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Sample records for cancer bone metastasis

  1. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    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

  2. 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.

  3. 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.

  4. Therapy for bone metastasis from different cancers

    Institute of Scientific and Technical Information of China (English)

    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.

  5. 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.

  6. Mechanisms of cancer metastasis to the bone

    Institute of Scientific and Technical Information of China (English)

    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.

  7. 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.

  8. [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.

  9. 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.

  10. 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...

  11. 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)

  12. 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

  13. 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.

  14. 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.

  15. 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

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

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    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.

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

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    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

  18. 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.

  19. The host microenvironment influences prostate cancer invasion, systemic spread, bone colonization, and osteoblastic metastasis

    Directory of Open Access Journals (Sweden)

    Sourik S Ganguly

    2014-12-01

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer death in men worldwide. Most PCa patients die with 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. In this revew, 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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  5. Tumor-Host Interaction in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2006-01-01

    immortalized osteoblasts. REPORTABLE OUTCOMES • Thesis , entitled “PDGF expression by breast cancer cells, and its role in regulating osteolytic...investigation of microenvironmental regulation of genes, including (MMP-11 and cathepsin K) in breast cancer that may impact the progression of bone...C, Fan D, O’Brian CA, et al. Modulation of doxorubicin sensitivity and level of p-glycoprotein expression in human colon carcinoma cells by ectopic

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

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    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.

  7. 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.

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

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    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.

  9. 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.

  10. 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

  11. 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).

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Raman spectroscopy of bone metastasis

    Science.gov (United States)

    Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

    2012-02-01

    Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

  17. 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.

  18. 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.

  19. 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.

  20. Targeting Neuropilin-1 in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2011-04-01

    Courilleau D, Mester J, Redeuilh G. (1999). Estrogen induction of the cyclin D1 promoter: involvement of a cAMP response-like element. Proc Natl...Sands MS, Ross FP, Teitelbaum SL, Novack DV. Critical role of beta3 integrin in experimental postmenopausal osteoporosis . J Bone Miner Res 2005;20(12...Amizuka N, Irie K, et al. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Com- mun

  1. 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

  2. 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.

  3. 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)

  4. Role of Katanin in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2009-01-01

    analyzed with TissueScan Prostate Cancer Panel I ( Origene , Rockville, MD), we found that KATNA1- E7 was expressed broadly in most of samples including...it also cross-reacts with some high molecular weight, non-specific proteins in cell lysates. Far before the B01P antibody coming to market , we had

  5. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    the presence of X-gal (LacZ re- porter gene transcription) and in the absence of leucine (LEU2 reporter gene transcription), histidine (selection for...and can function as a paracrine survival factor for humanmyeloma cells. Cancer Res 2003;63:912–6. 46. Labrinidis A, Diamond P,Martin S, Hay S, Liapis

  6. 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.

  7. 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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. [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.

  15. 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

  16. 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.

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

    Science.gov (United States)

    2009-01-01

    Plasmids. pCEP4-HIF-1α (MBA-2) was purchased from the ATCC; pCMV-Smad2 and - Smad3 were from Dr. David Wotton (University of Virginia); pCMV-Smad4 was...welcome addition to current armamentarium for bone metastases. 35 References 1. Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

    Directory of Open Access Journals (Sweden)

    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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

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

    Science.gov (United States)

    2009-03-14

    Pohl from Emory University to the Center for Disease Control at Atlanta. However, we will pursue this aim in collaboration with Dr. David Agus...bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593. doi: 10.1038/nrc867 30. Roodman GD (2004) Mechanisms of bone

  15. 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

  16. 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

  17. Global secretome analysis identifies novel mediators of bone metastasis

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0412 TITLE: "Targeting Prostate Cancer Metastasis " PRINCIPAL INVESTIGATOR: Yong Teng CONTRACTING ORGANIZATION: REPORT...ng Prost a t e Cancer Metastasi s Sb. GRANT NUMBER W81XWH- 14- 1- 0 41 2 Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER YongTeng Se...r egulator in contr olling metastasis of p r ost a t e cancer and i nhi b i t i ng i t prevent s met ast asis . There are no drugs available to tar

  19. 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

  20. 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...

  1. 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

  2. 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.

  3. 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.

  4. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  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. 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.

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

    Science.gov (United States)

    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.

  8. Metastasis and bone loss: Advancing treatment and prevention

    Science.gov (United States)

    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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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。

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. 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

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Science.gov (United States)

    2009-04-01

    2008) 27:41–55 70. Scott, L. J., Clarke, N.W., George, N. J., Shanks, J. H., Testa , N. G., & Lang, S. H. (2001). Interactions of human prostatic...structural alterations of bones in heparin-induced osteoporosis. Clin Rheumatol, 22, 432-6. 23 38. Moreno- Reyes , R., Egrise, D., Neve, J., Pasteels

  7. 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

  8. 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.

  9. 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。

  10. 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

  11. 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

  12. Imaging of bone metastasis: An update

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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

  15. 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

  16. 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.

  17. [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.

  18. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H;

    2013-01-01

    -specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six...

  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. 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.

  1. Incidence of bone metastasis in carcinoma buccal mucosa

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Pathobiology of cancer metastasis: a short account

    Directory of Open Access Journals (Sweden)

    Feller Liviu

    2012-06-01

    Full Text Available Abstract Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis. Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site. It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis.

  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. 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

  11. The negative prognostic impact of bone metastasis with a tumor mass

    Directory of Open Access Journals (Sweden)

    Birsen Yücel

    2015-08-01

    Full Text Available OBJECTIVE:Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer.METHODS:Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001.RESULTS:According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76. Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers, and spinal cord compression.CONCLUSION:Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.

  12. 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.

  13. 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.

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

    OpenAIRE

    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.

  15. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  16. Gastric metastasis of bilateral breast cancer

    Science.gov (United States)

    Belaïd, Asma; Mghirbi, Fahmi; Béhi, Khalil; Doghri, Raoudha; Benna, Farouk

    2017-01-01

    Breast cancer is the most common malignancy in women. The most frequent metastatic sites are lung, bone, liver and brain. On the other hand, gastric metastases are rare. Synchronous bilateral breast cancer (SBBC) occurs rarely. Lobular carcinoma is the histological type most often associated with bilateral breast carcinomas and gastric metastases. We made a retrospective study including four patients followed in the Salah Azaiez Institute, for a bilateral breast cancer with gastric metastases. We analyzed the epidemiological, anatomoclinical and therapeutic particularities of this rare entity. Symptoms were unspecific. The diagnosis of gastric metastasis of the SBBC was confirmed by a histopathological examination of an endoscopic biopsy. The median age was 46.2 years (range, 36–51 years) and the median time until the gastric involvement was 19 months (range, 0–41 months). None of patients had a surgical treatment for the gastric location. All Patients received at least one line of chemotherapy and radiotherapy. Median survival following the detection of gastric involvement was 22 months (range, 1–56 months). Gastric metastases from breast cancer are rare and frequently associated with other distant metastasis. Symptoms are unspecific and endoscopy may not be contributive. Therefore, gastric involvement is underestimated. Lobular infiltrating carcinoma (LIC) is the most histological type incriminated in its occurrence. The supply of immunohistochemistry is crucial to distinguish between primary or metastatic gastric cancer. PMID:28280631

  17. Cancer stem cells and metastasis.

    Science.gov (United States)

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  18. 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.

  19. 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.

  20. 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

  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. 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....

  3. 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

  4. Breast Cancer Metastasis to Pituitary Infandibulum

    Directory of Open Access Journals (Sweden)

    Maryam Poursadegh Fard

    2011-06-01

    Full Text Available Metastasis from breast cancer to other parts of the body is very common, but the spread of the tumor to pituitary gland, especially to infandibulum, is a rare presentation. At the time of pituitary metastasis, a majority of the patients have clinical and radiological evidence of the disease. It seems that the posterior area of the gland is the most common site of metastasis, probably due to highly rich blood supply through the hypophyseal artery. The present report introduces a case of a 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infandibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected

  5. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  6. 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.

  7. 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

    Paw withdrawal latency to thermal stimuli of radiant heat was measured using a device (Plantar test, 7370; Ugo Basile, Comerio, Italy). Briefly...1115. II. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous... hyperalgesia . Pain 32:77–88. FIGURE 3 LC CO Fatty Acids on MDA-231bone Bone Tumors of Tibial

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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。

  14. Receptor for Advanced Glycation End Products (RAGE) as a Novel Target for Inhibiting Breast Cancer Bone Metastasis

    Science.gov (United States)

    2013-04-01

    generated for studying the role of mS100a7a15 in psoriasis (26). To determine the role of mS100a7a15 in tumor- igenesis, we generated an inducible...been proposed for hS100A7, its biologic role particularly in breast cancer remains to be defined. In this study, we characterized the tumor-enhancing...mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 2006;95: 272–81. 22. Webb

  15. Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis

    DEFF Research Database (Denmark)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2016-01-01

    Secondary metastatic cancer remains the single biggest cause of mortality and morbidity across most solid tumors. In breast cancer, 100% of deaths are attributed to metastasis. At present, there are no "cures" for secondary metastatic cancer of any form and there is an urgent unmet clinical need...... to improve the tools available in our arsenal against this disease, both in terms of treatment, but also prevention. Recently, we showed that hypoxic induction of the extracellular matrix modifying enzyme lysyl oxidase (LOX) correlates with metastatic dissemination to the bone in estrogen receptor negative...... breast cancer and is essential for the formation of premetastatic osteolytic lesions. We showed that in models of breast cancer metastasis, targeting LOX, or its downstream effects, significantly inhibited premetastatic niche formation and the resulting metastatic burden, offering preclinical validation...

  16. Progress in the clinical use of radiotherapy for bone metastasis in breast cancer%放疗在乳腺癌骨转移中的临床应用进展

    Institute of Scientific and Technical Information of China (English)

    胡群超(综述); 俞晓立; 郭小毛(审校)

    2016-01-01

    骨转移是晚期乳腺癌最常见的远处转移,多伴有局部疼痛、肢体功能障碍等症状,常导致患者的生存质量下降。由骨转移引起的病理性骨折等骨相关事件(skeletal-related events,SREs)会显著增加乳腺癌患者的死亡风险。积极有效的骨转移治疗有重要的临床意义,放疗是重要的局部治疗手段。本文就放疗在乳腺癌骨转移中的临床应用进展进行综述,着重阐述放疗实施手段及综合治疗模式的循证医学证据。%Bone remains the predominant site of metastasis in advanced breast cancer. Bone metastases dramatically decrease the quality of life. Moreover, pathologic fractures and other skeletal-related events (SREs) caused by bone metastases could result in higher mortality risk in patients with breast cancer. Palliative radiotherapy is a crucial element in bone metastases treatment. The present review discusses the emerging evidence in bone metastases of breast cancer, focusing on optimized radiotherapy strategies and multidisciplinary management.

  17. Gastric metastasis from primary lung adenocarcinomamimicking primary gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Min Ji Kim; Ji Hyung Hong; Eun Su Park; Jae Ho Byun

    2015-01-01

    Gastric metastases from lung adenocarcinoma arerare. Because gastric metastasis grossly resemblesadvanced gastric cancer, it is difficult to diagnose gastricmetastasis especially when the histology of the primarylung cancer is adenocarcinoma. We describe a case ofgastric metastasis from primary lung adenocarcinomamimicking Borrmann type Ⅳ primary gastric cancer.A 68-year-old man with known lung adenocarcinomawith multiple bone metastases had been experiencingprogressive epigastric pain and dyspepsia over one year.Esophagogastroduodenoscopy revealed linitis plasticalikelesions in the fundus of the stomach. Pathologicexamination revealed a moderately differentiatedadenocarcinoma with submucosal infiltration. Positiveimmunohistochemical staining for thyroid transcriptionfactor-1 (TTF-1) and napsin A (Nap-A) confirmed thatthe metastasis was pulmonary in origin. The patienthad been treated with palliative chemotherapy for thelung cancer and had lived for over fifteen months afterthe diagnosis of gastric metastasis. Clinicians should beaware of the possibility of gastric metastasis in patientswith primary lung adenocarcinoma, and additionalimmunohistochemical staining for Nap-A as well as TTF-1may help in differentiating its origin.

  18. Subcapsular Orchiectomy in the Primary Therapy of Patients with Bone Metastasis in Advanced Prostate Cancer: An Anachronistic Intervention?

    Directory of Open Access Journals (Sweden)

    Oleg Rud

    2012-01-01

    Full Text Available Background. The therapeutic impact of palliative androgen deprivation in metastatic prostate cancer is indisputable. Bilateral orchiectomy represents the traditional method of AD but was reduced during the last years in favor for treatment with LHRH analogues. Due to limited economic resources of the health care system, the economically priced definite surgical castration might experience a renaissance. Methods. In this single-center retrospective study, 83 consecutive patients with osseous metastasized prostate cancer were evaluated, who had primarily been treated by subcapsular bilateral orchiectomy. Response to therapy, time until therapy failure, overall survival time, psychological disorders due to loss of organ, and disease-associated and postoperative surgical complications were recorded. The median followup was 35 months (IQR: 26–46. Results. Patients' mean age at surgery was 72.1 (54–91 years. Six patients (7.2% displayed immediate tumor progression after orchiectomy. Median time of tumor remission and overall survival time were 29 and 36 months, respectively. 14% of the study group showed minor postoperative complications. No psychological problems occurred following bilateral orchiectomy. Conclusion. Due to an effective and persistent oncological effectiveness, less morbidity, and absence of psychological implications, bilateral subcapsular orchiectomy seems to be a practicable and advisable alternative in the first-line therapy of metastasized PCa.

  19. 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.

  20. Biology of cancer invasion and metastasis.

    Science.gov (United States)

    Mareel, M M; Crombez, R

    1992-01-01

    Current concepts of invasion eventually leading to metastasis are discussed and exemplified by cancers of the head and neck mucosa. Invasion occurs at a number of steps, each step making an ecosystem comprising not only the neoplastic cells but also their normal counterparts, a variety of host cells and the extracellular matrix. The ecosystem concept may explain aspects of metastasis such as site-dependence and organ-specificity of cancer metastasis as well as invasiveness of normal leucocytes. Genes implicated in invasion and metastasis are actively searched for. Recently, the epithelial cell-cell adhesion molecule E-cadherin has been identified as an i- (invasion suppressor) gene product, i.e. a molecule the expression of which counterbalances i+ (invasion promotor) gene activity. Downregulation of E-cadherin in human head and neck cancers may account for their invasive and metastatic behaviour.

  1. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  2. 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

  3. Metastatic bone cancer as a recurrence of early gastric cancer - characteristics and possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Takehiro Okabayashi; Takeshi Sano; Keijiro Araki

    2005-01-01

    The surgical outcome of most early gastric cancer (EGC)is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed.Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan.This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Postoperative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases.

  4. Invasion and metastasis in pancreatic cancer.

    Science.gov (United States)

    Keleg, Shereen; Büchler, Peter; Ludwig, Roman; Büchler, Markus W; Friess, Helmut

    2003-01-22

    Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well. Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival. During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth. The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis. In this review we highlight the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.

  5. 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.

  6. 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.

  7. 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.

  8. Multiple Metastasis-Like Bone Lesions in Scintigraphic Imaging

    Directory of Open Access Journals (Sweden)

    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. 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.

  10. Revisiting the Seed-and-soil Theory of Cancer Metastasis

    Institute of Scientific and Technical Information of China (English)

    Chaonan QIAN

    2009-01-01

    @@ In 1889, Paget proposed a "Seed-and-Soil" theory for cancer metastasis.According to this theory, cancer metastasis is not random, and one remote organ is more prone to be the seat of secondary tumor growth than another.

  11. Ureteral metastasis from prostate cancer.

    Science.gov (United States)

    Hongo, Hiroshi; Kosaka, Takeo; Yoshimine, Shunsuke; Oya, Mototsugu

    2014-08-28

    A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. [Adenocarcinoma of lung cancer with solitary metastasis to the stomach].

    Science.gov (United States)

    Koh, Sung Ae; Lee, Kyung Hee

    2014-09-25

    Although hematogenous metastasis of cancer to the gastrointestinal track is rare, it sometime has been reported in patients with malignant melanoma and breast cancer. However, it is extremely rare for lung cancer to metastasize to the stomach, not to mention solitary gastric metastasis. Herein, the authors report a case of a 69-year-old man who was initially diagnosed with lung cancer with synchronous primary gastric cancer which proved to be lung cancer with solitary gastric metastasis after the operation.

  17. 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.

  18. 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.

  19. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan

    2016-10-01

    Full Text Available Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

  20. Cancer Cell Colonisation in the Bone Microenvironment

    Science.gov (United States)

    Kan, Casina; Vargas, Geoffrey; Le Pape, François; Clézardin, Philippe

    2016-01-01

    Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow. PMID:27782035

  1. 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

  2. Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis.

    Science.gov (United States)

    Cox, Thomas R; Gartland, Alison; Erler, Janine T

    2016-01-15

    Secondary metastatic cancer remains the single biggest cause of mortality and morbidity across most solid tumors. In breast cancer, 100% of deaths are attributed to metastasis. At present, there are no "cures" for secondary metastatic cancer of any form and there is an urgent unmet clinical need to improve the tools available in our arsenal against this disease, both in terms of treatment, but also prevention. Recently, we showed that hypoxic induction of the extracellular matrix modifying enzyme lysyl oxidase (LOX) correlates with metastatic dissemination to the bone in estrogen receptor negative breast cancer and is essential for the formation of premetastatic osteolytic lesions. We showed that in models of breast cancer metastasis, targeting LOX, or its downstream effects, significantly inhibited premetastatic niche formation and the resulting metastatic burden, offering preclinical validation of this enzyme as a therapeutic target for metastatic breast cancer. Our work is the latest in an emerging body of work supporting the targeting of LOX and calls for greater efforts in developing therapeutics against this extracellular secreted factor in the prevention of cancer progression across multiple solid tumor types.

  3. 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.

  4. Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities.

    Science.gov (United States)

    Yang, Wenyong; Zou, Linzhi; Huang, Canhua; Lei, Yunlong

    2014-08-01

    Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.

  5. Spinal Intramedullary Metastasis of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Recep Basaran

    2014-01-01

    Full Text Available Objective. Breast cancer accounts for approximately one-third of all cancers in females. Approximately 8.5 % of all central nervous system metastases are located in the spinal cord. These patients have rapidly progressing neurological deficits and require immediate examination. The aim of surgery is decompression of neural tissue and histological evaluation of the tumor. In this paper, we present a case of breast cancer metastasis in thoracic spinal intramedullary area which had been partially excised and then given adjuvant radiotherapy. Case. A 43-year-old female patient with breast cancer for 8 years was admitted to our hospital with complaints of weakness in both legs. Eight years ago, she received chemotherapy and radiotherapy. On her neurological examination, she had paraparesis (left lower extremity: 2/5, right lower extremity: 3/5 and urinary incontinence. Spinal MRI revealed a gadolinium enhancing intramedullary lesion. Pathologic examination of the lesion was consistent with breast carcinoma metastasis. The patient has been taken into radiotherapy. Conclusion. Spinal intramedullary metastasis of breast cancer is an extremely rare situation, but it has a high morbidity and mortality rate. Microsurgical resection is necessary for preservation or amelioration of neurological state and also for increased life expectancy and quality.

  6. Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Understanding and optimizing bone health in breast cancer.

    Science.gov (United States)

    Guise, Theresa A; Brufsky, Adam; Coleman, Robert E

    2010-12-01

    Bone is the preferred site of metastasis for breast cancer, and presence of skeletal lesions is associated with significant morbidity and poor prognosis. Skeletal-related effects such as pain, pathologic fractures, spinal compression, and hypercalcemia are frequent consequences of skeletal lesions of breast cancer that have debilitating effects on the patients' quality of life. In addition to direct cancer effects on the skeleton, therapies commonly used to treat patients with breast cancer such as chemotherapy and aromatase inhibitors (AI) result in cancer therapy-induced bone loss (CTIBL) which is associated with increased risk of skeletal complications such as fractures. Bisphosphonates are a class of antiresorptive drugs that are now firmly established as the cornerstone of the management of skeletal-related events due to breast cancer. Other novel bone-targeting agents such as the anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody denosumab are also showing promising activity in the treatment of bone metastasis secondary to breast cancer. Moreover, recent provocative evidence suggests that bisphosphonates might also exhibit antitumor activity via direct and indirect mechanisms. The goal of this review is to summarize the pathophysiology of osteolytic bone lesions secondary to breast cancer, provide clinical evidence of currently available bone-targeted drugs in the treatment of bone metastasis and CTIBL, and explore the antitumor activity of current bone-targeted agents in patients with breast cancer.

  9. MicroRNA regulation network in colorectal cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  10. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  11. 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.

  12. 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

  13. 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....

  14. 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.

  15. 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.

  16. Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

    Science.gov (United States)

    2008-04-01

    Sellinger, D. S., McBeath, A. A., and Engber, W. D. Metastatic breast cancer in the femur . A search for the lesion at risk of fracture . Clin Orthop...cancer, bone metastasis , animal model, radiation therapy, anabolic agents, bisphosphonates, biomechanical testing, histology 16. SECURITY...Current treatment for osteolytic breast cancer bone metastasis typically involves radiation therapy (RTX) to palliate bone pain and a

  17. Laryngeal metastasis from lung cancer

    OpenAIRE

    Umasankar Kalai; Karan Madan; Deepali Jain; Anant Mohan; Randeep Guleria

    2015-01-01

    Metastatic tumors of the larynx are rare. The most common tumors metastasizing to the larynx are melanoma and renal cell carcinoma. Bronchogenic carcinoma metastasizing to the larynx has been rarely described. Herein, we report the case of a 49-year-old, chronic smoker, who incidentally had a laryngeal growth detected during flexible bronchoscopy examination for evaluation of suspected lung cancer. Histopathological examination of the laryngeal nodule and the biopsy obtained from the main bro...

  18. 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。

  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. 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).

  1. An evidence-based knowledgebase of metastasis suppressors to identify key pathways relevant to cancer metastasis.

    Science.gov (United States)

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-10-21

    Metastasis suppressor genes (MS genes) are genes that play important roles in inhibiting the process of cancer metastasis without preventing growth of the primary tumor. Identification of these genes and understanding their functions are critical for investigation of cancer metastasis. Recent studies on cancer metastasis have identified many new susceptibility MS genes. However, the comprehensive illustration of diverse cellular processes regulated by metastasis suppressors during the metastasis cascade is lacking. Thus, the relationship between MS genes and cancer risk is still unclear. To unveil the cellular complexity of MS genes, we have constructed MSGene (http://MSGene.bioinfo-minzhao.org/), the first literature-based gene resource for exploring human MS genes. In total, we manually curated 194 experimentally verified MS genes and mapped to 1448 homologous genes from 17 model species. Follow-up functional analyses associated 194 human MS genes with epithelium/tissue morphogenesis and epithelia cell proliferation. In addition, pathway analysis highlights the prominent role of MS genes in activation of platelets and coagulation system in tumor metastatic cascade. Moreover, global mutation pattern of MS genes across multiple cancers may reveal common cancer metastasis mechanisms. All these results illustrate the importance of MSGene to our understanding on cell development and cancer metastasis.

  2. TGF-β in cancer and bone: implications for treatment of bone metastases.

    Science.gov (United States)

    Juárez, Patricia; Guise, Theresa A

    2011-01-01

    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  3. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  4. Progression and metastasis of lung cancer.

    Science.gov (United States)

    Popper, Helmut H

    2016-03-01

    Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack. Once in the blood stream, cells have to survive trapping by the coagulation system, to survive shear stress in small blood vessels, and to find the right location for extravasation. Once outside in the metastatic locus, tumor cells have to learn the communication with the "foreign" stroma cells to establish vascular supply and again express molecules, which induce immune tolerance.

  5. Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV-PymT mammary cancer cells in vivo.

    Science.gov (United States)

    Werbeck, J L; Thudi, N K; Martin, C K; Premanandan, C; Yu, L; Ostrowksi, M C; Rosol, T J

    2014-07-01

    Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment.

  6. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  7. [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.

  8. Pre-osteoblastic MC3T3-E1 promote breast cancer cell growth in bone in a murine xenograft model

    Science.gov (United States)

    The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cance...

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

    Science.gov (United States)

    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

  10. 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

  11. 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

  12. Solitary Spinal Epidural Metastasis from Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Taisei Sako

    2016-01-01

    Full Text Available Solitary epidural space metastasis of a malignant tumor is rare. We encountered a 79-year-old male patient with solitary metastatic epidural tumor who developed paraplegia and dysuria. The patient had undergone total gastrectomy for gastric cancer followed by chemotherapy 8 months priorly. The whole body was examined for suspected metastatic spinal tumor, but no metastases of the spine or important organs were observed, and a solitary mass was present in the thoracic spinal epidural space. The mass was excised for diagnosis and treatment and was histopathologically diagnosed as metastasis from gastric cancer. No solitary metastatic epidural tumor from gastric cancer has been reported in English. Among the Japanese, 3 cases have been reported, in which the outcome was poor in all cases and no definite diagnosis could be made before surgery in any case. Our patient developed concomitant pneumonia after surgery and died shortly after the surgery. When a patient has a past medical history of malignant tumor, the possibility of a solitary metastatic tumor in the epidural space should be considered.

  13. Altering the Microenvironment to Promote Dormancy of Metastatic Breast Cancer Cell in a 3D Bone Culture System

    Science.gov (United States)

    2015-12-01

    1138-1148. Carlsten, H. 2005. Immune responses and bone loss: the estrogen connection. Immunological reviews . 208:194- 206. 28 Gehler, S., S.M...factors to be considered in cancer recurrence ( reviewed by [6]). Das Roy et al. found an increase in lung and bone marrow metastasis using an...activation of COX-2, plays an important role in normal bone physiology as well as in cancer and bone metastasis ( review [43]). In the normal bone, PGE2 is the

  14. The role of GAGE cancer/testis antigen in metastasis

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Terp, Mikkel Green; Hansen, Malene Bredahl;

    2016-01-01

    with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  15. Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis.

    Science.gov (United States)

    Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi

    2016-10-05

    Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.

  16. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0316 TITLE: Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis PRINCIPAL...Cancer Brain Metastasis 5b. GRANT NUMBER W81XWH-12-1-0316 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Rolf A. Brekken...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Brain metastasis occurs in

  17. Calvarial Mass Confused With Trichilemmal Cyst: Hepatocellular Cancer Metastasis.

    Science.gov (United States)

    Polat, Gökhan; Sade, Recep

    2017-03-01

    The hepatocellular cancer calvarial metastasis is a rare condition that commonly presents cranial swelling. Therefore, calvarial swelling may confuse with frequent lesions of the scalp. The authors' patient was operated as trichilemmal cyst. But, intracranial extension was seen in operation. Calvarial metastasis of hepatocellular cancer was observed by examination of the patient.

  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. 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

  20. 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.

  1. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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.

  5. 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。

  6. Bisphosphonate-related osteonecrosis of jaws in advanced stage breast cancer was detected from bone scan: a case report

    Science.gov (United States)

    Chirappapha, Prakasit; Thongjood, Thanaporn; Aroonroch, Rangsima

    2017-01-01

    Bisphosphonates (BPs) are indicated to treat skeletal-related events (SREs) for cancer patients with bone metastasis. We report a 79-year-old woman with advanced stage breast cancer with bone metastasis who was prescribed BPs (zoledronate), then developed osteonecrosis of jaw. We provide a brief review of the pathogenesis, diagnosis and treatment of this complication. PMID:28210558

  7. 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.

  8. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. 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

  10. A case report of thyroid gland metastasis associated with lung metastasis from colon cancer.

    Science.gov (United States)

    Nakamura, Keisuke; Nozawa, Keijiro; Aoyagi, Yoshiko; Ishihara, Soichiro; Matsuda, Keiji; Fukushima, Junichi; Watanabe, Toshiaki

    2011-01-01

    Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.

    Science.gov (United States)

    He, Xinyu; Yu, Haijun; Bao, Xiaoyue; Cao, Haiqiang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2016-02-18

    Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.

  13. 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

  14. 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.

  15. Potential Anti-metastasis Natural Compounds for Lung Cancer.

    Science.gov (United States)

    Chanvorachote, Pithi; Chamni, Supakarn; Ninsontia, Chuanpit; Phiboonchaiyanan, Preeyaporn Plaimee

    2016-11-01

    As lung cancer is the most common malignancy worldwide and high mortalities are the result of metastasis, novel information surpassing the treatment strategies and therapeutic agents focusing on cancer dissemination are of interest. Lung cancer metastasis involves increased motility, survival in circulation and ability to form new tumors. Metastatic cells increase their aggressive features by utilizing several mechanisms to overcome hindrances of metastasis, including epithelial to mesenchymal transition (EMT), increased in cellular survival and migratory signals. Sufficient amounts of natural product-derived compounds have been shown to have promising anti-metastasis activities by suppressing key molecular features upholding such cell aggressiveness. The knowledge regarding molecular mechanisms rendering cell dissemination together with the anti-metastasis information of natural product-derived compounds may lead to development of novel therapeutic strategies.

  16. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

    Science.gov (United States)

    Yeung, Tsz-Lun; Leung, Cecilia S; Yip, Kay-Pong; Au Yeung, Chi Lam; Wong, Stephen T C; Mok, Samuel C

    2015-10-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

  17. 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.

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

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    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.

  19. Gastric Metastasis of Breast Cancer: A Case Series

    Science.gov (United States)

    dos Santos Fernandes, Gustavo; Batista Bugiato Faria, Luiza D.; de Assis Pereira, Isadora; Neves, Natália C. Moreira; Vieira, Yasmine Oliveira; Leal, Alessandro I. Cavalcanti

    2016-01-01

    Gastric metastasis is rare but it can be the initial symptom of cancer. The second leading cause of this type of metastasis is breast cancer. A lack of clinical signs and nonspecific side effects of the treatment of primary tumors can lead to the misdiagnosis of metastatic gastric cancer. Upper gastrointestinal endoscopy with biopsy and immunohistochemistry should be used for diagnosis. Treatment is palliative; it includes chemo, endocrine, and radiation therapies. Four patients with breast cancer and gastric metastasis were identified. All the patients tested positive for estrogen and progesterone receptors, and received chemotherapy and hormone therapy. One patient underwent surgery and two received radiation therapy. Patients with breast cancer and gastrointestinal symptoms should be investigated for gastric metastasis, given its morbidity and negative impact on quality of life.

  20. 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

  1. Optimal management of bone metastases in breast cancer patients

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    Wong MH

    2011-05-01

    Full Text Available MH Wong, N PavlakisDepartment of Medical Oncology, Royal North Shore Hospital, Sydney, NSW, AustraliaAbstract: Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.Keywords: breast cancer, bone metastases, bisphosphonates, denosumab, biomarkers, optimal management

  2. 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

  3. 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.

  4. 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

  5. Bilateral Choroidal Metastasis from Non-Small Cell Lung Cancer

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    Tariq Namad

    2014-01-01

    Full Text Available Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2–6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.

  6. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    Directory of Open Access Journals (Sweden)

    Priyank Ashok Shenoy

    2016-08-01

    Full Text Available The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  7. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats.

    Science.gov (United States)

    Shenoy, Priyank A; Kuo, Andy; Vetter, Irina; Smith, Maree T

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  8. Mandibular metastasis of adenocarcinoma from prostate cancer: case report according to epidemiology and current therapeutical trends of the advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Juliana Dreyer da Silva de Menezes

    2013-09-01

    Full Text Available Prostate cancer represents the most frequent non-cutaneous neoplasia in males. This type of neoplasia can develop peculiar patterns of evolution, presenting, in many cases, precocious relapses and metastasis. Bone metastasis in the mouth is extremely rare, and represents 1% of all malignant mouth neoplasias. The aim of the present study is to report a clinical case of bone metastasis in the mandibular region associated with a tumoral prostate adenocarcinoma, as well as to discuss connected aspects about diagnosis, prognosis and integrated treatment of this condition.

  9. A niche role for cancer exosomes in metastasis.

    Science.gov (United States)

    Zhang, Yun; Wang, Xiao-Fan

    2015-06-01

    Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.

  10. 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.

  11. Remodeling of the methylation landscape in breast cancer metastasis.

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    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  12. Active Roles of Tumor Stroma in Breast Cancer Metastasis

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    Zahraa I. Khamis

    2012-01-01

    Full Text Available Metastasis is the major cause of death for breast cancer patients. Tumors are heterogenous cellular entities composed of cancer cells and cells of the microenvironment in which they reside. A reciprocal dynamic interaction occurs between the tumor cells and their surrounding stroma under physiological and pathological conditions. This tumor-host communication interface mediates the escape of tumor cells at the primary site, survival of circulating cancer cells in the vasculature, and growth of metastatic cancer at secondary site. Each step of the metastatic process is accompanied by recruitment of stromal cells from the microenvironment and production of unique array of growth factors and chemokines. Stromal microenvironment may play active roles in breast cancer metastasis. Elucidating the types of cells recruited and signal pathways involved in the crosstalk between tumor cells and stromal cells will help identify novel strategies for cotargeting cancer cells and tumor stromal cells to suppress metastasis and improve patient outcome.

  13. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    OpenAIRE

    Priyank Ashok Shenoy; Andy Kuo; Irina Vetter; Maree Therese Smith

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century,...

  14. Post site metastasis of breast cancer after video-assisted thoracic surgery for pulmonary metastasis of breast cancer: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mee Hyun; Hwang, Ji Young; Hyun, Su Jeong; Lee, Yul; Woo, Ji Young; Yang, Ik; Hong, Hye Sook; Kim, Han Myun [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2016-05-15

    We reported a case of port site metastasis in a 57-year-old patient who underwent video-assisted thoracic surgery (VATS) resection of pulmonary metastasis from breast cancer. Port site metastasis after VATS is very rare in patients with breast cancer. However, when suspicious lesions are detected near the port site in patients who have undergone VATS for pulmonary metastasis, port site metastasis should be considered in the differential diagnosis.

  15. Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.

    Science.gov (United States)

    Chen, C; Wang, X; Xiong, X; Liu, Q; Huang, Y; Xu, Q; Hu, J; Ge, G; Ling, K

    2015-08-27

    Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.

  16. 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)

  17. Epithelial-mesenchymal transition in breast cancer progression and metastasis

    Institute of Scientific and Technical Information of China (English)

    Yifan Wang; Binhua P. Zhou

    2011-01-01

    Breast cancer is the most common cancer in women,and approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells.Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell movement during morphogenesis at the time of embryonic development.Tumor cells usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis.Several transcription factors and signals are involved in these events.In this review,we summarize recent advances in breast cancer researches that have provided new insights in the molecular mechanisms underlying EMT regulation during breast cancer progression and metastasis.We especially focus on the molecular pathways that control EMT.

  18. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced...... cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...

  19. Glycan changes: cancer metastasis and anti-cancer vaccines

    Indian Academy of Sciences (India)

    Min Li; Lujun Song; Xinyu Qin

    2010-12-01

    Complex carbohydrates, which are major components of the cell membrane, perform important functions in cell–cell and cell–extracellular matrix interactions, as well as in signal transduction. They comprise three kinds of biomolecules: glycoproteins, proteoglycans and glycosphingolipids. Recent studies have also shown that glycan changes in malignant cells take a variety of forms and mediate key pathophysiological events during the various stages of tumour progression. Glycosylation changes are universal hallmarks of malignant transformation and tumour progression in human cancer, which take place on the whole cells or some specific molecules. Accordingly, those changes make them prominent candidates for cancer biomarkers in the meantime. This review mainly focuses on the correlation between glycosylation and the metastasis potential of tumour cells from comprehensive aspects to further address the vital roles of glycans in oncogenesising. Moreover, utilizing these glycosylation changes to ward off tumour metastasis by means of anti-adhesion approach or devising anti-cancer vaccine is one of promising targets of future study.

  20. 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.

  1. 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

  2. MicroRNA-421 inhibits breast cancer metastasis by targeting metastasis associated 1.

    Science.gov (United States)

    Pan, Yongqin; Jiao, Genlong; Wang, Cunchuan; Yang, Jingge; Yang, Wah

    2016-10-01

    Dysregulation of microRNAs is involved in the initiation and progression of several human cancers, including breast cancer, as strong evidence of miRNAs acting as oncogenes or tumour suppressor genes has been found. This study was performed to investigate the biological functions of microRNA-421 (miR-421) in breast cancer and the underlying mechanisms. The expression level of miR-421 was detected in 50 pairs of surgical specimens and human breast cancer cell lines. The results showed that miR-421 is downregulated in breast cancer tissues and metastatic cell lines. In addition, the decrease in miR-421 levels was significantly associated with lymph node metastasis, recurrence/metastasis, or pTNM stage. Functions of miR-421 in cell migration and invasion were assessed through its silencing and overexpression. The results showed that miR-421 knockdown promotes invasion and metastasis in MCF-7 cells and its overexpression suppresses invasion and metastasis in MDA-MB-231 cells. The specific target genes of miR-421 were predicted by TargetScan algorithm and determined by dual luciferase reporter assay, quantitative reverse transcriptase PCR, and western blot analysis. miR-421 could suppress luciferase activity of the reporter containing 3'-untranslated region of metastasis associated 1 (MTA1), a potent oncogene. miR-421 overexpression or knockdown had no effect on the mRNA expression of MTA1, but it could modulate MTA1 protein level. Furthermore, MTA1 knockdown receded the effect of miR-421 inhibitor on invasion and metastasis of MCF-7 cells, and its overexpression receded the effect of miR-421 on invasion and metastasis of MDA-MB-231 cells. Our findings clearly demonstrate that miR-421 suppresses breast cancer metastasis by directly inhibiting MTA1 expression. The present study provides a new insight into the tumour suppressor roles of miR-421 and suggests that miR-421/MTA1 pathway is a putative therapeutic target in breast cancer.

  3. Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2014-03-01

    Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

  4. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia

    2008-01-01

    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

  5. Metastasis regulation by PPARD expression in cancer cells

    Science.gov (United States)

    Zuo, Xiangsheng; Xu, Weiguo; Xu, Min; Tian, Rui; Moussalli, Micheline J.; Mao, Fei; Zheng, Xiaofeng; Wang, Jing; Morris, Jeffrey S.; Eng, Cathy; Maru, Dipen M.; Rashid, Asif; Broaddus, Russell; Wei, Daoyan; Hung, Mien-Chie; Sood, Anil K.

    2017-01-01

    Peroxisome proliferator–activated receptor–δ (PPARD) is upregulated in many major human cancers, but the role that its expression in cancer cells has in metastasis remains poorly understood. Here, we show that specific PPARD downregulation or genetic deletion of PPARD in cancer cells significantly repressed metastasis in various cancer models in vivo. Mechanistically, PPARD promoted angiogenesis via interleukin 8 in vivo and in vitro. Analysis of transcriptome profiling of HCT116 colon cancer cells with or without genetic deletion of PPARD and gene expression patterns in The Cancer Genome Atlas colorectal adenocarcinoma database identified novel pro-metastatic genes (GJA1, VIM, SPARC, STC1, SNCG) as PPARD targets. PPARD expression in cancer cells drastically affected epithelial-mesenchymal transition, migration, and invasion, further underscoring its necessity for metastasis. Clinically, high PPARD expression in various major human cancers (e.g., colorectal, lung, breast) was associated with significantly reduced metastasis-free survival. Our results demonstrate that PPARD, a druggable protein, is an important molecular target in metastatic cancer. PMID:28097239

  6. Lung Cancer Presenting as a Soft-Tissue Metastasis

    Directory of Open Access Journals (Sweden)

    Candice Baldeo

    2015-04-01

    Full Text Available Soft-tissue metastasis refers to the growth of cancer cells, originating from internal cancer, in soft tissues. In most cases, soft-tissue metastases develop after initial diagnosis of the primary internal malignancy and late in the course of the disease. In very rare cases, they may occur at the same time or before the primary cancer has been detected. In our cases, the soft-tissue metastases and the primary lung cancer were diagnosed at the same time.

  7. Fyn: A Key Regulator of Metastasis in Prostate Cancer

    Science.gov (United States)

    2015-08-01

    reviewed manuscript entitled “SRC family kinase FYN promotes the neuroendocrine phenotype and visceral metastasis in advanced prostate cancer ”. This...Genitourinary Malignancies. Advances in Cancer Immunotherapy- Society of Immunologic Therapy for Cancer . June 19, 2015 26. Circulating tumor cell...Medical Center (2011-2014) • Cancer Quality Committee Member- Cedars Sinai Medical Center (2011-2014) • Protocol Review and Monitoring Committee

  8. 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.

  9. Breast Metastasis from Esophagogastric Junction Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Sanghamitra Jena

    2014-01-01

    Full Text Available Metastasis to breast from nonmammary malignancy is only about 1.3–2.7%. A few cases of squamous cell carcinoma of esophagus and adenocarcinoma of stomach metastasizing to breast have been reported, but this is probably the first report of breast metastasis from esophagogastric junction (EGJ cancer in the English literature. Herein we report a case of a 32-year-old patient diagnosed as adenocarcinoma of gastroesophageal junction, presenting with left breast metastasis two years after treatment. Given unusual site of metastasis in a follow-up case of EGJ cancer, not only it is challenging to differentiate it from primary carcinoma of breast but also it is important from treatment point of view. In our case, clinical data, radiology, histopathology, and immunohistochemistry (IHC led us to reach the diagnosis.

  10. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    RM: The pluripotency of hair follicle stem cells. Cell Cycle 2006, 5:232–233 54. Hirst CE, Ng ES, Azzola L, Voss AK, Thomas T, Stanley EG, Elefanty...analyze the role of gp140/CDCP1 in prostate cancer metastasis and to determine whether targeting gp140/CDCP1 could serve as a treatment against...KS, Xin H: Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 2008, 68

  11. 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

  12. AACR centennial series: the biology of cancer metastasis: historical perspective.

    Science.gov (United States)

    Talmadge, James E; Fidler, Isaiah J

    2010-07-15

    Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His "seed and soil" hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy.

  13. Isolated renal metastasis from squamous cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cai Jun

    2013-01-01

    Full Text Available Abstract Renal metastasis from non-small cell lung cancer is rather uncommon. The mechanism underlying the occurrence of metastasis in this site is still not well understood. We report a case of a 53-year-old Chinese woman who had moderately differentiated squamous cell carcinoma of the lung. After a ten months post-surgery interval of disease free survival, computed tomography (CT scan found that left renal parenchymal was occupied by a mass, confirmed by kidney biopsy to be a metastasis from squamous cell lung carcinoma. Based on this case, we are warned to be cautious in diagnosis and treatment when renal lesion are detected.

  14. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and metastasis

  15. Is Selenium a Potential Treatment for Cancer Metastasis?

    Directory of Open Access Journals (Sweden)

    Yu-Chi Chen

    2013-04-01

    Full Text Available Selenium (Se is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.

  16. Is selenium a potential treatment for cancer metastasis?

    Science.gov (United States)

    Chen, Yu-Chi; Prabhu, K Sandeep; Mastro, Andrea M

    2013-04-08

    Selenium (Se) is an essential micronutrient that functions as a redox gatekeeper through its incorporation into proteins to alleviate oxidative stress in cells. Although the epidemiological data are somewhat controversial, the results of many studies suggest that inorganic and organic forms of Se negatively affect cancer progression, and that several selenoproteins, such as GPXs, also play important roles in tumor development. Recently, a few scientists have examined the relationship between Se and metastasis, a late event in cancer progression, and have evaluated the potential of Se as an anti-angiogenesis or anti-metastasis agent. In this review, we present the current knowledge about Se compounds and selenoproteins, and their effects on the development of metastasis, with an emphasis on cell migration, invasion, and angiogenesis. In the cancers of breast, prostate, colorectal, fibrosarcoma, melanoma, liver, lung, oral squamous cell carcinoma, and brain glioma, there is either clinical evidence linking selenoproteins, such as thioredoxin reductase-1 to lymph node metastasis; in vitro studies indicating that Se compounds and selenoproteins inhibited cell motility, migration, and invasion, and reduced angiogenic factors in some of these cancer cells; or animal studies showing that Se supplementation resulted in reduced microvessel density and metastasis. Together, these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent.

  17. Blood clot formation does not affect metastasis formation or tumor growth in a murine model of breast cancer.

    Directory of Open Access Journals (Sweden)

    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.

  18. The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis

    Directory of Open Access Journals (Sweden)

    Yoshiro Itatani

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote cancer aggressiveness. Several types of host-derived myeloid cells reside in the tumor microenvironment, and the recruitment of them is under the control of chemokine signaling. In this review, we focus on the functions of chemokine signaling that may affect tumor immunity by recruiting several types of bone marrow-derived cells (BMDC to the tumor microenvironment of CRC.

  19. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    Directory of Open Access Journals (Sweden)

    Gruber Helen E

    2011-08-01

    Full Text Available Abstract Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA. Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17, interleukin-6 (IL-6, Pro- Matrix metallopeptidase 9 (Pro-MMP9, insulin like growth factor-II (GF-II and macrophage colony stimulating factor (M-CSF in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors

  20. Paeoniflorin inhibits macrophage-mediated lung cancer metastasis.

    Science.gov (United States)

    Wu, Qi; Chen, Gang-Ling; Li, Ya-Juan; Chen, Yang; Lin, Fang-Zhen

    2015-12-01

    Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P lung cancer cells (paeoniflorin 100 μmol·L(-1), P lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.

  1. 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

  2. Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer.

    Science.gov (United States)

    Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

    2016-08-01

    Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs.

  3. 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.

  4. Preoperative diagnosis of lymph node metastasis in thoracic esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Eguchi, Reiki; Yamada, Akiyoshi; Ueno, Keiko; Murata, Yoko [Tokyo Women`s Medical Coll. (Japan)

    1996-10-01

    From 1994 to 1995, to evaluate the utility of preoperative CT, EUS (endoscopic ultrasonography) and US in the diagnosis of lymph node metastasis in thoracic esophageal cancer, 94 patients with thoracic esophageal cancer who underwent esophagectomy were studied clinicopathologically. The sensitivity of EUS diagnosis of upper mediastinal lymph node metastasis (85%), left-sided paragastrin lymph node metastasis (73-77%), and especially lower paraesophageal lymph node metastasis (100%) were good. But due to their low-grade specificity in EUS diagnosis, their overall accuracy was not very good. On the other hand, the overall accuracy of the CT diagnosis of lymph node metastasis was fine. However, sensitivity, the most important clinical factor in the CT diagnosis of lymph node metastasis was considerably inferior to EUS. The assessment of the diagnosis of lymph node metastasis around the tracheal bifurcation and the pulmonary hilum and the left para-cardial lesion by CT or EUS was poor. It was concluded that lymph node metastasis of these area must be the pitfall in preoperative diagnosis. The average diameter of the lymph nodes and the proportion of cancerous tissue in the lymph nodes diagnosed as metastatic lymph nodes by CT was larger than that of the false negative lymph nodes. However, the lymph nodes diagnosed as true positives by EUS showed no such tendency. This must be the reason the sensitivity of the EUS diagnosis and specificity of the CT diagnosis were favorable, but the specificity of the EUS diagnosis and especially the sensitivity of the CT diagnosis were not as good. (author)

  5. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  6. Role of STAT3 in Cancer Metastasis and Translational Advances

    Directory of Open Access Journals (Sweden)

    Mohammad Zahid Kamran

    2013-01-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling.

  7. Role of STAT3 in Cancer Metastasis and Translational Advances

    Science.gov (United States)

    Patil, Prachi; Gude, Rajiv P.

    2013-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis. In this paper, we first describe the mechanism of STAT3 regulation followed by how STAT3 is involved in cancer metastasis, then we summarize the various small molecule inhibitors that inhibit STAT3 signaling. PMID:24199193

  8. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    represents the most devastating and feared consequence of breast cancer . BCBM is usually fatal and is increasing in frequency with occult brain...metastatic breast cancer (stage IV) patients with or without clinically diagnosed BCBM employing multiparametric flow cytometry (FACS; ARIA IIID system)(10...AWARD NUMBER: W81XWH-14-1-0214 TITLE: Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis PRINCIPAL INVESTIGATOR: Dario

  9. Cutaneous metastasis of colon cancer: case report and literature review.

    Science.gov (United States)

    Sheets, Nicholas; Powers, Jeremy; Richmond, Bryan

    2014-01-01

    Cutaneous metastases arising from an internal malignancy are a rare phenomenon, occurring in 0.001% of all skin biopsies performed. Of these, 6.5% originate from the a primary colon cancer. Colon cancer, when metastatic to the skin, typically appears as a painless flesh-colored nodule or as a mass with occasional ulceration. We report a case of a large cutaneous metastasis to the suprascapular region as the initial presenting symptom of an underlying colon cancer.

  10. Tumor Phagocytes Promote Breast Cancer Invasion and Metastasis

    Science.gov (United States)

    2010-10-14

    passive physiological event to clear unwanted cells, we hypothesize that clearance of apoptotic tumor cells by tumor phagocytes produce soluble...FACS assay. Introduction: The purpose of cancer chemotherapy and immunotherapy is to kill cancer cells, mostly by apoptosis. Phagocytes, which...microenvironment for metastasis. A major barrier to effective anti-cancer immunotherapy is the ability of the host to mount a durable anti-tumor response [4

  11. Targeting Master Regulators of the Breast Cancer Metastasis Transcriptome

    Science.gov (United States)

    2014-07-01

    rigorous state -of-the- art bioinformatic analysis, and functional models using isogenic human breast cancer cells with varying metastatic potential, we will...A, Ergun B, Erbersdobler A, Jung K, Stephan C. RECK overexpression decreases invasive potential in prostate cancer cells. Prostate 2012; 72: 948–954...Breast Cancer Metastasis Transcriptome PRINCIPAL INVESTIGATOR: Timothy A. Chan MD, PhD CONTRACTING ORGANIZATION: Sloan-Kettering Institute

  12. 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

  13. 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

  14. Choroidal metastasis from early rectal cancer: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Tei

    2014-01-01

    CONCLUSION: This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer.

  15. Testicular Metastasis of Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Ayumu Kusaka

    2014-09-01

    Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    I. Morales

    2016-03-01

    Full Text Available Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion.

  19. 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

  20. 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.)

  1. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes.

    Science.gov (United States)

    Tabariès, Sébastien; Dupuy, Fanny; Dong, Zhifeng; Monast, Anie; Annis, Matthew G; Spicer, Jonathan; Ferri, Lorenzo E; Omeroglu, Atilla; Basik, Mark; Amir, Eitan; Clemons, Mark; Siegel, Peter M

    2012-08-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.

  2. D-pinitol Inhibits Prostate Cancer Metastasis through Inhibition of αVβ3 Integrin by Modulating FAK, c-Src and NF-κB Pathways

    OpenAIRE

    Chih-Hsin Tang; Wen-Chi Chen; Hsin-Ho Liu; Shang-Sen Lee; Teng-Fu Hsieh; Chi-Cheng Chen; Tsung-Hsun Tsai; Tien-Huang Lin; Tzu-Wei Tan

    2013-01-01

    Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate ca...

  3. The cancer diaspora: Metastasis beyond the seed and soil hypothesis.

    Science.gov (United States)

    Pienta, Kenneth J; Robertson, Bruce A; Coffey, Donald S; Taichman, Russell S

    2013-11-01

    Do cancer cells escape the confinement of their original habitat in the primary tumor or are they forced out by ecologic changes in their home niche? Describing metastasis in terms of a simple one-way migration of cells from the primary to the target organs is an insufficient concept to cover the nuances of cancer spread. A diaspora is the scattering of people away from an established homeland. To date, "diaspora" has been a uniquely human term used by social scientists; however, the application of the diaspora concept to metastasis may yield new biologic insights as well as therapeutic paradigms. The diaspora paradigm takes into account, and models, several variables including: the quality of the primary tumor microenvironment, the fitness of individual cancer cell migrants as well as migrant populations, the rate of bidirectional migration of cancer and host cells between cancer sites, and the quality of the target microenvironments to establish metastatic sites. Ecologic scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies. For example, ecologic traps - habitats that lead to the extinction of a species - can be developed to attract cancer cells to a place where they can be better exposed to treatments or to cells of the immune system for improved antigen presentation. Merging the social science concept of diaspora with ecologic and population sciences concepts can inform the cancer field to understand the biology of tumorigenesis and metastasis and inspire new ideas for therapy.

  4. Angiotensin II facilitates breast cancer cell migration and metastasis.

    Directory of Open Access Journals (Sweden)

    Sylvie Rodrigues-Ferreira

    Full Text Available Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

  5. What Is Bone Cancer?

    Science.gov (United States)

    ... start in bone, muscle, fibrous tissue, blood vessels, fat tissue, as well as some other tissues. They can develop anywhere in the body. There are several different types of bone tumors. Their names are based on ...

  6. 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

  7. 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

  8. Advances in understanding the molecular mechanism of pancreatic cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yong-Xing Du; Zi-Wen Liu; Lei You; Wen-Ming Wu; Yu-Pei Zhao

    2016-01-01

    BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identiifed groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecu-lar mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015. The search was limited in English publications. RESULTS: PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inlfammation, stress response, and circulating tumor cells. CONCLUSIONS: Analyses of relevant gene functions and signaling pathways are needed to establish the gene regula-tory network and to deifne the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of per-sonalized therapy by identifying speciifc markers and targets.

  9. STRIPAK components determine mode of cancer cell migration and metastasis

    DEFF Research Database (Denmark)

    Madsen, Chris D; Hooper, Steven; Tozluoglu, Melda;

    2015-01-01

    and MST4 kinases, which promote the co-localization of the contractile actomyosin machinery with the Ezrin/Radixin/Moesin family proteins by phosphorylating the inhibitors of PPP1CB, PPP1R14A-D. Using computational modelling, in vitro cell migration assays and in vivo breast cancer metastasis assays we...

  10. Disrupting Ovarian Cancer Metastatic Colonization: Insights from Metastasis Suppressor Studies

    Directory of Open Access Journals (Sweden)

    Shaheena Khan

    2010-01-01

    Full Text Available Ovarian cancer affects approximately 25,000 women in the United States each year and remains one of the most lethal female malignancies. A standard approach to therapy is surgical cytoreduction, after which the remaining microscopic residual disease is treated with chemotherapy. The vast majority of patients have disease recurrence, underscoring the crucial need for approaches to control the regrowth, or colonization, of tissues after local treatment. Improved therapies require mechanistic information about the process of metastatic colonization, the final step in metastasis, in which cancer cells undergo progressive growth at secondary sites. Studies of metastasis suppressors are providing insights into events controlling metastatic colonization. This paper reviews our laboratory's approach to the identification, characterization, and functional testing of the JNKK1/MKK4 metastasis suppressor in ovarian cancer metastatic colonization. Specifically, we demonstrate that interaction of ovarian caner cells with the omental microenvironment activates JNKK1/MKK4 resulting in decreased proliferation without affecting apoptosis. The potential role of the omental microenvironment, specifically milky spot structures, is also described. It is our goal to provide this work as a usable paradigm that will enable others to study metastasis suppressors in clinical and experimental ovarian cancer metastases.

  11. The role of purinergic receptors in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Heegaard, Anne-Marie

    2012-01-01

    Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular...

  12. Roles of a metastasis-associated molecule, RTVP-1,in cancer immunosurveillance

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To elucidate distinct functions of a recently identified cancer metastasis-associated molecule, related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) in the mammalian immune system. Methods: Immunohistochemical assays and functional analysis on the immune system were performed on RTVP-/- mice and RTVP-1+/+ mice, Protein-protein interaction (PPI) was used to predict the functions of RTVP-1. Results: Abnormal lymphocyte growth kinetics and reduced numbers of CD8+ T cells were revealed in lymph nodes of RTVP-1-/- mice. Expression of phenotypic markers of maturation in bone marrow-derived dendritic cells (DC) was impaired in RTVP-1-/- DC following antigenic stimulation in vitro and RTVP-1-/- DC failed to provide normal CD4+ T cell stimulatory activities in vivo. RTVP-1-/- mice failed to generate normal CTL or antibody responses in vivo after vaccination. In vivo tumor challenge experiments using a mouse cancer cell line demonstrated that the growth rate of subcutaneous tumors in RTVP-1-/- mice was significantly increased and CD8+ T cell infiltration significantly reduced compared to RTVP-1+/+ mice. PPI showed that RTVP-1 protein closely interacted with molecules associated with immune response and cancer metastasis. Conclusion: RTVP-1 might function as a tumor metastasis suppressor and immunosurveillance molecule in cancer.

  13. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    Science.gov (United States)

    2015-11-01

    microenvironment. noncoding RNA | genome evolution | cancer immunology The recent development of total RNA sequencing has alloweda better appreciation of the...Award Number: W81XWH-13-1-0237 TITLE: IImpact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis PRINCIPAL INVESTIGATOR: David T...0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing

  14. A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ramyar Molania

    2014-01-01

    Full Text Available Colorectal cancer (CRC is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA genes was obtained using reverse transcription polymerase chain reaction (RT-PCR assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P<0.05. Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC.

  15. An alternative model of cancer cell growth and metastasis.

    Science.gov (United States)

    Vaidya, Jayant S

    2007-04-01

    I propose an alternative model of cancer in which metastasis need not all arise out of spread from the "original" tumour. The model assumes that cancer cells arise from stem cells that best grow in the organ of their differentiation. When the internal milieu allows it they also grow at other sites as well, thus complementing the conventional (spreading) metastatic process. Several phenomena in the natural history of cancer, especially breast cancer, that challenge the conventional model, fit well after inclusion of the new model. These are (a) a very modest benefit of screening (b) frequent sparing of lungs from haematogenous metastasis (c) presence of occult cancers in autopsy studies (d) only a modest effect of local treatment (e) relative ineffectiveness of high-dose chemotherapy (f) constant time between surgery and peak of hazard of relapse irrespective of stage of the tumour. All these phenomena are much easier to explain when one rejects the dogma that all metastasis arise only from the primary tumour. This paper is aimed only to suggest an alternative perspective of natural history of solid tumours--to stimulate research on the complex internal milieu that allows cancer cells to develop in new light.

  16. 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.

  17. Laparoscopic resection of colon cancer and synchronous liver metastasis.

    Science.gov (United States)

    Geiger, Timothy M; Tebb, Zachary D; Sato, Erika; Miedema, Brent W; Awad, Ziad T

    2006-02-01

    The recommended surgical approach to synchronous colorectal metastasis has not been clarified. Simultaneous open liver and colon resection for synchronous colorectal carcinoma has been shown beneficial when compared to staged resections. A review of the literature has shown the benefits of both laparoscopic colon resection for colorectal cancer and laparoscopic left lateral segmentectomy in liver disease. We present the case of a 60-year-old male with sigmoid colon carcinoma and a synchronous solitary liver metastasis localized to the left lateral segment. Using laparoscopic techniques, we were able to achieve simultaneous resection of the sigmoid colon and left lateral liver segment.

  18. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    Science.gov (United States)

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

  19. Bone-targeted therapy for metastatic breast cancer-Where do we go from here? A commentary from the BONUS 8 meeting.

    Science.gov (United States)

    Zhu, Xiaofu; Amir, Eitan; Singh, Gurmit; Clemons, Mark; Addison, Christina

    2014-03-01

    The annual Bone and The Oncologist New Updates (BONUS 8) conference focuses on the current understanding and dilemmas in the treatment and prevention of bone metastasis in cancer, as well as novel research on bone homeostasis and cancer-induced bone loss. We present commentaries from experts for their own take on where they feel the field of bone-targeted therapies for metastatic breast cancer is moving, or needs to move, if we are to make further progress.

  20. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

    Science.gov (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-03-31

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  1. Implication of platelet-derived growth factor receptor alpha in prostate cancer skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    Qingxin Liu; Danielle Jernigan; Yun Zhang; Alessandro Fatatis

    2011-01-01

    Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells andrepresents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.

  2. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Okuma Y

    2015-06-01

    Full Text Available Yusuke Okuma,1,2 Yuichiro Tanaka,3 Tina Kamei,1 Yukio Hosomi,1 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 2Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, 3Department of Ophthalmology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan Abstract: Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient’s remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash. Keywords: lung cancer, ALK rearrangement, alectinib, choroidal metastasis, molecular targeted

  3. 18F-NaF Positive Bone Metastases of Non 18F-FDG Avid Mucinous Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Çiğdem Soydal

    2015-10-01

    Full Text Available Detection of gastric cancer bone metastasis is crucial since its presence is an independent prognostic factor. In this case report, we would like to present 18F-NaF positive bone metastases of non 18F-FDG avid gastric mucinous cancer

  4. 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.

  5. Pain and nociception: mechanisms of cancer-induced bone pain.

    Science.gov (United States)

    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

  6. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  7. 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

  8. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Directory of Open Access Journals (Sweden)

    Bodour Salhia

    Full Text Available The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  9. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Science.gov (United States)

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T D; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N; DiPerna, Danielle M; Paquette, Kimberly M; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F; Liotta, Lance A; Ramanathan, Ramesh K; Berens, Michael E; Tran, Nhan L

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  10. Pattern of bone metastasis and treatment of Chinese patients with advanced non-small-cell lung cancer%非小细胞肺癌首发骨转移患者的临床特征、治疗及预后分析

    Institute of Scientific and Technical Information of China (English)

    姚舒洋; 王鑫; 李小雪; 张毅; 支修益

    2015-01-01

    Objective To investigate the characteristics of bone metastasis, prognosis and treatment strategies of non-small cell lung cancer( NSCLC) patients in China. Methods Totally 103 metastatic NSCLC patients with bone as the first metastatic organ seen between July 1, 2010 and Dec. 31, 2013 were retrospectively reviewed. Clinical pathologic characteristics and treatment outcomes were evaluated in the 103 cases. Results Median age of the patients was 59(32~82) years. Among them, 28 patient had bone metastasis as the only relapse site and the remaining were accompanied by involvement of other locations. Most bone metastases ( 95. 1%) were osteolytic. Overall survival of NSCLC bone metastases without visceral metastases was significantly longer than bone metastases with visceral metastases(18 months vs 14 months, P=0. 048). Most NSCLC bone metastases(77. 7%) were treated with chemotherapy, the response rate was 32. 5%, and the clinical benefit rate was 58. 8%. In terms of time to progression, there was significant difference between patients who received first-line chemotherapy and those who received the first-line targeted therapy(P=0. 000). Conclusion Patients just with bone metastases had better prognosis than bone metastases patients with visceral metastases. Patients with bone metastases should receive individualized anti-cancer treatment.%目的:探讨晚期非小细胞肺癌( non-small cell lung cancer,NSCLC)首发骨转移患者的临床特征、治疗及预后。方法收集2010年7月至2013年12月首都医科大学宣武医院肺癌中心诊治的103例晚期NSCLC首发骨转移患者的资料,回顾性分析其临床特点,探讨不同治疗策略和临床因素对预后的影响。结果患者年龄为59(32~82)岁,其中,单纯骨转移患者28例,其他患者均合并其他部位侵犯。 NSCLC骨转移多为溶骨性病变(95.1%)。其骨相关事件发生率仅为21.4%。单纯骨转移患者预后优于合并内脏器官转移的骨转移患者(P=0

  11. Therapy for non-small-cell lung cancer patients with brain metastasis Therapy for non-small-cell lung cancer patients with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yuchen Bao Co-first author; Bin Chen; Songwen Zhou

    2014-01-01

    Brain metastasis is a major cause of poor prognosis and high mortality for non-smal celllung cancer patients. The prognosis of non-smal-celllung cancer (NSCLC) patients with brain metastasis is generaly poor and more efective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

  12. The role of lysyl oxidase in SRC-dependent proliferation and metastasis of colorectal cancer

    DEFF Research Database (Denmark)

    Baker, Ann-Marie; Cox, Thomas Robert; Bird, Demelza;

    2011-01-01

    Emerging evidence implicates lysyl oxidase (LOX), an extracellular matrix-modifying enzyme, in promoting metastasis of solid tumors. We investigated whether LOX plays an important role in the metastasis of colorectal cancer (CRC).......Emerging evidence implicates lysyl oxidase (LOX), an extracellular matrix-modifying enzyme, in promoting metastasis of solid tumors. We investigated whether LOX plays an important role in the metastasis of colorectal cancer (CRC)....

  13. Metastin has potential as a suitable biomarker and novel effective therapy for cancer metastasis (Review)

    OpenAIRE

    SHOJI, SUNAO; TANG, XIAN YANG; SATO, HARUHIRO; Usui, Yukio; UCHIDA, TOYOAKI; Terachi, Toshiro

    2010-01-01

    Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas wit...

  14. Isolated Axillary Lymph Node Metastasis from Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Hemant Goyal

    2012-01-01

    Full Text Available A 68-year-old female with past medical history of stage IIIc serous ovarian cancer after cytoreductive surgery and adjuvant chemotherapy came to clinic for regular follow-up visit. Physical examination was completely normal except for an isolated left axillary lymph node enlargement. Patient's abdominal sonogram and CT scan of abdomen and pelvis did not show any other new metastasis. Surgical excisional biopsy of the lymph node was performed and pathology revealed features of metastatic serous ovarian carcinoma.

  15. Isolated metachronous splenic metastasis from synchronous colon cancer

    Directory of Open Access Journals (Sweden)

    Aker Fugen

    2006-07-01

    Full Text Available Abstract Background Isolated splenic metastases from colorectal cancer are very rare and there are only 13 cases reported in the English literature so far. Most cases are asymptomatic and the diagnosis is usually made by imaging studies during the evaluation of rising CEA level postoperatively. Case presentation A 76-year-old man underwent an extended left hemicolectomy for synchronous colon cancers located at the left flexure and the sigmoid colon. The tumors were staged as IIIC (T3N2M0 clinically and the patient received adjuvant chemotherapy. During the first year follow-up period, the patient remained asymptomatic with normal levels of laboratory tests including CEA measurement. However, a gradually rising CEA level after the 14th postoperative month necessitated further imaging studies including computed tomography of the abdomen which revealed a mass in the spleen that was subsequently confirmed by 18FDG- PET scanning to be an isolated metastasis. The patient underwent splenectomy 17 months after his previous cancer surgery. Histological diagnosis confirmed a metastatic adenocarcinoma with no capsule invasion. After an uneventful postoperative period, the patient has been symptom-free during the one-year of follow-up with normal blood CEA levels, although he did not accept to receive any further adjuvant therapy. To the best of our knowledge, this 14th case of isolated splenic metastasis from colorectal carcinoma is also the first reported case of splenic metastasis demonstrated preoperatively by 18FDG PET-CT fusion scanning which revealed its solitary nature as well. Conclusion Isolated splenic metastasis is a rare finding in the follow-up of colorectal cancer patients and long-term survival can be achieved with splenectomy.

  16. The Snail-Induced Sulfonation Pathway in Breast Cancer Metastasis

    Science.gov (United States)

    2014-09-01

    AD_________________ Award Number: W81XWH-11-1-0494   TITLE: The Snail -Induced Sulfonation... Snail -Induced Sulfonation Pathway in Breast Cancer Metastasis 5b. GRANT NUMBER W81XWH-11-1-0494 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dr...provided funding for a 3-year project that has resulted in fundamental new insights into how the transcription factor Snail can control gene

  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. Current status and progress in gastric cancer with liver metastasis

    Institute of Scientific and Technical Information of China (English)

    LIU Jing; CHEN Lin

    2011-01-01

    Objective This review discusses the current status and progress in studies on gastric cancer with liver metastasis (GCLM), involving the routes, subtypes, and prognosis of GCLM; the genes and molecules associated with metastasis;the feasibility and value of each imaging modality; and current treatment options.Data sources The data used in this review were mainly from Medline and PubMed published in English from 2005 to August 2010. The search terms were "gastric cancer" and "liver metastasis".Study selection Articles regarding the characteristics, diagnostic modalities, and vadous therapeutic options of GCLM were selected.Results The prognosis of GCLM is influenced by the clinicopathological characteristics of primary tumors, as well as the presence of liver metastases. Improved understanding of related genes and molecules will lead to the development of methods of early detection and targeted therapies. For the diagnosis of GCLM, each imaging modality has its relative benefits. There remains no consensus regarding therapeutic options.Conclusions Early detection and characterization of liver metastases is crucial for the prognosis of gastric cancer patients. Multidisciplinary team discussions are required to design optimal treatment strategies, which should be based on the clinicopathological characteristics of each patient.

  19. Surgery for Bone Cancer

    Science.gov (United States)

    ... be amputated mid-thigh, the lower leg and foot can be rotated and attached to the thigh bone. The old ankle joint becomes the new knee joint. This surgery is called rotationplasty (roh-TAY-shun-PLAS-tee). A prosthesis is used to make the new leg the ...

  20. Exosomes in tumor microenvironment influence cancer progression and metastasis.

    Science.gov (United States)

    Kahlert, Christoph; Kalluri, Raghu

    2013-04-01

    Exosomes are small membrane vesicles of endocytic origin with a size of 50-100 nm. They can contain microRNAs, mRNAs, DNA fragments, and proteins, which are shuttled from a donor cell to recipient cells. Many different cell types including immune cells, mesenchymal cells, and cancer cells release exosomes. There is emerging evidence that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with tumor environment. Here, we discuss different mechanisms associated with biogenesis, payload, and transport of exosomes. We highlight the functional relevance of exosomes in cancer, as related to tumor microenvironment, tumor immunology, angiogenesis, and metastasis. Exosomes may exert an immunosuppressive function as well as trigger an anti-tumor response by presenting tumor antigens to dendritic cells. Exosomes may serve as cancer biomarkers and aid in the treatment of cancer.

  1. Emerging roles of exosomes in cancer invasion and metastasis.

    Science.gov (United States)

    Soung, Young Hwa; Nguyen, Thalia; Cao, Hans; Lee, Janet; Chung, Jun

    2016-01-01

    Recent evidence has indicated that nano-sized vesicles called "exosomes" mediate the interaction between cancer cells and their microenvironment and play a critical role in the development of cancers. Exosomes contain cargo consisting of proteins, lipids, mRNAs, and microRNAs that can be delivered to different types of cells in nascent as well as distant locations. Cancer cell-derived exosomes (CCEs) have been identified in body fluids such as urine, plasma, and saliva from patients with cancer. Although their content depends on tumor type and stage, CCEs merit consideration as prognostic and diagnostic markers, as vehicles for drug delivery, and as potential therapeutic targets because they could transport various oncogenic elements. In this review, we summarize recent advances regarding the role of CCEs in cancer invasion and metastasis, as well as its potential clinical applications.

  2. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

  3. A Case of Urethral Metastasis from Sigmoid Colon Cancer Diagnostically and Prognostically Indicated by F 18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Han Seok; Kim, Eun Sil; Kim, Soyon; Im, Su Jin; Park, Yong Hyun; Lee, Ju Hyoung; Hur, So Chong [National Police Hospital, Seoul (Korea, Republic of)

    2011-12-15

    Urethral metastasis from colorectal cancer is rare and is known to have a poor prognosis. A 72 year old man with a history of colectomy and colostomy due to sigmoid colon cancer was admitted to the emergency room with bowel distension, rectal bleeding and urinary symptoms. Computed tomography of the abdominopelvis showed sigmoid colon cancer with multiple metastases involving the liver. Positron emission tomography with F 18 fluorodeoxyglucose (FDG) showed multiple hypermetabolic foci in the liver, penis and pubic bone, which otherwise could not be diagnosed. The lesions revealed no improvement with chemotherapy and urological surgery on follow up F 18 FDG PET/CT. We present a case of urethral metastasis of sigmoid colon cancer diagnostically and prognostically indicated by F 18 FDG PET/CT.

  4. An isolated vaginal metastasis from rectal cancer

    Directory of Open Access Journals (Sweden)

    Ai Sadatomo

    2016-02-01

    Conclusion: We should keep the vagina within the field of view of pelvic MRI, which is one of the preoperative diagnostic tools for colorectal cancer. If female patients show gynecological symptoms, gynecological examination should be recommended. Isolated vaginal metastases are an indication for surgical resection, and adjuvant chemotherapy is also recommended.

  5. Cancer as a Proinflammatory Environment: Metastasis and Cachexia

    Directory of Open Access Journals (Sweden)

    Nelson Inácio Pinto

    2015-01-01

    Full Text Available The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.

  6. Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

    Science.gov (United States)

    2014-08-01

    applied a dynamic flow-based E-selectin+SDF-1 coated micro -channel model to isolate and characterize a subpopulation of adhering prostate cancer cells...treatment. 15. SUBJECT TERMS prostate cancer, metastasis, selectin, circulating, Micro -vascular 16. SECURITY CLASSIFICATION OF: 17...utilized RNA interference to knock down ESL-1 expression in PC-3 and DU145 cells. Two shESL-1 (shESL-1#4 and shESL-1#5) and one scramble (scESL-1

  7. Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

    Energy Technology Data Exchange (ETDEWEB)

    Falchook, Aaron D. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Salloum, Ramzi G. [Department of Health Services Policy and Management, University of South Carolina, Columbia, South Carolina (United States); Hendrix, Laura H. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Chen, Ronald C., E-mail: ronald_chen@med.unc.edu [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)

    2014-06-01

    Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

  8. 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.

  9. Brain metastasis reirradiation in patients with advanced breast cancer

    Science.gov (United States)

    Huang, Zhou; Sun, Bing; Shen, Ge; Cha, Lei; Meng, Xiangying; Wang, Junliang; Zhou, Zhenshan; Wu, Shikai

    2017-01-01

    The outcome of recurrent brain metastasis is dismal. This study aims to assess the clinical outcomes and toxicity of reirradiation as a salvage treatment for progressive brain metastasis in patients with advanced breast cancer. Between July 2005 and September 2014, the medical records of 56 patients with brain metastasis from breast cancer were retrospectively reviewed. Of these patients, 39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation (Group 2). Overall survival (OS) and brain progression-free survival rates/times were calculated using the Kaplan–Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Change in neurologic function was also assessed. The median OS was 10.8 months (range, 1.3–56.8 months). In Group 1, the median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months. Multivariate analysis revealed that longer OS was significantly associated with a high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group 2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time was 10.8 months. Multivariate analysis revealed that longer OS was significantly associated with a high KPS (P = 0.018). The majority of the patients had improved or stable neurological function. Reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. It might delay the progression of intracranial disease and improve neurological function. A suitable patient selection for reirradiation was suggested. PMID:27707842

  10. 18F-FDG符合线路显像与99mTc-MDP骨显像及二者联合对乳腺癌骨转移的检出效能%18F-FDG SPECT coincidence, 99mTc-MDP bone scintigraphy and combination of the two techniques for detecting malignant bone metastasis from breast cancer

    Institute of Scientific and Technical Information of China (English)

    陆涤宇; 夏亮; 王志; 乔雪玲

    2012-01-01

    目的 采用ROC曲线比较18F-FDG符合线路显像、99mTc-MDP骨显像及二者联合对乳腺癌骨转移的检出效能.方法 收集手术病理诊断为乳腺癌的女性患者113例,均于4周内先后接受18F-FDG符合线路显像及99mTc-MDP骨显像;对两种显像结果按5分法评分,以二者评分之和为联合评分值,以病理诊断或临床随访为确诊“金标准”,比较ROC曲线下面积(AUC),评价99mTc-MDP骨显像、18F-FDG符合线路显像及联合评分法对乳腺癌骨转移患者的检出效能,比较不同方法在各自最佳诊断阈值下的灵敏度、特异度、准确率、阳性预测值(PPV)和阴性预测值(NPV).结果 113例中,12例(10.62%)最终确诊为骨转移,101例(89.38%)无骨转移.99mTc-MDP骨显像、18 F-FDG符合线路显像以及二者联合诊断评分的ROC曲线分析显示三者AUC分别为0.991、0.874和0.993,三种方法对乳腺癌骨转移的诊断效能均佳,尤以99mTc-MDP骨显像与联合诊断为最佳(P均<0.01).最佳阈值点下,单独18F-FDG符合线路显像、99mTc-MDP骨显像及联合检出骨转移患者的灵敏度分别为75.00%(9/12)、75.00%(9/12)、83.33%(10/12),特异度为100%(101/101)、98.02%(99/101)、98.02%(99/101),准确率为97.35%(110/113)、95.58%(108/113)、96.46%(109/113),PPV为100%(9/9)、81.82%(9/11)、83.33%(10/12),NPV为97.12%(101/104)、97.06%(99/102)、98.02%(99/101).结论 99mTc-MDP骨显像对乳腺癌骨转移患者的检出效能优于18F-FDG符合线路显像,二者联合可提高对骨转移患者的检出率.%Objective To observe the efficacy of 18F-FDG SPECT coincidence (18F-FDG SPECT) , 99mTc-MDP bone scintigraphy (BS) and combination of the two techniques (18F-FDG SPECT+99mTc-MDP BS) for detecting bone metastasis from breast cancer by ROC curve analysis. Methods Totally 113 patients with breast cancer underwent both 99mTc-MDP BS and 18F-FDG SPECT within 4 weeks. The images were interpreted according to 5

  11. 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.

  12. Studying liver cancer metastasis by in vivo imaging and flow cytometer

    Science.gov (United States)

    Wang, Chen; Gu, Zhengqin; Guo, Jin; Li, Yan; Liu, Guangda; Wei, Xunbin

    2009-11-01

    Primary liver cancer (hepatocellular carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. About 80% of people with primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help, one third of the patients have cancer that has not progressed beyond the liver. HCC may metastasize to the lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo with real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real- time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  13. 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.

  14. Definition of molecular determinants of prostate cancer cell bone extravasation.

    Science.gov (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

    2013-01-15

    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  15. D-pinitol Inhibits Prostate Cancer Metastasis through Inhibition of αVβ3 Integrin by Modulating FAK, c-Src and NF-κB Pathways

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    Chih-Hsin Tang

    2013-05-01

    Full Text Available Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145 at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.

  16. D-pinitol inhibits prostate cancer metastasis through inhibition of αVβ3 integrin by modulating FAK, c-Src and NF-κB pathways.

    Science.gov (United States)

    Lin, Tien-Huang; Tan, Tzu-Wei; Tsai, Tsung-Hsun; Chen, Chi-Cheng; Hsieh, Teng-Fu; Lee, Shang-Sen; Liu, Hsin-Ho; Chen, Wen-Chi; Tang, Chih-Hsin

    2013-05-08

    Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-kB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.

  17. Selectins mediate small cell lung cancer systemic metastasis.

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    Franziska Heidemann

    Full Text Available Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181. However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

  18. Trefoil factor-3 expression in human colon cancer liver metastasis.

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    Babyatsky, Mark; Lin, Jing; Yio, Xianyang; Chen, Anli; Zhang, Jie-yu; Zheng, Yan; Twyman, Christina; Bao, Xiuliang; Schwartz, Myron; Thung, Swan; Lawrence Werther, J; Itzkowitz, Steven

    2009-01-01

    Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

  19. Patterns of metastasis in colon and rectal cancer.

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    Riihimäki, Matias; Hemminki, Akseli; Sundquist, Jan; Hemminki, Kari

    2016-07-15

    Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis.

  20. New insights of epithelial-mesenchymal transition in cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yadi Wu; Binhua P.Zhou

    2008-01-01

    Epithelial-mesenchymal transition (EMT) is a key step during embryonic morphogenesis,heart development,chronic degenerative fibrosis,and cancer metastasis.Several distinct traits have been conveyed by EMT,including cell motility,invasiveness,resistance to apoptosis,and some properties of stem cells.Many signal pathways have contributed to the induction of EMT,such as transforming growth factor-β,Wnt,Hedgehog,Notch,and nuclear factor-κB.Over the last few years,increasing evidence has shown that EMT plays an essential role in tumor progression and metastasis.Understanding the molecular mechanism of EMT has a great effect in unraveling the metastatic cascade and may lead to novel interventions for metastatic disease.

  1. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase.

    Science.gov (United States)

    Cox, Thomas R; Rumney, Robin M H; Schoof, Erwin M; Perryman, Lara; Høye, Anette M; Agrawal, Ankita; Bird, Demelza; Latif, Norain Ab; Forrest, Hamish; Evans, Holly R; Huggins, Iain D; Lang, Georgina; Linding, Rune; Gartland, Alison; Erler, Janine T

    2015-06-04

    Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications.

  2. Nanotechnology-based intelligent drug design for cancer metastasis treatment.

    Science.gov (United States)

    Gao, Yu; Xie, Jingjing; Chen, Haijun; Gu, Songen; Zhao, Rongli; Shao, Jingwei; Jia, Lee

    2014-01-01

    Traditional chemotherapy used today at clinics is mainly inherited from the thinking and designs made four decades ago when the Cancer War was declared. The potency of those chemotherapy drugs on in-vitro cancer cells is clearly demonstrated at even nanomolar levels. However, due to their non-specific effects in the body on normal tissues, these drugs cause toxicity, deteriorate patient's life quality, weaken the host immunosurveillance system, and result in an irreversible damage to human's own recovery power. Owing to their unique physical and biological properties, nanotechnology-based chemotherapies seem to have an ability to specifically and safely reach tumor foci with enhanced efficacy and low toxicity. Herein, we comprehensively examine the current nanotechnology-based pharmaceutical platforms and strategies for intelligent design of new nanomedicines based on targeted drug delivery system (TDDS) for cancer metastasis treatment, analyze the pros and cons of nanomedicines versus traditional chemotherapy, and evaluate the importance that nanomaterials can bring in to significantly improve cancer metastasis treatment.

  3. Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis.

    Science.gov (United States)

    Pancione, Massimo; Giordano, Guido; Remo, Andrea; Febbraro, Antonio; Sabatino, Lina; Manfrin, Erminia; Ceccarelli, Michele; Colantuoni, Vittorio

    2014-01-01

    Over the past decade, growing evidence indicates that the tumor microenvironment (TME) contributes with genomic/epigenomic aberrations of malignant cells to enhance cancer cells survival, invasion, and dissemination. Many factors, produced or de novo synthesized by immune, stromal, or malignant cells, acting in a paracrine and autocrine fashion, remodel TME and the adaptive immune response culminating in metastasis. Taking into account the recent accomplishments in the field of immune oncology and using metastatic colorectal cancer (mCRC) as a model, we propose that the evasion of the immune surveillance and metastatic spread can be achieved through a number of mechanisms that include (a) intrinsic plasticity and adaptability of immune and malignant cells to paracrine and autocrine stimuli or genotoxic stresses; (b) alteration of positional schemes of myeloid-lineage cells, produced by factors controlling the balance between tumour-suppressing and tumour-promoting activities; (c) acquisition by cancer cells of aberrant immune-phenotypic traits (NT5E/CD73, CD68, and CD163) that enhance the interactions among TME components through the production of immune-suppressive mediators. These properties may represent the driving force of metastatic progression and thus clinically exploitable for cancer prevention and therapy. In this review we summarize results and suggest new hypotheses that favour the growing impact of tumor-infiltrating immune cells on tumour progression, metastasis, and therapy resistance.

  4. Cutaneous Metastasis of Large Cell Lung Cancer: A Case Report

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    Ižsmail Gedik

    2016-05-01

    Full Text Available Lung cancer has the highest incidence among all cancer types in the world. Skin is an uncommon organ that lung cancers metastasize and the incidence of cutaneous metastasis has been reported between 1-12%. In this report, we would like to present the case of a 67 year old male patient who admitted to our hospital with the complaint of multiple swollen masses on the different parts of his skin and has a homogenous mass with the width of 3 cm on chest x ray. The nodule at the intersection of the right 6th intercostal space and the mid-axillary line and with the dimensions of 1.5x1 cm was excised under local anesthesia and the specimen was sent to the pathology laboratory for histopathological examination. The diagnosis of %u201Clarge cell neuroendocrine carcinoma%u201D was made histopathologically. The patient was diagnosed as the distant metastasis of the large cell lung cancer, considered inoperable and referred to oncology clinics.

  5. Mitogen-activated protein kinase kinase 4 (MAP2K4 promotes human prostate cancer metastasis.

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    Janet M Pavese

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer death in the US. Death from PCa primarily results from metastasis. Mitogen-activated protein kinase kinase 4 (MAP2K4 is overexpressed in invasive PCa lesions in humans, and can be inhibited by small molecule therapeutics that demonstrate favorable activity in phase II studies. However, MAP2K4's role in regulating metastatic behavior is controversial and unknown. To investigate, we engineered human PCa cell lines which overexpress either wild type or constitutive active MAP2K4. Orthotopic implantation into mice demonstrated MAP2K4 increases formation of distant metastasis. Constitutive active MAP2K4, though not wild type, increases tumor size and circulating tumor cells in the blood and bone marrow. Complementary in vitro studies establish stable MAP2K4 overexpression promotes cell invasion, but does not affect cell growth or migration. MAP2K4 overexpression increases the expression of heat shock protein 27 (HSP27 protein and protease production, with the largest effect upon matrix metalloproteinase 2 (MMP-2, both in vitro and in mouse tumor samples. Further, MAP2K4-mediated increases in cell invasion are dependent upon heat shock protein 27 (HSP27 and MMP-2, but not upon MAP2K4's immediate downstream targets, p38 MAPK or JNK. We demonstrate that MAP2K4 increases human PCa metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. These findings provide a mechanistic explanation for human studies linking increases in HSP27 and MMP-2 to progression to metastatic disease. MAP2K4 is validated as an important therapeutic target for inhibiting human PCa metastasis.

  6. [A case of gastric metastasis and carcinomatous peritonitis of breast cancer with improved QOL by stent implantation and gemcitabine].

    Science.gov (United States)

    Mukaibashi, Tomoe; Kojima, Izumi; Yamanaka, Ayumi; Nishiyama, Sachiko; Yamanaka, Takashi; Nakayama, Hirotaka; Matsuura, Hitoshi; Matsuzu, Kenichi; Inaba, Masaaki; Yoshida, Akira; Shimizu, Satoru

    2013-08-01

    A 73-year-old woman had undergone mastectomy for left breast cancer. One year later, bone metastasis was detected. After 7 years, the patient experienced epigastric discomfort, and gastrointestinal endoscopy showed stenosis of the pylorus and enlarged gastric folds. Stomach cancer was suspected at first, but gastric metastasis of breast cancer was diagnosed on the basis of endoscopic reexamination and computed tomography(CT)images. The patient could not drink water, and therefore, gastrointestinal stenting was performed, which facilitated ingestion to some extent. However, at the same time, an elevated serum carcinoembryonic antigen(CEA)level and jaundice were observed. Therefore, biliary tract stenosis due to carcinomatous peritonitis was diagnosed. We attempted to treat the jaundice with endoscopic retrograde cholangiopancreatography( ERCP)or percutaneous transhepatic cholangiography(PTCD), but the treatment was not successful, and an increase in ascites was noted. Accordingly, gemcitabine was administered as systemic therapy. As a result, ascites decreased and jaundice improved. Patients with gastric metastasis of breast cancer have poor quality of life(QOL)because of difficulties in ingestion or vomiting, and poor prognoses, because of frequent concurrent carcinomatous peritonitis. We experienced a case of gastric metastasis and carcinomatous peritonitis, and were able to improve the patient's QOL by gastrointestinal stenting and gemcitabine administration.

  7. Metformin: An Emerging New Therapeutic Option for Targeting Cancer Stem Cells and Metastasis

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    Ramandeep Rattan

    2012-01-01

    Full Text Available Metastasis is an intricate process by which a small number of cancer cells from the primary tumor site undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Transition of a cancer cell from epithelial to mesenchymal phenotype is thought to be the first step in the progression of metastasis. Recently, the recognition of cancer stem cells has added to the perplexity in understanding metastasis, as studies suggest cancer stem cells to be the originators of metastasis. All current and investigative drugs have been unable to prevent or reverse metastasis, as a result of which most metastatic cancers are incurable. A potential drug that can be considered is metformin, an oral hypoglycemic drug. In this review we discuss the potential of metformin in targeting both epithelial to mesenchymal transition and cancer stem cells in combating cancer metastases.

  8. The metastasis suppressor RARRES3 as an endogenous inhibitor of the immunoproteasome expression in breast cancer cells

    Science.gov (United States)

    Anderson, Alison M.; Kalimutho, Murugan; Harten, Sarah; Nanayakkara, Devathri M.; Khanna, Kum Kum; Ragan, Mark A.

    2017-01-01

    In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions. Knockdown of RARRES3 in near-normal mammary epithelial and breast cancer cell lines increases overall transcript and protein levels of the IP subunits, but not of their constitutively expressed counterparts. RARRES3 mRNA expression is controlled by interferon regulatory factor IRF1, an inducer of the IP, and is sensitive to depletion of the retinoid-related receptor RORA that regulates various physiological processes including immunity through modulation of gene expression. Collectively, these findings identify a novel regulatory role for RARRES3 as an endogenous inhibitor of IP expression, and contribute to our evolving understanding of potential pathways underlying breast cancer driven immune modulation.

  9. Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

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    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.

  10. Inhibition of Spontaneous Breast Cancer Metastasis by Anti—Thomsen-Friedenreich Antigen Monoclonal Antibody JAA-F11

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    Jamie Heimburg

    2006-11-01

    Full Text Available Thomsen-Friedenreich antigen (TF-Ag is expressed in many carcinomas, including those of the breast, colon, bladder, prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAAF11, an anti -TF-Ag monoclonal antibody, may create a survival advantage for patients with TIF-Ag -expressing tumors by cytotoxicity, blocking of tumor cell adhesion, inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60 in in vitro static adhesion models, in a perfused ex vivo model, in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.

  11. MIM, a Potential Metastasis Suppressor Gene in Bladder Cancer

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    Young-Goo Lee

    2002-01-01

    Full Text Available Using a modified version of the mRNA differential display technique, five human bladder cancer cell lines from low grade to metastatic were analyzed to identify differences in gene expression. A 316-bp cDNA (C11300 was isolated that was not expressed in the metastatic cell line TccSuP. Sequence analysis revealed that this gene was identical to KIAA 0429, has a 5.3-kb transcript that mapped to 8824.1. The protein is predicted to be 356 amino acids in size and has an actin-binding WH2 domain. Northern blot revealed expression in multiple normal tissues, but none in a metastatic breast cancer cell line (SKBR3 or in metastatic prostatic cancer cell lines (LNCaP, PC3. We have named this gene Missing in Metastasis (MIM and our data suggest that it may be involved in cytoskeletal organization.

  12. A twist tale of cancer metastasis and tumor angiogenesis.

    Science.gov (United States)

    Tseng, Jen-Chieh; Chen, Hsiao-Fan; Wu, Kou-Juey

    2015-11-01

    Twist1 is an evolutionally conserved transcription factor. Originally identified in Drosophila as a key regulator for mesoderm development, it was later implicated in many human diseases, including Saethre-Chotzen syndrome and cancer. Twist1's involvement in cancer has been well recognized. Driven by hypoxia-induced factor-1 (HIF-1), Twist1 has been considered as a proto-oncogene and its overexpression has been observed in a wide variety of human cancers. High expression level of Twist1 is closely related to tumor aggressiveness and metastatic potential. In cancer cells, Twist1 has been shown to function as a key regulator of epithelial-mesenchymal transition (EMT), a critical process for metastasis initiation. Twist1 has also been implicated in maintaining cancer stemness for self-renewal and chemoresistance. This review first summarizes the roles of Twist1 in embryo development and Saethre-Chotzen syndrome followed by a discussion of Twist1's critical functions in cancer. In particular, the review focuses on the recent discovery of Twist1's capability to promote endothelial transdifferentiation of cancer cells beyond EMT.

  13. Ovarian Metastasis from Lung Cancer: A Rare Entity

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    Huseyin Cengiz

    2013-01-01

    Full Text Available This paper describes a case of ovarian metastasis from lung carcinoma along with its diagnostic challenges, clinical management, and review of the literature. A 49-year-old woman was admitted to our emergency department with complaints of abdominal pain and vomiting. A laparoscopic appendectomy was performed due to acute appendicitis, and a unilateral oophorectomy (left side via laparoscopy was performed due to the detection of an ovarian mass. Immunohistochemical staining of the ovarian mass revealed that it was reactive to cytokeratin-7 (CK-7 but negative for CK-20. The immunohistochemical and pathological features of the tumor indicated an ovarian metastasis of non-small-cell lung cancer. The patient underwent chemotherapy and was followed up by the oncology department. Her postoperative regular followup of 6 months showed that her condition was stable with no recurrence. The management of female patients with acute abdominal pain and pelvic masses should consist of a multidisciplinary approach to include the diagnosis of any distant organ metastasis.

  14. [Isolated bilateral adrenal metastasis from renal cancer. Case report].

    Science.gov (United States)

    Rabii, R; Joual, A; Naciri, K; Guessous, H; el Mrini, M; Benjelloun, S

    1999-01-01

    The authors report an uncommon case of bilateral synchronous adrenal gland metastases from left renal cell carcinoma. The diagnosis was established by abdominal ultrasound and computed tomography. The surgical approach initially consisted of left radical nephrectomy and ipsilateral adrenalectomy. Histologically, the tumor of the left adrenal gland was identical to the left renal cell carcinoma. Subsequent contralateral adrenalectomy showed an adrenal metastasis identical to the left renal cell carcinoma. Patient follow-up was good with no recurrence of the disease after one year. This is an uncommon case for renal cancer. The treatment and prognosis are discussed.

  15. Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

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    Jian Cao

    2014-03-01

    Full Text Available Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.

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

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    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.

  17. 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.

  18. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    OpenAIRE

    Gonzalez, Maria E.; Martin, Emily E.; Talha Anwar; Caroline Arellano-Garcia; Natasha Medhora; Arjun Lama; Yu-Chih Chen; Kevin S. Tanager; Euisik Yoon; Kidwell, Kelley M.; Chunxi Ge; Franceschi, Renny T.; Celina G. Kleer

    2017-01-01

    Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with co...

  19. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    NARCIS (Netherlands)

    Brisset, Jean-Christophe; Hoff, Benjamin A.; Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galban, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galban, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.; Schakel, Tim

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul

  20. 89SrCl2联合99Tc-MDP对乳腺癌骨转移骨痛治疗疗效%Therapeutic evaluation of 89SrCl2 combined with 99Tc-MDP in treat-ing bone pain of patients with breast cancer and osseous metastasis

    Institute of Scientific and Technical Information of China (English)

    刘恒超; 李卫鹏; 申勇; 胡永全; 马芳

    2015-01-01

    目的:观察放射性核素氯化锶(89SrCl2)联合锝-99-亚甲基二膦酸盐(99Tc-MDP)治疗乳腺癌骨转移的临床效果。方法:将80例乳腺癌骨转移患者随机分为89SrCl2治疗组30例、99Tc-MDP治疗组22例、89SrCl2与99Tc-MDP联合治疗组28例3组,观察各组骨痛缓解、骨转移病灶好转和生活质量评分提高情况。结果:骨痛缓解总有效率、生活质量评分提高率在联合治疗组为92.9%(26/28)、78.6%(22/28),均明显高于89SrCl2治疗组的73.3%(22/30)、53.3%(16/30)和99Tc-MDP治疗组的63.6%(14/22)、45.5%(10/22),差异具有统计学意义(P0.05)。结论:89SrCl2联合99Tc-MDP治疗可显著提高乳腺癌骨转移骨痛疗效,且无明显不良反应。%Objective:To evaluate the clinical value of radioactive nuclide strontium chloride (89SrCl2) combined with 99Tc-MDP in treating patients with breast cancer and osseous metastasis. Methods:A total of 80 patients with breast cancer and experiencing bone pain from osseous metastasis were randomly categorized into three groups. 22 patients were treated with 99Tc-MDP (99Tc-MDP group), 30 were treated with 89SrCl2 (89SrCl2 group), and 28 were treated with the combination therapy of 89SrCl2 and 99Tc-MDP (combination group). The analgesic effect, remission of bone metastases, and quality of life of patients in the three groups were observed before and after treatment. Side effect was also monitored. Results:In the combination group, the overall pain relief rate and the increase rate of life quality score were 92.9%(26/28) and 78.6%(22/28), respectively. The combination group was statistically significantly different from the two single-treatment groups (P0.05). Conclusion:The treatment of 89SrCl2 com-bined with 99Tc-MDP can increase the analgesic effect and significantly improve the curative effect without overt side effects in patients with breast cancer and bone metastasis.

  1. Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

    Science.gov (United States)

    Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

    2016-02-01

    Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

  2. Serpins promote cancer cell survival and vascular co-option in brain metastasis.

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

    2014-02-27

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers.

  3. Metachronous penile metastasis from rectal cancer after total pelvic exenteration

    Institute of Scientific and Technical Information of China (English)

    Yuta Kimura; Dai Shida; Keiichi Nasu; Hiroki Matsunaga; Masahiro Warabi; Satoru Inoue

    2012-01-01

    Despite its abundant vascularization and extensive circulatory communication with neighboring organs,metastases to the penis are a rare event.A 57-yearold male,who had undergone total pelvic exenteration for rectal cancer sixteen months earlier,demonstrated an abnormal uptake within his penis by positron emission tomography/computed tomography.A single elastic nodule of the middle penis shaft was noted deep within Bucks fascia.No other obvious recurrent site was noted except the penile lesion.Total penectomy was performed as a curative resection based on a diagnosis of isolated penile metastasis from rectal cancer.A histopathological examination revealed an increase of well differentiated adenocarcinoma in the corpus spongiosum consistent with his primary rectal tumor.The immunohistochemistry of the tumor cells demonstrated positive staining for cytokeratin 20 and negative staining for cytokeratin 7,which strongly supported a diagnosis of penile metastasis from the rectum.The patient is alive more than two years without any recurrence.

  4. 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

  5. Research Progress of Lung Cancer with Leptomeningeal Metastasis

    Directory of Open Access Journals (Sweden)

    Chunhua MA

    2014-09-01

    Full Text Available Leptomeningeal metastases is one of the most serious complications of lung cancer, the patients with poor prognosis. Leptomeningeal metastasis in patients with lack specificity of clinical manifestations. The main clinical performance are the damage of cerebral symptoms, cranial nerve and spinal nerve. The diagnosis primarily based on the history of tumor, clinical symptoms, enhance magnetic resnance image (MRI scan and cerebrospinal fluid cytology. In recent years, new ways of detecting clinically, significantly increase the rate of early detection of leptomeningeal metastases. The effect of comprehensive treatments are still sad. The paper make a review of research progress in pathologic physiology, clinical manifestations, diagnosis methods and treatments of lung cancer with leptomeningeal metastases.

  6. The cancer glycome: carbohydrates as mediators of metastasis.

    Science.gov (United States)

    Glavey, Siobhan V; Huynh, Daisy; Reagan, Michaela R; Manier, Salomon; Moschetta, Michele; Kawano, Yawara; Roccaro, Aldo M; Ghobrial, Irene M; Joshi, Lokesh; O'Dwyer, Michael E

    2015-07-01

    Glycosylation is a frequent post-translational modification which results in the addition of carbohydrate determinants, "glycans", to cell surface proteins and lipids. These glycan structures form the "glycome" and play an integral role in cell-cell and cell-matrix interactions through modulation of adhesion and cell trafficking. Glycosylation is increasingly recognized as a modulator of the malignant phenotype of cancer cells, where the interaction between cells and the tumor micro-environment is altered to facilitate processes such as drug resistance and metastasis. Changes in glycosylation of cell surface adhesion molecules such as selectin ligands, integrins and mucins have been implicated in the pathogenesis of several solid and hematological malignancies, often with prognostic implications. In this review we focus on the functional significance of alterations in cancer cell glycosylation, in terms of cell adhesion, trafficking and the metastatic cascade and provide insights into the prognostic and therapeutic implications of recent findings in this fast-evolving niche.

  7. 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.

  8. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics

    OpenAIRE

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment...

  9. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    Science.gov (United States)

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  10. 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.)

  11. 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

  12. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics.

    Science.gov (United States)

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

  13. Advancing Treatment for Metastatic Bone Cancer: Consensus Recommendations from the Second Cambridge Conference

    Science.gov (United States)

    Coleman, Robert E.; Guise, Theresa A.; Lipton, Allan; Roodman, G. David; Berenson, James R.; Body, Jean-Jacques; Boyce, Brendan F.; Calvi, Laura M.; Hadji, Peyman; McCloskey, Eugene V.; Saad, Fred; Smith, Matthew R.; Suva, Larry J.; Taichman, Russell S.; Vessella, Robert L.; Weilbaecher, Katherine N.

    2009-01-01

    Purpose Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer. Experimental Design A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies. Results A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years. Conclusions Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments. PMID:18927277

  14. 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

  15. Serological diagnostic factors for liver metastasis in patients with colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the serological diagnostic factors for liver metastasis in patients with colorectal cancer.METHODS:One hundred and six adult in-patients with colorectal cancer were studied and divided into patients with liver metastasis(n = 56) and patients without liver metastasis(n = 50).Serum levels of tumor and biochemical markers for liver were measured at the time of diagnosis.RESULTS:The mean survival time was 55.9 mo,36.8 mo and 68.3 mo for the overall patients,patients with liver metastasis and ...

  16. Multiple bone metastases detected on 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography in a breast cancer patient: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Zeki Dostbil

    2012-09-01

    Full Text Available Bone scintigraphy has been widely used to assess skeletal metastasis in patients with breast cancer. 18F-FDGPET/CT is another imaging modality that has gained previously wide use to determine metastasis based on increased glucose metabolism in malignant cells. Generally, these two modalities give similar results in evaluation of bone metastasis of breast cancer. In this breast cancer case, 99mTc-MDP bone scintigraphy showed normal findings in regards to skeletal metastasis while 18FFDG-PET/CT, contrast-enhanced CT and MRI revealed multiple metastatic focuses. J Clin Exp Invest 2012; 3 (3: 426-429Key words: 18F-fluorodeoxyglucose, bone metastasis, bone scintigraphy, positron emission tomography

  17. Hopes Dashed for Rare Bone Cancer Treatment

    Science.gov (United States)

    ... news/fullstory_160652.html Hopes Dashed for Rare Bone Cancer Treatment Extra chemo drugs failed to change course of ... t benefit patients with a rare type of bone cancer, according to a new ... teenagers. With current treatments, only 65 to 70 percent of patients live ...

  18. Lymphangiogenesis and lymph node metastasis in breast cancer

    Directory of Open Access Journals (Sweden)

    Subramanian Ashok

    2008-03-01

    Full Text Available Abstract Introduction There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival. The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival. Results There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression. Conclusion In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.

  19. 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.

  20. Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.

    Science.gov (United States)

    Maimaiti, Yusufu; Jie, Tan; Jing, Zhou; Changwen, Wang; Pan, Yu; Chen, Chen; Tao, Huang

    2016-04-22

    Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

  1. Dietary energy balance modulates ovarian cancer progression and metastasis.

    Science.gov (United States)

    Al-Wahab, Zaid; Tebbe, Calvin; Chhina, Jasdeep; Dar, Sajad A; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2014-08-15

    A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.

  2. {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.

  3. Investigation of the roles of exosomes in colorectal cancer liver metastasis.

    Science.gov (United States)

    Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

    2015-05-01

    The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

  4. Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer

    Directory of Open Access Journals (Sweden)

    Wen-Bo Jin

    2013-01-01

    Full Text Available Objective: The purpose of this study is to analyze a single institution experience with pleuropneumonectomy for pleural metastasis and malignant pleural effusion in primary lung cancer. Materials and Methods: From August 1978 to August 2011, 66 consecutive patients with lung cancer underwent pleuropneumonectomy. Patients were followed-up after the operation. The quality-of-life and the survival time were recorded. Results: All the 66 patients were successfully operated on, including 38 patients in early years (1978-1993 and 28 patients in recent years (1994-2011. Two patients in early years died after the operation. Post-operative complications occurred including heart arrhythmia, respiratory insufficiency and bacterial infection of residual lung, chylothoraxin and mental disorder. A total of 61 patients have been successfully followed-up and three patients in early years were lost in 1 year after the operation. Local recurrence was found in seven cases (4 in early years, 3 in recent years and distant metastasis was found in 48 cases (29 in early years, 19 in recent years. A total of 54 patients died from tumors, seven patients survived. The actuarial 1, 2 and 3-year survival rates are 72.7%, 27.2% and 6.1% of 36 in patients of early years and 85.7%, 46.4% and 21.4% in 28 patients of recent years. The mean survival and the median survival of the total 64 patients were 20.0 ± 10.9 months and 17 months respectively. Further analysis showed that the mean survival and the median survival of the 36 patients in early years were 17.2 ± 9.7 months and 15 months, in contrast to 23.4 ± 11.3 months and 18 months of the 28 patients in recent years. Conclusion: Pleuropneumonectomy is an option of patients with advanced-stage lung cancer associated with uncontrolled malignant pleural fluid by conservative therapies. Strict selection of patient to be operated, careful procedures to eradicate obvious tumors and metastasis and enhanced post-operative combined

  5. An In Vivo Mouse Model for Human Prostate Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Aaron M. Havens

    2008-04-01

    Full Text Available We developed a sensitive real-time polymerase chain reaction (QPCR assay that allows us to track early lodging/homing events in vivo. We used this technology to develop a metastasis assay of human prostate cancer (PCa growth in severe combined immunodeficient mice. For this purpose, marked human PCa cell lines were implanted subcutaneously or in the prostate (orthotopically of severe combined immunodeficient mice as models of primary tumors. Mice were then sacrificed at various time points, and distant tissues were investigated for the presence of metastatic cells. At 3 weeks, a number of tissues were recovered and evaluated by QPCR for the presence of metastatic cells. The data demonstrate that several PCa cell lines are able to spread from the primary lesion and take up residence in distant sites. If the primary tumors were resected at 3 weeks, in several cases, metastastic lesions were identified over the course of 9 months. We propose that this new model may be particularly useful in exploring the molecular events in early metastasis, identifying the metastatic niche, and studying issues pertaining to dormancy.

  6. Increased entropy of signal transduction in the cancer metastasis phenotype

    Directory of Open Access Journals (Sweden)

    Teschendorff Andrew E

    2010-07-01

    Full Text Available Abstract Background The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Results Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may

  7. The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts

    Directory of Open Access Journals (Sweden)

    Anna Kuchnio

    2015-08-01

    Full Text Available Several questions about the role of the oxygen sensor prolyl-hydroxylase 2 (PHD2 in cancer have not been addressed. First, the role of PHD2 in metastasis has not been studied in a spontaneous tumor model. Here, we show that global PHD2 haplodeficiency reduced metastasis without affecting tumor growth. Second, it is unknown whether PHD2 regulates cancer by affecting cancer-associated fibroblasts (CAFs. We show that PHD2 haplodeficiency reduced metastasis via two mechanisms: (1 by decreasing CAF activation, matrix production, and contraction by CAFs, an effect that surprisingly relied on PHD2 deletion in cancer cells, but not in CAFs; and (2 by improving tumor vessel normalization. Third, the effect of concomitant PHD2 inhibition in malignant and stromal cells (mimicking PHD2 inhibitor treatment is unknown. We show that global PHD2 haplodeficiency, induced not only before but also after tumor onset, impaired metastasis. These findings warrant investigation of PHD2’s therapeutic potential.

  8. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    Directory of Open Access Journals (Sweden)

    Maria E. Gonzalez

    2017-01-01

    Full Text Available Increased collagen deposition by breast cancer (BC-associated mesenchymal stem/multipotent stromal cells (MSC promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2 is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  9. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth.

    Science.gov (United States)

    Gonzalez, Maria E; Martin, Emily E; Anwar, Talha; Arellano-Garcia, Caroline; Medhora, Natasha; Lama, Arjun; Chen, Yu-Chih; Tanager, Kevin S; Yoon, Euisik; Kidwell, Kelley M; Ge, Chunxi; Franceschi, Renny T; Kleer, Celina G

    2017-01-31

    Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  10. Pre-osteoblastic MC3T3-E1 cells promote breast cancer growth in bone in a murine xenograft model

    Institute of Scientific and Technical Information of China (English)

    Thomas M. Bodenstine; Benjamin H. Beck; Xuemei Cao; Leah M. Cook; Aimen Ismai; J. Kent Powers; Andrea M. Mastro; Danny R. Welch

    2011-01-01

    The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.

  11. 临床药师对1例肺癌骨转合并粒缺性发热患者的药学监护%Pharmaceutical care for a Patient with Bone Metastasis Complicating with Febrile Neutropenia in Lung Cancer by Clinical Pharmacist

    Institute of Scientific and Technical Information of China (English)

    朱智云; 王爱英

    2016-01-01

    目的:通过对化疗患者提供药学监护,促进临床合理用药,保障患者用药安全。方法:临床药师对1例肺癌骨转移患者用药过程进行全程药学监护。结果:通过全程药学监护,患者化疗过程中出现的并发症得到合理解决。结论:临床药师为肿瘤患者提供全程药学监护,对促进患者用药合理化具有重要意义。%Objective: Clinical pharmacist provided a Whole-course pharmaceutical to a tumor patient so as to promote clinical rational use of drugs and to ensure the safety of patient.Methods: Clinical pharmacist provided whole-course pharmaceutical care for one patient with bone metastasis of lung Cancer.Results: Through the whole process of pharmaceutical care, the complications of chemotherapy had been effectively performed. Conclusion: Clinical pharmacists provide clinical pharmaceutical services for tumor patients, and promote rational drug use.

  12. CANCER METASTASIS DIRECTLY ERADICATED BY TARGETED THERAPY WITHA MODIFIED SALMONELLA TYPHYMURIUM

    OpenAIRE

    Hayashi, Katsuhiro; Ming ZHAO; Yamauchi, Kensuke; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Hoffman, Robert M.

    2009-01-01

    Cancer metastasis is the life-threatening aspect of cancer and is usually resistant to standard treatment. We report here a targeted therapy strategy for cancer metastasis using a modified strain of Salmonella typhimurium. The genetically modified strain of S. typhimurium is auxotrophic for the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in tumor cells. The tumor-targeting strain of S. typhimurium, termed A1-R and ex...

  13. Thyroid gland metastasis arising from breast cancer: A case report.

    Science.gov (United States)

    Yang, Mei; Wang, Wei; Zhang, Chenfang

    2013-06-01

    The thyroid gland is an uncommon site for metastasis to develop and thus metastases arising from breast cancer are rarely observed. In the present study, we describe a case of a 45-year-old female with a three-year history of breast cancer who presented with a thyroid mass that was diagnosed as metastatic breast carcinoma by histopathological analysis of the subtotal thyroidectomy specimen. To ascertain the diagnosis of metastatic breast cancer, we evaluated two types of markers; those that possessed a similar expression status in the original and metastatic lesions [ER, PR and CerbB-2 (HER2/neu)], and those that are capable of differentiating between metastatic lesions and the surrounding thyroid components (TG and TTF-1). The results showed that ER, PR and CerbB-2 demonstrated a similar expression pattern in primary breast carcinoma and thyroid lesions. Meanwhile, in the thyroid lesions, the malignant cells showed negative staining for TG and TTF-1, which confirmed that lesions were not thyroid in origin. This case may prompt clinicians that although thyroid gland are uncommon metastatic site, a diagnosis of metastatic disease should be considered when new aggregates are identified in the thyroid glands and histopathological analysis may aid the diagnosis.

  14. Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis.

    Science.gov (United States)

    Kang, Shin-Ae; Hasan, Nafis; Mann, Aman P; Zheng, Wei; Zhao, Lichao; Morris, Lynsie; Zhu, Weizhu; Zhao, Yan D; Suh, K Stephen; Dooley, William C; Volk, David; Gorenstein, David G; Cristofanilli, Massimo; Rui, Hallgeir; Tanaka, Takemi

    2015-06-01

    Shear-resistant adhesion and extravasation of disseminated cancer cells at the target organ is a crucial step in hematogenous metastasis. We found that the vascular adhesion molecule E-selectin preferentially promoted the shear-resistant adhesion and transendothelial migration of the estrogen receptor (ER)(-)/CD44(+) hormone-independent breast cancer cells, but not of the ER(+)/CD44(-/low) hormone-dependent breast cancer cells. Coincidentally, CD44(+) breast cancer cells were abundant in metastatic lung and brain lesions in ER(-) breast cancer, suggesting that E-selectin supports hematogenous metastasis of ER(-)/CD44(+) breast cancer. In an attempt to prevent hematogenous metastasis through the inhibition of a shear-resistant adhesion of CD44(+) cancer cells to E-selectin-expressing blood vessels on the premetastatic niche, an E-selectin targeted aptamer (ESTA) was developed. We demonstrated that a single intravenous injection of ESTA reduced metastases to a baseline level in both syngeneic and xenogeneic forced breast cancer metastasis models without relocating the site of metastasis. The effect of ESTA was absent in E-selectin knockout mice, suggesting that E-selectin is a molecular target of ESTA. Our data highlight the potential application of an E-selectin antagonist for the prevention of hematogenous metastasis of ER(-)/CD44(+) breast cancer.

  15. Significance of Lymph Node Metastasis in Cancer Dissemination of Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Jae-Keun Cho

    2015-04-01

    Full Text Available Lymph node metastasis (LNM in many solid cancers is a well-known prognostic factor; however, it has been debated whether regional LNM simply reflects tumor aggressiveness or is a source for further tumor dissemination. Similarly, the metastatic process in head and neck cancer (HNC has not been fully evaluated. Thus, we aimed to investigate the relative significance of LNM in metastatic cascade of HNC using functional imaging of HNC patients and molecular imaging in in vivo models. First, we analyzed 18Fluorodeoxyglucose positron emission tomography (PET parameters of 117 patients with oral cancer. The primary tumor and nodal PET parameters were measured separately, and survival analyses were conducted on the basis of clinical and PET variables to identify significant prognostic factors. In multivariate analyses, we found that only the metastatic node PET values were significant. Next, we compared the relative frequency of lung metastasis in primary ear tumors versus lymph node (LN tumors, and we tested the rate of lung metastasis in another animal model, in which each animal had both primary and LN tumors that were expressing different colors. As a result, LN tumors showed higher frequencies of lung metastasis compared to orthotopic primary tumors. In color-matched comparisons, the relative contribution to lung metastasis was higher in LN tumors than in primary tumors, although both primary and LN tumors caused lung metastases. In summary, tumors growing in the LN microenvironment spread to systemic sites more commonly than primary tumors in HNC, suggesting that the adequate management of LNM can reduce further systemic metastasis.

  16. Lung cancer with skin and breast metastasis: a case report and literature review.

    Science.gov (United States)

    Bhattarai, Bikash; Schmidt, Marie Frances; Ghosh, Meenakshi; Sinha Ray, Abhisekh; Manhas, Saveena; Oke, Vikram; Agu, Chidozie Charles; Basunia, Md Rawshan; Enriquez, Danilo; Quist, Joseph; Bianchi, Catherine; Hans, Ravi; Kandel, Saroj

    2015-01-01

    Lung cancer is one of the most common cancers in America. Frequent sites of metastasis include the Hilar lymph nodes, adrenal glands, liver, brain, and bone. The following case report is of a primary lung cancer with metastases to the breast and skin. Case. A 48-year-old African American male with a past medical history of poorly differentiated left breast cancer status after modified radical mastectomy (MRM), chronic obstructive pulmonary disease, and smoking (20 pack-years) presents to the ER with progressive shortness of breath on exertion, upper back pain, and weight loss for 2 months in duration. On physical examination he is found to have a MRM scar on his left breast and a left periumbilical cutaneous mass. Chest X-ray and chest CT reveal a right upper lobe mass and biopsies from the breast, lung, and the periumbilical mass indicate a poorly differentiated carcinoma of unclear etiology; all tumor markers are negative. The patient is male and a chronic smoker; therefore the diagnosis is made as lung carcinoma with metastases to the breast and skin. Conclusion. A high index of suspicion for cutaneous metastases should be cast when investigating cutaneous pathologies in patients at risk for primary lung malignancy.

  17. Metformin may protect nondiabetic breast cancer women from metastasis.

    Science.gov (United States)

    El-Haggar, Sahar Mohammed; El-Shitany, Nagla A; Mostafa, Mohamed Farouk; El-Bassiouny, Noha Ahmed

    2016-04-01

    Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR.

  18. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

    DEFF Research Database (Denmark)

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes......, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge...... of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte...

  19. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    Science.gov (United States)

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  20. 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

  1. Novel candidate metastasis genes as putative drug targets for breast cancer

    NARCIS (Netherlands)

    Roosmalen, Wilhelmina Paulina Elisabeth van

    2012-01-01

    Despite extensive studies to unravel molecular mechanisms underlying breast cancer metastasis, still 3500 women die of the results of this disease in the Netherlands each year. Improving our understanding of metastasis formation remains a challenge for further drug development. The scope of this the

  2. The microRNA-218 and ROBO-1 signaling axis correlates with the lymphatic metastasis of pancreatic cancer.

    Science.gov (United States)

    He, Hang; Di, Yang; Liang, Minrui; Yang, Feng; Yao, Lie; Hao, Sijie; Li, Ji; Jiang, Yongjian; Jin, Chen; Fu, Deliang

    2013-08-01

    papillary mucinous neoplasm (IPMN), pancreatic cancer to metastatic lymph nodes by ISH. Among 8 predicted target genes of miRNA-218, rodent bone (ROBO-1) was confirmed to be upregulated in both mRNA and protein levels in pancreatic cancer. In conclusion, we established a screening strategy based on microarray results and found miRNA-218 to be a notable gene related to lymphatic metastasis of pancreatic cancer. Downregulation of miRNA-218 and upregulation of ROBO-1 were first demonstrated in pancreatic cancer. The miRNA-218 and ROBO-1 signaling axis may contribute to the lymphatic metastasis of pancreatic cancer.

  3. Endotracheal metastasis seen on FDG PET/CT in a patient with previous colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Hye Kyung; Kwon, Hyung Woo; Kim, Tae Sung; Kim, Seok Ki [National Cancer Center, Gayang (Korea, Republic of)

    2010-12-15

    Endotracheal/endobronchial metastasis, which is from either primary bronchogenic carcinoma or a tumor of non-pulmonary origin, is a rare but life-threatening condition. Among the different locations in the tracheobronchial tree, the trachea is an extremely rare location for metastasis from extrapulmonary tumor. To the best of our knowledge, endotracheal metastasis that was clearly visualized by F-18 FDG PET/CT has not been previously reported. We herein report on a patient with a FDG-avid endotracheal eccentric mass that was confirmed as metastasis from rectal cancer

  4. 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. ...

  5. Therapeutic options for peritoneal metastasis arising from colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Gabriel Glockzin; Hans J Schlitt; Pompiliu Piso

    2016-01-01

    Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer(pm CRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standar-dization of oncologic treatment regimens for pm CRC. The addition of further therapeutic options such as neo-adjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investig-ated to optimize therapeutic regimens and further improve the oncological outcome.

  6. Dynamics of tissue topology during cancer invasion and metastasis

    Science.gov (United States)

    Munn, Lance L.

    2013-12-01

    During tumor progression, cancer cells mix with other cell populations including epithelial and endothelial cells. Although potentially important clinically as well as for our understanding of basic tumor biology, the process of mixing is largely a mystery. Furthermore, there is no rigorous, analytical measure available for quantifying the mixing of compartments within a tumor. I present here a mathematical model of tissue repair and tumor growth based on collective cell migration that simulates a wide range of observed tumor behaviors with correct tissue compartmentalization and connectivity. The resulting dynamics are analyzed in light of the Euler characteristic number (χ), which describes key topological features such as fragmentation, looping and cavities. The analysis predicts a number of regimes in which the cancer cells can encapsulate normal tissue, form a co-interdigitating mass, or become fragmented and encapsulated by endothelial or epithelial structures. Key processes that affect the topological changes are the production of provisional matrix in the tumor, and the migration of endothelial or epithelial cells on this matrix. Furthermore, the simulations predict that topological changes during tumor invasion into blood vessels may contribute to metastasis. The topological analysis outlined here could be useful for tumor diagnosis or monitoring response to therapy and would only require high resolution, 3D image data to resolve and track the various cell compartments.

  7. STRIPAK components determine mode of cancer cell migration and metastasis

    Science.gov (United States)

    Madsen, Chris D.; Hooper, Steven; Tozluoglu, Melda; Bruckbauer, Andreas; Fletcher, Georgina; Erler, Janine T.; Bates, Paul A.; Thompson, Barry; Sahai, Erik

    2017-01-01

    The contractile actomyosin cytoskeleton and its connection to the plasma membrane are critical for control of cell shape and migration. We identify three STRIPAK complex components, FAM40A, FAM40B, and STRN3, as regulators of the actomyosin cortex. We show that FAM40A negatively regulates the MST3 and MST4 kinases, which promote the co-localisation of the contractile actomyosin machinery with the Ezrin/Radixin/Moesin family proteins by phosphorylating the inhibitors of PPP1CB, PPP1R14A-D. Using computational modelling, in vitro cell migration assays and in vivo breast cancer metastasis assays we demonstrate that co-localisation of contractile activity and actin-plasma membrane linkage reduces cell speed on planar surfaces, but favours migration in confined environments similar to those observed in vivo. We further show that FAM40B mutations found in human tumours uncouple it from PP2A and enable it to drive a contractile phenotype, which may underlie its role in human cancer. PMID:25531779

  8. Status and prognosis of lymph node metastasis in patients with cardia cancer - a systematic review

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Svendsen, Lars Bo; Achiam, Michael P

    2014-01-01

    BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality...... identifying relevant studies describing lymph node metastasis and the associated prognosis. Lymph node stations were classified according to the Japanese Gastric Cancer Association guidelines. RESULTS: The highest incidence of metastasis is seen in the nearest regional lymph nodes, station no. 1......-3 and additionally in no. 7, 9 and 11. Correspondingly the best survival is seen when metastasis remain in the most locoregional nodes and survival equally tends to decrease as the metastasis become more distant. Furthermore, the presence of lymph node metastasis significantly correlates to the TNM-stage. Incidences...

  9. Meaningful prevention of breast cancer metastasis: candidate therapeutics, preclinical validation, and clinical trial concerns.

    Science.gov (United States)

    Zimmer, Alexandra S; Steeg, Patricia S

    2015-01-01

    The development of drugs to treat breast and other cancers proceeds through phase I dose finding, phase II efficacy, and phase III comparative studies in the metastatic setting, only then asking if metastasis can be prevented in adjuvant trials. Compounds without overt cytotoxic activity, such as those developed to inhibit metastatic colonization, will likely fail to shrink established lesions in the metastatic setting and never be tested in a metastasis prevention scenario where they were preclinically validated. We and others have proposed phase II primary and secondary metastasis prevention studies to address this need. Herein, we have asked whether preclinical metastasis prevention data agrees with the positive adjuvant setting trials. The data are limited but complimentary. We also review fundamental pathways involved in metastasis, including Src, integrins, focal adhesion kinase (FAK), and fibrosis, for their clinical progress to date and potential for metastasis prevention. Issues of inadequate preclinical validation and clinical toxicity profiles are discussed.

  10. Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer

    Science.gov (United States)

    2013-10-01

    Target for Progression and Metastasis of Prostate Cancer PRINCIPAL INVESTIGATOR: Jean C. Shih, Ph.D. CONTRATING ORGANIZATION...aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services

  11. Complex pattern of colon cancer recurrence including a kidney metastasis: A case report

    Institute of Scientific and Technical Information of China (English)

    Helfried Waleczek; Moritz N Wente; Jürgen Kozianka

    2005-01-01

    We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancreatoduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colon. Although intraluminal implantation of colon cancer cells in the renal pelvic mucosa from ureteric metastasis has been described, metastasis of a colorectal cancer in the kidney parenchyma is extremely rare and can be treated in an organ preserving manner. A complex pattern of colon cancer recurrence with unusual and rare sites of metastasis is reported.

  12. MiR-888 regulates side population properties and cancer metastasis in breast cancer cells.

    Science.gov (United States)

    Huang, Shengjian; Chen, Liangbiao

    2014-08-01

    Cancer stem cells (CSCs) have recently been reported to possess properties related to cancer metastasis. However, the mechanism by which microRNAs (miRNAs) regulate these properties remains unclear. This study aims to investigate a correlation between miRNAs and the side population (SP) of human breast cancer cell line MCF-7 with CSC properties. miR-888 was found in our previous study to be up-regulated in SP cells and predicted to target E-Cadherin directly, indicating a potential role in maintaining SP properties and regulating the epithelial-mesenchymal transition (EMT) and cancer metastasis. After the over-expression of miR-888 in MCF-7 cells and knock-down of its expression in SP cells, we found that miR-888 played a role in maintaining CSC-related properties. Next, miR-888 was found to regulate the EMT process by targeting related gene expression. Lastly, MCF-7 cells over-expressing miR-888 exhibited a significant reduction in their ability to adhere to the extracellular matrix and an increased potential for migration and invasion, whereas knock-down of miR-888 expression in SP cells reversed these trends. In conclusion, miR-888 maintains SP properties and regulates EMT and metastasis in MCF-7 cells, potentially by targeting E-Cadherin expression.

  13. MicroRNAs:regulators of cancer metastasis and epithelial-mesenchymal transition (EMT)

    Institute of Scientific and Technical Information of China (English)

    Xiang-Ming Ding

    2014-01-01

    Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition (EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated during cancer invasion and metastasis. MicroRNAs (miRNAs) are smal , non-coding RNAs that provide widespread expressional control by repressing mRNA translation and inducing mRNA degradation. The fundamental roles of miRNAs in tumor growth and metastasis have been increasingly wel recognized. A growing number of miRNAs are reported to regulate tumor invasion/metastasis through EMT-related and/or non-EMT-related mechanisms. In this review, we discuss the functional role and molecular mechanism of miRNAs in regulating cancer metastasis and EMT.

  14. Relationship between Preoperative Clinicopathologic Characteristics and Lymph Node Metastasis in Early Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    LIU Cai-Gang; LU Ping; LU Yang; ZHANG Rui-shan; JIN Feng; XU Hui-mian; WANG Shu-bao; CHEN Jun-qing

    2007-01-01

    Objective: To investigate the features of the preoperative clinicopathologic characteristics in correlation with lymph node metastasis. Methods: The preoperative clinicopathologic characteristics and lymph node metastasis of 265 patients with early gastric carcinoma were analyzed retrospectively. Results: The three clinicopathologic characteristics, maximum cancer diameter >2cm under endoscope, poor differentiation and excavated type were significant high risk independent preoperative clinicopathologic characteristics(P<0.05). The patients who had none of the three preoperative clinicopathologic characteristics had no lymph node metastasis, while 27.27% of the patients who had all the three preoperative clinicopathologic characteristics had N2 lymph node metastasis. Conclusion: The three preoperative clinicopathologic characteristics, maximum cancer diameter under endoscope, cell differentiation and gross type were very useful to evaluate the extent of lymph node metastasis.

  15. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Science.gov (United States)

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  16. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  17. Palliative Surgery for Rare Cases of Anterior Urethral Metastasis in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Enrique Gómez Gómez

    2014-01-01

    Full Text Available Penis metastasis from prostate cancer is very rare, and its management varies from case to case as there are very few cases reported in the literature. We describe a patient with prostate cancer treated with radiotherapy and androgen deprivation therapy who presented with urethral bleeding as a symptom of anterior urethral metastasis during followup. We propose a way to manage this and review the literature.

  18. Palliative Surgery for Rare Cases of Anterior Urethral Metastasis in Prostate Cancer

    Science.gov (United States)

    Gómez Gómez, Enrique; Carrasco Aznar, Jose Carlos; Moreno Rodríguez, Maria del Mar; Valero Rosa, José; Requena Tapia, Maria José

    2014-01-01

    Penis metastasis from prostate cancer is very rare, and its management varies from case to case as there are very few cases reported in the literature. We describe a patient with prostate cancer treated with radiotherapy and androgen deprivation therapy who presented with urethral bleeding as a symptom of anterior urethral metastasis during followup. We propose a way to manage this and review the literature. PMID:25161796

  19. Comparison of gene sets for expression profiling: prediction of metastasis from low-malignant breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja;

    2007-01-01

    -six tumors from low-risk patients and 34 low-malignant T2 tumors from patients with slightly higher risk have been examined by genome-wide gene expression analysis. Nine prognostic gene sets were tested in this data set. RESULTS: A 32-gene profile (HUMAC32) that accurately predicts metastasis has previously...... sets, mainly developed in high-risk cancers, predict metastasis from low-malignant cancer....

  20. Clinical application of whole blood red cell distribution width in lung cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    徐阳飏

    2014-01-01

    Objective To investigate the clinical value of whole blood red cell distribution width(RDW)in discriminating lung cancer metastasis.Methods A retropective analysis was conducted on the patients who were initially diagnosed as primary lung cancer.A total of 525 patients were included for analysis between January 2012 and July2013,stratified by different stages and metastasis scenarios.RDW data was investigated.Kruskal-Wallis H tests

  1. Metastin has potential as a suitable biomarker and novel effective therapy for cancer metastasis (Review).

    Science.gov (United States)

    Shoji, Sunao; Tang, Xian Yang; Sato, Haruhiro; Usui, Yukio; Uchida, Toyoaki; Terachi, Toshiro

    2010-09-01

    Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas without affecting tumorigenicity. KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues. The peptide was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor and termed 'metastin'. The literature reports metastin related to human carcinoma, such as melanoma, thyroid cancer, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma, pancreatic carcinoma, as well as breast, ovarian, bladder and kidney cancer. These malignancies are difficult to treat and, even in early-stage cancer, a number of patients develop metastasis shortly after surgery. Studies have suggested that metastin inhibits tumor invasion or migration through focal adhesion kinase, paxillin, MAP kinase or Rho A. Additionally, metastin may be a biomarker in ESCC, pancreatic carcinoma and bladder cancer. Metastin has potential as a suitable biomarker in the identification of tumors with high metastatic potential and as a novel effective treatment modality for patients with metastasis.

  2. A CLINICOPATHOLOGICAL STUDY OF MEDIASTINAL LYMPH NODE METASTASIS OF LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective:To investigate pathologically the characteristics of lung cancer metastasis by mediastinal lymph node ways (N2). Methods: Of 398 lung cancer patients who underwent radical pulmonectomy and extensive lymph node dissection, 160 patients were diagnosed as with N2 metastasis, their 352 groups of mediastinal lymph nodes invaded were subject to the pathological study. Results: Evidences showed that the N2 metastasis of lung cancer was very active. It appears as single group or multi-group or jumping-form metastasis, rating 41.2%, 58.8% and 29.3% respectively. In addition, the extension of N2 metastasis was large, the most concentrated site was the 7th group lymph node (48.8%), then the 4th, 3rd and 5th group, rating 45.6%, 31.3% and 25.6% respectively. The occurrence of N2 metastasis was highly correlated with the site, size, histopathological type and the grade of differentiation of the cancer. An another feature of N2 metastasis was the invasion of metastasized lymph node into the bronchial wall, especially in adenocarcinoma. Conclusion: In order to achieve the radical removal of tumor, it is necessary to dissect the lymph nodes of the hilar and upper and lower mediastinum at the homolateral thoracic cavity actively and completely; beside, attention may be paid to the bronchial wall invasion caused by the lymph nodes metastasized.

  3. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  4. Antiresorptive therapy in the management of cancer treatment-induced bone loss.

    Science.gov (United States)

    Garg, Ashwani; Leitzel, Kim; Ali, Suhail; Lipton, Allan

    2015-04-01

    Cancer treatment-induced bone loss treatment has an important role to prevent bone loss-related events like fracture, significant morbidity, mortality, disfigurement and loss of self-esteem, and health-care expenditure. Numerous factors, including treatment regimens and bone metastasis, increase the risk of osteoporosis or local bone destruction in most breast and prostate cancer patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to premature menopause and decrease bone mineral density. Over 60 % of breast cancer patients within 1 year of beginning postoperative adjuvant chemotherapy experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to treat prostate cancer) cause substantial bone loss. In this article, we will focus mainly on antiresorptive therapy in the management of cancer treatment-induced bone loss (CTIBL). An understanding of CTIBL is critical for determining how to assess the risk and identify which patients may benefit from preventive therapy.

  5. Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis

    Directory of Open Access Journals (Sweden)

    Hon S. Leong

    2014-09-01

    Full Text Available Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin, maturation (Tks5, or function (Tks4 resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.

  6. Role of CXCL12 in metastasis of human ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Yu-ping; WU Xiao-hua; XING Han-ying; DU Xing-yan

    2007-01-01

    Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer.Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetrazolium (MTT) was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C (VEGF-C) mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12.Results Under serum-free suboptimal culture conditions, CXCL12 (100 ng/ml) significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups (0.428±0.051 vs. 0.325±0.045 and 0.328±0.039, P<0.05). This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control (migration: 523.3±25.2 vs 108.0±7.2; invasion: 39.3±4.0 vs. 4.0±1.0). The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 (100 ng/ml vs10 ng/ml: migration, 523.3±25.2 vs 211.7±24.7; invasion, 39.3±4.0 vs 15.7±3.1, P<0.05), and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly

  7. Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway.

    Science.gov (United States)

    Cai, Wen-Song; Shen, Fei; Feng, Zhe; Chen, Ji-Wei; Liu, Qi-Cai; Li, Er-Mao; Xu, Bo; Cao, Jie

    2015-08-01

    Liver metastasis is a major cause of mortality from colon cancer. To investigate the role of cyclin-dependent kinase 8 (CDK8) in the progression of colon cancer hepatic metastasis. In this present study, human colon cancer HCT116 or HCT116-LUC-GFP cells were transfected with Lentiviral vector-mediated knockdown of CDK-8. After transfection, metastasis and invasion potential of colon cancer cell was investigated by wound healing and transwell invasion assays, respectively. A mice model of colon cancer liver metastases was established and observed with bioluminescence imaging. The protein expression of CDK-8, β-catenin, E2F1, MMP-7 and E-cadherin in liver tissues were detected by Western Blot. Our results revealed that lentiviral vector-mediated knockdown of CDK-8 inhibited metastasis and invasion of colon cancer cells in vitro and in vivo, respectively. Protein expression of CDK-8, β-catenin, MMP-7 and E-cadherin were inhibited, but protein expression of E2F1 was enhanced. In sum, our data provided compelling evidence that CDK-8 played a significant role in colon cancer hepatic metastasis by regulating the Wnt/β-catenin signal pathway and might sever as a potential therapeutic target for colon cancer patients.

  8. BRMS1 Suppresses Breast Cancer Metastasis to Bone via Its Regulation of MicroRNA-125b and Downstream Attenuation of TNF-alpha and HER2 Signaling Pathways

    Science.gov (United States)

    2013-10-01

    Tang CK, Kurosumi M, Yamamoto S, et al. (1999) Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B...functional, heterotrimeric complexes by co-expression of subunits in Escherichia coli . Protein Expr Purif 30: 230-237. 7. Hardie DG, Alessi DR (2013) LKB1...Lelsani PC, Awasthi S, Singhal SS. The sensors and regulators of cell-matrix surveil- lance in anoikis resistance of tumors. Int J Cancer 2011;128: 743

  9. Isolated Liver Metastasis in Hürthle Cell Thyroid Cancer Treated with Microwave Ablation

    Directory of Open Access Journals (Sweden)

    Konstantinos Segkos

    2017-01-01

    Full Text Available Hürthle cell thyroid cancer (HCTC is a less common form of differentiated thyroid cancer. It rarely metastasizes to the liver, and when it does, the metastasis is almost never isolated. Here we report a 62-year-old male with widely invasive Hürthle cell thyroid cancer, who underwent total thyroidectomy and received adjuvant treatment with I-131 with posttreatment scan showing no evidence of metastatic disease. His thyroglobulin however continued to rise after that and eventually an isolated liver metastasis was identified. He underwent laparoscopic microwave ablation of the liver metastasis, with dramatic decline in thyroglobulin and no structural disease identified to date. This case highlights the rare occurrence of isolated liver metastasis from HCTC and also illustrates the utility of thermoablation as an alternative to surgical resection in the treatment of small isolated liver metastases from HCTC.

  10. Isolated Liver Metastasis in Hürthle Cell Thyroid Cancer Treated with Microwave Ablation.

    Science.gov (United States)

    Segkos, Konstantinos; Schmidt, Carl; Nabhan, Fadi

    2017-01-01

    Hürthle cell thyroid cancer (HCTC) is a less common form of differentiated thyroid cancer. It rarely metastasizes to the liver, and when it does, the metastasis is almost never isolated. Here we report a 62-year-old male with widely invasive Hürthle cell thyroid cancer, who underwent total thyroidectomy and received adjuvant treatment with I-131 with posttreatment scan showing no evidence of metastatic disease. His thyroglobulin however continued to rise after that and eventually an isolated liver metastasis was identified. He underwent laparoscopic microwave ablation of the liver metastasis, with dramatic decline in thyroglobulin and no structural disease identified to date. This case highlights the rare occurrence of isolated liver metastasis from HCTC and also illustrates the utility of thermoablation as an alternative to surgical resection in the treatment of small isolated liver metastases from HCTC.

  11. Cell membrane fluid-mosaic structure and cancer metastasis.

    Science.gov (United States)

    Nicolson, Garth L

    2015-04-01

    Cancer cells are surrounded by a fluid-mosaic membrane that provides a highly dynamic structural barrier with the microenvironment, communication filter and transport, receptor and enzyme platform. This structure forms because of the physical properties of its constituents, which can move laterally and selectively within the membrane plane and associate with similar or different constituents, forming specific, functional domains. Over the years, data have accumulated on the amounts, structures, and mobilities of membrane constituents after transformation and during progression and metastasis. More recent information has shown the importance of specialized membrane domains, such as lipid rafts, protein-lipid complexes, receptor complexes, invadopodia, and other cellular structures in the malignant process. In describing the macrostructure and dynamics of plasma membranes, membrane-associated cytoskeletal structures and extracellular matrix are also important, constraining the motion of membrane components and acting as traction points for cell motility. These associations may be altered in malignant cells, and probably also in surrounding normal cells, promoting invasion and metastatic colonization. In addition, components can be released from cells as secretory molecules, enzymes, receptors, large macromolecular complexes, membrane vesicles, and exosomes that can modify the microenvironment, provide specific cross-talk, and facilitate invasion, survival, and growth of malignant cells.

  12. Significant overexpression of DVL1 in Taiwanese colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Huang, Ming-Yii; Yen, Li-Chen; Liu, Hsueh-Chiao; Liu, Po-Ping; Chung, Fu-Yen; Wang, Tsu-Nai; Wang, Jaw-Yuan; Lin, Shiu-Ru

    2013-10-14

    Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2) in the cancer patients. We used a weighted enzymatic chip array (WEnCA) including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I-III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC) method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214) of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588-12.837; p liver metastasis status (all p liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients.

  13. Late recurrence of large peri-stomal metastasis following abdomino-perineal resection of rectal cancer

    Directory of Open Access Journals (Sweden)

    Noormohamed Saleem

    2008-09-01

    Full Text Available Abstract Background Cutaneous metastasis from colorectal cancer after excision of the primary is a rare occurrence and presents as cutaneous or subcutaneous nodules or as a rash commonly on the anterior abdominal wall. Case presentation This is a case description of the management of a large fungating peristomal cutaneous metastasis occurring 14 years after abdomino-perineal excision of the primary cancer. The gross appearance initially suggested possibility of a true metachronous cancer with peristomal spread. But histopathology of the resected specimen showed no colonic mucosal involvement suggesting a true large cutaneous peristomal metastasis which has not been reported previously. Literature review of presentation, management and prognosis of cutaneous metastasis from colorectal cancer is described Conclusion Cutaneous metastasis following colorectal cancer resection is a well-recognised entity though rare. Any unusual skin lesions especially on the abdominal wall skin, previous incision scars or near the stoma should be biopsied early to rule out metastatic disease and systematic work-up should be carried out to rule out any metachronous tumour or metastasis elsewhere in the body.

  14. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Kelly M. [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); Kirby, John A. [Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Lennard, Thomas W.J. [Faculty of Medical Sciences, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Meeson, Annette P., E-mail: annette.meeson@ncl.ac.uk [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom)

    2011-04-19

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  15. Docosahexaenoic acid suppresses breast cancer cell metastasis by targeting matrix-metalloproteinases

    Science.gov (United States)

    Shin, Soyeon; Kim, Soyeon; Heo, Jun-Young; Kweon, Gi-Ryang; Wu, Tong; Park, Jong-Il; Lim, Kyu

    2016-01-01

    Breast cancer is one of the most prevalent cancers in women, and nearly half of breast cancer patients develop distant metastatic disease after therapy. Despite the significant advances that have been achieved in understanding breast cancer metastasis in the past decades, metastatic cancer is still hard to cure. Here, we demonstrated an anti-cancer mechanism of docosahexaenoic acid (DHA) that suppressed lung metastasis in breast cancer. DHA could inhibit proliferation and invasion of breast cancer cells in vitro, and this was mainly through blocking Cox-2-PGE2-NF-κB-MMPs cascades. DHA treatment significantly decreased Cox-2 and NF-κB expression as well as nuclear translocation of NF-κB in MDA-MB-231 cells. In addition, DHA also reduced NF-κB binding to DNA which may lead to inactivation of MMPs. Moreover, in vivo studies using Fat-1 transgenic mice showed remarkable decrease of tumor growth and metastasis to EO771 cells to lung in DHA-rich environment. In conclusion, DHA attenuated breast cancer progression and lung metastasis in part through suppressing MMPs, and these findings suggest chemoprevention and potential therapeutic strategy to overcome malignant breast cancer. PMID:27363023

  16. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  17. 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.

  18. Systemic Delivery of an Oncolytic Adenovirus Expressing Decorin for the Treatment of Breast Cancer Bone Metastases.

    Science.gov (United States)

    Yang, Yuefeng; Xu, Weidong; Neill, Thomas; Hu, Zebin; Wang, Chi-Hsiung; Xiao, Xianghui; Stock, Stuart R; Guise, Theresa; Yun, Chae-Ok; Brendler, Charles B; Iozzo, Renato V; Seth, Prem

    2015-12-01

    The development of novel therapies for breast cancer bone metastasis is a major unmet medical need. Toward that end, we have constructed an oncolytic adenovirus, Ad.dcn, and a nonreplicating adenovirus, Ad(E1-).dcn, both containing the human decorin gene. Our in vitro studies showed that Ad.dcn produced high levels of viral replication and the decorin protein in the breast tumor cells. Ad(E1-).dcn-mediated decorin expression in MDA-MB-231 cells downregulated the expression of Met, β-catenin, and vascular endothelial growth factor A, all of which are recognized decorin targets and play pivotal roles in the progression of breast tumor growth and metastasis. Adenoviral-mediated decorin expression inhibited cell migration and induced mitochondrial autophagy in MDA-MB-231 cells. Mice bearing MDA-MB-231-luc skeletal metastases were systemically administered with the viral vectors, and skeletal tumor growth was monitored over time. The results of bioluminescence imaging and X-ray radiography indicated that Ad.dcn and Ad(E1-).dcn significantly inhibited the progression of bone metastases. At the terminal time point, histomorphometric analysis, micro-computed tomography, and bone destruction biomarkers showed that Ad.dcn and Ad(E1-).dcn reduced tumor burden and inhibited bone destruction. A nonreplicating adenovirus Ad(E1-).luc expressing the luciferase 2 gene had no significant effect on inhibiting bone metastases, and in several assays, Ad.dcn and Ad(E1-).dcn were better than Ad.luc, a replicating vir