WorldWideScience

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. 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...

  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. 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

  10. 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.

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

    International Nuclear Information System (INIS)

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

  12. Crosstalk between cancer cells and bone microenvironment in bone metastasis

    International Nuclear Information System (INIS)

    Bone, as well as lung and liver, is one of the most preferential metastatic target sites for cancers including breast, prostate, and lung cancers. Although the precise molecular mechanisms underlying this preference need to be elucidated, it appears that bone microenvironments possess unique biological features that enable circulating cancer cells to home, survive and proliferate, and destroy bone. In conjunction, cancers that develop bone metastases likely have the capacity to utilize these unique bone environments for colonization and bone destruction. This crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for bone metastases

  13. Pubic bone metastasis as first manifestation of lung cancer:

    OpenAIRE

    HOMMA, SHINSUKE; KODAMA, TAKAHIDE; SATOH, HIROAKI; Sekizawa, Kiyohisa; Ueno, Takahiro

    2003-01-01

    Background. Pubic bone metastasis as the initial manifestation of lung cancer is very rare, and it may simulate parasymphyseal insufficiency fracture of thepubic bone, which is observed in postmenopausal women and elderly people. Case report. A 65-year-old woman developed pain in the right flank, which extended to the anterior aspect of the thigh. A pelvic X-ray showed osteolyticlesion in the right pubic ramus. Chest radiograph revealed a nodularmass in the right middle lobe of the lung. Tran...

  14. 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

  15. Pubic bone metastasis as first manifestation of lung cancer

    International Nuclear Information System (INIS)

    Background. Pubic bone metastasis as the initial manifestation of lung cancer is very rare, and it may simulate parasymphyseal insufficiency fracture of the pubic bone, which is observed in postmenopausal women and elderly people. Case report. A 65-year-old woman developed pain in the right flank, which extended to the anterior aspect of the thigh. A pelvic X-ray showed osteolytic lesion in the right pubic ramus. Chest radiograph revealed a nodular mass in the right middle lobe of the lung. Transbronchal biopsy of the mass led to the diagnosis of lung adenocarcinoma. The patient was given radiotherapy of osteolytic lesion in her right pubic ramus and the pain was controlled with a combination of morphine sulfate. Conclusions. When unusual bone metastasis is found in the absence of a primary tumor, investigation must include chest radiographs. (author)

  16. 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.

  17. 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 ...

  18. 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...

  19. 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......), following patients from BM diagnosis until death, emigration or until 31 December 2012, whichever came first. RESULTS: Survival decreased with more advanced stage of disease at the time of breast cancer diagnosis; risk of mortality during the first year following a BM diagnosis was over two times higher for...

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

    OpenAIRE

    Jeong, Joon; Lee, Kyung Sun; Choi, Yang-Kyu; Oh, Young Ju; Lee, Hy-De

    2011-01-01

    Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incid...

  5. 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...

  6. Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo.

    Science.gov (United States)

    Holen, I; Walker, M; Nutter, F; Fowles, A; Evans, C A; Eaton, C L; Ottewell, P D

    2016-03-01

    Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER+ve (MCF7, T47D) or ER-ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 μg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER+ve cells to bone in 80-100 % of animals whereas bone metastases from ER-ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER+ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER-ve cells require increased osteoclast activity to grow in bone whereas ER+ve cells do not. Zol does not affect ER+ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER+ve breast cancer cells in bone. PMID:26585891

  7. 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...

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. The incidence of bone metastasis after early-stage breast cancer in Canada.

    Science.gov (United States)

    Liede, Alexander; Jerzak, Katarzyna J; Hernandez, Rohini K; Wade, Sally W; Sun, Ping; Narod, Steven A

    2016-04-01

    Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000. Data were abstracted from medical records and pathology reports in the HBBC database; follow-up extended to end of data availability or August 31, 2015. Actuarial survival analyses provided cumulative incidence of bone metastases at 5, 10, and 15 years after breast cancer diagnosis. Kaplan-Meier curves describe breast cancer mortality. Regression models assessed patient, tumor, and treatment characteristics as predictors of bone metastases with all-cause mortality as a competing risk. Among 2097 women studied, the 5-, 10-, and 15-year probability of bone metastasis was 6.5, 10.3, and 11.3 % for the first recurrence, and 8.4, 12.5, and 13.6 % for any bone recurrence. At median follow-up (12.5 years), 13.2 % of patients had bone metastases. Median survival was 1.6 years following bone metastasis, and shorter if both bone and visceral metastases occurred. Advanced age and adjuvant treatment with tamoxifen were protective against bone metastasis. In this representative cohort of women diagnosed with early-stage breast cancer in Ontario, Canada, with long follow-up, the incidence of bone metastases was consistent with longitudinal studies from the United Kingdom, Denmark, and the US. PMID:27083181

  19. 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...

  20. 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...

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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

  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. 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.

  10. 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.

  11. 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

  12. 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.

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

    OpenAIRE

    D. Santini; Procopio, G; Porta, C; Ibrahim, T; Barni, S.; Mazzara, C; Fontana, A.; Berruti, A; R. Berardi; Vincenzi, B; Ortega, C; Ottaviani, D; Carteni, G; Lanzetta, G; Virzì, V

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Patients and methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 25 months ...

  14. Skeletal-related events in urological cancer patients with bone metastasis. A multicenter study in Japan

    International Nuclear Information System (INIS)

    The objective of this study was to investigate the incidence of skeletal-related events (SRE) in urological cancer patients with bone metastases in Japan. Five hundred eleven patients with urological cancer and documented bone metastases treated from January 2003 to April 2008 in ten Japanese institutions were included in a retrospective analysis. Type and incidence of SRE (fracture, radiotherapy, spinal cord compression, surgery, hypercalcemia, and bone pain) were determined from patient medical records. The overall incidence of SRE, including 'pain', was 61%. The most common event was radiotherapy for bone metastases, with an incidence of 31%. The overall incidence of events seemed to be similar among Japanese and Western patients with prostate cancer and renal cell carcinoma when comparing data with previously published reports. Nevertheless, a much lower incidence of fracture (19.1%) was observed in Japanese renal cell carcinoma patients. The overall incidence of SRE in Japanese urological cancer patients with bone metastasis was similar to that in Western patients, but the incidence of fracture was lower in Japanese renal cancer patients. (author)

  15. 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

  16. 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

  17. 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.

  18. 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

  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. Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231 BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization

  1. 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)

  2. 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.

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

    Science.gov (United States)

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

    2016-05-01

    Breast cancer (BCa) bone metastases cause osteolytic bone lesions, which result from the interactions of metastatic BCa cells with osteoclasts and osteoblasts. Osteoclasts differentiate from myeloid lineage cells. To understand the cell-specific role of transforming growth factor beta (TGF-β) in the myeloid lineage, in BCa bone metastases, MDA-MB-231 BCa cells were intra-tibially or intra-cardially injected into LysM(Cre)/Tgfbr2(floxE2/floxE2) knockout (LysM(Cre)/Tgfbr2 KO) or Tgfbr2(floxE2/floxE2) mice. Metastatic bone lesion development was compared by analysis of both lesion number and area. We found that LysM(Cre)/Tgfbr2 knockout significantly decreased MDA-MB-231 bone lesion development in both the cardiac and tibial injection models. LysM(Cre)/Tgfbr2 knockout inhibited the tumor cell proliferation, angiogenesis and osteoclastogenesis of the metastatic bones. Cytokine array analysis showed that basic fibroblast growth factor (bFGF) was downregulated in MDA-MB-231-injected tibiae from the LysM(Cre)/Tgfbr2 KO group, and intravenous injection of the recombinant bFGF to LysM(Cre)/Tgfbr2 KO mice rescued the inhibited metastatic bone lesion development. The mechanism by which bFGF rescued the bone lesion development was by promotion of tumor cell proliferation through the downstream mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK)-cFos pathway after binding to the FGF receptor 1 (FGFR1). Consistent with animal studies, we found that in human BCa bone metastatic tissues, TGF-β type II receptor (TβRII) and p-Smad2 were expressed in osteoclasts and tumor cells, and were correlated with the expression of FGFR1. Our studies suggest that myeloid-specific TGF-β signaling-mediated bFGF in the bone promotes BCa bone metastasis. PMID:26279296

  4. 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.

  5. 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

  6. 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...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...

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

    Directory of Open Access Journals (Sweden)

    Koizumi Mitsuru

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniele Santini

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

  9. 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.

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. Toe metastasis: A rare pattern of cervical cancer spread ☆

    OpenAIRE

    Ciccone, Marcia A.; Conturie, Charlotte L.; Lee, Cassie M.; Matsuo, Koji

    2014-01-01

    Highlights • Toe metastasis is a rare pattern of cervical cancer spread. • Enlarged erythematous toe is an important sign suggesting bone metastasis. • Toe metastasis represents a grave prognostic indicator of cervical cancer.

  17. 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...

  18. 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.

  19. Diagnostic value of urinary pyridinoline for determining bone metastasis in patients with non-metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Fatma Uçar

    2011-12-01

    Full Text Available Objective: In this study, urinary pyridinoline (uPYR, urinary deoxypyridinoline (uDPD and serum alkaline phosphatase (sALP levels were measured in patients without metastatic breast cancer and the role of uPYR and uDPD as biochemical markers of bone metastases were examined during a six years follow-up.Materials and methods: Totally, 34 patients without bone metastasis and 40 healthy individuals as a control group were included in the study.Results: Urinary pyridinoline and uDPD levels were significantly higher in patients without bone metastasis than in normal controls (p<0,05, except sALP levels. As a result of a 6-year follow-up of patients, 20.5% had metastasis. The distribution of metastasis types was as follows: 2.9% of those patients had local, 2.9% had liver, 5.9% had lung and 8.8% had bone metastasis. The cut off value, sensitivity and specifity of uPYR was established as 47,3 pmol/μmol creatinin, 82% and 80% respectively. The cut off value, sensitivity and specifity of uDPD were determined as 9.53 pmol/μmol creatinin, 76%, 72% respectively.Conclusions: This study demonstrated that measurement of urinary collagen cross-links assay may contribute to the early detection of metastatic spread to bone in breast cancer. However further studies with larger scaled groups should be performed. J Clin Exp Invest 2011; 2 (4: 420-424

  20. 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

  1. The impact of bone morphogenetic protein 4 (BMP4) on breast cancer metastasis in a mouse xenograft model.

    Science.gov (United States)

    Ampuja, M; Alarmo, E L; Owens, P; Havunen, R; Gorska, A E; Moses, H L; Kallioniemi, A

    2016-06-01

    Bone morphogenetic protein 4 (BMP4) is a key regulator of cell proliferation and differentiation. In breast cancer cells, BMP4 has been shown to reduce proliferation in vitro and interestingly, in some cases, also to induce migration and invasion. Here we investigated whether BMP4 influences breast cancer metastasis formation by using a xenograft mouse model. MDA-MB-231 breast cancer cells were injected intracardially into mice and metastasis formation was monitored using bioluminescence imaging. Mice treated with BMP4 developed metastases slightly earlier as compared to control animals but the overall number of metastases was similar in both groups (13 in the BMP4 group vs. 12 in controls). In BMP4-treated mice, bone metastases were more common (10 vs. 7) but adrenal gland metastases were less frequent (1 vs. 5) than in controls. Immunostaining revealed no differences in signaling activation, proliferation rate, blood vessel formation, EMT markers or the number of cancer-associated fibroblasts between the treatment groups. In conclusion, BMP4 caused a trend towards accelerated metastasis formation, especially in bone. More work is needed to uncover the long-term effects of BMP4 and the clinical relevance of these findings. PMID:26970275

  2. 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.

  3. 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

  4. 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.

  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

    2013-01-01

    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

  6. Lung Metastasis From Prostate Cancer Revealed by 18F-FDG PET/CT Without Osseous Metastasis on Bone Scan.

    Science.gov (United States)

    Su, Hung-Yi; Chen, Meng-Lin; Hsieh, Ping-Ju; Hsieh, Teh-Sheng; Chao, Ing-Ming

    2016-05-01

    A 54-year-old man, a case of prostate cancer, underwent radical prostatectomy and hormone therapy. Elevated prostate-specific antigen level developed 7 years later, but pelvic MRI and bone scan revealed negative results. Radiotherapy was performed under the suspicion of local recurrence but in vain. F-FDG PET/CT performed 1 more year later showed 3 FDG-avid lesions in the right lung and mediastinum. Lung and lymph node metastases were proved with video-assisted thoracoscopic surgery. Bone scan remained negative at that time. PMID:26859201

  7. The impact of bisphosphonate therapy on survival of lung cancer patients with bone metastasis

    OpenAIRE

    Theodoros Kontakiotis; Georgios Ballasoulis; Theodora Tsiouda; Hellie Lithoxopoulou; Vasiliki Zarogoulidou; Efimia Boutsikou; Konstantinos Zarogoulidis

    2009-01-01

    SUMMARY. INTRODUCTION: Bone metastases occur in 20% to 40% of patients with lung cancer. Recent studies (most in vitro) demonstrate an anti-proliferative effect of third-generation biphosphonates (BPs) on lung tumours which may, indirectly, have an impact on the survival. OBJECTIVES: This was a study of the effects of treatment with BPs on the course and survival of lung cancer patients with bone metastases. PATIENTS AND METHODS: For the study 108 male patients with lung cancer (stage IV) wer...

  8. 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.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-15

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

  11. 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...

  12. The impact of bisphosphonate therapy on survival of lung cancer patients with bone metastasis

    Directory of Open Access Journals (Sweden)

    Theodoros Kontakiotis

    2009-01-01

    Full Text Available SUMMARY. INTRODUCTION: Bone metastases occur in 20% to 40% of patients with lung cancer. Recent studies (most in vitro demonstrate an anti-proliferative effect of third-generation biphosphonates (BPs on lung tumours which may, indirectly, have an impact on the survival. OBJECTIVES: This was a study of the effects of treatment with BPs on the course and survival of lung cancer patients with bone metastases. PATIENTS AND METHODS: For the study 108 male patients with lung cancer (stage IV were recruited consecutively. Of these, 55/108 patients with positive bone scan experienced bone pain and received Nitrogen BPs (NBPs, specifically zoledronic acid (ZOL, 4 mg i.v. every 21 days (Group A. The other 53 patients received no NBPs, of which 30/53 had a positive bone scan (Group B and 23/53 a negative bone scan (Group C. All patients were treated with combination chemotherapy consisting of Docitaxel 100 mg/m2 and Carboplatin AUC = 6. RESULTS: Group A had a statistically significantly longer mean survival and time to progression than Groups B and C (p0.05. CONCLUSION: The addition of NBPs to the treatment regime appears to increase overall survival in lung cancer patients with bone metastases. Further studies are needed to support the potential usefulness of NBPs as an independent therapeutic agent against lung cancer. Pneumon 2009; 22(1:25–37

  13. 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...

  14. 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...

  15. 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

  16. 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

  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. Global secretome analysis identifies novel mediators of bone metastasis.

    Science.gov (United States)

    Blanco, Mario Andres; LeRoy, Gary; Khan, Zia; Alečković, Maša; Zee, Barry M; Garcia, Benjamin A; Kang, Yibin

    2012-09-01

    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. PMID:22688892

  1. Analysis of bone metastasis in head and neck squamous cell carcinoma: Experience of a regional cancer center

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Background: Bone metastasis is a rare occurrence in head and neck squamous cell carcinoma (HNSCC. This retrospective study was performed to analyze the frequency and patterns of skeletal metastasis in HNSCC. Materials and Methods : We analyzed records of 8326 HNSCC patients attending our oncology outpatient department from January 2000 to December 2013. All statistical calculations were performed using MedCalc software for windows, version 12.5.0 (Osterd, Belgium. Results : Bone metastasis was found in 25 patients (0.3% of total HNSCC patients, nasopharynx excluded. 10 patients (0.66% of carcinoma tonsil had skeletal metastasis. The patients of younger age groups had higher frequency of bone metastasis; 1.56% patients of age group 20-29 years while 0.26% patients of 60-69 years age group had skeletal metastasis (P 70 years age was found to have bone metastasis. Most common site of metastasis was spine (56% followed by pelvis (32%. Isolated involvement of a single bony site was present in 64% of the metastatic cases. Conclusion: Bone metastasis though very rare, should be considered for evaluation in patients of HNSCC especially in younger patients.

  2. 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

  3. Targeting Breast Cancer Metastasis

    OpenAIRE

    Xin Jin; Ping Mu

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  4. Bone Cancer

    Science.gov (United States)

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

  5. Bone Cancer

    Science.gov (United States)

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

  6. 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.

  7. 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.

  8. 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...

  9. Gingival Metastasis from Gallbladder Cancer

    Directory of Open Access Journals (Sweden)

    Te-Sheng Chang

    2002-08-01

    Full Text Available Gallbladder cancer is generally diagnosed at an advanced stage. The liver is the mostcommonly invaded organ by direct extension and/or metastasis, followed by regional lymphnodes. Oral soft tissue metastasis is extremely unusual. This report describes the case of a62-year-old woman diagnosed with advanced metastatic gallbladder cancer, who initiallypresented with abdominal pain. Diagnosis of gallbladder cancer was made about 3 monthsafter her symptoms developed, when a laparoscopic cholecystectomy was performedbecause of the suspicion of gallstones. Liver metastasis was also discovered during surgery.A postoperative investigation revealed additional lung and bone metastases. A visible leftgingival tumor was found on physical examination and was confirmed as gallbladder cancermetastasis by compatible histopathology 1 month after surgery. The patient responded poorlyto chemotherapy and unfortunately died 5 months after the diagnosis. The clinical presentationof gallbladder cancer was relatively typical, apart from the unusual gingival metastasis.The medical literature contains quite a few examples of metastatic lesions locatedstrictly in the oral soft tissue, however no case of gallbladder cancer metastasizing to theoral soft tissue has been previously reported.

  10. The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches.

    Science.gov (United States)

    Özdemir, Berna C; Hensel, Janine; Secondini, Chiara; Wetterwald, Antoinette; Schwaninger, Ruth; Fleischmann, Achim; Raffelsberger, Wolfgang; Poch, Olivier; Delorenzi, Mauro; Temanni, Ramzi; Mills, Ian G; van der Pluijm, Gabri; Thalmann, George N; Cecchini, Marco G

    2014-01-01

    The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this

  11. RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer.

    Science.gov (United States)

    Wang, Fangfang; Chen, Lei; Zhang, Rui; Chen, Zhongping; Zhu, Li

    2014-12-28

    Targeting αvβ3 integrin is particularly promising for the treatment of bone metastases by targeting integrin-rich tumor cells and by inhibiting integrin-involved bone metastases. In this work, a liposomal drug delivery system conjugated with cyclic arginine-glycine-aspartic acid-tyrosine-lysine peptide (cRGDyk) as αvβ3 integrin ligand was thus developed to improve therapeutic efficacy in a mice model of bone metastasis from prostate cancer. The resultant liposomes were characterized in terms of size, morphology, zeta potential, stability, drug encapsulation percentage and loading efficiency, and drug release. Compared with free cisplatin and cRGDyk-free liposomes, cRGDyk conjugated liposomes showed significantly higher cellular uptake and higher cytotoxicity of loaded cisplatin, as evidenced by in vitro cell experiments. In vivo results revealed that free cisplatin and free cRGDyk could relieve tumor-induced pain but had no contributions to tumor regression and overall survival improvement. cRGDyk-free liposomal drug system with prolonged blood circulation time could accumulated in the tumor sites in the bone through enhanced permeability and retention (EPR) effects and however, did not exhibit desirable therapeutic efficacy superior to free cisplatin and free cRGDyk. This strongly suggested that ERP effects were not effective in treating metastases. By taking advantages of targeted drug delivery and synergistic antitumor activity of cRGDyk and loaded cisplatin, cRGDyk conjugated liposomal drug system could inhibit osteoclastic and osteoblastic bone lesions, relieve pain, and improve overall survival. Inspired by their enhanced therapeutic efficacy and low organ toxicity, cRGDyk conjugated liposomes could serve as an effective drug system for targeted and synergistic therapy of bone metastases. PMID:25456829

  12. 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

  13. 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.

  14. 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)

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  16. 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.

  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. 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

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

    Directory of Open Access Journals (Sweden)

    Xianbo Peng

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

  1. Bone Positron Emission Tomography with or without CT Is More Accurate than Bone Scan for Detection of Bone Metastasis

    OpenAIRE

    Lee, Soo Jin; Lee, Won Woo; Kim, Sang Eun

    2013-01-01

    Objective Na18F bone positron emission tomography (bone PET) is a new imaging modality which is useful for the evaluation of bone diseases. Here, we compared the diagnostic accuracies between bone PET and bone scan for the detection of bone metastasis (BM). Materials and Methods Sixteen cancer patients (M:F = 10:6, mean age = 60 ± 12 years) who underwent both bone PET and bone scan were analyzed. Bone PET was conducted 30 minutes after the injection of 370 MBq Na18F, and a bone scan was perfo...

  2. 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。

  3. 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

  4. 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.

  5. 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

  6. 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)

  7. 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.

  8. 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

  9. 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...

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

    Science.gov (United States)

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

    2011-01-01

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

  11. 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

  12. 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)

  13. 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.

  14. Pleiotropic activity of lysophosphatidic acid in bone metastasis.

    Science.gov (United States)

    Peyruchaud, Olivier; Leblanc, Raphael; David, Marion

    2013-01-01

    Bone is a common metastatic site for solid cancers. Bone homeostasis is tightly regulated by intimate cross-talks between osteoblast (bone forming cells) and osteoclasts (bone resorbing cells). Once in the bone microenvironment, metastatic cells do not alter bone directly but instead perturb the physiological balance of the bone remodeling process controlled by bone cells. Tumor cells produce growth factors and cytokines stimulating either osteoclast activity leading to osteolytic lesions or osteoblast function resulting in osteoblastic metastases. Growth factors, released from the resorbed bone matrix or throughout osteoblastic bone formation, sustain tumor growth. Therefore, bone metastases are the sites of vicious cycles wherein tumor growth and bone metabolism sustain each other. Lysophosphatidic acid (LPA) promotes the growth of primary tumors and metastatic dissemination of cancer cells. We have shown that by acting on cancer cells via the contribution of blood platelets and the LPA-producing enzyme Autotaxin (ATX), LPA promotes the progression of osteolytic bone metastases in animal models. In the light of recent reports it would appear that the role of LPA in the context of bone metastases is complex involving multiple sources of lipid combined with direct and indirect effects on target cells. This review will present our current knowledge on the LPA/ATX axis involvement in osteolytic and osteoblastic skeletal metastases and will discuss the potential activity of LPA upstream and downstream metastasis seeding of cancer cells to bone as well as its implication in cancer induced bone pain. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. PMID:22710393

  15. 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.

  16. Incidence of bone metastasis in carcinoma buccal mucosa

    Science.gov (United States)

    Bhandari, Virendra

    2016-01-01

    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.

  17. 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

  18. 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.

  19. 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)

  20. 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.

  1. 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.

  2. 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. PMID:24839990

  3. 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.

  4. Osteoblast-derived sphingosine 1-phosphate to induce proliferation and confer resistance to therapeutics to bone metastasis-derived prostate cancer cells.

    Science.gov (United States)

    Brizuela, Leyre; Martin, Claire; Jeannot, Pauline; Ader, Isabelle; Gstalder, Cécile; Andrieu, Guillaume; Bocquet, Magalie; Laffosse, Jean-Michel; Gomez-Brouchet, Anne; Malavaud, Bernard; Sabbadini, Roger A; Cuvillier, Olivier

    2014-10-01

    Sphingosine 1-phosphate (S1P) plays important roles in cell proliferation, differentiation or survival mainly through its surface G-protein-coupled receptors S1P1-5. Bone represents the major site of metastasis for prostate cancer (CaP) cells, which rely on bone-derived factors to support their proliferation and resistance to therapeutics. In the present work we have found that conditioned medium (CM) from the MC3T3 osteoblastic cell line or primary murine and human osteoblast-like cells, as well as co-culture with MC3T3 stimulate proliferation of CaP lines in S1P-dependent manner. In addition, osteoblastic-derived S1P induces resistance of CaP cells to therapeutics including chemotherapy and radiotherapy. When S1P release from osteoblastic cells is decreased (inhibition of SphK1, knock-down of SphK1 or the S1P transporter, Spns2 by siRNA) or secreted S1P neutralized with anti-S1P antibody, the proliferative and survival effects of osteoblasts on CaP cells are abolished. Because of the paracrine nature of the signaling, we studied the role of the S1P receptors expressed on CaP cells in the communication with S1P secreted by osteoblasts. Strategies aimed at down-regulating S1P1, S1P2 or S1P3 (siRNA, antagonists), established the exclusive role of the S1P/S1P1 signaling between osteoblasts and CaP cells. Bone metastases from CaP are associated with osteoblastic differentiation resulting in abnormal bone formation. We show that the autocrine S1P/S1P3 signaling is central during differentiation to mature osteoblasts by regulating Runx2 level, a key transcription factor involved in osteoblastic maturation. Importantly, differentiated osteoblasts exhibited enhanced secretion of S1P and further stimulated CaP cell proliferation in a S1P-dependent manner. By establishing the dual role of osteoblast-borne S1P on both osteoblastic differentiation and CaP cell proliferation and survival, we uncover the importance of S1P in the bone metastatic microenvironment, which may open

  5. 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.

  6. 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

  7. 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.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    Richhariya A

    2012-02-01

    Full Text Available 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 patients with bone metastases secondary to breast or prostate cancer (BC or PC in the clinic setting.Methods: Eligible BC or PC patients with bone metastases scheduled to receive IV ZA were observed at seven US-based oncology clinics. Trained observers recorded the time for preinfusion tasks, ZA drug preparation, intravenous infusion, and follow-up activities.Results: Data are reported for 39 patients (BC: 24; PC: 15. Mean administration time was 69 (standard deviation [SD] 42 minutes for all patients combined, 72 (SD 47 minutes for BC, and 65 (SD 33 minutes for PC. Activity times were comparable between tumor types. Mean time for preinfusion tasks (eg, assessment of vital signs, blood draw and ZA preparation were 12 (SD 20 minutes and 2 (SD 1 minutes, respectively. Mean time required for intravenous infusion (ZA infusion and hydration, when provided and follow-up activities were 54 (SD 31 minutes and 2 (SD 1 minutes, respectively.Conclusion: Infusion time was the greatest time commitment associated with IV ZA administration, representing 78% of the total time on average. Time for preinfusion activities varied substantially. Overall, the mean time for ZA administration represents a notable time burden for healthcare providers and patients.Keywords: time and motion, bisphosphonates, zoledronic acid, intravenous administration

  10. 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

  11. Solitary pulmonary metastasis from prostate sarcomatoid cancer

    OpenAIRE

    Oyamada Yoshitaka; Maeshima Arafumi; Goto Taichiro; Kato Ryoichi

    2010-01-01

    Abstract Background Pulmonary metastasis from prostate cancer is considered to be a late event, and patients can be treated with chemotherapy or hormonal manipulation. However, there has been only a few reports on surgical resection for pulmonary metastasis from prostate cancer. Case Presentation We present a surgical case of solitary pulmonary metastasis from prostate cancer. A 73-year-old man underwent pelvic evisceration for prostate cancer. Histopathological examination revealed a poorly ...

  12. Metabolism in cancer metastasis.

    Science.gov (United States)

    Weber, Georg F

    2016-05-01

    Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology. PMID:26355498

  13. 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

  14. 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...

  15. Bone position emission tomography with or without CT Is more accurate than bone scan for detection of bone metastasis

    International Nuclear Information System (INIS)

    Na18F bone positron emission tomography (bone PET) is a new imaging modality which is useful for the evaluation of bone diseases. Here, we compared the diagnostic accuracies between bone PET and bone scan for the detection of bone metastasis (BM). Sixteen cancer patients (M:F = 10:6, mean age = 60 ± 12 years) who underwent both bone PET and bone scan were analyzed. Bone PET was conducted 30 minutes after the injection of 370 MBq Na18F, and a bone scan was performed 3 hours after the injection of 1295 MBq 99mTc-hydroxymethylene diphosphonate. In the patient-based analysis (8 patients with BM and 8 without BM), the sensitivities of bone PET (100% 8/8) and bone scan (87.5% = 7/8) were not significantly different (p > 0.05), whereas the specificity of bone PET (87.5% = 7/8) was significantly greater than that of the bone scan (25% = 2/8) (p 8F bone PET is more accurate than bone scan for BM evaluation.

  16. 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.

  17. 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

  18. 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 ...

  19. Metastasis-Initiating Cells in Renal Cancer

    OpenAIRE

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  20. Technetium-99m methylene diphosphonate uptake in the brachialis muscle hematoma in a patient with prostate cancer and coagulation disorder mimicking bone metastasis evaluated by single-photon emission tomography-computed tomography/computed tomography

    International Nuclear Information System (INIS)

    We report a case of 79-year-old male with prostate cancer and coagulation disorder presented with left shoulder pain. He underwent bone scintigraphy to rule out metastasis, which showed intense foci of tracer activity in the left axilla. Hybrid single-photon emission tomography-computed tomography (SPECT/CT) of the shoulder region localized tracer uptake to the left brachialis muscle hematoma. (author)

  1. Prostatic adenocarcinoma with and without metastasis to bone in dogs

    International Nuclear Information System (INIS)

    The signalment, clinical signs, and histologic tumor pattern were compared retrospectively in 12 dogs having primary prostatic adenocarcinoma with (5 cases) and without metastasis (7 cases) to bone. Weight loss and lumbar pain were observed more frequently in dogs having prostatic adenocarcinoma with metastasis to bone. A distinctive histologic pattern was not associated with prostatic adenocarcinoma that had metastasized to bone. The alveolar papillary pattern was the predominant histologic type observed in both groups. Metastasis to extra pelvic bony sites included the scapulas, ribs, and digits. The results of this study indicate that skeletal metastasis was not uncommon in dogs having prostatic adenocarcinoma

  2. Pulmonary metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Although thyroid cancer (TC) in its differentiated form is generally associated with a good prognosis and a near normal life expectancy, a subset of patients especially with distant metastatic disease may run an aggressive course leading to poor survival and early death. The clinical presentation and the manner in which the disease progresses differs with the site and type of the metastatic disease. The behaviour and course of skeletal metastasis has been described elsewhere. The biological behaviour and treatment of pulmonary metastatic disease is focussed on

  3. 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

  4. 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

  5. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

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

  6. Role of the nervous system in cancer metastasis.

    Science.gov (United States)

    Li, Sha; Sun, Yanlai; Gao, Dongwei

    2013-04-01

    The notion that tumors lack innervation was proposed several years ago. However, nerve fibers are irregulatedly found in some tumor tissues. Their terminals interaction with cancer cells are considered to be neuro-neoplastic synapses. Moreover, neural-related factors, which are important players in the development and activity of the nervous system, have been found in cancer cells. Thus, they establish a direct connection between the nervous system and tumor cells. They modulate the process of metastasis, including degradation of base membranes, cancer cell invasion, migration, extravasation and colonization. Peripheral nerve invasion provides another pathway for the spread of cancer cells when blood and lymphatic metastases are absent, which is based on the interactions between the microenvironments of nerve fibers and tumor cells. The nervous system also modulates angiogenesis, the tumor microenvironment, bone marrow, immune functions and inflammatory pathways to influence metastases. Denervation of the tumor has been reported to enhance cancer metastasis. Stress, social isolation and other emotional factors may increase distant metastasis through releasing hormones from the brain, the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Disruption of circadian rhythms will also promote cancer metastasis through direct and indirect actions of the nervous system. Therefore, the nervous system plays an important role in cancer metastasis. PMID:23599747

  7. 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 ...

  8. 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.

  9. Lymph Node Metastasis of Gastric Cancer

    International Nuclear Information System (INIS)

    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

  10. 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.

  11. Unusual bone metastasis from follicular carcinoma thyroid: presenting as a primary bone malignancy

    Directory of Open Access Journals (Sweden)

    Saurabh Varshney

    2014-12-01

    Full Text Available Osseous metastasis in patients of thyroid carcinoma is not very common, and appendicular skeleton is very rare. Bone metastasis represents a complication, especially of follicular thyroid carcinoma and severely reduces the quality of life causing pain, and fractures. Diagnosis is typically done by correlating clinical suspicion with imaging. Occult clinical presentations usually delay the detection and management of patients with bone metastasis from thyroid carcinoma. There is limited information about the clinical presentations and prognosis of patients with follicular thyroid carcinoma with bone metastasis. We hereby present a case report of right arm swelling diagnosed as metastatic carcinoma having metastasis from thyroid primary.

  12. 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.

  13. Suppression of cancer relapse and metastasis by inhibiting cancer stemness

    OpenAIRE

    Li, Youzhi; Rogoff, Harry A.; Keates, Sarah; Gao, Yuan; Murikipudi, Sylaja; Mikule, Keith; Leggett, David; Li, Wei; Pardee, Arthur B.; Li, Chiang J.

    2015-01-01

    Current cancer treatments ultimately fail owing to metastasis and relapse. The discovery of therapeutic approaches that counteract relapse and metastasis is, therefore, extremely important for advancing cancer medicine. Hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, have been isolated from patients with a variety of tumor types and found to be highly malignant, tumorigenic, and resistant to chemotherapies. Our data that BBI608, a cancer stemness inhibitor...

  14. 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

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Bone scanning in the evaluation of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk [School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    1994-05-15

    We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%.

  2. Stereotactic Body Radiation Therapy for Treatment of Spinal Bone Metastasis.

    Science.gov (United States)

    Cihan, Yasemin Benderli

    2016-01-01

    Stereotactic body radiation therapy (SBRT) appears an effective and safe treatment modality for spinal bone metastasis, which can enhance local control and improve quality of life. Life expectation, predicted fracture risk, localization, quality, size and number of metastasis and presence or absence of nerve compression seem to be important factors in decision-making for treatment. Further studies are needed to identify subsets of patient which will most benefit from treatment. PMID:27039816

  3. 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.

  4. 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

  5. Detection of cancer before distant metastasis

    International Nuclear Information System (INIS)

    To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the first metastasis has formed from a primary breast cancer tumor. The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TXNXM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1BNXM0 (25% of total patients with T1BNXM0). Validation of the model was done with data for all patients. From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1B patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TXNXM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood. To reduce the rate of distant metastasis in surgically treated TXNXM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be

  6. 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...

  7. 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...

  8. 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...

  9. 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

  10. 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...

  11. Bone scintigraphy, plasma ALP, TAP and PAP in patients with prostatic cancer

    International Nuclear Information System (INIS)

    This study assessed the ability of bone scintigraphy, alkaline phosphatase (ALP), total acid phosphatase (TAP), and prostatic acid phosphatase (PAP) to diagnose bone metastasis in a series of 62 patients with histologically proven prostatic cancer. Abnormal uptake was seen on the bone scan in 49 patients (79 %). A final diagnosis of bone metastasis was made in 40 patients (65 %). The sensitivity and specificity were 100 % and 59 %, respectively, for bone scintigraphy; 50 % and 96 % for ALP; 65 % and 82 % for TAP; and 73 % and 77 % for PAP. For 40 patients with bone metastasis, all of the ALP, TAP, and PAP were positive in 17 patients (43 %) and negative in 8 patients (20 %). Higher levels of ALP, TAP, and PAP tended to be associated with more extensive bone metastasis. Although serological examination showed lower sensitivity than bone scintigraphy in the diagnosis of bone metastasis, PAP may be most frequently used as a screening procedure of bone metastasis. (Namekawa, K.)

  12. 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.

  13. 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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Gayed Isis W

    2009-08-01

    Full Text Available Abstract Background 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. Methods 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. Results 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Brain Metastasis in Pancreatic Cancer

    OpenAIRE

    Marko Kornmann; Doris Henne-Bruns; Jan Scheele; Christian Rainer Wirtz; Thomas Kapapa; Johannes Lemke

    2013-01-01

    Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreat...

  4. Bone cancer risk

    International Nuclear Information System (INIS)

    In view of the considerable disparity in published values of the risk for bone cancers from ionising radiation, the article 'An analysis of bone and head sinus cancers in radium dial painters using a two-mutation carcinogenesis model' by Leenhouts and Brugmans in the June 2000 issue of this Journal deserves further comment and consideration. The letter concludes that radiological protection and risk estimation has acquired an extra dimension, and it is clear that the risk of bone cancer from exposure to ionising radiation needs further review. Letter-to-the-editor

  5. 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. ...

  6. 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.

  7. 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

  8. 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 ...

  9. 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

  10. 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. PMID:26910109

  11. Cancer metastasis detected by NMR

    International Nuclear Information System (INIS)

    A narrow NMR line originating from the plasma membrane of a cancer cell is unexpected. The behaviour of these lines is explained in terms of fundamental physics and chemistry. There is biochemical evidence to support the presence of neutral lipid domains in the plasma membrane. T2 relaxation and clinical implications are briefly discussed

  12. 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 ...

  13. Spinal Leptomeningeal Metastasis from Gastric Cancer: Case Report

    OpenAIRE

    Çokmert, Suna; Doğanay, Latife; Paköz, Burak; Yüksel, Alper; Gezer, Emrah; Alakavuklar, Mehmet Niyazi

    2015-01-01

    Leptomeninges are a rare region for metastasis in solid tumors. The most common causes of leptomeningeal metastasis are breast cancer, lung cancer, melanoma and leukemia-lymphomas. Leptomeningeal metastasis associated with gastric cancer is an exceedingly rare condition but it is rapidly progressive and poor prognosis. The diagnosis is confirmed by examination of the cerebrospinal fluid and imaging methods. There are several treatment options for patients with LMC, including intrathecal chemo...

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

    Science.gov (United States)

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

  16. 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...

  17. 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

  18. 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)

  19. 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

  20. The frequency of osteolytic bone metastasis is determined by conditions of the soil, not the number of seeds; evidence from in vivo models of breast and prostate cancer

    OpenAIRE

    Wang, N; Reeves, K.J.; Brown, H.K.; Fowles, A.C.M.; Docherty, F.E.; Ottewell, P.D.; Croucher, P.I.; Holen, I; Eaton, C.L.

    2015-01-01

    Background While both preclinical and clinical studies suggest that the frequency of growing skeletal metastases is elevated in individuals with higher bone turnover, it is unclear whether this is a result of increased numbers of tumour cells arriving in active sites or of higher numbers of tumour cells being induced to divide by the bone micro-environment. Here we have investigated how the differences in bone turnover affect seeding of tumour cells and/or development of overt osteolytic b...

  1. 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

  2. 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

  3. Solitary Metastasis of Gastric Cancer to Fibula: A Case Report

    International Nuclear Information System (INIS)

    Gastric cancer is one of the most common and most fatal neoplasms in human. Its skeletal metastasis is less frequent, particularly when solitary. The objective of this article is to represent a case of solitary fibular metastasis from this cancer not reported before based on Medline search

  4. 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.

  5. 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

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

    Science.gov (United States)

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

    2009-01-01

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

  7. 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

  8. 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.

  9. 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.

  10. Unusual splenic metastasis from oesophageal cancer.

    OpenAIRE

    Murthy S; Prabhakaran P; Rao S; Kumar R

    1991-01-01

    The most common visceral metastasis from oesophageal carcinomas are lungs and liver. A case of splenic metastasis from a squamous carcinoma of oesophagus is reported. To our knowledge, splenic metastasis without any nodal disease has not been described previously. The pattern of reported metastasis is summarised.

  11. 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.

  12. 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)

  13. 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.

  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. Survey for primary tumor site in patients with initial clinical presentation of bone metastasis

    International Nuclear Information System (INIS)

    Among the patients who were examined with bone scintigraphy between April 1985 and March 1991, there were 27 patients whose initial clinical manifestation was bone metastasis and who were surveyed for the primary tumor site. The primary tumor site could be identified in 20 patients (74%), consisting of 9 patients with lung cancer, 3 with prostate cancer, 3 with hepatoma, 2 with renal cancer, and one each with thyroid cancer, adrenal cancer, and pleural malignant mesothelioma. In 17 of the 20 patients, the primary site had been detected within two months after presentation. Examinations which were helpful in identifying the primary site included chest radiography, sputum cytology, abdominal sonography, serum prostatic acid phosphatase level and pathologic examination of biopsy specimens. 99mTc-pyridoxylenemethyl tryptophan (99mTc-PMT) scintigraphy was useful in the diagnosis of the hepatoma when accumulation was observed at the metastatic sites. In 2 patients, lung cancer had been recognized using follow-up chest, radiography 3 and 6 months after presentation, respectively. One patient was diagnosed at autopsy as having adrenal cancer. In 7 patients the primary site remains unknown. Histology examination of the biopsy specimen performed in 6 of these patients revealed 4 to be adenocarcinoma and 2 undifferentiated carcinoma. The average survival period of the 17 patients who died was 9.5 months. Four patients are alive, and the outcome in the remaining 6 could not be determined. (author)

  16. Contribution of whole body FDG-PET to the detection of distant metastasis in pancreatic cancer

    International Nuclear Information System (INIS)

    Accurate baseline staging is necessary to appropriately treat pancreatic cancer. The present study was undertaken to evaluate the clinical contribution of whole body fluorodeoxyglucose (FDG)-PET to the detection of distant metastasis in pancreatic cancer. A total of consecutive 42 patients with previously untreated pancreatic cancer were examined. Whole body FDG-PET imaging for initial staging was performed with a 3D acquisition and iterative reconstruction on Siemens ECAT HR+ scanner at 1 hour post 185-200 MBq 18F-FDG injection. PET findings were correlated with clinical and radiological data to determine the impact of PET on staging. In 16 patients, there were one or more sites of metastasis based on clinical data. FDG-PET correctly identified the presence of metastasis in 13 of 16 patients and its absence in 23 of the remaining 26 patients. Thus, FDG-PET missed 4 metastatic sites in 4 patients (liver and lung metastasis). FDG-PET correctly identified 8 metastatic sites in 7 patients (peritoneal dissemination and liver, bone and supraclavicular lymph node metastasis), which were missed on CT imaging. Based on whole body FDG-PET, the clinical stage was changed in 5 of 42 patients (11.9%). These results suggest that FDG-PET and CT appear to have a complementary role in the detection of distant metastasis in patients with pancreatic cancer. (author)

  17. 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.

  18. 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.

  19. Monoclonal Antibody Testing for Cancer Metastasis

    Science.gov (United States)

    1993-01-01

    Malignant cells are characterized by the ability to invade surrounding normal tissues. Tumor invasion is abetted by proteolytic enzymes that have been correlated with recurrent disease and metastasis. These enzymes are involved in a cascade of proteolytic interactions with other enzymes and inhibitors which allow cancer cells to dissolve surrounding extracellular matrix, thereby enabling the cells to rapidly invade adjacent tissues and migrate to metastatic sites distant from the primary tumor. Among these proteases are the plasminogen activators (PA), collagenase IV, faminase, and in some cases cathepsin D, which together mediate key steps in the invasion process of metastasis. Cells which have the selective advantage for invasion and metastasis are those capable of regulating their proteolytic activity and proliferation. Cells in the process of invasion would be probably down-regulated for proliferation, but subsequent to attachment and adhesion at a distant site, would then be in a proliferative mode, up-regulating DNA replication. Urokinase (uPA) can be present in the tissues in several molecular forms. The inactive proenzyme is a single chain protein (scuPA) that is cleaved at Lys. 158 to form the double chain, high molecular weight active form (HMW-uPA) of 54 kD. A low molecular weight form (LMW-uPA) can also be produced by cleavage of the HMW-U PA at Lys. 135 - Lys. 136 giving a 35 kD active enzyme. Recently, it has been shown that the HMW active form of urokinase, bound to the tumor cell membrane, is responsible for the local lysis of the extracellular matrix, hence the tissue invasion mechanism for metastasis (Andreasen et al, 19861. Receptor- (membrane) bound uPA is twice as efficient (catalytically) as free fluid-phase uPA. Tho unbound uPA and the LMW form is not responsible for most of the local dissolution of extracellular matrix in the immediate vicinity of the metastatic tumor cell. High levels of urokinase (greater than 3.49 ng/mg of total protein

  20. 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

  1. 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...

  2. 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...

  3. Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

    OpenAIRE

    Xu, Mei; Chen, Gang; Fu, Wei; Liao, Mingjun; FRANK, JACQUELINE A.; Bower, Kimberly A.; Fang, Shengyun; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2012-01-01

    Both epidemiological and experimental studies indicate that ethanol exposure enhances tumor progression. Ethanol exposure promotes cancer cell invasion and is implicated in tumor metastasis. Metastasis consists of multiple processes involving intravasation and extravasation of cancer cells across the blood vessel walls. The integrity of the vascular endothelial barrier that lines the inner surface of blood vessels plays a critical role in cancer cell intravasation/extravasation. We examined t...

  4. 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...

  5. Genes that mediate breast cancer metastasis to the brain

    OpenAIRE

    Bos, Paula D.; Zhang, Xiang H.-F.; Nadal, Cristina; Shu, Weiping; Gomis, Roger R; Nguyen, Don X.; Minn, Andy J.; Vijver, Marc; Gerald, William; Foekens, John A.; Massagué, Joan

    2009-01-01

    The molecular basis for breast cancer metastasis to the brain is largely unknown1,2. Brain relapse typically occurs years after the removal of a breast tumour2–4, suggesting that disseminated cancer cells must acquire specialized functions to overtake this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood–brain barrier crossing and brain colonization. We isolated c...

  6. The use of palliative radiotherapy for bone metastasis

    International Nuclear Information System (INIS)

    Background: The value of palliative radiotherapy (PRT) for bone metastases is well established, but little is known about its use in the general population. Purpose: To describe the use of PRT for bone metastases in Ontario. Materials and methods: This was a retrospective cohort study. Treatment records from all Ontario RT departments were linked to a population-based cancer registry to describe the use of PRT. Results: 12.2% of the 434,241 patients, who died of cancer in Ontario between 1984 and 2004, received at least one course of PRT for bone metastases in the last 2 years of life. The rate of use of PRT varied across the province (inter-county range, 8.2-18.6%). Older patients and residents of poorer areas were less likely to receive PRT (p < 0.0001). Patients diagnosed with cancer in a hospital with a radiotherapy facility and those who lived closer to a radiotherapy centre were more likely to receive PRT (p < 0.0001). Over the study period, the use of PRT decreased in breast cancer and myeloma, but increased in prostate cancer (p < 0.0001). Conclusions: Access to PRT appears to be inequitable. More effort is required to make this useful treatment available to all those who would benefit from it.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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...

  12. 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...

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. 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.

  20. 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...

  1. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer

    OpenAIRE

    Sawant, Anandi; Deshane, Jessy; Jules, Joel; Lee, Carnella M.; Harris, Brittney A.; Feng, Xu; Ponnazhagan, Selvarangan

    2012-01-01

    Enhanced bone destruction is a hallmark of various carcinomas such as breast cancer, where osteolytic bone metastasis is associated with increased morbidity and mortality. Immune cells contribute to osteolysis in cancer growth but the factors contributing to aggressive bone destruction are not well understood. In this study, we demonstrate the importance of myeloid-derived suppressor cells (MDSC) in this process at bone metastatic sites. Since MDSC originate from the same myeloid lineage as m...

  2. Bone health in cancer patients

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  3. 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

  4. 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...

  5. 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 ...

  6. 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...

  7. 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.

  8. Complexity and Dynamic Heterogeneity of the Process of Cancer Metastasis

    Science.gov (United States)

    Chambers, Ann

    2010-03-01

    Cancer metastasis -- the spread of cancer from a primary tumor to distant parts of the body -- is responsible for most cancer deaths. If cancer is detected early, before it has spread, it can often be treated with local therapies like surgery and radiation. If cancer is detected after it has already spread, it is much harder to treat successfully. Cancer cells may be distributed to many organs, may be present as tiny micrometastases that are hard to detect, and cancer cells can be in a dormant state that may be resistant to treatment that is directed against actively dividing cells. A better understanding of the process of metastasis thus is needed in order to improve survival from cancer. Cancer is not a static disease, but one that can undergo stepwise evolution and progression from early, treatable cancer to aggressive cancer that is harder to treat. Furthermore, cancers are made up of many cells, and there is considerable heterogeneity among the cells in a tumor. Thus, cancer is ``plastic,'' with heterogeneity among cancer cells and changes over time. Understanding this ``dynamic heterogeneity'' has proven to be difficult. Input from physical sciences disciplines may help to shed light on this complex aspect of cancer biology. Here the process of cancer metastasis will be discussed, and experimental models for imaging the process described. The concept of ``dynamic heterogeneity'' of the metastatic process will be discussed, and some of the questions that need to be addressed for better understanding of metastasis will be outlined. An evolving dialogue between cancer biologists and physical scientists may lead to new ways of studying and understanding this lethal aspect of cancer.

  9. 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 ...

  10. Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

    OpenAIRE

    Santini Daniele; Barni Sandro; Intagliata Salvatore; Falcone Alfredo; Ferraù Francesco; Galetta Domenico; Moscetti Luca; La Verde Nicla; Ibrahim Toni; Petrelli Fausto; Vasile Enrico; Ginocchi Laura; Ottaviani Davide; Longo Flavia; Ortega Cinzia

    2015-01-01

    We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59...

  11. Metastasis features of 546 patients with stage IV non-small cell lung cancer at first visit and the significance in radiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical metastasis features and the possibility of 3 dimensional radiotherapy of stage IV non-small cell lung cancer (NSCLC). Methods: The clinical materials of 546 patients with stage IV NSCLC and the relationship b T and N stage and metastasis were retrospectively analyzed. Results In 546 patients with stage IV NSCLC, the number with bone metastasis was 294, the number with brain metastasis was 167, the number with lung metastasis was 137, the number with liver metastasis was 79, the number with adrenal gland metastasis was 66, 37 with lymph node metastasis, 35 with subcutaneous metastasis and 10 with other organ metastasis. The number with single organ metastasis was 379 (69.4%) ,in which 37.7% with bone metastasis, 19.8% with brain metastasis, 16.9% with lung metastasis, 7.4% with liver metastasis, 7.4% with adrenal gland metastasis, 4.5% with lymph node metastasis, 5.5% with subcutaneous metastasis and 0.8% with other organ metastasis. The bone metastasis probability of T3+4 patient was similar with T1+2 (69.4%, 30.6%, χ2 = 7.65, P = 0.067), but N2+3 patient was more than N0+1 (69.7%, 30.3%, χ2 = 7.89, P = 0.044). The brain metastasis probability of T3+4 patient was more than T1+2 (70.7%, 29.3%, χ2 = 10.64, P = 0.018), but N2+3 patient was similar with N0+1 (54.5%, 45.5%, χ2 = 7.14, P = 0.079), and N1+3+3 patient was more than N0 (86.8%, 13.2%, χ2 = 10.26, P = 0.024). Conclusions: In 546 patients with stage IV NSCLC, the most common metastatic organ is bone, the second is brain, the third is lung, the forth is liver, followed by adrenal gland; single organ metastasis is more common than multiple organ metastasis. The later the T stage is, the more severe is the metastasis. Through 3 dimensional radiotherapy, not only the quality of life of some stage IV patients is improved, but also the survival time was prolonged observably. (authors)

  12. h-prune affects anaplastic thyroid cancer invasion and metastasis.

    Science.gov (United States)

    Nambu, Junko; Kobayashi, Tsuyoshi; Hashimoto, Masakazu; Tashiro, Hirotaka; Sugino, Keizo; Shimamoto, Fumio; Kikuchi, Akira; Ohdan, Hideki

    2016-06-01

    Anaplastic thyroid cancer is one of the most aggressive human malignancies and is resistant to multimodal treatments. The expression of h-prune, the human homologue of Drosophila prune, has been reported to be correlated with progression and aggressiveness in various cancers including breast, colorectal and pancreatic cancers. We examined the role of h-prune in anaplastic thyroid cancer cell migration, invasion and metastasis. Immunohistochemical analysis of h-prune was performed with 15 surgically resected specimens of anaplastic thyroid cancers. To investigate cell motility, Boyden chamber, wound healing and matrigel invasion assays were performed using cells from anaplastic thyroid cancer cell lines. A murine orthotopic thyroid cancer model was used to investigate metastatic ability. In the immunohistochemical analysis, only weak focal or no staining of h-prune was observed in non-tumor tissue. In contrast, diffuse staining of h-prune was observed in anaplastic thyroid cancer and lymph node metastasis samples. Both inhibition of h-prune phosphodiesterase activity with dipyridamole and small interfering RNA for h-prune suppressed 8505C and KTC-3 cell motility. In addition, treatment with dipyridamole and decreased expression of h-prune suppressed tumor invasion and pulmonary metastasis in a NOD/Shi-scid, IL-2Rγnull (NOG) mouse orthotopic thyroid cancer model. In conclusion, h-prune is frequently expressed in anaplastic thyroid cancer cells and lymph nodes metastasis, and promotes migration and invasion of anaplastic thyroid cancer cells and metastasis in an anaplastic thyroid cancer model. Thus, h-prune shows promise as a targeting candidate against anaplastic thyroid cancer. PMID:27109060

  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. 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.

  15. 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...

  16. 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

  17. 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...

  18. Pituitary metastasis from breast cancer presenting as diabetes insipidus

    OpenAIRE

    Gormally, Joseph F; Izard, Michael A.; Robinson, Bruce G.; Boyle, Frances M

    2014-01-01

    An 83-year-old woman developed pituitary metastasis while being treated for metastatic breast cancer. She presented with visual disturbance and headache followed by thirst, nocturia and polyuria. A visual field defect was present. MRI revealed a sellar mass consistent with metastasis to the pituitary gland. She was successfully treated with radiotherapy to the sella and had improvement of her visual symptoms and visual field defect. She then required ongoing treatment for diabetes insipidus. ...

  19. 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...

  20. FH535 inhibited metastasis and growth of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Wu MY

    2015-07-01

    Full Text Available Meng-Yao Wu,1,* Rong-Rui Liang,1,* Kai Chen,1 Meng Shen,1 Ya-Li Tian,1,2 Dao-Ming Li,1 Wei-Ming Duan,1 Qi Gui,1 Fei-Ran Gong,3 Lian Lian,1,2 Wei Li,1,6 Min Tao1,4–61Department of Oncology, The First Affiliated Hospital of Soochow University, 2Department of Oncology, Suzhou Xiangcheng People’s Hospital, 3Department of Hematology, The First Affiliated Hospital of Soochow University, 4Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 5Institute of Medical Biotechnology, Soochow University, Suzhou, 6PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workAbstract: FH535 is a small-molecule inhibitor of the Wnt/β-catenin signaling pathway, which a substantial body of evidence has proven is activated in various cancers, including pancreatic cancer. Activation of the Wnt/β-catenin pathway plays an important role in tumor progression and metastasis. We investigated the inhibitory effect of FH535 on the metastasis and growth of pancreatic cancer cells. Western blotting and luciferase reporter gene assay indicated that FH535 markedly inhibited Wnt/β-catenin pathway viability in pancreatic cancer cells. In vitro wound healing, invasion, and adhesion assays revealed that FH535 significantly inhibited pancreatic cancer cell metastasis. We also observed the inhibitory effect of FH535 on pancreatic cancer cell growth via the tetrazolium and plate clone formation assays. Microarray analyses suggested that changes in the expression of multiple genes could be involved in the anti-cancer effect of FH535 on pancreatic cancer cells. Our results indicate for the first time that FH535 inhibits pancreatic cancer cell metastasis and growth, providing new insight into therapy of pancreatic cancer.Keywords: pancreatic cancer, FH535, β-catenin, metastasis, growth

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-23

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

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

    Directory of Open Access Journals (Sweden)

    Yoshiro Itatani

    2016-04-01

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

  4. Predicting sentinel lymph node metastasis in breast cancer with lymphoscintigraphy

    International Nuclear Information System (INIS)

    Lymphoscintigraphy is an effective method for detecting sentinel lymph nodes (SLNs). However, the rate and degree of SLN detection is not uniform. We quantified SLNs detected with lymphoscintigraphy, and investigated correlations with factors that may influence detection. We then attempted to predict SLN metastasis from lymph node counts, comparing the predictions to subsequent biopsy results. We assessed lymph node counts in 100 breast cancer patients in whom a single SLN was detected with a fixed lymphoscintigraphy procedure. We examined correlations between the counts and factors known to influence lymphoscintigraphic SLN detection (age, body mass index, tumor size, and presence or absence of metastasis), and determined reference values (lymph node counts of 10.0, 19.4 and 53.0) which were used to predict SLN metastasis in 100 subsequent patients. The predictions were then compared with the SLN biopsy findings. SLN counts correlated strongly with the presence or absence of metastasis, with metastasis-positive lymph nodes showing significantly lower counts than negative nodes (p<0.001). Prediction of SLN metastasis achieved a 100% positive predictive value at a reference value of 10.0, and a 100% negative predictive value at a reference value of 53.0. At a reference value of 19.4, the sensitivity, specificity, and diagnostic accuracy were 77.8, 73.2, and 74.0%, respectively. The SLN counts detected with lymphoscintigraphy were significantly lower in metastasis-positive lymph nodes than in metastasis-negative lymph nodes. This suggests that prediction of SLN metastasis in breast cancer is possible using lymphoscintigraphy. (author)

  5. 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 & ...

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

    International Nuclear Information System (INIS)

    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. 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. 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 facilitating tumor progression and metastasis in

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

    Directory of Open Access Journals (Sweden)

    Gruber Helen E

    2011-08-01

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

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

    International Nuclear Information System (INIS)

    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)

  9. 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

  10. BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

    Directory of Open Access Journals (Sweden)

    Yuan Hu

    2015-01-01

    Full Text Available Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT. This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.

  11. Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer

    International Nuclear Information System (INIS)

    To diagnose and explore the serological diagnostic factors for liver metastasis in patients with breast cancer before symptoms occur. A total of 430 female in-patients with breast cancer of stages 0 to IIIC who came to Tianjin Medical University Cancer Institute and Hospital from January 2003 to January 2004 were studied and followed up until May 2011. Serum levels of biochemical markers for tumor and liver were measured at the time of diagnosis. Liver metastasis was more likely to occur in patients with stage III cancer or c-erbB-2-positive expression. Alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase (LDH), and carbohydrate antigen 153 (CA153) levels were significantly higher in patients with liver metastasis than those without liver metastasis. Diagnostic indices of LDH, GGT, and CA153 were 174 U/L, 32 U/L, and 26.48 µg/L, respectively. The areas under the curves of LDH, GGT, and CEA were 0.795, 0.784, and 0.661, respectively, and sensitivities of parallel tests for LDH and CA153 and for GGT and CA153 were 88.6% and 85.7%, respectively. The specificity of serial tests for both pairs of enzymes was 97.7%. The sensitivity and specificity of combined tumor and biochemical markers could be used as indicators during screening for breast-liver metastasis

  12. 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

  13. 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...

  14. A Population-based Study of the Fractionation of Palliative Radiotherapy for Bone Metastasis in Ontario

    International Nuclear Information System (INIS)

    Purpose: To describe the use of palliative radiotherapy (PRT) for bone metastases in Ontario between 1984 and 2001 and identify factors associated with the choice of fractionation. Methods and Materials: Electronic RT records from the nine provincial RT centers in Ontario were linked to the Ontario Cancer Registry to identify all courses of PRT for bone metastases. Results: Between 1984 and 2001, 44,884 patients received 74,432 courses of PRT for bone metastases in Ontario. The mean number of courses per patient was 1.7, and 65% of patients received only a single course of PRT for bone metastasis. The mean number of fractions per course was 3.9. The proportion of patients treated with a single fraction increased from 27.2% in 1984-1986 to 40.3% in 1987-1992 and decreased thereafter. Single fractions were used more frequently in patients with a shorter life expectancy, in older patients, and in patients who lived further from an RT center. Single fractions were used more frequently when the prevailing waiting time for RT was longer. There were wide variations in the use of single fractions among the different RT centers (intercenter range, 11.8-62.3%). Intercenter variations persisted throughout the study period and were not explained by differences in case mix. Conclusions: Despite increasing evidence of the effectiveness of single-fraction PRT for bone metastases, most patients continued to receive fractionated PRT throughout the two decades of this study. Single fractions were used more frequently when waiting times were longer. There was persistent, unexplained variation in the fractionation of PRT among different centers

  15. 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

  16. 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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    I. Morales

    2016-03-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    biomarker in isolated metastases, in patients with liver metastasis of colorectal cancer (mCRC). Clinicopathological data of 166 patients with mCRC who had surgical resection between 2001 and 2011 were collected retrospectively. All primary tumors have been already resected. The platelet count was evaluated......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...

  20. 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.

  1. 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...

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

    OpenAIRE

    Mitsuyoshi Tei; Masaki Wakasugi; Hiroki Akamatsu

    2014-01-01

    INTRODUCTION: Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. PRESENTATION OF CASE: A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye an...

  3. Two cases of gastrointestinal stromal tumor of the small intestine with liver and bone metastasis.

    Science.gov (United States)

    Aktan, Meryem; Koc, Mehmet; Yavuz, Berrin Benli; Kanyilmaz, Gul

    2015-10-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors most commonly occur in the stomach (60%), jejunum and ileum (30%). Metastasis is characteristically the malignant behavior of the GISTs. GISTs most frequently metastasize to the liver and peritoneum, whereas bone and lung metastases are uncommon sites. Here, we described two cases of bone and liver metastases in patients with advanced GISTs. Both of them showed liver metastasis at disease presentation and bone metastasis in early time after the diagnosis. Bone metastases involved the lumber spine and right femur in first patient and L2 vertebral body in the second case. All of the lesions presented a lytic pattern. These cases are presented because of the rare incidence of bone metastasis to femur and vertebral bodies. More attention should be paid to the diagnosis of bone metastases from GISTs in clinical practice despite the shortage of available data on the sensitivity and specificity of bone scintigraphy and PET-CT. PMID:26605305

  4. 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

  5. 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.

  6. 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

  7. Hypoxia and metastasis in an orthotopic cervix cancer xenograft model

    International Nuclear Information System (INIS)

    Background: Hypoxia can promote tumor metastasis by mechanisms that are believed to result from changes in gene expression. The current study examined the role of putative metastatic genes regulated by cyclic hypoxia in relation to metastasis formation in orthotopic models of cervix cancer. Methods: Orthotopic tumors derived from ME180 human cervix cancer cells or from early generation human cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth in vivo and tumor growth and lymphnode metastases were monitored. Expression of the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth. Results: As reported previously, exposure of tumor bearing mice to cyclic hypoxia caused a reduction of tumor growth but a large increase in metastasis. Inhibition of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor size and reduced lymphatic metastasis to levels below those seen in control mice exposed to normoxic conditions. Conclusion: Blocking CXCR4 or Hh gene expression are potential therapeutic pathways for improving cervix cancer treatment

  8. Hypodense area within a meningioma: Metastasis from breast cancer

    International Nuclear Information System (INIS)

    A case of an intracranial meningioma containing a metastasis from breast cancer is reported. CT demonstrated a hypodense area within the meningioma and angiography showed a relatively less evident blush in the same area. The correlation of the neuroradiological with the pathological findings is discussed. (orig.)

  9. 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.

  10. Isolated splenic metastasis from colon cancer: Case report

    OpenAIRE

    Abdou, Jiddou; Omor, Youssef; Boutayeb, Saber; Elkhannoussi, Basma; Errihani, Hassan

    2016-01-01

    Isolated splenic metastases from colorectal cancer are very rare clinical entities and when they are present, they usually manifest widely disseminated disease. In this paper we report a case of metachronous solitary isolated splenic metastasis from colon cancer in a 64-year-old woman who was successfully treated by laparoscopic splenectomy. We discuss the pathological and clinical aspects of this condition. We furthermore comment on the diagnostic and therapeutic options of this rare entity ...

  11. 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 ...

  12. Molecular Aspects of Breast Cancer Metastasis to the Brain

    OpenAIRE

    Leonard Da Silva; Simpson, Peter T.; Sunil R. Lakhani; Saunus, Jodi M; Majid Momeny

    2011-01-01

    Our knowledge of the biology underlying the development of brain metastases (BM) from breast cancer has improved over the last decade due to large clinical epidemiological studies, animal models of metastasis, and the use of high-resolution gene expression profiling technologies. However, there are still major gaps in our understanding of the mechanisms utilized by breast cancer cells to colonize the brain microenvironment, thus our arsenal of therapies remains relatively nonspecific, and the...

  13. 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.

  14. 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.

  15. 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.

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

    OpenAIRE

    Oyewumi, Moses O.; Adnan Alazizi; Daniel Wehrung; Rami Manochakian; Safadi, Fayez F.

    2014-01-01

    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 q...

  17. Brain metastasis in breast cancer: a comprehensive literature review.

    Science.gov (United States)

    Rostami, Rezvan; Mittal, Shivam; Rostami, Pooya; Tavassoli, Fattaneh; Jabbari, Bahman

    2016-05-01

    This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER-, 36 % progesterone receptor (PR)+, 34 % PR-, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2-, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the

  18. 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

  19. 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...

  20. 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

  1. 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 ...

  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. Radioiodine therapy for pulmonary metastasis of differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Factors affecting the effect of radioiodide treatment for pulmonary metastasis of 26 patients with differentiated thyroid cancer were studied. The first treatments on the patients at Tokyo Women's Medical College were performed during 1973 and 1981, and the successive treatments were repeated until August, 1985. The X-ray findings of pulmonary metastasis were divided into three groups, ''Fine type'', ''Coarse type'', and ''Occult type''. Occult type was defined as the cases with diffuse I-131 uptake in the lung while the chest X-ray finding was normal. we evaluated the effect of I-131 treatment by means of changes in the number and size of metastatic shadows on chest X-ray or the degree of the I-131 accumulation in the lung on scintigram. Fourteen cases of 26 (53.8 %) were estimated to be treated successfully. Those under 40 years of age, with ''Fine type'' and with high I-131 uptake showed the best response to the treatment than others. The degree of I-131 uptake in the pulmonary metastasis had close relation with age and type of pulmonary metastasis defind by X-ray films and scintigrams, but little relationship with histology. Complete disappearance or decrease in number and size of metastatic shadows were shown in the majority of cases with good I-131 uptake and also ''Occult'' or ''Fine'' type. These results indicate that not only the degree of I-131 but age and type of pulmonary metastasis are important factors in predicting the effect of radioiodide treatment for pulmonary metastasis from differentiated thyroid cancer. (author)

  4. 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)

  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. 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

  7. Spontaneous regression of bone metastasis from renal cell carcinoma; A case report

    International Nuclear Information System (INIS)

    Spontaneous regression of metastatic renal cell carcinoma is rarely observed. Metastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells. We report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously

  8. 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)

  9. 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

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

    International Nuclear Information System (INIS)

    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)

  11. 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

  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. Intrapancreatic bile duct metastasis from colon cancer after resection of liver metastasis with intrabiliary growth: a case report.

    Science.gov (United States)

    Kawakatsu, Shoji; Kaneoka, Yuji; Maeda, Atsuyuki; Takayama, Yuichi; Fukami, Yasuyuki; Onoe, Shunsuke

    2015-01-01

    An extremely rare case of intrapancreatic bile duct metastasis from sigmoid colon adenocarcinoma is herein presented. Sigmoid colon cancer (T3, N0, M0, stage IIA) had been diagnosed and treated by sigmoidectomy in October 1993. In December 2002, a liver metastasis with intrabiliary growth was found, and this was treated by extended right hepatic lobectomy and caudate lobectomy with extrahepatic bile duct resection. In February 2014, intrapancreatic bile duct metastasis was found, and this was treated by subtotal stomach-preserving pancreatoduodenectomy. The intrapancreatic metastasis was judged to have arisen from cancer cell implantation, either by spontaneous shedding of cancer cells or as a complication of percutaneous transhepatic biliary drainage. Twelve months have passed since the last surgical intervention, and there has been no sign of local recurrence or distant metastasis. Differential diagnosis between intrahepatic cholangiocarcinoma and intrabiliary growth of a liver metastasis originating from colorectal adenocarcinoma is difficult but very important for determining the therapeutic strategy. Careful examination is needed to diagnose intrahepatic biliary dilatation, especially for patients with a history of carcinoma in the digestive tract and even if years have passed since curative resection of the digestive tract cancer. Aggressive surgical management for localized recurrence of a hepatic metastasis from colorectal adenocarcinoma may improve patient survival. PMID:26293132

  14. 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...

  15. Caecal metastasis from breast cancer presenting as intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Siddiqui Muhammad S

    2008-05-01

    Full Text Available Abstract Background Gastrointestinal metastsasis from the breast cancer are rare. We report a patient who presented with intestinal obstruction due to solitary caecal metastasis from infiltrating ductal carcinoma of breast. We also review the available literature briefly. Case presentation A 72 year old lady with past history of breast cancer presented with intestinal obstruction due to a caecal mass. She underwent an emergency right hemicolectomy. The histological examination of the right hemicolectomy specimen revealed an adenocarcinoma in caecum staining positive for Cytokeratin 7 and Carcinoembryonic antigen and negative for Cytokeratin 20, CDX2 and Estrogen receptor. Eight out of 11 mesenteric nodes showed tumour deposits. A histological diagnosis of metastatic breast carcinoma was given. Conclusion To the best of our knowledge, this is the first case report of solitary metastasis to caecum from infiltrating ductal carcinoma of breast. Awareness of this possibility will aid in appropriate management of such patients.

  16. The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis

    Science.gov (United States)

    Lebrun, Jean-Jacques

    2012-01-01

    The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects.

  17. 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...

  18. 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.)

  19. 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...

  20. Internal targeted radiotherapy for bone metastasis: what about underlying physiopathology

    International Nuclear Information System (INIS)

    Once tumours metastasize to bone, they are usually incurable and responsible for several devastating consequences: severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression and other nerve-compression syndromes. Understanding of physiopathological mechanisms responsible for these symptoms is critical for therapeutic approach, especially pain treatments. Three types of pain occur in tumour bone involvement: tonic or background pain, which are deep non-specific ache rising in intensity as the disease progresses; incident pain on movement (allodynia); and spontaneous pain which can be severe. Bone metastases could be osteolytic or osteoblastic. However, this classification actually represents two extremes of a continuum characterized by dys-regulation of the normal bone remodeling process. Biochemical mediators production is crucial as a part of this process. The bone microenvironment plays a critical role in the formation of osteoclasts through the production of macrophage colony-stimulating factor, receptor activator of nuclear factor kB ligand (RANKL)... Many of these mediators of osteolysis also have been shown to activate nociceptors: prostaglandins A and E, IL-1, IL-6, TNF. Thus there is a link between osteolytic destruction, inflammation and pain. It explains that severe pain could occur independently from fractures and in absence of any bone structure alteration and nervous compression. Also, pain is often disproportionate to tumour size or degree of bone involvement. Inflammatory and osteolytic processes depend on number, localization and organization of tumour cells inside bone and bone marrow tissues. All these parameters are crucial to take into account for a good understanding of treatments mechanisms of action, especially anti-inflammatory drugs (corticosteroid and others), bi-phosphonates, internal radiotherapy (strontium 89 or radiolabelled bi-phosphonates), external radiotherapy and chemotherapy or hormonotherapy

  1. Research Progress of Lung Cancer with Leptomeningeal Metastasis

    OpenAIRE

    MA, CHUNHUA; Jiang, Rong; LI, JINDUO; Wang, Bin(Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240, China); Sun, Liwei; Lv, Yuan

    2014-01-01

    Leptomeningeal metastases is one of the most serious complications of lung cancer, the patients with poor prognosis. Leptomeningeal metastasis in patients with lack specificity of clinical manifestations. The main clinical performance are the damage of cerebral symptoms, cranial nerve and spinal nerve. The diagnosis primarily based on the history of tumor, clinical symptoms, enhance magnetic resnance image (MRI) scan and cerebrospinal fluid cytology. In recent years, new ways of detecting cli...

  2. Isolated metachronous splenic metastasis from synchronous colon cancer

    Directory of Open Access Journals (Sweden)

    Aker Fugen

    2006-07-01

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

  3. MT1-MMP: Endosomal delivery drives breast cancer metastasis.

    Science.gov (United States)

    Linder, Stefan

    2015-10-26

    The membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) mediates proteolysis-based invasive tumor growth. In this issue, Marchesin et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201506002) describe a tug-of-war mechanism regulating dynein and kinesin motors to drive endosome tubulation and MT1-MMP delivery to the surface of cancer cells, identifying a crucial regulatory axis for tumor metastasis. PMID:26504163

  4. [Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer].

    Science.gov (United States)

    Hayashi, Nakamasa; Mitsuya, Koichi; Harada, Hideyuki; Watanabe, Junichiro; Nishimura, Tetsuo; Nakasu, Yoko

    2016-05-01

    Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years(average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination. PMID:27166841

  5. 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.

  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. 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

  8. 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.

  9. Treatment of Brain Metastasis from Lung Cancer

    OpenAIRE

    Alexander Chi; Ritsuko Komaki

    2010-01-01

    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 com...

  10. Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma.

    Science.gov (United States)

    Takigawa, Hidehiko; Kitadai, Yasuhiko; Shinagawa, Kei; Yuge, Ryo; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2016-05-01

    Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma-associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor-β (PDGFR-β) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-β, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor-promoting effect of CAFs/MSCs. KM12SM human colon cancer cells alone or KM12SM cells with MSCs were transplanted into the cecal wall of nude mice. Co-implantation of KM12SM cells with MSCs into the cecal wall of nude mice produced tumors with abundant stromal component and promoted tumor growth and lymph node metastasis. Single treatment with regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction. This tumor-inhibitory effect of regorafenib was more obvious in tumors developed by co-implanting KM12SM cells with MSCs. Our data suggested that targeting of the tumor microenvironment with regorafenib affected tumor cell-MSC interaction, which in turn inhibited the growth and metastasis of colon cancer. PMID:26865419

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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...

  16. Mechanisms of cancer-induced bone pain

    OpenAIRE

    Lozano-Ondoua, AN; Symons-Liguori, AM; Vanderah, TW

    2013-01-01

    Cancerous cells can originate in a number of different tissues such as prostate, breast and lung, yet often go undetected and are non-painful. Many types of cancers will metastasize toward the bone microenvironment first. Tumor burden within the bone causes excruciating breakthrough pain with properties of continual pain inadequately managed with current analgesics. Part of this failure is due to the poor understanding of the etiology of cancer pain. Animal models of cancer-induced bone pain ...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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

  3. Blood-Brain Barrier Integrity and Breast Cancer Metastasis to the Brain

    OpenAIRE

    Hava Karsenty Avraham; Shalom Avraham; Christopher Sy; Lili Wang; Farheen Arshad

    2011-01-01

    Brain metastasis, an important cause of cancer morbidity and mortality, occurs in at least 30% of patients with breast cancer. A key event of brain metastasis is the migration of cancer cells through the blood-brain barrier (BBB). Although preventing brain metastasis is immensely important for survival, very little is known about the early stage of transmigration and the molecular mechanisms of breast tumor cells penetrating the BBB. The brain endothelium plays an important role in brain meta...

  4. 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...

  5. 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)

  6. 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

  7. 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

  8. Cutaneous metastasis as the first sign of lung cancer

    Directory of Open Access Journals (Sweden)

    Ðurić Milivoje

    2013-01-01

    Full Text Available Cutaneous metastases of lung tumors are occurring in 1-12% of cases. High prevalence of lung cancer increases the likelihood of finding these changes in clinical practice. They are usually in the form of a firm, mobile and painless nodule on the head, neck and chest, and their appearance is a sign of advanced disease. Cutaneous metastases are rarely the first sign of malignancy. A 62-year-old patient presented to her doctor a fast-growing nodule on the forehead. Extirpation of the nodule and further diagnosis showed that it was a metastasis of small cell lung cancer localized in the right lung with extensive metastases to the contralateral lung, liver and spine. Cutaneous metastases may be the first sign of malignancy or the first sign of progression of already diagnosed malignancy. A diagnosis of metastatic disease should be considered in patients with risk factors or a known cancer. The presence of a skin metastasis in a patient with a lung cancer indicates poor prognosis.

  9. 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. PMID:24211475

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

    Directory of Open Access Journals (Sweden)

    Chih-Hsin Tang

    2013-05-01

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

  11. 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

  12. Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

    Directory of Open Access Journals (Sweden)

    Biswas Swati

    2010-05-01

    Full Text Available Abstract Background Transforming Growth Factor β (TGF-β plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173 or bones (SCP2TR, SCP25TR, 2860TR, 3847TR. Results Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones in vitro. Moreover, both antagonists inhibited TGF-β stimulated in vitro migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones in vivo, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer. Conclusions In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic

  13. 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...

  14. 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...

  15. Evolution of cellular morpho-phenotypes in cancer metastasis.

    Science.gov (United States)

    Wu, Pei-Hsun; Phillip, Jude M; Khatau, Shyam B; Chen, Wei-Chiang; Stirman, Jeffrey; Rosseel, Sophie; Tschudi, Katherine; Van Patten, Joshua; Wong, Michael; Gupta, Sonal; Baras, Alexander S; Leek, Jeffrey T; Maitra, Anirban; Wirtz, Denis

    2015-01-01

    Intratumoral heterogeneity greatly complicates the study of molecular mechanisms driving cancer progression and our ability to predict patient outcomes. Here we have developed an automated high-throughput cell-imaging platform (htCIP) that allows us to extract high-content information about individual cells, including cell morphology, molecular content and local cell density at single-cell resolution. We further develop a comprehensive visually-aided morpho-phenotyping recognition (VAMPIRE) tool to analyze irregular cellular and nuclear shapes in both 2D and 3D microenvironments. VAMPIRE analysis of ~39,000 cells from 13 previously sequenced patient-derived pancreatic cancer samples indicate that metastasized cells present significantly lower heterogeneity than primary tumor cells. We found the same morphological signature for metastasis for a cohort of 10 breast cancer cell lines. We further decipher the relative contributions to heterogeneity from cell cycle, cell-cell contact, cell stochasticity and heritable morphological variations. PMID:26675084

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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...

  2. 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

  3. An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer.

    Science.gov (United States)

    Xu, Song; Zhang, Zhengyu; Ogawa, Osamu; Yoshikawa, Takeshi; Sakamoto, Hiromasa; Shibasaki, Noboru; Goto, Takayuki; Wang, Liming; Terada, Naoki

    2014-09-01

    EP4 is one of the prostaglandin E2 receptors, which is the most common prostanoid and is associated with inflammatory disease and cancer. We previously reported that over-expression of EP4 was one of the mechanisms responsible for progression to castration-resistant prostate cancer, and an EP4 antagonist ONO-AE3-208 in vivo suppressed the castration-resistant progression regulating the activation of androgen receptor. The aim of this study was to analyze the association of EP4 with prostate cancer metastasis and the efficacy of ONO-AE3-208 for suppressing the metastasis. The expression levels of EP4 mRNA were evaluated in prostate cancer cell lines, LNCaP, and PC3. EP4 over-expressing LNCaP was established, and their cell invasiveness was compared with the control LNCaP (LNCaP/mock). The in vitro cell proliferation, invasion, and migration of these cells were examined under different concentrations of ONO-AE3-208. An in vivo bone metastatic mouse model was constructed by inoculating luciferase expressing PC3 cells into left ventricle of nude mice. Their bone metastasis was observed by bioluminescent imaging with or without ONO-AE3-208 administration. The EP4 mRNA expression levels were higher in PC3 than in LNCaP, and EP4 over-expression of LNCaP cells enhanced their cell invasiveness. The in vitro cell invasion and migration were suppressed by ONO-AE3-208 in a dose-dependent manner without affecting cell proliferation. The in vivo bone metastasis of PC3 was also suppressed by ONO-AE3-208 treatment. EP4 expression levels were correlated with prostate cancer cell invasiveness and EP4 specific antagonist ONO-AE3-208 suppressed cell invasion, migration, and bone metastasis, indicating that it is a potential novel therapeutic modality for the treatment of metastatic prostate cancer. PMID:24744183

  4. Relation between serum PAP (prostate acid phosphatase) and bone scintigraphy in prostatic cancer

    International Nuclear Information System (INIS)

    Seventy-seven patients with prostatic cancer were treated at our department in the last 5 years. Of these patients 30 cases were followed by bone scintigraphy and serum PAP. In 27 follow-up scintigraphy procedures changes of bone scintigraphy corresponded to changes in serum PAP levels. Changes of PAP levels did not always correspond to changes of scintigraphy, but almost all cases in which the level of PAP increased in a short period showed progression of bone metastasis. A 3-month interval between bone scintigraphy procedure in stage D2 prostatic cancer patients is generally recommended. However, we think that in prostatic cancer patients follow-up bone scintigraphy at regular short intervals is unnecessary if there is no change in serum PAP levels, symptoms or physical condition. Bone scintigraphy should be performed when the tumor marker changes rapidly or when any physical symptom appears. (author)

  5. 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

  6. What's New in Bone Cancer Research and Treatment?

    Science.gov (United States)

    ... resources for bone cancer What’s new in bone cancer research and treatment? Research on bone cancer is now ... Your Doctor After Treatment What`s New in Bone Cancer Research? AdditionalResources Other Resources and References Cancer Information Cancer ...

  7. Metachronous pulmonary metastasis after radical esophagectomy for esophageal cancer: prognosis and outcome

    OpenAIRE

    Takemura Masashi; Sakurai Katsunobu; Takii Mamiko; Yoshida Kayo

    2012-01-01

    Abstract Background Few reports discuss the outcome of pulmonary metastasis after radical esophagectomy for esophageal cancer. To clarify the data from such cases, we conducted a retrospective study on the clinical outcome of patients who developed pulmonary metastasis after undergoing radical esophagectomy. Methods We retrospectively reviewed the prognosis and clinical outcome of 25 patients who developed metachronous pulmonary metastasis after esophagectomy for esophageal cancer. Results Th...

  8. 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.

  9. 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.

  10. 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.

  11. Research Progress of Lung Cancer with Leptomeningeal Metastasis

    Directory of Open Access Journals (Sweden)

    Chunhua MA

    2014-09-01

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

  12. 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

  13. 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...

  14. 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

  15. 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.

  16. Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

    OpenAIRE

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

    2014-01-01

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pa...

  17. 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...

  18. 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

  19. A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, N.; Morita, R.; Yamamoto, T.; Muranaka, A.; Tomomitsu, T.; Yanagimoto, S.; Sone, T.; Fukunaga, M.

    1985-04-01

    In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.

  20. A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy

    International Nuclear Information System (INIS)

    In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Janet E. Brown

    2010-09-01

    Full Text Available 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 affecting PSA levels. As bone metastases develop, factors derived from bone metabolism are released into blood and urine, including N- and C-terminal peptide fragments of type 1 collagen and bone-specific alkaline phosphatase, which represent potentially useful biomarkers for monitoring metastatic bone disease. A number of clinical trials have investigated these bone biomarkers with respect to their diagnostic, prognostic, and predictive values. Results suggest that higher levels of bone biomarkers are associated with an increased risk of skeletal-related events and/or death. As a result of these findings, bone biomarkers are now being increasingly used as study end points, particularly in studies investigating novel agents with putative bone effects. Data from prospective clinical trials are needed to validate the use of bone biomarkers and to confirm that marker levels provide additional information beyond traditional methods of response evaluation for patients with metastatic prostate cancer.

  3. Radiation therapy for bone metastasis from hepatocellular carcinoma. Evaluation of pain relief and tumor regression

    Energy Technology Data Exchange (ETDEWEB)

    Wakisaka, Masaki; Mori, Hiromu; Matsumoto, Akira; Ochotorena, I. J.; Funakoshi, Takeshi [Oita Medical Univ. (Japan)

    1999-01-01

    The purpose of this retrospective study is to analyze the effectiveness of radiation therapy (RT) for the patients with bone metastasis from HCC with regard to tumor regression and pain relief. Twenty-five patients (42-78 years old) with 32 bone metastases (7 ribs, 13 vertebras, 6 iliums, 3 humeruses, 2 femurs and 1 scapula) from HCC received RT (10-60 Gy, mean 35.9 Gy). RT was performed using 5-10 MV x-rays or 12-18 MeV electron beams from a linear accelerator. Additional transcatheter arterial injection of anti-cancer drugs (TAI) and/or arterial embolization (TAE) were carried out for five lesions. Pain relief was obtained in 22 patients with 26 lesions (81%). Pain relief appeared at a dose of 12-30 Gy with a mean of 18.5 Gy. In 9 patients (82%) with 12 lesions out of 11 patients with 15 lesions who could be evaluated for duration of pain relief, recurrence of pain was not noted up to the last follow-up day or to the death of the patients (1-36 months). In 13 lesions, tumor regression was evaluated by CT and/or MRI; Complete regression (CR) was noted in 1 lesion, partial regression (PR) in 6 lesions, no change (NC) in 2 lesions, and progressive disease (PD) in 4 lesions. The tumor regression (CR+PR) rate was 53.8%. In 8 lesions treated with RT alone, there was PR in 2 lesions, NC in 2 lesions, PD in 4 lesions, and CR was not seen. In 5 lesions treated with a combination of RT and TAI and/or TAE, CR was noted in 1 lesion, PR in 4 lesions and no NC or PD. There was a correlation between the initial tumor volume and the degree of pain before RT, but there was no correlation between tumor regression and pain relief after RT. The one-year survival rate was 17%, and the two-year rate was 8%. (K.H.)

  4. 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

  5. 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

  6. 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

  7. 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 ...

  8. 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

  9. Studies of radiation effect on cancer metastasis. History and present status

    International Nuclear Information System (INIS)

    Local control of cancers by radiotherapy has been greatly improved by its recent progress like heavy ion therapy and intensity modulated radiotherapy, but its outcome is not fully satisfactory because of metastasis, the concept proposed about 200 years ago, as one of death courses. From this aspect, here are described the mechanism of metastasis, radiation effect on it and its relation to hypoxic circumstance in cancers. The author explains the sequence of metastasis as those steps of cancer cell proliferation at the primary site, cellular release from there, intravasation to distribute in the blood, adhesion to vascular endotherial cells of an organ, cellular extravasation into that organ and growth there (metastasis), organ specificity and Seed/Soil theory, and cancer cells with accelerated metastatic activity in animal models. For radiation effect on metastasis, whether low linear energy transfer (LET) radiation to the primary site affects the incidence of distant metastasis seems to be mostly dependent on the total dose. Authors observation is that lung metastasis is insignificant between mice gamma-ray irradiated at their tumor transplanted site (femur) at 0 and 10-20 Gy but significant in animals with higher dose. As for factors affecting metastasis, radiation effect is contradictory for cellular activities of migration and invasion, and for angiogenesis, seemingly depends on the dose and radio-sensitivity in cancer and endothelium cells. There are many reports that high LET radiation like carbon ion suppresses metastasis in animals even at the dose where low LET radiation often promotes it. It is suggestive that carbon ion suppresses macromolecules concerned to migration and invasion. Hypoxia occurring in cancer tissue is known to be related with patient's poor prognosis due to therapy resistance, local relapse and distant metastasis. Now that there are various radiotherapies greatly improving the local control of cancers, further studies on metastasis are

  10. 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...

  11. 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

  12. 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.

  13. Signatures of breast cancer metastasis at a glance.

    Science.gov (United States)

    Karagiannis, George S; Goswami, Sumanta; Jones, Joan G; Oktay, Maja H; Condeelis, John S

    2016-05-01

    Gene expression profiling has yielded expression signatures from which prognostic tests can be derived to facilitate clinical decision making in breast cancer patients. Some of these signatures are based on profiling of whole tumor tissue (tissue signatures), which includes all tumor and stromal cells. Prognostic markers have also been derived from the profiling of metastasizing tumor cells, including circulating tumor cells (CTCs) and migratory-disseminating tumor cells within the primary tumor. The metastasis signatures based on CTCs and migratory-disseminating tumor cells have greater potential for unraveling cell biology insights and mechanistic underpinnings of tumor cell dissemination and metastasis. Of clinical interest is the promise that stratification of patients into high or low metastatic risk, as well as assessing the need for cytotoxic therapy, might be improved if prognostics derived from these two types of signatures are used in a combined way. The aim of this Cell Science at a Glance article and accompanying poster is to navigate through both types of signatures and their derived prognostics, as well as to highlight biological insights and clinical applications that could be derived from them, especially when they are used in combination. PMID:27084578

  14. 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

  15. 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.

  16. 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

  17. Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

    International Nuclear Information System (INIS)

    Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm2) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm2). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo

  18. 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.

  19. Radiation therapy for brain metastasis from lung cancer

    International Nuclear Information System (INIS)

    The prognosis for patients with brain metastasis from lung cancer following radiation therapy was evaluated. Seventy-eight patients received brain irradiation in the Osaka Prefectural Habikino Hospital between April 1985 and March 1989. Almost all patients had conventional radiotherapy of the whole brain, with a single dose of 2 or 3 Gy. Patients characteristics associated with favorable prognosis were as follows: Performance status of 0∼1, age≤49, female, histology of adenocarcinoma. Patients who received radiotherapy of 56 Gy10 or more, had longer survival time. The findings in the brain CT were evaluated, but the number, size, site of metastases, and mass effect to ventricular system were not related to the prognosis. The overall median survival was 3.5 months and the 1-year survival rate was 9.0%. Further clinical studies are necessary to improve the prognosis in brain metastases. (author)

  20. 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.

  1. Quantitative evaluation of bone metastases in patients with advanced prostate cancer during endocrine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yahara, Jyunro [Kurume Univ., Fukuoka (Japan). School of Medicine

    2003-02-01

    A well-recognized difficulty in assessing the response to therapy for advanced prostate cancer is the infrequency of measurable metastatic disease. The most common metastatic site is bone, and it is manifested by diffuse ostoblastic lesions that cannot be measured reliably to allow for assessments of therapeutic benefits. We assessed the clinical usefulness of quantifying the extent of disease on bone scans in monitoring treatment response in patients with advance prostate cancer using computer-assisted image analysis. Percentage of the positive area on the bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program. Serial measurements of %PABS in 44 patients with bone metastasis from prostate cancer followed for a mean of 33 month (range 4 to 72) with hormonal therapy were compared with those of the extent of disease (EOD) grades in bone lesions and serum prostate specific antigen (PSA) levels according to treatment response. Serial measurements of EOD grades and %PABS in 13 patients with partial response (PR) disease and those in 12 patients with progressive disease (PD) who did not show bone metastasis progression demonstrated a downward trend during the treatment. On the other hand, changes of EOD grades and %PABS in the remaining 19 patients with PD who showed bone metastasis progression demonstrated an upward trend. Estimated survival curves showed that %PABS was a useful prognostic indicator, with the patients who showed a 25% decline in %PABS surviving longer than the patients who showed a less than 25% decline in %PABS after treatment (p=0.0207). The %PABS is a simple and reproducible estimate of the percentage of the skeleton involving tumors in patients with advanced prostate cancer, and serial measurements of %PABS can assist in monitoring the treatment response in patients with bone metastatic prostate cancer. (author)

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. Surgical Treatment for Non-small Cell Lung Cancer Patients with Synchronous Solitary Brain Metastasis

    OpenAIRE

    Bai, Hao; Han, Baohui

    2013-01-01

    Background and objective Brain metastases are common in non-small cell lung cancer. Usual treatments include radiotherapy and chemotherapy. However, these methods result in poor patient prognosis. The aim of this study is to assess the effectiveness of surgical resection in the multimodality management of non-small cell lung cancer patients with synchronous solitary brain metastasis. Methods The clinical data of 46 non-small cell lung cancer patients with synchronous solitary brain metastasis...

  7. 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.

  8. STAT3 regulated ARF expression suppresses prostate cancer metastasis

    Science.gov (United States)

    Pencik, Jan; Schlederer, Michaela; Gruber, Wolfgang; Unger, Christine; Walker, Steven M.; Chalaris, Athena; Marié, Isabelle J.; Hassler, Melanie R.; Javaheri, Tahereh; Aksoy, Osman; Blayney, Jaine K.; Prutsch, Nicole; Skucha, Anna; Herac, Merima; Krämer, Oliver H.; Mazal, Peter; Grebien, Florian; Egger, Gerda; Poli, Valeria; Mikulits, Wolfgang; Eferl, Robert; Esterbauer, Harald; Kennedy, Richard; Fend, Falko; Scharpf, Marcus; Braun, Martin; Perner, Sven; Levy, David E.; Malcolm, Tim; Turner, Suzanne D.; Haitel, Andrea; Susani, Martin; Moazzami, Ali; Rose-John, Stefan; Aberger, Fritz; Merkel, Olaf; Moriggl, Richard; Culig, Zoran; Dolznig, Helmut; Kenner, Lukas

    2015-01-01

    Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19ARF as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14ARF expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition. PMID:26198641

  9. 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

  10. 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)

  11. Subtle pleural metastasis without large effusion in lung cancer patients: preoperative detection on CT

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jung Hwa; Kwon, Kui Hyang; Goo, Dong Erk [Soonchunhyang University Hospital, Seoul (Korea, Republic of); Song, Koun Sik; Park, Seung Il; Lim, Tae Hwan [Asan medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    We wanted to describe the retrospective CT features of subtle pleural metastasis without large effusion that would suggest inoperable lung cancer. We enrolled 14 patients who had open thoracotomy attempted for lung cancer, but they were proven to be inoperable due to pleural metastasis. Our study also included 20 control patients who were proven as having no pleural metastasis. We retrospectively evaluated the nodularity and thickening of the pleura and the associated pleural effusion on the preoperative chest CT scans. We reviewed the histologic cancer types, the size, shape and location of the lung cancer and the associated mediastinal lymphadenopathy. Subtle pleural nodularity or focal thickening was noted in seven patients (50%) having pleural metastasis and also in three patients (15%) of control group who were without pleural metastasis. More than one of the pleural changes such as subtle pleural nodularity, focal thickening or effusion was identified in eight (57%) patients having pleural metastasis and also in three patients (15%) of the control group, and these findings were significantly less frequent in the control group patients than for the patients with pleural metastasis ({rho} = 0.02). The histologic types of primary lung cancer in patients with pleural metastasis revealed as adenocarcinoma in 10 patients (71%) and squamous cell carcinoma in four patients (29%). The location, size and shape of the primary lung cancer and the associated mediastinal lymphadenopathy showed no significant correlation with pleural metastasis. If any subtle pleural nodularity or thickening is found on preoperative chest CT scans of patients with lung cancer, the possibility of pleural metastasis should be considered.

  12. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis

    Directory of Open Access Journals (Sweden)

    Cheng Ji-Xin

    2009-01-01

    Full Text Available Abstract Background Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Methods Coherent anti-Stokes Raman scattering (CARS microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. Results CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs. Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Conclusion Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis.

  15. Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis

    International Nuclear Information System (INIS)

    Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer metastasis

  16. 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...

  17. 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...

  18. 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

  19. Arteria1 microvascularization and breast cancer colonization in bone

    OpenAIRE

    Yoneda, T

    1997-01-01

    Bone is one of the most preferential target organs of cancer metastases. Breast, prostate and lung cancers have a special predilection for colonization in bone. In an animal model in which inoculation of cancer cells into the left cardiac ventricle selectively develops osteolytic bone metastases but rarely forms metastases in non-bone organs, the pattern of breast cancer colonization in bone was studied radiologically and histologically. Colonization of cancer ...

  20. Bone Cancer - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bone Cancer URL of this page: https://medlineplus.gov/languages/bonecancer.html Other topics A-Z A B ...

  1. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  2. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    International Nuclear Information System (INIS)

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

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

    Institute of Scientific and Technical Information of China (English)

    Helfried Waleczek; Moritz N Wente; Jürgen Kozianka

    2005-01-01

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

  4. Simultaneous thigh muscle metastasis from lung cancer and Escherichia coli gas producing myonecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Gonzalo E. [Hospital Italiano, Department of Radiology, Cordoba (Argentina); Coursey, Courtney A.; Martinez, Salutario [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Dodd, Leslie [Duke University Medical Center, Department of Pathology, Durham, NC (United States)

    2008-08-15

    We present the case of a 41-year-old man with known large cell lung cancer who had undergone left pneumonectomy 7 months prior and who presented with a large intramuscular mass involving the posterior left thigh and upper calf. This thigh mass was ultimately surgically explored, and specimens yielded both Escherichia coli organisms and cells reflecting a skeletal muscle metastasis from the patient's known lung cancer. The patient was also found to have a rectal metastasis from his lung cancer. Intramuscular abscesses produced by gastrointestinal tract flora are a well-known presentation of colon cancer. To our knowledge, this is the first case report of the simultaneous occurrence of a skeletal muscle metastasis and an E. coli abscess in the same anatomic location. We believe the patient's rectal metastasis may have been the intermediate step in this process. (orig.)

  5. Simultaneous thigh muscle metastasis from lung cancer and Escherichia coli gas producing myonecrosis

    International Nuclear Information System (INIS)

    We present the case of a 41-year-old man with known large cell lung cancer who had undergone left pneumonectomy 7 months prior and who presented with a large intramuscular mass involving the posterior left thigh and upper calf. This thigh mass was ultimately surgically explored, and specimens yielded both Escherichia coli organisms and cells reflecting a skeletal muscle metastasis from the patient's known lung cancer. The patient was also found to have a rectal metastasis from his lung cancer. Intramuscular abscesses produced by gastrointestinal tract flora are a well-known presentation of colon cancer. To our knowledge, this is the first case report of the simultaneous occurrence of a skeletal muscle metastasis and an E. coli abscess in the same anatomic location. We believe the patient's rectal metastasis may have been the intermediate step in this process. (orig.)

  6. Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways.

    Science.gov (United States)

    Liu, Jiao; Chen, Sheng; Wang, Wei; Ning, Bei-Fang; Chen, Fei; Shen, Weifeng; Ding, Jin; Chen, Wansheng; Xie, Wei-Fen; Zhang, Xin

    2016-08-28

    Fibroblasts are rich in the surrounding microenvironment of hepatocellular carcinoma (HCC) because most HCCs occur in fibrotic or cirrhotic livers. However, the role of cancer-associated fibroblasts (CAFs) in HCC metastasis remains obscure. Here, we reported that CAFs promote the migration and invasion of HCC cells in vitro and facilitate the HCC metastasis to the bone, brain and lung in NOD/SCID mice. The RayBio human chemokine antibody array revealed that CAFs secret higher levels of CCL2, CCL5, CCL7 and CXCL16 than peri-tumor fibroblasts. CCL2 and CCL5 increase the migration but not the invasion of HCC cells, while CCL7 and CXCL16 promote both migration and invasion of HCC cells. Moreover, CCL2 and CCL5 stimulate the activation of the hedgehog (Hh) pathway, while CCL7 and CXCL16 enhance the activity of the transforming growth factor-β (TGF-β) pathway in HCC cells. The neutralizing antibodies of chemokines notably attenuate the effect of CAFs on HCC metastasis and compromised the activation of Hh and TGF-β pathways in HCC cells. In summary, CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. PMID:27216982

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

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer.

    Science.gov (United States)

    Adjei, Isaac M; Sharma, Blanka; Peetla, Chiranjeevi; Labhasetwar, Vinod

    2016-06-28

    Advanced-stage prostate cancer usually metastasizes to bone and is untreatable due to poor biodistribution of intravenously administered anticancer drugs to bone. In this study, we modulated the surface charge/composition of biodegradable nanoparticles (NPs) to sustain their blood circulation time and made them small enough to extravasate through the openings of the bone's sinusoidal capillaries and thus localize into marrow. NPs with a neutral surface charge, achieved by modulating the NP surface-associated emulsifier composition, were more effective at localizing to bone marrow than NPs with a cationic or anionic surface charge. These small neutral NPs (~150nm vs. the more usual ~320nm) were also ~7-fold more effective in localizing in bone marrow than large NPs. We hypothesized that NPs that effectively localize to marrow could improve NP-mediated anticancer drug delivery to sites of bone metastasis, thereby inhibiting cancer progression and preventing bone loss. In a PC-3M-luc cell-induced osteolytic intraosseous model of prostate cancer, these small neutral NPs demonstrated greater accumulation in bone within metastatic sites than in normal contralateral bone as well as co-localization with the tumor mass in marrow. Significantly, a single-dose intravenous administration of these small neutral NPs loaded with paclitaxel (PTX-NPs), but not anionic PTX-NPs, slowed the progression of bone metastasis. In addition, neutral PTX-NPs prevented bone loss, whereas animals treated with the rapid-release drug formulation Cremophor EL (PTX-CrEL) or saline (control) showed >50% bone loss. Neutral PTX-NPs did not cause acute toxicity, whereas animals treated with PTX-CrEL experienced weight loss. These results indicate that NPs with appropriate physical and sustained drug-release characteristics could be explored to treat bone metastasis, a significant clinical issue in prostate and other cancers. PMID:27090164

  10. 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

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

    Institute of Scientific and Technical Information of China (English)

    Xiang-Ming Ding

    2014-01-01

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

  12. Reconstruction with a pectoralis major myocutaneous flap after left first rib and clavicular chest wall resection for a metastasis from laryngeal cancer.

    Science.gov (United States)

    Caronia, Francesco Paolo; Fiorelli, Alfonso; Zanchini, Fabio; Santini, Mario; Lo Monte, Attilio Ignazio; Castorina, Sergio

    2016-05-01

    We presented a case of recurrent metastasis from epidermoid cancer that occurred in the left clavicle of a patient with a history of laryngeal cancer treated on April 2005 with extended hemilaryngectomy, neck dissection and chemoradiation therapy. On September 2008, he developed a left clavicular metastasis. The disease was initially well controlled by chemoradiotherapy but it recurred 17 months later. The optimal treatment plan was established by several multidisciplinary meetings and the patient subsequently underwent an en bloc resection of the left clavicle, first rib and all the other involved structures. Coverage of the thoracic defect was achieved using pectoralis major myocutaneous flap. The patient had a successful surgical outcome. At 1-year follow-up, he had no evidence of disease, a good cosmetic result and returned to normal daily activity. He died for bone metastasis with an overall 21 months post-surgical survival. PMID:25319560

  13. Loss of P53 facilitates invasion and metastasis of prostate cancer cells.

    Science.gov (United States)

    Wang, Yi; Zhang, Y X; Kong, C Z; Zhang, Z; Zhu, Y Y

    2013-12-01

    Prostate cancer is a lethal cancer for the invasion and metastasis in its earlier period. P53 is a tumor suppressor gene which plays a critical role on safeguarding the integrity of genome. However, loss of P53 facilitates or inhibits the invasion and metastasis of tumor is still suspended. In this study, we are going to explain whether loss of P53 affect the invasion and metastasis of prostate cancer cells. To explore whether loss of P53 influences the invasion and metastasis ability of prostate cancer cells, we first compared the invasion ability of si-P53 treated cells and control cells by wound healing, transwell assay, and adhesion assay. We next tested the activity of MMP-2, MMP-9, and MMP-14 by western blot and gelatin zymography. Moreover, we employed WB and IF to identify the EMT containing E-cad, N-cad, vimentin, etc. We also examined the expression of cortactin, cytoskeleton, and paxillin by immunofluorescence, and tested the expression of ERK and JNK by WB. Finally, we applied WB to detect the expression of FAK, Src, and the phosphorylation of them to elucidate the mechanism of si-P53 influencing invasion and metastasis. According to the inhibition rate of si-P53, we choose the optimized volume of si-P53. With the volume, we compare the invasion and metastasis ability of Du145 and si-P53 treated cells. We find si-P53 promotes the invasion and metastasis in prostate cancer cells, increases the expression and activity of MMP-2/9 and MMP-14. Also, si-P53 promotes EMT and cytoskeleton rearrangement. Further analyses explain that this effect is associated with FAK-Src signaling pathway. Loss of P53 promotes the invasion and metastasis ability of prostate cancer cells and the mechanism is correlated with FAK-Src signaling pathway. P53 is involved in the context of invasion and metastasis. PMID:23982184

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Enrique Gómez Gómez

    2014-01-01

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

  16. Solitary pulmonary metastasis of pancreatic cancer presenting a thin-walled cavity

    OpenAIRE

    Katsunari Matsuoka; Mitsuhiro Ueda; Yoshihiro Miyamoto

    2015-01-01

    Because the prognosis of the patients with pancreatic cancer is very poor, there are few opportunities to perform surgery for pulmonary metastasis. Here we report the resection of a solitary pulmonary metastasis from pancreatic cancer, appearing as thin-walled cavity, which appeared 5 years after pancreaticoduodenectomy. Although the present patient underwent incomplete resection because of malignant pleural effusion and pleural dissemination, he is currently still alive without evident recur...

  17. Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

    OpenAIRE

    Lorger, Mihaela; Felding-Habermann, Brunhilde

    2010-01-01

    Brain metastases are difficult to treat and mostly develop late during progressive metastatic disease. Patients at risk would benefit from the development of prevention and improved treatments. This requires knowledge of the initial events that lead to brain metastasis. The present study reveals cellular events during the initiation of brain metastasis by breast cancer cells and documents the earliest host responses to incoming cancer cells after carotid artery injection in immunodeficient an...

  18. Association between brain metastasis from lung cancer and the serum level of myelin basic protein

    OpenAIRE

    Liu, Wei; Zhao, Jing; WEI, YUJUAN

    2015-01-01

    The aim of the present study was to determine the association between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. A total of 68 lung cancer patients, treated in the Department of Respiratory Medicine of the People’s Hospital of Rizhao (Rizhao, China), were divided into two groups, those with brain metastasis (32 cases) and those without brain metastasis (36 cases). The expression levels of myelin basic protein were measured for all the p...

  19. Leptomeningeal metastasis of uterine cervical cancer 17 years after primary tumor treatment

    OpenAIRE

    Oike, Takahiro; Ohno, Tatsuya; Noda, Shin‐Ei; Murata, Tomomi; Hirakawa, Takashi; Hirato, Junko; Furuya, Mio; Sato, Hiro; Hirota, Yuka; Minegishi, Takashi; Nakano, Takashi

    2015-01-01

    Key Clinical Message Leptomeningeal metastasis (LM) of uterine cervical cancer is extremely rare. A 54‐year‐old woman with uterine cervical cancer treated with surgery and radiotherapy developed LM manifesting as ptosis 17 years later. Although rare, LM should be considered in patients with a history of uterine cervical cancer presenting with cranial nerve symptoms.

  20. Deconvoluting the relationships between autophagy and metastasis for potential cancer therapy.

    Science.gov (United States)

    Yao, Dahong; Wang, Peiqi; Zhang, Jin; Fu, Leilei; Ouyang, Liang; Wang, Jinhui

    2016-06-01

    Autophagy is a highly conserved lysosome-dependent degradation process that may digest some long-lived proteins and damaged organelles. As an essential homeostasis maintaining system in normal cells, autophagy plays a key role in several pathological settings, especially cancer. Metastasis, known as a crucial hallmark of cancer progression, is the primary cause of cancer lethality. The role of autophagy in metastasis is quite complex as supportive evidence has indicated both pro-metastatic and anti-metastatic functions of autophagy. Autophagy can inhibit metastasis by restricting necrosis and mediating autophagic cell death, whereas it may also promote metastasis by enhancing cancer cell fitness in response to stress. Moreover, the function of autophagy is context- and stage-dependent. Specifically, during the early steps of metastasis, autophagy mainly serves as a suppressor, while it plays a pro-metastatic role in the later steps. Here, we focus on highlighting the dual roles of autophagy in metastasis and address the molecular mechanisms involved in this process, which may provide a new insight into cancer biology. While, we also summarize several anti-metastatic agents manipulating autophagy, in the hope of shedding light on exploration of potential novel drugs for future cancer therapy. PMID:27003389

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

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

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

  2. Scintigraphic dynamics valuation of bone metastasis in the course of the treatment of 153Sm-oksabifor

    International Nuclear Information System (INIS)

    In the present study we examined the role of bone scan with 99mTc-pyrophosphate treatment planning 153Sm-oksabifor followed by analysis of post-treatment monitoring of cancer patients with bone metastases

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

    Directory of Open Access Journals (Sweden)

    Hon S. Leong

    2014-09-01

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

  4. Complete pathologic response of HER2-positive breast cancer liver metastasis with dual Anti-HER2 antagonism

    International Nuclear Information System (INIS)

    Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease. We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM. The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM

  5. Management of bone metastases in refractory prostate cancer--role of denosumab.

    Science.gov (United States)

    Paller, Channing J; Carducci, Michael A; Philips, George K

    2012-01-01

    This article reviews the problem of bone disease in prostate cancer and the evolving role of the novel agent denosumab, a fully human monoclonal antibody that inhibits the receptor activator of nuclear factor-κB ligand, in suppressing bone resorption and offering bone protection in this disease. Prostate cancer frequently metastasizes to bone, and additionally its treatment with androgen deprivation leads to accelerated bone loss resulting in clinically relevant skeletal complications associated with disabling symptoms. Among the bone-targeting therapeutic strategies investigated for the prevention of bone complications, the potent bisphosphonate zoledronic acid has been the most widely used agent for bone protection in the past decade. Denosumab is the first among a new class of osteoclast-targeting agents to show superior efficacy in several clinical scenarios in both prostate and breast cancer, as well as in osteoporosis, but the focus of this review will be on its role in prostate cancer. The safety and efficacy of denosumab versus zoledronic acid was established in a randomized trial, demonstrating a delay in skeletal-related events in metastatic castration-resistant prostate cancer patients. This study led to the approval of denosumab in the US. The chief risks of denosumab were hypocalcemia and osteonecrosis of the jaw. Denosumab was also approved for fracture risk reduction in patients on androgen-deprivation therapy for nonmetastatic prostate cancer. Although denosumab extended bone metastasis-free survival in a Phase III trial in men with castration-resistant nonmetastatic prostate cancer to a statistically significant degree, a Food and Drug Administration committee found that the effect was not sufficiently clinically meaningful for regulatory approval, and the Food and Drug Administration issued a letter concurring with the committee's recommendation. The role of denosumab in prostate cancer will continue to evolve either as monotherapy or in

  6. CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

    OpenAIRE

    Sebastiano Cavallaro

    2013-01-01

    Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases...

  7. Is 18F-FDG PET/CT more reliable than 99mTc-MDP planar bone scintigraphy in detecting bone metastasis in nasopharyngeal carcinoma?

    International Nuclear Information System (INIS)

    Bone metastasis occurs frequently in naso-pharyngeal carcinoma (NPC) patients. The aim of this study was to compare the clinical value of 18F-FDG PET/CT with that of 99mTc-MDP planar bone scintigraphy (PBS) for detecting bone metastasis in NPC patients. Thirty-five histologically proven NPC patients were enrolled in this retrospective study. They underwent both 18F-FDG PET/CT and PBS within 7 days in our department. In a lesion-based analysis, the skeletal system, excluding the head, was divided into four regions: the spine, the pelvis, the thorax, and the appendix. Bone metastasis was considered to be present by either biopsy or clinical follow-up for at least 6 months. PET/CT and PBS were compared by McNemar's paired-sample test. A total of 50 lesions were confirmed to be malignant (spine 27, thorax 11, pelvis 8 and appendix 4). Although PET/CT was found to be more sensitive on lesion level than PBS (sensitivity 70.0 versus 42.0%; P=0.044), there were still 14 metastatic (28.0%) lesions that could be detected by PBS while negative in PET/CT imaging. In a patient-based analysis, fifteen (42.9%) of 35 eligible patients were found to have bone metastasis. The sensitivity, specificity and accuracy of PET/CT was 60.0% (9/15), 100% (20/20) and 82.9% (29/35); as for PBS, it was 66.7% (10/15), 85.0% (17/20) and 77.1% (27/35), respectively. There was no statistical difference between PET/CT and PBS (P > 0.05). PBS, as a conventional imaging, should be used as an important complement for detecting bone metastasis in NPC patients. (author)

  8. Non small-cell lung cancer with metastasis to thigh muscle and mandible: two case reports

    OpenAIRE

    Giugliano, Francesca Maria; Alberti, Domingo; Guida, Giovanna; Palma, Giampaolo De; Iadanza, Luciano; Mormile, Maria; Cammarota, Fabrizio; Montanino, Agnese; Fulciniti, Franco; Ravo, Vincenzo; Muto, Paolo

    2013-01-01

    Introduction Lung cancer is the leading cause of cancer-related death in Europe and the US. Isolated metastases to skeletal muscle and the mandible are very uncommon. Case presentation This report presents two cases. Case 1 concerns a 45-year-old Caucasian woman affected by muscle metastasis of the right thigh from non-small-cell lung cancer. Case 2 concerns a 61-year-old Caucasian man affected by mandible metastasis from non-small-cell lung cancer. Both metastases were detected by diagnostic...

  9. Differentiation of multiple myeloma and metastasis : emphasis on bone marrow involvement pattern of spine in sagittal MR images

    International Nuclear Information System (INIS)

    To differentiate multiple myeloma and metastasis of the spine. Retrospective analysis of MR images of the patients with multifocal spinal involvement of multiple myeloma and metastasis was done. Analysis was done in viw points of bone marrow involvement pattern(focal, diffuse, and mixed), margin, number, size and uniformity of the focal lesions, involvement of pedicle and posterior element, and epidural and paravertebral mass formation. Multiple myeloma predominantly showed diffuse pattern (11/21, 52.4%) of marrow involvement, while metastasis showed mainly focal pattern (18/21, 85.7%). Margin of the focal lesions were distinct in majority (8/10, 80%) of multiple myeloma and indistinct in majority (16/21, 76.2%) of metastasis. Size of the focal lesions were smaller in cases of multiple myeloma than those of metastasis, but number and standard deviation of the size of the focal lesions did not show significant difference between the two diseases. Involvement of posterior element were more common in multiple myeloma, and epidural mass formation and paravertebral mass formation were more common in metastasis. The diffuse pattern of marrow involvement alone suggests multiple myeloma. When a focal or a mixed pattern is found, distinct margin and smaller focal lesions are suggestive of multiple myeloma, and indistinct margin and larger focal lesions and epidural/ paravertebral mass formation are suggestive of metastasis

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-19

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Noormohamed Saleem

    2008-09-01

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

  14. Correlation of baseline biomarkers with clinical outcomes and response to fulvestrant with vandetanib or placebo in patients with bone predominant metastatic breast cancer: An OCOG ZAMBONEY sub-study

    Directory of Open Access Journals (Sweden)

    Christina L. Addison

    2015-06-01

    Conclusions: In this clinical trial, sVEGFR2 appeared prognostic for OS, hence validation of sVEGFR2 should be conducted. Moreover, the role of sVEGFR2 in breast cancer bone metastasis progression should be elucidated.

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

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

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

  16. Liposomes Coated with Isolated Macrophage Membrane Can Target Lung Metastasis of Breast Cancer.

    Science.gov (United States)

    Cao, Haiqiang; Dan, Zhaoling; He, Xinyu; Zhang, Zhiwen; Yu, Haijun; Yin, Qi; Li, Yaping

    2016-08-23

    Cancer metastasis leads to high mortality of breast cancer and is difficult to treat because of the poor delivery efficiency of drugs. Herein, we report the wrapping of a drug-carrying liposome with an isolated macrophage membrane to improve delivery to metastatic sites. The macrophage membrane decoration increased cellular uptake of the emtansine liposome in metastatic 4T1 breast cancer cells and had inhibitory effects on cell viability. In vivo, the macrophage membrane enabled the liposome to target metastatic cells and produced a notable inhibitory effect on lung metastasis of breast cancer. Our results provide a biomimetic strategy via the biological properties of macrophages to enhance the medical performance of a nanoparticle in vivo for treating cancer metastasis. PMID:27454827

  17. Denbinobin suppresses breast cancer metastasis through the inhibition of Src-mediated signaling pathways.

    Science.gov (United States)

    Chen, Pei-Hsuan; Peng, Chieh-Yu; Pai, Hui-Chen; Teng, Che-Ming; Chen, Chien-Chih; Yang, Chia-Ron

    2011-08-01

    Denbinobin (5-hydroxy-3,7-dimethoxy- 1,4-phenanthraquinone), a biologically active chemical isolated from Ephemerantha lonchophylla, has been demonstrated to display anti-cancer activity. Breast cancer is the leading cause of female mortality, and the high mortality is mainly attributable to metastasis. Src kinase activity is elevated in many human cancers, including breast cancer, and is often associated with aggressive disease. In the present study, we examined the anti-metastatic effects of denbinobin through decreasing Src kinase activity in human and mouse breast cancer cells. Denbinobin caused significant block of Src kinase activity in both human and mouse breast cancer cells. Moreover, phosphorylation of the signaling molecules focal adhesion kinase, Crk-associated substrate and paxillin downstream of Src was also inhibited by denbinobin. Furthermore, denbinobin inhibited the in vitro migration, invasion and in vivo metastasis of breast cancers in a mouse metastatic model. The denbinobin-treated group showed a significant reduction in tumor metastasis, orthrotopic tumor volume, and spleen enlargement compared to the control group. In addition, transfection of breast cancer cells with a plasmid coding for a constitutively active Src prevented the denbinobin-mediated phosphorylation of Src and downstream molecules and cell migration. Our findings provide evidences that denbinobin inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and metastasis, suggesting that it has therapeutic potential in breast cancer treatment. PMID:21062671

  18. Acupuncture for cancer-induced bone pain?

    OpenAIRE

    Mark I Johnson; Bennett, Michael I; Paley, Carole A.

    2011-01-01

    Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing...

  19. Evaluation of the prognosis of cancer patients with metastatic bone tumors based on serial bone scintigrams

    Energy Technology Data Exchange (ETDEWEB)

    Ohmori, Kazuo; Matsui, Hisao; Yasuda, Taketoshi; Kanamori, Masahiko; Yudoh, Kazuo; Seto, Hikaru; Tsuji, Haruo [Toyama Medical and Pharmaceutical University (Japan)

    1997-08-01

    We counted the lesions at the time of detection of bone metastases and calculated the rate of increase in the number of bone metastases from changes in serial bone scintigrams, and investigated the usefulness of serial scintigrams as a prognostic indicator in patients with metastatic bone tumors. Subjects were 112 patients with bone metastases from four types of primary lesion: 21 with prostate cancer, 27 breast cancer, 39 lung cancer and 25 stomach cancer. Of these, 18 (prostate), 19 (breast), nine (lung) and eight (stomach) underwent serial bone scintigrams in which bone metastases were first detected and identified as progressing. The numbers of lesions at the time of detection of bone metastases for prostate and stomach cancers were significantly greater than those for lung cancer. The rate of increase in the number of bone metastases for stomach cancer was significantly higher than that for prostate or breast cancers. There was no correlation between the survival time after the detection of bone metastases and the number of lesions at the time of detection in the four types of cancer. However, in prostate cancer, a negative correlation existed between the survival time after the detection of bone metastases and the rate of increase in the number of bone metastases. Thus, in patients with bone metastases from prostate cancer, it appears that the rate of increase in the number of bone metastases, estimated from serial bone scintigrams, was indicative of prognosis. (author)

  20. Metastasis Suppressor Genes

    OpenAIRE

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2013-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinica...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

  2. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    OpenAIRE

    Adem Dayan; Dogan Koca; Tulay Akman; Ilhan Oztop; Hulya Ellidokuz; Ugur Yilmaz

    2012-01-01

    Background: To evaluate the factors that have an impact on the development of brain metastasis in patients with breast cancer. Materials and Methods: Among the patients who were followed-up and treated for breast cancer between January 2000 and January 2010, the ones with brain metastasis were included to the analysis. Metastatic breast cancer patients without brain metastasis, which had similar duration of follow-up and median age were included as the control group. Both group were compa...

  3. Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis

    International Nuclear Information System (INIS)

    This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). Effective control of peritoneal seeding—induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis

  4. Ovarian metastasis in colorectal cancer: retrospective review of 180 cases

    Directory of Open Access Journals (Sweden)

    Omranipour R

    2009-12-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Routine oophorectomy in women with colorectal cancer is under debate, the aim of this study is to determine incidence, clinicopathologic features and prognostic factors of ovarian involvement in primary colorectal cancer (CRC and to clear the role of prophylactic oophorectomy."n"nMethods: Data from primary CRC women treated between years 1990 and 2004 were retrieved and clinical and pathologic features of those who had undergone oophorectomy during CRC surgery were reviewed."n"nResults: One hundred eighty cases (mean age 47.5 years were included. In 120(66.6%, ovaries were preserved and 60(33.3% cases underwent bilateral oophorectomy in addition to primary CRC resection. Reasons for oophorectomy were prophylactic in 22(36.6%, abnormal morphology in 35(58.3%, and undetermined in 3(5% cases. There were five metastatic carcinomas, eight primary ovarian tumors and 47 normal ovaries in pathologic evaluation. No complication directly related to oophorectomy was noted. Patients with ovarian metastases had higher stages of tumor. Ovarian metastases were not related to menstrual status, CRC location, size, differentiation, and mucin production, as well as abnormal morphology of ovary. The global prevalence of

  5. Active Tobacco Smoking and Distant Metastasis in Patients With Oropharyngeal Cancer

    International Nuclear Information System (INIS)

    Purpose: Distant metastasis is the site of first relapse in approximately one-third of patients with locally advanced oropharyngeal carcinoma, irrespective of human papillomavirus status. Yet the risk factors associated with distant metastasis are not well characterized. We sought to characterize the relationship between smoking status and distant metastasis. Methods and Materials: We evaluated the association between tobacco smoking status and distant metastasis in a retrospective cohort study of 132 patients who underwent definitive radiation therapy and chemotherapy for Stage III–IVA/B oropharyngeal cancer. Information on tobacco smoking was prospectively collected by patient questionnaires and physician notes at the time of diagnosis. Thirty-three percent of the patients were nonsmokers, 51% were former smokers, 16% were active smokers. The cumulative lifetime tobacco smoking in pack-years was 20 (range, 0–150). Results: With a median follow-up time of 52 months, the overall rate of distant metastasis at 4 years was 8%. Distant metastasis was the most common first site of relapse, occurring in 56% of the patients with recurrences. Active smokers had higher rates of distant metastasis than non-active smokers (including never- and former smokers; 31% vs. 4%, p 20 and ≤20 (10% vs. 4%, p = 0.19). In univariate analysis, active smoking (p = 0.0004) and N category (p = 0.009) were predictive of increased risk of distant metastasis. In multivariate analysis, active smoking was the most significant predictive factor for increased risk of distant metastasis (hazard ratio, 12.7, p < 0.0001). Conclusions: This study identified a strong association between active smoking and distant metastasis in patients with oropharyngeal cancer.

  6. ERβ regulates miR-21 expression and inhibits invasion and metastasis in cancer cells

    Science.gov (United States)

    Tian, Junmei; Tu, Zhenzhen; Chen, Wei R.; Gu, Yueqing

    2012-03-01

    In human, estrogens play important roles in many physiological processes, and is also found to be connected with numerous cancers. In these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many current clinical diagnosis. Two forms of the estrogen receptor have been identified, ERα and ERβ, and show different and specific functions. The two estrogen receptors belong to a family of ligand-regulated transcription factors. Estrogen via ERα stimulates proliferation in the breast, uterus, and developing prostate, while estrogen via ERβ inhibits proliferation and promotes differentiation in the prostate, mammary gland, colon, lung, and bone marrow stem cells. MicroRNAs (miRs) are small non-coding RNA molecules that occur naturally and downregulate protein expression by translational blockade of the target mRNA or by promoting mRNA decay. MiR-21 is one of the most studied miRNAs in cancers. MiR-21 is overexpressed in the most solid tumors, promoting progression and metastasis. The miR-21 gene is located on the chromosome 17, in the 10th intron of a protein-coding gene, TMEM49. While, the function of TMEM49 is currently unknown. Our experiment is designed to identity the relationship between miR-21 and ERβ in cancer progression. The human cancer cells were transfected with ERβ. Real-time PCR analysis showed that the expression level of miR-21 was significantly inhibited down by ERβ treatment. As MTT assay showed the tumor cell survival rate was also inhibited significantly. Go/Gl phase cell cycle arrest was founded and tumor cell apoptosis was induced in ERβ group.

  7. Exosomes mediated pentose phosphate pathway in ovarian cancer metastasis: a proteomics analysis

    OpenAIRE

    Yi, Huan; Zheng, Xiangqin; Song, Jianrong; Shen, Rongkai; Su, Yanzhao; Lin, Danmei

    2015-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancies for readily metastasis. Exosomes have played an influential role in carcinogenicity and cancer progression. Our aim is to discover exosome-related mechanisms in ovarian cancer progress and explore potential diagnostic biomarkers and therapeutic targets of ovarian cancer. We initially presented the proteomic profiles of exosomes derived from two late-stage ovarian cell lines, OVCA429 and HO8910PM. A total of 2940 exosomal ...

  8. The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis

    OpenAIRE

    Xu, Kun; Tian, Xuejun; Oh, Sun Y.; Movassaghi, Mohammad; Naber, Stephen P.; Kuperwasser, Charlotte; Buchsbaum, Rachel J

    2016-01-01

    Background The tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis may lead to new therapeutic approaches against advanced breast cancer. Methods We use a novel method for manipulating three-dimensional...

  9. Outcomes in 12 gynecologic cancer patients with brain metastasis: a single center’s experience

    OpenAIRE

    CÖMERT, Esra ÇABUK; BİLDACI, Tevfik Berk; KARAKAYA, Burcu KISA; TARHAN, Nefise Çağla; Özlem ÖZEN; Gülşen, Salih; Dursun, Polat; Ayhan, Ali

    2012-01-01

    To present 12 gynecologic cancer cases with brain metastasis and a discussion of the relevant literature. Gynecologic malignancy is the second most common cancer in elderly women, following breast cancer. These cancers usually spread locally at first, and common distant metastatic sites are the lungs, liver, spleen, and distant lymph nodes. The brain is not a usual site of metastatic involvement. Materials and methods: The study included 12 cases with various gynecologic malignancies that w...

  10. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    OpenAIRE

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustai...

  11. CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo

    OpenAIRE

    Lv, Zhi-Dong; Kong, Bin; Liu, Xiang-Ping; Dong, Qian; Niu, Hai-tao; Wang, Yong-Hua; Li, Fu-Nian; Wang, Hai-Bo

    2014-01-01

    Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the exp...

  12. SPECT-CT bone scintigraphy in cancer patients

    International Nuclear Information System (INIS)

    %) lesions caused by direct infiltration of bone structures was observed in 6 pts . 4. 21 (15%) lesions with prevailing 'cold' osteolytic component were observed in 8 pts with renal, endometrial, colorectal or urinary bladder cancer. 5. 17 (12%) 'mixed-type' lesions - osteolytic and osteosclerotic were obtained in 6 cases. 6. Two pts were with 2 (1.9%) single extraosseous lesions: one - with myositis ossificans and the second -with soft tissue calcified metastasis in the right abdomen due to appendicitis cancer Conclusion: SPECT-CT increases the value of bone scintigraphy avoiding false-positive interpretation of areas with physiological tracer uptake, also facilitating the exact location and extent of tumor involvement.

  13. Disseminated Breast Cancer Cells Acquire a Highly Malignant and Aggressive Metastatic Phenotype during Metastatic Latency in the Bone

    OpenAIRE

    Marsde