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Sample records for cancer bone metastasis

  1. Bone Targeted Therapies for Bone Metastasis in Breast Cancer

    OpenAIRE

    Wajeeha Razaq

    2013-01-01

    Cancer metastasis to the bone develops commonly in patients with various malignancies, and is a major cause of morbidity and diminished quality of life in many affected patients. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to the bone metastasis. The tendency of cancer cells to metastasize to bone is probably the end result of many factors including vascular pathways, the highly ...

  2. 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.

  3. Nanoradiopharmaceuticals for Bone Cancer Metastasis Imaging.

    Science.gov (United States)

    Coelho, Bianca Feliciano; de Souza Albernaz, Marta; Iscaife, Alexandre; Moreira Leite, Katia Ramos; de Souza Junqueira, Mara; Bernardes, Emerson Soares; da Silva, Emerson Oliveira; Santos-Oliveira, Ralph

    2015-01-01

    Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radiopharmaceuticals for many years; however, their use as nanoradiopharmaceuticals is very innovative and creates a new way to establish radiopharmacy in this new scenario offered by nanotechnology. In this study we developed and tested nano-MDP-labelled with 99mTc in rats induced with bone cancer metastasis and the results showed that it may work in patients. However, some further experiments are required in order to initiate protocols in humans. PMID:25847010

  4. Steps in Prostate Cancer Progression that lead to Bone Metastasis

    OpenAIRE

    Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

    2011-01-01

    Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current...

  5. Dissociation of bone formation markers in bone metastasis of prostate cancer.

    OpenAIRE

    Koizumi, M; Maeda, H.; Yoshimura, K; Yamauchi, T.; Kawai, T.; Ogata, E

    1997-01-01

    To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression...

  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. Protocadherin-7 induces bone metastasis of breast cancer

    International Nuclear Information System (INIS)

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer

  8. Protocadherin-7 induces bone metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ai-Min [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China); Tian, Ai-Xian [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Zhang, Rui-Xue [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Sun, Xuan [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Cao, Xu-Chen, E-mail: caoxuch@126.com [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-07-05

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  9. Review of Animal Models of Prostate Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    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. Usefulness of Bone Metabolic Markers in the Diagnosis of Bone Metastasis from Lung Cancer

    OpenAIRE

    Chung, Jae Ho; Park, Moo Suk; Kim, Young Sam; Chang, Joon; Kim, Joo Hang; Kim, Sung Kyu; Kim, Se Kyu

    2005-01-01

    Bone metastasis is common in lung cancer patient and the diagnosis of bone metastasis is usually made by using imaging techniques, especially bone scintigraphy. However, the diagnostic yield from bone scintigraphy is limited. The aim of this study is to assess the clinical usefulness of urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment of bone metastasis in patients with lung cance...

  11. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    International Nuclear Information System (INIS)

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

  12. Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

    Science.gov (United States)

    Morris, Emma V.; Edwards, Claire M.

    2016-01-01

    The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease.

  13. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    OpenAIRE

    Thobe, Megan N.; Rinker-Schaeffer, Carrie W.; Clark, Robert J; Bainer, Russell O.; Prasad, Sandip M.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules ...

  14. 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...... and length of BM-free interval (BMFI). SETTING: Denmark. PARTICIPANTS: 2427 women with a breast cancer diagnosis between 1997 and 2011 in the Danish Cancer Registry and a concurrent or subsequent BM diagnosis in the Danish National Registry of Patients. PRIMARY AND SECONDARY OUTCOME MEASURES: Survival (crude......) based on Kaplan-Meier method and mortality risk (crude and adjusted for age, year of diagnosis, estrogen receptor status and comorbidity) based on Cox proportional hazards regression analyses by stage of disease at breast cancer diagnosis and by length of BMFI (time from breast cancer to BM diagnosis...

  15. Advances in cancer pain from bone metastasis

    OpenAIRE

    Zhu XC; JL Zhang; Ge CT; Yu YY; Wang P; Yuan TF; Fu CY

    2015-01-01

    Xiao-Cui Zhu,1 Jia-Li Zhang,1 Chen-Tao Ge,1 Yuan-Yang Yu,1 Pan Wang,1 Ti-Fei Yuan,2 Cai-Yun Fu1,31College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 2School of Psychology, Nanjing Normal University, Nanjing, 3Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, People’s Republic of ChinaAbstract: With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out h...

  16. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  18. Bioinformatics analysis of breast cancer bone metastasis related geneCXCR4

    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 upregulated in the tissue with breast cancer bone metastasis.Compared with the tissue without hone metastasis,there was significant difference,which indicated that CXCR4 played a vital role in breast cancer bone metastasis.Conclusions:The hioinformatics 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.

  19. ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

    OpenAIRE

    Mourskaia, Anna A; Amir, Eitan; Dong, Zhifeng; Tiedemann, Kerstin; Cory, Sean; Omeroglu, Atilla; Bertos, Nicholas; Ouellet, Véronique; Clemons, Mark; Scheffer, George L.; Park, Morag; Hallett, Michael; Svetlana V Komarova; Siegel, Peter M.

    2012-01-01

    Introduction Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture micr...

  20. Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

    OpenAIRE

    Sugiura, Hideshi; Yamada, Kenji; Sugiura, Takahiko; Hida, Toyoaki; Mitsudomi, Tetsuya

    2008-01-01

    The prognosis of patients with bone metastasis from lung cancer has not been well documented. We assessed the survival rates after bone metastasis and prognostic factors in 118 patients with bone metastases from lung cancer. The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1–74.5 months). A favorable prognosis was more likely in women and patients w...

  1. Tumor-derived Jagged1 Promotes Osteolytic Bone Metastasis of Breast Cancer by Engaging Notch Signaling in Bone Cells

    OpenAIRE

    Sethi, Nilay; Dai, Xudong; Winter, Christopher G.; Kang, Yibin

    2011-01-01

    Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway’s contribution to metastasis remains unknown. Here we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of bone metastasis by activating the Notch pathway in bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the bone metastasis cyto...

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

    Directory of Open Access Journals (Sweden)

    Yoshimoto Masataka

    2010-07-01

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

  3. RUNX2 promotes breast cancer bone metastasis by increasing integrin α5-mediated colonization.

    Science.gov (United States)

    Li, Xiao-Qing; Lu, Jun-Tao; Tan, Cong-Cong; Wang, Qing-Shan; Feng, Yu-Mei

    2016-09-28

    Runt-related transcription factor 2 (RUNX2) is regarded as an important contributor to breast cancer bone metastasis. However, previous studies did not provide direct clinical evidence for a role of RUNX2 in bone-specific metastasis in breast cancer, and the mechanism of RUNX2 in cancer cell recruitment and adhesion to the bone remains unclear. In this study, we showed that RUNX2 expression is positively correlated with the risk of bone-specific metastasis in lymph node-negative breast cancer patients. Then, we identified ITGA5 as a transcriptional target of RUNX2 from multiple candidate genes encoding adhesion molecules or chemokine receptors. We further provided experimental and clinical evidence that RUNX2, in an integrin α5-dependent manner, promotes the attraction and adhesion of breast cancer cells to the bone and confers cancer cell survival and bone colonization advantages. Overall, our findings clarify an adhesion-dependent mechanism of RUNX2 for the osteotropism and bone colonization of breast cancer cells and implicate RUNX2 and integrin α5 as potential molecular markers for the prediction of bone metastasis and therapeutic targets for the treatment of breast cancer bone metastasis. PMID:27317874

  4. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

    International Nuclear Information System (INIS)

    Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer

  5. 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.

  6. Up-regulation of bone marrow stromal protein 2 (BST2 in breast cancer with bone metastasis

    Directory of Open Access Journals (Sweden)

    Zheng Xin

    2009-04-01

    Full Text Available Abstract Background Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. Methods cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO and a primary human breast cancer cell line (MDA-231. The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. Results The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO compared to the primary human breast cancer cell line (MDA-231. The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor

  7. DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA

    OpenAIRE

    Rahman, M.; Veigas, Maria; Williams, Paul J.; Fernandes, Gabriel

    2013-01-01

    Breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Attenuation of breast cancer metastasis to bone and associated osteolysis by fish oil (FO), rich in EPA and DHA, has been demonstrated previously. However, it was not known whether EPA and DHA differentially or similarly affect breast cancer bone metastasis and associated osteolysis. In vitro culture of parental and luciferase gene encoded MDA-MB-231 human breast can...

  8. Targeting Bone Remodeling by Isoflavone and 3,3′-Diindolylmethane in the Context of Prostate Cancer Bone Metastasis

    OpenAIRE

    Yiwei Li; Dejuan Kong; Aamir Ahmad; Bin Bao; Sarkar, Fazlul H

    2012-01-01

    Prostate cancer (PCa) bone metastases have long been believed to be osteoblastic because of bone remodeling leading to the formation of new bone. However, recent studies have shown increased osteolytic activity in the beginning stages of PCa bone metastases, suggesting that targeting both osteolytic and osteoblastic mediators would likely inhibit bone remodeling and PCa bone metastasis. In this study, we found that PCa cells could stimulate differentiation of osteoclasts and osteoblasts throu...

  9. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  11. A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

    Directory of Open Access Journals (Sweden)

    Laure Thibaudeau

    2014-02-01

    Full Text Available The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo.

  12. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis.

    Science.gov (United States)

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

    2016-01-01

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

  13. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis.

    Science.gov (United States)

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

    2016-01-01

    Bone is one of the most common metastatic sites of breast cancer, but the underlying mechanisms remain unclear, in part due to an absence of advanced platforms for cancer culture and study that mimic the bone microenvironment. In the present study, we integrated a novel stereolithography-based 3D printer and a unique 3D printed nano-ink consisting of hydroxyapatite nanoparticles suspended in hydrogel to create a biomimetic bone-specific environment for evaluating breast cancer bone invasion. Breast cancer cells cultured in a geometrically optimized matrix exhibited spheroid morphology and migratory characteristics. Co-culture of tumor cells with bone marrow mesenchymal stem cells increased the formation of spheroid clusters. The 3D matrix also allowed for higher drug resistance of breast cancer cells than 2D culture. These results validate that our 3D bone matrix can mimic tumor bone microenvironments, suggesting that it can serve as a tool for studying metastasis and assessing drug sensitivity. From the Clinical Editor: Cancer remains a major cause of mortality for patients in the clinical setting. For breast cancer, bone is one of the most common metastatic sites. In this intriguing article, the authors developed a bone-like environment using 3D printing technology to investigate the underlying biology of bone metastasis. Their results would also allow a new model for other researchers who work on cancer to use. PMID:26472048

  14. Three-Dimensional Cancer-Bone Metastasis Model Using Ex-Vivo Co-Cultures of Live Calvarial Bones and Cancer Cells

    OpenAIRE

    Curtin, Paul; Youm, Helen; Salih, Erdjan

    2011-01-01

    One of the major limitations of studying cancer-bone metastasis has been the lack of an appropriate ex-vivo model which can be used under defined conditions that simulates closely the in vivo live bone microenvironment in response to cancer-bone interactions. We have developed and utilized a three-dimensional (3D) cancer-bone metastasis model using free floating live mouse calvarial bone organs in the presence of cancer cells in a roller-tube system. In such co-cultures under hypoxia and a sp...

  15. Dual function of ERR alpha in breast cancer and bone metastasis formation: implication of VEGF and osteoprotegerin.

    OpenAIRE

    Fradet, Anais; Sorel, Helene; Bouazza, Lamia; Goehrig, Delphine; Depalle, Baptiste; Bellahcene, Akeila; Castronovo, Vincenzo; Follet, Helene; Descotes, Francoise; Aubin, Jane E; Clezardin, Philippe; Bonnelye, Edith

    2011-01-01

    Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRalpha) has been implicated in breast cancer and bone development, prompting us to examine whether ERRalpha may function in promoting the osteolytic growth of breast cancer cells in bone. In a mouse xenograft model of metastatic human breast cancer, overexpression of wild-type ERRalpha reduced metastasis, whereas overexpression of a dominant negative mut...

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

    Science.gov (United States)

    Erdogan, Bulent; Cicin, Irfan

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-23

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

  18. Correlation of the Levels of the Bone Turnover Markers BAP and β-CTX with Bone Metastasis Progress in Lung Cancer Patients

    OpenAIRE

    Tang, Qiong; Zhao, Hui; JIA, RUI; Liu, Linlin

    2013-01-01

    Background and objective Bone metastasis is common in lung cancer patients. The β isomer of the C-terminal telopeptide of type I collagen (β-CTX) and bone-specific alkaline phosphates (BAP) are regarded as important bone turnover markers in bone resorption and formation. Thus, the aims of this study are to determine the correlation of these bone turnover markers with the extent of bone metastasis of lung cancer. Methods A total of 92 patients with bone metastasis of lung cancer from Tianjin U...

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

    Science.gov (United States)

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

    2015-10-13

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

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

    International Nuclear Information System (INIS)

    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 18F-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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-06-15

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

  3. RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis

    International Nuclear Information System (INIS)

    Prostate cancer is the third leading cause of male cancer deaths in the developed world. The current lack of highly specific detection methods and efficient therapeutic agents for advanced disease have been identified as problems requiring further research. The integrins play a vital role in the cross-talk between the cell and extracellular matrix, enhancing the growth, migration, invasion and metastasis of cancer cells. Progression and metastasis of prostate adenocarcinoma is strongly associated with changes in integrin expression, notably abnormal expression and activation of the β3 integrins in tumour cells, which promotes haematogenous spread and tumour growth in bone. As such, influencing integrin cell expression and function using targeted therapeutics represents a potential treatment for bone metastasis, the most common and debilitating complication of advanced prostate cancer. In this review, we highlight the multiple ways in which RGD-binding integrins contribute to prostate cancer progression and metastasis, and identify the rationale for development of multi-integrin antagonists targeting the RGD-binding subfamily as molecularly targeted agents for its treatment

  4. 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).

  5. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice

    OpenAIRE

    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto, Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Ming ZHAO

    2014-01-01

    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  6. 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

  7. 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.

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

    International Nuclear Information System (INIS)

    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

  9. Targeting bone remodeling by isoflavone and 3,3'-diindolylmethane in the context of prostate cancer bone metastasis.

    Directory of Open Access Journals (Sweden)

    Yiwei Li

    Full Text Available Prostate cancer (PCa bone metastases have long been believed to be osteoblastic because of bone remodeling leading to the formation of new bone. However, recent studies have shown increased osteolytic activity in the beginning stages of PCa bone metastases, suggesting that targeting both osteolytic and osteoblastic mediators would likely inhibit bone remodeling and PCa bone metastasis. In this study, we found that PCa cells could stimulate differentiation of osteoclasts and osteoblasts through the up-regulation of RANKL, RUNX2 and osteopontin, promoting bone remodeling. Interestingly, we found that formulated isoflavone and 3,3'-diindolylmethane (BR-DIM were able to inhibit the differentiation of osteoclasts and osteoblasts through the inhibition of cell signal transduction in RANKL, osteoblastic, and PCa cell signaling. Moreover, we found that isoflavone and BR-DIM down-regulated the expression of miR-92a, which is known to be associated with RANKL signaling, EMT and cancer progression. By pathway and network analysis, we also observed the regulatory effects of isoflavone and BR-DIM on multiple signaling pathways such as AR/PSA, NKX3-1/Akt/p27, MITF, etc. Therefore, isoflavone and BR-DIM with their multi-targeted effects could be useful for the prevention of PCa progression, especially by attenuating bone metastasis mechanisms.

  10. Functional screen identifies kinases driving prostate cancer visceral and bone metastasis.

    Science.gov (United States)

    Faltermeier, Claire M; Drake, Justin M; Clark, Peter M; Smith, Bryan A; Zong, Yang; Volpe, Carmen; Mathis, Colleen; Morrissey, Colm; Castor, Brandon; Huang, Jiaoti; Witte, Owen N

    2016-01-12

    Mutationally activated kinases play an important role in the progression and metastasis of many cancers. Despite numerous oncogenic alterations implicated in metastatic prostate cancer, mutations of kinases are rare. Several lines of evidence suggest that nonmutated kinases and their pathways are involved in prostate cancer progression, but few kinases have been mechanistically linked to metastasis. Using a mass spectrometry-based phosphoproteomics dataset in concert with gene expression analysis, we selected over 100 kinases potentially implicated in human metastatic prostate cancer for functional evaluation. A primary in vivo screen based on overexpression of candidate kinases in murine prostate cells identified 20 wild-type kinases that promote metastasis. We queried these 20 kinases in a secondary in vivo screen using human prostate cells. Strikingly, all three RAF family members, MERTK, and NTRK2 drove the formation of bone and visceral metastasis confirmed by positron-emission tomography combined with computed tomography imaging and histology. Immunohistochemistry of tissue microarrays indicated that these kinases are highly expressed in human metastatic castration-resistant prostate cancer tissues. Our functional studies reveal the strong capability of select wild-type protein kinases to drive critical steps of the metastatic cascade, and implicate these kinases in possible therapeutic intervention. PMID:26621741

  11. 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.

  12. 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

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease......-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...... or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt...

  13. 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.

  14. Microarrays bring new insights into understanding of breast cancer metastasis to bone

    International Nuclear Information System (INIS)

    Using a microarray approach, Kang and colleagues identified several genes involved in the generation of breast cancer metastasis in bone and demonstrated their roles in bone colonization in vivo. Their findings and interpretations are reviewed in the context of recent array studies that compared gene expression in primary tumors and metastases. RNA expression array results have already demonstrated value in predicting whether metastases will develop in patients. They have also shown that expression patterns are similar in primary tumors and metastases. The latter data have invited re-examination of long-held notions related to mechanisms of metastasis. While the arrays show promise for improving diagnostic capability in breast cancers, ascribing mechanistic interpretations to correlative data should be done with extreme caution. Kang and colleagues' paper in Cancer Cell elegantly reinforces the concepts that efficiency of the metastatic process is dependent on the coordinated expression of multiple genes and that the expression of metastasis-associated genes is sometimes dependent on the microenvironment in which cells find themselves

  15. Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts.

    Directory of Open Access Journals (Sweden)

    Marion David

    Full Text Available BACKGROUND: Bone metastases are highly frequent complications of breast cancers. Current bone metastasis treatments using powerful anti-resorptive agents are only palliative indicating that factors independent of bone resorption control bone metastasis progression. Autotaxin (ATX/NPP2 is a secreted protein with both oncogenic and pro-metastatic properties. Through its lysosphospholipase D (lysoPLD activity, ATX controls the level of lysophosphatidic acid (LPA in the blood. Platelet-derived LPA promotes the progression of osteolytic bone metastases of breast cancer cells. We asked whether ATX was involved in the bone metastasis process. We characterized the role of ATX in osteolytic bone metastasis formation by using genetically modified breast cancer cells exploited on different osteolytic bone metastasis mouse models. METHODOLOGY/PRINCIPAL FINDINGS: Intravenous injection of human breast cancer MDA-B02 cells with forced expression of ATX (MDA-B02/ATX to immunodeficiency BALB/C nude mice enhanced osteolytic bone metastasis formation, as judged by increased bone loss, tumor burden, and a higher number of active osteoclasts at the metastatic site. Mouse breast cancer 4T1 cells induced the formation of osteolytic bone metastases after intracardiac injection in immunocompetent BALB/C mice. These cells expressed active ATX and silencing ATX expression inhibited the extent of osteolytic bone lesions and decreased the number of active osteoclasts at the bone metastatic site. In vitro, osteoclast differentiation was enhanced in presence of MDA-B02/ATX cell conditioned media or recombinant autotaxin that was blocked by the autotaxin inhibitor vpc8a202. In vitro, addition of LPA to active charcoal-treated serum restored the capacity of the serum to support RANK-L/MCSF-induced osteoclastogenesis. CONCLUSION/SIGNIFICANCE: Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a

  16. Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

    OpenAIRE

    Bäuerle, Tobias; Komljenovic, Dorde; Martin R. Berger; Semmler, Wolfhard

    2012-01-01

    Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.

  17. The Micro environmental Effect in the Progression, Metastasis, and Dormancy of Breast Cancer: A Model System within Bone Marrow

    International Nuclear Information System (INIS)

    Despite diagnostic advances, breast cancer remains the most prevalent cancer among women in the United States. The armamentarium of treatment options for metastatic disease is limited and mostly ineffective with regards to eradicating cancer. However, there have been novel findings in the recent literature that substantiate the function of the microenvironment in breast cancer progression and the support of metastasis to tertiary sites such as bone marrow. The uncovered significance of the microenvironment in the pathophysiology of breast cancer metastasis has served to challenge previously widespread theories and introduce new perspectives for the future research to eradicate breast cancer. This paper delineates the current understanding of the molecular mechanisms involved in the interactions between breast cancer cells and the microenvironment in progression, metastasis, and dormancy. The information, in addition to other mechanisms described in bone marrow, is discussed in the paper

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

    International Nuclear Information System (INIS)

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

  19. Predictive value of serum prostate specific antigen in detecting bone metastasis in prostate cancer patients using bone scintigraphy

    International Nuclear Information System (INIS)

    Radionuclide bone scan (BS) used to be the investigation of choice for detecting osseous metastases in prostate cancer. Now, with the availability serum prostate specific antigen (PSA) testing, clinicians do have a timely, cost-effective method to determine those patients who are highly unlikely to have osseous metastases. We determine the utility of PSA for predicting the presence of skeletal metastasis on BSs in prostate cancer patients. Retrospective analysis of medical records of 322 consecutive prostate cancers patients subjected to BS during the last 3 years was done. 52 cases were excluded due to following reasons: Serum PSA not available, hormonal or other therapy given prior to serum PSA measurement, and/or BS, and symptomatic for bone metastasis. In remaining 270 cases, PSA value and BS were evaluated. BS was performed with Tc99m methylene diphosphonate (MDP) as per the standard protocol. BS was found to be positive in 153/270 (56%) and negative in 117 (46%) patients. Of the 153 positive cases, 108 (70%) had serum PSA > 100 ng/ml, 42 (28%) had PSA of 20-100 ng/ml and only 3 (2%) had PSA < 20 ng/ml. All the patients with PSA > 100 ng/ml had multiple skeletal metastasis. Of the 117 negative cases, 110 (94%) had a PSA < 20 ng/ml, 5 had between 20 and 100 ng/ml and only 2 (1.8%) had PSA > 100 ng/ml. Of the 113 patients with serum PSA < 20 ng/ml, 110 (97.4%) did not show any bony metastasis. 150/157 (95.5%) patients with PSA > 20 ng/ml had bone metastasis. Using this criterion, 110 (40.7%) scans would have been omitted. Serum PSA < 20 ng/ml have high predictive value in ruling out skeletal metastasis. Our data are in corroboration with results from previous studies that BS should be performed only if PSA > 20 ng/ml. Using this cut-off, unnecessary investigation can be avoided. Avoiding BS in this group of patients would translate into a significant cost-saving and reduction in their psychological and physical burden

  20. Effects of Sangu Decoction on Osteoclast Activity in a Rat Model of Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Bo Deng

    2012-01-01

    Full Text Available Bone metastasis (BM is a major clinical problem for which current treatments lack full efficacy. The Traditional Chinese Medicine (TCM Sangu Decoction (SGD has been widely used to treat BM in China. However, no in vivo experiments to date have investigated the effects of TCM on osteoclast activity in BM. In this study, the protective effect and probable mechanism of SGD were evaluated. The model was established using the breast cancer MRMT-1 cells injected into the tibia of rat. SGD was administrated, compared with Zoledronic acid as a positive control. The development of the bone tumor and osteoclast activity was monitored by radiological analysis. TRAP stain was used to identify osteoclasts quantity and activity. TRAP-5b in serum or bone tumor and TRAP mRNA were also quantified. Radiological examination showed that SGD inhibited tumor proliferation and preserved the cortical and trabecular bone structure. In addition, a dramatic reduction of TRAP positive osteoclasts was observed and TRAP-5b levels in serum and bone tumor decreased significantly. It also reduced the mRNA expression of TRAP. The results indicated that SGD exerted potent antiosteoclast property that could be directly related to its TRAP inhibited activity. In addition it prevented bone tumor proliferation in BM model.

  1. 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.

  2. Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies

    International Nuclear Information System (INIS)

    Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer

  3. 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

  4. 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.

  5. 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.

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

    International Nuclear Information System (INIS)

    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 18F fluorodeoxyglucose (18F 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 18F 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 18F 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 18F 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

  7. Wnt and Wnt inhibitors in bone metastasis

    OpenAIRE

    Sottnik, Joseph L; Christopher L. Hall; Zhang, Jian; Evan T. Keller

    2012-01-01

    Bone metastasis is a clinically devastating development of progressive cancers including prostate carcinoma, breast carcinoma and multiple myeloma. Bone metastases are typically painful, lead to adverse skeletal-related events, such as fracture, and are highly resistant to therapy. A major contribution to the ability of cancers to successfully establish bone metastases is their ability to exploit mechanisms of normal bone remodeling. Wnts are a large family of morphogenic proteins that are cr...

  8. 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

  9. 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

  10. [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.

  11. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Significance of CEA, CA15-3 and biochemical markers of bone turnover in the diagnosis of bone metastasis from breast cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the significance of tumor markers CEA and CA15-3, and biochemical markers of bone turnover (total procollagen type Ⅰ amino-terminal propeptide (TP Ⅰ NP), β-isomerized carboxyterminal propeptide (β-CTx), ALP and PTH) in the diagnosis of bone metastasis from breast cancer. Methods: A total of 78 patients (all females) with mean age (56.72 ± 10.76) years, who were diagnosed with breast cancer, were included in this study. The patients were divided into two groups based on radionuclide bone imaging: with bone metastasis (n=32) and without bone metastasis (n=46). The serum concentrations of CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH, ALP were measured. Gleason scores were evaluated. The diagnostic value was evaluated by ROC curve.The two groups were compared using two-sample t test. The correlations between bone metastasis and tumor markers, bone metastasis and biochemical markers of bone turnover were analyzed with Pearson correlation and logistic analysis. Results: The serum levels of CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH and ALP were significantly higher in the group with bone metastasis than those in the group without bone metastasis (t: 4.16-7.56, all P<0.05). For the diagnosis of bone metastasis from breast cancer, the AUC of CEA, CA15-3, TP Ⅰ NP, [β-CTx, PTH and ALP was 0.815, 0.887, 0.869, 0.852, 0.844, 0.731, respectively. Using the cut-off values of 4.18 μg/L for CEA, 0.04 U/L for CA15-3, 49.70 μg/L for TP Ⅰ NP, 0.47 pg/L for β-CTx,54.90 ng/L for PTH and 49.90 U/L for ALP, the sensitivities were 56.3% (18/32), 75.0% (24/32), 78.1% (25/32), 81.3% (26/32), 78.1% (25/32), 68.8% (22/32) and the specificities were 80.4% (37/46), 84.8% (39/46), 76.1% (35/46), 78.3% (36/46), 69.6% (32/46), 58.7% (27/46), respectively. CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH, ALP and Gleason score were positively correlated with the presence of bone metastasis (r: 0.267-0.636, all P<0.05). CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH and Gleason score were independent

  14. 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.

  15. 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.

  16. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

    OpenAIRE

    Zheng Xin; Li Zhen; Cao Jie; Cai Dongqing; Yao Yao; Li Wanglin; Yuan Ziqiang

    2009-01-01

    Abstract Background Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic bre...

  17. 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.

  18. 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.

  19. 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. PMID:27177471

  20. 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.

  1. The content of 153Sm-oxabifor in cancer patients blood in the treatment of bone metastasis

    International Nuclear Information System (INIS)

    Concentration 153Sm in the blood of patients with bone metastasis after radionuclide therapy was determined. Considerable variation of the content of 153Sm in blood of patients with various primary cancers from 10 to 65 Bq/ml is found. The effective half-life of 153Sm in the blood of patients was estimated at more than 10 days during the course of the therapy in time interval more than 7 days

  2. Kinetics of 153Sm oxabiphor in the blood of cancer patients undergoing complex therapy for bone metastasis

    International Nuclear Information System (INIS)

    Concentration 153Sm in the blood of patients with bone metastasis after radionuclide therapy was determined. Considerable variation of the content of 153Sm in blood of patients with various primary cancers from 10 to 65 Bq/ml is found. The effective half-life of 153Sm in the blood of patients was estimated at more than 10 days during the course of the therapy.

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

    Science.gov (United States)

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

    2015-01-01

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

  4. 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

    2013-01-01

    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

  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. Talin1 phosphorylation activates β1 integrins: a novel mechanism to promote prostate cancer bone metastasis.

    Science.gov (United States)

    Jin, J-K; Tien, P-C; Cheng, C-J; Song, J H; Huang, C; Lin, S-H; Gallick, G E

    2015-04-01

    Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that β1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph nodes and bone. However, how β1 integrins are activated in PCa cells is unknown. In this study, we identified a novel mechanism of β1 integrin activation. Using knockdown experiments, we first demonstrated that talin1, but not talin2, is important in β1 integrin activation. We next showed that talin1 S425 phosphorylation, but not total talin1 expression, correlates with metastatic potential of PCa cells. Expressing a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 and C4-2B4 PCa cells, decreased activation of β1 integrins, integrin-mediated adhesion, motility and increased the sensitivity of the cells to anoikis. In contrast, reexpression of the phosphorylation-mimicking mutant talin1(S425D) led to increased β1 integrin activation and generated biologic effects opposite to talin1(S425A) expression. In the highly metastatic PC3-MM2 cells, expression of a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 cells, abolished their ability to colonize in the bone following intracardiac injection, while reexpression of phosphorylation-mimicking mutant talin1(S425D) restored their ability to metastasize to bone. Immunohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in human bone metastases when compared with normal tissues, primary tumors or lymph node metastases. We further showed that p35 expression, an activator of Cdk5, and Cdk5 activity were increased in metastatic tumor cells, and that Cdk5 kinase activity is responsible for talin1 phosphorylation and subsequent β1 integrin activation. Together, our study reveals Cdk5-mediated phosphorylation of talin1 leading

  7. 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

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. Metastasis and bone loss: Advancing treatment and prevention

    OpenAIRE

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

    2010-01-01

    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...

  11. 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.

  12. Regulation of Gene Expression and Inhibition of Experimental Prostate Cancer Bone Metastasis by Dietary Genistein

    OpenAIRE

    Yiwei Li; Mingxin Che; Sunita Bhagat; Kerrie-Lynn Ellis; Omer Kucuk; Doerge, Daniel R.; Judith Abrams; Cher, Michael L.; Sarkar, Fazlul H

    2004-01-01

    Prostate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary g...

  13. Regulation of Gene Expression and Inhibition of Experimental Prostate Cancer Bone Metastasis by Dietary Genistein1

    OpenAIRE

    Li, Yiwei; Che, Mingxin; Bhagat, Sunita; Ellis, Kerrie-Lynn; KUCUK, Omer; Doerge, Daniel R.; Abrams, Judith; Cher, Michael L.; Sarkar, Fazlul H

    2004-01-01

    Prostate cancer frequently metastasizes to the bone, and the treatment outcome for metastatic prostate cancer has been disappointing so far. Dietary genistein, derived primarily from soy product, has been proposed to be partly responsible for the low rate of prostate cancer in Asians. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells, but there are no studies documenting comprehensive gene expression profiles and antitumor effects of dietary g...

  14. Gut-derived serotonin induced by depression promotes breast cancer bone metastasis through the RUNX2/PTHrP/RANKL pathway in mice.

    Science.gov (United States)

    Zong, Jian-Chun; Wang, Xing; Zhou, Xiang; Wang, Chen; Chen, Liang; Yin, Liang-Jun; He, Bai-Cheng; Deng, Zhong-Liang

    2016-02-01

    Breast cancer metastasizes to the bone in a majority of patients with advanced disease resulting in bone destruction. The underlying mechanisms are complex, and both processes are controlled by an interaction between locally and systemically derived signals. Clinically, breast cancer patients with depression have a higher risk of bone metastasis, yet the etiology and mechanisms are yet to be elucidated. MDA‑MB‑231 breast cancer cells were used to establish a bone metastasis model by using intracardiac injection in nude mice. Chronic mild stress (CMS) was chosen as a model of depression in mice before and after inoculation of the cells. Knockdown of the RUNX‑2 gene was performed by transfection of the cells with shRNA silencing vectors against human RUNX‑2. A co‑culture system was used to test the effect of the MDA‑MB‑231 cells on osteoclasts and osteoblasts. RT‑PCR and western blotting were used to test gene and protein expression, respectively. We confirmed that depression induced bone metastasis by promoting osteoclast activity while inhibiting osteoblast differentiation. Free serotonin led to an increase in the expression of RUNX2 in breast cancer cells (MDA‑MB‑231), which directly inhibited osteoblast differentiation and stimulated osteoclast differentiation by the PTHrP/RANKL pathway, which caused bone destruction and formed osteolytic bone lesions. Additionally, the interaction between depression and breast cancer cells was interrupted by LP533401 or RUNX2 knockdown. In conclusion, depression promotes breast cancer bone metastasis partly through increasing levels of gut‑derived serotonin. Activation of RUNX2 in breast cancer cells by circulating serotonin appears to dissociate coupling between osteoblasts and osteoclasts, suggesting that the suppression of gut‑derived serotonin decreases the rate of breast cancer bone metastasis induced by depression. PMID:26573960

  15. Cellulitis-like symptoms manifested by bone metastasis of lung cancer in a patient living with human immunodeficiency virus.

    Science.gov (United States)

    Kashima, Jumpei; Okuma, Yusuke; Watanabe, Kageaki; Ajisawa, Atushi; Hishima, Tsunekazu

    2016-09-01

    Human immunodeficiency virus (HIV)-infected patients are at a high risk of cancer compared with the general population. As the use of antiretroviral therapy (ART) has increased, non-AIDS-defining cancers have also increased in the past decade. A 61-year-old man with HIV infection on ART developed a painful, erythematous and oedematous lower left leg and an associated fever. He was initially treated with antibiotics for cellulitis but there was no improvement, which warranted further investigation. A translucent lesion was found by X-ray imaging and bone scintigraphy showed bone metastasis from a primary adenocarcinoma of the lung, documented by chest computed tomography and an axillary lymph node biopsy. The patient died three months after the diagnosis despite undergoing chemotherapy. This case demonstrates that physicians should consider metastatic malignancies as a differential diagnoses for diverse skin changes in HIV-infected patients. PMID:26404113

  16. 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

  17. Bone metastasis in breast cancer: The story of RANK-Ligand

    International Nuclear Information System (INIS)

    The primary cellular mechanism responsible for osteolytic bone metastases is osteoclastic activation. Preclinical models have shown that breast cancer cells can produce parathyroid hormone-related protein (PTHrP), and other osteolytic molecules, which stimulate excessive osteoclastic bone resorption and establishment of osteolytic lesions. It has been shown that PTHrP by itself cannot directly induce osteoclastic activation, but it mediates its effect through the transactivation of RANK-ligand (RANKL) gene on stromal and osteoblastic cells. Accordingly RANKL up-regulation has been considered as a prerequisite in virtually all conditions of cancer induced bone destruction. Hence, therapeutic targeting of RANKL seems to be a rational approach to treat or even to prevent the process of bone metastases. In this review, we will focus on the unique pathophysiological aspects related to the evolution of bone metastases in breast cancer, emphasizing the pivotal role of RANKL and some other key molecules in osteoclastic bone resorption. We will discuss the therapeutic interventions using bisphosphonates and RANKL inhibitors in patients with bone metastases and the outcome of this novel approach

  18. BSP gene silencing inhibits migration, invasion, and bone metastasis of MDA-MB-231BO human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Jie Wang

    Full Text Available Bone sialoprotein (BSP has been implicated in a variety of physiological and pathophysiological events, including tumor cell invasion, bone homing, adhesion, and matrix degradation. To explore the potential involvement of BSP in human breast cancer cell invasion and metastasis, we used retrovirus-mediated RNAi to deplete BSP levels in the human bone-seeking breast cancer cell line MDA-MB-231BO (231BO and established the 231BO-BSP27 and 231BO-BSP81 cell clones. Cell proliferation, colony formation, wound healing, and the ability to invade into matrigel of these BSP-depleted clones were all decreased. Both 231BO-BSP27 cells and 231BO-BSP81 cells showed a significant (15.4% and 28.6% respectively reduction of bone metastatic potential following intracardiac injection as determined by X-ray detection and by hematoxylin and eosin staining. Moreover, the expression of integrins αvβ3 and β3 was decreased in the BSP-silenced cells whereas ectopic BSP expression increased the integrins αvβ3 and β3 levels. These results together suggest that BSP silencing decreased the integrin αvβ3 and β3 levels, in turn inhibiting cell migration and invasion and decreasing the ability of the cells to metastasize to bone.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Molecular Mechanisms of Bone Metastasis and Associated Muscle Weakness

    OpenAIRE

    Waning, David L.; Guise, Theresa A.

    2014-01-01

    Bone is a preferred site for breast cancer metastasis and leads to pathological bone loss due to increased osteoclast-induced bone resorption. The homing of tumor cells to the bone depends on the support of the bone microenvironment in which the tumor cells prime the pre-metastatic niche. The colonization and growth of tumor cells then depends on adaptations in the invading tumor cells to take advantage of normal physiological responses by mimicking bone marrow cells. This concerted effort by...

  5. 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.

  6. 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.

  7. 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.

  8. Dynamic modeling of bone metastasis, microenvironment and therapy: Integrating parathyroid hormone (PTH) effect, anti-resorptive and anti-cancer therapy.

    Science.gov (United States)

    Coelho, Rui Moura; Lemos, João Miranda; Alho, Irina; Valério, Duarte; Ferreira, Arlindo R; Costa, Luís; Vinga, Susana

    2016-02-21

    Bone is a common site for the development of metastasis, as its microenvironment provides the necessary conditions for the growth and proliferation of cancer cells. Several mathematical models to describe the bone remodeling process and how osteoclasts and osteoblasts coupled action ensures bone homeostasis have been proposed and further extended to include the effect of cancer cells. The model proposed here includes the influence of the parathyroid hormone (PTH) as capable of triggering and regulating the bone remodeling cycle. It also considers the secretion of PTH-related protein (PTHrP) by cancer cells, which stimulates the production of receptor activator of nuclear factor kappa-B ligand (RANKL) by osteoblasts that activates osteoclasts, increasing bone resorption and the subsequent release of growth factors entrapped in the bone matrix, which induce tumor growth, giving rise to a self-perpetuating cycle known as the vicious cycle of bone metastases. The model additionally describes how the presence of metastases contributes to the decoupling between bone resorption and formation. Moreover, the effects of anti-cancer and anti-resorptive treatments, through chemotherapy and the administration of bisphosphonates or denosumab, are also included, along with their corresponding pharmacokinetics (PK) and pharmacodynamics (PD). The simulated models, available at http://sels.tecnico.ulisboa.pt/software/, are able to describe bone remodeling cycles, the growth of bone metastases and how treatment can effectively reduce tumor burden on bone and prevent loss of bone strength. PMID:26657065

  9. Cytogenetic analysis of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone cancer metastasis

    International Nuclear Information System (INIS)

    The 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 153 Sm-EDTMP at cellular level. The present study was conducted with the aim of evaluating the cytogenetic effects of 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 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 before153 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 153 Sm-EDTMP, did not influence these parameters. The obtained data showed that the therapy with 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)

  10. 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.

  11. 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.

  12. 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。

  13. 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.

  14. 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

  15. Targeting of αv-Integrins in Stem/Progenitor Cells and Supportive Microenvironment Impairs Bone Metastasis in Human Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    2011-06-01

    Full Text Available Acquisition of an invasive phenotype by cancer cells is a requirement for bone metastasis. Transformed epithelial cells can switch to a motile, mesenchymal phenotype by epithelial-mesenchymal transition (EMT. Recently, it has been shown that EMT is functionally linked to prostate cancer stem cells, which are not only critically involved in prostate cancer maintenance but also in bone metastasis. We showed that treatment with the non-peptide αv-integrin antagonist GLPG0187 dose-dependently increased the E-cadherin/vimentin ratio, rendering the cells a more epithelial, sessile phenotype. In addition, GLPG0187 dose-dependently diminished the size of the aldehyde dehydrogenase high subpopulation of prostate cancer cells, suggesting that αv-integrin plays an important role in maintaining the prostate cancer stem/progenitor pool. Our data show that GLPG0187 is a potent inhibitor of osteoclastic bone resorption and angiogenesis in vitro and in vivo. Real-time bioluminescent imaging in preclinical models of prostate cancer demonstrated that blocking αv-integrins by GLPG0187 markedly reduced their metastatic tumor growth according to preventive and curative protocols. Bone tumor burden was significantly lower in the preventive protocol. In addition, the number of bone metastases/mouse was significantly inhibited. In the curative protocol, the progression of bone metastases and the formation of new bone metastases during the treatment period was significantly inhibited. In conclusion, we demonstrate that targeting of integrins by GLPG0187 can inhibit the de novo formation and progression of bone metastases in prostate cancer by antitumor (including inhibition of EMT and the size of the prostate cancer stem cell population, antiresorptive, and antiangiogenic mechanisms.

  16. Bone Cancer

    Science.gov (United States)

    ... cancer. Surgery is often the main treatment for bone cancer. Other treatments may include amputation, chemotherapy, and radiation therapy. Because bone cancer can come back after treatment, regular follow-up visits are important. NIH: National ...

  17. 18F-fluoride PET imaging in a nude rat model of bone metastasis from breast cancer: Comparison with 18F-FDG and bioluminescence imaging

    International Nuclear Information System (INIS)

    Introduction: Clinically-relevant animal models and appropriate imaging diagnostic tools are essential to study cancer and develop novel therapeutics. We evaluated a model of bone metastasis in nude rats by micro-PET and bioluminescence imaging. Methods: A bone metastasis model was produced by intracardiac injection of osteotropic MDA-MB-231Bo-Luc human breast cancer cells into nude rats. Bioluminescence imaging and micro-PET scans using 18F-FDG and 18F-fluoride were acquired serially for 5 weeks. We correlated bioluminescence imaging, 18F-FDG and 18F-fluoride PET images, and histological slides. Results: Multiple bone metastases were successfully evaluated by bioluminescence imaging and 18F-FDG and 18F-fluoride PET scans. Bioluminescence photon flux increased exponentially on weekly follow-up. 18F-FDG PET revealed increased FDG uptake at the spine and bilaterally in the hind legs in week 2 images, and showed a progressive pattern up to 4 weeks that correlated with bioluminescence imaging. 18F-fluoride PET showed minimal abnormal findings in week 2 images, but it showed an irregular pattern at the spine from week 3 or 4 images. On quantitative analysis with standardized uptake values, a pattern of gradual increase was observed from week 2 to week 4 in both 18F-FDG PET and fluoride PET. Histopathological examination confirmed the formation of osteolytic metastasis and necrosis of the distal femur, which appeared as a photon defect on PET scans. Conclusion: Developing bone metastasis from breast cancer in a nude rat model was successfully evaluated with an animal PET imaging system and bioluminescence imaging. This nude rat model of bone metastasis, which can be evaluated by PET imaging, may be a valuable tool for evaluating early responses to novel therapeutics

  18. 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

  19. 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.

  20. Multi-modal imaging of angiogenesis in a nude rat model of breast cancer bone metastasis using magnetic resonance imaging, volumetric computed tomography and ultrasound.

    Science.gov (United States)

    Bäuerle, Tobias; Komljenovic, Dorde; Berger, Martin R; Semmler, Wolfhard

    2012-01-01

    Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques. For this purpose, we injected 10(5) MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US). MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated

  1. 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.

  2. Correlation of the Levels of the Bone Turnover Markers BAP and β-CTX with Bone Metastasis Progress in Lung Cancer Patients%BAP和β-CTX与肺癌骨转移进展程度的相关性

    Institute of Scientific and Technical Information of China (English)

    唐琼; 赵辉; 贾锐; 刘林林

    2013-01-01

    背景与目的 肺癌易发生骨转移,Ⅰ型胶原羧基端肽β特殊序列(β isomer of C-terminal telopeptide of type Ⅰ collagen,β-CTX)和骨源性碱性磷酸酶(bone-specific alkaline phosphates,BAP)在骨质代谢中是重要的生化标记物,本研究旨在探讨骨代谢生化指标和肺癌骨转移进展程度的相关性,有助于早期判断是否有肺癌骨转移的发生.方法 天津市人民医院2009年7月-2012年7月共收治92例肺癌并发生骨转移患者,全部病例其原发灶均经细胞学检查证实,骨转移灶的数目及类型经ECT结合X线片、CT证实,采用ELISA方法检测血β-CTX、BAP的浓度水平.结果 收集的92例肺癌伴骨转移的患者中,转移灶<3处为58例,≥3处为34例;溶骨型68例,成骨型9例,混合型15例.血β-CTX、BAP水平在不同的骨转移数目组间差异有统计学意义(P<0.05),β-CTX在肺癌溶骨型骨转移患者中具有较高的敏感性.结论 骨代谢生化指标β-CTX、BAP对肺癌骨转移具有辅助诊断意义,是判断转移进展程度的良好指标.%Background and objective Bone metastasis is common in lung cancer patients. The β isomer of the C-terminal telopeptide of type Ⅰ collagen (β-CTX) and bone-specific alkaline phosphates (BAP) are regarded as important bone turnover markers in bone resorption and formation. Thus, the aims of this study are to determine the correlation of these bone turnover markers with the extent of bone metastasis of lung cancer. Methods A total of 92 patients with bone metastasis of lung cancer from Tianjin Union Medicine Center were enrolled in this study between July 2009 and July 2012. The bone metastasis lesion was diagnosed by ECT combined with X-ray and CT imaging. Trie bone turnover marker levels of β-CTX and BAP were measured by ELISA. Results Among the 92 patients, 58 cases had 3; 68 cases had osteolytic bone metastasis, 9 had osteoblastic bone metastasis, and 15 had mixed bone metastases. The serum levels

  3. 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.

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

    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.

  5. ECT在乳腺癌骨转移的临床应用价值%Clinical Application value of ECT in bone Metastasis of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    李明浩; 崔时珍; 玄日

    2013-01-01

    Objective Clinical application value of ECT in breast cancer bone metastasis .Method Of the 76 cases confirmed by pathology to breast cancer patients give systemic ECT inspection and analysis and summary information .Results In breast cancer patients combined with bone metastases ,ECT high diagnostic value,signifi-cantly higher than the CT and x-ray.Conclusion ECT in the early detection of breast cancer bone metastasis has been of great value.%目的探讨ECT在乳腺癌骨转移的临床应用价值。方法对76例经病理证实为乳腺癌患者行全身 ECT检查,并分析总结资料。结果在乳腺癌骨转移患者中,ECT诊断价值较高,明显高于CT及X线。结论 ECT在早期发现乳腺癌骨转移方面有重要价值。

  6. 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.)

  7. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  8. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    International Nuclear Information System (INIS)

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

  9. Nasopharyngeal carcinoma with bone marrow metastasis.

    Science.gov (United States)

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  10. Evaluation of sequential FDG-PET/CT for monitoring bone metastasis of breast cancer during therapy. Correlation between morphological and metabolic changes with tumor markers

    International Nuclear Information System (INIS)

    The purpose of this study was to clarify the significance of positron emission tomography (PET) and computed tomography (CT) findings for evaluating the bone metastasis of breast cancer during therapy. Forty-seven patients with bone metastases from breast cancer who underwent sequential 18F-flourodeoxyglucose (FDG)-PET/CT studies during therapy were enrolled. A total of 771 lesions were identified. The changes in the PET and CT findings were compared with the tumor marker levels in each patient by calculating the weighted kappa value. The correlation between the PET and CT findings was examined for each lesion by an adjusted Chi-square test. The change in the tumor marker levels was substantially correlated with the PET findings and moderately correlated with the CT findings (weighted kappa=0.780 and 0.585 for quadratic weighting, respectively). An increase in FDG uptake was correlated with lytic changes on the CT images (62/65, 95.4%, p<0.05). Sclerotic changes suggested improvement, but sclerosis and progression occurred at the same time in some lesions. Changes of FDG uptake are useful for evaluating individual bone metastases in cases of breast cancer during therapy. Lytic change on CT images suggests progression of bone metastasis. The lysis-progression/sclerosis-improvement pattern was observed in the majority of subjects, but a sclerosis-progression pattern was also observed. The hybrid pattern of increase of FDG uptake on PET/lytic change on CT is most accurate to show progression of bone metastases. Assessments of these processes during therapy are necessary for the precise evaluation of bone metastases. (author)

  11. 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.

  12. 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

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

    OpenAIRE

    Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-ichi; GOTO, Noriko(Graduate school of Education,Tokyo Gakugei University); Mukaida, Naofumi

    2016-01-01

    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 ch...

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-15

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

  16. [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.

  17. Bone Metastasis from Renal Cell Carcinoma

    Science.gov (United States)

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

  18. Endobronchial metastasis in breast cancer.

    OpenAIRE

    Albertini, R E; Ekberg, N L

    1980-01-01

    Ten patients with endobronchial metastasis from primary breast cancer were found among 1200 fibreoptic bronchoscopies. Six of these patients had radiological signs suggesting bronchial obstruction. The diagnosis was verified in nine cases by means of bronchoscopic biopsy or cytology and in one by thoracotomy. Endobronchial metastasis should be considered when symptoms or chest films suggest endobronchial disease in a patient with a history of breast cancer.

  19. Bone metastases in breast cancer and its risk factor

    International Nuclear Information System (INIS)

    Breast cancer is considered to often involve bone metastasis. Early detection and treatment of bone metastasis are essential in improving the prognosis of this disease. In 47 patients with bone metastasis confirmed with bone scintigraphy, we examined the appearance time of bone metastasis; bone metastasis was frequently observed with the progress of stage, but no association with the appearance time was found. Age was not associated with the incidence of bone metastasis but was found to be closely related to its appearance time. That is to say, patients with breast cancer below 40 years of age showed relatively early bone metastasis. Bone scintigraphy is required every 6 months at least for 3 years after the operation. In patients over 40 years of age, on the other hand, bone scintigraphy is required only once a year but has to be continued for 5 years or more, because they often show relatively late bone metastasis. (author)

  20. 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.

  1. 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.

  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

    International Nuclear Information System (INIS)

    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 clinical value of SPECT/CT fusion imaging in the diagnosis of bone metastasis of breast cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical value of SPECT/CT fusion imaging in the diagnosis and differential diagnosis the characteristic of the whole body bone scan radioactive hot lesions in patients with breast cancer. Methods: The abnormal radioactive hot lesions of whole body bone scan in 25 patients with breast cancer underwent SPECT/CT fusion imaging immediately. Another whole body bone scan and SPECT/CT fusion imaging were carried out 4 to 8 months later in all these patients. The whole body bone scan images, SPECT/CT images and fusion images were analyzed independently by two experienced nuclear medicine physicians and some of the equivocal CT images were analyzed by an experienced radiologist. Results: Among all the 37 abnormal radioactive hot bone lesions, 29 (29/37, 78.38%) lesions were confirmed metastatic lesions,including 2 vertebral lesions classified as benign lesions on the basis of the first examinations data; and 8 lesions were benign,including a rib lesion classified as benign lesion according to the first examinations data. The difference between whole body bone scan and SPECT/CT examination was statistically significant (χ2=6.975, P<0.05). The bone metastases are located mainly in spine and ribs. The sensitivity,specificity, positive and negative predictive values, and accuracy of whole-body bone scan and SPECT/CT fusion imaging were 82.76%, 75.00%, 92.31%, 54.55%, 81.08% and 93.10%, 87.50%, 96.43%, 77.78%, 91.89%, respectively. The area under the receiver operating characteristics curve was 0.860±0.056 for whole body bone scan and 0.974±0.020 for SPECT/CT. The area under the curve for SPECT/CT was significantly larger compared with the whole body bone scan (χ2=9.924, P<0.001). Conclusions: SPECT/CT fusion imaging is better than whole body bone scan alone to characterize the abnormal bone radioactive hot lesions and it can improve the accuracy of diagnosis. The patients should repeat the modality 4 to 8 months later if necessary. (authors)

  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. High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

    Science.gov (United States)

    Shimazu, Kazuhiro; Fukuda, Koji; Yoshida, Taichi; Inoue, Masahiro; Shibata, Hiroyuki

    2016-01-01

    AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis. METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 mL of peripheral venous blood drawn using a CellSearch kit and a CellTracks AutoPrep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells (CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 mL of peripheral blood (median of 1724). These values were much higher than common gastric cancers (2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d (median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance (Y = 234.6 - 0.03X, P = 0.085). CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.

  6. 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.

  7. Pathobiology of cancer metastasis: a short account.

    Science.gov (United States)

    Feller, Liviu; Kramer, Beverley; Lemmer, Johan

    2012-01-01

    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. PMID:22676510

  8. MRI联合PSA在前列腺癌骨转移中的诊断价值研究%The diagnosis value of MRI combined PSA in prostate cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    吴俊勇; 王炜; 李彤

    2012-01-01

    OBJECTIVE To investigate the application value of MRI combined PSA in prostate cancer bone metastasis. METHODS 74 prostate cancer patients were selected in our hospital, patients were tested for the serum PSA level and MRI after admission to detect the expression of prostate cancer bone metastasis. RESULTS All 74 patients in our group, the positive cases of prostate cancer bone metastasis were 43 cases (58.1%) , positive cases in prostate cancer bone metastasis with PSA≥ 20 μg/L group was 69.6%, significantly higher than PSA μg/L) < 20 μg/L groups 22.2%, the difference had a statistical significance, P< 0.05. CONCLUSION PSA has a good prediction effect on prostate cancer bone metastasis. When PSA ≥20 μg, the probability of prostate cancer bone metastasis increases significantly. PSA ≥20μg/L combined MRI can significantly improve the detection rate in prostate cancer bone metastasis.%目的 探讨MRI联合PSA检测在诊断前列腺癌骨转移中的应用价值.方法 选择某院收入的前列腺癌患者共74例,患者入院后检测血清PSA水平及MRI情况,从而检测前列腺癌骨转移患者表达情况.结果 所有74例患者中,前列腺癌骨转移阳性共43例(58.1%),PSA≥20 μg/L组患者前列腺癌骨转移阳性率为69.6%,显著高于PSA< 20 μg/L组的22.2%,两组对比差异有统计学意义(P<0.05).PSA≥20 μg/L组敏感度显著高于PSA(μg/L)<20 μg/L组,两组患者敏感性对比差异有统计学意义(P<0.05).结论 PSA具有较好的预测前列腺癌骨转移的作用,当PSA≥20 μg时,患者发生前列腺癌骨转移的概率显著增加.PSA≥20μg/L时再结合MRI检测,能显著提高前列腺瘤骨转移的诊断水平.

  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. The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors

    Directory of Open Access Journals (Sweden)

    Lucia D’Amico

    2015-01-01

    Full Text Available Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporting the vicious cycle of bone metastasis. This review summarizes the current knowledge on the interactions among bone, immune, and tumor cells aiming to provide an overview of the osteoimmunology field in bone metastasis from solid tumors.

  11. 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.

  12. 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.

  13. Bone health in cancer patients

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival.......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...

  14. 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.

  15. Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

    Science.gov (United States)

    Sonn, Kevin A; Kannan, Abhishek S; Bellary, Sharath S; Yun, Chawon; Hashmi, Sohaib Z; Nelson, John T; Ghodasra, Jason H; Nickoli, Michael S; Parimi, Vamsi; Ghosh, Anjan; Shawen, Nicholas; Ashtekar, Amruta; Stock, Stuart R; Hsu, Erin L; Hsu, Wellington K

    2016-07-01

    Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3)  p/s/cm(2) /sr (Group A) and 1.11 × 10(4)  p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016. PMID:26694749

  16. Bone metastasis in patients with non-small cell lung cancer: The diagnostic role of F-18 FDG PET/CT

    International Nuclear Information System (INIS)

    Purpose: To evaluate the performance of F-18 FDG PET/CT in the detection of bone metastasis in non-small cell lung cancer (NSCLC) patients. Materials and methods: Three hundred and sixty-two consecutive NSCLC patients who underwent F-18 FDG PET/CT scanning were retrospectively analyzed. Each image of PET/CT, combined CT, and PET was performed at 10 separate areas and interpreted blindly and separately. The sensitivity, specificity and accuracy of F-18 FDG PET/CT, combined CT and F-18 FDG PET were calculated and the results were statistically analyzed. Results: Bone metastasis was confirmed in 82 patients with 331 positive segments based on the image findings and clinical follow-up. On patient-based analysis, the sensitivity of F-18 FDG PET/CT (93.9%) was significantly higher than those of combined CT (74.4%) and F-18 FDG PET (84.1%), respectively (p < 0.05). The overall specificity and accuracy of combined CT, F-18 FDG PET, and F-18 FDG PET/CT were 90.7%, 93.2%, 98.9% and 87.0%, 91.2%, and 97.8%, respectively (compared with PET/CT, p < 0.05). On segment-based analysis, the sensitivity of the three modalities were 79.5%, 94.3%, and 98.8%, respectively (compared with PET/CT, p < 0.05). The overall specificity and accuracy of the three modalities were 87.9%, 89.2%, 98.6% and 84.5%, 91.2%, 98.7%, respectively (compared with PET/CT, p < 0.05). Conclusion: F-18 FDG PET/CT is superior to F-18 FDG PET or combined CT in detecting bone metastasis of NSCLC patients because of the complementation of CT and PET. It is worth noting that the added value of F-18 FDG PET/CT may beneficially impact the clinical management of NSCLC.

  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. Value of SPECT/CT whole body bone imaging in the diagnosis of bone metastasis of lung cancer%SPECT/CT融合显像在肺癌骨转移中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    李征

    2014-01-01

    Objective To explore the value of SPECT / CT fusion imaging in the diagnosis of bone metastasis of lung cancer .Methods A total of 160 patients who were pathologically diagnosed with lung cancer were examed by whole body bone imaging and SPECT / CT fusion imaging ,the resulting images were observed and analyzed ,as well as the accuracy in diagnosis of lung cancer patients with bone metastases through different imaging methods were judged .Results After examination ,there were 52 patients had bone metastasis in lung cancer .The sensitivity of whole body bone imaging was 59 .6% ,specificity was 37 .0% ,accuracy of diagnosis was 44 .4% .The sensitivity of SPECT / CT fusion imaging was 96 .2% ,specificity was 88 .0% ,accuracy of diagnosis was 90 .6% .The negative pre-dictive value of whole body bone imagirg and SPECT /CT fusion imaging were 40 .40% and 95 .95% respectively ,the positive predictive value were 50 .82% and 81 .97% respectively .The accuracy rate of SPECT /CT fusion imaging were significant higher than that of whole body bone imaging (P < 0 .05) .Conclusion SPECT / CT fusion imaging has higher value in diagnosis of bone metastasis of lung cancer ,compared to whole body bone imaging .%目的:探究 SPECT /CT 融合显像在肺癌骨转移诊断中的价值。方法选择北京世纪坛医院2013年8月1日至2013年11月1日160例经病理诊断确诊为肺癌的患者为研究对象,对所有患者进行全身骨显像和SPECT /CT 融合显像检查,观察并分析所获得的图像,对比不同显像方式下肺癌骨转移患者的诊断准确率、特异度、敏感度。结果160例患者经检查确诊发生肺癌骨转移52例。全身骨显像敏感度为59.6%,特异度为37.0%,诊断正确率为44.4%,阴性预测值为40.40%,阳性预测值为50.82%;SPECT /CT 融合显像检查敏感度为96.2%,特异度为88.0%,诊断正确率为90.6%,阴性预测值95.95%,阳性预测值81.97

  19. Bone metastases: When and how lung cancer interacts with bone

    OpenAIRE

    Roato, Ilaria

    2014-01-01

    Bone metastasis is a common and debilitating consequence of lung cancer: 30%-40% of patients with non-small cell lung cancer develop bone metastases during the course of their disease. Lung cancer cells find a favorable soil in the bone microenvironment due to factors released by the bone matrix, the immune system cells, and the same cancer cells. Many aspects of the cross-talk among lung tumor cells, the immune system, and bone cells are not clear, but this review aims to summarize the recen...

  20. Preliminary Study on 41Ca-AMS Technology for Early Diagnosis and Monitoring of Bone Cancer

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    The annual incidence of new cancer patients in China is about 2 million,50%-60%of which will end up with bone metastasis.The bone metastasis of cancer and bone cancer usually causes a variety of bone-related events,such as the pathological fracture,malignant hypercalcemia and bone marrow

  1. Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival.

    Science.gov (United States)

    Ma, Yifei; Zhou, Wang; He, Shaohui; Xu, Wei; Xiao, Jianru

    2016-09-15

    Bone metastasis from cancer of unknown primary (BMCUP) brings poor survival prognosis and its management remains controversial. Sunitinib (SUTENT) proved effective in many sorts of solid tumors but has never been applied for patients with occult primary cancers, and there is no study to identify sensitive or resistant biomarkers for sunitinib therapy in CUP patients. An analysis was carried out to investigate the efficacy of sunitinib by multivariate survival analysis of 286 patients with BMCUP. We further carried out multivariate analysis to identify histological and clinical biomarkers that could predict sensitivity or resistance for sunitinib therapy. Of the 286 patients included from January 2011 to March 2016, sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive and resistant biomarkers were identified in histological specimen of patients receiving sunitinib therapy. Clinical factors were also identified that predict poor survival prognosis for sunitinib therapy. Sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive markers for sunitinib therapy include KDR positivity and early-developed treatment-induced hypertension. Resistance factors for sunitinib include VEGF positivity, CAIX positivity and squamous cell carcinoma pathology type. Prolonged symptom time and severe weight loss before therapy seemed to be associated with poor survival prognosis for sunitinib therapy. PMID:27164264

  2. 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.

  3. 肿瘤标志物对肺癌分期和骨转移诊断的价值%The diagnosis value of serum tumor marker for bone metastasis and stages of lung cancer

    Institute of Scientific and Technical Information of China (English)

    何泽来; 王火强; 宋玉

    2011-01-01

    目的 探讨肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19的片段(CYFRA21-1)、神经稀醇酶(NSE)、糖类抗原(CA153)血清水平对肺癌分期及肺癌骨转移的辅助诊断价值.方法 检测206例肺癌患者血清4种标志物水平,比较各期肺癌之间、骨转移组和无骨转移组之间的肿瘤标志物表达水平和阳性率的差异.结果 骨转移组4项标志物水平均高于无骨转移组(P均<0.05);肺癌分期越晚,4项标志物阳性率越高;4项联检时灵敏度、准确率等均优于单项检查.结论 肿瘤标志物水平的检测对肺癌骨转移的诊断、肺癌分期(特别是肺癌后期)诊断有辅助价值,联合检查优于单项检查.%Objective To approach the auxiliary diagnosis value of serum tumor markers CEA,CYFRA21-1 ,NSE and CA153 levels for bone metastasis and stages of lung cancer.Methods To collect the serum tumor markers levels of 206 lung cancer patients with whole bone scanning, to analysis the difference of the express level and positive ratio of every stage patients and between bone metastasis group and non-bone metastasis group.Results The four kinds markers levels of bone metastasis group were all higher than non-bone metas tasis group(P all <0.05 ).Four tumor markers positive ratio were increasing with lung cancer stage developing.The sensitivity and accuracy when unite four tumor markers were superior to single marker inspect.Conclusions To detect four kinds tumor markers serum levels for bone metastasis and stages of lung cancer( special later stage of lung cancer) have assist diagnosis value.

  4. The role of versican G3 domain in regulating breast cancer cell motility including effects on osteoblast cell growth and differentiation in vitro – evaluation towards understanding breast cancer cell bone metastasis

    Directory of Open Access Journals (Sweden)

    Du William

    2012-08-01

    Full Text Available Abstract Background Versican is detected in the interstitial tissues at the invasive margins of breast carcinoma, is predictive of relapse, and negatively impacts overall survival rates. The versican G3 domain is important in breast cancer cell growth, migration and bone metastasis. However, mechanistic studies evaluating versican G3 enhanced breast cancer bone metastasis are limited. Methods A versican G3 construct was exogenously expressed in the 66c14 and the MC3T3-E1 cell line. Cells were observed through light microscopy and viability analyzed by Coulter Counter or determined with colorimetric proliferation assays. The Annexin V-FITC apoptosis detection kit was used to detect apoptotic activity. Modified Chemotactic Boyden chamber migration invasion assays were applied to observe tumor migration and invasion to bone stromal cells and MC3T3-E1 cells. Alkaline phosphatase (ALP staining and ALP ELISA assays were performed to observe ALP activity in MC3T3-E1 cells. Results In the four mouse breast cancer cell lines 67NR, 66c14, 4T07, and 4T1, 4T1 cells expressed higher levels of versican, and showed higher migration and invasion ability to MC3T3-E1 cells and primary bone stromal cells. 4T1 conditioned medium (CM inhibited MC3T3-E1 cell growth, and even lead to apoptosis. Only 4T1 CM prevented MC3T3-E1 cell differentiation, noted by inhibition of alkaline phosphatase (ALP activity. We exogenously expressed a versican G3 construct in a cell line that expresses low versican levels (66c14, and observed that the G3-expressing 66c14 cells showed enhanced cell migration and invasion to bone stromal and MC3T3-E1 cells. This observation was prevented by selective EGFR inhibitor AG1478, selective MEK inhibitor PD 98059, and selective AKT inhibitor Triciribine, but not by selective JNK inhibitor SP 600125. Versican G3 enhanced breast cancer cell invasion to bone stromal cells or osteoblast cells appears to occur through enhancing EGFR/ERK or AKT signaling

  5. Effects of proteasome inhibitors on bone cancer

    OpenAIRE

    Terpos, Evangelos; Christoulas, Dimitrios

    2013-01-01

    Bone metastasis is a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer, while bone disease is also the characteristic clinical feature of multiple myeloma. Skeletal-related events can be devastating, with major effect on the quality of life and survival. Bisphosphonates are the mainstay of therapeutic management of bone disease of solid tumors and myeloma, and denosumab has recently been approved for patients with bone metastases. Both...

  6. Optimal management of bone metastases in breast cancer patients

    OpenAIRE

    Wong MH; Pavlakis N

    2011-01-01

    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 ...

  7. 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

  8. 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.

  9. Breast metastasis from vaginal cancer.

    Science.gov (United States)

    Chandrasekaran, Neeraja; Scharifker, Daniel; Varsegi, George; Almeida, Zoyla

    2016-01-01

    Vaginal cancer is a rare malignancy accounting for 1-2% of all pelvic neoplasms. Dissemination usually occurs through local invasion and rarely metastasises to distal locations. Metastasis of vaginal cancer to the breast is extremely infrequent and unique. A 66-year-old Asian woman presented with vaginal bleeding and was found to have a vaginal mass and a left breast mass. Pathological assessment of the biopsies revealed identical squamous cell characteristics of both masses. We describe a very rare and novel case of a distally located vaginal carcinoma with metastasis to the breast Federation of Gynecology and Obstetrics (FIGO) stage IV (FIGO IVB). Robot-assisted extrafascial total hysterectomy with local vaginal mass excision and partial mastectomy of the left breast were performed. After surgery, the patient underwent adjuvant chemotherapy followed by breast and pelvic radiotherapy, with maintained complete remission after 3 years of follow-up. This combination of findings and treatment is very distinct with a unique and favourable response. PMID:27444140

  10. High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report

    Directory of Open Access Journals (Sweden)

    Zhou T

    2016-01-01

    patient quality of life, relieve pain, and help prolong patient survival. This article reports the treatment procedure and adverse reactions in a patient who was treated with high-dose OxyContin, with the aim of providing a reference for other clinical practitioners. Keywords: pain, OxyContin, bone metastasis, palliative care

  11. Volume of Bone Metastasis Assessed with Whole-Body Diffusion-weighted Imaging Is Associated with Overall Survival in Metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Perez-Lopez, Raquel; Lorente, David; Blackledge, Matthew D; Collins, David J; Mateo, Joaquin; Bianchini, Diletta; Omlin, Aurelius; Zivi, Andrea; Leach, Martin O; de Bono, Johann S; Koh, Dow-Mu; Tunariu, Nina

    2016-07-01

    Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26807894

  12. Lymph Node Metastasis of Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Akagi, Tomonori, E-mail: tomakagi@med.oita-u.ac.jp [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Shiraishi, Norio [Surgical division, Center for community medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan); Kitano, Seigo [Oita University Faculty of Medicine, Department of Gastroenterological Surgery, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593 (Japan)

    2011-04-26

    Despite a decrease in incidence in recent decades, gastric cancer is still one of the most common causes of cancer death worldwide [1]. In areas without screening for gastric cancer, it is diagnosed late and has a high frequency of nodal involvement [1]. Even in early gastric cancer (EGC), the incidence of lymph node (LN) metastasis exceeds 10%; it was reported to be 14.1% overall and was 4.8 to 23.6% depending on cancer depth [2]. It is important to evaluate LN status preoperatively for proper treatment strategy; however, sufficient results are not being obtained using various modalities. Surgery is the only effective intervention for cure or long-term survival. It is possible to cure local disease without distant metastasis by gastrectomy and LN dissection. However, there is no survival benefit from surgery for systemic disease with distant metastasis such as para-aortic lymph node metastasis [3]. Therefore, whether the disease is local or systemic is an important prognostic indicator for gastric cancer, and the debate continues over the importance of extended lymphadenectomy for gastric cancer. The concept of micro-metastasis has been described as a prognostic factor [4-9], and the biological mechanisms of LN metastasis are currently under study [10-12]. In this article, we review the status of LN metastasis including its molecular mechanisms and evaluate LN dissection for the treatment of gastric cancer.

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

    Science.gov (United States)

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

    2016-04-01

    Metastatic cancer remains the leading cause of death for patients with breast cancer. To understand the mechanisms underlying the development of distant metastases to specific sites is therefore important and of potential clinical value. From 157 primary breast tumours of the patients with known metastatic disease, gene expression profiling data were generated and correlated to metastatic behaviour including site-specific metastasis, metastasis pattern and survival outcomes. We analysed gene expression signatures specifically associated with the development of bone metastases. As a validation cohort, we used a published dataset of 376 breast carcinomas for which gene expression data and site-specific metastasis information were available. 80.5 % of luminal-type tumours developed bone metastasis as opposed to 41.7 % of basal and 55.6 % of HER2-like tumours. A novel 15-gene signature identified 82.4 % of the tumours with bone metastasis, 85.2 % of the tumours which had bone metastasis as first site of metastasis and 100 % of the ones with bone metastasis only (p 9.99e-09), in the training set. In the independent dataset, 81.2 % of the positive tested tumours had known metastatic disease to the bone (p 4.28e-10). This 15-gene signature showed much better correlation with the development of bone metastases than previously identified signatures and was predictive in both ER-positive as well as in ER-negative tumours. Multivariate analyses revealed that together with the molecular subtype, our 15-gene expression signature was significantly correlated to bone metastasis status (p 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 novel 15-gene expression signature associated with the development of bone metastases in breast cancer patients. This bone metastasis signature is the first to be

  14. Tracheal metastasis of small cell lung cancer

    OpenAIRE

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  15. Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis

    OpenAIRE

    Richhariya A; Qian Y; Zhao Y.; Chung K

    2012-01-01

    Akshara Richhariya1, Yi Qian2, Yufan Zhao2, Karen Chung11Amgen Inc, Global Health Economics, Thousand Oaks, CA, USA; 2Amgen Inc, Global Biostatistical Sciences, Thousand Oaks, CA, USAPurpose: Intravenous (IV) zoledronic acid (ZA) is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in ...

  16. 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

  17. The protein C pathway in cancer metastasis.

    Science.gov (United States)

    Spek, C Arnold; Arruda, Valder R

    2012-04-01

    Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that anticoagulant treatment seems to benefit cancer patients, recent experiments aimed to elucidate the importance of the natural anticoagulant protein C pathways in cancer progression. Interestingly, these experiments showed that the repeated administration of exogenous activated protein C limits cancer cell extravasation in experimental animal models. In line, reducing endogenous activated protein C activity dramatically increased the number of experimental metastasis. These data thus strongly suggest that exogenous activated protein C administration may be a novel therapeutic avenue to limit cancer metastasis thereby prolonging overall survival of cancer patients. The current review provides an overview of recent data on the role of the protein C pathway in cancer metastasis. It discusses the potential of activated protein C as a novel target to reduce cancer progression, it points to several limitations of activated protein C administration in the setting of cancer cell metastasis and it suggest zymogen protein C as an attractive alternative. PMID:22682140

  18. 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

    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......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...... 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...

  19. 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.

  20. An isolated vaginal metastasis from rectal cancer

    OpenAIRE

    Ai Sadatomo; Koji Koinuma; Hisanaga Horie; Lefor, Alan K.; Naohiro Sata

    2015-01-01

    Introduction: Isolated vaginal metastases from colorectal cancer are extremely rare. There are only a few reported cases in the English literature, and the characteristics of such cases of metastasis remain relatively unknown. Presentation of case: We present a case of isolated vaginal metastasis from rectal cancer in a 78-year-old female patient. The patient had no symptoms related to vaginal tumor. Magnetic resonance imaging (MRI) showed thickening of the middle rectum and a vaginal tumo...

  1. 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.

  2. Case report and nursing observation of pressure sores at left femur in a lung cancer patient with bone metastasis%1例肺癌骨转移并发左股骨转子处压疮的护理

    Institute of Scientific and Technical Information of China (English)

    李艳; 刘佳丽

    2011-01-01

    目的 探讨肺癌骨转移并发左股骨转子处压疮的护理原则.方法对1例肺癌骨转移并发左股骨转子处压疮,采用湿性愈合治疗,观察治疗过程及疗效情况.结果 本例经积极护理及治疗处理后,左股骨转子处压疮创面完全愈合,周围皮肤痊愈,于治疗后11 d出院.出院后2周定期随访,无压疮复发情况发生.结论 肺癌骨转移并发左股骨转子处压疮的治疗关键在于正确的压疮分级评定、合理的治疗和并发症的预防.%Objective To evaluate the nursing principles of pressure sores at left femur in a lung cancer patient with bone metastasis.Methods Moist healing treatment was applied to a lung cancer patient with bone metastasis who has pressure sores at left femur and treatment process and its efficacy was closely observed.Results Pressure sores at left femur and around skin were completely healed, and left hospital after 11 days' treatment.After 2 weeks, a follow- up visit found no recurrence.Conclusion The key points of treatment in pressure sores at left femur in a lung cancer patient with bone metastasis were accurate pressure sores grade assessment, reasonable treatment and prevention of complications.

  3. 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.

  4. 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

  5. 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.

  6. Breast Cancer Metastasis to the Stomach Resembling Early Gastric Cancer

    OpenAIRE

    Eo, Wan Kyu

    2008-01-01

    Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infi...

  7. Predictors of Time to Metastasis in Castration-Resistant Prostate Cancer.

    OpenAIRE

    Moreira, DM; Howard, LE; Sourbeer, KN; Amarasekara, HS; Chow, LC; Cockrell, DC; Hanyok, BT; Aronson, WJ; Kane, CJ; Terris, MK; Amling, CL; Cooperberg, MR; Liede, A; Freedland, SJ

    2016-01-01

    To investigate predictors of time to metastasis among men treated with androgen deprivation therapy (ADT) for non-metastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.Retrospective analysis of 458 non-metastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time ze...

  8. Hematogenous Gastric Metastasis of Pancreatic Cancer

    Science.gov (United States)

    Sasajima, Junpei; Okamoto, Kotaro; Taniguchi, Masato

    2016-01-01

    While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas.

  9. 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.

  10. 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

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

    Institute of Scientific and Technical Information of China (English)

    王如良; 江泽飞

    2015-01-01

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

  12. Bone scintigraphy for metastasis detection in canine osteosarcoma

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma

  13. 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.

  14. Involvement of chemokine receptors in breast cancer metastasis

    Science.gov (United States)

    Müller, Anja; Homey, Bernhard; Soto, Hortensia; Ge, Nianfeng; Catron, Daniel; Buchanan, Matthew E.; McClanahan, Terri; Murphy, Erin; Yuan, Wei; Wagner, Stephan N.; Barrera, Jose Luis; Mohar, Alejandro; Verástegui, Emma; Zlotnik, Albert

    2001-03-01

    Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

  15. 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.

  16. Stress Proteins and Pancreatic Cancer Metastasis

    OpenAIRE

    Cano, Carla E.; Iovanna, Juan L.

    2010-01-01

    Tumor metastasis is challenged by its resistance to microenvironmental stress infringed during escape from the primary tumor and the colonization of a foreign secondary tissue. Because of its great metastatic potential and its strong resistance to anticancer drugs, pancreatic cancer is regarded as a paradigm of the adaptation of cancer cells to microenvironmental stress. Thus, to understand how pancreatic cancer cells adapt to the different endogenous and therapy-related stresses is crucial f...

  17. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  18. 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.

  19. Bone metastasis in patients with para neoplastic myasthenic syndrome - Possible indication for bone scintigraphy

    International Nuclear Information System (INIS)

    Full text: Myasthenia gravis (MG) is a neuromuscular disorder caused by a decrease in the number of acetylcholine receptors at neuromuscular junctions and consequently characterized by weakness and fatigue. Paraneoplastic myasthenic syndrome (PMS) is a neurological disorder often difficult to diagnose in clinical practice, due to the lack, in most cases, of any sign of malignancy at the time when neurological impairment occurs. The connection between MG and pathological alterations of the thymus as well as between the presynaptic membrane alteration (Lambert-Eaton myasthenic syndrome) and the small-cell lung cancer is often demonstrated. Most researchers agree that myasthenic syndrome noticed in aged persons should be investigated as a possible paraneoplastic disorder. The aim of our study was to find if suspected PMS could be an indication to perform a bone scan, in presence of parameters suggesting malignancy (such as elevated serum levels of alkaline phosphatase, elevated tumor markers, unexplained bone pain etc.). Another question is whether bone metastases occur more frequently in malignancies associated with PMS than in the same diseases without neurological involvement, taking into account that neurological disorders are not produced by metastatic or direct invasion of the nervous system by the cancer. Our observations included 28 patients (13 men and 15 women), aged 42-80 years with myasthenic syndrome, who were referred by the neurology department for suspicion of bone metastasis. All patients had elevated serum levels of alkaline phosphatase, 18 patients had therapy-resistant bone and joints pain. Conventional imaging procedures (abdominal ultrasound, chest X-ray and computer tomography) were performed in all patients. Only in 6 patients the primary malignancy was diagnosed prior to bone scan (5 cases with thymoma and 1 case of digestive neoplasm). Bone scan was performed on a Diacam Siemens gamma camera and consisted of whole-body examination after

  20. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  1. 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.

  2. 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...

  3. 双侧乳腺癌伴骨及宫颈转移一例报告并文献复习%A Case Report and a Review of the Literature of Bilateral Breast Cancer with Bone and Cervical Metastasis

    Institute of Scientific and Technical Information of China (English)

    陆晓峰; 苏磊; 王雪晨

    2015-01-01

    Objective To study the clinical diagnosis and treatment of bilateral breast cancer with bone and cervical metastasis. Methods We retrospectively analyzed the clinical data of a case of bilateral breast cancer with bone and cervical metastasis in our hospital. Results The patient was a 52-year-old female,admitted for the right breast mass, which had been found more than one month before. Breast ultrasound showed substantial occupying lesions of bilateral breasts. The pathologic results of bilateral breast mass indicated all invasive lobular carcinoma. ECT of the whole body bone scanning showed systemic multiple bone metastases. B ultrasound in gynecology showed cervical hypoechoic occupying lesion. After the neoadjuvant chemotherapy, we performed operations of bilateral breast modified radical mastectomy and cervical neoplasm electrotomy. The postoperative pathological results showed that the bilateral breast tumors were invasive lobular carcinoma associated with axilla-ry lymph node metastasis. The pathological staging was IV( T1b ,N3 ,M1 ) . The result of immunohistochemistry showed that CK, S100, Mummaglobin and GCDFP-15 were positive, Ki67 was about 3% positive,ER was about 40% positive,PR was about 20% positive,while CerbB2 was negative. Then, the patient accepted the postoperative systemic treatment,such as chemother-apy, and endocrine therapy. The patient was checked every three months with a stable condition, and continued endocrine therapy. Conclusion The bone metastasis from breast cancer is a common condition,while the occurrence of metastasis to the neck of uterus is rare. The histopathological analysis combined with immunohistochemical detection is of great value in diagno-sis and treatment.%目的:探讨双侧乳腺癌伴骨及宫颈转移的临床诊治要点。方法对我院收治的双侧乳腺癌伴骨及宫颈转移1例的临床资料进行回顾性分析。结果本例52岁,因发现右乳腺包块1月余入院。乳腺彩色多普勒超声

  4. Suddenly occurring pain in the shin due to solitary metastasis to bone from a non-recognised primary tumour

    DEFF Research Database (Denmark)

    Chatterjee, Shefali Anup; Isaksen, Christin R Graff

    2014-01-01

    A woman who had formerly had adequately treated breast cancer presented with symptoms of pain in the right shin. An X-ray of the punctum maximum for the pain showed a bone lesion. Biopsy revealed that it came from an adenocarcinoma of the lung, contrary to the first diagnosis of breast cancer meta......-stasis. The lung lesion had been seen on a subsequent com-puted tomography. There were no presenting symptoms relating to lung cancer. This case is interesting as adenocar-cinoma metastasis to bone rarely occurs in the tibia and below the knee....

  5. TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

    OpenAIRE

    Iwai, Akio; Ozono, Seiichiro; Tanaka, Yozo; Nagayoshi, Junichi; Hirayama, Akihide; Kumon, Toshihiko; Joko, Masanori; Hirata, Naoya; Yoshikawa, Motoyoshi; Tabata, Shoichi; Uemura, Hirotsugu; Moriya, Akira; Kaneko, Yoshiteru; Okamoto, Shinji; Hirao, Yoshihiko

    1991-01-01

    We compared prostatic specific acid phosphatase (PAP), prostatic specificantigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection ofbone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It se...

  6. Gastric Metastasis of Lung Cancer Mimicking an Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Tsung I Hung

    2014-03-01

    Full Text Available Lung cancer is one of the leading causes of cancer deaths worldwide. Metastatic spreads of lung cancer are often found in the adrenal glands, bone, liver, brain and kidneys; the gastrointestinal tract is less commonly involved. However, according to some reports in the literature, the incidence of gastrointestinal metastases, most of them asymptomatic, might be as frequent as 11% in autopsy studies of lung cancer, which suggests that this condition is not as rare as it was previously considered. We report a very rare case of small cell lung cancer with a solitary gastric metastasis mimicking an adrenal tumor which was belatedly diagnosed due to its unusual presentation and treated actively with surgery and chemotherapy, achieving a relatively favorable outcome.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Paola Maroni

    2015-11-01

    Full Text Available 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.

  9. 肺癌骨转移同期放化疗临床疗效分析%Prospective clinical study of chemotherapy combined with radiotherapy in treatment of lung cancer patients with bone metastasis

    Institute of Scientific and Technical Information of China (English)

    韩萍

    2011-01-01

    目的 探讨同期放、化疗治疗肺癌骨转移临床疗效.方法 分析我院2004年1月~2008年1月收治的63例肺癌骨转移患者,A组同期放、化疗+帕米膦酸二钠;B组序贯放、化疗+帕米膦酸二钠.结果 A、B组治疗疼痛缓解率86.7%、39.4%,差异有统计学意义A、B组治疗局部病灶的总有效率60.0%、33.3%,差异有统计学意义;两个组2年生存率的差异有统计学意义;A、B组治疗前后生存质量比较及A、B组之间生存质量比较无统计学意义.结论 肺癌骨转移后采取同期放、化疗为主的综合治疗可明显减轻症状,延长患者生存时间.%Objective To research the clinical efficacy of simultaneous radiotherapy and chemotherapy for lung cancer with bone metastasis. Methods Analyzing 63 cases of lung cancer with bone metastasis in our hospital from January 2004 to January 2008. Group A : simultaneous radiotherapy and chemotherapy + pamidronate disodium; Group B : sequential radiotherapy and chemotherapy + pamidronate disodium. Results The pain relief rate was 86. 7% in group A and 39. 4% in group B. There was a statistical difference between group A and group B. The total effective rate of partial focus was 60. 0% in group A and 33. 3% in group B. There was a statistical difference hetween group A and group B ; There was a statistical difference between group A and group B;In the 2-year survival rate , There was no a statistical difference between group A and group B in the quality of life before and after the treatment. Conclusion The comprehensive treatment of simultaneous radiotherapy and chemotherapy for lung cancer with bone metastasis can noticeably alleviate the symptoms, extend the survival time of patients.

  10. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  11. 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.

  12. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    International Nuclear Information System (INIS)

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  13. Role of plasmacytoid dendritic cells in breast cancer bone dissemination

    OpenAIRE

    Sawant, Anandi; Ponnazhagan, Selvarangan

    2013-01-01

    Elevated levels of plasmacytoid dendritic cells (pDC) have been observed as breast cancer disseminates to the bone. The selective depletion of pDC in mice led to a total abrogation of bone metastasis as well as to an increase in TH1 antitumor response, suggesting that pDC may be considered as a potential therapeutic target for metastatic breast cancer.

  14. 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

  15. 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. PMID:27067726

  16. 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.

  17. 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

  18. Serum procollagen 1 amino-terminal propeptide (P1NP) in prostate cancer; pitfalls of its use as an early surrogate marker for bone metastasis

    International Nuclear Information System (INIS)

    Procollagen 1 amino-terminal propeptide (P1NP) is a bone formation marker and has been shown to have a strong association with the extent of bone metastases (BM) in patients with advanced prostate cancer. More recently, its levels were found to be affected by androgen deprivation therapies and bisphosphonates. We investigated the role of P1NP as a surrogate marker of sub-radiological skeletal metastases in prostate cancer patients with biochemical failure (BF). BePrepared is a prospective longitudinal substudy of RADAR trial in which serial P1NPs were collected at regular intervals for 123 patients who had completed RADAR protocol treatment. There was no trend identified in P1NP levels prior to diagnosis of BM. We found that there was no difference in P1NP concentrations at the time of diagnosis of BM in the group that developed BM compared with P1NP levels in groups with only nodal metastases or BF. In the group of patients who did not experience BF, P1NP was affected by previous luteinizing hormone-releasing hormone-agonist and bisphosphonate therapy. Hence, patients who received an 18-month course of androgen deprivation without bisphosphonates had significantly higher P1NP values than patients with shorter androgen deprivation therapy (ADT) course combined with a course of bisphosphonates. P1NP is not a sensitive serum marker of early BM in high-risk prostate cancer patients with BF and low prostate-specific antigen levels as its levels are affected by prior history of bone remodelling therapies such as ADT and bisphosphonates.

  19. 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.

  20. 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.

  1. 前列腺特异性抗原及骨标志物检测对前列腺癌骨转移患者诊断的意义%Significance of prostate specific antigen and markers of bone formation or resorption in diagnosis of bone metastasis of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    楼慧玲; 陈巧聪

    2012-01-01

    目的 探讨前列腺特异性抗原(PSA)、骨形成标志物碱性磷酸酶(ALP)与骨吸收标志物抗酒石酸酸性磷酸酶5b(TRACP5b)、Ⅰ型胶原吡啶交联终肽(ICTP)在前列腺癌骨转移诊断的意义. 方法 通过测定57例老年前列腺癌患者(年龄61~90岁)PSA、TRACP5b、ALP、ICTP血清浓度,分成骨转移(27例)与非骨转移(30例)两组,以转移灶在5个及以上者划分为进展性(18例)和局限性骨转移(39例).采用受试者工作特征曲线( ROC)评估各标志物诊断前列腺癌骨转移的价值.结果 PSA、TRACP5b、ALP、ICTP血清浓度在前列腺癌骨转移组均高于非骨转移组(P<0.05);与局限性骨转移组比较,PSA、TRACP5b、ALP、ICTP、Gleason评分在进展性骨转移组中均有明显升高(P<0.05);PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的曲线下面积(AUC)分别为0.796、0.657、0.762、0.743,最高诊断价值的是PSA,ALP、ICTP与之相当,TRACP5b次之,其敏感性分别为66.7%、59.3%、37.0%、59.3%,特异性则为90.0%、96.7%、80.0%、76.7%;PSA、ALP、ICTP与Gleason评分是预测前列腺癌骨转移的独立性因素,总符合率为84.2%. 结论 PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的价值相当,联合检测并动态观察可能有利于前列腺癌骨转移的早期诊断.%Objective To evaluate the significances of prostate specific antigen(PSA),alkaline phosphatase(ALP) as a marker of bone formation,tartrate-resistant acid phosphatase 5b(TRACP5b) and pyridinoline cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(ICTP) as markers of bone resorption in diagnosis of bone metastasis of prostate cancer. Methods Totally 57 elderly patients aged 61-90 years with prostate cancer were divided into groups with bone metastasis(n=27)and without bone metastasis (n=30) according to radionuclide bone imaging,and into progressive(n=18) and limited metastasis groups(n=39) by EOD score.Serum concentrations of

  2. 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.

  3. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Hu C

    2015-03-01

    Full Text Available Chenxia Hu,1 Martin Niestroj,2,3 Daniel Yuan,4 Steven Chang,5 Jie Chen5,6 1Faculty of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Canadian Light Source, Saskatoon, SK, Canada; 3Physics Department, Bonn University, Bonn, Germany; 4Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; 5Faculty of Engineering, University of Alberta, Edmonton, AB, Canada; 6Canadian National Research Council/National Institute for Nanotechnology, Edmonton, AB, Canada Abstract: Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain. Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs with thio-PEG (polyethylene glycol and thio-glucose, the resulting functionalized GNPs (Glu-GNPs were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption

  4. Evaluation of treatment response of cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET with 18F-FDG.

    Science.gov (United States)

    Cheng, Caixa; Komljenovic, Dorde; Pan, Leyun; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig; Bäuerle, Tobias

    2011-01-01

    The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with (18)F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The (18)F-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutic impact on (18)F-FDG kinetics. PMID:21512659

  5. 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.

  6. 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.

  7. 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.

  8. How Is Bone Cancer Diagnosed?

    Science.gov (United States)

    ... with bone cancer. Accurate diagnosis of a bone tumor often depends on combining information about its location (what bone is affected and even which part of the bone is involved), appearance on x-rays, and appearance under a microscope. ...

  9. Limb Salvage After Bone Cancer

    Science.gov (United States)

    ... Blog Donate Now Select Page Limb Salvage After Bone Cancer Home > Understanding Children’s Cancer > Late Effects of Treatment > Limb Salvage After Bone Cancer Limb salvage is a surgical procedure that replaces ...

  10. Drugs Approved for Bone Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Bone Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Bone Cancer Abitrexate (Methotrexate) Cosmegen (Dactinomycin) Dactinomycin Denosumab Doxorubicin Hydrochloride ...

  11. 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.

  12. 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.

  13. 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。

  14. Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

    International Nuclear Information System (INIS)

    The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

  15. 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.

  16. 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

  17. 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.

  18. Role of periostin and its antagonist PNDA-3 in gastric cancer metastasis.

    Science.gov (United States)

    Liu, Guo-Xiao; Xi, Hong-Qing; Sun, Xiao-Yan; Wei, Bo

    2015-03-01

    The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. Periostin participates in normal physiological activities such as cardiac development, but is also involved in pathophysiological processes in vascular diseases, wound repair, bone formation, and tumor development. It is of increasing interest in tumor biology because it is frequently overexpressed in a variety of epithelial carcinomas and is functionally involved in multiple steps of metastasis progression. These include the maintenance of stemness, niche formation, EMT, the survival of tumor cells, and angiogenesis, all of which are indispensable for gastric cancer metastasis. Periostin has been reported to activate the PI-3K/AKT, Wnt, and FAK-mediated signaling pathways to promote metastasis. Therefore, periostin represents a potentially promising candidate for the inhibition of metastasis. In this review article, we summarize recent advances in knowledge concerning periostin, its antagonist PNDA-3, and their influence on such key processes in cancer metastasis as maintenance of stemness, niche formation, epithelial-to-mesenchymal transition, tumor cell survival, and angiogenesis. In particular, we focus our attention on the role of periostin in gastric cancer metastasis, speculate as to the usefulness of periostin as a therapeutic and diagnostic target for gastric cancer metastasis, and consider potential avenues for future research. PMID:25759527

  19. 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 ...

  20. 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

  1. Clinical background and its relation to results of percutaneous needle biopsy of suspected bone metastasis under guidance with CT fluoroscopy

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the clinical background of needle biopsy of suspected bone metastasis under guidance with CT fluoroscopy. During a 3-year period (from April 2000 to March 2003), 103 needle biopsies on 101 lesions of 90 patients were performed for pathological evaluation of suspected bone metastasis. The clinical course of these patients prior to biopsy and its relation to the biopsy results were retrospectively reviewed. Sixty-two patients (69% of total cases) were referred for biopsy from orthopedic surgeons, and 51 of these patients consulted orthopedic surgeons on the initial presentation. Malignancy was pathologically proved in 47 (76%) of the 62 orthopedic patients, and in 19 (68%) of the 28 patients referred from other clinicians. Thirteen (21%) of the orthopedic patients had a history of malignancy, while 22 (78%) of the non-orthopedic patients were cancer patients. Metastasis was pathologically proved in 23 (66%) of the 35 patients with a history of malignancy, while malignancy was pathologically proved in 43 (78%) of the 55 patients without known malignancy. Diagnostic accuracy of the needle bone biopsy was 96%, and its complication rate was 0.7%. In the era of CT fluoroscopy, needle biopsy for suspected bone metastasis was most frequently requested for the patients who consulted orthopedic surgeons for the occurrence of local bone pain as the initial symptom of unknown malignancy. Frequency of malignancy proved by the biopsy in those patients was as high as that in the cancer patients referred from other clinicians. (author)

  2. FEATURES OF BILATERAL BREAST CANCER NODAL METASTASIS

    Directory of Open Access Journals (Sweden)

    Ye. A. Fesik

    2014-01-01

    Full Text Available This article focuses on issues related to the identification and investigation of the lymph node metastases with bilateral breast cancer. The presence of metastases in the lymph nodes determines the stage of the disease, and introducing a form of tumor progression, characterizes the course and prognosis for the future in a specific patient. Thus, the identification of possible morphological and immunohistochemical characteristics of the tumor tissue and their comparison with the frequency and severity of regional lymph nodes would help to solve the problem of the identification of prognostic factors and markers associated with the risk of nodal metastasis in bilateral breast cancer. This work is relevant due to the fact that the literature on this issue to date are treated ambiguously, and answers to many questions, unfortunately, no.The authors performed a morphological study of the tumor tissue from 600 patients suffering from unilateral and bilateral breast cancer. To avoid false results were studied only cases corresponding to the histological type of invasive carcinoma of non-specific type. The study found that a greater number and a greater percentage of the affected lymph node metastases were observed in patients with bilaterally synchronous tumors. The patients of this group of metastatic lymph nodes was detected more frequently in the presence of infiltrative component of three or more types of structures with the presence of these discrete groups of tumor cells, and the observed maximum degree of inflammatory infiltration of the tumor stroma. In the group of patients with unilateral breast cancer nodal metastasis often detects when triple negative molecular genetic type of the lesion, with large amounts of tumor site, in the presence of infiltrative component of three or more types of structures with the obligatory presence of these microalveolar structures and discretely spaced groups of tumor cells and the highest severity of

  3. Penile metastasis as a first sign of lung cancer

    Directory of Open Access Journals (Sweden)

    Sevket Ozkaya

    2009-07-01

    Full Text Available Sevket Ozkaya1, Serhat Findik2, Atilla G Atici21Samsun Chest Diseases and Thoracic Surgery Hospital, Samsun, Turkey; 2Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, TurkeyAbstract: Lung cancer does not generally produce any symptoms at the early stages and it rapidly metastasizes. Although lung cancer has a potential of metastasis to all organs and tissues, metastasis to the penis from lung cancer is very rare. We present a case with a penile lesion as the first sign of lung cancer.Keywords: lung cancer, metastasis, penis

  4. Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer

    OpenAIRE

    Zhao, Ende; Wang, Lin; Dai, Jinlu; Kryczek, Ilona; Wei, Shuang; Vatan, Linda; Altuwaijri, Saleh; Sparwasser, Tim; Wang, Guobin; Evan T. Keller; Zou, Weiping

    2012-01-01

    Human prostate cancer frequently metastasizes to bone marrow. What defines the cellular and molecular predilection for prostate cancer to metastasize to bone marrow is not well understood. CD4+CD25+ regulatory T (Treg) cells contribute to self-tolerance and tumor immune pathology. We now show that functional Treg cells are increased in the bone marrow microenvironment in prostate cancer patients with bone metastasis, and that CXCR4/CXCL12 signaling pathway contributes to Treg cell bone marrow...

  5. CXCR4 and Axillary Lymph Nodes: Review of a Potential Biomarker for Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    David Hiller

    2011-01-01

    Full Text Available CXCR4 is a 7-transmembrane G-protein chemokine receptor that allows for migration of hematopoietic cells from the bone marrow to the peripheral lymph nodes. Research has shown CXCR4 to be implicated in the invasion and metastasis of several cancers, including carcinoma of the breast. CXCL12 is the ligand for CXCR4 and is highly expressed in areas common for breast cancer metastasis, including the axillary lymph nodes. Axillary lymph nodes positive for breast carcinoma have been an important component of breast cancer diagnosis, treatment, and subsequent research. The goal of this paper is to analyze the literature that has explained the pathways from CXCR4 expression to breast cancer metastasis of the lymph nodes and the prognostic and/or predictive implications of lymph node metastases in the presence of elevated CXCR4.

  6. CXCR4 and Axillary Lymph Nodes: Review of a Potential Bio marker for Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    CXCR4 is a 7-transmembrane G-protein chemokine receptor that allows for migration of hematopoietic cells from the bone marrow to the peripheral lymph nodes. Research has shown CXCR4 to be implicated in the invasion and metastasis of several cancers, including carcinoma of the breast. CXCL12 is the ligand for CXCR4 and is highly expressed in areas common for breast cancer metastasis, including the axillary lymph nodes. Axillary lymph nodes positive for breast carcinoma have been an important component of breast cancer diagnosis, treatment, and subsequent research. The goal of this paper is to analyze the literature that has explained the pathways from CXCR4 expression to breast cancer metastasis of the lymph nodes and the prognostic and/or predictive implications of lymph node metastases in the presence of elevated CXCR4

  7. 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.

  8. 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.

  9. 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%Study on the Clinical Value of Pulmonary Tumor Markers and Bone Alkafine Phosphatase Detection in Early Diagnosis of Bone Metastasis of Lung Cancer

    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

  10. 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

  11. 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.

  12. Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells.

    Science.gov (United States)

    Alasmari, Abeer; Lin, Shih-Chun; Dibart, Serge; Salih, Erdjan

    2016-08-01

    Anti-resorptive bisphosphonates (BPs) have been clinically used to prevent cancer-bone metastasis and cancer-induced bone pathologies despite the fact that the phenotypic response of the cancer-bone interactions to BP exposure is "uncharted territory". This study offers unique insights into the interplay between cancer stem cells and osteocytes/osteoblasts and mesenchymal stem cells using a three-dimensional (3D) live cancer-bone interactive model. We provide extraordinary cryptic details of the biological events that occur as a result of alendronate (ALN) treatment using 3D live cancer-bone model systems under specific bone remodeling stages. While cancer cells are susceptible to BP treatment in the absence of bone, they are totally unaffected in the presence of bone. Cancer cells colonize live bone irrespective of whether the bone is committed to bone resorption or formation and hence, cancer-bone metastasis/interactions are though to be "independent of bone remodeling stages". In our 3D live bone model systems, ALN inhibited bone resorption at the osteoclast differentiation level through effects of mineral-bound ALN on osteocytes and osteoblasts. The mineral-bound ALN rendered bone incapable of osteoblast differentiation, while cancer cells colonize the bone with striking morphological adaptations which led to a conclusion that a direct anti-cancer effect of BPs in a "live or in vivo" bone microenvironment is implausible. The above studies were complemented with mass spectrometric analysis of the media from cancer-bone organ cultures in the absence and presence of ALN. The mineral-bound ALN impacts the bone organs by limiting transformation of mesenchymal stem cells to osteoblasts and leads to diminished endosteal cell population and degenerated osteocytes within the mineralized bone matrix. PMID:27155840

  13. CXCR4 and Axillary Lymph Nodes: Review of a Potential Biomarker for Breast Cancer Metastasis

    OpenAIRE

    David Hiller; Quyen D. Chu

    2011-01-01

    CXCR4 is a 7-transmembrane G-protein chemokine receptor that allows for migration of hematopoietic cells from the bone marrow to the peripheral lymph nodes. Research has shown CXCR4 to be implicated in the invasion and metastasis of several cancers, including carcinoma of the breast. CXCL12 is the ligand for CXCR4 and is highly expressed in areas common for breast cancer metastasis, including the axillary lymph nodes. Axillary lymph nodes positive for breast carcinoma have been an important c...

  14. Treatment of Brain Metastasis from Lung Cancer

    International Nuclear Information System (INIS)

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well

  15. 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.

  16. 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.

  17. 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。

  18. Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

    Directory of Open Access Journals (Sweden)

    Linda Vona-Davis

    2014-01-01

    Full Text Available Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n=42 or visceral sites (n=53. Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P=0.042. More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P=0.0002. There were 135/574 women (23.5% with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P=0.033. Triple-negative tumors that metastasized to visceral sites were larger (P=0.007. Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

  19. Tumor microenvironment: The culprit for ovarian cancer metastasis?

    Science.gov (United States)

    Luo, Zhongyue; Wang, Qiu; Lau, Wayne Bond; Lau, Bonnie; Xu, Lian; Zhao, Linjie; Yang, Huiliang; Feng, Min; Xuan, Yu; Yang, Yanfei; Lei, Lingzi; Wang, Chenlu; Yi, Tao; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

    2016-07-28

    Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice. PMID:27131957

  20. Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

    2012-03-15

    A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

  1. Superparamagnetic iron oxide (SPIO) MRI contrast agent for bone marrow imaging. Differentiating bone metastasis and osteomyelitis

    International Nuclear Information System (INIS)

    We explored appropriate scan timing for bone marrow imaging enhanced using superparamagnetic iron oxide (SPIO) and evaluated the usefulness of SPIO in differentiating metastasis and osteomyelitis in patients. The method of this study was to determine the adequate scan timing after administration of SPIO, 5 healthy subjects were examined using a 1.5T magnetic resonance (MR) imaging scanner. Sagittal images of their lumbar spines were obtained using short-TI inversion recovery (STIR) sequence before and 3, 6, 9, 24, and 48 hours after intravenous injection of 8 μmol Fe/kg SPIO (ferucarbotran). MR signal intensities (SIs) were evaluated. Based on the results, 12 patients, five with bone metastasis and seven with vertebral osteomyelitis, were examined using the same procedure before and 3 hours after intravenous injection of ferucarbotran at the same dose. SIs of the bone metastases, osteomyelitis, and surrounding normal bone marrow were measured, and relative enhancement (RE) was calculated for each lesion. In the healthy volunteers, maximum reduction in signal was observed 3 to 24 hours (P<0.05) after administration of SPIO; thereafter and up to 48 hours, the SI gradually recovered. In the patients, the RE of the bone metastases was -12.2%, which was significantly higher than that in the osteomyelitis (- 35.0%, P<.001) and normal bone marrow (-46.6%, P<.0005). Maximum suppression of signal intensity in bone marrow was seen 3 hours after injection of ferucarbotran, the point at which ferucarbotran allows differentiation of bone metastasis from ostoemyelitis. (author)

  2. Penile metastasis as a first sign of lung cancer

    OpenAIRE

    Findik, Serhat; Özkaya, Şevket; Gatici,A

    2009-01-01

    Sevket Ozkaya1, Serhat Findik2, Atilla G Atici21Samsun Chest Diseases and Thoracic Surgery Hospital, Samsun, Turkey; 2Department of Pulmonary Medicine, Faculty of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, TurkeyAbstract: Lung cancer does not generally produce any symptoms at the early stages and it rapidly metastasizes. Although lung cancer has a potential of metastasis to all organs and tissues, metastasis to the penis from lung cancer is very rare. We present a case with a peni...

  3. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    OpenAIRE

    Yongqi CUI; Geng, Qin; Gu, Aiqin; Miaoxin ZHU; Hanwei KONG; Sun, Lei; Liu, Lei; Yan, Mingxia; Yao, Ming

    2013-01-01

    Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left ca...

  4. Laparoscopic partial nephrectomy of thyroid cancer metastasis: case report and review of the literature

    Science.gov (United States)

    Cochetti, Giovanni; Puxeddu, Efisio; Zingaro, Michele Del; D’Amico, Francesco; Cottini, Emanuele; Barillaro, Francesco; Mearini, Ettore

    2013-01-01

    Background Follicular cell thyroid carcinoma is a quite aggressive form of thyroid cancer. About 10% of follicular thyroid carcinoma shows multiple metastases: lung and bone are the most common sites of metastasis. Renal involvement from thyroid primary cancer is very rare with incidence of 4.5%–5.9%. Purpose We report the first laparoscopic conservative treatment of renal metastasis from thyroid cancer. This is a new and useful approach in order to delay malignant disease progression and to reduce the surgical discomfort of the patient. Patients and methods We present the case of a 67-year-old woman, undergoing total thyroidectomy for follicular thyroid cancer with bone and lung metastasis. During adjuvant radiometabolic treatment, renal metastasis was diagnosed. Renal metastasis showed high metabolic activity, reducing the effectiveness of radioiodine therapy for secondary lesions. For this reason, we performed a laparoscopic simple enucleation of the single renal metastasis using extraperitoneal access and a clampless procedure. Results The excision of the renal lesion improved the effectiveness of adjuvant radioiodine therapy: two months after surgery, the patient underwent adjuvant radiometabolic treatment with iodine-131 (150 mCi) and the following whole body scan showed only a small uptaking area at the level of the vertebral metastasis. The lung micrometastases were not detectable. At 36 months follow-up, malignant disease was clinically stable and well controlled. Conclusion Minimally invasive renal surgery with preservation of renal function and rapid recovery contributed to the success of radioiodine therapy and delayed the progression of the disease. PMID:23596352

  5. 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.

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Romeeta Trehan

    2015-01-01

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

  10. 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

  11. An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

    Science.gov (United States)

    Paschall, Amy V; Liu, Kebin

    2016-01-01

    Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo. PMID:27584043

  12. New mechanistic insights of integrin β1 in breast cancer bone colonization

    OpenAIRE

    Thibaudeau, Laure; Taubenberger, Anna V.; Theodoropoulos, Christina; Holzapfel, Boris M.; Ramuz, Olivier; Straub, Melanie; Hutmacher, Dietmar W.

    2014-01-01

    Bone metastasis is a frequent and life-threatening complication of breast cancer. The molecular mechanisms supporting the establishment of breast cancer cells in the skeleton are still not fully understood, which may be attributed to the lack of suitable models that interrogate interactions between human breast cancer cells and the bone microenvironment. Although it is well-known that integrins mediate adhesion of malignant cells to bone extracellular matrix, their role during bone colonizati...

  13. Monitoring Metastasis and Cachexia in a Patient with Breast Cancer: A Case Study

    Science.gov (United States)

    Consul, Nikita; Guo, Xiaotao; Coker, Courtney; Lopez-Pintado, Sara; Hibshoosh, Hanina; Zhao, Binsheng; Kalinsky, Kevin; Acharyya, Swarnali

    2016-01-01

    Cachexia, a wasting syndrome associated with advanced cancer and metastasis, is rarely documented in breast cancer patients. However, the incidence of cachexia in breast cancer is now thought to be largely underestimated. In our case report of a breast cancer patient with bone metastasis monitored during the course of her treatment, we document the development of cachexia by image analysis in relation to her metastatic burden. Elucidation of the link between metastatic burden and cachexia could unveil a highly specific screening process for metastasis, by assessing true muscle mass loss. Our patient was a 49-year-old premenopausal woman, with metastatic invasive ductal breast carcinoma in the vertebral and iliac bones on presentation, which progressed with new metastases to her hips, thigh bones, and vertebrae. In the two-year period, that is between her diagnosis and death, she lost >10% of her baseline weight. During these two years, we retrospectively identified a decrease in paraspinal muscle (PM) at the third lumbar vertebra followed by a sharp decline in weight. The increased tumor burden over time in metastatic sites was accompanied by a decrease in abdominal muscle and visceral and subcutaneous fat and was followed by the patient’s demise. The increasing tumor burden in the patient was correlated with the mass of other tissues to determine the tissue that could best serve as a surrogate marker to cachexia and tumor burden. We noted a strong negative correlation between PM area and metastatic tumor area at the third lumbar vertebral level, with PM loss correlating to increasing tumor burden. The monitoring of PM wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and extent of metastatic disease, especially in breast cancer, where metastasis to bone is frequent. Based on our data and review of the literature in this case study, longitudinal monitoring of cachexia in the selected muscle groups can give clinicians early

  14. S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction

    OpenAIRE

    Mathias Dahlmann; Dennis Kobelt; Wolfgang Walther; Giridhar Mudduluru; Ulrike Stein

    2016-01-01

    The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, w...

  15. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    Directory of Open Access Journals (Sweden)

    Yongqi CUI

    2013-09-01

    Full Text Available Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left cardiac ventricle of mice in the four experimental groups (0.2 mL/mouse respectively; meanwhile, mice in the control group were injected with normal saline (0.2 mL/mouse in the same manner. Periodical radiological examination was carried out to supervise the variation of the mice since the second week after injection. When mice in each group became thin obviously, end the experiment of this group. Before the end, pathological sections of bone tissues were made. We classified the bone metastatic sites into axial skeleton and limb bone, in order to compare the metastatic rates of these two different parts. The bone metastatic abilities of the four cell lines was statistically analyzed by comparing the average time cost in the appearance of bone metastases and the percentage of bone metastases among the experimental groups. Results Different metastatic sites which had been identified both by MicroCT and pathological sections appeared in each group of the four experimental groups. By contrast, no metastasis was observed in the control group. The percentage of cancer metastasizing to axial skeleton was remarkably higher than the percentage of tumor metastasizing to the limb bone in each experimental group, which was consistent with the clinical regularity and characteristics of skeletal metastases with lung cancer. Thus, the model has been established triumphantly. However, there were no statistical differences in the average time consumed and skeletal metastatic

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Optimal management of bone metastases in breast cancer patients

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  19. Active Roles of Tumor Stroma in Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    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.

  20. Effects of simvastatin on human breast cancer osteolytic bone metastasis in a nude mice model%辛伐他汀在裸鼠模型中对乳腺癌骨转移的影响

    Institute of Scientific and Technical Information of China (English)

    陈明霞; 张蔚; 曲建力; 李强; 王海

    2015-01-01

    目的 观察辛伐他汀在裸鼠模型中对乳腺癌骨转移的作用.方法采用完全随机分组方法 将60只裸鼠分为3组,每组20只,裸鼠左心腔注射乳腺癌骨转移细胞株(MDA-MB-231),7d后,分别皮下注射辛伐他汀、生理盐水及无任何处理(2次/周,19 d).应用图像分析软件评估骨转移瘤的面积.随后处死裸鼠,用放射免疫法检测骨转移癌髓腔内甲状旁腺素相关蛋白(PTHrP)浓度;应用骨密度检测软件进行组织形态学分析,计数骨转移灶每毫米癌组织与临近骨小梁之间破骨细胞的数量.计量资料比较采用方差分析,P<0.05为差异有统计学意义.结果 与生理盐水组和无处理组相比,注射辛伐他汀的裸鼠骨转移癌面积明显减小(0.51±0.18 mm2 vs 2.13±1.24 mm2 vs 2.29±1.22 mm2;F=15.600,P=0.002; F=15.673,P=0.001),骨转移癌周围髓腔内PTHrP浓度明显降低(0.98±0.20 pmol/L vs 2.11±0.31 pmol/L vs 1.99±0.29 pmol/L;F=61.469,P<0.001;F=58.274,P<0.001),并且其转移灶破骨细胞的数量明显减少(4.00±1.73个/mm vs 11.40 ±4.93个/mm vs 10.91±3.87个/mm;F=17.820,P=0.001,F=17.184,P=0.002).结论 辛伐他汀能够降低乳腺癌细胞PTHrP的分泌,从而抑制乳腺癌细胞在骨内生长及其对骨质的破坏.%Objective To observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model.Methods Sixty mice were divided into three groups randomly with 20 in each group.Mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle.After 7 days,mice were treated with either simvastatin,saline,or nothing twice per week for 19 days.The area of osteolytic metastases was subsequently measured in long bones of all mice using an image analysis system.After sacrifice,parathyroid hormone-related protein (PTHrP) concentrations in bone marrow from all mice were determined using a two-site immunoradiometric assay.Osteoclast number expressed per millimeter of tumor/bone interface was assessed

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

    Institute of Scientific and Technical Information of China (English)

    杨士军; 谭维琴; 鲍艳梅

    2011-01-01

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

  2. Acidic microenvironment and bone pain in cancer-colonized bone

    OpenAIRE

    Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki; Okui, Tatsuo; White, Fletcher A.

    2015-01-01

    Solid cancers and hematologic cancers frequently colonize bone and induce skeletal-related complications. Bone pain is one of the most common complications associated with cancer colonization in bone and a major cause of increased morbidity and diminished quality of life, leading to poor survival in cancer patients. Although the mechanisms responsible for cancer-associated bone pain (CABP) are poorly understood, it is likely that complex interactions among cancer cells, bone cells and periphe...

  3. 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.

  4. High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report.

    Science.gov (United States)

    Zhou, Tao; Zhang, Xia; Dong, Yan; Zhuang, Feifei; Jiang, Fengquan; Yu, Jinming; Zhang, Bin

    2016-01-01

    Pain management is an important topic that has received extensive attention from clinical practitioners. Nearly all patients with malignant tumors suffer pain at the advanced stage of their disease. Oxycodone is a first-line choice for treating moderate-to-severe cancer-related pain, and OxyContin, a controlled-release oxycodone hydrochloride tablet, is internationally recognized as a safe and effective opioid analgesic. OxyContin has the characteristics of both immediate release and sustained release, with a time to onset and peak similar to those of immediate-release morphine. It acts on both μ and κ receptors and has been shown to be effective in treating different types of pain, especially neuropathic pain, theoretically without a dose cap. However, the dose is limited in clinical applications due to various factors that are likely to affect its analgesic effect and reduce patient quality of life. Cooperation with a patient's family members is required during the treatment of cancer pain. Chronic cancer pain has a long disease course, which could easily cause complex psychological symptoms due to their important role in the pain experience. Pain is controllable, and patients have a right to not experience pain. An optimal living state can be achieved through collaboration between physicians and patients. Rational personalized treatment of cancer pain can improve patient quality of life, relieve pain, and help prolong patient survival. This article reports the treatment procedure and adverse reactions in a patient who was treated with high-dose OxyContin, with the aim of providing a reference for other clinical practitioners. PMID:26855563

  5. 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.

  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. 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.

  8. 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.

  9. Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

    OpenAIRE

    Linda Vona-Davis; Rose, David P.; Vijaya Gadiyaram; Barbara Ducatman; Gerald Hobbs; Hannah Hazard; Sobha Kurian; Jame Abraham

    2014-01-01

    Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n = 42) or visceral sites (n = 53). Metastases to viscera occurred within five years, a latent period which was ...

  10. A Case of Sweet's Panniculitis Associated with Spinal Metastasis from Prostate Cancer

    OpenAIRE

    Kim, Jihyun; Choi, Yoon Jin; Oh, Sang Ho; Lee, Kwang Hoon

    2010-01-01

    Sweet's panniculitis is a rare variant of Sweet's syndrome in which neutrophilic infiltrate can be found either in the subcutaneous fat or in both the dermis and the subcutaneous tissue. Due to the rarity of this entity, the association between Sweet's panniculitis and malignancies is inconclusive, but cases of Sweet's panniculitis have largely been associated with hematological malignancies. Herein, we present a case of Sweet's panniculitis accompanied by bone metastasis from prostate cancer...

  11. Primary breast cancer stem-like cells metastasise to bone, switch phenotype and acquire a bone tropism signature

    OpenAIRE

    D′Amico, L; Patanè, S; Grange, C.; Bussolati, B; Isella, C.; Fontani, L; Godio, L; Cilli, M; D′Amelio, P; Isaia, G; Medico, E; Ferracini, R; Roato, I

    2013-01-01

    Background: Bone metastases represent a common and severe complication in breast cancer, and the involvement of cancer stem cells (CSCs) in the promotion of bone metastasis is currently under discussion. Here, we used a human-in-mice model to study bone metastasis formation due to primary breast CSCs-like colonisation. Methods: Primary CD44+CD24− breast CSCs-like were transduced by a luciferase-lentiviral vector and injected through subcutaneous and intracardiac (IC) routes in non-obese/sever...

  12. 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

  13. 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.

  14. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer1

    OpenAIRE

    Brown, Janet E.; Sim, Sheryl

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  15. Kinetic Analysis of 18F-Fluoride PET Images of Breast Cancer Bone Metastases

    OpenAIRE

    Doot, Robert K; Muzi, Mark; Peterson, Lanell M.; Schubert, Erin K; Gralow, Julie R.; Specht, Jennifer M.; Mankoff, David A.

    2010-01-01

    The most common site of metastasis for breast cancer is bone. Quantitative 18F-fluoride PET can estimate the kinetics of fluoride incorporation into bone as a measure of fluoride transport, bone formation, and turnover. The purpose of this analysis was to evaluate the accuracy and precision of 18F-fluoride model parameter estimates for characterizing regional kinetics in metastases and normal bone in breast cancer patients.

  16. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer

    OpenAIRE

    Brown, Janet E.; Sheryl Sim

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  17. 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

  18. Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

    OpenAIRE

    He, Bei Ping; Wang, Jian Jun; Zhang, Xian; Wu, Yan; Wang, Miao; Bay, Boon-Huat; Chang, Alex Yuang-Chi

    2006-01-01

    The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidat...

  19. 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.

  20. 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.

  1. 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.

  2. CSR1 Suppresses Tumor Growth and Metastasis of Prostate Cancer

    OpenAIRE

    Yu, Guoying; Tseng, George C.; Yu, Yan Ping; Gavel, Tim; Nelson, Joel; Wells, Alan; Michalopoulos, George; Kokkinakis, Demetrius; Luo, Jian-Hua

    2006-01-01

    Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in pr...

  3. 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.

  4. Radionuclide therapy for thyroid cancer with nervous system metastasis

    International Nuclear Information System (INIS)

    Differentiated thyroid cancer is 85% of all thyroid cancer, and is known to have good prognosis with proper surgery and radioiodine therapy. But 4% of papillary carcinoma and 36% of follicular carcinoma present with distant metastasis. Even if the patient had distant metastasis, total thyroidectomy and radioiodine therapy show good response. Forty seven percent of bone metastases are found in the initial diagnosis, in which vertebral metastases is 29%, pelvic metastases 22%. The metastases to vertebrae often combine spinal cord compression, making it difficult to deliver enough radiation dose to the lesion with radioiodine or external beam irradiation. Brain metastases is found in less than 1% of thyroid cancer, and is also difficult to cure. In Korea Cancer Center Hospital, from 1997 to 2002, we analyzed 437 patients with thyroid cancer who were treated with radioiodine after total thyroidectomy. There were four patients with brain metastases, and 32 patients with vertebral metastases. In four patients with brain metastases, one patient, who also had bone metastases, received high dose radioiodine therapy after total thyroidectomy, and is alive for more than 15 months. Another patients received total thyroidectomy, radioiodine therapy and external irradiation therapy, and survived 22 months. Two patients refused further treatment and died in one month. I-131 uptake in the metastatic lesion in brain is reported to be 17%, and multimodality therapy with surgery, radioiodine therapy, external irradiation and chemotherapy may improve the prognosis. In 32 patients with vertebral metastases, 19 patients (59.4%) showed I-131 uptake after high dose radioiodine therapy, and 5 year survival rate was 65.8%. 13 patients without I-131 uptake after radioiodine therapy had 26.9% of 5 year survival rate. In 11 patients with spinal cord compression, 7 patients received high dose radioiodine therapy and external irradiation after total thyroidectomy and spinal surgery, and six

  5. Bone and cancer: the osteoncology

    OpenAIRE

    Ibrahim, Toni; Mercatali, Laura; Amadori, Dino

    2013-01-01

    In recent years clinicians have witnessed a radical change in the relationship between bone and cancer, with in particular an increase in bone metastases incidence due to an improvement of patients survival. Bone metastases are responsible for the high morbidity in cancer patients with a strong clinical impact. For all these reasons, efforts have been directed to this important field with the foundation of the osteoncology, a new scientific and clinical branch involved in the management of pa...

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

    OpenAIRE

    Ali Murat Tatlı; Seyda Gunduz; Sema Sezgin Göksu; Deniz Arslan; Mukremin Uysal; Cumhur İbrahim Başsorgun; Hasan Şenol Coşkun

    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 ...

  7. 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.

  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. Pancreatic solitary and synchronous metastasis from breast cancer: a case report and systematic review of controversies in diagnosis and treatment

    OpenAIRE

    Molino, Carlo; Mocerino, Carmela; Braucci, Antonio; Riccardi, Ferdinando; Trunfio, Martino; Carrillo, Giovanna; Vitale, Maria Giuseppa; Cartenì, Giacomo; De Sena, Guido

    2014-01-01

    Background Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare, and more frequently discovered after a primary diagnosis of breast cancer. Solitary pancreatic metastases from breast cancer, without widespread disease, are actually unusual, and only 19 cases have been previously described; truly exceptional is a solitary pancreatic metastasis becoming evident together with the pri...

  10. 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

  11. 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.

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

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    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.

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

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    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)

  14. Laparoscopic partial nephrectomy of thyroid cancer metastasis: case report and review of the literature

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    Cochetti G, Puxeddu E, Del Zingaro M, D’Amico F, Cottini E, Barillaro F, Mearini E

    2013-04-01

    Full Text Available Giovanni Cochetti,1 Efisio Puxeddu,2 Michele Del Zingaro,3 Francesco D’Amico,1 Emanuele Cottini,1 Francesco Barillaro,1 Ettore Mearini11Department of General Surgery and Surgical Specialties, Urological Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Terni, Italy; 2Departmentof Internal Medicine, 3Departmentof Surgical Specialties and PublicHealth, Urological Clinic, Universityof Perugia, Perugia, ItalyBackground: Follicular cell thyroid carcinoma is a quite aggressive form of thyroid cancer. About 10% of follicular thyroid carcinoma shows multiple metastases: lung and bone are the most common sites of metastasis. Renal involvement from thyroid primary cancer is very rare with incidence of 4.5%–5.9%.Purpose: We report the first laparoscopic conservative treatment of renal metastasis from thyroid cancer. This is a new and useful approach in order to delay malignant disease progression and to reduce the surgical discomfort of the patient.Patients and methods: We present the case of a 67-year-old woman, undergoing total thyroidectomy for follicular thyroid cancer with bone and lung metastasis. During adjuvant radiometabolic treatment, renal metastasis was diagnosed. Renal metastasis showed high metabolic activity, reducing the effectiveness of radioiodine therapy for secondary lesions. For this reason, we performed a laparoscopic simple enucleation of the single renal metastasis using extraperitoneal access and a clampless procedure.Results: The excision of the renal lesion improved the effectiveness of adjuvant radioiodine therapy: two months after surgery, the patient underwent adjuvant radiometabolic treatment with iodine-131 (150 mCi and the following whole body scan showed only a small uptaking area at the level of the vertebral metastasis. The lung micrometastases were not detectable. At 36 months follow-up, malignant disease was clinically stable and well controlled.Conclusion: Minimally invasive renal

  15. Role of STAT3 in Cancer Metastasis and Translational Advances

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    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.

  16. 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

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

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    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

  18. 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.

  19. 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. PMID:27512840

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

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    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.

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

    OpenAIRE

    Yang, Mei; WANG, WEI; ZHANG, CHENFANG

    2013-01-01

    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 p...

  2. 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.

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

    Science.gov (United States)

    Morales, I; Bassa, C; Pavlovic, A; Morales, C

    2016-03-01

    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. PMID:26793587

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

    Science.gov (United States)

    Morales, I.; Bassa, C.; Pavlovic, A.; Morales, C.

    2015-01-01

    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. PMID:26793587

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy

    Science.gov (United States)

    Lu, Tianzhu; Guo, Qiaojuan; Cui, Xiaofei; Chen, Zhuhong; Lin, Shaojun; Xu, Luying; Lin, Jin; Zong, Jingfeng

    2016-01-01

    Purpose To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. Materials and Methods Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. Results The median follow-up time was 15.5 months (range, 2–67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (pnumber of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis. PMID:27189275

  10. 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.

  11. 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.)

  12. Farnesoid X receptor, overexpressed in pancreatic cancer with lymph node metastasis promotes cell migration and invasion

    OpenAIRE

    Lee, J Y; Lee, K. T.; Lee, J. K.; Lee, K. H.; Jang, K-T; Heo, J S; Choi, S. H.; Kim, YIl; Rhee, J. C.

    2011-01-01

    Background: Lymph node metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers and therapeutic targets for pancreatic cancer. Methods: DNA microarray study was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with lymph node metastasis and 17 pancreatic cancer tissues without lymph node metastasis. The microarray results were validate...

  13. Osteolytic bone metastasis is hampered by impinging on the interplay among autophagy, anoikis and ossification.

    Science.gov (United States)

    Maroni, P; Bendinelli, P; Matteucci, E; Locatelli, A; Nakamura, T; Scita, G; Desiderio, M A

    2014-01-01

    Here we show that the fate of osteolytic bone metastasis depends on the balance among autophagy, anoikis resistance and ossification, and that the hepatocyte growth factor (HGF) signaling pathway seems to have an important role in orchestrating bone colonization. These findings are consistent with the pathophysiology of bone metastasis that is influenced by the cross-talk of supportive and neoplastic cells through molecular signaling networks. We adopted the strategy to target metastasis and stroma with the use of adenovirally expressed NK4 (AdNK4) and Dasatinib to block HGF/Met axis and Src activity. In human bone metastatic 1833 cells, HGF conferred anoikis resistance via Akt and Src activities and HIF-1α induction, leading to Bim isoforms degradation. When Src and Met activities were inhibited with Dasatinib, the Bim isoforms accumulated conferring anoikis sensitivity. The proviability effect of HGF, under low-nutrient stress condition, was related to a faster autophagy deactivation with respect to HGF plus Dasatinib. In the 1833 xenograft model, AdNK4 switched metastasis vasculature to blood lacunae, increasing HIF-1α in metastasis. The combination of AdNK4 plus Dasatinib gave the most relevant results for mice survival, and the following molecular and cellular changes were found to be responsible. In bone metastasis, we observed a hypoxic condition - marked by HIF-1α - and an autophagy failure - marked by p62 without Beclin-1. Then, osteolytic bone metastases were largely prevented, because of autophagy failure in metastasis and ossification in bone marrow, with osteocalcin deposition. The abnormal repair process was triggered by the dysfunctional autophagy/anoikis interplay. In conclusion, the concomitant blockade of HGF/Met axis and Src activity seemed to induce HIF-1α in metastasis, whereas the bone marrow hypoxic response was reduced. As a consequence, anoikis resistance might be hampered favoring, instead, autophagy failure and neoformation of woven

  14. 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. PMID:24100626

  15. 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.

  16. 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

  17. What Is Bone Cancer?

    Science.gov (United States)

    ... our document called Osteosarcoma . Chondrosarcoma: Chondrosarcoma (KON-droh-sar-KOH-muh) is a cancer of cartilage cells. ... AdditionalResources Other Resources and References Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & ...

  18. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

    OpenAIRE

    Lu Zhao; Jianhua Xu; Fang Liang; Ao Li; Yong Zhang; Jue Sun

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also assoc...

  19. Contralateral axillary node metastasis from recurrence after conservative breast cancer surgery.

    Science.gov (United States)

    Nishimura, Satoko; Koizumi, Mitsuru; Kawakami, Junko; Koyama, Masamichi

    2014-02-01

    Sentinel lymph node detection (SLND) with radiocolloid has become widely used for evaluation of nodal metastasis in primary breast cancer. However, the procedure for recurrent breast cancer is not well established. Contralateral axillary node metastasis is uncommon. We report 2 cases of contralateral axillary node metastasis with recurrent breast cancer. In the first case, contralateral node metastasis was found by SLND. In the other case without SLND, contralateral node metastasis developed after resection of local recurrence. FDG-avid contralateral node was pathologically diagnosed as metastasis. The SLND might be useful in patients with local recurrence after conservative breast cancer surgery. PMID:24368539

  20. Multimodality Therapy: Bone-Targeted Radioisotope Therapy of Prostate Cancer

    Science.gov (United States)

    Tu, Shi-Ming; Lin, Sue-Hwa; Podoloff, Donald A.; Logothetis, Christopher J.

    2016-01-01

    Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy. PMID:20551894

  1. 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

  2. The influence of the pre-metastatic niche on breast cancer metastasis.

    Science.gov (United States)

    Ursini-Siegel, Josie; Siegel, Peter M

    2016-09-28

    The emergence of metastatic disease constitutes a significant life-threatening development during cancer progression. To date, intensive efforts have been focused on understanding the intrinsic properties that confer malignant potential to cancer cells, as well as the role of the primary tumour microenvironment in promoting cancer metastasis. Beyond events occurring at the primary site, the metastatic cascade is composed of numerous barriers that must be overcome in order for disseminating cancer cells to form distal metastases. The most formidable of these is the ability of cancer cells to seed and grow in a completely foreign microenvironment. Interestingly, solid malignancies often display a particular tropism for specific tissue sites. For example, breast patients with metastatic disease will often develop bone, lung, liver or brain metastases. This mini-review will explore aspects of pre-existing and induced metastatic niches and focus on how the unique composition and function of diverse niche components, within common sites of breast cancer metastasis, enable the survival and growth of disseminated cancer cells. These common supportive functions of the niche are provided by a complex array of stromal components and molecular mechanisms that are, in part, reflective of the tissue in which the metastases arise. Finally, the metastatic niche is a dynamic structure that is continually altered and sculpted by the cancer cells during progression of the metastatic lesion. PMID:26577808

  3. 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.

  4. Thrombocytosis of Liver Metastasis from Colorectal Cancer as Predictive Factor

    DEFF Research Database (Denmark)

    Josa, Valeria; Krzystanek, Marcin; Vass, Tamas;

    2015-01-01

    There is increasing evidence that thrombocytosis is associated with tumor invasion and metastasis formation. It was shown in several solid tumor types that thrombocytosis prognosticates cancer progression. The aim of this study was to evaluate preoperative thrombocytosis as a potential prognostic...

  5. Cardiac metastasis from colorectal cancer: A case report

    Institute of Scientific and Technical Information of China (English)

    Pyong Wha Choi; Chul Nam Kim; Sun Hee Chang; Woo Ik Chang; Chang Young Kim; Hyun Min Choi

    2009-01-01

    The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm × 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated lobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer (T4N2). Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation.Histological examination revealed adenocarcinoma,which was identical to the primary lesion. Although twodimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

  6. Predictive factors for lymph node metastasis in early gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chang-Mu; Sung; Chen-Ming; Hsu; Jun-Te; Hsu; Ta-Sen; Yeh; Chun-Jung; Lin; Tse-Ching; Chen; Cheng-Tang; Chiu

    2010-01-01

    AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors ...

  7. 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.

  8. 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.

  9. 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

    2015-01-01

    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. PMID:25775533

  10. Non-coding RNAs in cancer brain metastasis.

    Science.gov (United States)

    Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

    2016-01-01

    More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can't penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed. PMID:26709907

  11. 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. PMID:26082648

  12. Experience on breast cancer with brain metastasis in Kanagawa Cancer Center

    International Nuclear Information System (INIS)

    We studied the relationship between clinicopathologic findings and effect of adjuvant therapy on brain metastasis in breast cancer in order to clarify risk factors for brain metastasis in breast cancer patients. We divided patients into a group treated up until December 1999 (Group 1) and a group treated after January 2000 (Group 2), in whom adjuvant therapy was not generalized. Estrogen receptor-negative patients and cases more advanced than T2 showed a high risk of brain metastasis. The time interval to brain metastasis in Group 1 and 2 were 25 and 49.6 months, respectively, showing a significant difference. Taxan derivatives were used in 1.6% of Group 1 and 76% of Group 2. Estrogen receptor negativity, cancer more advanced than T2, and adjuvant therapy are risk factors for brain metastasis. (author)

  13. 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.

  14. Diagnosis of benign and metastatic bone lesions on breast MRI in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Bo Bae; Hwang, Ji Young; Cha, Eun Suk [Dept. of Radiology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2014-02-15

    To differentiate between the MRI findings for benign bone lesion and metastasis detected by breast MRI in patients with breast cancer and to evaluate the conspicuity of bone lesions according to MR sequences. In 14 patients with 15 bone lesions, the MRI findings were statistically analyzed to differentiate between benign bone lesion and metastasis. We considered margin, signal intensity on T2-weighted image (T2WI) with spectral attenuated inversion recovery (SPAIR), enhancement, and patterns of bone lesions (focal mass, diffuse infiltration, and extraosseous soft tissue change), as well as the conspicuity of bone lesions in each MR sequence. There was a statistically significant difference in the frequency of a solitary focal mass pattern between benign bone lesion and metastasis (p = 0.044). The margin, signal intensity on T2WI with SPAIR, and enhancement were not significantly different between benign bone lesion and metastasis. Both T2WI with SPAIR and delayed phase of contrast enhanced MRI were superior to other sequences in terms of lesion conspicuity. A solitary focal mass pattern indicates a high probability of benign bone lesion on breast MRI in patients with breast cancer. Bone lesions tend to have greater conspicuity on T2WI with SPAIR and delayed phase image of contrast enhanced MRI, compared to results for other MR sequences.

  15. Diagnosis of benign and metastatic bone lesions on breast MRI in patients with breast cancer

    International Nuclear Information System (INIS)

    To differentiate between the MRI findings for benign bone lesion and metastasis detected by breast MRI in patients with breast cancer and to evaluate the conspicuity of bone lesions according to MR sequences. In 14 patients with 15 bone lesions, the MRI findings were statistically analyzed to differentiate between benign bone lesion and metastasis. We considered margin, signal intensity on T2-weighted image (T2WI) with spectral attenuated inversion recovery (SPAIR), enhancement, and patterns of bone lesions (focal mass, diffuse infiltration, and extraosseous soft tissue change), as well as the conspicuity of bone lesions in each MR sequence. There was a statistically significant difference in the frequency of a solitary focal mass pattern between benign bone lesion and metastasis (p = 0.044). The margin, signal intensity on T2WI with SPAIR, and enhancement were not significantly different between benign bone lesion and metastasis. Both T2WI with SPAIR and delayed phase of contrast enhanced MRI were superior to other sequences in terms of lesion conspicuity. A solitary focal mass pattern indicates a high probability of benign bone lesion on breast MRI in patients with breast cancer. Bone lesions tend to have greater conspicuity on T2WI with SPAIR and delayed phase image of contrast enhanced MRI, compared to results for other MR sequences.

  16. 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

  17. 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.

  18. Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

    International Nuclear Information System (INIS)

    Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

  19. 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)

  20. 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

  1. 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.

  2. Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin-like growth factor and hypoxia

    OpenAIRE

    Kuchimaru, Takahiro; Hoshino, Takuya; Aikawa, Tomoya; Yasuda, Hisataka; KOBAYASHI, Tatsuya; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

    2014-01-01

    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 resorp...

  3. Intussusception due to intestinal metastasis from lung cancer

    Directory of Open Access Journals (Sweden)

    Kini Sangeeta

    2010-01-01

    Full Text Available Intestinal metastasis from lung primary is very uncommon and seen at the terminal stage of the disease. Clinically, patients present as perforation or bleeding and rarely as intussusception. We report the case of a 78-year-old man who came with sudden onset of abdominal complaints of four to five days duration. A computerized tomography (CT - scan abdomen showed mural thickening of short loop of jejunum with ileoileal intussusception. Resection-anastomosis revealed two separate nodules in the small intestine. The patient, a diagnosed case of primary carcinoma of lung seven months ago, had been treated with one cycle of chemotherapy. Histopathology of the small intestinal nodules showed features of adenocarcinoma consistent with the known primary lung cancer. We present this case to arouse a clinical suspicion of intestinal metastasis in known cases of primary lung cancer presenting with the sudden onset of abdominal complaints. Early diagnosis and management improves the survival of these patients.

  4. 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

  5. 18F-NaF Positive Bone Metastases of Non 18F-FDG Avid Mucinous Gastric Cancer

    OpenAIRE

    Çiğdem Soydal; Elgin Özkan; Özlem Nuriye Küçük

    2015-01-01

    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.

  6. Diet Modulation is an Effective Complementary Agent in Preventing and Treating Breast Cancer Lung Metastasis

    OpenAIRE

    Zhao, Xiangmin; Rezonzew, Gabriel; Wang, Dezhi; Siegal, Gene P.; Hardy, Robert W.

    2014-01-01

    A significant percentage of breast cancer victims will suffer from metastases indicating that new approaches to preventing breast cancer metastasis are thus needed. Dietary stearate and chemotherapy have been shown to reduce breast cancer metastasis. We tested the complementary use of dietary stearate with a taxol-based chemotherapy which work through separate mechanisms to reduce breast cancer metastasis. We therefore carried out a prevention study in which diets were initiated prior to huma...

  7. ICTP in Bone Metastases of Lung Cancer

    OpenAIRE

    Franjević, Ana; Pavićević, Radomir; Bubanović, Gordana

    2011-01-01

    Bone metastases often appear in advanced stages of lung cancer. They are the result of modulation of bone metabolism by tumor cells that migrated into bone microenvironment and degraded bone organic matrix. Measurement of C-terminal telopeptide of type I collagen (ICTP) in the serum of subjects with lung cancer with and without bone metastases and healthy population is the way to explore bone resorption. In 343 subjects included in this research ICTP level was significantly higher...

  8. 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.

  9. Cancer of the Bone and Joint

    Science.gov (United States)

    ... a third party. HPF: SEER Stat Fact Sheets: Bone and Joint Cancer Expand All Collapse All Lifetime risk estimates are ... 5 Years Or More after Being Diagnosed with Bone and Joint Cancer? Relative survival statistics compare the survival of patients ...

  10. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer.

    Science.gov (United States)

    Wu, Buchu; Hu, Ke; Li, Shu; Zhu, Jing; Gu, Liying; Shen, Haoran; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-01-01

    Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration. PMID:22025319

  11. 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.

  12. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

    OpenAIRE

    Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste...

  13. Detection and correlation analysis of serum cytokines in non-small-cell lung cancer patients with bone and non-bone metastases

    Directory of Open Access Journals (Sweden)

    Sun Y

    2015-08-01

    Full Text Available Yingjia Sun, Xinghao Ai, Shengping Shen, Linping Gu, Shun Lu Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Objective: To detect and analyze 13 cytokines that may be related to bone metastasis in the serum of non-small-cell lung cancer (NSCLC patients with bone metastases and NSCLC patients with non-bone metastases.Patients and methods: The Luminex LiquiChip system was used to detect the concentration of 13 cytokines that may be related to bone metastasis in the serum of 30 NSCLC patients with bone metastases and 30 with non-bone metastases.Results: The concentration of insulin-like growth factor binding protein-3 (IGFBP-3 in the serum of NSCLC patients with bone metastases was obviously higher than in non-bone metastasis patients (P=0.014. The serum concentration of other cytokines showed no significant difference (P>0.05 between the two groups. The concentration of IGFBP-3 in the serum of the bone metastasis group was positively correlated to VEGF concentration (r=0.804, P=0.009 and monocyte chemotactic protein 1 (MCP-1 concentration (r=0.785, P=0.012, but had no correlation to other factors (P>0.05. No correlation was found between serum concentrations of cytokines in bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to the presence or absence of pain at diagnosis (r=0.701, P=0.036 and performance status (PS score (r=0.670, P=0.048, and correlated with the number of bone metastases, sex, age, pathological characteristics, T stage, and N stage (P>0.05.Conclusion: The findings of this study suggest important clinical implications to detect the concentration of IGFBP-3 in the serum of lung cancer patients so as to evaluate the diagnosis and degree of bone metastasis. Concentration of IGFBP-3 in the serum of bone metastasis patients was positively correlated to concentration of VEGF and MCP-1, which may be

  14. 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.

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

    International Nuclear Information System (INIS)

    The usefulness of 18F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [18F]-3-fluoro-alpha-methyl tyrosine (18F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of 18F-FAMT PET/CT to complement 18F-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 18F-FDG and 18F-FAMT PET/CT within 1 month of each other. 18F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the 18F-FAMT in the corresponding lesions were evaluated. A total of 72 18F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. 18F-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 18F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher 18F-FAMT uptake than those of adenocarcinoma. No significant difference in 18F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of 18F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that 18F-FAMT uptake was confirmed by 18F-FDG uptake suggests that 18F-FAMT PET/CT has the potential to complement 18F-FDG PET/CT for the detection of bone metastases. (orig.)

  16. 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.

  17. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  18. 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.

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

    OpenAIRE

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

    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 cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI a...

  20. Cancer treatment-related bone disease

    OpenAIRE

    Brown, Sue A.; Guise, Theresa A.

    2009-01-01

    Bone health may be impaired in many patients being treated for cancer. Primary tumors that reside in or form metastases to bone can result in compromised skeletal integrity. It has also been increasingly recognized that patients undergoing therapies for treatment of cancer are at higher risk of bone loss. These include androgen-deprivation therapy for prostate cancer and aromatase inhibitor therapy for breast cancer among others. Hypogonadism induced by many of these cancer treatments results...

  1. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies.

  2. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

  3. Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis.

    Science.gov (United States)

    Foda, H D.; Zucker, S

    2001-05-01

    Matrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer as well as in numerous other diseases. In this article, we summarize the current views on the role of MMPs in cancer with respect to invasion, metastasis and angiogenesis. A positive correlation between tumor progression and the expression of multiple MMP family members in tumor tissues has been demonstrated in numerous human and animal studies. It has been assumed that cancer cells are responsible for producing the MMPs in human tumors. However, recent evidence suggests that tumor cells have docking sites that bind stromal-cell-secreted MMPs. Furthermore, the role of MMPs produced by endothelial cells, especially MMP-2 and MT1-MMP, appear to be crucial for tumor angiogenesis, which is a requirement for cancer growth and dissemination. PMID:11344033

  4. 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

  5. Selectins mediate small cell lung cancer systemic metastasis.

    Directory of Open Access Journals (Sweden)

    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.

  6. Nomogram for overall survival of Japanese patients with bone-metastatic prostate cancer

    OpenAIRE

    Miyoshi, Yasuhide; Noguchi, Kazumi; Yanagisawa, Masahiro; Taguri, Masataka; Morita, Satoshi; Ikeda, Ichiro; Fujinami, Kiyoshi; Miura, Takeshi; Kobayashi, Kazuki; Uemura, Hiroji

    2015-01-01

    Background We analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis. Methods From 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validat...

  7. 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.

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

    Science.gov (United States)

    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.

  9. Patterns of metastasis in colon and rectal cancer.

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27416752

  10. Lineage tracing of metastasis in a mouse model for Non-small cell lung cancer (NSCLC)

    OpenAIRE

    Thakur, Chitra

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the deadliest form of lung cancer and has a poor prognosis due to its high rate of metastasis. Notably, metastasis is one of the leading causes of death among cancer patients. Despite the clinical importance, the cellular and molecular mechanisms that govern the initiation, establishment and progression of metastasis remain unclear. Moreover, knowledge gained on metastatic process was largely based on cultured or in vitro manipulated cells that were reint...

  11. 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.

  12. 核素骨显像联合肿瘤标志物检测在肺癌骨转移诊断中的价值%Evaluation of tumor marker and ECT in diagnosis of bone metastasis in lung cancer

    Institute of Scientific and Technical Information of China (English)

    段玉龙; 解洪泉; 范向辉; 赵诚; 丁朝鹏

    2009-01-01

    Objective To evaluate the value of tumor markers(CEA NSE cYFRA 21-1)and ECT in diagnosis of bone metastasis jn lung cancer.Methods Two hundred and sixty-three patients with lung cancer were examined by radionuclied bone imaging and serum CEA.NSE and CYFRA 21-1 in the sernm by ELECSYS 2010.Results The sensitivity,differential,veracity of tumor markers(CEA,NSE,CYFRA 21-1)and ECT were 88.9%(152/171),96.7%(89/92),91.6%(241/263),and it was 65.5%(112/171),87.0%(80/92),73.0%(192/263)of SPECT.It had significant difference(P<0.01)between tumor markers (CEA,NSE,CYFRA21-1) and ECT vs SPECT.Conclusions ECT and tumor markers has an important value in diagnosis of bone metastasis in lung cancer.%目的 探讨放射性核素骨显像(ECT)与肿瘤标志物CEA、NSE和CYFRA 21-1检测在肺癌骨转移诊断中的价值.方法 时263例肺癌患者进行单光子发射计算机断层仪(SPECT)全身骨显像的同时,采用罗氏电化学发光免疫系统检测其血清CEA、CYFRA21-1、NSE肿瘤标志物水平.结果 ECT联合CEA+NSE+CYFRA21-1检测和ECT诊断肺癌骨转移的敏感性、特异性、准确性分别为88.9%(152/171)和65.5%(112/171)、96.7%(89/92)和87.0%(80/92)、91.6%(241/263)和73.0%(192/263),ECT联合CEA+NSE+CYFRA 21-1检测优于单独SPECT检查(P<0.01).结论 核素骨显像与肿瘤标志物联合检测在肺癌骨转移诊断中有较高临床价值.

  13. 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.

  14. 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.

  15. CSR1 suppresses tumor growth and metastasis of prostate cancer.

    Science.gov (United States)

    Yu, Guoying; Tseng, George C; Yu, Yan Ping; Gavel, Tim; Nelson, Joel; Wells, Alan; Michalopoulos, George; Kokkinakis, Demetrius; Luo, Jian-Hua

    2006-02-01

    Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a two- to threefold decrease in colony formation and a 10-fold reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had an average threefold decrease in their ability to invade in vitro. Expression of CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The present findings suggest that CSR1 is a potent tumor sup-pressor gene. PMID:16436673

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  19. The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

    International Nuclear Information System (INIS)

    The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes

  20. Breast Cancer-derived Dickkopf1 Inhibits Osteoblast Differentiation and Osteoprotegerin Expression: Implication for Breast Cancer Osteolytic Bone Metastases

    OpenAIRE

    Bu, Guojun; Lu, Wenyan; Liu, Chia-Chen; Selander, Katri; Yoneda, Toshiyuki; Hall, Christopher; Evan T. Keller; Li, Yonghe

    2008-01-01

    Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/β-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/β-catenin antagonist. In the present study, we demonstrated that activation of Wnt/β-catenin signaling enhanced Dkk1 expression i...

  1. The clinical value of SPECT/CT fusion imaging in the diagnosis of bone metastasis of breast cancer%乳腺癌患者骨病灶SPECT/CT融合显像的临床价值

    Institute of Scientific and Technical Information of China (English)

    樊孝廉; 鲁胜男; 古炎发; 张爱芳

    2013-01-01

    Objective To evaluate the clinical value of SPECT/CT fusion imaging in the diagnosis and differential diagnosis the characteristic of the whole body bone scan radioactive hot lesions in patients with breast cancer.Methods The abnormal radioactive hot lesions of whole body bone scan in 25 patients with breast cancer underwent SPECT/CT fusion imaging immediately.Another whole body bone scan and SPECT/CT fusion imaging were carried out 4 to 8 months later in all these patients.The whole body bone scan images,SPECT/CT images and fusion images were analyzed independently by two experienced nuclear medicine physicians and some of the equivocal CT images were analyzed by an experienced radiologist.Results Among all the 37 abnormal radioactive hot bone lesions,29 (29/37,78.38%) lesions were confirmed metastatic lesions,including 2 vertebral lesions classified as benign lesions on the basis of the first examinations data; and 8 lesions were benign,including a rib lesion classified as benign lesion according to the first examinations data.The difference between whole body bone scan and SPECT/CT examination was statistically significant (x2=6.975,P<0.05).The bone metastases are located mainly in spine and ribs.The sensitivity,specificity,positive and negative predictive values,and accuracy of whole-body bone scan and SPECT/CT fusion imaging were 82.76%,75.00%,92.31%,54.55%,81.08% and 93.10%,87.50%,96.43%,77.78%,91.89%,respectively.The area under the receiver operating characteristics curve was 0.860±0.056for whole body bone scan and 0.974±0.020 for SPECT/CT.The area under the curve for SPECT/CT was significantly larger compared with the whole body bone scan (x2=9.924,P<0.001).Conclusions SPECT/CT fusion imaging is better than whole body bone scan alone to characterize the abnormal bone radioactive hot lesions and it can improve the accuracy of diagnosis.The patients should repeat the modality 4 to 8 months later if necessary.%目的 探讨SPECT/CT

  2. Preliminary clinical study of 99Tcm-HL91 imaging in bone metastasis

    International Nuclear Information System (INIS)

    Objective: 99Tcm-4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime (HL91), a new type of hypoxic agents, accumulates in tumor hypoxic tissue specifically. The aim of this study was to evaluate the value of 99Tcm-HL91 imaging in the diagnosis of bone metastasis. Methods: Nine- teen cases with bone metastasis (without any treatment) and 8 cases with benign lesions underwent SPECT imaging at 4 h after injection of 740 MBq of 99Tcm-HL91 along with 99Tcm-methylene diphosphonic acid (MDP) imaging. Regions of interest (ROIs) were drawn in tumor tissue and contralateral normal tissue respectively, and the radioactivity ratios of tumor-to-normal (T/N) were calculated. The t-test was used for data analysis with SPSS 11.0. Results: There were visible uptake of 99Tcm-HL91 in 79 out of 85 focuses in 19 patients of bone metastasis; however, there was no obvious uptake of 99Tcm-HL91 in 12 focuses of 8 patients of benign lesions. Significant difference existed between the T/N values of malignant (1.877 ± 0.288) and benign lesions [(0.735 ± 0.236); t=13.065, P0.05). Conclusion: The results indicated that 99Tcm-HL91 was useful in diagnosing the malignant and benign bone lesions. (authors)

  3. An Unusual Case of Gastric Cancer Presenting with Breast Metastasis with Pleomorphic Microcalcifications

    Science.gov (United States)

    Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai

    2012-01-01

    Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatment. PMID:23091550

  4. An Unusual Case of Gastric Cancer Presenting with Breast Metastasis with Pleomorphic Microcalcifications

    OpenAIRE

    Luk, Yiu Shiobhon; Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai

    2012-01-01

    Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatm...

  5. Do we need to redefine a cancer metastasis and staging definitions?

    OpenAIRE

    Welch, Danny R.

    2006-01-01

    Metastasis is the most lethal attribute of cancer cells and clinical decisions regarding treatment are based largely upon the likelihood of developing metastases. However, improvements in detection as well as recent experimental data have raised questions about the most appropriate definition of a metastasis, especially whether the mere presence of cells at secondary sites constitute a metastatic lesion. After reviewing the experimental basis of metastasis, a definition of metastasis is proff...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. Cancer to bone: a fatal attraction

    OpenAIRE

    Weilbaecher, Katherine N.; Guise, Theresa A.; McCauley, Laurie K

    2011-01-01

    When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and...

  9. Prostate Cancer and Bone: The Elective Affinities

    OpenAIRE

    Nadia Rucci; Adriano Angelucci

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing c...

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

    DEFF Research Database (Denmark)

    Cox, Thomas R; Rumney, Robin M H; Schoof, Erwin M;

    2015-01-01

    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......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...

  11. Ovarian Metastasis from Lung Cancer: A Rare Entity

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    Science.gov (United States)

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

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

    Directory of Open Access Journals (Sweden)

    Tobias Bäuerle

    2008-05-01

    Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

  15. 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

    2016-01-01

    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 hypoxia1. Tumour-secreted proteins play a crucial role in these interactions2–5 and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable6. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality6,7. 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 ER-negative breast cancer patients. 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 colonise 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. PMID:26017313

  16. A role for collagen XXIII in cancer cell adhesion, anchorage-independence, and metastasis

    OpenAIRE

    Spivey, Kristin A.; Chung, Ivy; Banyard, Jacqueline; Adini, Irit; Feldman, Henry A.; Bruce R Zetter

    2011-01-01

    Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer that has been used as a tissue and fluid biomarker for non-small cell lung cancer and prostate cancer. To determine whether collagen XXIII facilitates cancer cell metastasis in vivo and to establish a function for collagen XXIII in cancer progression, collagen XXIII knockdown cells were examined for alterations in in vivo metastasis as well as in vitro cell adhesion. In experimental and...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. Tumor markers and bone scan in breast cancer patients

    International Nuclear Information System (INIS)

    Full text: The objective of this study was to compare the levels of CA15-3 and CEA with the bone scan findings in patients with breast cancer. Retrospective analysis of 76 bone scans from 61 patients diagnosed with breast cancer in the last 5 years was performed by two nuclear medicine specialists. All bone scans were performed after surgical treatment of the disease. Patients with loco-regional residual disease or distant metastases in the liver, lung or the brain were excluded from the study. According to the bone scan the patients were divided in 5 groups: normal bone scan (N), equivocal bone scan (E), single metastasis (1MS), three metastases (3MS) and multiple metastases (MMS). Tumor markers were determined within a month before or after the bone scan was performed. Cut-off value for CA 15-3 was 35 U/ml, and for CEA 3 ng/ml. Statistical analysis was performed using descriptive statistic and Kolmogorov-Smirnov test. Bone metastases were revealed in 38% of the patients referred for bone scintigraphy out of which 26% had MMS, 7.8% had single MS and 4% had 3MS. The results of 6.5% of the patients were determined as equivocal. The values of CA15-3 were higher in all patient groups compared with the group that had normal bone scan, but this difference reached statistical significance only in groups with 3MS and MMS (p < 0.01). The values of CEA were significantly higher only in patients with multiple metastases when compared with group N (p < 0.01). Values higher than cut-off value for CA 15-3 was found in 9 patients out of 42 in the group with normal bone scan. The highest value of CA 15-3 in this group was 47 U/ml. Only one patient in this group showed elevated levels for CEA. Three patients in the group with single metastasis had normal CA 15-3, while CEA was elevated only in one patient. All patients in the group with 3MS had elevated levels of CA 15-3 while CEA was in the normal range. All patients with MMS had elevated CA 15-3 values while CEA was elevated in

  2. Bladder cancer will grow anywhere: report of a urothelial carcinoma drop metastasis to the vagina and literature review.

    Science.gov (United States)

    Uhlman, Matthew A; Bevill, Mark D; Goodheart, Michael J; Brown, James A; O'Donnell, Michael A

    2016-08-01

    Urothelial carcinoma is the 2nd most common cancer of the urinary tract and accounts for the majority of cases of bladder cancer. Metastases are not infrequently encountered, increasing with disease stage and are most commonly seen in the bones and lungs. Many other sites have been described including the omentum, liver, and ovaries. An extremely rare site of metastatic disease however is within the vagina. Here we present a case of a probable vaginal 'drop metastasis' from previously treated urothelial carcinoma in the ureter and bladder. PMID:27544563

  3. 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.

  4. Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases.

    Science.gov (United States)

    Watanabe, Kenta; Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Maruyama, Takayuki; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato; Inada, Masaki

    2016-09-01

    The metastasis of tumors to bone is known to be promoted by prostaglandin E2 (PGE2) produced by the tumor host stromal tissue. Although bone metastases frequently occur in prostate cancer patients, the significance of PGE2 in stromal responses to the tumor is not known. In this study, we report that PGE2 and its receptor EP4 play a pivotal role in bone destruction and metastasis in an experimental metastasis model of prostate cancer in nude mice. Using human prostate cancer PC-3 cells that are stably transfected with luciferase, we showed that the development of bone metastasis was accompanied by increased osteoclastic bone resorption in the bone metastasis microenvironment, and could be abrogated by an EP4 receptor antagonist. The growth of PC-3 cells in vitro was not influenced by PGE2 or by the EP4 receptor. However, cell-cell interactions between fixed PC-3 cells and host osteoblasts induced PGE2 production and RANKL expression in the osteoblasts. Addition of an EP4 antagonist suppressed both PGE2 and RANKL expression induced by the PC3-osteoblast interaction, which would have consequent effects on osteoclast activation and osteolysis. These results indicate that the blockage of PGE2-EP4 signaling prevents the bone destruction required for prostate cancer metastases, and that this is, in part due to the abrogation of bone cell responses. The study provides further evidence that an EP4 antagonist is a candidate for the treatment of prostate cancer in the blockade of bone metastasis. PMID:27450806

  5. Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer

    OpenAIRE

    Samardzija, Chantel; Luwor, Rodney B.; Quinn, Michael A; Kannourakis, George; Jock K Findlay; Ahmed, Nuzhat

    2016-01-01

    Background Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer meta...

  6. 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

  7. 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

  8. A Digital Squamous Cell Carcinoma Mimicking a Diabetic Foot Ulcer, With Early Inguinal Metastasis and Cancer-Related Lymphedema.

    Science.gov (United States)

    Park, Hyun Chul; Kwon, Hyoung Il; Kim, Hyun Woo; Kim, Jeong Eun; Ro, Young Suck; Ko, Joo Yeon

    2016-02-01

    Although squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer, clinicians have difficulty diagnosing SCC of the toe because its clinical features can mimic other less serious diseases. Clinicians are especially prone to misdiagnose SCC of the toe as diabetic foot ulcer in patients with diabetes mellitus because of the clinical similarity of the 2 ailments. SCC of the toe is generally considered to have a low risk of metastasis. Locoregional or distant metastases without bone or tendon involvement are particularly rare. The authors report here an interesting case of rapidly spreading SCC of the toe with metastasis to multiple lymph nodes and cancer-related lymphedema. Physicians should be aware of the possibility of malignancy when they encounter chronic and recalcitrant ulcerative lesions of the digits. PMID:26825165

  9. 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.)

  10. 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.

  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. 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.

  13. Host b7x promotes pulmonary metastasis of breast cancer.

    Science.gov (United States)

    Abadi, Yael M; Jeon, Hyungjun; Ohaegbulam, Kim C; Scandiuzzi, Lisa; Ghosh, Kaya; Hofmeyer, Kimberly A; Lee, Jun Sik; Ray, Anjana; Gravekamp, Claudia; Zang, Xingxing

    2013-04-01

    B7x (B7-H4 or B7S1) is an inhibitory member of the B7 family of T cell costimulation. It is expressed in low levels in healthy peripheral tissues, such as the lung epithelium, but is overexpressed in a variety of human cancers with negative clinical associations, including metastasis. However, the function of B7x in the context of cancer, whether expressed on cancer cells or on surrounding "host" tissues, has not been elucidated in vivo. We used the 4T1 metastatic breast cancer model and B7x knockout (B7x (-/-)) mice to investigate the effect of host tissue-expressed B7x on cancer. We found that 4T1 cells were B7x negative in vitro and in vivo, and B7x(-/-) mice had significantly fewer lung 4T1 tumor nodules than did wild-type mice. Furthermore, B7x(-/-) mice showed significantly enhanced survival and a memory response to tumor rechallenge. Mechanistic studies revealed that the presence of B7x correlated with reduced general and tumor-specific T cell cytokine responses, as well as with an increased infiltration of immunosuppressive cells, including tumor-associated neutrophils, macrophages, and regulatory T cells, into tumor-bearing lungs. Importantly, tumor-associated neutrophils strongly bound B7x protein and inhibited the proliferation of both CD4 and CD8 T cells. These results suggest that host B7x may enable metastasizing cancer cells to escape local antitumor immune responses through interactions with the innate and adaptive immune systems. Thus, targeting the B7x pathway holds much promise for improving the efficacy of immunotherapy for metastatic cancer. PMID:23455497

  14. 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 ...

  15. MicroRNAs in the control of metastatic bone disease

    OpenAIRE

    Browne, Gillian; Taipaleenmäki, Hanna; Stein, Gary S.; Stein, Janet L.; Lian, Jane B.

    2014-01-01

    Bone metastasis is a common and devastating complication of late stage breast and prostate cancer. Complex interactions between tumor cells, bone cells and a milieu of components in their microenvironment contribute to the osteolytic, osteoblastic or mixed lesions present in patients with metastasis to bone. In the last decade, miRNAs have emerged as key players in cancer progression yet the importance of miRNAs in regulating cancer metastasis to bone is now being appreciated. Here, we emphas...

  16. Pharmacologic inhibitors of IkappaB kinase suppress growth and migration of mammary carcinosarcoma cells in vitro and prevent osteolytic bone metastasis in vivo.

    Science.gov (United States)

    Idris, Aymen I; Libouban, Hélène; Nyangoga, Hervé; Landao-Bassonga, Euphemie; Chappard, Daniel; Ralston, Stuart H

    2009-08-01

    The NF-kappaB signaling pathway is known to play an important role in the regulation of osteoclastic bone resorption and cancer cell growth. Previous studies have shown that genetic inactivation of IkappaB kinase (IKK), a key component of NF-kappaB signaling, inhibits osteoclastogenesis, but the effects of pharmacologic IKK inhibitors on osteolytic bone metastasis are unknown. Here, we studied the effects of the IKK inhibitors celastrol, BMS-345541, parthenolide, and wedelolactone on the proliferation and migration of W256 cells in vitro and osteolytic bone destruction in vivo. All compounds tested inhibited the growth and induced apoptosis of W256 cells as evidenced by caspase-3 activation and nuclear morphology. Celastrol, BMS-345541, and parthenolide abolished IL1beta and tumor necrosis factor alpha-induced IkappaB phosphorylation and prevented nuclear translocation of NF-kappaB and DNA binding. Celastrol and parthenolide but not BMS-345541 prevented the activation of both IKKalpha and IKKbeta, and celastrol inhibited IKKalpha/beta activation by preventing the phosphorylation of TAK1, a key receptor-associated factor upstream of IKK. Celastrol and parthenolide markedly reduced the mRNA expression of matrix metalloproteinase 9 and urinary plasminogen activator, and inhibited W256 migration. Administration of celastrol or parthenolide at a dose of 1 mg/kg/day suppressed trabecular bone loss and reduced the number and size of osteolytic bone lesions following W256 injection in rats. Histomorphometric analysis showed that both compounds decreased osteoclast number and inhibited bone resorption. In conclusion, pharmacologic inhibitors of IKK are effective in preventing osteolytic bone metastasis in this model and might represent a promising class of agents to the prevention and treatment of metastatic bone disease associated with breast cancer. PMID:19671767

  17. MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis

    OpenAIRE

    Chan, S-H; Huang, W-C; Chang, J-W; Chang, K-J; Kuo, W-H; Wang, M-Y; Lin, K-Y; Uen, Y-H; Hou, M-F; Lin, C-M; Jang, T-H; Tu, C-W; Lee, Y-R; Lee, Y-H; Tien, M-T

    2014-01-01

    Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT...

  18. Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner

    Science.gov (United States)

    Volk-Draper, Lisa; Hall, Kelly; Griggs, Caitlin; Rajput, Sandeep; Kohio, Pascaline; DeNardo, David; Ran, Sophia

    2014-01-01

    Emerging evidence suggests that cytotoxic therapy may actually promote drug resistance and metastasis while inhibiting the growth of primary tumors. Work in preclinical models of breast cancer have shown that acquired chemoresistance to the widely used drug paclitaxel (PXL) can be mediated by activation of the Toll-like receptor TLR4 in cancer cells. In this study, we determined the pro-metastatic effects of tumor-expressed TLR4 and PXL therapy and we investigated the mechanisms mediating these effects. While PXL treatment was largely efficacious in inhibiting TLR4-negative tumors, it significantly increased the incidence and burden of pulmonary and lymphatic metastasis by TLR4-positive tumors. TLR4 activation by PXL strongly increased the expression of inflammatory mediators, not only locally in the primary tumor microenvironment but also systemically in the blood, lymph nodes, spleen, bone marrow and lungs. These pro-inflammatory changes promoted the outgrowth of Ly6C+ and Ly6G+ myeloid progenitor cells and their mobilization to tumors, where they increased blood vessel formation but not invasion of these vessels. In contrast, PXL-mediated activation of TLR4-positive tumors induced de novo generation of deep intratumoral lymphatic vessels that were highly permissive to invasion by malignant cells. These results suggest that PXL therapy of patients with TLR4-expressing tumors may activate systemic inflammatory circuits that promote angiogenesis, lymphangiogenesis and metastasis, both at local sites and premetastatic niches where invasion occurs in distal organs. Taken together, our findings suggest that efforts to target TLR4 on tumor cells may simultaneously quell local and systemic inflammatory pathways that promote malignant progression, with implications for how to prevent tumor recurrence and the establishment of metastatic lesions, either during chemotherapy or after it is completed. PMID:25274031

  19. Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells.

    Science.gov (United States)

    Liu, Bo; Cui, Jian; Sun, Jing; Li, Juan; Han, Xiuchun; Guo, Jie; Yi, Min; Amizuka, Norio; Xu, Xin; Li, Minqi

    2016-08-01

    The aim of the present study was to investigate the expression of matrix metalloproteinase (MMP)9 and MMP2, and their potential roles in bone metastasis nests using a well-standardized model of breast cancer bone metastasis in nude mice. BALB/c nu/nu mice (5-week-old; n=10) were subjected to intracardiac injection of MDA-MB-231 human breast cancer cells. After 4 weeks, the mice exhibiting radiolucent lesions in tibiae were sacrificed, and the tibiae were removed for histochemical analysis. The gene expression of MMP2 and MMP9 in the tumor cells, metaphysis and diaphysis of normal BALB/c nu/nu mice were determined using reverse transcription-polymerase chain reaction analysis. The metastatic tumor tissue occupied almost the entire bone marrow cavity. Numerous tartrate-resistant acid phosphatase-positive osteoclasts were found in the metastasized lesions. The invaded tumor cells positive for mammaglobin 1 exhibited different proliferation activities and apoptosis between the metaphysis and diaphysis. Proliferating cell nuclear antigen was expressed at high levels in the metaphyseal area, whereas TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were more evident in the diaphysis area. Of note, MMP9 was expressed predominantly in the proliferating cell nuclear antigen‑positive area, whereas the expression of MMP2 was observed predominantly in the diaphysis, which had more TUNEL‑positive cells. Taken together, the results suggested that MMP9 and MMP2 may have their own importance in extracellular matrix degradation and trabecular bone damage in different zones of bone metastasis, including the metaphysis and diaphysis. PMID:27278284

  20. 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

  1. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

    Science.gov (United States)

    Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub

    2016-01-01

    Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.

  2. Sur8 mediates tumorigenesis and metastasis in colorectal cancer

    Science.gov (United States)

    Lee, Young-Mi; Kaduwal, Saluja; Lee, Kug Hwa; Park, Jong-Chan; Jeong, Woo-Jeong; Choi, Kang-Yell

    2016-01-01

    Sur8, a scaffold protein of the Ras pathway, interacts with Ras and Raf and modulates the Ras-extracellular signal-regulated kinase (ERK) pathway. Here we show that Sur8 is overexpressed in established human colorectal cancer (CRC) cell lines and CRC patient tissues. Moreover, Sur8 expression is increased during liver metastasis in CRC patients. Sur8 knockdown decreases ERK and Akt activities in CRC cell lines, regardless of their K-Ras, B-Raf or PI3K mutation status. Overexpression or knockdown of Sur8 increases or decreases, respectively, the proliferation or transformation of CRC cell lines. Sur8 knockdown attenuates the migration and invasion of HCT116 CRC cells. Subcutaneous or orthotopic injection of HCT116 cells harboring a doxycycline (Dox)-mediated Sur8 knockdown system in nude mice resulted in decreased tumorigenic potential and inhibited the liver metastatic potential of HCT116 cells. Taken together, our data support the role of Sur8 as a promoter of tumorigenesis and liver metastasis in CRC through its modulation of the Ras-ERK and PI3K-Akt signaling pathways. PMID:27469030

  3. 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.

  4. 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.

  5. Clinical Effect of Xeloda Combined with Zoledronic Acid on Treatment of Multiple Bone Metastasis of Breast Cancer%希罗达和唑来膦酸联合治疗乳腺癌多发骨转移的临床效果研究

    Institute of Scientific and Technical Information of China (English)

    闫睿

    2015-01-01

    Objective:To study and analyze the clinical effect of Xeloda combined with zoledronic acid on treatment of multiple bone metastasis of breast cancer.Method: 40 breast cancer patients with multiple bone metastases in our hospital were selected from December 1, 2011 to December 1,2014 ,they were randomly divided into combined treatment group and single drug group by using random number table method, 20 cases in each group.Single drug group was given capecitabine, combination treatment group was given intravenous zoledronic acid on the base of control group, two groups curative effect were recorded.Result:The analgesic effective rate of combination treatment group was 85.00% obvious higher than single drug group of 55.00%; bone metastasis therapy effective rate of combination treatment group was 65.00% obvious than single drug group of 35.00%, the differences were statistically significant (P<0.05).Conclusion:The clinical effect of Xeloda combined with zoledronic acid has obvious effect on treatment of breast cancer multiple bone metastases,it is worthy of promotion.%目的:研究分析希罗达和唑来磷酸联合治疗乳腺癌多发骨转移的临床效果。方法:选取2011年12月1日-2014年12月1日经本院诊断并治疗的乳腺癌多发骨转移患者40例,采用随机数字表法将患者分为联合用药组和单一用药组,每组各20例。单一用药组给予希罗达,联合用药组在单一用药组的基础上给予静脉注射唑来磷酸治疗,分别记录两组患者治疗后的效果。结果:根据分析可得出联合用药组止痛有效率为85.00%,单一用药组止痛有效率为55.00%,联合用药组有效率明显高于单一用药组;且联合用药组骨转移灶治疗总有效率为65.00%明显高于单一用药组的35.00%,两组比较差异均有统计学意义(P<0.05)。结论:希罗达和唑来磷酸联合治疗乳腺癌多发骨转移效果好,安全性高,可以及时缓解疾病对患者造

  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. Prediction of gastric cancer metastasis through urinary metabolomic investigation using GC/MS

    Institute of Scientific and Technical Information of China (English)

    Jun-Duo Hu; Hui-Qing Tang; Qiang Zhang; Jing Fan; Jing Hong; Jian-Zhong Gu; Jin-Lian Chen

    2011-01-01

    AIM: To gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic values to predict tumor metastasis.METHODS: Human gastric cancer SGC-7901 cells were implanted into 24 severe combined immune deficiency (SCID) mice, which were randomly divided into metastasis group (n = 8), non-metastasis group (n = 8), and normal group (n = 8). Urinary metabolomic information was obtained by gas chromatography/mass spectrometry (GC/MS).RESULTS: There were significant metabolic differences among the three groups (t test, P < 0.05). Ten selected metabolites were different between normal and cancer groups (non-metastasis and metastasis groups), and seven metabolites were also different between non-metastasis and metastasis groups. Two diagnostic models for gastric cancer and metastasis were constructed respectively by the principal component analysis (PCA). These PCA models were confirmed by corresponding receiver operating characteristic analysis (area under the curve = 1.00).CONCLUSION: The urinary metabolomic profile is different,and the selected metabolites might be instructive to clinical diagnosis or screening metastasis for gastric cancer.

  8. Impact of Bone-Targeted Treatments on Skeletal Morbidity and Survival in Breast Cancer.

    Science.gov (United States)

    Coleman, Robert E

    2016-08-01

    Bone health is of increasing clinical importance throughout the clinical course of breast cancer. First, many breast cancer treatments have effects on reproductive hormones that are critical for bone health. This endocrine disturbance results in accelerated bone loss and an increased risk of fractures that can have a significant negative impact on cancer survivors. Second, the bone marrow microenvironment is intimately involved in the metastatic processes required for cancer dissemination, and may be modified by agents that influence bone cell physiology; there is now strong clinical trial evidence that the use of adjuvant bisphosphonates reduces metastasis to bone by one-third and reduces breast cancer mortality by one-sixth in postmenopausal or premenopausal women undergoing ovarian function suppression. Finally, bone metastases are common in advanced breast cancer, and may be associated with serious morbidity, including fractures, pain, nerve compression, and hypercalcemia. Through optimum multidisciplinary management and the use of bone-targeted treatments such as bisphosphonates or denosumab, patients with advanced breast cancer have experienced a major reduction in skeletal complications, less bone pain, and an improved quality of life. PMID:27528238

  9. The Microenvironment Matters: Estrogen Deficiency Fuels Cancer Bone Metastases

    OpenAIRE

    Wright, Laura E; Guise, Theresa A.

    2014-01-01

    Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth and a bone-resorptive phenotype in cancer cells. Post-menopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anti-cancer benefit of the bone-specific anti-resorptive agent zoledronic acid in the post-menopausal setting.

  10. 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.

  11. Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

    DEFF Research Database (Denmark)

    Schoof, Erwin; Erler, Janine

    cancer networks using Network Biology. Technologies key to this, such as Mass Spectrometry (MS), Next-Generation Sequencing (NGS) and High-Content Screening (HCS) are briefly described. In Chapter II, we cover how signaling networks and mutational data can be modeled in order to gain a better...... number of biological aspects that would need to be understood to enable comprehensive treatment regimens specific to each patient (i.e. personalized medicine). However, in the approaches outlined in this thesis, we chose metastasis as a key process for interrogating the clinical potential of targeting...... can be generated using MS, and how this can be modeled using a computational framework for deciphering kinase-substrate dynamics. This framework is described in depth in Article 3, and covers the design of KinomeXplorer, which allows the prediction of kinases responsible for modulating observed...

  12. Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis.

    Science.gov (United States)

    Vadrevu, Surya Kumari; Sharma, Sharad; Chintala, Navin; Patel, Jalpa; Karbowniczek, Magdalena; Markiewski, Maciej

    2016-01-01

    This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer metastasis. The 4T1 cells expressing GFP in combination with imaging and confocal microscopy are used to monitor tumor growth, track metastasizing tumor cells, and quantify the metastatic burden. These approaches are supplemented by digital histopathology that allows the automated and unbiased quantification of metastases. In this method the routinely prepared histological lung sections, which are stained with hematoxylin and eosin, are scanned and converted to the digital slides that are then analyzed by the self-trained pattern recognition software. In addition, we describe the flow cytometry approaches with the use of multiple cell surface markers to identify alveolar macrophages in the lungs. To determine impact of alveolar macrophages on metastases and antitumor immunity these cells are depleted with the clodronate-containing liposomes administrated intranasally to tumor-bearing mice. This approach leads to the specific and efficient depletion of this cell population as confirmed by flow cytometry. Tumor volumes and lung metastases are evaluated in mice depleted of alveolar macrophages, to determine the role of these cells in the metastatic progression of breast cancer. PMID:27403530

  13. 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 ...

  14. Aerosol delivery of small hairpin osteopontin blocks pulmonary metastasis of breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Kyeong-Nam Yu

    Full Text Available BACKGROUND: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed. METHODOLOGY/PRINCIPAL FINDING: Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model. CONCLUSION/SIGNIFICANCE: Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

  15. Distant metastasis from oral cancer: A review and molecular biologic aspects.

    Science.gov (United States)

    Irani, Soussan

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been estimated to be the sixth most common cancer worldwide. The distant metastasis plays a critical role in the management and prognosis in oral cancer patients. Regarding the distant metastasis from the oral cancer, the hypopharynx is the most common primary site, followed by the base of tongue and anterior tongue. The present review article analyzes the characteristics of the distant metastases from the oral cavity from 1937 to 2015. PMID:27583211

  16. Impact of tumor chronology and tumor biology on lymph node metastasis in breast cancer

    OpenAIRE

    Smeets, Ann; Ryckx, Andries; Belmans, Ann; Wildiers, Hans; Neven, Patrick; Floris, Giuseppe; Schöffski, Patrick; Christiaens, Marie-Rose

    2013-01-01

    Synopsis The significance of nodal metastasis in breast cancer is under discussion. We investigated the impact of variables of tumor chronology and tumor biology on the presence of lymph node metastases. Purpose Lymph node involvement is the main prognostic factor in breast cancer. However, it is under discussion whether nodal metastasis in breast cancer only reflects the chronological age of the tumor or whether it is also a marker of tumor biology. The goal of our study was to investigate t...

  17. Distant metastasis from oral cancer: A review and molecular biologic aspects

    Science.gov (United States)

    Irani, Soussan

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been estimated to be the sixth most common cancer worldwide. The distant metastasis plays a critical role in the management and prognosis in oral cancer patients. Regarding the distant metastasis from the oral cancer, the hypopharynx is the most common primary site, followed by the base of tongue and anterior tongue. The present review article analyzes the characteristics of the distant metastases from the oral cavity from 1937 to 2015.

  18. 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

  19. 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. PMID:26902691

  20. 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.

  1. 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.

  2. 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.

  3. 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...... 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......, 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...

  4. Myc Is a Metastasis Gene for Non-Small-Cell Lung Cancer

    OpenAIRE

    Rapp, U R; Korn, C.; Ceteci, F.; Karreman, C; Luetkenhaus, K.; Serafin, V; Zanucco, E.; Castro, I.; Potapenko, T.

    2009-01-01

    Background Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. Methodology/Principal Findings Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c...

  5. Serum CA125 is a novel predictive marker for pancreatic cancer metastasis and correlates with the metastasis-associated burden

    OpenAIRE

    Liu, Liang; Xu, Hua-Xiang; Wang, Wen-Quan; Wu, Chun-tao; Xiang, Jin-Feng; Liu, Chen; Long, Jiang; Xu, Jin; Fu, De-Liang; Ni, Quan-Xing; Houchen, Courtney W.; Postier, Russell G.; Li, Min; Yu, Xian-Jun

    2016-01-01

    This study evaluated potential of serum tumor markers to predict the incidence and intensity of pancreatic cancer metastasis as well as patient survival. Retrospective records from 905 patients and prospective data from 142 patients were collected from two high-volume institutions. The levels of eight serum tumor markers (CA19-9, CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) commonly used in gastroenterological cancer were analyzed in all stages of pancreatic cancer. Serum CA125 levels wer...

  6. A solitary pleural metastasis of benign giant cell tumor of bone

    Science.gov (United States)

    Mitsui, Ai; Doi, Masatomo; Hoshikawa, Masahiro; Hayashi, Akinobu; Nakamura, Haruhiko

    2016-01-01

    Abstract Giant cell tumor of bone (GCTB) usually appears as a benign tumor. We describe an extremely rare case of a metastatic pleural tumor arising from a benign GCTB. The patient had undergone radial resection of a GCTB in his left wrist. After 6 years, he was sent to us for diagnosis of a large mass detected upon routine radiographic screening. We resected the tumor, which was found to be a solitary pleural metastasis of GCTB and had evidently spread arterially. To our knowledge, this is the first report of its kind.

  7. 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.

  8. Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases

    Directory of Open Access Journals (Sweden)

    Moses O. Oyewumi

    2014-01-01

    Full Text Available Lung cancer is the second most common cancer and the leading cause of cancer related mortality in both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. It is widely accepted that tumor metastasis is a formidable barrier to effective treatment of lung cancer. The bone is one of the frequent metastatic sites for lung cancer occurring in a large number of patients. Bone metastases can cause a wide range of symptoms that could impair quality of life of lung cancer patients and shorten their survival. We strongly believe that molecular targets (tumor-related and bone microenvironment based that have been implicated in lung cancer bone metastases hold great promise in lung cancer therapeutics. Thus, this paper discusses some of the emerging molecular targets that have provided insights into the cascade of metastases in lung cancer with the focus on bone invasion. It is anticipated that the information gathered might be useful in future efforts of optimizing lung cancer treatment strategies.

  9. SPECT/CT fusion imaging for differential diagnosis of bone solitary metastases in patients with lung cancer

    International Nuclear Information System (INIS)

    Background: Making an accurate diagnosis of bone metastasis earlier is very important for lung cancer clinical stage and making treatment plans. SPECT/CT fusion imaging provides more information than SPECT in diagnosing bone metastases from benign lesions of the solitary abnormal radioactive nuclide distribution in patients with lung cancer. Purpose: We want to investigate the value of SPECT/CT fusion imaging in identifying solitary bone metastases in patients with lung cancer. Methods: 196 patients with lung cancer, whose bone scintigraphy demonstrated solitary abnormal radioactive nuclide distribution, were selected. SPECT/CT was employed for those lesions. SPECT and SPECT/CT bone images were analyzed by two seasoned nuclear medicine physicians separately. Each lesion was diagnosed with metastasis and benign lesion, The diagnosed results were compared with the final diagnosis. Results: 196 patients with lung cancer had 196 lesions, 112 bone metastatic lesions were proved to be bone metastatic criterion, 89 metastatic lesions were found by SPECT, and 106 metastatic lesions were found by SPECT/CT. The sensitivity, specificity and accuracy of SPECT/CT and SPECT in the diagnosis of bone metastasis were 94.6% (106/112), 92.9% (78/84), 93.9% (184/196); 79.5% (89/112), 78.6% (78/84) and 79.1% (155/196), respectively. The sensitivity, specificity and accuracy of SPECT/CT were higher than those of SPECT (χ2=11.25, P<0.05; χ2=7.00, P<0.05; χ2=18.35, P<0.05). Conclusions: SPECT/CT fusion imaging provided more information than SPECT imaging in distinguishing metastases from benign lesions of the solitary abnormal radioactive nuclide distribution in patients with lung cancer and improved the accuracy of the diagnosis of solitary bone metastasis of lung cancer. (authors)

  10. Tpl2 induces castration resistant prostate cancer progression and metastasis.

    Science.gov (United States)

    Lee, Hye Won; Cho, Hyun Jung; Lee, Se Jeong; Song, Hye Jin; Cho, Hee Jin; Park, Min Chul; Seol, Ho Jun; Lee, Jung-Il; Kim, Sunghoon; Lee, Hyun Moo; Choi, Han Yong; Nam, Do-Hyun; Joo, Kyeung Min

    2015-05-01

    Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC. PMID:25274482

  11. 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