumors in 10 patients. RESULTS: The prevalence was similar in males and females (05 cases - 50%; three cases presented in the 2nd and 4th decades of life (30 - 30%. About half of the cases of metastases occurred in the maxilla and half in the mandible. The thyroid and prostate glands were the most prevalent

  1. RARE CASE OF COLONIC METASTASIS

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-04-01

    Full Text Available Colon cancer is the second most common type of cancer in females and the third in males worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this case report, an extremely rare case of colon adenocarcinoma with metastasis to the philtrum with extensive peritoneal and bowel involvement is presented. A 44 year old male presented with a change in bowel habits, melena and weight loss . Diagnosed to have carcinoma rectum underwent Abdominoperenial resection (APR two y ears back. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Now presented with swelling over philtrum . Fine needle aspiration (FNAC was done suggestive of adenocarcinoma. This case presented for its uncommon presentation.

  2. The behaviour of fatigue-induced microdamage in compact bone samples from control and ovariectomised sheep.

    Science.gov (United States)

    Kennedy, Oran D; Brennan, Orlaith; Mauer, Peter; O'Brien, Fergal J; Rackard, Susan M; Taylor, David; Lee, T Clive

    2008-01-01

    This study investigates the effect of microdamage on bone quality in osteoporosis using an ovariectomised (OVX) sheep model of osteoporosis. Thirty-four sheep were divided into an OVX group (n=16) and a control group (n=18). Fluorochromes were administered intravenously at 3 monthly intervals after surgery to label bone turnover. After sacrifice, beams were removed from the metatarsal and tested in three-point bending. Following failure, microcracks were identified and quantified in terms of region, location and interaction with osteons. Number of cycles to failure (Nf) was lower in the OVX group relative to controls by approximately 7%. Crack density (CrDn) was higher in the OVX group compared to controls. CrDn was 2.5 and 3.5 times greater in the compressive region compared to tensile in control and OVX bone respectively. Combined results from both groups showed that 91% of cracks remained in interstitial bone, approximately 8% of cracks penetrated unlabelled osteons and less than 1% penetrated into labelled osteons. All cases of labelled osteon penetration occurred in controls. Crack surface density (CrSDn), was 25% higher in the control group compared to OVX. It is known that crack behaviour on meeting microstructural features such as osteons will depend on crack length. We have shown that osteon age also affects crack propagation. Long cracks penetrated unlabelled osteons but not labelled ones. Some cracks in the control group did penetrate labelled osteons. This may be due the fact that control bone is more highly mineralized. CrSDn was increased by 25% in the control group compared to OVX. Further study of these fracture mechanisms will help determine the effect of microdamage on bone quality and how this contributes to bone fragility.

  3. Inguinal lymph node metastasis of colon cancer

    Directory of Open Access Journals (Sweden)

    Sloane McGraw

    2011-01-01

    Full Text Available We present a case of adenocarcinoma of colon with unusual metastasis to inguinal lymph nodes. Our patient is a young male with bilateral inguinal lymphadenopathy, bone pains, and jaundice who presented as carcinoma of unknown primary. He was diagnosed as widely metastatic adenocarcinoma of colon for which he received chemotherapy and has had a good response to the treatment.

  4. Microenvironment Determinants of Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  5. Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

    Directory of Open Access Journals (Sweden)

    Tobias Bäuerle

    2008-05-01

    Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

  6. Study on the Clinical Value of Pulmonary Tumor Markers and Bone Alkafine Phosphatase Detection in Early Diagnosis of Bone Metastasis of Lung Cancer%肺肿瘤标志物及碱性磷酸酶对肺癌骨转移早期诊断的临床意义

    Institute of Scientific and Technical Information of China (English)

    李殿波; 姜格宁

    2015-01-01

    Objective To study the clinical significance of pulmonary tumormarkers:cytokeratin19 solu-ble fragments ( CYFRA21-1 ) , carcinoembryonic antigen ( CEA ) , neuron specific enolase ( NSE ) , carbohy-drate antigen 125(CA125) and bone alkaline phosphatase(BALP) in early diagnosis of bone metastasis of lung cancer.Methods A total of 123 patients hospitalized in Linyi Tumor Hospital from Jul.2009 to Dec. 2011[including 47 cases of lung benign tumor(as the benign lung tumor group),40 cases of lung cancer without bone metastases(as the lung cancer without bone metastases group),and 36 cases of lung cancer with bone metastases( as the bone metastasis of lung cancer group ) ] were selected.The enzyme-linked immu-nosorbent assay was applied to detect the expression levels of CYFRA21-1,CEA,NSE,CA125 and BALP in the serum of all the patients,and such levels were compared among the groups.Results The expression lev-els of CYFRA 21-1,CEA,NSE,CA125,BALP of benign lung tumor group were (5.0 ±0.8) μg/L,(6.7 ± 0.5) pg/L,(18.9 ±2.5)μg/L,(29.0 ±2.8) kU/L,( 224.7 ±16.5) U/L;those of the lung cancer with-out bone metastases group were (15.1 ±2.7) μg/L,(10.6 ±1.7) pg/L,(30.2 ±4.2) μg/L,(60.1 ± 4.7) kU/L,(454.6 ±32.7) U/L;and those of the bone metastasis of lung cancer group were (29.7 ± 8.8) μg/L, (18.2 ±1.8) pg/L,(58.2 ±6.9) μg/L,(100.7 ±8.8) kU/L, (668.2 ±45.8) U/L.Such levels of the lung cancer without bone metastases group and bone metastasis of lung cancer group significantly increased compared with benign lung tumor group ( P <0.05 ).Such levels of the bone-metastasis of lung cancer group were also significantly higher than those of the lung cancer without bone metastases group ( P<0.05).Conclusion Detection of serum levels of CYFRA21-1,CEA,NSE,CA125 and BALP in patients with bone metastases of lung cancer can reveal the biological changes of such patients and has certain signifi-cance in the early diagnosis of bone-metastasis of lung cancer.%目的:探讨肺

  7. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  8. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  9. Decoding Melanoma Metastasis

    Directory of Open Access Journals (Sweden)

    Marcus Bosenberg

    2010-12-01

    Full Text Available Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  10. Cytogenetic analysis of {sup 153} Sm-EDTMP in peripheral lymphocytes from patients with bone cancer metastasis; Analise citogenetica do {sup 153} Sm-EDTMP em linfocitos perifericos de pacientes com cancer osseo matastatico

    Energy Technology Data Exchange (ETDEWEB)

    Silva, M.A. da; Suzuki, M.F.; Rogero, J.R.; Okazaki, K. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil); Guimaraes, M.I.C.C.; Buchpiguel, C.A. [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Centro de Medicina Nuclear

    2002-07-01

    The {sup 153} Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of {sup 153} Sm-EDTMP at cellular level. The present study was conducted with the aim of evaluating the cytogenetic effects of {sup 153} Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique. For that, the blood samples were collected before and one hour after the endovenous administrations of {sup 153} Sm-EDTMP (mean activity of 42.53 {+-} 5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before{sup 153} Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with {sup 153} Sm-EDTMP, did not influence these parameters. The obtained data showed that the therapy with {sup 153} Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes one hour after its administration in patients, although, theoretically, a long term stochastic effect cannot be disregarded. (author)

  11. Inhibitory Acting Mechanism of Psoralen-Osthole on Bone Metastasis of Breast Cancer-An Expatiation Viewing from OPG/RANKL/RANK System%从OPG/RANKL/RANK系统阐述补骨脂-蛇床子抑制乳腺癌骨转移的机制

    Institute of Scientific and Technical Information of China (English)

    刘胜; 吴春宇; 程旭锋; 杨顺芳; 宋晓耘

    2011-01-01

    Objective To find the optimal proportion of Composite Fructus Psoraleae and Fructus Cnidii (CFPC) for inhibiting the bone metastasis of breast cancer by way of exploring its acting mechanism viewing from OPG/RANKL/RANK system. Methods The human bone metastasis of breast cancer model was established by injecting tumor cells of MDA-MB-231 BO cell line into the left cardiac ventricle of nude mice. The modeled mice were randomly divided into seven groups: the blank group administered with normal saline by gastrogavage, the positive control group with zoledronic acid via peritoneal injection, and the 5 tested group with CFPC in different proportions of Fructus Psoraleae and Fructus Cnidii, i.e. ( A, 4:0; B, 3:1; C, 1: 1; D, 1: 3, and E 0: 4), given by gastric infusion. The treatment started from 1 week after modeling and lasted for six weeks. By the end of the experiment, the metastatic foci in bone were imaged by radionuclide tracing method and X-ray photograph, and separated for detecting gene and protein expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), interleukin-8 (IL-8), parathyroid hormone-related protein (PTHrP), macrophage colony stimulating factor (MCSF) by Real-time PCR and Westem blot respectively. Results Inhibition of bone metastasis gene was displayed to some extent in all the tested groups treated with CFPC, showing an increased level of OPG mRNA expression ( It was 60. 343 ±6.274 in the tested group C), and decreased mRNA expressions of IL-8, PTHrP, MCSF, RANKL (218.010 ± 12.802, 232.399 ± 14. 354, 319.831 ±5.322, and 195.701 ± 4. 862, respectively in the tested group C). The optimal effect was shown in the tested group C, showing significant difference to that in the blank group ( P<0. 01 ). Meanwhile, the OPG in the bone metastatic foci could be up-regulated and protein expressions of RANKL/IL-8/PTHrP/MCSF down-regulated in all the tested groups. The optimal effect was shown in the tested group C

  12. A proteomic study of protein variation between osteopenic and age-matched control bone tissue.

    Science.gov (United States)

    Chaput, Christopher D; Dangott, Lawrence J; Rahm, Mark D; Hitt, Kirby D; Stewart, Donald S; Wayne Sampson, H

    2012-05-01

    The focus of this study was to identify changes in protein expression within the bone tissue environment between osteopenic and control bone tissue of human femoral neck patients with osteoarthritis. Femoral necks were compared from osteopenic patients and age-matched controls. A new method of bone protein extraction was developed to provide a swift, clear view of the bone proteome. Relative changes in protein expression between control and osteopenic samples were quantified using difference gel electrophoresis (DIGE) technology after affinity chromatographic depletion of albumin and IgG. The proteins that were determined to be differentially expressed were identified using standard liquid chromatography mass spectrometry (LC/MS/MS) and database searching techniques. In order to rule out blood contamination, blood from age-matched osteoporotic, osteopenic and controls were analyzed in a similar manner. Image analysis of the DIGE gels indicated that 145 spots in the osteopenic bone samples changed at least ± 1.5-fold from the control samples (P proteins were identified by LC/MS/MS. Of the proteins that increased in the osteopenic femurs, two were especially significant: carbonic anhydrase I and phosphoglycerate kinase 1. Apolipoprotein A-I was the most prominent protein that significantly decreased in the osteopenic femurs. The blood samples revealed no significant differences between groups for any of these proteins. In conclusion, carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis.

  13. Peptide receptor radionuclide therapy with lutetium-177 DOTATATE in a case of recurrent extradrenal retroperitoneal malignant paraganglioma with nodal and bone metastasis

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Extra-adrenal retroperitoneal paragangliomas (PGLs are rare tumors causing considerable difficulty in both, diagnosis and treatment. They can be unicentric or multicentric, tend to be locally invasive and therefore have a high incidence of local recurrence. PGLs shows somatostatin receptor positivity, which can be imaged with technetium-99m (Tc-99m-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC and can be treated with lutetium-177 (Lu-177 DOTATATE. We present a case of recurrent unresectable retroperitoneal PGL with nodal and bone metastases in a 27-year-old male, 6 months postsurgery detected with Tc-99m-HYNIC-TOC and was administered with peptide receptor radionuclide therapy using Lu-177 DOTATATE.

  14. 以骨转移为首发症状的分化型甲状腺癌的临床特征与生存分析%Differentiated thyroid carcinoma patients with bone metastasis as the initial presentation:clinical characteristics and survival analysis

    Institute of Scientific and Technical Information of China (English)

    许艳红; 宋红俊; 邱忠领; 陈立波; 罗全勇

    2011-01-01

    Objective: To evaluate the clinical characteristics and survival of differentiated thyroid carcinoma (DTC) patients with bone metastasis as the initial presentation. Methods: The clinical data from 1 546 DTC patients undergoing 1311 treatment were retrospectively analyzed, and the clinical characteristics of DTC patients with bone metastasis as the initial presentation were collected. The distribution of bone metastasis was analyzed, and the survival rate was calculated. Results: A total of 120 DTC patients had bone metastasis, 28 (23.3%) of whom had bone metastasis as the initial presentation.Of these 28 patients, 20 had follicular carcinoma, 6 had papillary carcinoma, and 2 had follicular variant of papillary carcinoma. The most clinical manifestation was bone pain (n=26, 92.9%): one patient had a lumbar fracture and two patients had femur fractures. Two patients presented with no symptoms, and however, occipital metastasis and rib lesions were found by physical examination. These 28 patients had 73 bone metastatic lesions which were frequently found in the pelvis and vertebrae (63.0%, 46/73).There were 12 patients presented with other distant metastases (42.9%). The 5-year and 10-year survival rates in these 28 patients were 93.0% and 71.0%, respectively. The 20-year survival rate of these 28 patients was higher than the remaining 92 patients with post-operatively proved bone metastasis (P=0.012). Conclusion: The occurrence of DTC is occult in some patients. Once local bone pain,pathological fracture and bone destruction in the absence of known causes, further examinations should be needed to exclude bone metastasis from DTC. The prognosis of DTC patients with bone metastasis as the initial presentation is superior to the DTC patients with post-operatively proven bone metastasis.%目的:探讨以骨转移为首发症状的分化型甲状腺癌(differentiated thyroid carcinoma,DTC)的临床特征,并进行生存分析.方法:对拟行131I治疗的1

  15. Unexplained Bone Pain Is an Independent Risk Factor for Bone Metastases in Newly Diagnosed Prostate Cancer

    DEFF Research Database (Denmark)

    Zacho, Helle D; Mørch, Carsten D; Barsi, Tamás;

    2017-01-01

    OBJECTIVE: To determine the relationship between bone pain and bone metastases in newly diagnosed prostate cancer. PATIENTS AND METHODS: This prospective study of bone scintigraphy enrolled 567 consecutive patients with newly diagnosed prostate cancer. The presence of all-cause bone pain, known b......: Unexplained bone pain was a strong independent risk factor for bone metastasis. Guidelines should recommend staging bone scintigraphy in patients with unexplained bone pain, regardless of other risk factors....

  16. Unusual Metastasis from Carcinoma Cervix.

    Science.gov (United States)

    Bhandari, Virendra; Kausar, Mehlam; Naik, Ayush; Batra, Manika

    2016-10-01

    Although the incidence of cancer cervix has reduced in India during the last two decades, still most of the patients presenting in tertiary care centers are in advanced stages. At this center, we see 6% of cancer cervix cases every year, and most of these cases are in stage III and IVa. All these patients have squamous cell carcinoma and were treated with a combination of external and intracavitary radiotherapy along with concurrent cisplatin given once weekly. Eighty-nine point nine % patients had achieved a complete response. Local recurrence was seen in 17.9% at a median duration of 10.5 months, and 8.17% developed distant metastasis involving lung, liver, bone, and supraclavicular lymph nodes. Three patients developed metastasis at unusual sites involving breast, paraspinal muscles, and duodenum which are very rarely involved. These patients were treated with chemotherapy using carboplatin and Paclitaxel combination but succumbed within 8-10 months of development of metastasis. The cause of involvement of these unusual sites is not clear, but it may be hematological spread, and we want to share these reports such that these sites are seen during follow-up of patients of cancer cervix.

  17. 前列腺癌组织中P504S表达和Gleason评分与骨转移的相关性研究%Role of P504S and Gleason scores in prostate cancer patients with bone metastasis

    Institute of Scientific and Technical Information of China (English)

    张培新; 艾尼娃; 李鸣; 贾宏亮; 蒲春林

    2014-01-01

    目的 探讨前列腺癌组织中P504S/AMACR表达和Gleason评分与骨转移的相关性.方法 选取2012年7月至2013年6月之间本院收治的前列腺癌58例,其中骨转移患者32例;无骨转移患者26例.采用EnVision免疫组化二步法检测前列腺癌组织中P504S/AMACR的表达,同时分析P504S/AMACR表达和Gleason评分与骨转移的关系.结果 骨转移与P504S/AMACR相关系数为0.818(说明正相关,关系较密切,P <0.05);骨转移和Gleason做相关性分析,相关系数为0.474(说明正相关,P<0.007).经秩和检验分析得骨转移组和无骨转移组的P504S/AMACR表达差异有统计学意义(Z=-4.110,P<0.001),经秩和检验分析得骨转移组和无骨转移组的Gleason评分差异有统计学意义(Z=-3.372,P=0.001).结论 前列腺癌骨转移患者的组织中P504S/AMACR表达增高,可能为预测前列腺癌骨转移诊断以及预后判断提供更多的依据.%Objectives To investigate the correlation between bone metastases in patients with prostate cancer and P504S expression,Gleason score.Methods From July 2012 to June 2013,58 patients with prostate cancer were collected in our hospital,in which 32 with bone metastasis and 26 without bone metastasis.P504S expression in tissue of prostate cancer were measured using immunohistochemical two-steping of EnVision,All of patients underwent whole body radionuclide bone scan.The role of P504S and Gleason score in bone metastasis were analyzed.Results For prostate cancer with bone metastasis,P504S expression was strength,correlation coefficients were 0.818,there are statistically significant differences (P <0.05) ; correlation coefficient with the Gleason scores was 0.474,P < 0.007.By rank and inspection analysis in groups and no bone metastases of bone metastases,P504S expression difference was statistically significant (Z =4.110,P < 0.001),the rank and inspection analysis of bone metastases group and no group of bone metastases of Gleason score

  18. The Multiple Roles of Exosomes in Metastasis.

    Science.gov (United States)

    Weidle, Ulrich H; Birzele, Fabian; Kollmorgen, Gwen; Rüger, Rüdiger

    2017-01-02

    Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes.

  19. Analysis on 57 Extracellular Bbone Marrow Tumors Which Bone Metastasis as First Symptom%以骨髓转移癌为首发表现的骨髓外肿瘤57例分析

    Institute of Scientific and Technical Information of China (English)

    卢焰; 宋建新

    2013-01-01

    Objective:To understand the clinical feature and laboratory examination of metastases cancer of bone marrow(MCBM)which bone metastasis as first symptom and to enhance the cognition of MCBM.Methods:Retrospective analysis of 57 cases of MCBM.Results:In MCBM patients,the most common clinical symptom is anemia,then bone pain and fever;the abnormal hemogram include anemia,thrombocytopenia;immature erythrocytes and granulocyte were seen on the peripheral blood smear;ESR,AKP,LDH and tumor markers increased and with coagulation disorders;all of patients were found cancer cells in heaps or single cancer cell in marrow cytological examination.Conclusion:The clinical symptom of MCBM patients is commonly include anemia,bone pain, fever,immature erythrocytes and granulocyte were seen on the peripheral blood smear,ESR,AKP,LDH and tumor markers increased. When we found patients with above mentioned symptom,we should consider there may be MCBM and do marrow cytological examination earlier.It’s necessary to pay much attention to coagulation disorders in MCBM patients to avoid bone marrow necrosis.%  目的:了解以骨髓转移首发的骨髓转移癌患者的临床特征及实验室检查特点,提高对该疾病的认识。方法:对57例骨髓转移癌患者的临床特征及实验室检查结果进行回顾分析。结果:临床上以贫血最为常见,其次为骨痛及发热;常见的血象异常包括贫血、血小板减少、外周血涂片出现幼红、幼粒细胞,血沉增高,碱性磷酸酶、乳酸脱氢酶升高,肿瘤标志物增高及凝血功能障碍;骨髓细胞学检查均找到数量不等的癌细胞团和(或)单个散落的癌细胞,多见于片尾及边缘。结论:骨髓转移癌患者临床以不明原因的贫血、骨痛、发热等症状且伴有外周血涂片出现幼红、幼粒细胞,血沉增高,碱性磷酸酶、乳酸脱氢酶升高,肿瘤标志物增高等为主要特点;发现有此现象的患者,应

  20. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer.

    Science.gov (United States)

    Yang, Ying-Hua; Buhamrah, Asma; Schneider, Abraham; Lin, Yi-Ling; Zhou, Hua; Bugshan, Amr; Basile, John R

    2016-01-01

    Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects.

  1. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Ying-Hua Yang

    Full Text Available Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects.

  2. [Diagnostic value of MRI versus 99Tcm-MDP bone scan in osseous metastasis of prostate cancer: a meta-analysis].

    Science.gov (United States)

    Shen, Guohua; Zhou, Luyi; Jia, Zhiyun; Zhang, Wenjie; Wang, Qiao; Deng, Houfu

    2014-08-01

    This paper is aimed to assess the diagnostic value of MRI versus 99 Tcm-methylene diphosphonate (99 Tcm- MDP) bone scan (BS) for osseous metastases in patients with prostate cancer. The computer-based retrieval was conducted on PubMed, EMBASE, EBSCO, Web of Knowledge, the Cochrane Library and Ovid data bases to search for trials about diagnosing osseous metastases of prostate cancer with MRI and 99Tc"m-MDP BS. Selected with time acceptance and time exclusion criteria, the data quality were evaluated with QUADAS quality assessment tool and collected. We used the Meta-Disc software to conduct meta-analysis, and then calculated the pooled sensitivity, specificity and diagnostic odds ratio (DOR), drew the summary receiving operating characteristic (SROC) curve, and measured the area under curve (AUC) and Q value. Then five studies were included, involving 353 patients. The pooled sensitivity of MRI and BS was 0. 95 (95% CI 0. 90~0. 98) and 0. 67 (95% CI 0. 58~0. 75), respectively. The pooled specificity was 0. 97 (95% CI 0. 94~0. 99) and 0. 88 (95% CI 0. 83~0. 91), respectively. The pooled DOR was 402.99 (95% CI 119. 05 ~1364. 15) and 23. 85 (95% CI 1. 32~431. 48), respectively. The AUC was 0. 990 1 and 0. 624 1, respectively. The Q was 0. 958 7 and 0. 593 8. It can well be concluded that MRI is more effective than 99 Tcm-MDP BS in the diagnosis of osseous metastases in patients with prostate cancer.

  3. Metastatic tumors in the jaw bones: A retrospective clinicopathological study of 12 cases at Tertiary Cancer Center

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    Kundan Kisanrao Nawale

    2016-01-01

    Conclusion: Metastasis to jaw bones is rare and may be the first manifestation of unknown primary. A lesion predominantly involving bone with unusual morphology should raise a possibility of metastasis.

  4. MEK/ERK 通路蛋白在肾癌骨转移患者的表达%Expression of MEK/ERK signal pathways in renal cell carcinoma with bone metasta-sis

    Institute of Scientific and Technical Information of China (English)

    秦彩朋; 刘春雷; 赵燕辉; 殷华奇; 杜依青; 胡风战; 盛正祚; 徐涛

    2016-01-01

    目的:探讨 MEK/ERK 通路蛋白在肾癌骨转移患者原发灶及转移灶表达的差异及其意义,并探索这种差异的发生机制。方法:选择北京大学人民医院2009年1月至2010年1月7例肾癌骨转移患者的原发灶及转移灶组织标本,应用免疫组织化学法分析 VEGFR-2、MEK、ERK 蛋白在原发灶与转移灶表达的差异,VEGFR-2、MEK、ERK 的Ⅰ抗工作浓度(体积比)分别为1∶200、1∶25、1∶250,应用 PCR 技术检测 PDGFRA 基因20号外显子,K-ras基因2号外显子,Braf基因15号外显子和 MEK1基因2号外显子的相关突变。结果:免疫组织化学结果判读:细胞阳性率≤5%为1分,6%~50%为2分,51%~100%为3分;染色强度:不着色为1分,淡黄色细颗粒状为2分,黄色颗粒状为3分,棕黄色粗颗粒状为4分,将两个得分数相乘得到其表达强度。本组7例肾癌骨转移患者VEGFR-2在原发灶(2.86±2.27)和骨转移灶(2.67±1.85)表达差异无统计学意义(P =0.901),而 MEK(1.33±0.51 vs.6.10±4.10,P =0.015)和 ERK(4.43±2.84 vs.9.10±2.24,P =0.021)表达差异有统计学意义;在原发灶及转移灶标本中并未检测到相关的基因突变。结论:MEK/ERK 通路蛋白在肾癌骨转移患者原发灶和转移灶表达的差异可能与其转移过程有关,也可能是影响靶向治疗效果的原因之一。%Objective:To investigate the expression of MEK/ERK signaling pathways in renal cell car-cinoma with bone metastasis,and to analyze the differences of expressions of VEGFR-2,MEK,ERK on the primary and metastasis tissue and its mechanism.Methods:The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology,Peking University People’s Hos-pital from January 1,2009 to January 1,2010.The expression of MEK/ERK signaling pathways was de-tected in the 7 renal cell carcinoma

  5. Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

    Science.gov (United States)

    Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

    2015-10-01

    To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

  6. Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial.

    Science.gov (United States)

    Fuchs, R K; Bauer, J J; Snow, C M

    2001-01-01

    Physical activity during childhood is advocated as one strategy for enhancing peak bone mass (bone mineral content [BMC]) as a means to reduce osteoporosis-related fractures. Thus, we investigated the effects of high-intensity jumping on hip and lumbar spine bone mass in children. Eighty-nine prepubescent children between the ages of 5.9 and 9.8 years were randomized into a jumping (n = 25 boys and n = 20 girls) or control group (n = 26 boys and n = 18 girls). Both groups participated in the 7-month exercise intervention during the school day three times per week. The jumping group performed 100, two-footed jumps off 61-cm boxes each session, while the control group performed nonimpact stretching exercises. BMC (g), bone area (BA; cm2), and bone mineral density (BMD; g/cm2) of the left proximal femoral neck and lumbar spine (L1-L4) were assessed by dual-energy X-ray absorptiometry (DXA; Hologic QDR/4500-A). Peak ground reaction forces were calculated across 100, two-footed jumps from a 61-cm box. In addition, anthropometric characteristics (height, weight, and body fat), physical activity, and dietary calcium intake were assessed. At baseline there were no differences between groups for anthropometric characteristics, dietary calcium intake, or bone variables. After 7 months, jumpers and controls had similar increases in height, weight, and body fat. Using repeated measures analysis of covariance (ANCOVA; covariates, initial age and bone values, and changes in height and weight) for BMC, the primary outcome variable, jumpers had significantly greater 7-month changes at the femoral neck and lumbar spine than controls (4.5% and 3.1%, respectively). In repeated measures ANCOVA of secondary outcomes (BMD and BA), BMD at the lumbar spine was significantly greater in jumpers than in controls (2.0%) and approached statistical significance at the femoral neck (1.4%; p = 0.085). For BA, jumpers had significantly greater increases at the femoral neck area than controls (2

  7. Blood clot formation does not affect metastasis formation or tumor growth in a murine model of breast cancer.

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    Stephanie Rossnagl

    Full Text Available Cancer is associated with increased fracture risk, due either to metastasis or associated osteoporosis. After a fracture, blood clots form. Because proteins of the coagulation cascade and activated platelets promote cancer development, a fracture in patients with cancer often raises the question whether it is a pathologic fracture or whether the fracture itself might promote the formation of metastatic lesions. We therefore examined whether blood clot formation results in increased metastasis in a murine model of experimental breast cancer metastasis. For this purpose, a clot was surgically induced in the bone marrow of the left tibia of immundeficient mice. Either one minute prior to or five minutes after clot induction, human cancer cells were introduced in the circulation by intracardiac injection. The number of cancer cells that homed to the intervention site was determined by quantitative real-time PCR and flow cytometry. Metastasis formation and longitudinal growth were evaluated by bioluminescence imaging. The number of cancer cells that homed to the intervention site after 24 hours was similar to the number of cells in the opposite tibia that did not undergo clot induction. This effect was confirmed using two more cancer cell lines. Furthermore, no difference in the number of macroscopic lesions or their growth could be detected. In the control group 72% developed a lesion in the left tibia. In the experimental groups with clot formation 79% and 65% developed lesions in the left tibia (p = ns when comparing each experimental group with the controls. Survival was similar too. In summary, the growth factors accumulating in a clot/hematoma are neither enough to promote cancer cell homing nor support growth in an experimental model of breast cancer bone metastasis. This suggests that blood clot formation, as occurs in traumatic fractures, surgical interventions, and bruises, does not increase the risk of metastasis formation.

  8. Value of the Joint Detection of PSA and ALP in the Early Diagnosis of Prostate Cancer Bone Metastasis%前列腺特异抗原和碱性磷酸酶联合检测在早期诊断前列腺癌骨转移中的应用

    Institute of Scientific and Technical Information of China (English)

    郭枫; 陈琳; 李运柱; 彭松; 李国灏; 朱晨曦; 余家俊; 王勇; 万志华

    2012-01-01

    Objective: To investigate the role and significance of the joint detection of prostatic specific antigen (PSA) and alkaline phosphatase (ALP) in the early diagnosis of prostate cancer bone metastasis. Methods: By radionuclide bone imaging, 98 cases of prostate cancer were divided into bone metastasis group and non-metastasis group. Serum levels of PSA and the ALP were detected in all patients, and the results were analyzed and compared statistically between the two groups in relation to metastasis status. Radionuclide bone scintigraphy were adopted to find radioactive foci. Results: The serum PSA and ALP levels were higher in bone metastasis group than in non-metastasis group (P0. 05). The sensitivity (specificity) of joint detection were significantly different from that of ALP or PSA alone. The radionuclide bone scintigra-phy positive rate was 58. 2% , and abnormal radioactive dense foci were located in the thoracic and lumbar parts. Conclusion: PAS and ALP joint detection is useful for the early diagnosis of prostate cancer bone metastases, and can improve the diagnostic rate.%目的:探讨前列腺特异抗原(PSA)和碱性磷酸酶(ALP)联合检测在早期诊断前列腺癌骨转移中的作用及意义.方法:经核素骨显像将98例前列腺癌患者分为骨转移组和非骨转移组,所有患者均检测PSA和ALP,对比分析两组患者PSA和ALP检测结果、阳性率及与骨转移关系,分析二者联合检测与单项检测对前列腺癌骨转移的敏感度与特异度,以及核素骨显像异常放射性浓聚灶分布情况.结果:骨转移组血清PSA和ALP水平均高于非骨转移组,相比均有显著性差异(P<0.05);PSA单项检测结果骨转移组与非骨转移组阳性率相比无显著性差异(P>0.05),ALP相比有显著性差异(P<0.05);目PSA和ALP值随着骨转移分级增加而增加,呈正相关;PSA和ALLP联合检测与单项检测敏感度相比有显著性差异(P<0.05),特异度有极显著性差异(P<0

  9. 99mTc-MDP 全身骨扫描和血清 CEA、NSE、CYFR21-1、CA125 测定对小细胞肺癌骨转移的临床评价%Clinical evaluation of 99mTc-MDP bone scintigraphy and serum CEA, NSE,CYFRA21-1 and CA125 in skeletal metastasis of the small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张炜; 郭万华

    2015-01-01

    目的:分析99m Tc-MDP全身骨扫描小细胞肺癌骨转移病灶分布特点及血清肿瘤标志物CEA、NSE、CYFRA21-1、CA125与小细胞肺癌骨转移发生的相关性. 方法:回顾性分析56例经病理证实的小细胞肺癌患者 99m Tc-MDP全身骨扫描影像表现及血清肿瘤标志物水平,用ROC曲线及Spearman相关分析评价肿瘤标志物水平对肺癌骨转移发生及发展的诊断意义. 结果:21 例骨转移阳性病灶中胸部占46.60%,脊柱34.95%,骨盆9.71%,四肢5.83%,头颅2.91%. 骨转移阳性组CEA、NSE 质量浓度高于骨转移阴性组(均P<0.05),曲线下面积(AUC)分别为0.789、0.717,且CEA、NSE质量浓度与骨转移分级呈正相关(r值分别为0.540、0.417). 结论:小细胞肺癌以胸部及脊柱等中轴骨多发性骨转移为主,CEA、NSE血清水平随着骨转移病灶数的增加有显著上升趋势,对判定小细胞肺癌骨转移的发生及发展有一定的参考意义.%Objective:To analyze the distribution characteristic of the skeletal metastasis lesion in 99mTc-MDP bone scintigraphy and the correlation between serum tumor marker (CEA,NSE, CYFRA21-1 and CA125) and skeletal metastasis in small cell lung cancer .Methods:56 cases with small cell lung confirmed by pathology were examined with 99m Tc-MDP bone scintigraphy .Serum concentration of CEA , NSE, CYFRA21-1 and CA125 were measured one week before whole-body bone scanning .ROC curve and spearman correlation analysis were used to evaluate the serum tumor markers in diagnose the development of the skeletal metastasis .Results: 21 imaging positive lesions were identified as the skeletal metastasis .The distribution of the skeletal metastasis lesions were:chest(46.60%), spine(34.95%), pelvis(9.71%), four limbs(5.83%), skull(2.91%).CEA,NSE levels in bone metastasis group were significant higher than those in the negative group ( P<0.05 ) and the area of ROC curve were 0.789 and 0.717 respectively(P<0.05).There was a correlation between

  10. Popliteal lymph node metastasis of tibial osteoblastic osteosarcoma.

    Science.gov (United States)

    Dirik, Yalın; Çınar, Arda; Yumrukçal, Feridun; Eralp, Levent

    2014-01-01

    We report a case with lymph node metastasis of osteosarcoma, which is a rare entity in comparison to hematogeneous lung or bone metastasis. Twenty-seven years old male patient referred to our clinic complaining of ongoing left knee pain and swelling since one month without a history of prior trauma. Magnetic resonance imaging (MRI) revealed a mass of malignant nature which causes more prominent expansion and destruction of the bone distally with periosteal reaction. A lymphadenomegaly 16mm×13mm in diameter was also present in the popliteal fossa having the same signal pattern with the primary lesion. Thirteen weeks following the first referral of the patient, wide resection and reconstruction with modular tumor prosthesis was performed. Popliteal lymph node was excised through the same incision. Pathologic examination of the resected speciman reported osteoblastic osteosarcoma. The lymph node extirpated from the popliteal fossa was reported to be a metastasis of the primary tumor. Osteosarcoma of the long bones is the most common primary malignant bone neoplasm of both childhood and adulthood. Osteosarcomas commonly metastasize hematogeneously to the lungs and bones. Lymph node metastasis is a rare entity. Similar studies report rates between 2.3% and 4%. It is not clearly explained, how lymph node metastasis in osteosarcoma occurs despite lack of lymphatic drainage in normal cortical and spongious bone. Lymph node metastasis of osteosarcoma is a rare entity and metastatic patterns could not be clearly explained. On the other hand, the effects of lymph node metastasis on prognosis are also not clearly defined and further studies are needed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Pulmonary Metastasis from Pseudomyxoma Peritonei

    Directory of Open Access Journals (Sweden)

    Toshiyuki Kitai

    2012-01-01

    Full Text Available Pseudomyxoma peritonei (PMP is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.

  12. Sink or swim? Bone density as a mechanism for buoyancy control in early cetaceans.

    Science.gov (United States)

    Gray, Noel-Marie; Kainec, Kimberly; Madar, Sandra; Tomko, Lucas; Wolfe, Scott

    2007-06-01

    Previous analyses have shown that secondarily aquatic tetrapods, including whales, exhibit osteological adaptations to life in water as part of their complex buoyancy control systems. These structural specializations of bone span hyperostosis through osteoporosis. The past 15 years of paleontological effort has provided an unprecedented opportunity to examine the osteological transformation of whales as they make their transition to an obligate aquatic lifestyle over a 10-million-year period. It is hypothesized that whales manifest their osteological specialization in the same manner as extant semiaquatic and fully aquatic mammals. This study presents and analysis of the microstructural features of bone in early and late archaic cetaceans, and in a comparative sample of modern terrestrial, semiaquatic, and aquatic mammals. Bone histology was examined from the ribs of 10 fossilized individuals representing five early cetacean families, including Pakicetidae, Ambulocetidae, Protocetidae, Remintonocetidae, and Basilosauridae. Comparisons were then made with rib histology from nine genera of extant mammals including: Odocoileus (deer), Bos (cow), Equus (horse), Canis (dog), Lutra (river otter), Enhydra (sea otter), Choeropsis (pygmy hippo), Trichechus (sea cow), and Delphinus (dolphin). Results show that the transition from terrestrial, to semiaquatic, to obligate aquatic locomotion in archaeocetes involved a radical shift in bone function achieved by means of profound changes at the microstructural level. A surprising finding was that microstructural change predates gross anatomical shift in archaeocetes associated with swimming. Histological analysis shows that high bone density is an aquatic specialization that provides static buoyancy control (ballast) for animals living in shallow water, while low bone density is associated with dynamic buoyancy control for animals living in deep water. Thus, there was a shift from the typical terrestrial form, to osteopetrosis

  13. Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe.

    Science.gov (United States)

    Merletti, Franco; Richiardi, Lorenzo; Bertoni, Franco; Ahrens, Wolfgang; Buemi, Antoine; Costa-Santos, Cristina; Eriksson, Mikael; Guénel, Pascal; Kaerlev, Linda; Jöckel, Karl-Heinz; Llopis-Gonzalez, Agustin; Merler, Enzo; Miranda, Ana; Morales-Suárez-Varela, Maria M; Olsson, Håkan; Fletcher, Tony; Olsen, Jorn

    2006-02-01

    We investigated the association between occupational factors and risk of bone sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case-control study was conducted in 7 European countries in 1995-97. Ninety-six cases aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides. Response proportions were 90% among cases and 66% among controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for selected categories of job titles and branches of industry and for use of pesticides. We found an increased OR for bone sarcoma among blacksmiths, toolmakers, machine-tool operators (OR = 2.14, 95% CI 1.08-4.26), woodworkers (OR = 2.68, 95% CI 1.36-5.29) and construction workers (OR = 1.62, 95% CI 0.92-2.87). Ever users of pesticide had an OR of 2.33 (95% CI 1.31-4.13), with similar risks for exposure to insecticides and exposure to herbicides. Neither duration of employment in any of the analyzed occupational categories nor duration of use of pesticides showed an increasing trend in the risk of bone sarcoma. ORs of bone sarcoma were 1.03 (95% CI 0.23-4.57), 3.13 (95% CI 1.26-7.76) and 1.44 (95% CI 0.43-4.85) for the first, second and third tertile of days of use of pesticides. Our study suggests that novel and previously reported (woodworking) occupational factors play a role in the aetiology of bone sarcomas.

  14. Nanofibrous yet injectable polycaprolactone-collagen bone tissue scaffold with osteoprogenitor cells and controlled release of bone morphogenetic protein-2

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, Gayathri; Bialorucki, Callan [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Yildirim-Ayan, Eda, E-mail: eda.yildirimayan@utoledo.edu [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614 (United States)

    2015-06-01

    In this work, we developed a nanofibrous, yet injectable orthobiologic tissue scaffold that is capable of hosting osteoprogenitor cells and controlling kinetic release profile of the encapsulated pro-osteogenic factor without diminishing its bioactivity over 21 days. This innovative injectable scaffold was synthesized by incorporating electrospun and subsequently O{sub 2} plasma-functionalized polycaprolactone (PCL) nanofibers within the collagen type-I solution along with MC3T3-E1 cells (pre-osteoblasts) and bone morphogenetic protein-2 (BMP2). Through changing the PCL nanofiber concentration within the injectable scaffolds, we were able to tailor the mechanical strength, protein retention capacity, bioactivity preservation, and osteoinductive potential of the scaffolds. The nanofibrous internal structure of the scaffold allowed us to use a low dose of BMP2 (200 ng/ml) to achieve osteoblastic differentiation in in vitro culture. The osteogenesis capacity of the injectable scaffolds were evaluated though measuring MC3T3-E1 cell proliferation, ALP activity, matrix mineralization, and early- and late-osteoblast specific gene expression profiles over 21 days. The results demonstrated that the nanofibrous injectable scaffold provides not only an osteoinductive environment for osteoprogenitor cells to differentiate, but also a suitable biomechanical and biochemical environment to act as a reservoir for osteogenic factors with controlled release profile. - Highlights: • Injectable nanofibrous scaffold with osteoprogenitor cells and BMP2 was synthesized. • PCL nanofiber concentration within collagen scaffold affected the BMP2 retention and bioactivity. • Optimal PCL concentration was identified for mechanical stability, injectability, and osteogenic activity. • Scaffolds exhibited long-term osteoinductive capacity for bone repair and regeneration.

  15. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

    Directory of Open Access Journals (Sweden)

    Fu YC

    2015-12-01

    Full Text Available Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid microspheres (SIM/PLGA that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration

  16. Effects of lifestyle exercise on premenopausal bone health: a randomised controlled trial.

    Science.gov (United States)

    Babatunde, Opeyemi; Forsyth, Jacky

    2014-09-01

    Osteoporosis, a slowly evolving public health epidemic, often with an insidious presentation is largely preventable but the optimal dimensions of exercise that may be prescribed for enhancing bone-health among premenopausal adults are yet to be elucidated. Hence, the escalating incidence and burden of prevalence of osteoporosis is yet unabated. Considering that exogenous hormones in the form of hormonal contraception are known to modulate bone mass, investigations of their possible influence on the translation of exercise-induced osteogenic stimuli on the mature bone is pertinent. The aim of this study was to examine the effect of specified lifestyle exercise on bone-health of premenopausal women. Premenopausal women (n = 96, mean age: 22.25 ± 3.5 years; mean BMI: 23.43 ± 3.5 kg/m(2)) participated in a 6-month randomised controlled trial involving home-based rest-interspersed bouts of high-impact exercise for the intervention group and sham exercise for the control group. Approximately half (47) of the participants (24-exercise, 23-control) were on hormonal-based contraception while the other half (49: 24-exercise, 25-control) were not on hormonal contraception. The regime led to a significant 3.7 % increase in broadband ultrasound attenuation of exercisers compared to controls; hormonal contraceptive use did not appear to potentiate the osteogenic effects of the lifestyle exercise regime. The research highlights that short, discrete bouts of high-impact exercise may be a potential public health prescription for enhancing premenopausal bone-health regardless of hormonal contraceptive use.

  17. Skeletal metastasis: treatments, mouse models,and the Wnt signaling

    Institute of Scientific and Technical Information of China (English)

    Kenneth C.Valkenburg; Matthew R.Steensma; Bart O.Williams; Zhendong Zhong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality.This is particularly true of cancers with a strong predilection for the bone,such as breast,prostate,and lung cancers.There is currently no reliable cure for skeletal metastasis,and palliative therapy options are limited.The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target.Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments.In this review,we discuss pathologic process of bone metastasis,the roles of the Wnt signaling,and the available experimental models and treatments.

  18. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  19. Serum Chemerin Levels in relation to Osteoporosis and Bone Mineral Density: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Jing He

    2015-01-01

    Full Text Available Background. To evaluate serum chemerin levels in patients with osteoporosis and healthy controls and to investigate the relationship between serum chemerin levels and bone mineral density (BMD. Methods. An age- and gender-matched case-control study was conducted. Pearson’s correlation test was performed to investigate the relationship between serum chemerin levels and BMD. Results. There were 93 patients included in the osteoporosis group and 93 matched controls. Serum chemerin level was significantly higher in patients with osteoporosis (87.27±5.80 ng/mL than patients in control (71.13±5.12 ng/mL (P<0.01. There was a negative correlation between femoral bone mineral density and chemerin in both groups (R=-0.395, P<0.01 in osteoporosis group; R=-0.680, P<0.01 in control and also a negative correlation between lumbar bone mineral density with chemerin in both groups (R=-0.306, P<0.01 in osteoporosis group; R=-0.362, P<0.01 in control. Conclusions. Patients with osteoporosis presented a higher level of serum chemerin, which witnessed an inverse correlation with BMD. Further studies are needed to explore the role of chemerin in the pathophysiology of osteoporosis.

  20. Significance and therapeutic implications of endothelial progenitor cells in angiogenic-mediated tumour metastasis.

    Science.gov (United States)

    Flamini, Valentina; Jiang, Wen G; Lane, Jane; Cui, Yu-Xin

    2016-04-01

    Cancer conveys profound social and economic consequences throughout the world. Metastasis is responsible for approximately 90% of cancer-associated mortality and, when it occurs, cancer becomes almost incurable. During metastatic dissemination, cancer cells pass through a series of complex steps including the establishment of tumour-associated angiogenesis. The human endothelial progenitor cells (hEPCs) are a cell population derived from the bone marrow which are required for endothelial tubulogenesis and neovascularization. They also express abundant inflammatory cytokines and paracrine angiogenic factors. Clinically hEPCs are highly correlated with relapse, disease progression, metastasis and treatment response in malignancies such as breast cancer, ovarian cancer and non-small-cell lung carcinoma. It has become evident that the hEPCs are involved in the angiogenesis-required progression and metastasis of tumours. However, it is not clear in what way the signalling pathways, controlling the normal cellular function of human BM-derived EPCs, are hijacked by aggressive tumour cells to facilitate tumour metastasis. In addition, the actual roles of hEPCs in tumour angiogenesis-mediated metastasis are not well characterised. In this paper we reviewed the clinical relevance of the hEPCs with cancer diagnosis, progression and prognosis. We further summarised the effects of tumour microenvironment on the hEPCs and underlying mechanisms. We also hypothesized the roles of altered hEPCs in tumour angiogenesis and metastasis. We hope this review may enhance our understanding of the interaction between hEPCs and tumour cells thus aiding the development of cellular-targeted anti-tumour therapies.

  1. Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study.

    Science.gov (United States)

    Constantin, Tina; Tangpricha, Vin; Shah, Reshma; Oyesiku, Nelson M; Ioachimescu, Octavian C; Ritchie, James; Ioachimescu, Adriana G

    2017-07-01

    Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. To evaluate calcium and bone metabolism in active and treated acromegaly. We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent.

  2. Green tea polyphenols and Tai Chi for bone health: designing a placebo-controlled randomized trial.

    Science.gov (United States)

    Shen, Chwan-Li; Chyu, Ming-Chien; Yeh, James K; Felton, Carol K; Xu, Ke T; Pence, Barbara C; Wang, Jia-Sheng

    2009-09-04

    effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. We present the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women.

  3. Green tea polyphenols and Tai Chi for bone health: Designing a placebo-controlled randomized trial

    Directory of Open Access Journals (Sweden)

    Chyu Ming-Chien

    2009-09-01

    model of repeated measurements with random effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. Discussion We present the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women. Trial registration ClinicalTrials.gov identifier: NCT00625391

  4. An Optimal Control of Bone Marrow in Cancer Chemotherapy by Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    H. Hosseinipour

    2015-09-01

    Full Text Available Although neural network models for cancer chemotherapy have been analyzed since the early seventies, less research has been done in actually formulating them as optimal control problems. In this paper an artificial neural networks-based method for optimal control of bone marrow in cell-cycle-specific chemotherapy is proposed. In this method, we use artificial neural networks for approximating the optimal control problem which maximizes both bone marrow mass and drug`s dose at the same time. The corresponding model be transfer to Hamiltonian function and using Pontryagin principle we create the boundary conditions. After defining boundary conditions, we use the approximating property of artificial networks and put the boundary conditions in error functions to satisfy the limitations..

  5. Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study

    DEFF Research Database (Denmark)

    Møller, U K; Við Streym, S; Mosekilde, L

    2012-01-01

    In a controlled cohort study, bone mineral density (BMD) was measured in 153 women pre-pregnancy; during pregnancy; and 0.5, 4, 9, and 19 months postpartum. Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Pregnancy and breastfeeding cause a reversible bone...... loss, which, initially, is most pronounced at trabecular sites but also involves cortical sites during prolonged breastfeeding. INTRODUCTION: Conflicting results have been reported on effects of pregnancy and breastfeeding on BMD and body composition (BC). In a controlled cohort study, we elucidate...... changes in BMD and BC during and following a pregnancy. METHODS: We measured BMD and BC in 153 women planning pregnancy (n = 92 conceived), once in each trimester during pregnancy and 15, 129, and 280 days postpartum. Moreover, BMD was measured 19 months postpartum (n = 31). Seventy-five age...

  6. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    Science.gov (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  7. Evaluation of the dinical curative effect of using 153Sm-EDTMP in painful bone metastasis of malignant tumor%153Sm-乙二胺四甲基撑膦酸治疗恶性肿瘤骨转移疼痛

    Institute of Scientific and Technical Information of China (English)

    张晓娟; 晋建华; 刘建中; 李思进; 李险峰; 张承刚; 郭睿; 宁艳丽

    2008-01-01

    目的 评价153Sm-乙二胺四甲基撑膦酸(153Sm-EDTMP)在恶性肿瘤骨转移疼痛治疗中的临床应用价值.方法 对80例骨转移癌患者进行153Sm-EDTMP治疗,按22.2~37 MBq/kg体重一次性静脉注射给药.按照视觉模拟评分法和Kamofsky评分标准,分别评价治疗前后患者疼痛缓解及生活质量改善情况.结果 153Sm-EDTMP治疗的80例骨转移癌患者中,疼痛缓解总有效率为68.75%.其中前列腺癌骨转移癌痛缓解率最高,达81.82%,其次为乳腺癌和肺癌,分别为80.00%、75.00%.分析治疗前后Karnofsky评分变化情况,发现疼痛级别越高生活质量改善越明显.结论 153Sm-EDTMP对恶性肿瘤骨转移所致的疼痛具有较好的缓解作用,对中、重度骨痛患者的生活质量有明显的改善,该法是使用放疗、镇痛药物等方法治疗骨转移癌痛的有益补充.%Objective To evaluate the clinical curative effect of using 153Sm-EDTMP in painful bone metastasis of malignant tumor. Methods Eighty patients with bone metastasis of malignant rumor underwent radionuclide bone palliation therapy were analysed.The treatment efficacy was evaluated by visual analogue scale (VAS) and Kamofsky performance scale.Results 68.75% of patients had a positive response.A better analgesic effect was found in cases of lung,prostate and breast carcinoma metastasm compared to metastasis from other malignant lesions.Improvement of performance in Karnofsky scale was found in cases of midrange and heavy range patients.Conclusion The analgesic effects of 153Sm-EDTMP is obvious in painful bone metastasis of malignant tumor.Improvement of life quality is significant in cases of midrange and heavy range patients.The therapeusis is a beneficial supplement of radiotherapy and odynolysis therapy.

  8. Prevention of Bone Loss with Risedronate in Breast Cancer Survivors: A Randomized, Controlled Clinical Trial

    Science.gov (United States)

    Greenspan, Susan L.; Vujevich, Karen T.; Brufsky, Adam; Lembersky, Barry C.; van Londen, G.J.; Jankowitz, Rachel C.; Puhalla, Shannon L.; Rastogi, Priya; Perera, Subashan

    2016-01-01

    Purpose Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone receptor positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if 1) oral bisphosphonate therapy can prevent bone loss in women on an AI and, 2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). Methods We conducted a 2 year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an aromatase inhibitor (AI-anastrozole, letrozole, or exemestane) for hormone receptor positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)] and safety. Results Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p<0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 µg/mL for P1NP (both p<0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p<0.05). The oral therapy was safe and well tolerated. Conclusion In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health. PMID:25792492

  9. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  10. Assessment of lumbar trabecular bone density by means of single energy quantitative CT in hospital control children and bone metabolic disorders, 1

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Kazutoshi; Miyamoto, Akie; Imai, Kaoru; Mochizuki, Yumiko; Hayashi, Kitami; Mitsuishi, Yoichi; Fukuyama, Yukio; Kohno, Atsushi; Shigeta, Teiko (Tokyo Women' s Medical Coll. (Japan))

    1990-03-01

    We studied the 3rd lumbar vertebral trabecular bone mineral density in 59 cross-sectional pictures of quantitative computed tomography (QCT) with CaCO{sub 3} phantom for 28 hospital control children and 30 cases of suspected bone metabolic disorders. The QCT value of bone mineral density of control children showed neither age dependency nor sexual difference before puberty: for males was 221.8{plus minus}30.2 mg CaCO{sub 3}/cm{sup 3} (Mean{plus minus}SD) under 4 years, 218.1{plus minus}39.7 at 5{approx}9 years and 217.2{plus minus}30.9 at 10{approx}15 years; and for females 220.9{plus minus}18.3 under 4 years and 240.0{plus minus}29.4 at 5{approx}9 years. The QCT values of bone mineral density in bed-ridden patients, children receiving glucocorticoids, and children receiving anticonvulsants were significantly lower than that in control children (p<0.005). The QCT value of bone mineral density of bed-ridden patients was significantly lower than that of children receiving glucocorticoids and of children receiving anticonvulsants (p<0.05, p<0.005 respectively). Our study confirmed that single energy quantitative CT was very useful in pediatric clinical application. (author).

  11. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.

    Science.gov (United States)

    Madeira, Mila F M; Queiroz-Junior, Celso M; Montero-Melendez, Trinidad; Werneck, Silvia M C; Corrêa, Jôice D; Soriani, Frederico M; Garlet, Gustavo P; Souza, Daniele G; Teixeira, Mauro M; Silva, Tarcilia A; Perretti, Mauro

    2016-12-01

    Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, but whether such protection takes place in infection-induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aa-induced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp(8)-γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aa-infected mice treated with DTrp(8)-γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle-treated animals; these actions were associated with reduced periodontal levels of TNF-α, IFN-γ, and IL-17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp(8)-γMSH. Thus, melanocortin agonism could represent an innovative way to tame overexuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection.-Madeira, M. F. M., Queiroz-Junior, C. M., Montero-Melendez, T., Werneck, S. M. C., Corrêa, J. D., Soriani, F. M., Garlet, G. P., Souza, D. G., Teixeira, M. M., Silva, T. A., Perretti, M. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection. © FASEB.

  12. CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d.

    Science.gov (United States)

    Tsai, Hsiao-Chi; Su, Hong-Lin; Huang, Chun-Yin; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2014-06-15

    Osteosarcoma, the most common primary malignant bone tumor, shows potent capacity for local invasion and distant metastasis. Connective tissue growth factor (CTGF/CCN2), a secreted protein, binds to integrins, modulates invasive behavior of certain human cancer cells. Effect of CTGF in metastasis of human osteosarcoma is unknown. We found overexpression of CTGF increasing matrix metalloproteinases (MMPs)-2 and MMP-3 expression as well as promoting cell migration. MicroRNA (miRNA) analysis of CTGF-overexpressed osteosarcoma versus control cells probed mechanisms of CTGF-mediated promotion of migration. Among miRNAs regulated by CTGF, miR-519d was most downregulated after CTGF treatment. Co-transfection with miR-519d mimic reversed CTGF-mediated MMPs expression and cell migration. Also, MEK and ERK inhibitors or mutants reduced CTGF-increased cell migration and miR-519d suppression. By contrast, knockdown of CTGF diminished lung metastasis in vivo. Clinical samples indicate CTGF expression as linked with clinical stage and tumor metastasis. Taken together, data show CTGF elevating MMPs expression and subsequently promoting tumor metastasis in human osteosarcoma, down-regulating miR-519d via MEK and ERK pathways, making CTGF a new molecular therapeutic target in osteosarcoma metastasis.

  13. CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d

    Science.gov (United States)

    Tsai, Hsiao-Chi; Su, Hong-Lin; Huang, Chun-Yin; Fong, Yi-Chin; Hsu, Chin-Jung; Tang, Chih-Hsin

    2014-01-01

    Osteosarcoma, the most common primary malignant bone tumor, shows potent capacity for local invasion and distant metastasis. Connective tissue growth factor (CTGF/CCN2), a secreted protein, binds to integrins, modulates invasive behavior of certain human cancer cells. Effect of CTGF in metastasis of human osteosarcoma is unknown. We found overexpression of CTGF increasing matrix metalloproteinases (MMPs)-2 and MMP-3 expression as well as promoting cell migration. MicroRNA (miRNA) analysis of CTGF-overexpressed osteosarcoma versus control cells probed mechanisms of CTGF-mediated promotion of migration. Among miRNAs regulated by CTGF, miR-519d was most downregulated after CTGF treatment. Co-transfection with miR-519d mimic reversed CTGF-mediated MMPs expression and cell migration. Also, MEK and ERK inhibitors or mutants reduced CTGF-increased cell migration and miR-519d suppression. By contrast, knockdown of CTGF diminished lung metastasis in vivo. Clinical samples indicate CTGF expression as linked with clinical stage and tumor metastasis. Taken together, data show CTGF elevating MMPs expression and subsequently promoting tumor metastasis in human osteosarcoma, down-regulating miR-519d via MEK and ERK pathways, making CTGF a new molecular therapeutic target in osteosarcoma metastasis. PMID:25003330

  14. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2016-10-01

    deficiency on global CD8+ T cell gene expression using an RNAseq approach. Figure 1. HIF1 inhibition could slow down prostate tumor growth...1. RNAseq and network analysis reveals CD8 T cell gene expression in the setting of HIF-1 deficiency Metabolic factors and processes play a...contribution of HIF-1 to these important agents of cell- mediated immunity. 4 To this end we utilized a whole transcriptome analysis approach ( RNASeq ) to

  15. Imaging Primary Prostate Cancer and Bone Metastasis

    Science.gov (United States)

    2007-04-01

    AAPM 48th Annual Meeting, Orlando, FL, July 2006 Zhang X, Cao F, Cai W, Schreibmann E, Wu Y, Wu JC, Xing L, Chen X. 18F-Labeled Bombesin...147– 155 . 3. Chung DH, Evers BM, Beauchamp RD, et al. Bombesin stimulates growth of human gastrinoma. Surgery. 1992;112:1059–1065. 4. Glover SC

  16. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  17. Comparison of the clinic value of whole body MR diffusion weighted imaging and radionuclide bone scan in the diagnosis of skeletal metastasis of breast cancer%全身弥散加权成像与同位素骨扫描诊断乳腺癌骨转移对比研究

    Institute of Scientific and Technical Information of China (English)

    林建华; 谭理连; 何伟红; 黄勇; 李敏红; 邬恒夫

    2011-01-01

    目的:比较全身弥散加权成像(WB-DWI)、同位素骨扫描(radionuclide bone scan)技术在乳腺癌骨转移的应用价值.方法:40例经病理证实为乳腺癌的患者分别作WB-DWI及同位素骨扫描检查.WB-DWI检查使用反转恢复平面回波弥散序列行全身扫描,将骨骼系统分为3个区域,分别记录每个患者各区域WB-DWI阳性病例数.对所有WB-DWI及同位素骨扫描影像表现的乳腺癌转移例数及发生部位行统计学比较.结果:WB-DWI阳性病例为35例,共检出病灶数为146个;同位素骨扫描阳性病例为30例,共检出病灶数为141个,WB-DWI的病灶检出率高于同位素骨扫描;WB-DWI与同位素骨扫描诊断乳腺癌骨转移例数及发生部位无统计学差异.结论:WB-DWI检查无辐射,覆盖范围大,具有较高的敏感性,对乳腺癌骨转移早期筛查、诊断及预后评价方面具有重要的临床应用价值.%Objective:To compare the value of MR whole body diffusion weighted imaging (WB-DWI) and radionuclide bone scan (RN) in the detection of bone metastasis of breast cancer. Methods: Forty patients with pathology proved breast cancer were enrolled. All patients underwent MR WB-DWI and RN,inversion recovery echo-planar diffusion scan sequence from head to foot was used for WB-DWI. The skeletal system was divided into three regions and the positive cases were recorded patient by patient in each region. Chi-square test was performed in patients and regions of bone metastasis detected by WB-DWI and RN for comparison. Results: A total of 146 metastasis lesions in 35 patients were detected by WBDWI while 141 lesions in 30 patients by RN. The detection rate of WB-DWI was higher than that of RN. No statistic differences were assessed in the number and locations of the bone metastasis diagnosed by WB-DWI and RN. Conclusion: MR WBDWI has no radiation,large coverage and high sensitivity,which plays a significant role in early bone metastasis screening, diagnosis and

  18. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  19. Modulation of Memory T Cells to Control Acquired Bone Marrow Failure

    Science.gov (United States)

    2016-01-01

    Hemby, S., Kersh, E. & Ahmed, R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111, 837-851 (2002). 11. Lanzavecchia...analysis of histone methylation reveals chromatin state- based regulation of gene transcription and function of memory CD8+ T cells. Immunity 30, 912...AWARD NUMBER: W81XWH-11-1-0294 TITLE: Modulation of Memory T Cells to Control Acquired Bone Marrow Failure PRINCIPAL INVESTIGATOR: Yi

  20. Metabolic control and bone health in adolescents with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Mohan Subburaman

    2011-10-01

    Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

  1. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial.

    Science.gov (United States)

    Primrose, John; Falk, Stephen; Finch-Jones, Meg; Valle, Juan; O'Reilly, Derek; Siriwardena, Ajith; Hornbuckle, Joanne; Peterson, Mark; Rees, Myrddin; Iveson, Tim; Hickish, Tamas; Butler, Rachel; Stanton, Louise; Dixon, Elizabeth; Little, Louisa; Bowers, Megan; Pugh, Siân; Garden, O James; Cunningham, David; Maughan, Tim; Bridgewater, John

    2014-05-01

    Surgery for colorectal liver metastases results in an overall survival of about 40% at 5 years. Progression-free survival is increased with the addition of oxaliplatin and fluorouracil chemotherapy. The addition of cetuximab to these chemotherapy regimens results in an overall survival advantage in patients with advanced disease who have the KRAS exon 2 wild-type tumour genotype. We aimed to assess the benefit of addition of cetuximab to standard chemotherapy in patients with resectable colorectal liver metastasis. Patients with KRAS exon 2 wild-type resectable or suboptimally resectable colorectal liver metastases were randomised in a 1:1 ratio to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done using minimisation with factors of surgical centre, poor prognostic tumour (one or more of: ≥ 4 metastases, N2 disease, or poor differentiation of primary tumour), and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m(2) intravenously over 2 h and fluorouracil bolus 400 mg/m(2) intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m(2) repeated every 2 weeks (regimen one) or oxaliplatin 130 mg/m(2) intravenously over 2 h and oral capecitabine 1000 mg/m(2) twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m(2) intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given as an intravenous dose of 500 mg/m(2) every 2 weeks with regimen one and three or a loading dose of 400 mg/m(2) followed by a weekly infusion of 250 mg/m(2) with regimen two. The primary endpoint was progression-free survival. This is an interim analysis, up to Nov 1, 2012, when the trial was closed, having met protocol-defined futility criteria. This trial is registered, ISRCTN22944367. 128 KRAS exon 2 wild-type patients were randomised to chemotherapy

  2. Targeting Breast Cancer Metastasis

    OpenAIRE

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  3. Bone Mineral Density, Bone Turnover Markers and Fractures in Patients with Systemic Sclerosis: A Case Control Study: e66991

    National Research Council Canada - National Science Library

    Marco Atteritano; Stefania Sorbara; Gianluca Bagnato; Giovanni Miceli; Donatella Sangari; Salvatore Morgante; Elisa Visalli; Gianfilippo Bagnato

    2013-01-01

    .... BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline...

  4. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study

    National Research Council Canada - National Science Library

    Atteritano, Marco; Sorbara, Stefania; Bagnato, Gianluca; Miceli, Giovanni; Sangari, Donatella; Morgante, Salvatore; Visalli, Elisa; Bagnato, Gianfilippo

    2013-01-01

    .... BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline...

  5. Soft tissue sarcoma with metastasis to the stomach: A case report

    Institute of Scientific and Technical Information of China (English)

    Lemuel; Leon; Dent; Cesar; Yamil; Cardona; Michael; Clause; Buchholz; Roosevelt; Peebles; Julie; Denise; Scott; Derrick; Jerome; Beech; Billy; Ray; Ballard

    2010-01-01

    Soft tissue sarcomas are unusual malignancies comprising 1% of cancer diagnoses in the United States. Undifferentiated pleomorphic sarcoma accounts for approximately 5% of sarcomas occurring in adults. The most common site of metastasis is the lung, with other sites being bone, the brain, and the liver. Metastasis to the gastrointestinal tract has rarely been documented. We present an unusual case of high-grade pleomorphic sarcoma with metastasis to the stomach, complicated by upper gastrointestinal bleedin...

  6. Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway.

    Science.gov (United States)

    Xie, Tao; Ren, Hai-Yong; Lin, Hai-Qing; Mao, Jin-Ping; Zhu, Ting; Wang, Sheng-Dong; Ye, Zhao-Ming

    2016-05-01

    Osteosarcoma is the most common primary malignant tumor of the bone. The long-term survivals continue to be unsatisfactory for patients with metastatic and recurrent disease. Metastasis is still a severe challenge in osteosarcoma treatment. Sinomenine, an alkaloid from traditional Chinese medicine, has been proved to possess potent antitumor and anti-invasion effect on various cancers. However, the effect of sinomenine on human osteosarcoma and the underlying mechanisms remains unknown. We report here that sinomenine inhibited proliferation by inducing S phase arrest and suppressing the clone formation. Significant inhibitory effects were found in invasion and metastasis in osteosarcoma, but little cytotoxicity was observed in tested concentrations. Exposure to sinomenine resulted in suppression of invasion and migration in osteosarcoma cells as well as tube formation ability in the human umbilical vein endothelial cells (HUVEC) and U2OS cells. Furthermore, it demonstrated that CXCR4 played a key role contributing to invasion in osteosarcoma which is considered to be a core target site in sinomenine treatment. Sinomenine inhibited invasion by suppressing CXCR4 and STAT3 phosphorylation then downregulating the expression of MMP-2, MMP-9, RANKL, VEGF downstream. In addition, then RANKL-mediated bone destruction stimulated by osteoclastogenesis and VEGF-related neovascularization were restrained. Importantly, in vivo, sinomenine suppressed proliferation, osteoclastogenesis and bone destruction. Through these various comprehensive means, sinomenine inhibits metastasis in osteosarcoma. Taken together, our results revealed that sinomenine caused S phase arrest, inhibited invasion and metastasis via suppressing the CXCR4-STAT3 pathway and then osteoclastogenesis-mediated bone destruction and neovascularization in osteosarcoma. Sinomenine is therefore a promising adjuvant agent for metastasis control in osteosarcoma.

  7. A novel controlled-release system for antibacterial enzyme lysostaphin delivery using hydroxyapatite/chitosan composite bone cement

    National Research Council Canada - National Science Library

    Xue, Bai; Zhang, Cheng; Wang, Yihan; Wang, Jincheng; Zhang, Jien; Lu, Min; Li, Guodong; Cao, Zhizhong; Huang, Qingshan

    2014-01-01

    In this work, a lysostaphin-loaded, control-released, self-setting and injectable porous bone cement with efficient protein delivery was prepared by a novel setting method using hydroxyapatite/chitosan (HA/CS) composite scaffold...

  8. A Novel Controlled-Release System for Antibacterial Enzyme Lysostaphin Delivery Using Hydroxyapatite/Chitosan Composite Bone Cement: e113797

    National Research Council Canada - National Science Library

    Bai Xue; Cheng Zhang; Yihan Wang; Jincheng Wang; Jien Zhang; Min Lu; Guodong Li; Zhizhong Cao; Qingshan Huang

    2014-01-01

      In this work, a lysostaphin-loaded, control-released, self-setting and injectable porous bone cement with efficient protein delivery was prepared by a novel setting method using hydroxyapatite/chitosan (HA/CS) composite scaffold...

  9. Metastasis from breast cancer presenting as an epulis in the upper gingiva

    Directory of Open Access Journals (Sweden)

    Shah Mita

    2009-01-01

    Full Text Available Oral metastasis of breast cancer is less common than metastasis to other sites like the lung and liver. Breast cancer can metastasize to the oral cavity, with presentation like a benign oral lesion. We present an interesting case of breast cancer involving the gingiva with sparing of the underlying bone.

  10. Controlled multiple growth factor delivery from bone tissue engineering scaffolds via designed affinity.

    Science.gov (United States)

    Suárez-González, Darilis; Lee, Jae Sung; Diggs, Alisha; Lu, Yan; Nemke, Brett; Markel, Mark; Hollister, Scott J; Murphy, William L

    2014-08-01

    It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were "dip coated" in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (β-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated β-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dose-dependent manner in a sheep intramuscular implantation model. This approach demonstrates a "modular design" approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating.

  11. Diagnostic value and imaging characteristics of SPECT/CT fusion imaging to bone metastasis of prostate cancer%SPECT/CT同机融合显像对前列腺癌骨转移的诊断价值及影像学特征的研究

    Institute of Scientific and Technical Information of China (English)

    张瑜; 陈跃; 朱艳; 郑文璐

    2015-01-01

    Objective To research the diagnostic value of 99mTc-MDP SPECT/CT fusion imaging to bone metastasis of prostate cancer and the imaging features. Methods: 92 patients with pathologically confirmed prostate cancer and highly suspected bone metastasis received 99mTc-MDP whole body bone scan and SPECT/CT fusion imaging at the same time. The sensitivity, specificity and accuracy of the two methods were compared. Results The sensitivity of whole body bone scan and SPECT/CT fusion imaging was 87.5% and 95.7%. The specificity was 55.7%and 89.1%, and the accuracy was 62%and 92.3% respectively. The accuracy of SPECT/CT was higher than that of whole body bone scan (P< 0.05). Of 242 bone metastasis, 38.4% in the pelvis, 30.9% in the spine, 15.3% in the extremities, 11.6% in the chest, and 3.7% in the skull. CT images showed that osteoblastic metastasis accounted for 90.5%, mixed meta stasis 7.8%, and lytic metastasis 1.7%. Conclusion99mTc-MDP SPECT/CT fusion imaging has higher sensitivity, specificity, and accuracy in diagnosis of bone metastasis of prostate cancer, with good clinical application value. Imaging features showed that most metastases occur in the axial skeleton, with multifocal metastasis. CT features showed that osteoblastic metastasis is more common than mixed and osteolytic metastases.%目的::通过对前列腺癌患者进行99mTc-MDP SPECT/CT同机融合显像,研究99mTc-MDP SPECT/CT融合显像在前列腺癌骨转移诊断中的价值及其影像学特征。方法:入选92例经病理证实为前列腺癌且高度怀疑有骨转移患者,同时行99mTc-MDP全身骨扫描及SPECT/CT融合显像。通过对比分析二者的灵敏度、特异性、准确性,进而评价SPECT/CT融合显像在前列腺癌骨转移定性诊断中的价值。并分析骨转移灶的部位、数量以及悦栽表现特点,以获得前列腺癌骨转移放射性分布特征以及骨质破坏特征。结果:全身骨显像与SPECT/CT融合显像诊断前列腺癌

  12. Quantitative protein profiling of tumor angiogenesis and metastasis biomarkers in mouse and human models

    Science.gov (United States)

    Tumor and stromal cells secrete a variety of proteins acting as extracellular signals and creating a supportive microenvironment for tumor development, angiogenesis, and metastasis. We used the Luminex immunoassay platform (including MILLIPLEX® MAP cytokine/chemokine, bone metabolism, adipocyte, M...

  13. Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β-SMAD3 pathway in non-small cell lung adenocarcinoma.

    Science.gov (United States)

    Risolino, Maurizio; Mandia, Nadia; Iavarone, Francescopaolo; Dardaei, Leila; Longobardi, Elena; Fernandez, Serena; Talotta, Francesco; Bianchi, Fabrizio; Pisati, Federica; Spaggiari, Lorenzo; Harter, Patrick N; Mittelbronn, Michel; Schulte, Dorothea; Incoronato, Mariarosaria; Di Fiore, Pier Paolo; Blasi, Francesco; Verde, Pasquale

    2014-09-01

    Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial-mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β. Here we show that, in addition to inhibiting primary tumor growth, PREP1 is a novel EMT inducer and prometastatic transcription factor. In human non-small cell lung cancer (NSCLC) cells, PREP1 overexpression is sufficient to trigger EMT, whereas PREP1 down-regulation inhibits the induction of EMT in response to TGF-β. PREP1 modulates the cellular sensitivity to TGF-β by inducing the small mothers against decapentaplegic homolog 3 (SMAD3) nuclear translocation through mechanisms dependent, at least in part, on PREP1-mediated transactivation of a regulatory element in the SMAD3 first intron. Along with the stabilization and accumulation of PBX1, PREP1 induces the expression of multiple activator protein 1 components including the proinvasive Fos-related antigen 1 (FRA-1) oncoprotein. Both FRA-1 and PBX1 are required for the mesenchymal changes triggered by PREP1 in lung tumor cells. Finally, we show that the PREP1-induced mesenchymal transformation correlates with significantly increased lung colonization by cells overexpressing PREP1. Accordingly, we have detected PREP1 accumulation in a large number of human brain metastases of various solid tumors, including NSCLC. These findings point to a novel role of the PREP1 homeoprotein in the control of the TGF-β pathway, EMT, and metastasis in NSCLC.

  14. Brain metastasis: new opportunities to tackle therapeutic resistance.

    Science.gov (United States)

    Seoane, Joan; De Mattos-Arruda, Leticia

    2014-09-12

    Brain metastasis is a devastating complication of cancer with unmet therapeutic needs. The incidence of brain metastasis has been rising in cancer patients and its response to treatment is limited due to the singular characteristics of brain metastasis (i.e., blood-brain-barrier, immune system, stroma). Despite improvements in the treatment and control of extracranial disease, the outcomes of patients with brain metastasis remain dismal. The mechanisms that allow tumor cells to promulgate metastases to the brain remain poorly understood. Further work is required to identify the molecular alterations inherent to brain metastasis in order to identify novel therapeutic targets and explicate the mechanisms of resistance to systemic therapeutics. In this article, we review current knowledge of the unique characteristics of brain metastasis, implications in therapeutic resistance, and the possibility of developing biomarkers to rationally guide the use of targeted agents.

  15. Fast and automatic depth control of iterative bone ablation based on optical coherence tomography data

    Science.gov (United States)

    Fuchs, Alexander; Pengel, Steffen; Bergmeier, Jan; Kahrs, Lüder A.; Ortmaier, Tobias

    2015-07-01

    Laser surgery is an established clinical procedure in dental applications, soft tissue ablation, and ophthalmology. The presented experimental set-up for closed-loop control of laser bone ablation addresses a feedback system and enables safe ablation towards anatomical structures that usually would have high risk of damage. This study is based on combined working volumes of optical coherence tomography (OCT) and Er:YAG cutting laser. High level of automation in fast image data processing and tissue treatment enables reproducible results and shortens the time in the operating room. For registration of the two coordinate systems a cross-like incision is ablated with the Er:YAG laser and segmented with OCT in three distances. The resulting Er:YAG coordinate system is reconstructed. A parameter list defines multiple sets of laser parameters including discrete and specific ablation rates as ablation model. The control algorithm uses this model to plan corrective laser paths for each set of laser parameters and dynamically adapts the distance of the laser focus. With this iterative control cycle consisting of image processing, path planning, ablation, and moistening of tissue the target geometry and desired depth are approximated until no further corrective laser paths can be set. The achieved depth stays within the tolerances of the parameter set with the smallest ablation rate. Specimen trials with fresh porcine bone have been conducted to prove the functionality of the developed concept. Flat bottom surfaces and sharp edges of the outline without visual signs of thermal damage verify the feasibility of automated, OCT controlled laser bone ablation with minimal process time.

  16. The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

    Science.gov (United States)

    DeWoody, Yssa

    1996-01-01

    The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques require