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Sample records for cancer bone metastasis

  1. Bone Metastasis

    Science.gov (United States)

    ... help reduce pain and other symptoms of bone metastases. Symptoms Sometimes, bone metastasis causes no signs and ... cancers most likely to cause bone metastasis include: Breast cancer Kidney cancer Lung cancer Lymphoma Multiple myeloma Prostate ...

  2. Osthole inhibits bone metastasis of breast cancer

    OpenAIRE

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-01-01

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potent...

  3. Osthole inhibits bone metastasis of breast cancer.

    Science.gov (United States)

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-08-29

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potential mechanism of this inhibition. In the murine model of breast cancer osseous metastasis, mice that received osthole developed significantly less bone metastases and displayed decreased tumor burden when compared with mice in the control group. Osthole inhibited breast cancer cell growth, migration, and invasion, and induced apoptosis of breast cancer cells. Additionally, it also regulated OPG/RANKL signals in the interactions between bone cells (osteoblasts and osteoclasts) and cancer cells. Besides, it also inhibited TGF-β/Smads signaling in breast cancer metastasis to bone in MDA-231BO cells. The results of this study suggest that osthole has real potential as a therapeutic candidate in the treatment of breast cancer patients with bone metastases.

  4. Regulation of Prostate Cancer Bone Metastasis by DKK1

    Science.gov (United States)

    2012-09-01

    blocks the formation of osteoblastic bone lesions in animal models of bone metastasis. We have now shown that human prostate cancer cell lines...that produce osteolytic, but not osteoblastic, bone lesions in animal models of bone metastasis express significant amounts of DKK1 and this expression...cancer bone metastasis typically results in massive osteolysis from the secretion of osteoclast-activating factors, such as parathyroid hormone-related

  5. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Christiansen, Christian F; Ulrichsen, Sinna P

    2017-01-01

    between 1994 and 2010, subsequently diagnosed with BM until 2012. We followed patients from date of bone metastasis diagnosis until death, emigration or 31 December 2012, whichever came first. We computed 1-year, 3-year and 5-year survival (%) and the corresponding 95% CIs stratified on primary cancer...... type. Comparing patients with bone metastasis only and patients with other synchronous metastases, we estimated crude and adjusted HRs and corresponding 95% CI for mortality. RESULTS: We included 17 251 patients with bone metastasis. The most common primary cancer types with bone metastasis were...... prostate (34%), breast (22%) and lung (20%). One-year survival after bone metastasis diagnosis was lowest in patients with lung cancer (10%, 95% CI 9% to 11%) and highest in patients with breast cancer (51%, 50% to 53%). At 5 years of follow-up, only patients with breast cancer had over 10% survival (13...

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

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

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

  7. Bone fracture in breast cancer patients with isolated bone metastasis.

    Science.gov (United States)

    Dibekoglu, C; Turanli, S; Karaman, N; Ozcelik, K Caglar; Erdogan, O

    2015-01-01

    To analyse the incidence of bone fracture of breast cancer patients with isolated bone metastasis and its effect on survival. We tried to find an answer to the question of "Can the development of bone fracture be predicted?" Between 1993-2006, 139 breast cancer patients with isolated bone metastasis were examined. Patients were divided into two groups depending on the development of pathologic bone fracture. Fractures were developed in 41 patients (29.5%)within 41 months of follow-up. The locations of pathologic bone fracture were vertebral fracture in 26 patients (63.4%),femur fracture in 11 patients (26.8%), and hip fracture in four patients (9.8%). Fracture rates in hormone sensitive and resistant patients were 31.2% and 14.3%, respectively. The fracture rates in 13 triple negative and non triple negative patients were 7.7% and 31.4%, respectively (p=0.07). High CA 15-3 levels at the time of metastasis in patients with and without fractures were 68.4% and 61.1%, respectively. The risk for fracture was also high in Her2-neu positive patients (38.7% vs. 26.5%). While the incidence of fracture with the presence of one factor mentioned above was 22.2%, it was increased to 36.1% in the presence of two or three factors(p=0.13). Median survivals of the patients with and without fractures were 48 and 39 months, respectively (p= 0.65). Hormone sensitivity, high CA 15-3 levels and positive Her2-neu status are slight risk factors for bone fractures. Survival was not different in patients with or without bone fractures. Celsius.

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

    Science.gov (United States)

    2017-02-01

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

  9. A Case of Maxillary Bone Metastasis from Lung Cancer

    National Research Council Canada - National Science Library

    Kusunoki, Takeshi; Homma, Hirotomo; Kidokoro, Yoshinobu; Yanai, Aya; Ikeda, Katsuhisa; Wada, Ryo

    2015-01-01

    We experienced a very rare case of maxillary bone metastasis from lung cancer. The patient was a 77-year-old Japanese man with 1-month history of right alar swelling with hard pain as his chief complaint...

  10. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2015-10-01

    efferocytosis. The translation of this functional role during pathophysiological states such as tumor metastasis to the skeleton is unknown. The purpose of this...COLLABORATING ORGANIZATIONS What individuals have worked on the project? Name: L.C. Hofbauer Institution: Department of Endocrinology, Diabetes , and Bone

  11. 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.

  12. Predicting the risk of bone metastasis in prostate cancer.

    Science.gov (United States)

    Briganti, Alberto; Suardi, Nazareno; Gallina, Andrea; Abdollah, Firas; Novara, Giacomo; Ficarra, Vincenzo; Montorsi, Francesco

    2014-02-01

    The ability to identify prostate cancer patients at 'high risk' for bone metastasis development could allow early selection of those most likely to benefit from interventions to prevent or delay bone metastasis. This review is aimed to identify potential predictors of risk for bone metastasis in newly diagnosed patients and in those who have already received treatment. At diagnosis, established predictors of prostate cancer aggressiveness (e.g. PSA level, clinical stage, Gleason score) can identify patients at risk for bone metastasis. Following treatment of the disease, increasing evidence suggests that absolute PSA levels and other measures of PSA kinetics are useful to aid prediction of bone metastasis risk in patients both with and without a history of ADT. However, which PSA parameter most accurately predicts risk and the cut-off values that should be employed are unclear. Inclusion of PSA parameters to identify a high risk population may be beneficial in whom bone-modifying treatments are being considered. Other novel (but unvalidated) biomarkers that potentially predict the development of bone metastases have been identified, although it is unclear whether they will have value as independent markers or when combined with other parameters (e.g. measures of PSA kinetics). Further prospective studies of PSA kinetics and other predictive markers are, therefore, required to define the optimal criteria for identifying patients at high risk of bone metastases and those who are most likely to benefit from intensive monitoring and therapeutic intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. [Serum osteoprotegerin as a novel marker of bone metastasis in prostate cancer].

    Science.gov (United States)

    Chen, Hai-xin; Li, Han-zhong; Li, Hong-jun; Shi, Bing-bing; Jin, Wei; Cheng, Xin-qi

    2007-03-15

    To evaluate the diagnostic usefulness of serum osteoprotegerin (OPG) in prostate cancer bone metastasis. Serum osteoprotegerin were measured by ELISA assay in 30 healthy men, 30 patients with benign prostatic hyperplasia, 66 patients with prostate cancer including 36 without bone metastasis (30 with localized cancer, 6 with lymph node metastasis) and 30 with bone metastasis. The results associated with clinical data were calculated statistically. Serum osteoprotegerin were significantly increased in patients with bone metastasis compared with others (PGleason score or grade (r=0.427, 0.277; Pbone metastasis in prostate cancer. Serum osteoprotegerin could be used as a marker for diagnosis of bone metastasis in prostate cancer.

  14. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2016-10-01

    mass and alter bone remodeling. 15. SUBJECT TERMS Macrophages, Efferocytosis, Prostate Cancer, Bone 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...cytokines, interfering with HIF-1 also promotes the generation of a specialized tumor- killing class of T cells - the so-called “cytotoxic T lymphocytes...cells possess higher killing capacity compared to WT cells (data not shown). 6 Summary: In summary, we have made considerable progress in our

  15. Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance

    Science.gov (United States)

    2007-05-01

    calvarial osteoblast proliferation and cranial suture fusion. Cleft Palate Craniofacial Journal, 39, 487–496. 86. Chikazu, D., Katagiri, M., Ogasawara, T...and lung cancer models. These observations identify AM as a significant target for therapeutic intervention in bone metastasis. Small molecules

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

    Science.gov (United States)

    Wu, Fei

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

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

    Directory of Open Access Journals (Sweden)

    Megan N. Thobe

    2011-01-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

    2011-01-27

    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.

  19. 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 ...

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

    Science.gov (United States)

    Yasuda, Hiromi; Shimura, Tadanobu; Okigami, Masato; Yoshiyama, Shigeyuki; Ohi, Masaki; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

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

  2. Prognostic significance of global grading system of Gleason score in patients with prostate cancer with bone metastasis

    National Research Council Canada - National Science Library

    Kambara, Tsunehito; Oyama, Tetsunari; Segawa, Atsuki; Fukabori, Yoshitatsu; Yoshida, Ken-Ichiro

    2010-01-01

    ...) on prediction of prognosis for patients with prostate cancer with bone metastasis. PATIENTS AND METHODS Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS...

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

    National Research Council Canada - National Science Library

    Selvamurugan, Nagarajan

    2006-01-01

    .... But the expression level of MMP-8 was not detected by Western blot analysis. The molecular mechanisms of how TGF-BetaI mediates stimulation of invasion and formation of bone metastasis have yet to be completely determined. ATF-3...

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

    Science.gov (United States)

    2017-02-01

    within the skeletal niche and consequently represent promising targets for intervention in BrCa patients with bone metastasis. The scope of research...subtypes with comprehensive clinical and pathological information, including the presence of distant metastasis. Sixteen cases had presence of bone...of association between DDR1 expression levels and age , race, menopausal status, estrogen receptor (ER), progesterone receptor (PR), HER2-neu

  5. Inhibitory Effects of Megakaryocytes in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2010-04-01

    modulate osteoblast synthesis of type-l collagen, osteoprotegerin, and RANKL. Bone 36(5):812-9. 15. Kacena MA, Gundberg CM, Horowitz MC 2006 A...Jeong SS, Chen R, Weilbaecher K 2008 APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. J Cell Biochem 104(4):1311-23

  6. Modern Detection of Prostate Cancer's Bone Metastasis: Is the Bone Scan Era Over?

    Directory of Open Access Journals (Sweden)

    Bertrand Tombal

    2012-01-01

    Full Text Available Prostate cancer cells have an exquisite tropism for bone, which clinically translates into the highest rate of bone metastases amongst male cancers. Although in the latest years there has been an active development of new “bone targeted” therapies, modern diagnostic techniques for bone metastases still relies mostly on 99mTc bone scanning (BS and plain X-ray. BS dramatically lacks specificity and sensitivity. Recent publications using modern imaging technologies have clearly pinpointed that BS grossly underestimates the true prevalence of bone metastasis. In addition BS does not allow tumour measurement and is, therefore, not appropriate to monitor response to therapy. This might be extremely important in patients harbouring high-risk localized disease that are eventually candidate for local therapy. Here we reviewed what are the emerging imaging strategies that are likely to supplant BS and to what extent they can be used in the clinic already.

  7. A retrospective study of incidence of bone metastasis in head and neck cancer.

    Science.gov (United States)

    Bhandari, Virendra; Jain, Ravi Kant

    2013-01-01

    The incidence of bone metastasis in head and neck Squamous cell carcinoma is very uncommon. This retrospective study was done to identify the frequency, clinical presentation, and the clinical course of the metastatic disease to bone from head and neck primary. Out of 624 patients of head and neck cancers seen in our clinic 6 patients developed metastasis to solitary or multiple bones during the course of the disease. Postoperative patients had multiple bone involvement whereas others had solitary bone involvement. Main bones involved were parietal bone of skull, shaft of humerus and femur, sacrum, and ribs. All the patients had survival of few months only after developing metastasis. Improvement in technology has resulted in improved results in advanced head and neck cancer patients; hence measures should be taken for complete responders to diagnose this metastasis early and treat them appropriately.

  8. A retrospective study of incidence of bone metastasis in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Virendra Bhandari

    2013-01-01

    Full Text Available The incidence of bone metastasis in head and neck Squamous cell carcinoma is very uncommon. Aim: This retrospective study was done to identify the frequency, clinical presentation, and the clinical course of the metastatic disease to bone from head and neck primary. Material and Methods: Out of 624 patients of head and neck cancers seen in our clinic 6 patients developed metastasis to solitary or multiple bones during the course of the disease. Results: Postoperative patients had multiple bone involvement whereas others had solitary bone involvement. Main bones involved were parietal bone of skull, shaft of humerus and femur, sacrum, and ribs. All the patients had survival of few months only after developing metastasis. Conclusion: Improvement in technology has resulted in improved results in advanced head and neck cancer patients; hence measures should be taken for complete responders to diagnose this metastasis early and treat them appropriately.

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

    Science.gov (United States)

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

    2017-01-25

    To investigate the risk factors of metachronous bone metastasis after radical resection of colorectal cancer within 5 years. Clinical data of 1 749 patients with colorectal cancer, of whom 50(2.8%) patients developed metastasis to bone after operation, in the Department of Colorectal Surgery, Changhai Hospital of The Second Military Medical University from January 2001 to December 2010 were analyzed retrospectively. Univariate and multivariate analysis were performed to find the risk factors of metachronous bone metastasis from colorectal cancer using Chi square test and Logistic regression, respectively. Of 50 colorectal cancer cases with bone metastasis, 29 were male and 21 were female. The age was ≥ 60 years old in 28 cases. Tumors of 36 cases were located in the rectum and of 14 cases located in the colon. Pathology examination showed 43 cases were adenocarcinomas, 7 cases were mucinous adenocarcinoma. Forty-two cases had T3-4 stage lesions, 30 cases had lymph node metastasis, 14 cases had pulmonary metastasis, and 5 cases had liver metastasis. Univariate Chi square test indicated that factors associated with the metachronous bone metastasis of colorectal cancer within 5 years were tumor site (χ2=4.932, P=0.026), preoperative carbohydrate antigen 199 (CA199) level (χ2=4.266, P=0.039), lymph node metastasis (χ2=13.054, P=0.000) and pulmonary metastasis(χ2=35.524, P=0.000). The incidence of bone metastasis in patients with rectal cancer (3.6%, 36/991) was higher compared to those with colon cancer (1.8%, 14/758). The incidence of bone metastasis in patients with higher(> 37 kU/L) preoperative serum CA199 level (4.9%, 12/245) was higher compared to those with lower serum CA199 level (2.5%, 38/1504). The incidence of bone metastasis in patients with lymph node metastasis(4.8%,30/627) and pulmonary metastasis (11.6%, 14/121) was significantly higher compared to those without lymph node metastasis (1.8%, 20/1122) and pulmonary metastasis(2.2%, 36

  10. Transcriptional Network Analysis Identifies BACH1 as a Master Regulator of Breast Cancer Bone Metastasis

    Science.gov (United States)

    Liang, Yajun; Wu, Heng; Lei, Rong; Chong, Robert A.; Wei, Yong; Lu, Xin; Tagkopoulos, Ilias; Kung, Sun-Yuan; Yang, Qifeng; Hu, Guohong; Kang, Yibin

    2012-01-01

    The application of functional genomic analysis of breast cancer metastasis has led to the identification of a growing number of organ-specific metastasis genes, which often function in concert to facilitate different steps of the metastatic cascade. However, the gene regulatory network that controls the expression of these metastasis genes remains largely unknown. Here, we demonstrate a computational approach for the deconvolution of transcriptional networks to discover master regulators of breast cancer bone metastasis. Several known regulators of breast cancer bone metastasis such as Smad4 and HIF1 were identified in our analysis. Experimental validation of the networks revealed BACH1, a basic leucine zipper transcription factor, as the common regulator of several functional metastasis genes, including MMP1 and CXCR4. Ectopic expression of BACH1 enhanced the malignance of breast cancer cells, and conversely, BACH1 knockdown significantly reduced bone metastasis. The expression of BACH1 and its target genes was linked to the higher risk of breast cancer recurrence in patients. This study established BACH1 as the master regulator of breast cancer bone metastasis and provided a paradigm to identify molecular determinants in complex pathological processes. PMID:22875853

  11. SPARC inhibits breast cancer bone metastasis and may be a clinical therapeutic target.

    Science.gov (United States)

    Ma, Jingjing; Gao, Sheng; Xie, Xiju; Sun, Erhu; Zhang, Min; Zhou, Qian; Lu, Cheng

    2017-11-01

    Breast cancer is one of the most common types of cancer in females worldwide, and metastasis to bone is an important characteristic of malignancy. The present study aimed to investigate the molecular mechanism of breast cancer to bone metastasis of secreted protein acidic and rich in cysteine (SPARC). Immunohistochemistry was performed to examine the expression of SPARC in primary breast tumors and bone metastatic foci. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression level of SPARC in several types of breast cancer cell. A Transwell filter assay was used to assess the effect of SPARC on breast cancer cell invasion ability, and an osteoblast differentiation assay was employed to analyze the effect of SPARC on the differentiation ability of mesenchymal stem cells. Clinical data revealed that decreased stromal SPARC expression is associated with breast cancer to bone metastasis. Gain- and loss-of-function studies reveal that SPARC inhibits the migration and invasion of breast cancer cells, and suppresses osteoclast activation in the breast cancer microenvironment. SPARC serves an important role in breast cancer bone metastasis and may be a promising therapeutic target for the treatment of breast cancer bone metastasis.

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

    OpenAIRE

    Yasuda, Hiromi; Shimura, Tadanobu; Okigami, Masato; Yoshiyama, Shigeyuki; Ohi, Masaki; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2016-01-01

    A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macr...

  13. 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.

  14. Retrospective study of predictors of bone metastasis in prostate cancer cases.

    Science.gov (United States)

    Ho, Christopher Chee Kong; Seong, Poh Keat; Zainuddin, Zulkifli Md; Abdul Manaf, Mohd Rizal; Parameswaran, Muhilan; Razack, Azad H A

    2013-01-01

    The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was 69.2 ± 7.3 years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among those with a low PSA level less than 20 ng/ml, and less than 10 ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10 ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml) +1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=2.718 x/1+2.718 x. Newly diagnosed prostate cancer patients with a PSA level of 10 ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

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

    Science.gov (United States)

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

    2017-08-26

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

  16. 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.

  17. Tumor-expressed adrenomedullin accelerates breast cancer bone metastasis.

    Science.gov (United States)

    Siclari, Valerie A; Mohammad, Khalid S; Tompkins, Douglas R; Davis, Holly; McKenna, C Ryan; Peng, Xianghong; Wessner, Lisa L; Niewolna, Maria; Guise, Theresa A; Suvannasankha, Attaya; Chirgwin, John M

    2014-12-02

    Adrenomedullin (AM) is secreted by breast cancer cells and increased by hypoxia. It is a multifunctional peptide that stimulates angiogenesis and proliferation. The peptide is also a potent paracrine stimulator of osteoblasts and bone formation, suggesting a role in skeletal metastases-a major site of treatment-refractory tumor growth in patients with advanced disease. The role of adrenomedullin in bone metastases was tested by stable overexpression in MDA-MB-231 breast cancer cells, which cause osteolytic bone metastases in a standard animal model. Cells with fivefold increased expression of AM were characterized in vitro, inoculated into immunodeficient mice and compared for their ability to form bone metastases versus control subclones. Bone destruction was monitored by X-ray, and tumor burden and osteoclast numbers were determined by quantitative histomorphometry. The effects of AM overexpression on tumor growth and angiogenesis in the mammary fat pad were determined. The effects of AM peptide on osteoclast-like multinucleated cell formation were tested in vitro. A small-molecule AM antagonist was tested for its effects on AM-stimulated ex vivo bone cell cultures and co-cultures with tumor cells, where responses of tumor and bone were distinguished by species-specific real-time PCR. Overexpression of AM mRNA did not alter cell proliferation in vitro, expression of tumor-secreted factors or cell cycle progression. AM-overexpressing cells caused osteolytic bone metastases to develop more rapidly, which was accompanied by decreased survival. In the mammary fat pad, tumors grew more rapidly with unchanged blood vessel formation. Tumor growth in the bone was also more rapid, and osteoclasts were increased. AM peptide potently stimulated bone cultures ex vivo; responses that were blocked by small-molecule adrenomedullin antagonists in the absence of cellular toxicity. Antagonist treatment dramatically suppressed tumor growth in bone and decreased markers of

  18. Trolox inhibits osteolytic bone metastasis of breast cancer through both PGE2-dependent and independent mechanisms.

    Science.gov (United States)

    Lee, Jong-Ho; Kim, Bongjun; Jin, Won Jong; Kim, Jung-Wook; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2014-09-01

    Bone is a preferred site of metastasis from breast cancer, and increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of Trolox, a vitamin E analog, led us to investigate whether Trolox inhibits bone metastasis and osteolysis caused by breast cancer. Administration of Trolox markedly inhibited osteolytic bone metastasis in an experimental metastasis model by intracardiac injection of 4T1 breast cancer cells. Trolox inhibited proliferation of 4T1 cells in the bone marrow but not in the mammary fat pad. In addition, Trolox could reduce tumor burden, osteolysis, and prostaglandin E2 (PGE2) production induced by direct inoculation of 4T1 cells into the marrow cavity of the tibia. Trolox decreased the migratory and invasive activities of 4T1 cells via PGE2-dependent and independent mechanisms. It also inhibited the ability of 4T1 cells to stimulate the expression of receptor activator of nuclear factor-κB ligand (RANKL), a key cytokine for osteoclast differentiation factor, in osteoblasts. In addition, Trolox suppressed RANKL expression in osteoblasts induced by soluble factors from 4T1 cells. Furthermore, Trolox suppressed 4T1 cell-induced osteoclast differentiation in the co-culture of bone marrow cells and osteoblasts via both PGE2-dependent and independent mechanisms. Taken together, these results suggest that Trolox inhibits breast cancer cell-induced osteoclast differentiation and the invasive behavior of cancer cells through PGE2-dependent and independent mechanisms, thereby suppressing osteolytic bone metastasis of breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2012-05-01

    megakaryocytes promote osteoblast synthesis of type I collagen, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (RANKL), all of...clinical benefits of anti-platelet agents (such as aspirin and heparin) in cancer patients [56]. Macrophages Promote Tumor Growth and Metastasis in Bone...2005) Megakaryocytes modulate osteoblast synthesis of type- l collagen, osteoprotegerin, and RANKL. Bone 36(5):812–819. doi:10.1016/j.bone.2004.12.006

  20. Genomic Copy Number Imbalances Associated with Bone and Non-bone Metastasis of Early-Stage Breast Cancer

    Science.gov (United States)

    Liu, Yanhong; Zhou, Renke; Baumbusch, Lars O.; Tsavachidis, Spyros; Brewster, Abenaa M.; Do, Kim-Anh; Sahin, Aysegul; Hortobagyi, Gabriel N.; Taube, Joseph H.; Mani, Sendurai A.; Aarøe, Jørgen; Wärnberg, Fredrik; Børresen-Dale, Anne-Lise; Mills, Gordon B.; Thompson, Patricia A.; Bondy, Melissa L.

    2014-01-01

    Purpose To identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Patients and Methods Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Results Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3–22.2, 3q27.1, 10q23.1, and 14q13.2–3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios (HRs). For bone metastasis, the hazard (95% confidence interval) for the low-risk group was 0.32 (0.11–0.92) compared to the intermediate-risk group and 2.99 (1.74–5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17–0.66) and 2.33 (1.59–3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Conclusions Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk. PMID:24305980

  1. Animal Models of Bone Metastasis

    Science.gov (United States)

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  2. Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis.

    Science.gov (United States)

    Feng, Shengmei; Zhu, Guochun; McConnell, Matthew; Deng, Lianfu; Zhao, Qiang; Wu, Mengrui; Zhou, Qi; Wang, Jinshen; Qi, Jin; Li, Yi-Ping; Chen, Wei

    2013-01-01

    Previous studies have shown that Atp6v1c1, a regulator of the assembly of the V0 and V1 domains of the V-ATPase complex, is up-regulated in metastatic oral tumors. Despite these studies, the function of Atp6v1c1 in tumor growth and metastasis is still unknown. Atp6v1c1's expression in metastatic oral squamous cell carcinoma indicates that Atp6v1c1 has an important function in cancer growth and metastasis. We hypothesized that elevated expression of Atp6v1c1 is essential to cancer growth and metastasis and that Atp6v1c1 promotes cancer growth and metastasis through activation of V-ATPase activity. To test this hypothesis, a Lentivirus-mediated RNAi knockdown approach was used to study the function of Atp6v1c1 in mouse 4T1 mammary tumor cell proliferation and migration in vitro and cancer growth and metastasis in vivo. Our data revealed that silencing of Atp6v1c1 in 4T1 cancer cells inhibited lysosomal acidification and severely impaired 4T1 cell growth, migration, and invasion through Matrigel in vitro. We also show that Atp6v1c1 knockdown with Lenti-c1s3, a lentivirus targeting Atp6v1c1 for shRNA mediated knockdown, can significantly inhibit 4T1 xenograft tumor growth, metastasis, and osteolytic lesions in vivo. Our study demonstrates that Atp6v1c1 may promote breast cancer growth and bone metastasis through regulation of lysosomal V-ATPase activity, indicating that Atp6v1c1 may be a viable target for breast cancer therapy and silencing of Atp6v1c1 may be an innovative therapeutic approach for the treatment and prevention of breast cancer growth and metastasis.

  3. Bisphosphonate-related atypical femoral fracture with bone metastasis of breast cancer: case report and review.

    Science.gov (United States)

    Hayashi, Kazunori; Aono, Masanari; Shintani, Kousuke; Kazuki, Kenichi

    2014-03-01

    Intravenous bisphosphonates (BPs) have been used to reduce the frequency of skeletal-related events due to bone metastases of several kinds of cancers. Although many studies on BP-related atypical fractures (BRAFs) due to the use of BP for osteoporosis treatment have been reported, few reports on BRAFs arising as a complication of long-term BP use for bone metastasis of cancer are available. A 62-year-old woman with a history of breast cancer presented with right thigh pain after she had a fall. Radiographs indicated a transverse fracture in the shaft of the right femur. She had been on zoledronate treatment for six years. Based on radiographic and histopathological findings, we concluded that the fracture was not a pathological fracture associated with metastasis but was a complication of long-term BP treatment. Clinical oncologists should consider the possibility of BRAFs in patients on long-term zoledronate treatment for bone metastases.

  4. Solitary bone metastasis to the tibia from colorectal cancer- A case report

    Directory of Open Access Journals (Sweden)

    Abdulsalam Alnajjar

    2014-12-01

    Full Text Available The onset of osseous metastases during the course of colorectal cancer is not common. Although rare, they usually appear in the axial skeleton. In our report, we refer to the case of a 48-year-old patient who presented with colon cancer and eventually developed a solitary bone metastasis in the upper end of left tibia. At the time of diagnosis and staging investigations, the patient had only a primary disease.------------------------------------------------Cite this article as:Alnajjar A, Mohanty AK. Solitary bone metastasis to the tibia from colorectal cancer- A case report. Int J Cancer Ther Oncol 2014; 2(4:02045. DOI: 10.14319/ijcto.0204.5

  5. Assessment of bone metastasis using nuclear medicine imaging in breast cancer: comparison between PET/CT and bone scan

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Dae Hyoun; Ahn, Byeong Cheol; Kang, Sung Min [Kyungpook National University Medical School, Daegu (Korea, Republic of)] (and others)

    2007-02-15

    Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with {sup 18}F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. The study group comprised 157 women patients (range: 28 {approx} 78 years old, mean {+-} SD = 49.5 {+-}8.5) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Six patients (4.4%) showed metastatic bone lesions. Four (66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients (100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion (4.79 {+-} 3.32 vs 1

  6. ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling.

    Science.gov (United States)

    Wang, Jun; Rouse, Clay; Jasper, Jeff S; Pendergast, Ann Marie

    2016-02-02

    Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastasis, a process that requires the activation of osteoclasts, cells that break down bone. We report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor cells and the bone microenvironment. ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast-activating factors interleukin-6 (IL-6) and matrix metalloproteinase 1 (MMP1). Furthermore, in breast cancer cells, ABL kinases increased the abundance of the Hippo pathway mediator TAZ and the expression of TAZ-dependent target genes that promote bone metastasis. Knockdown of ABL kinases or treatment with ABL-specific allosteric inhibitor impaired osteolytic metastasis of breast cancer cells in mice. These findings revealed a role for ABL kinases in regulating tumor-bone interactions and provide a rationale for using ABL-specific inhibitors to limit breast cancer metastasis to bone. Copyright © 2016, American Association for the Advancement of Science.

  7. Survival benefit with radium-223 dichloride in a mouse model of breast cancer bone metastasis.

    Science.gov (United States)

    Suominen, Mari I; Rissanen, Jukka P; Käkönen, Rami; Fagerlund, Katja M; Alhoniemi, Esa; Mumberg, Dominik; Ziegelbauer, Karl; Halleen, Jussi M; Käkönen, Sanna-Maria; Scholz, Arne

    2013-06-19

    Bone metastases are associated with increased morbidity and poor prognosis in breast cancer patients. Radium-223 dichloride is a calcium mimetic that localizes to bone, providing targeted therapy for skeletal metastasis. We investigated the mode of action of radium-223 dichloride using breast cancer cell, osteoclast, and osteoblast cultures as well as a mouse model of breast cancer bone metastasis. A single dose of radium-223 dichloride was used in three different settings mimicking the prevention or treatment of bone metastasis. Disease progression was monitored using fluorescence and radiographic imaging and histological analyses. The effect of radium-223 dichloride alone and in combination with doxorubicin or zoledronic acid on survival of mice was analyzed by Kaplan-Meier methods. All statistical tests used were two-sided. Radium-223 dichloride incorporated into bone matrix and inhibited proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (all P values radium-223 dichloride prevented tumor-induced cachexia (0/14 vs 7/14 control mice) and decreased osteolysis by 56% and tumor growth by 43% (all P values Radium-223 dichloride induced double-strand DNA breaks in cancer cells in vivo. Finally, radium-223 dichloride extended survival as a monotherapy (29.2 days, 95% confidence interval [CI] = 26.6 to 31.8 days, P = .039) and in combination with zoledronic acid (31.4 days, 95% CI = 28.8 to 34.0 days, P = .004) or doxorubicin (31.5 days, 95% CI = 29.5 to 33.5 days, P radium-223 dichloride was administered in a preventive or micrometastatic setting. Our findings strongly support the development of radium-223 dichloride for the treatment of breast cancer patients with or at high risk of developing bone metastases.

  8. Survival of cancer patients after radiotherapy for bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Matsubayashi, Takashi; Murata, Koichiro; Ikeda, Toshiaki; Tadokoro, Katsumi; Nishimaki, Hiroshi; Ohta, Akishige

    1988-12-01

    From January 1972 through April 1985, a total of 270 patients were treated with palliative radiation therapy for bone metastases. The lung and breast accounted for 52 % of the primary sites. A single target volume, in principle, receieved 1.7 to 2.5 Gy daily 6 times a week to a total dosage of 40-50 Gy. When there were two or more target volumes, a total of 20-30 Gy was delivered synchronously or metachronously to each irradiation field. According to the primary sites, median survivals after the beginning of radiation therapy were short for the lung (3.3 mo), stomach (2.1 mo), and uterine cervix (4.8 mo), in contrast to the breast (26.9 mo), thyroid (23.5 mo), and salivary gland (14.0 mo). Seven patients with breast cancer and one patient with thyroid cancer were alive 5 years or more after palliative radiation therapy. For these patients, the time of radiation therapy ranged from 6 mo before surgery to 88.6 mo after surgery. Four patients had one target volume, 3 had 2 volumes, and one had 4 volumes. Histological comparison for lung cancer revealed no significant difference in survivals between adenocarcinoma and squamous cell carcinoma. The primary site of cancer seems to be a contributing factor to the probability of longer survivals after palliative radiation therapy. In maintaining quality of life for long-term survivors, not only pain relief but also prevention of pathologic fracture and delayed radiation effects should be taken into account. (N.K.).

  9. The Role of Megakaryocytes in Breast Cancer Metastasis to Bone

    Science.gov (United States)

    2014-05-01

    vonWillibrand factor+, multinucleated cells were used to determine MK numbers. Blood platelets, serum levels of thrombopoietin ( TPO ) and SDF-1 were measured. In...together produced factor(s) that increase MK differentiation. In the meantime TPO -/- mouse embryos were regenerated and mice were backcrossed to...Balb/c so that metastasis could be determined in MK deficient mice. The TPO -/- mice appear to be more susceptible to metastasis than the wildtype, with

  10. 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.; Zhao, Ming

    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...

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Natural history of malignant bone disease in gastric cancer: final results of a multicenter bone metastasis survey.

    Science.gov (United States)

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

    2013-01-01

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

  13. Natural history of malignant bone disease in gastric cancer: final results of a multicenter bone metastasis survey.

    Directory of Open Access Journals (Sweden)

    Nicola Silvestris

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

  14. 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

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2016-12-01

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

  18. Galectin-3 Cleavage Alters Bone Remodeling: Different Outcomes in Breast and Prostate Cancer Skeletal Metastasis.

    Science.gov (United States)

    Nakajima, Kosei; Kho, Dhong Hyo; Yanagawa, Takashi; Harazono, Yosuke; Hogan, Victor; Chen, Wei; Ali-Fehmi, Rouba; Mehra, Rohit; Raz, Avraham

    2016-03-15

    Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche. ©2016 American Association for Cancer Research.

  19. RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

    Directory of Open Access Journals (Sweden)

    Elena Bevilacqua

    2012-01-01

    genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatic analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs.

  20. Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis.

    Science.gov (United States)

    Naruse, Katsuya; Yamada, Yoshiaki; Aoki, Shigeyuki; Taki, Tomohiro; Nakamura, Kogenta; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Sai, Shotoku; Nishio, Yoshitaka; Inoue, Yasusuke; Noguchi, Hiroshi; Hondai, Nobuaki

    2007-05-01

    We analyzed clinical data to identify prognostic indicators in prostate cancer patients with bone metastasis. The subjects were 60 patients with bone metastasis out of 165 patients diagnosed with prostate cancer at our clinic over 6 years from January 1998 to December 2003. The age at the initial diagnosis was 61 to 91 (mean: 73.7 +/- 7.5) years old. The following items were considered to be possible prognostic indicators: T (type) classification, N (node) classification, Gleason score, prostate specific antigen (PSA) value before therapy, disease grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum calcium (Ca), hemoglobin (Hgb), and platelet count (Plt). The 5-year overall survival rate was 45.7% in the 60 patients. Univariate analysis showed statistically significant differences in N (1), Gleason score 7 + 8/Gleason score 9 + 10, and LDH level (p = 0.0053, 0.0261, and 0.0049, respectively). Multivariate Cox proportional hazard analysis of these three items showed a statistically significant difference in LDH level and Gleason score 9 +/- 10 (p = 0.0167 and 0.0371). LDH was suggested to be an excellent prognostic indicator, because of its objectivity and convenience of measurement, in prostate cancer patients with bone metastasis.

  1. [Cancer metastasis].

    Science.gov (United States)

    Berner, A; Bryne, M; Thrane, P S

    1996-03-20

    Despite increasing insight into the biology of tumour development, the number of cancer deaths has not been subsequently reduced. This may be because approximately half of the cancers have metastasized already at the time of initial diagnosis. It seems important therefore, to learn more about the complex metastatic process. This process includes several linked sequential steps, and depends on an intimate interaction between the metastatic cells and the environment. In this review, we discuss these steps with emphasis on recent studies of the various cellular interactions that take place. Understanding these factors should result in diagnostic improvements and more effective treatment of cancer metastasis.

  2. Predictors of Positive Bone Metastasis in Newly Diagnosed Prostate Cancer Patients.

    Science.gov (United States)

    Chien, Tsu-Ming; Lu, Yen-Man; Geng, Jiun-Hung; Huang, Tsung-Yi; Ke, Hung-Lung; Huang, Chun-Nung; Li, Ching-Chia; Chou, Yii-Her; Wu, Wen-Jeng; Huang, Shu-Pin

    2016-01-01

    The prevalence of prostate cancer (PCa) has been increasing in recent years. Treatment strategies are largely based on the results of bone scan screening. Therefore, our aim was to investigate predictors of positive bone metastasis in newly diagnosed PCa patients. After extensive review, 336 consecutive patients newly diagnosed with PCa between April 2010 and November 2013 at our institution were enlisted in the study. Patients were divided into two groups according to bone scan results. Univariate analyses (Chi-square test for discrete variables and independent t-test for continuous variables) were applied to determine the potentially significant risk factors associated with distant bone metastasis. Binary logistic regression analyses were used to further investigate the influence of these factors on bone metastasis. The patient mean age was 71.9 ± 8.6 years (range: 48 to 94 years). The mean prostate specific antigen (PSA) level and biopsy Gleason score were 260.2 ± 1107.8 ng/mL and 7.4 ± 1.5, respectively. The body mass index (BMI) for the series was 24.5 ± 3.4 kg/m2. Sixty-four patients (19.0%) had a positive bone scan result. Patients with positive bone scan results had a significantly lower BMI (23.3 ± 3.5 vs. 24.8 ± 3.3; p=0.003), a higher Gleason score (8.5 ± 1.1 vs. 7.1 ± 1.5; p bone metastasis. Multivariate logistic regression analysis employing the above independent predictors demonstrated that a Gleason score of ≥7, clinical stage ≥T3, BMI ≤22 kg/m2, and an initial PSA level of ≥20 ng/mL were all independent predictors of bone metastasis. A bone scan might be necessary in newly diagnosed PCa patients with any of the following criteria: clinical stage T3 or higher, a Gleason score of 7 or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.

  3. Clinical features and treatment strategies for older prostate cancer patients with bone metastasis.

    Science.gov (United States)

    Yang, Cheng; Qi, Gui-Sheng; Rong, Rui-Ming; He, Jian

    2013-11-01

    To identify the clinical features and independent predictors of survival in older patients with bone metastasis from prostate cancer (PCa). We retrospectively analysed 205 older patients with bone metastases from PCa between 1997 and 2012. The Kaplan-Meier method was used with the log-rank test for survival rate calculations and to evaluate each variable. Multivariate analysis was performed with the Cox regression model. The chi-squared test was used to compare survival rates between older and younger (n=197) patients. All patients were followed up. The 1-, 2-, 3- and 5-year survival rates were 95.5%, 77.5%, 68.5% and 33.7%, respectively. Gleason score, radiotherapy of the primary tumour, the number of bone metastases, the alkaline phosphatase alkaline phosphatase (ALP) level, organ metastasis and regional lymph node metastasis were associated with the survival rates. Multivariate Cox regression analysis showed that Gleason score at diagnosis of the primary tumour was a significant predictor of overall survival following the diagnosis of bone metastases. In addition, the overall survival rates of older patients were higher compared with younger patients, but older patients who underwent radiotherapy had higher mortality. These data may serve as a guide for creating clinical prediction models in further studies.

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

    Directory of Open Access Journals (Sweden)

    Shikha Vashisht

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

  5. 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

    or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt...... with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p ......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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  7. Contribution of bone tissue modulus to breast cancer metastasis to bone.

    Science.gov (United States)

    Guelcher, Scott A; Sterling, Julie A

    2011-12-01

    Certain tumors, such as breast, frequently metastasize to bone where they can induce bone destruction. Currently, it is well-accepted that the tumor cells are influenced by other cells and growth factors present in the bone microenvironment that lead to tumor-induced bone disease. Over the past 20 years, many groups have studied this process and determined the major contributing factors; however, these results do not fully explain the changes in gene expression and cell behavior that occur when tumor cells metastasize to bone. More recently, groups studying metastasis from soft tissue sites have determined that the rigidity of the microenvironment, which increases during tumor progression in soft tissue, can regulate tumor cell behavior and gene expression. Therefore, we began to investigate the role of the rigid bone extracellular matrix in the regulation of genes that stimulate tumor-induced bone disease. We found that the rigidity of bone specifically regulates parathyroid hormone-related protein (PTHrP) and Gli2 expression in a transforming growth factor β (TGF-β) and mechanotransduction-dependent mechanism. In this review, we summarize the mechanotransduction signaling pathway and how this influences TGF-β signaling and osteolytic gene expression.

  8. 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

    2010-03-01

    Full Text Available 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.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.Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a factor that stimulates directly cancer growth and metastasis, and

  9. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    Small Animal Bone Phenotyping Core, respectively. The authors thank Enid Keyser for technical assistance in flow cytometry and sorting and the...Receptor. Structure 2012;20:1971–82. 40. Cummings SR, SanMartin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in

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

    Directory of Open Access Journals (Sweden)

    Zhou Zhen

    2012-04-01

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

  11. Metastasis to Bone in Human Cancer Is Associated with Loss of Occludin Expression.

    Science.gov (United States)

    Martin, Tracey A; Jordan, Nicola; Davies, Eleri L; Jiang, Wen G

    2016-03-01

    Occludin is an integral membrane protein localised at tight junctions (TJ). There is no consensus regarding its paramount role in TJ. In previous work we showed that occludin is aberrantly expressed in both human breast tissues and cancer cell lines. This study demonstrates a link to bone metastasis in human cancer. Primary breast tumours (n=124) and matched normal tissues (n=30) were processed for quantitative polymerase chain reaction (QPCR) analysis. A hammerhead ribozyme was constructed to create occludin knockdown cell lines, MDA-MB-231(ΔOcc) and PC-3(ΔOcc). The effect of human bone matrix extract (BME) was investigated using cell growth and electric cell impedance sensing (ECIS) technology to measure changes in attachment/migration. Trans-epithelial resistance (TER) was measured for assessing changes in TJ function. Cells used were MDA-MB-231, PC-3, CORL-23, SKMES-1 and A-549 human cancer cell lines. Tumours from patients with bone metastasis had significantly lower occludin expression compared to those remaining alive/well (60.7±21 vs. 331±98, respectively, p=0.008). This was striking in ductal carcinomas, where patients alive/well had significantly higher occludin expression compared to those with bone metastasis (391±12.5 vs. 67.9±28, respectively, p=0.0014). ECIS demonstrated that MDA-MB-231(ΔOcc) showed reduced attachment to 5% BME compared to controls (84% vs. 100%) that prevented closure of wounded cell layers. Moreover, these cells had reduced growth on BME. In addition, BME changed the TER of a number of human cell lines and was able to effect changes in the growth of MDA-MB-241 and PC-3 cells, with greater effect on knockdown cells. This is the first study to demonstrate that occludin expression has a clear relationship with bone metastasis in human cancer. The discrepancy between this and the in vitro data indicating a reduction in migration/growth rate of occludin knockdown indicates that loss of occludin leads to complex changes in human

  12. Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis

    Science.gov (United States)

    2004-11-01

    pep6de gene. Genes Dev. 1994;8(3):277-289. 10. Wysolmerskijj, Philbrick WM, Dunbar ME, La.nske B, Kronwberg H, Broadus AE. Rescue of the para- thyroid ...mechanism for stem cell homing. Bone.l006;38(4):497-508. 63. Guise TA, et al. Evidence for a causal role of para- thyroid hormone-related protein in...proliferative capacity and increased apoptosis in multiple tissues, retarded growth, early senescence and malnutrition leading to an early death [53]. In

  13. Tumor-Host Interaction in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2006-01-01

    Kallioniemi, O.-P., and Ethier, S. P. Molecular cytogenetic analysis of 11 new breast cancer cell lines. Br J Cancer, 81: 1328-1334, 1999. 26. Harris, A...1.318480186 NM_000546 TP53 Tumor protein p53 (Li-Fraumeni syndrome ) 0.875703301 NM_006670 TPBG Trophoblast glycoprotein 1.130637565 NM_003379 VIL2 Villin...primary tumors was determined according to the Richardson– Bloom grading system [17]. BM assessment BM (10 cc) was aspirated from the sternum and both

  14. Potential Role of CD68 in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2013-01-01

    antibody (AB-108-C) were also obtained from R&D Systems. Animals C57BL/6 mice were purchased from Harlan Industries (Indianapolis, IN). Mice were...Sotiriou C, Lacroix M, Lagneaux L, Berchem G, Body JJ: The aspirin metabolite salicylate inhibits breast cancer cells growth and their synthesis of the

  15. ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFβ Signaling Pathway.

    Science.gov (United States)

    Li, Xiao-Qing; Du, Xin; Li, Dong-Mei; Kong, Peng-Zhou; Sun, Yan; Liu, Pei-Fang; Wang, Qing-Shan; Feng, Yu-Mei

    2015-08-15

    Bone metastasis affects more than 70% of advanced breast cancer patients, but the molecular mechanisms of this process remain unclear. Here, we present clinical and experimental evidence to clarify the role of the integrin β-like 1 (ITGBL1) as a key contributor to bone metastasis of breast cancer. In an in vivo model system and in vitro experiments, ITGBL1 expression promoted formation of osteomimetic breast cancers, facilitating recruitment, residence, and growth of cancer cells in bone microenvironment along with osteoclast maturation there to form osteolytic lesions. Mechanistic investigations identified the TGFβ signaling pathway as a downstream effector of ITGBL1 and the transcription factor Runx2 as an upstream activator of ITGBL1 expression. In support of these findings, we also found that ITGBL1 was an essential mediator of Runx2-induced bone metastasis of breast cancer. Overall, our results illuminate how bone metastasis occurs in breast cancer, and they provide functional evidence for new candidate biomarkers and therapeutic targets to identify risk, to prevent, and to treat this dismal feature of advanced breast cancer. ©2015 American Association for Cancer Research.

  16. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    Science.gov (United States)

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2017-12-30

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Bone metastasis in prostate cancer: Recurring mitochondrial DNA mutation reveals selective pressure exerted by the bone microenvironment.

    Science.gov (United States)

    Arnold, Rebecca S; Fedewa, Stacey A; Goodman, Michael; Osunkoya, Adeboye O; Kissick, Haydn T; Morrissey, Colm; True, Lawrence D; Petros, John A

    2015-09-01

    Cancer progression and metastasis occur such that cells with acquired mutations enhancing growth and survival (or inhibiting cell death) increase in number, a concept that has been recognized as analogous to Darwinian evolution of species since Peter C. Nowell's description in 1976. Selective forces include those intrinsic to the host (including metastatic site) as well as those resulting from anti-cancer therapies. By examining the mutational status of multiple tumor sites within an individual patient some insight may be gained into those genetic variants that enhance site-specific metastasis. By comparing these data across multiple individuals, recurrent patterns may identify alterations that are fundamental to successful site-specific metastasis. We sequenced the mitochondrial genome in 10 prostate cancer patients with bone metastases enrolled in a rapid autopsy program. Patients had late stage disease and received androgen ablation and frequently other systemic therapies. For each of 9 patients, 4 separate tissues were sequenced: the primary prostate cancer, a soft tissue metastasis, a bone metastasis and an uninvolved normal tissue that served as the non-cancerous control. An additional (10th) patient had no primary prostate available for sequencing but had both metastatic sites (and control DNA) sequenced. We then examined the number and location of somatically acquired mitochondrial DNA (mtDNA) mutations in the primary tumor and two metastatic sites in each individual patient. Finally, we compared patients with each other to determine any common patterns of somatic mutation. Somatic mutations were significantly more numerous in the bone compared to either the primary tumor or soft tissue metastases. A missense mutation at nucleotide position (n.p.) 10398 (A10398G; Thr114Ala) in the respiratory complex I gene ND3 was the most common (7 of 10 patients) and was detected only in the bone. Other notable somatic mutations that occurred in more than one patient

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

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    Donna M. Sosnoski

    2012-01-01

    Full Text Available 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-231BRMS1GFP, 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.

  19. [The management of bone metastasis].

    Science.gov (United States)

    Bonetto, Rémi; Tallet, Agnès; Mélot, Anthony; Calderon, Benoît; Barlesi, Fabrice

    2017-06-01

    Bone metastasis are the most common cause of pain related to cancer, reducing patients' quality of life, and sometimes threatening their life-expectancy. Their management has to be pluridisciplinary, because of all the therapeutic options and the diversity of bone metastasis locations. The aim of this work is to propose a rational decisional algorithm for the treatment strategy of these secondary locations. Anti-resorbtive drugs with systemic action, surgery, conventional or stereotactic radiation therapy, and new techniques of interventional radiology are options that could be used separately or combined. They have shown benefits on symptomatic treatment, improving quality of life. Their indications vary according to the tumor site (short vs. long bones, carrier vs. non-carrier bones), the symptomatology (pain, neurologic symptoms), and the presence of complications (most of all fractures). The diverse presentations lead us to define this decisional algorithm, to guide the practice, while giving the maximal benefit to each patient according to each metastasis. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

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

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    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

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

    Science.gov (United States)

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

    2013-01-01

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

  2. [Bone metastasis of lung cancer in a mouse model with normal immune function].

    Science.gov (United States)

    Meng, Yue; Li, Chunyu; Hao, Song; Hu, Shaoyu; Lin, Zhen; Yuan, Liang; Li, Wei; Yan, Wenjuan; Chen, Jianting; Yang, Dehong

    2014-05-01

    To establish a model bearing human lung cancer xenograft with bone metastasis in mice with normal immune function. Forty female C57BL/6J mice were randomly allocated into 4 equal groups, including a control group and 3 immunosuppression groups treated with low, moderate, and high doses of dexamethasone (50, 100, and 150 mg, respectively). Four days after immune suppression, the mice were subjected to percutaneous injection of1.0×10(9) L(-1) A549 cells into the tibial plateau, and the bone defects were assessed radiographically 28 days after modeling. HE staining and immunohistochemical staining were used to examine the tumor tissues and bone tissue damages. In each of the 4 groups one mouse died during tumor cell injection. Only 1 mouse showed tumor formation in low-dose immunosuppression group, as compared to 7 and 4 in moderate- and high-dose immunosuppression groups. X-ray and microCT scan showed significant tibial bone destruction in moderate- and high-dose groups. The moderate- and high-dose groups showed similar ALP activities but both were significantly higher than those in the other two groups (Pdexamethasone results in longer survival time of the human lung cancer xenograft-bearing model mice as well as a higher tumor formation rate.

  3. Treatment patterns in patients with prostate cancer and bone metastasis among US community-based urology group practices.

    Science.gov (United States)

    Freedland, Stephen J; Richhariya, Akshara; Wang, Huei; Chung, Karen; Shore, Neal D

    2012-08-01

    To evaluate a cohort of United States-based urology practices for patterns related to screening, diagnosis, and treatment of bone metastases in men with castration-resistant prostate cancer. Chart audits at 15 community-based urology group practices were conducted in the United States. Patient charts were eligible for study inclusion and review if they had documented bone metastasis secondary to castration-resistant prostate cancer. Data abstracted include site and patient demographics, diagnosis patterns, and bone metastases treatment between July 2006 and July 2009. A sample of approximately 10 charts per practice was used, starting with the most recent patient who met eligibility requirements. Eligible patients (n = 147) from 15 practices had a mean (SD) age of 67.8 (9.3) years at prostate cancer diagnosis and 72.5 (8.6) years at diagnosis of bone metastasis. Bone metastasis occurred 31.3 months (median) after cancer diagnosis. Seventy-three percent (n = 108) of patients had multiple bone metastases, and 82% (n = 120) had bone metastases in weight-bearing bones at last follow-up. Intravenous bisphosphonates were administered to 49% (72/147) of patients, with 97% (70/72) receiving zoledronic acid. Among patients with castration-resistant prostate cancer and documented bone metastases, approximately one half received intravenous zoledronic acid. This suggests that the other half of patients with bone metastases from prostate cancer remained undertreated for the prevention of skeletal complications based on National Comprehensive Cancer Network guidelines during the study time period. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-01

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

  5. The role of radiotherapy in the treatment of bone metastasis of prostate cancer

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    Takahashi, Iku; Shinozaki, Jun; Nakamura, Yuhji; Takahashi, Mitsuhiro; Ikeda, Hajime; Mitsuhashi, Norio; Niibe, Hideo (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-11-01

    Pain relief is an important problem in the management of patients with prostate cancer because of the high frequency of bone metastasis. We analyzed the effects of radiotherapy on 157 sites of bone metastases in 39 patients with prostate cancer from 1970 to 1988. The radiation dose at which patients noticed some relief from pain for the first time was up to 20 Gy in 86% of the cases and up to 30 Gy in 98%. The effects of radiation in relieving pain, so that the patients could live as before pain first occurred, was recognized in 91% within the dose range of 20 Gy to 30 Gy. Fourteen patients who died within 6 months did not need re-irradiation applied to the same site, and only 12 out of a total of 80 irradiated sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. The maximum number of re-irradiation treatment applied to the same site was 4 to the sacrum at intervals of 10 to 18 months. As more that 60% of the patients who needed irradiation to control bone metastases died within a year, it was thought to be very important from the viewpoint of a useful life to get pain relief by irradiation immediately and safely. (author).

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  8. [Biology of cancer metastasis].

    Science.gov (United States)

    Robert, Jacques

    2013-04-01

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

  9. 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.

  10. Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone

    Science.gov (United States)

    Sloan, Erica K; Pouliot, Normand; Stanley, Kym L; Chia, Jenny; Moseley, Jane M; Hards, Daphne K; Anderson, Robin L

    2006-01-01

    Introduction Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear. Methods We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays. Results The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell

  11. In vitro design of mesenchymal to epithelial transition of prostate cancer metastasis using 3D nanoclay bone-mimetic scaffolds.

    Science.gov (United States)

    Molla, Md Shahjahan; Katti, Dinesh R; Katti, Kalpana S

    2017-06-11

    Nanocomposite scaffolds show extensive applications in regenerative medicine and have shown promise as in vitro analogues of human tissue that can be used for the study of diseases. The complex nature of cancer metastasis is recently investigated using several 3D scaffold models. Herein, we report a polymer-nanoclay-based in vitro tumour model that recapitulates early stage of prostate cancer (PCa) colonization during skeletal metastasis on bone mimetic scaffolds. A unique cell culture system termed as "sequential culture (SC)" has been applied to create a bone-mimetic niche for colonization of PCa cells. Human mesenchymal stem cells (MSCs) were seeded on the bone-mimetic scaffolds, where they differentiated into bone cells and then formed mineralized bone matrix without osteogenic supplements. Further, PCa was seeded on MSCs-seeded scaffolds. Sequentially cultured PCa cells with MSCs formed self-organized multicellular tumoroids with distinct tight cellular junctions and hypoxic core regions. Extensive quantitative reverse transcription-polymerase chain reaction experiments were performed to evaluate the expressions of genes related to osteotropic bone metastasis of PCa. On the nanoclay scaffolds, the MSCs differentiated to mature osteoblasts and epithelial to mesenchymal transition was inhibited whereas mesenchymal to epithelial transition was enhanced, as also the hypoxia increased angiogenesis, and finally, PCa cells initiated osteoblastic lesion. Further, the SC technique has significant effects on expression of key metastasis-related genes. Therefore, the SC-based tumour model can be applied to recapitulate more consistent osteotropic cancer cell behavior in understanding tumour biology. This model also can be implemented for drug screening to target colonization stage of PCa cells in the bone microenvironment. Copyright © 2017 John Wiley & Sons, Ltd.

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

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

    2016-04-15

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

  13. 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.

  14. Inhibition of Prostate Cancer Bone Metastasis by Synthetic TF Antigen Mimic/Galectin-3 Inhibitor Lactulose-l-Leucine

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    Olga V. Glinskii

    2012-01-01

    Full Text Available Currently incurable, prostate cancer metastasis has a remarkable ability to spread to the skeleton. Previous studies demonstrated that interactions mediated by the cancer-associated Thomsen-Friedenreich glycoantigen (TF-Ag and the carbohydrate-binding protein galectin-3 play an important role in several rate-limiting steps of cancer metastasis such as metastatic cell adhesion to bone marrow endothelium, homotypic tumor cell aggregation, and clonogenic survival and growth. This study investigated the ability of a synthetic small-molecular-weight nontoxic carbohydrate-based TF-Ag mimic lactulose-l-leucine (Lac-l-Leu to inhibit these processes in vitro and, ultimately, prostate cancer bone metastasis in vivo. Using an in vivo mouse model, based on intracardiac injection of human PC-3 prostate carcinoma cells stably expressing luciferase, we investigated the ability of Lac-l-Leu to impede the establishment and growth of bone metastasis. Parallel-flow chamber assay, homotypic aggregation assay, modified Boyden chamber assay, and clonogenic growth assay were used to assess the effects of Lac-l-Leu on tumor cell adhesion to the endothelium, homotypic tumor cell aggregation, transendothelial migration, and clonogenic survival and growth, respectively. We report that daily intraperitoneal administration of Lac-l-Leu resulted in a three-fold (P < .05 decrease in metastatic tumor burden compared with the untreated control. Mechanistically, the effect of Lac-l-Leu, which binds and inhibits galectins by mimicking essential structural features of the TF-Ag, was associated with a dose-dependent inhibition of prostate cancer cell adhesion to bone marrow endothelium, homotypic aggregation, transendothelial migration, and clonogenic growth. We conclude that small-molecular-weight carbohydrate-based compounds targeting β-galactoside-mediated interactions could provide valuable means for controlling and preventing metastatic prostate cancer spread to the skeleton.

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

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    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

  16. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    TAKURO ISODA

    2017-01-01

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

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

    Science.gov (United States)

    Isoda, Takuro; BaBa, Shingo; Maruoka, Yasuhiro; Kitamura, Yoshiyuki; Tahara, Keiichiro; Sasaki, Masayuki; Hatakenaka, Masamitsu; Honda, Hiroshi

    2017-01-01

    BONENAVI, a computer-aided diagnostic system, is used in bone scintigraphy. This system provides the artificial neural network (ANN) and bone scan index (BSI) values. ANN is associated with the possibility of bone metastasis, while BSI is related to the amount of bone metastasis. The degree of uptake on bone scintigraphy can be affected by the type of bone metastasis. Therefore, the ANN value provided by BONENAVI may be influenced by the characteristics of bone metastasis. In this study, we aimed to assess the relationship between ANN value and characteristics of bone metastasis. We analyzed 50 patients (36 males,14 females; age range: 87-42 yrs median age:72.5 yrs) with prostate, breast, or lung cancer who had undergone bone scintigraphy and were diagnosed with bone metastasis (32 cases of prostate cancer, nine cases of breast cancer, and nine cases of lung cancer). Those who had received systematic therapy over the past years were excluded. Bone metastases were diagnosed clinically, and the type of bone metastasis (osteoblastic, mildly osteoblastic, osteolytic, and mixed components) was decided visually by the agreement of two radiologists. We compared the ANN values (case-based and lesion-based) among the three primary cancers and four types of bone metastasis. There was no significant difference in case-based ANN values among prostate, breast, and lung cancers. However, the lesion-based ANN values were the highest in cases with prostate cancer and the lowest in cases of lung cancer (median values: prostate cancer, 0.980; breast cancer 0.909; and lung cancer, 0.864). Mildly osteoblastic lesions showed significantly lower ANN values than the other three types of bone metastasis (median values: osteoblastic,; 0.939 mildly osteoblastic; 0.788, mixed type; 0.991, and osteolytic. 0.969) The possibility of a lesion-based ANN value below 0.5 was %10.9 for bone metastasis in prostate cancer, %12.9 for breast cancer, and %37.2 for lung cancer. The corresponding

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-15

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

  1. Predictors of bone metastasis in pre-treatment staging of asymptomatic treatment-naïve patients with prostate cancer.

    Science.gov (United States)

    Moslehi, M; Cheki, M; Salehi-Marzijarani, M; Amuchastegui, T; Gholamrezanezhad, A

    2013-01-01

    There is no general consensus on the optimal criteria for the application of bone scintigraphy in screening of bone metastasis in patients with prostate cancer. Our study was conducted to assess the value of bone scan for pre-treatment staging of asymptomatic treatment-naïve patients with prostate cancer. A total of 203 consecutive asymptomatic and treatment-naïve patients with prostate cancer (age: 67.6±6.4 years) who were referred to our department for whole body bone scintigraphy were enrolled in the study. Three hours after intravenous injection of 20mCi (99m)Tc-MDP, all patients underwent whole body bone scanning using a single head gamma camera. The planar images were supplemented with SPECT as needed for questionable abnormalities or those having uncertain location on planar images. The mean serum PSA levels, serum alkaline phosphatase (ALP) and Gleason score (GS) were 42.41±37.1ng/ml, 223.9±129.9IU/L and 6.7±1.1, respectively. A total of 55 cases (27.1%) out of 203 patients had bone metastases. The univariate analysis showed that serum PSA levels, GS and ALP were all significant predictors of bone metastases. However, only serum PSA and ALP levels were found to be independent predictors of bone metastasis in the multivariate logistic regression analysis. The combination of PSA and ALP (in which patients with either elevated PSA [>20ng/ml] or elevated ALP were considered as positive) had the best screening value, with 98.2% sensitivity and 48.6% specificity. Serum ALP screening can be employed as a tool to detect the subgroup of patients who are at high risk of bone metastases, while having a PSA of bone metastasis in newly diagnosed patients with prostate cancer, without affecting staging accuracy. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  2. Multicentric Primary Angiosarcoma of Bone Mimicking Metastasis on (18)F-FDG PET/CT in a Patient with a History of Sigmoid Colon Cancer: a Case Report.

    Science.gov (United States)

    Yoo, Min Young; Lee, Eun Seong; Kim, Seok-Ki; Park, Seog-Yun; Kwon, Youngmee; Yun, Tak; Kim, Tae Sung

    2015-12-01

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

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

    Science.gov (United States)

    2009-03-14

    staining osteoclasts in mouse bone upon the introduction of ARCaPM compared to ARCaPE cells (33 ± 9 vs. 9 ± 1 TRAP-positive multinucleated osteo- clasts ...through interaction with RANK, a cell surface receptor of osteo- clasts . However, our results show that functional RANKL 604 Clin Exp Metastasis...switch from a tightly clustered cobblestone-like appearance to loosely associated spindle- shaped mes- enchymal stromal morphology characterizes EMT

  4. Intrathoracic stomach mimicking bone metastasis from thyroid cancer in whole-body iodine-131 scan diagnosed by SPECT/CT

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Gomez, Francisco Javier; Riva-Perez, Pablo Antonio de la; Calvo-Moron, Cinta; Bujan-Lloret, Cristina; Cambil-Molina, Teresa; Castro-Montano, Juan [Dept. of Nuclear Medicine, Virgen Macarena University Hospital, Sevilla (Spain)

    2017-05-15

    The whole-body iodine-131 scintigraphy is an imaging technique in monitoring patients with a history of thyroid cancer. Although the rate of false positives is negligible, it is not nonexistent. We report the case of an intervened and treated patient for thyroid cancer with good clinical and biochemical response. Scintigraphic findings were consistent with unsuspected bone metastasis. Fused SPECT/CT data allowed accurate diagnosis of giant diaphragmatic hernia associated with intrathoracic stomach, a very rare pathology that can lead to false positive results. (author)

  5. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT.

    Science.gov (United States)

    Peng, Xinsheng; Guo, Wei; Liu, Tiejian; Wang, Xi; Tu, Xiang'an; Xiong, Dafu; Chen, Song; Lai, Yingrong; Du, Hong; Chen, Guangfu; Liu, Guanglin; Tang, Yubo; Huang, Shuai; Zou, Xuenong

    2011-01-01

    The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.

  6. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT.

    Directory of Open Access Journals (Sweden)

    Xinsheng Peng

    Full Text Available The principal problem arising from prostate cancer (PCa is its propensity to metastasize to bone. MicroRNAs (miRNAs play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.

  7. Oxidative stress and antioxidant status in prostate cancer patients: relation to Gleason score, treatment and bone metastasis.

    Science.gov (United States)

    Battisti, Vanessa; Maders, Liési D K; Bagatini, Margarete D; Reetz, Luiz Gustavo B; Chiesa, Juarez; Battisti, Iara E; Gonçalves, Jamile F; Duarte, Marta M F; Schetinger, Maria R C; Morsch, Vera M

    2011-10-01

    Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. 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.

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

    National Research Council Canada - National Science Library

    Knudsen, Beatrice

    2004-01-01

    The hypothesis of this grant proposal is that androgen-ablative therapy paradoxically increases growth factor secretion from bone stromal cells and that this may stimulate the growth of prostate cancer metastases...

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

    National Research Council Canada - National Science Library

    Knudsen, Beatrice S

    2006-01-01

    The hypothesis of this grant proposal is that androgen-ablative therapy paradoxically increases growth factor secretion from bone stromal cells and that this may stimulate the growth of prostate cancer metastases...

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

    Science.gov (United States)

    2009-01-01

    ASBMR John Haddad Young Investigator award, American Society for Bone and Mineral Research. 2008 Noa Siris Schwartz Research Award, Bone and Cancer...Riggins for their technical assistance . 40 Funding Disclosure This work was supported by a Department of Defense (DoD) predoctoral fellowship

  12. Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer.

    Science.gov (United States)

    Smith, Matthew R; Cook, Richard; Lee, Ker-Ai; Nelson, Joel B

    2011-05-15

    The natural history of castration-resistant nonmetastatic prostate cancer is poorly defined. The authors used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases in men with prostate cancer, rising prostate-specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases. Relations between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N-telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin. At 2 years, 46% of subjects had developed bone metastases, and 20% had died. Median bone metastasis-free survival was 25 months. In multivariate analyses, baseline PSA ≥ 13.1 ng/mL was associated with shorter overall survival (relative risk [RR], 2.34; 95% confidence interval [CI], 1.71-3.21; P bone metastasis (RR, 1.98; 95% CI, 1.43-2.74; P bone metastasis-free survival (RR, 1.98; 95% CI, 1.45-2.70; P bone metastasis-free survival. Other covariates were not consistently associated with clinical outcomes. In men with progressive castration-resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis-free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes. 2010 American Cancer Society.

  13. Loss of TGF-β signaling in osteoblasts increases basic-FGF and promotes prostate cancer bone metastasis.

    Science.gov (United States)

    Meng, Xiangqi; Vander Ark, Alexandra; Daft, Paul; Woodford, Erica; Wang, Jie; Madaj, Zachary; Li, Xiaohong

    2018-04-01

    TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2 Col1CreERT KO) or in osteoclasts (Tgfbr2 LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2 Col1CreERT KO mice, but was inhibited in the Tgfbr2 LysMCre KO mice, relative to their respective control Tgfbr2 FloxE2 littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2 Col1CreERT KO mouse model. We found that bFGF was upregulated in osteoblasts from PC3-injected tibiae of Tgfbr2 Col1CreERT KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced bone lesions in Tgfbr2 Col1CreERT KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

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

  15. Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis

    DEFF Research Database (Denmark)

    Fabian, Katalin; Puskás, Rita; Kakuk, Tímea

    2017-01-01

    Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for chan...

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

    Directory of Open Access Journals (Sweden)

    Aiko Shigemitsu

    2010-12-01

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

  17. Reverse-phase protein array for prediction of patients at low risk of developing bone metastasis from breast cancer.

    Science.gov (United States)

    Hayashi, Naoki; Manyam, Ganiraju C; Gonzalez-Angulo, Ana M; Niikura, Naoki; Yamauchi, Hideko; Nakamura, Seigo; Hortobágyi, Gabriel N; Baggerly, Keith A; Ueno, Naoto T

    2014-09-01

    A biomarker that predicts bone metastasis based on a protein laboratory assay has not been demonstrated. Reverse-phase protein array (RPPA) enables quantification of total and phosphorylated proteins, providing information about their functional status. The aim of this study was to identify bone-metastasis-related markers in patients with primary breast cancer using RPPA analysis. Tumor samples were obtained from 169 patients with primary invasive breast carcinoma who underwent surgery. The patients were categorized by whether they developed breast cancer bone metastasis (BCBM) during follow-up. Clinical characteristics and protein expression by RPPA were compared and verified by leave-one-out cross-validation. Lymph node status (p = .023) and expression level of 22 proteins by RPPA were significantly correlated with BCBM in logistic regression analysis. These variables were used to build a logistic regression model. After filtering the variables through a stepwise algorithm, the final model, consisting of 8 proteins and lymph node status, had sensitivity of 30.0%, specificity of 90.5%, positive predictive value of 30.0%, and negative predictive value of 90.5% in the cross-validation. Most of the identified proteins were associated with cell cycle or signal transduction (CDK2, CDKN1A, Rb1, Src, phosphorylated-ribosomal S6 kinase, HER2, BCL11A, and MYH11). Our validated model, in which the primary tumor is tested with RPPA, can predict patients who are at low risk of developing BCBM and thus who likely would not benefit from receiving a bisphosphonate in the adjuvant setting. Clinical trials excluding these patients have the potential to clarify the benefit of bisphosphonates in the adjuvant setting. ©AlphaMed Press.

  18. Correlation and diagnostic performance of the prostate-specific antigen level with the diagnosis, aggressiveness, and bone metastasis of prostate cancer in clinical practice

    Directory of Open Access Journals (Sweden)

    Bannakij Lojanapiwat

    2014-09-01

    Conclusions: The data showed a strong correlation of PSA level with tumor diagnosis, tumor aggressiveness, and bone metastasis. The prevalence of prostate cancer in this cohort was 35.39%. The chance of diagnosis of prostate cancer was greater than that for benign prostatic hyperplasia when the PSA level was higher than 20 ng/mL.

  19. 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.

  20. 177Lu-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment

    OpenAIRE

    Bergmann, Ralf; Meckel, Marian; Kub??ek, Vojt?ch; Pietzsch, Jens; Steinbach, J?rg; Hermann, Petr; R?sch, Frank

    2016-01-01

    Background Metastatic bone lesion is a common syndrome of many cancer diseases in an advanced state. The major symptom is severe pain, spinal cord compression, and pathological fracture, associated with an obvious morbidity. Common treatments including systemic application of bisphosphonate drugs aim on pain reduction and on improving the quality of life of the patient. Particularly, patients with multiple metastatic lesions benefit from bone-targeting therapeutic radiopharmaceuticals. Agents...

  1. Prognostic significance of global grading system of Gleason score in patients with prostate cancer with bone metastasis.

    Science.gov (United States)

    Kambara, Tsunehito; Oyama, Tetsunari; Segawa, Atsuki; Fukabori, Yoshitatsu; Yoshida, Ken-Ichiro

    2010-06-01

    To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score or = 8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. Patients with a Gleason score of score of > or = 8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness.

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

    Directory of Open Access Journals (Sweden)

    Siddharth P Pathi

    2010-01-01

    Full Text Available 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.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.Our results indicate that HA promotes features associated with the neoplastic and metastatic growth of breast carcinoma cells in bone and that IL-8 may play an important role in this process. The developed mineralized tumor models may help to reveal the underlying cellular and molecular mechanisms that may ultimately enable more efficacious therapy of patients with advanced breast cancer.

  3. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer.

    Science.gov (United States)

    Diessner, Joachim; Wischnewsky, Manfred; Stüber, Tanja; Stein, Roland; Krockenberger, Mathias; Häusler, Sebastian; Janni, Wolfgang; Kreienberg, Rolf; Blettner, Maria; Schwentner, Lukas; Wöckel, Achim; Bartmann, Catharina

    2016-05-12

    The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms "exhausted CHAID (Chi-square Automatic Interaction Detectors)" and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.

  4. Cholinesterase activities and biochemical determinations in patients with prostate cancer: influence of Gleason score, treatment and bone metastasis.

    Science.gov (United States)

    Battisti, Vanessa; Bagatini, Margarete D; Maders, Liési D K; Chiesa, Juarez; Santos, Karen F; Gonçalves, Jamile F; Abdalla, Fátima H; Battisti, Iara E; Schetinger, Maria R C; Morsch, Vera M

    2012-06-01

    Prostate cancer (PCa) is the sixth most common type of cancer worldwide. Cholinesterase is well known as having non-cholinergic functions such as cellular proliferation and differentiation, suggesting a possible influence of cholinesterase in tumorogenesis. Thus, the aim of this study was to investigate the whole blood acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) activities and some biochemical parameters in PCa patients. This study was performed in 66 PCa patients and 40 control subjects. AChE and BChE activities were determined in PCa patients and the influence of the Gleason score; bone metastasis and treatment in the enzyme activities were also verified. Furthermore, we also analyzed possible biochemical alterations in these patients. AChE and BChE activities decreased in PCa patients in relation to the control group and various biochemical changes were observed in these patients. Moreover, Gleason score, metastasis and treatment influenced cholinesterase activities and biochemical determinations. Our results suggest that cholinesterases activities and biochemical parameters are altered in PCa. These facts support the idea that the drop in the cholinesterase activity and the consequent increased amount of acetylcholine could lead to a cholinergic overstimulation and increase the cell proliferation in PCa. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.

    Science.gov (United States)

    Jeffery, Justin J; Lux, Katie; Vogel, John S; Herrera, Wynetta D; Greco, Stephen; Woo, Ho-Hyung; AbuShahin, Nisreen; Pagel, Mark D; Chambers, Setsuko K

    2014-04-01

    Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.

  6. Identification of Genes Associated with Breast Cancer Metastasis to Bone on a Protein-Protein Interaction Network with a Shortest Path Algorithm.

    Science.gov (United States)

    Cai, Yu-Dong; Zhang, Qing; Zhang, Yu-Hang; Chen, Lei; Huang, Tao

    2017-02-03

    Tumor metastasis is defined as the spread of tumor cells from one organ or part to another that is not directly connected to it, which significantly contributes to the progression and aggravation of tumorigenesis. Because it always involves multiple organs, the metastatic process is difficult to study in its entirety. Complete identification of the genes related to this process is an alternative way to study metastasis. In this study, we developed a computational method to identify such genes. To test our method, we selected breast cancer bone metastasis. A large network was constructed using human protein-protein interactions. On the basis of the validated genes related to breast and bone cancer, a shortest path algorithm was applied to the network to search for novel genes that may mediate breast cancer metastasis to bone. In addition, further rules constructed using the permutation FDR, the betweenness ratio, and the max-min interaction score were also employed in the method to make the inferred genes more reliable. Eighteen putative genes were identified by the method and were extensively analyzed. The confirmation results indicate that these genes participate in metastasis.

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

    Directory of Open Access Journals (Sweden)

    Berna C Özdemir

    Full Text Available 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

  8. [When should we perform a bone scintigraphy in patients with new diagnosis of asymptomatic prostate cancer in order to detect bone metastasis?].

    Science.gov (United States)

    Márquez-López, Javier; Gómez-Gómez, Enrique; Anaya-Henares, Fernando; Robles-Casilda, Rafael; Requena-Tapia, María José

    2015-03-01

    To define, based on PSA value, Gleason score (GS), clinical stage and age, those patients diagnosed with asymptomatic prostate cancer whose cases warrant further study of bone metastasis (BMet). From January 2006 to May 2010, we evaluated 263 patients diagnosed with prostate cancer who were chosen for further study of bone scintigraphy following the consensus protocol accepted by the Ministry of Health of Andalusia (Integrated Andalusian Process Prostate Cancer-BPH). All selected studies met the criteria defined in the test indications: PSA >10 or Gleason score (GS) ≥7 or positive biopsy of seminal vesicles, all without symptoms of bone pain. A multivariate analysis of potential predictive factors for positive bone scintigraphy was performed and cutoffs were determined by calculating the following diagnostic rates: sensitivity, specificity and positive and negative predictive values with their respective confidence intervals at 95% certainty. BMet were detected in 29 cases (11%). The average age of the patients with a positive bone scan was 65.5 and 68.4 years in those with a negative result (p=0.03). Multivariate analysis showed that GS OR: 2.08 [95% CI (1.34 - 3.18)] (pbone scan. The cutoffs were estimated by ROC curve analysis, resulting in a cutoff of 16.18 ng/ml for PSA value and 7 for GS (larger area under the curve: 0.864 with a sensitivity of 94.5% and specificity of 47%). In the group of patients defined in our study, diagnosed with asymptomatic prostate cancer, the assessment of BMet using a bone scan should be carried out with a PSA level ≥ 16.18 ng/ml and GS ≥7 as reference points.

  9. Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: influence of Gleason score, treatment and bone metastasis.

    Science.gov (United States)

    Battisti, Vanessa; Maders, Liési D K; Bagatini, Margarete D; Battisti, Iara E; Bellé, Luziane P; Santos, Karen F; Maldonado, Paula A; Thomé, Gustavo R; Schetinger, Maria R C; Morsch, Vera M

    2013-04-01

    The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer.

    Science.gov (United States)

    Josson, Sajni; Gururajan, Murali; Hu, Peizhen; Shao, Chen; Chu, GinaChia-Yi; Zhau, Haiyen E; Liu, Chunyan; Lao, Kaiqin; Lu, Chia-Lun; Lu, Yi-Tsung; Lichterman, Jake; Nandana, Srinivas; Li, Quanlin; Rogatko, Andre; Berel, Dror; Posadas, Edwin M; Fazli, Ladan; Sareen, Dhruv; Chung, Leland W K

    2014-09-01

    miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens. miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models. Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with progression-free survival of patients with prostate cancer. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor-treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival compared with control vehicle-treated cells. miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer. ©2014 American Association for Cancer Research.

  11. miR-409-3p/-5p promotes tumorigenesis, epithelial to mesenchymal transition and bone metastasis of human prostate cancer

    Science.gov (United States)

    Josson, Sajni; Gururajan, Murali; Hu, Peizhen; Shao, Chen; Chu, Gina Chia-Yi; Zhau, Haiyen E.; Liu, Chunyan; Lao, Kaiqin; Lu, Chia-Lun; Lu, Yi-Tsung; Lichterman, Jake; Nandana, Srinivas; Li, Quanlin; Rogatko, Andre; Berel, Dror; Posadas, Edwin M.; Fazli, Ladan; Sareen, Dhruv; Chung, Leland W. K.

    2014-01-01

    Purpose miR-409-3p/-5p is a microRNA expressed by embryonic stem cells and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines, therefore we defined the biological impact of manipulation of miR-409-3p/-5p in prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens. Experimental Design miRNA profiling of prostate cancer bone metastatic EMT cell line model was performed. Gleason score human tissue array was probed for validation of specific miRNAs. Additionally, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, epithelial to mesenchymal transition (EMT) and bone metastasis in mouse models. Results Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with prostate cancer patient progression free survival. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed, EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor treated bone metastatic ARCaPM prostate cancer cells in mice, led to decreased bone metastasis and increased survival compared to control vehicle-treated cells. Conclusion miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT and bone metastasis. This finding bear’s particular translational importance since miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bones metastatic prostate cancer. PMID:24963047

  12. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model.

    Science.gov (United States)

    Murray, Lesley J; Abrams, Tinya J; Long, Kelly R; Ngai, Theresa J; Olson, Lisa M; Hong, Weiru; Keast, Paul K; Brassard, Jacqueline A; O'Farrell, Anne Marie; Cherrington, Julie M; Pryer, Nancy K

    2003-01-01

    The aim of the study was to investigate inhibitory effects of the receptor tyrosine kinase (RTK) inhibitor SU11248 against CSF-1R and osteoclast (OC) formation. We developed an in vivo model of breast cancer metastasis to evaluate efficacy of SU11248 against tumor growth and tumor-induced osteolysis in bone. The in vitro effects of SU11248 on CSF-1R phosphorylation, OC formation and function were evaluated. Effects on 435/HAL-Luc tumor growth in bone were monitored by in vivo bioluminescence imaging (BLI), and inhibition of osteolysis was evaluated by measurement of serum pyridinoline (PYD) concentration and histology. Phosphorylation of the receptor for M-CSF (CSF-1R) expressed by NIH3T3 cells was inhibited by SU11248 with an IC50 of 50-100 nM, consistent with CSF-1R belonging to the class III split kinase domain RTK family. The early M-CSF-dependent phase of in vitro murine OC development and function were inhibited by SU11248 at 10-100 nM. In vivo inhibition of osteolysis was confirmed by significant lowering of serum PYD levels following SU11248 treatment of tumor-bearing mice (P = 0.047). Using BLI, SU11248 treatment at 40 mg/kg/day for 21 days showed 64% inhibition of tumor growth in bone (P = 0.006), and at 80 mg/kg/day showed 89% inhibition (P = 0.001). Collectively, these data suggest that SU11248 may be an effective and tolerated therapy to inhibit growth of breast cancer bone metastases, with the additional advantage of inhibiting tumor-associated osteolysis.

  13. Breast Cancer Metastasis

    Science.gov (United States)

    Marino, Natascia; Woditschka, Stephan; Reed, L. Tiffany; Nakayama, Joji; Mayer, Musa; Wetzel, Maria; Steeg, Patricia S.

    2014-01-01

    Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient’s primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed. PMID:23895915

  14. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Gabet Yankel

    2010-09-01

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

  16. Metastasis of breast cancer cells to the bone, lung, and lymph nodes promotes resistance to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Takamitsu [Gunma Prefectural College of Health Sciences, Department of Radiological Technology, School of Radiological Technology, Gunma, Maebashi (Japan); Iwadate, Manabu [Fukushima Medical University, Department of Thyroid and Endocrinology, School of Medicine, Fukushima (Japan); Tachibana, Kazunoshin [Fukushima Medical University, Department of Breast Surgery, School of Medicine, Fukushima (Japan); Waguri, Satoshi [Fukushima Medical University, Department of Anatomy and Histology, School of Medicine, Fukushima (Japan); Takenoshita, Seiichi [Fukushima Medical University, Advanced Clinical Research Center, Fukushima Global Medical Science Center, School of Medicine, Fukushima (Japan); Hamada, Nobuyuki [Central Research Institute of Electric Power Industry (CRIEPI), Radiation Safety Research Center, Nuclear Technology Research Laboratory, Tokyo, Komae (Japan)

    2017-10-15

    Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis. The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X-ray-induced clonogenic inactivation and apoptosis in vitro. Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance. (orig.) [German] Metastasierung ist die Hauptursache fuer den toedlichen Verlauf von Brustkrebserkrankungen. Darauf muessen spezifische Behandlungsstrategien ausgerichtet werden. Sowohl primaere als auch metastatische Brustkrebsarten koennen mit einer Strahlentherapie behandelt werden, allerdings sind die Unterschiede in der Reaktion auf ionisierende Strahlung bis heute nicht vollstaendig verstanden. In dieser Studie wird zum ersten Mal die Strahlenantwort einer Brustkrebszelllinie mit der ihrer metastatischen Varianten verglichen und die erhoehte Strahlenresistenz der metastatischen Varianten gezeigt. Eine Luciferase-exprimierende Zelllinie wurde aus humanen basaloiden Brustadenokarzinomen

  17. 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.

  18. Cancer patients use hospital-based care until death: a further analysis of the Dutch Bone Metastasis Study.

    Science.gov (United States)

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

    2011-10-01

    To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. The Dutch Bone Metastasis Study (DBMS) was a nationwide study proving equal effectiveness of single fraction palliative radiotherapy compared with multiple fractions for painful bone metastases in 1157 patients. The 860 (74%) patients who died during follow-up were included in the current analysis. The main outcome was the frequency of hospital-based (outpatient contact or admission) and/or general practitioner (GP) contact during the last 12 weeks of life. Changes in HCU towards death were related to data on quality of life and pain intensity using a multilevel regression model. Hospital-based HCU was reported in 1801 (63%) returned questionnaires, whereas GP contact was stated in 1246 (43%). In 573 (20%) questionnaires, both types of HCU were reported. In multilevel regression analyses, the frequency of outpatient contacts remained constant during the weeks towards death, whereas the frequency of GP contacts increased. Lower valuation of quality of life was related to both GP- and hospital-based HCU. There was a high consumption of hospital-based HCU in the last 12 weeks of life of cancer patients with bone metastases. Hospital-based HCU did not decrease during the weeks towards death, despite an increase in GP contacts. Future planning of palliative care and training programs should encompass close collaboration between medical specialists and GPs to optimize end-of-life care.

  19. 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

  20. Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

    Science.gov (United States)

    Nozawa, Masahiro; Hara, Isao; Matsuyama, Hideyasu; Iki, Masayuki; Nagao, Kazuhiro; Nishioka, Tsukasa; Komura, Takahiro; Esa, Atsunobu; Uejima, Shigeya; Imanishi, Masaaki; Uekado, Yasunari; Ogawa, Takatoshi; Kajikawa, Hiroshi; Uemura, Hirotsugu

    2015-09-01

    This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

  1. Inhibition of the RANK/RANKL signaling with osteoprotegerin prevents castration-induced acceleration of bone metastasis in castration-insensitive prostate cancer.

    Science.gov (United States)

    Takayama, Koichiro; Inoue, Takamitsu; Narita, Shintaro; Maita, Shinya; Huang, Mingguo; Numakura, Kazuyuki; Tsuruta, Hiroshi; Saito, Mitsuru; Maeno, Atsushi; Satoh, Shigeru; Tsuchiya, Norihiko; Habuchi, Tomonori

    2017-07-01

    Androgen deprivation therapy (ADT) for patients with metastatic or locally advanced prostate cancer reduces bone mineral density by stimulating receptor activator of nuclear factor kappa-B (RANK) signaling in osteoclasts. The involvement of the RANK/RANKL signaling in ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer was examined in a murine model using osteoprotegerin (OPG). Male Balb/c nude mice were divided into three groups: the non-castration, castration, and castration + OPG groups. PC-3M-luc-C6 was injected into the left ventricle of the mice. Recombinant OPG was injected intravenously twice weekly in the castration + OPG group. In-vivo imaging system (IVIS ® ) determined that the prevalence and photon counts of bone metastasis in the castration group were significantly higher than that in the non-castration and castration + OPG groups. The mean number of RANKL-positive osteoblasts and the mean serum RANKL level in the castration group were significantly higher than those in the non-castration group. RANKL-enhanced activation of osteoclasts was attenuated in the castration + OPG group. These results suggest that the mechanisms of RANK/RANKL signaling are involved in the ADT-induced acceleration of bone metastasis in castration-insensitive prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    2009-04-01

    mice or rats . Further manipulation of the bioreactor may allow the time frame to be shortened. We have not seen osteocytes at 5 months but we have...bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone

  3. 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.

  4. Diagnostic performance of a computer-assisted diagnosis system for bone scintigraphy of newly developed skeletal metastasis in prostate cancer patients: search for low-sensitivity subgroups.

    Science.gov (United States)

    Koizumi, Mitsuru; Motegi, Kazuki; Koyama, Masamichi; Terauchi, Takashi; Yuasa, Takeshi; Yonese, Junji

    2017-08-01

    The computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems. An artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient's situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded. BONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion. BONENAVI with BS has good sensitivity and specificity for detecting prostate cancer's osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.

  5. Pristimerin Inhibits Prostate Cancer Bone Metastasis by Targeting PC-3 Stem Cell Characteristics and VEGF-Induced Vasculogenesis of BM-EPCs

    Directory of Open Access Journals (Sweden)

    Shuai Huang

    2015-08-01

    Full Text Available Background/Aims: Prostate cancer (PCa is one of the most common malignant cancers and a major leading cause of cancer deaths in men. Cancer stem-like cells are shown to be highly tumorigenic, pro-angiogenic and can significantly contribute to tumor new vessel formation and bone marrow derived-EPCs (BM-EPCs are shown to recruit to the angiogenic switch in tumor growth and metastatic progression, suggesting the importance of targeting cancer stem cells (CSCs and EPCs for novel tumor therapies. Pristimerin, an active component isolated from Celastraceae and Hippocrateaceae, has shown anti-tumor effects in some cell lines in previous studies. However, the effect and mechanism of Pristimerin on CSCs and EPCs in PCa bone metastasis are not well studied. Methods: The effect of Pristimerin on PC-3 stem cell characteristics and metastasis were detected by spheroid formation, CD133 and CD44 protein expression, matrix-gel invasive assay and colony-formation assay in vitro, VEGF and pro-inflammatory cytokines expression by ELISA assay, and tumor tumorigenicity by X-ray and MR in NOD-SCID mice model in vivo. In addition, we also detected the effect of Pristimerin on VEGF-induced vasculogenesis and protein expression of BM-EPCs. Results: Pristimerin could significantly inhibit spheroid formation and protein expression of CD133 and CD44, reduce VEGF and pro-inflammation cytokines expression of PC-3 cell, and prevent the xenografted PC-3 tumor growth in the bone of nude mice. The present data also showed that Pristimerin significantly inhibited VEGF-induced vasculogenesis of BM-EPCs by suppressing the EPCs functions including proliferation, adhesion, migration, tube formation and inactivation the phosphorylation of VEGFR-2, Akt and eNOS. Conclusion: These data provide evidence that Pristimerin has strong potential for development as a novel agent against prostate bone metastasis by suppressing PC-3 stem cell characteristics and VEGF-induced vasculogenesis of BM-EPCs.

  6. Breast cancer-derived bone metastasis can be effectively reduced through specific c-MET inhibitor tivantinib (ARQ 197) and shRNA c-MET knockdown.

    Science.gov (United States)

    Previdi, Sara; Abbadessa, Giovanni; Dalò, Francesca; France, Dennis S; Broggini, Massimo

    2012-01-01

    Breast cancer exhibits a propensity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. We have shown the involvement of the HGF/c-MET system in tumor-bone interaction contributing to human breast cancer metastasis. Therefore, disruption of HGF/c-MET signaling is a potential targeted approach to treating metastatic bone disease. In this study, we evaluated the effects of c-MET inhibition by both an oral, selective, small-molecule c-MET inhibitor, tivantinib, and a specific short hairpin RNA (shRNA) against c-MET in a mouse model of human breast cancer. Tivantinib exhibited dose-dependent antimetastatic activity in vivo, and the 120 mg/kg dose, proven to be suboptimal in reducing subcutaneous tumor growth, induced significant inhibition of metastatic growth of breast cancer cells in bone and a noteworthy reduction of tumor-induced osteolysis. shRNA-mediated c-MET silencing did not affect in vitro proliferation of bone metastatic cells, but significantly reduced their migration, and this effect was further enhanced by tivantinib. Both observations were confirmed in vivo. Indeed, more pronounced tumor growth suppression with concomitant marked decreases of lytic lesions and prolongation of survival were achieved by dual c-MET inhibition using both tivantinib and RNA interference strategies. Overall, our findings highlighted the effectiveness of c-MET inhibition in delaying the onset and progression of bone metastases and strongly suggest that targeting c-MET may have promising therapeutic value in the treatment of bone metastases from breast cancer. ©2011 AACR.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

  8. A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis.

    Science.gov (United States)

    LaBerge, Greggory S; Duvall, Eric; Grasmick, Zachary; Haedicke, Kay; Pawelek, John

    2017-01-01

    Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma. Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML), developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes. DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor. The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease.

  9. CXXL 14 Blockade of CXCL12/CXCR4 Signaling in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2016-10-01

    in breast cancer, hepatocellular carcinoma , gastric cancer, colon cancer, mouse acute myeloid leukemia, and neuroendocrine tumors (19-26). However...were analyzed for CXCL14 protein expression . Immunocytochemical CXCL14 staining was almost exclusively restricted to the cytoplasm (data not shown...2012;135(3):725-35. 21. Wang W, Huang P, Zhang L, et al. Antitumor efficacy of C-X-C motif chemokine ligand 14 in hepatocellular carcinoma in vitro

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

    Science.gov (United States)

    2008-10-01

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

  11. Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone

    Science.gov (United States)

    Leblanc, Raphael; Lee, Sue-Chin; David, Marion; Bordet, Jean-Claude; Norman, Derek D.; Patil, Renukadevi; Miller, Duane; Sahay, Debashish; Ribeiro, Johnny; Clézardin, Philippe; Tigyi, Gabor J.

    2014-01-01

    Autotaxin (ATX), through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed in multiple types of cancers, and together with LPA generated during platelet activation promotes skeletal metastasis of breast cancer. However, the pathophysiological sequelae of regulated interactions between circulating LPA, ATX, and platelets remain undefined in cancer. In this study, we show that ATX is stored in α-granules of resting human platelets and released upon tumor cell-induced platelet aggregation, leading to the production of LPA. Our in vitro and in vivo experiments using human breast cancer cells that do not express ATX (MDA-MB-231 and MDA-B02) demonstrate that nontumoral ATX controls the early stage of bone colonization by tumor cells. Moreover, expression of a dominant negative integrin αvβ3-Δ744 or treatment with the anti-human αvβ3 monoclonal antibody LM609, completely abolished binding of ATX to tumor cells, demonstrating the requirement of a fully active integrin αvβ3 in this process. The present results establish a new mechanism for platelet contribution to LPA-dependent metastasis of breast cancer cells, and demonstrate the therapeutic potential of disrupting the binding of nontumor-derived ATX with the tumor cells for the prevention of metastasis. PMID:25277122

  12. Correlation and diagnostic performance of the prostate-specific antigen level with the diagnosis, aggressiveness, and bone metastasis of prostate cancer in clinical practice.

    Science.gov (United States)

    Lojanapiwat, Bannakij; Anutrakulchai, Wisan; Chongruksut, Wilaiwan; Udomphot, Chaichawan

    2014-09-01

    The common tool for diagnosing prostate cancer is serum prostate-specific antigen (PSA) testing and digital rectal examination, but the disadvantage of the high sensitivity and low specificity of PSA testing in the diagnosis of prostate cancer is a problem in clinical practice. We studied the correlation and diagnostic performance of the PSA level with cancer diagnosis, aggressiveness of prostate cancer (Gleason score>7), and bone metastasis. A total 1,116 patients who underwent transrectal ultrasound and prostate biopsy were retrospectively studied. The patients were divided into subgroups by baseline PSA level as follows: ≤4, 4.1-10, 10.1-20, 20.1-50, 50.1-100, and >100 ng/mL. The area under the receiver operating characteristic curve (AuROC), sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of each PSA level were evaluated for correlation and diagnostic performance with positive biopsy, Gleason score for aggressiveness, and bone metastasis. A positive biopsy result was found in 395 patients (35.39%). The PSA level corresponded well with the diagnosis of prostate cancer and a positive bone scan but moderately well with Gleason score as shown by AuROC for diagnosis of prostate cancer (0.82), positive bone scan (0.88), and Gleason score>7 (0.78). The specificity of a PSA level of 4.1-10, 10.1-20, 21.1-50, 50.1-100, and >100 ng/mL in the diagnosis prostate cancer was 9.3, 55.5, 87.5, 98.2, and 99.7, respectively. The data showed a strong correlation of PSA level with tumor diagnosis, tumor aggressiveness, and bone metastasis. The prevalence of prostate cancer in this cohort was 35.39%. The chance of diagnosis of prostate cancer was greater than that for benign prostatic hyperplasia when the PSA level was higher than 20 ng/mL.

  13. Cancer metastasis: issues and challenges.

    Science.gov (United States)

    Qian, Chao-Nan; Mei, Yan; Zhang, Jian

    2017-04-03

    Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied. Using The Cancer Genome Atlas datasets to re-analyze the effect of some previously reported metastatic genes-e.g., JAM2, PPARGC1A, SIK2, and TRAF6-on overall survival of patients with renal and liver cancers, we found that these genes are actually protective factors for patients with cancer. The role of epithelial-mesenchymal transition (EMT) in single-cell metastasis has been well-documented. However, in metastasis caused by cancer cell clusters, EMT may not be necessary. A novel role of epithelial marker E-cadherin, as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling, has been found. This editorial also discusses the obstacles for developing anti-metastatic drugs, including the lack of high-throughput technologies for identifying metastasis inhibitors, less application of animal models in the pre-clinical evaluation of the leading compounds, and the need for adjustments in clinical trial design to better reflect the anti-metastatic efficacy of new drugs. We are confident that by developing more effective high-throughput technologies to identify metastasis inhibitors, we can better predict, prevent, and treat cancer metastasis.

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

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

    2007-08-15

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

  15. BRMS1 Suppresses Breast Cancer Metastasis to Bone via its Regulation of microRNA-125b and Downstream Attenuation of TNF-alpha and HER2 Signaling Pathways

    Science.gov (United States)

    2012-10-01

    capabilities to metastasize to ovaries, liver, lungs, kidneys, and bones following intravenous injection. We also observed skull -restricted bioluminescent...MP, Shen J, Chang SS, Yu D, Steeg PS, and Hung MC. (2012) A novel model of breast cancer metastasis: killing two birds with one stone. AACR Annual...novel model of breast cancer metastasis: killing two birds with one stone Yekaterina B. Khotskaya1, Mariano Ponz Sarvice1, Jia Shen1,2, Shih-Shin

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

    NARCIS (Netherlands)

    Wymenga, L. F.; Groenier, K.; Schuurman, J.; Boomsma, J. H.; Elferink, R. O.; Mensink, H. J.

    2001-01-01

    OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were

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

    Directory of Open Access Journals (Sweden)

    Yamamoto Y

    2013-10-01

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

  18. Serum alkaline phosphatase differentiates prostate-specific antigen flare from early disease progression after docetaxel chemotherapy in castration-resistant prostate cancer with bone metastasis.

    Science.gov (United States)

    Han, Kyung Seok; Hong, Sung Joon

    2014-10-01

    A transient rise in prostate-specific antigen (PSA) after the initiation of chemotherapy, called as PSA flare, has been frequently reported in patients with castration-resistant prostate cancer (CRPC) but there has been no way to differentiate PSA rises in CRPC. We investigated whether bone-related serum markers differentiate PSA flare from progression in CRPC patients with bone metastasis. We reviewed CRPC patients with bone metastasis who received systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP), calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow-up serum parameters after the first cycle of chemotherapy were included in statistical analyses. PSA increased in 38 patients (45.8 %) at the first evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or did not decrease to the stabilization level by the third evaluation in 22 (26.5 %) patients, while PSA decreased to the stabilization or response level by the third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The univariate analyses showed that no baseline parameters were associated with PSA flare, but the initial ALP decrease, changed ALP ratio, and median calcium level were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012, respectively). Multivariate logistic regression analysis showed that a change in the ALP level is an independent predictive factor for PSA flare (p = 0.017). ALP is a useful biomarker to differentiate PSA flare from early PSA progression during docetaxel chemotherapy in CRPC patients with bone metastasis.

  19. Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.

    Science.gov (United States)

    Fitzgerald, Kathleen A; Guo, Jianfeng; Raftery, Rosanne M; Castaño, Irene Mencía; Curtin, Caroline M; Gooding, Matt; Darcy, Raphael; O' Brien, Fergal J; O' Driscoll, Caitriona M

    2016-09-25

    siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was reduced by∼50% by day 7 in the co-culture system relative to monoculture (PC3 and LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone metastasis) was secreted into the media (1.2-4-fold increase depending on the co-culture system). A cationic cyclodextrin gene delivery vector proved significantly less toxic in the co-culture system relative to the commercially available vector Lipofectamine 2000(®). In addition, knockdown of both the GAPDH gene (minimum 15%) and RelA subunit of the NF-κB transcription factor (minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant vs the monoculture. This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-15

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

  1. Nitric oxide in cancer metastasis.

    Science.gov (United States)

    Cheng, Huiwen; Wang, Lei; Mollica, Molly; Re, Anthony T; Wu, Shiyong; Zuo, Li

    2014-10-10

    Cancer metastasis is the spread and growth of tumor cells from the original neoplasm to further organs. This review analyzes the role of nitric oxide (NO), a signaling molecule, in the regulation of cancer formation, progression, and metastasis. The action of NO on cancer relies on multiple factors including cell type, metastasis stage, and organs involved. Various chemotherapy drugs cause cells to release NO, which in turn induces cytotoxic death of breast, liver, and skin tumors. However, NO has also been clinically connected to a poor cancer prognosis because of its role in angiogenesis and intravasation. This supports the claim that NO can be characterized as both pro-metastatic and anti-metastatic, depending on specific factors. The inhibition of cell proliferation and anti-apoptosis pathways by NO donors has been proposed as a novel therapy to various cancers. Studies suggest that NO-releasing non-steroidal anti-inflammatory drugs act on cancer cells in several ways that may make them ideal for cancer therapy. This review summarizes the biological significance of NO in each step of cancer metastasis, its controversial effects for cancer progression, and its therapeutic potential. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    2014-08-01

    E-selectin ligands and prostate cancer bone metastasis (Barthel et al., 2007; Barthel et al., 2008; Dimitroff et al., 2005; Gout et al., 2008). In...induced by ESL-1 can serve as a principle for developing targeted therapy for those patients who have higher levels of ESL-1 in their CTCs...Vesuna, F., et al. (2013). The Twist Box Domain is Required for Twist1-induced Prostate Cancer Metastasis. Mol Cancer Res. Gout , S., Morin, C., Houle, F

  3. Protein kinase C-beta inhibitor enzastaurin (LY317615.HCI) enhances radiation control of murine breast cancer in an orthotopic model of bone metastasis.

    Science.gov (United States)

    Dudek, Arkadiusz Z; Zwolak, Pawel; Jasinski, Piotr; Terai, Kaoru; Gallus, Nathan J; Ericson, Marna E; Farassati, Faris

    2008-02-01

    Radiation therapy is a widely used treatment for metastatic bone cancer, but the rapid onset of tumor radioresistance is a major problem. We investigated the radiosensitizing effect of enzastaurin, a protein kinase Cbeta (PKCbeta) inhibitor, on bone tumor growth and tumor-related pain. We found that enzastaurin enhanced the effect of ionizing radiation on cultured murine 4T1 breast cancer and murine endothelial cells, suppressing their proliferation and colony formation. Enzastaurin and ionizing radiation also induced caspase-mediated apoptosis of 4T1 cells to a greater degree than radiation alone. Enzastaurin treatment of 4T1 cells blocked the phosphorylation of PKCbeta, as well as Ras and two of its downstream effectors ERK1/2 and RAL-GTP. Using an orthotopic model of bone metastasis, we observed that a combination of enzastaurin and localized radiation treatment reduced tumor blood vessel density, bone destruction and pain compared to single modality treatment. In conclusion, we demonstrate that inhibition of PKCbeta in combination with localized radiation treatment suppresses tumor growth and alleviates pain as compared to radiation-only treatment. We also show that the radiosensitizing effect of enzastaurin is associated with suppression of tumor cell proliferation and tumor-induced angiogenesis possibly through inhibition of the Ras pathway.

  4. 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.

  5. Pathobiology of cancer metastasis: a short account

    Directory of Open Access Journals (Sweden)

    Feller Liviu

    2012-06-01

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

  6. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

    Science.gov (United States)

    Gu, Z; Thomas, G; Yamashiro, J; Shintaku, I P; Dorey, F; Raitano, A; Witte, O N; Said, J W; Loda, M; Reiter, R E

    2000-03-02

    Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0. 021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.

  7. Thrombospondin-2 promotes prostate cancer bone metastasis by the up-regulation of matrix metalloproteinase-2 through down-regulating miR-376c expression

    Directory of Open Access Journals (Sweden)

    Po-Chun Chen

    2017-01-01

    Full Text Available Abstract Background Thrombospondin-2 (TSP-2 is a secreted matricellular glycoprotein that is found to mediate cell-to-extracellular matrix attachment and participates in many physiological and pathological processes. The expression profile of TSP-2 on tumors is controversial, and it up-regulates in some cancers, whereas it down-regulates in others, suggesting that the functional role of TSP-2 on tumors is still uncertain. Methods The expression of TSP-2 on prostate cancer progression was determined in the tissue array by the immunohistochemistry. The molecular mechanism of TSP-2 on prostate cancer (PCa metastasis was investigated through pharmaceutical inhibitors, siRNAs, and miRNAs analyses. The role of TSP-2 on PCa metastasis in vivo was verified through xenograft in vivo imaging system. Results Based on the gene expression omnibus database and immunohistochemistry, we found that TSP-2 increased with the progression of PCa, especially in metastatic PCa and is correlated with the matrix metalloproteinase-2 (MMP-2 expression. Additionally, through binding to CD36 and integrin ανβ3, TSP-2 increased cell migration and MMP-2 expression. With inhibition of p38, ERK, and JNK, the TSP-2-induced cell migration and MMP-2 expression were abolished, indicating that the TSP-2’s effect on PCa is MAPK dependent. Moreover, the microRNA-376c (miR-376c was significantly decreased by the TSP-2 treatment. Furthermore, the TSP-2-induced MMP-2 expression and the subsequent cell motility were suppressed upon miR-376c mimic stimulation. On the other hand, the animal studies revealed that the bone metastasis was abolished when TSP-2 was stably knocked down in PCa cells. Conclusions Taken together, our results indicate that TSP-2 enhances the migration of PCa cells by increasing MMP-2 expression through down-regulation of miR-376c expression. Therefore, TSP-2 may represent a promising new target for treating PCa.

  8. Does Cytoreductive Prostatectomy Really Have an Impact on Prognosis in Prostate Cancer Patients with Low-volume Bone Metastasis?

    DEFF Research Database (Denmark)

    Steuber, Thomas; Berg, Kasper D; Røder, Martin A

    2017-01-01

    The impact of cytoreductive radical prostatectomy (CRP) on oncological outcomes in patients with prostate cancer (PCa) and distant metastases has been demonstrated by retrospective data with their potential selection bias. Using prospective institutional data, we compared the outcomes between 43...... PCa patients with low-volume bone metastases (1-3 lesions) undergoing CRP (median follow-up 32.7 mo) and 40 patients receiving best systemic therapy (BST; median follow-up 82.2 mo). The inclusion criteria for both cohorts were identical. So far, no significant difference in castration resistant...... risks of CRP. However, patients benefit from a significant reduction in locoregional complications (7.0% vs 35%; pimpact of surgery in patients with prostate cancer and bone metastases. Using prospective data, we could not show...

  9. Mitochondrial dysfunction and cancer metastasis.

    Science.gov (United States)

    Chen, Emily I

    2012-12-01

    Mitochondria have an essential role in powering cells by generating ATP following the metabolism of pyruvate derived from glycolysis. They are also the major source of generating reactive oxygen species (ROS), which have regulatory roles in cell death and proliferation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial metabolism have been frequently described in human tumors. Although the role of oxidative stress as the consequence of mtDNA mutations and/or altered mitochondrial functions has been demonstrated in carciongenesis, a causative role of mitochondria in tumor progression has only been demonstrated recently. Specifically, the subject of this mini-review focuses on the role of mitochondria in promoting cancer metastasis. Cancer relapse and the subsequent spreading of cancer cells to distal sites are leading causes of morbidity and mortality in cancer patients. Despite its clinical importance, the underlying mechanisms of metastasis remain to be elucidated. Recently, it was demonstrated that mitochondrial oxidative stress could actively promote tumor progression and increase the metastatic potential of cancer cells. The purpose of this mini-review is to summarize current investigations of the roles of mitochondria in cancer metastasis. Future development of diagnostic and therapeutic strategies for patients with advanced cancer will benefit from the new knowledge of mitochondrial metabolism in epithelial cancer cells and the tumor stroma.

  10. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

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

  11. Increased expression of a set of genes enriched in oxygen binding function discloses a predisposition of breast cancer bone metastases to generate metastasis spread in multiple organs.

    Science.gov (United States)

    Capulli, Mattia; Angelucci, Adriano; Driouch, Keltouma; Garcia, Teresa; Clement-Lacroix, Philippe; Martella, Francesco; Ventura, Luca; Bologna, Mauro; Flamini, Stefano; Moreschini, Oreste; Lidereau, Rosette; Ricevuto, Enrico; Muraca, Maurizio; Teti, Anna; Rucci, Nadia

    2012-11-01

    Bone is the preferential site of distant metastasis in breast carcinoma (BrCa). Patients with metastasis restricted to bone (BO) usually show a longer overall survival compared to patients who rapidly develop multiple metastases also involving liver and lung. Hence, molecular predisposition to generate bone and visceral metastases (BV) represents a clear indication of poor clinical outcome. We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from BO and BV patients. The unsupervised hierarchical clustering of the resulting transcriptomes correlated with the clinical progression, segregating the BO from the BV profiles. Matching the twofold significantly regulated genes from Affymetrix and Agilent chips resulted in a 15-gene signature with 13 upregulated and two downregulated genes in BV versus BO bone metastasis samples. In order to validate the resulting signature, we isolated different MDA-MB-231 clonal subpopulations that metastasize only in the bone (MDA-BO) or in bone and visceral tissues (MDA-BV). Six of the signature genes were also significantly upregulated in MDA-BV compared to MDA-BO clones. A group of upregulated genes, including Hemoglobin B (HBB), were involved in oxygen metabolism, and in vitro functional analysis of HBB revealed that its expression in the MDA subpopulations was associated with a reduced production of hydrogen peroxide. Expression of HBB was detected in primary BrCa tissue but not in normal breast epithelial cells. Metastatic lymph nodes were frequently more positive for HBB compared to the corresponding primary tumors, whereas BO metastases had a lower expression than BV metastases, suggesting a positive correlation between HBB and ability of bone metastasis to rapidly spread to other organs. We propose that HBB, along with other genes involved in oxygen metabolism, confers a more aggressive metastatic phenotype in BrCa cells disseminated to bone. Copyright © 2012

  12. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels.

    Science.gov (United States)

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-03-01

    Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. Treatment-naïve patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of bone lesions (P < 0.001). During the follow-up period (median, 39.9 months; interquartile range, 21.5-65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS ≥ 1, and higher PSA nadir independently predicted CSS. PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values.

  13. Prostate cancer metastasis to the mandible: case report | Parkins ...

    African Journals Online (AJOL)

    Prostate cancer is recognised to be the commonest type of malignancy in the male in many parts of the world. Prostate cancer has a propensity to metastasize to bone, however metastasis to the jaw is uncommon and indeed among metastatic tumours of the jaws which are a rarity, only about 9% originate from a prostatic ...

  14. Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Young Mi Hong

    2016-06-01

    Full Text Available The bone is a common site for metastasis in hepatocellular carcinoma (HCC. However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin. Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

  15. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    achieve this goal, we cultured high-invasive prostate cancer PC3 cells and treated them with the drugs/inhibitors that were proposed to target WASF3...groups (treated by DMSO), either treated by 100 μM CYT997 or 10 μM Dasatinib suppressed the cells to spread throughout the fish body (Fig. 4). As...have scr eened t he e f fect s o f mor e t han 40 drugs on invasion using cul tur ed prost ate cancer cells and f ound t hat tar geting multiple

  16. Breast Cancer Metastasis to Pituitary Infandibulum

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    Maryam Poursadegh Fard

    2011-06-01

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

  17. Mechanisms involved in breast cancer liver metastasis.

    Science.gov (United States)

    Ma, Rui; Feng, Yili; Lin, Shuang; Chen, Jiang; Lin, Hui; Liang, Xiao; Zheng, Heming; Cai, Xiujun

    2015-02-15

    Liver metastasis is a frequent occurrence in patients with breast cancer; however, the available treatments are limited and ineffective. While liver-specific homing of breast cancer cells is an important feature of metastasis, the formation of liver metastases is not random. Indeed, breast cancer cell factors contribute to the liver microenvironment. Major breakthroughs have been achieved recently in understanding breast cancer liver metastasis (BCLM). The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver microenvironment. A further understanding of the roles of breast cancer cells and the liver microenvironment is crucial to guide future work in clinical treatments. In this review we discuss the contribution of breast cancer cells and the liver microenvironment to liver metastasis, with the aim to improve therapeutic efficacy for patients with BCLM.

  18. 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.

    Science.gov (United States)

    Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshakh; Madhavan, Devdas; Shinto, Ajit Sugunan

    2013-10-01

    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.

  19. 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

  20. 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.

    Science.gov (United States)

    Du, William Weidong; Fang, Ling; Yang, Weining; Sheng, Wang; Zhang, Yaou; Seth, Arun; Yang, Burton B; Yee, Albert J

    2012-08-03

    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. 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. 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. G3 expressing MC3T3-E1 cells showed inhibited cell

  1. 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

    Science.gov (United States)

    2012-01-01

    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. G3 expressing MC3T3-E1

  2. Despite the lack of association between different genotypes and the presence of prostate cancer, endothelial nitric oxide synthase a/b (eNOS4a/b) polymorphism may be associated with advanced clinical stage and bone metastasis.

    Science.gov (United States)

    Sanli, Oner; Kucukgergin, Canan; Gokpinar, Murat; Tefik, Tzevat; Nane, Ismet; Seckin, Sule

    2011-01-01

    To investigate the relationship between the distribution of endothelial NO synthase (eNOS4a/b) gene polymorphism and clinical features of prostate cancer (PCa). One hundred thirty-two patients with PCa (mean age 64.10 ± 7.23 years) and 158 healthy controls (mean age 62.50 ± 7.53 years) with normal serum total prostate specific antigen (PSA) levels (bone metastasis (Group 2), and patients with bone metastasis (Group 3). Genotypes (aa, bb, ab) for eNOS4a/b gene polymorphisms were identified by polymerase chain reaction analysis. Meanwhile, plasma nitrate and nitrite levels (NO(x)) were used to estimate the amounts of endogenous NO formation for both groups of patients. Despite lack of statistically significant differences between PCa patients and the control group in terms of distribution of genotypes and frequency of alleles, plasma NO(x) levels were found to be significantly increased in PCa patients compared with controls. Meanwhile, there was no significant difference between the group of PCa patients with high and low grade tumors (Gleason score ≥ 7 vs. bone metastasis in comparison with bb genotype. Moreover, multivariable logistic regression analysis revealed that eNOS4a/b polymorphism and plasma NOx levels were predictive factors for developing bone metastasis and high stage disease after adjustment for age and BMI. Our data did not reveal any relationship between any of these genotypes and the presence of PCa. However, the finding that PCa patients with bb genotype generally manifest localized disease and develop bone metastasis less frequently in comparison patients with a-allele may indicate an important role for this polymorphism in the molecular pathophysiology of PCa. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. RANKL: A promising circulating marker for bone metastasis response

    Science.gov (United States)

    Ibrahim, Toni; Ricci, Marianna; Scarpi, Emanuela; Bongiovanni, Alberto; Ricci, Rossana; Riva, Nada; Liverani, Chiara; De Vita, Alessandro; La Manna, Federico; Oboldi, Devil; Serra, Patrizia; Foca, Flavia; Cecconetto, Lorenzo; Amadori, Dino; Mercatali, Laura

    2016-01-01

    Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54–0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still

  4. 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

  5. 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.

  6. Brain metastasis from ovarian cancer: a systematic review.

    Science.gov (United States)

    Pakneshan, Shabnam; Safarpour, Damoun; Tavassoli, Fattaneh; Jabbari, Bahman

    2014-08-01

    To review the existing literature on brain metastasis (BM) from ovarian cancer and to assess the frequency, anatomical, clinical and paraclinical information and factors associated with prognosis. Ovarian cancer is a rare cause of brain metastasis with a recently reported increasing prevalence. Progressive neurologic disability and poor prognosis is common. A comprehensive review on this subject has not been published previously. This systematic literature search used the Pubmed and Yale library. A total of 66 publications were found, 57 of which were used representing 591 patients with BM from ovarian cancer. The median age of the patients was 54.3 years (range 20-81). A majority of patients (57.3 %) had multiple brain lesions. The location of the lesion was cerebellar (30 %), frontal (20 %), parietal (18 %) and occipital (11 %). Extracranial metastasis was present in 49.8 % of cases involving liver (20.7 %), lung (20.4 %), lymph nodes (12.6 %), bones (6.6 %) and pelvic organs (4.3 %). The most common symptoms were weakness (16 %), seizures (11 %), altered mentality (11 %) visual disturbances (9 %) and dizziness (8 %). The interval from diagnosis of breast cancer to BM ranged from 0 to 133 months (median 24 months) and median survival was 8.2 months. Local radiation, surgical resection, stereotactic radiosurgery and medical therapy were used. Factors that significantly increased the survival were younger age at the time of ovarian cancer diagnosis and brain metastasis diagnosis, lower grade of the primary tumor, higher KPS score and multimodality treatment for the brain metastases. Ovarian cancer is a rare cause of brain metastasis. Development of brain metastasis among older patients and lower KPS score correlate with less favorable prognosis. The more prolonged survival after using multimodality treatment for brain metastasis is important due to potential impact on management of brain metastasis in future.

  7. Efficacy of combined androgen blockade with zoledronic acid treatment in prostate cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade trial on prostate cancer) study.

    Science.gov (United States)

    Ueno, Satoru; Mizokami, Atsushi; Fukagai, Takashi; Fujimoto, Naohiro; Oh-Oka, Hitoshi; Kondo, Yukihiro; Arai, Gaku; Ide, Hisamitsu; Horie, Shigeo; Ueki, Osamu; Kawaguchi, Kouhei; Shimamura, Masayoshi; Orito, Matsuo; Ishida, Takeyuki; Ikeda, Daisuke; Namiki, Mikio

    2013-09-01

    Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in castration-resistant prostate cancer (CRPC) with bone metastasis and improves quality of life. It remains unclear when clinicians should initiate ZA treatment. Hormone-naïve patients were randomized to a combined androgen blockade (CAB) group or CAB with ZA group (CAB-ZA) based on Gleason score (GS) or extent of disease. The primary end-point of the study was progression-free survival (PFS) and the secondary end-point was incidence of SREs and bone pain. Thirty-one and 29 patients among 60 enrolled patients were assigned to the CAB group and the CAB-ZA group, respectively. There was no significant difference in PFS between the two groups. Subgroup analyses revealed better PFS in the CAB-ZA group with GS ≥8 (p=0.021). Moreover, incidence of SREs, including bone pain, was lower in the CAB-ZA group (p=0.019). CAB-ZA treatment was found to improve PFS for patients with prostate cancer with high GS. CAB-ZA treatment could be recommended for treatment of patients with prostate cancer.

  8. Lymph Node Metastasis of Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Seigo Kitano

    2011-04-01

    Full Text Available 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. Metastasis: an early event in cancer progression.

    Science.gov (United States)

    Hu, Yijun; Yu, Xiya; Xu, Guixia; Liu, Shanrong

    2017-05-01

    Metastasis is the leading cause of death for a majority of cancer patients, and thus the need to understand the biology of metastasis becomes increasingly acute. When metastasis is initiated in tumor progression remains obscure. Better understanding of mechanisms regulating acquisition of metastatic ability in tumor cells will provide novel therapeutic targets and prevention of metastasis in clinics accompanied with the treatment of the primary tumor might be helpful in reducing metastasis-related mortality. A literature search was performed in multiple electronic databases. Research papers from clinical reports to experimental studies on metastasis were analyzed. The article discusses tumor heterogeneity and genomic instability in the context of metastasis and tumor cell dissemination. And then we review biological mechanism of metastasis at an early stage in both intracellular (CSCs and CTCs) and extracellular (microenvironment) context. Finally, current development of anti-metastatic therapies is summarized. Metastasis could be initiated at an early point of tumor progression. Therefore, early intervention on metastasis should be applied among cancer patients in clinical settings.

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

    Science.gov (United States)

    2013-07-30

    TNF-α), endothelin-1 (ET-1) and parathyroid hormone-related peptide (PTHrP), that are abundant in the metastatic bone tumor microenvironment...related pain behaviors in the scid mouse xenografts on the 7th week post cell injection, we euthanized these animals and performed ex vivo analysis of...whole animal perfusion with fixative, and subsequently removed the femur and tibia-fibula for tissue sectioning and H&E, as well as immunostainging

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

    Directory of Open Access Journals (Sweden)

    Shahrbanoo Keihanian

    2013-06-01

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

  12. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

    Directory of Open Access Journals (Sweden)

    Mary C. Farach-Carson

    2017-08-01

    Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

  13. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

    Science.gov (United States)

    Farach-Carson, Mary C; Lin, Sue-Hwa; Nalty, Theresa; Satcher, Robert L

    2017-01-01

    Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER) signaling pathways indicate a role for ER beta (ERβ). Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a "feminization" of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males may feminize the bone

  14. A case of rectal cancer with sternal metastasis as initial presentation.

    OpenAIRE

    Choi, J. H.; Kim, S. J.; Oh, J. Y.; Ryu, S. R.; Shim, K. S.; Kim, K. H.; Baek, S. Y.; Choi, H. Y.; Lee, S. W.; Kim, M. J.

    1995-01-01

    Colorectal cancer with bone metastasis as initial manifestation is a very rare event. We have reported a case of rectal cancer presenting with sternal metastasis. A 30 year-old man was evaluated due to pain in the sternal area with a bulging mass. History and physical examination did not suggest any specific disease. A radionuclide bone scan revealed increased uptake in the sternal area, right 6th rib, and sacrum. Microscopic examination of a biopsy specimen from the sternum showed metastatic...

  15. 68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml

    DEFF Research Database (Denmark)

    Petersen, Lars J; Nielsen, Julie B; Dettmann, Katja

    2017-01-01

    /computed tomography ((68)Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on (68)Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (...Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography...... with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics....

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

    Directory of Open Access Journals (Sweden)

    Sandra Casimiro

    2016-08-01

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

  17. Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.

    Science.gov (United States)

    Purushotham, A; Shamil, E; Cariati, M; Agbaje, O; Muhidin, A; Gillett, C; Mera, A; Sivanadiyan, K; Harries, M; Sullivan, R; Pinder, S E; Garmo, H; Holmberg, L

    2014-07-01

    Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood. Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006. Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis. These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Mucinous Breast Cancer with Solitary Metastasis to Humeral Head: A Case Report

    Directory of Open Access Journals (Sweden)

    Adil Aljarrah

    2013-09-01

    Full Text Available Breast cancer is the most common cause of metastatic deposits in the skeleton, and bone is the most common site of recurrence of breast cancer. Breast cancer metastasis most commonly affects the spine, ribs, pelvis, and proximal long bones; however, only 3.5% of breast cancer patients develop long-bone metastases. The humerus is the most common upper-extremity site for bony metastasis, and pathologic fractures can result. The patient in the current study presented with breast cancer and discovered to have humeral head metastasis during initial workup. The dilemma was in investigation the modality to confirm humeral head metastasis as there are many differential diagnoses with similar findings. After staging workup, the patient was treated with neoadjuvant chemotherapy followed by modified radical mastectomy and radiotherapy of the chest wall and the shoulder. The lesion in humerus was well healed.

  19. Hyoid bone chondrosarcoma with cervical nodal metastasis:

    Directory of Open Access Journals (Sweden)

    Hisham Mostafa Abdel-Fattah

    2016-09-01

    Conclusions: Although the tumor was low grade, it showed cervical lymph node metastasis months after its surgical excision. This shows the importance of scheduled CT scan of the neck during follow-up of these cases.

  20. 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

  1. Risk factors and characteristics of prostate cancer bone metastases

    Directory of Open Access Journals (Sweden)

    Jun-ming LIN

    2017-10-01

    Full Text Available Objective To analyze the risk factors and characteristics of bone metastases in patients with prostate cancer. Methods Patients who were diagnosed as prostate cancer by biopsy and histopathologic analysis between June 2006 and June 2016 were included in this study. The clinical data of the patients were reviewed, and the demographic data, laboratory examination results and Gleason score were recorded. The correlations between clinical factors and bone metastasis were analyzed, and the risk factors of bone metastasis were identified. Results A total of 585 patients were recruited in this study, including 228 with bone metastasis and 357 without bone metastasis. Of the patients with bone metastasis, the incidence of pelvic metastasis was the highest, accounting for 81.58%, followed by spin (63.16% and rib (58.33%, and the incidence of clavicle metastasis was the lowest (14.47%. Logistic regression analysis showed that age 85.5U/L, prostate-specific antigen >79.88μg/L and Gleason score >7.5 were the risk factors of bone metastasis in prostate cancer. ROC curve analysis showed that the sensitivity of diagnosing bone metastasis was 56.1%, 66.7%, 68.4% and 56.1%, and the specificity was 56.6%, 81.8%, 70.0% and 65.3%, respectively for above 4 factors. Conclusions The most common site of bone metastasis in patients with prostate cancer is pelvis. Patients' age, concentrations of plasma ALP and PSA, and Gleason score are the risk factors for bone metastasis in patients with prostate cancer. DOI: 10.11855/j.issn.0577-7402.2017.08.09

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

    Science.gov (United States)

    2015-11-01

    amplification) breast cancer (TNBC) is an aggressively metastatic subtype that preferentially metastasizes to visceral organs including the lungs...Determination of the transcriptome of breast cancer cells that selectively home to the lungs and bones. P.2 lung metastases and corresponding mammary...Troester MA, Herschkowitz JI, Oh DS, He X, Hoadley KA, Barbier CS, Perou CM. Gene expression patterns associated with p53 status in breast cancer . BMC

  3. The protein C pathway in cancer metastasis

    NARCIS (Netherlands)

    Spek, C. Arnold; Arruda, Valder R.

    2012-01-01

    Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that

  4. A CASE REPORT OF PANCREATIC METASTASIS FROM PROSTATE CANCER.

    Science.gov (United States)

    Hakamata, Yasuhiro; Kanda, Yuka; Sugiura, Kota; Imai, Shin; Yoneda, Tatsuaki

    2016-01-01

    We report a case of pancreatic metastasis from prostate cancer. A 65 year-old man developed gross hematuria, and was found to have a markedly elevated PSA and abnormal CT findings indicating mass lesions in bilateral lungs, and pancreatic head, and osteoblastic lesions in pelvic bone. He was referred to the department of Urology and Gastroenterology at Seirei Hamamatsu General Hospital. Digital rectal examination revealed a hen's egg-sized, stony-hard prostate. A systematic needle biopsy of the prostate demonstrated adenocarcinoma (Gleason score 4+4=8). We diagnosed multiple lung and bone metastases from prostate cancer, and suspected that a primary pancreatic ductal carcinoma. The patient was started on an androgen deprivation therapy (ADT) with bicalutamide and degarelix. After 4 months from the initiation of ADT, an MRI of the pancreas showed decreased size of the pancreatic head mass from 18 mm to 7 mm in diameter. We concluded that the pancreatic head mass was metastasis from prostate cancer, and currently continue ADT. Pancreatic metastasis from prostate cancer is very rare, and further accumulation of cases will be required.

  5. Bone marrow macrophages support prostate cancer growth in bone.

    Science.gov (United States)

    Soki, Fabiana N; Cho, Sun Wook; Kim, Yeo Won; Jones, Jacqueline D; Park, Serk In; Koh, Amy J; Entezami, Payam; Daignault-Newton, Stephanie; Pienta, Kenneth J; Roca, Hernan; McCauley, Laurie K

    2015-11-03

    Resident macrophages in bone play important roles in bone remodeling, repair, and hematopoietic stem cell maintenance, yet their role in skeletal metastasis remains under investigated. The purpose of this study was to determine the role of macrophages in prostate cancer skeletal metastasis, using two in vivo mouse models of conditional macrophage depletion. RM-1 syngeneic tumor growth was analyzed in an inducible macrophage (CSF-1 receptor positive cells) ablation model (MAFIA mice). There was a significant reduction in tumor growth in the tibiae of macrophage-ablated mice, compared with control non-ablated mice. Similar results were observed when macrophage ablation was performed using liposome-encapsulated clodronate and human PC-3 prostate cancer cells where tumor-bearing long bones had increased numbers of tumor associated-macrophages. Although tumors were consistently smaller in macrophage-depleted mice, paradoxical results of macrophage depletion on bone were observed. Histomorphometric and micro-CT analyses demonstrated that clodronate-treated mice had increased bone volume, while MAFIA mice had reduced bone volume. These results suggest that the effect of macrophage depletion on tumor growth was independent of its effect on bone responses and that macrophages in bone may be more important to tumor growth than the bone itself. In conclusion, resident macrophages play a pivotal role in prostate cancer growth in bone.

  6. 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...

  7. An integrated analysis identifies STAT4 as a key regulator of ovarian cancer metastasis.

    Science.gov (United States)

    Zhao, L; Ji, G; Le, X; Luo, Z; Wang, C; Feng, M; Xu, L; Zhang, Y; Lau, W B; Lau, B; Yang, Y; Lei, L; Yang, H; Xuan, Y; Chen, Y; Deng, X; Yi, T; Yao, S; Zhao, X; Wei, Y; Zhou, S

    2017-06-15

    Epithelial ovarian cancer (EOC) is one of the most common gynecological cancers, with diagnosis often at a late stage. Metastasis is a major cause of death in patients with EOC, but the underlying molecular mechanisms remain obscure. Here, we utilized an integrated approach to find potential key transcription factors involved in ovarian cancer metastasis and identified STAT4 as a critical player in ovarian cancer metastasis. We found that activated STAT4 was overexpressed in epithelial cells of ovarian cancer and STAT4 overexpression was associated with poor outcome of ovarian cancer patients, which promoted metastasis of ovarian cancer in both in vivo and in vitro. Although STAT4 mediated EOC metastasis via inducing epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells in vivo, STAT4 failed to induce EMT directly in vitro, suggesting that STAT4 might mediate EMT process via cancer-stroma interactions. Further functional analysis revealed that STAT4 overexpression induced normal omental fibroblasts and adipose- and bone marrow-derived mesenchymal stem cells to obtain cancer-associated fibroblasts (CAF)-like features via induction of tumor-derived Wnt7a. Reciprocally, increased production of CAF-induced CXCL12, IL6 and VEGFA within tumor microenvironment could enable peritoneal metastasis of ovarian cancer via induction of EMT program. In summary, our study established a model that STAT4 promotes ovarian cancer metastasis via tumor-derived Wnt7a-induced activation of CAFs.

  8. On the Origin of Cancer Metastasis

    OpenAIRE

    Seyfried, Thomas N.; Huysentruyt, Leanne C.

    2013-01-01

    Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality. In order to complete the metastatic cascade, cancer cells must detach from the primary tumor, intravasate into the circulatory and lymphatic systems, evade immune attack, extravasate at distant capillary beds, and invade and proliferate in distant organs. Currently, several hypotheses have been advanced to explain the or...

  9. Radiological diagnosis of bone metastasis of hepatoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Hajime; Kaneko, Kuniyuki; Nakayama, Chikashi; Kimoto, Tatsuya; Nakayama, Takashi (Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine)

    1984-08-01

    Six cases of bone metastases were detected among 80 hepatomas diagnosed during the period from December 1980 to February 1983. Four of them presented with the bone metastases as their initial symptoms. The majority of the metastases were found in the thorax, spine and sacrum. Bone scintigraphy and X-ray examination were the most effective means for diagnosis while /sup 67/Ga scintigraphy and CT were complementary in some cases. Since bone metastases is not rare in hepatoma, its evaluation is essential for the proper management of the patient.

  10. Maxillofacial metastasis from breast cancer.

    Science.gov (United States)

    Namad, Tariq; Benbrahim, Zineb; Najib, Rajae; Mohammed, Afif; Baggar, Soufiane; Bouyahia, Nezar; Arifi, Samia; Mellas, Nawfel

    2014-01-01

    Metastatic tumors to paranasal sinuses are exclusively rare. In this paper, we report a case of breast carcinoma metastasizing to the right maxilla. The metastasis occurred 5 years after radical mastectomy and presented as a primary sinonasal mass. The diagnosis was confirmed with histopathologic and immunohistochemical examination however the patient died before starting any specific treatment because of tumor bleeding.

  11. Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

    Science.gov (United States)

    Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-06-01

    Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2009-06-01

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

  13. Thyroid gland metastasis of rectal cancer.

    Science.gov (United States)

    Ozawa, Tsuyoshi; Saito, Shinsuke; Matsuura, Sohei; Kishi, Hirohisa; Maeda, Mamoru; Watanabe, Toshiaki

    2015-05-07

    A 72-year-old woman with a history of rectal cancer was admitted to our hospital to undergo thyroidectomy and left adrenalectomy. She had undergone low anterior resection and regional lymph node dissection for rectal cancer 52 months pre-admission (T3 N1 M0, stage IIIb according to International Union Against Cancer tumor-node-metastasis), and she had also undergone metastasectomy for lung metastases and right adrenal gland metastasis after the rectal surgery. Follow-up computed tomography scans detected nodules in the bilateral lobes of the thyroid gland and in the left adrenal gland. Subtotal thyroidectomy and left adrenalectomy were performed, and pathological examination revealed metastases of rectal cancer to the thyroid gland and left adrenal gland. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2015.

  14. 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.

  15. Metastasis of Colon Cancer to the Breast

    Directory of Open Access Journals (Sweden)

    Swei H. Tsung

    2017-01-01

    Full Text Available Breast metastases from extramammary neoplasms are extremely rare, and even more so is metastasis of colon cancer to the breast. Despite its rarity, metastatic disease to the breast is an important diagnostic issue because its treatment differs greatly from that of primary cancer. Proper diagnosis of this rare event requires an accurate clinical history, proper immunohistochemical workup, and a high level of suspicion.

  16. Gastric Metastasis of Ectopic Breast Cancer Mimicking Axillary Metastasis of Primary Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Selami Ilgaz Kayılıoğlu

    2014-01-01

    Full Text Available Ectopic breast tissue has the ability to undergo all the pathological changes of the normal breast, including breast cancer. Gastrointestinal metastasis of breast cancer is rarely observed and it is very difficult to differentiate gastric metastases from primary gastric cancer. We present a case of 52-year-old female, who suffered from abdominal pain. Physical examination showed a palpable mass in the left anterior axilla and computerized tomography revealed gastric wall thickening with linitis plastica. When gastroscopic biopsy showed no signs of malignancy, excisional biopsy was performed in the left axilla. Histological examination revealed invasive lobular carcinoma of the breast, consistent with ectopic breast cancer. Further gastroscopic submucosal biopsies and immunohistochemical studies revealed gastric metastases of invasive lobular carcinoma. Axillary ectopic breast tissue carcinomas can mimic axillary lymphadenopathies. Additionally, gastric metastasis of breast cancer is an uncommon but possible condition. To the best of our knowledge, this is the first report of ectopic breast cancer with gastric metastasis.

  17. Spinal Intramedullary Metastasis of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Recep Basaran

    2014-01-01

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

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

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    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.

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

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    Alison Gartland

    2016-09-01

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

  20. Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients

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    Wouter Huysse

    2017-10-01

    Full Text Available We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT and axial skeleton magnetic resonance imaging (MRI prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3–4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

  1. Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients.

    Science.gov (United States)

    Huysse, Wouter; Lecouvet, Frédéric; Castellucci, Paolo; Ost, Piet; Lambrecht, Valerie; Artigas, Carlos; Denis, Marie-Laurence; Man, Kathia De; Delrue, Louke; Jans, Lennart; Bruycker, Aurélie De; Vos, Filip De; Meerleer, Gert De; Decaestecker, Karel; Fonteyne, Valerie; Lambert, Bieke

    2017-10-17

    We compared fluor-18 choline positron emission tomography/computed tomography (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively obtained for the detection of bone metastases in non-castrated patients with biochemically recurrent prostate cancer following primary treatment. PET/CT was performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were initially blinded from other results and all scans underwent independent double reading. The best valuable comparator (BVC) defined the metastatic status. On the basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a patient level, the sensitivity and specificity of MRI and PET were not significantly different. On a lesion level, the sensitivity of MRI was significantly better compared to PET, and the specificity did not differ significantly. In conclusion, axial MRI is an interesting screening tool for the detection of bone metastases because of its low probability of false negative results. However, F-18 choline PET is a valuable addition as it can overrule false positive MRI results and detect non-axial metastases.

  2. Physiopathology of Spine Metastasis

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    Giulio Maccauro

    2011-01-01

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

  3. Cancer Cell Colonisation in the Bone Microenvironment

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    Casina Kan

    2016-10-01

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

  4. Management of long bone metastases: recommendations from the Italian Orthopaedic Society bone metastasis study group.

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    Capanna, Rodolfo; Piccioli, Andrea; Di Martino, Alberto; Daolio, Primo Andrea; Ippolito, Vincenzo; Maccauro, Giulio; Piana, Raimondo; Ruggieri, Pietro; Gasbarrini, Alessandro; Spinelli, Maria Silvia; Campanacci, Domenico Andrea

    2014-10-01

    The purpose of this article is to outline the current approach to patients affected by metastasis to the long bones and to present a clinical and surgical algorithm available for clinicians and for future research. A modern approach to patients affected by long bone metastasis in fact requires a multidisciplinary contest where oncologists, radiotherapists, surgeons and physical therapists cooperate with a shared vision, in order to provide the best possible integrated treatments available. The authors of this article constitute the Bone Metastasis Study Group of the Italian Orthopaedic Society (SIOT): a national group of orthopedic tumor surgeons who are dedicated to studying the approach, techniques and outcomes of surgery for metastatic tumours of the musculoskeletal system.

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

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

    2017-01-01

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

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

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    Jonathan Gill

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

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

    Science.gov (United States)

    Zhao, Min; Li, Zhe; Qu, Hong

    2015-10-21

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

  8. Site of metastasis and breast cancer mortality: a Danish nationwide registry-based cohort study.

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    Ording, Anne Gulbech; Heide-Jørgensen, Uffe; Christiansen, Christian Fynbo; Nørgaard, Mette; Acquavella, John; Sørensen, Henrik Toft

    2017-01-01

    Survival among patients with metastatic breast cancer may vary according to the site of metastasis and receptor status. We used Danish nationwide medical registries to establish a cohort of patients with metastatic breast cancer (870 with de novo metastatic disease and 3518 with recurrent disease with distant metastasis) diagnosed during 1997-2011. We examined 1-year and >1 to 5-year mortality associated with first site of metastasis and receptor expression status of the primary tumor. Cox proportional regression was used to compute confounder-adjusted mortality rate ratios (MRRs) associated with site of metastasis, stratified by receptor status. Overall 1-year and >1 to 5-year mortality risks were 36 and 69 %, respectively. Risk of death within 1 year was highest for brain-only (62 %) and liver-only (43 %) involvement and nearly the same for patients with lung-only (32 %), bone-only (32 %) involvement, and other/combination of sites (34 %). Using bone-only metastasis as reference, women with brain-only metastasis had more than two-fold increased risk of dying. The adjusted MRR for women with liver-only metastasis also was increased, though less pronounced. Patients with lung-only [adjusted MRR 0.9 (95 % confidence interval (CI) 0.8, 1.1)] or other metastases [adjusted MRR 1.0 (95 % CI 0.9, 1.2)] had similar mortality as patients with bone-only metastasis. Positive hormonal receptor status was a favorable prognostic factor. Metastatic breast cancer has a serious prognosis. Patients with brain-only metastasis had the highest mortality. Positive hormonal receptor status on the primary tumor was a favorable prognostic factor for all metastatic sites.

  9. Tumor Microenvironment Regulates Metastasis and Metastasis Genes of Mouse MMTV-PymT Mammary Cancer Cells In Vivo

    Science.gov (United States)

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

    2014-01-01

    Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment. PMID:24091811

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

    Science.gov (United States)

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

    2014-07-01

    Metastasis is the primary cause of death in breast cancer patients, yet there are challenges to modeling this process in vivo. The goal of this study was to analyze the effects of injection site on tumor growth and metastasis and gene expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat pad, tail vein, intracardiac, and intratibial), and tumors and metastases were monitored using bioluminescent imaging and confirmed with gross necropsy and histopathology. Met-1 tumors were analyzed based on morphology and changes in gene expression in each tissue microenvironment. There were 6 permissible sites of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary, bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors (highest Ki-67 index). Morphologic differences were evident in each tumor microenvironment. Finally, 7 genes were differentially expressed in the Met-1 tumors in the 6 sites of growth or metastasis. This investigation demonstrates that breast cancer progression and metastasis are regulated by not only the tumor cells but also the experimental model and unique molecular signals from the tumor microenvironment. © The Author(s) 2013.

  11. Predictors of Time to Metastasis in Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Moreira, Daniel M; Howard, Lauren E; Sourbeer, Katharine N; Amarasekara, Hiruni S; Chow, Lydia C; Cockrell, Dillon C; Hanyok, Brian T; Aronson, William J; Kane, Christopher J; Terris, Martha K; Amling, Christopher L; Cooperberg, Matthew R; Liede, Alex; Freedland, Stephen J

    2016-10-01

    To investigate predictors of time to metastasis among men treated with androgen deprivation therapy for nonmetastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital cohort. This is a retrospective analysis of 458 nonmetastatic 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 zero. A total of 256 (56%) men were diagnosed with metastatic disease over a median follow-up of 36 months. Metastasis-free survival was 79%, 65%, 52%, 47%, and 41% at 1, 2, 3, 4, and 5 years after CRPC, respectively. In multivariable analysis, Gleason score 8-10 (hazard ratio [HR] = 1.61; P = .026), receiving primary localized treatment (HR = 1.38; P = .028), higher prostate-specific antigen (PSA) levels at CRPC diagnosis (logPSA HR = 1.64; P metastasis. Race, year of CRPC, age, and time from androgen deprivation therapy to CRPC were not associated with metastasis. Among nonmetastatic CRPC men, nearly 60% developed metastatic disease during the first 5 years, with most of the metastasis occurring within the first 3 years. Higher Gleason score, receiving primary treatment, higher PSA, and shorter PSA doubling time were independently associated with shorter time to metastasis. Therefore, these variables can be used to stratify patients according to metastasis risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Cranium metastasis of a squamous cell carcinoma with extensive bone destruction

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    Cahit Kural

    2011-12-01

    Full Text Available The musculoskeletal metastasis of the lung cancers is rare and locates usually at the spine, pelvis and femur. The cranial metastasis of lung cancer is very rare and generally in small size. Large bone destruction is not reported yet. Fifty six years old male patient was admitted to our hospital with the complaints of cough and respiratory difficulty. The needle biopsy of the lung revealed the diagnosis of squamous cell lung carcinoma (Grade 4 and the patient underwent palliative radiotherapy. The patient was admitted to our hospital 6 month later with rapidly growing mass lesion on the forehead. The radiological examination showed an extraaxial mass lesion 10x9x8 cm in size, which compressed on the brain tissue and caused large destruction in the frontal bone. The mass lesion was removed surgically, the brain tissue was decompressed and the bone defect was repaired with synthetic material. Although similar cases were reported previously, a lung carcinoma, which caused bone defect in this size, was not reported. For such metastases, removal of the mass lesion and cranioplasty are suggested.

  13. Animal models of colorectal cancer with liver metastasis.

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    Oh, Bo Young; Hong, Hye Kyung; Lee, Woo Yong; Cho, Yong Beom

    2017-02-28

    Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Burned-out seminoma revealed by solitary rib bone metastasis

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    Nishisho, Toshihiko; Miyagi, Ryo; Sairyo, Koichi [Tokushima University Graduate School, Department of Orthopedics, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan); Sakaki, Mika [Saitama Medical University International Medical Center, Department of Pathology, Hidaka-city, Saitama (Japan); Takao, Shoichiro [Tokushima University Graduate School, Department of Radiology, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan)

    2017-10-15

    Burned-out tumor is a rare phenomenon in which a testicular tumor regresses in the primary lesion and progresses in a metastatic lesion. We report the case of a 30-year-old male with burned-out seminoma revealed by open biopsy of solitary 10th rib bone metastasis. He underwent inguinal orchiectomy, which revealed hyalinization, indicating a spontaneously regressed testicular tumor. Chemotherapy for seminoma was administered in three cycles of bleomycin + etoposide + cisplatin therapy. The chemotherapy was effective, and wide resection of the rib was subsequently performed. No postoperative chemotherapy was performed, and there has been no evidence of recurrence for 3 years postoperatively. (orig.)

  15. Solitary Spinal Epidural Metastasis from Gastric Cancer

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    Taisei Sako

    2016-01-01

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

  16. Optimal surveillance for postoperative metastasis in breast cancer patients.

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    Makita, Masujiro; Sakai, Takehiko; Ogiya, Akiko; Kitagawa, Dai; Morizono, Hidetomo; Miyagi, Yumi; Iijima, Kotaro; Iwase, Takuji

    2016-03-01

    To establish an optimal surveillance schedule after surgery for breast cancer, patients included in an institutional database were retrospectively investigated with respect to the first metastatic site and timing of recurrence. We investigated 11,676 pT1-4pN0-2M0 breast cancer patients treated from 1985 to 2009 and followed up until June 2014. Our surveillance protocol included physician visits and examinations with bone scans, liver echography, chest roentgenography and laboratory tests. We evaluated the liver, bones, lungs and pleura as surveillance covering sites (SCS) in addition to parameters such as time points exceeding 80 % with respect to the accumulated percentage of patients of recurrence and the number of surveillance per one recurrence (NSR), calculated by dividing the number of patients at risk of recurrence at the start of a particular time frame by the number of patients of recurrence at SCS within that period. There were a total of 1,962 recurrent patients, including 601 patients with locoregional recurrence, nine patients with recurrence in the opposite breast, 1,349 patients with recurrence at distant sites and three unknown patients. The number of patients with the bones, lungs, liver and pleura as the first site of recurrence was 447, 324, 144 and 69, respectively, and 72.9 % of the distant metastatic lesions belonged to SCS. The five-year overall survival rate after recurrence among the patients with single recurrent site was longer than that observed among the patients with multiple sites of recurrence (43.3 vs 25.3 %; p metastasis were detected within 5 years after surgery, while 80 % of the patients of pleura metastasis were detected within 10 years. The NSR was below 200 for the 10-year period, as was the NSR of the patients with lymph node metastasis and a positive hormone receptor status. In contrast, the NSR of the patients with a negative hormone receptor status was above 200 after 5 years. In this study, the prognosis of the patients

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

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

    2016-01-01

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

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

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    Mohammad Taher Rajabi

    2014-01-01

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

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

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    Lin Xie

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

  20. Bone Cancer - Multiple Languages

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    ... 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 Expand Section ...

  1. Synchronous disruption of anisotropic arrangement of the osteocyte network and collagen/apatite in melanoma bone metastasis.

    Science.gov (United States)

    Sekita, Aiko; Matsugaki, Aira; Ishimoto, Takuya; Nakano, Takayoshi

    2017-03-01

    Cancer metastasis to bones increases the risk of fragility fracture by altering bone metabolism and disrupting bone structure. Osteocytes, which organize a dense network that is closely linked with the circumambient matrix, play a key role in regulation of bone microstructure and material properties. The aim of this study was to elucidate the influence of cancer metastasis on the organization of the osteocyte network and collagen/biological apatite (BAp) microstructure in the context of osteocyte/matrix coupling. Using a mouse model intracardially injected with B16F10 melanoma cells or vehicle, the geometric and metabolic changes to osteocytes were analyzed by nano-computed tomography (nano-CT) and histology, and the alignment of collagen fibrils and BAp was analyzed by birefringence measurement and microbeam-X-ray diffraction, respectively. The material properties of bones were further analyzed with nanoindentation method. These experiments revealed that the osteocyte network was markedly disorganized in cancer-bearing bone tissues. The osteocytes showed a variety of residing states in the lacunae; some lacunae were osteolytic while some were replete with immature matrix, suggesting significant disruption in osteocyte/matrix coupling. Collagen/BAp microstructure was also disorganized in cancer-bearing bones as observed by significant decreases in the preferential alignment of both collagen fibrils and BAp; the latter was further shown to be significantly correlated with Young's modulus. The present study revealed that the disruption in the arrangement of the osteocyte network and collagen/BAp microstructure and the deterioration of mechanical function occurred synchronously during cancer bone metastasis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. FEATURES OF BILATERAL BREAST CANCER NODAL METASTASIS

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    Ye. A. Fesik

    2014-01-01

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

  3. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

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    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.

  4. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  5. Bone Marrow Microenvironmental Control of Prostate Cancer Skeletal Localization

    Science.gov (United States)

    2011-05-01

    implicate PTHrP derived from prostate cancer in the pathogenesis of prostate cancer metastasis to bone. This aspect of the project is complete...presented initial findings as an invited speaker at the Cancer Induced Bone Disease meeting in Chicago (abstract appended). There was a statistically...Affiliations: 1 Department of Periodontics and Oral Medicine, the University of Michigan School of Dentistry, Ann Arbor, MI; 2 Departments of

  6. A zebrafish xenograft model for studying human cancer stem cells in distant metastasis and therapy response.

    Science.gov (United States)

    Chen, L; Groenewoud, A; Tulotta, C; Zoni, E; Kruithof-de Julio, M; van der Horst, G; van der Pluijm, G; Ewa Snaar-Jagalska, B

    2017-01-01

    Lethal and incurable bone metastasis is one of the main causes of death in multiple types of cancer. A small subpopulation of cancer stem/progenitor-like cells (CSCs), also known as tumor-initiating cells from heterogenetic cancer is considered to mediate bone metastasis. Although over the past decades numerous studies have been performed in different types of cancer, it is still difficult to track small numbers of CSCs during the onset of metastasis. With use of noninvasive high-resolution imaging, transparent zebrafish embryos can be employed to dynamically visualize cancer progression and reciprocal interaction with stroma in a living organism. Recently we established a zebrafish CSC-xenograft model to visually and functionally analyze the role of CSCs and their interactions with the microenvironment at the onset of metastasis. Given the highly conserved human and zebrafish genome, transplanted human cancer cells are able to respond to zebrafish cytokines, modulate the zebrafish microenvironment, and take advantage of the zebrafish stroma during cancer progression. This chapter delineates the zebrafish CSC-xenograft model as a useful tool for both CSC biological study and anticancer drug screening. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    Science.gov (United States)

    2015-11-01

    Award Number: W81XWH-13-1-0237 TITLE: IImpact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis PRINCIPAL INVESTIGATOR: David T...Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0237 5c. PROGRAM ELEMENT...repeat expression in pancreatic cancer metastatic potential. An inducible over-expression vector was created and was successfully used in cancer cell

  8. Denosumab: a new option in the treatment of bone metastases from urological cancers

    Directory of Open Access Journals (Sweden)

    Yonese J

    2012-09-01

    Full Text Available Takeshi Yuasa, Shinya Yamamoto, Shinji Urakami, Iwao Fukui, Junji YoneseDepartment of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, JapanAbstract: Bone metastases often create serious clinical problems: they lead to poor performance status due to pathologic fractures, spinal cord compression and intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK, the RANK ligand (RANKL, and osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone metastasis. Denosumab (XGEVA; Amgen, Thousand Oaks, CA, a fully human monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various malignancies. In the context of urological cancer, three main Phase III clinical studies have been published in prostate cancer. This article provides a brief overview of the characteristics of bone metastasis in urological cancers, reviews the mechanisms of bone metastasis, including the RANK/RANKL/osteoprotegerin axis, the current standard of care, zoledronic acid, and describes the efficacy of the novel bone-targeted agent denosumab in bone metastasis. Denosumab is emerging as a key therapeutic option in the treatment of bone metastases from urological cancers.Keywords: bone metastasis, denosumab, prostate cancer, renal cell cancer, urothelial cancer, zoledronic acid

  9. Management of patients with metastasis to the vertebrae: recommendations from the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group.

    Science.gov (United States)

    Gasbarrini, Alessandro; Boriani, Stefano; Capanna, Rodolfo; Casadei, Roberto; Di Martino, Alberto; Silvia Spinelli, Maria; Papapietro, Nicola; Piccioli, Andrea

    2014-02-01

    The purpose of this article is to outline the current approach to patients affected by metastasis to the spine and to present a clinical and surgical algorithm available for clinicians and for future research. A modern approach to the patients affected by spinal metastasis in fact requires a multidisciplinary contest where oncologists, radiotherapists, surgeons and physical therapists cooperate with shared vision to provide the best possible integrated treatments available. The authors of this article constitute the Bone Metastasis Study Group of the Italian Orthopaedic Society (SIOT): a national group of orthopedic tumor surgeons who are dedicated to studying the approach, techniques and outcomes of surgery for metastatic tumors of the musculoskeletal system.

  10. 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.

  11. Treatment of Brain Metastasis from Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Alexander [Department of Radiation Oncology, University of Arizona, 1501 N Campbell Ave., Tucson, AZ 85724 (United States); Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States)

    2010-12-15

    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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the “seed-and-soil” hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease. PMID:26224579

  14. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Breast ductal carcinoma metastasis to jaw bones: a case report

    Directory of Open Access Journals (Sweden)

    Mahmood Reza AshabYamin

    2014-04-01

    Full Text Available Malignant tumors of the oral cavity which are metastatic are very rare and consist of 1% of malignancies of the oral cavity. Numbness or paresthesia of the lower lip or the chin is the main feature of presence of metastasis in the jaw. Our patient was a 38 year old woman with chief complaint of pain in the right half of her face, jaw and teeth. Her medical history revealed a radical mastectomy with lymphadenectomy in the left breast because of invasive ductal carcinoma grade II/III and stage IIIA (T2N2M0 without distant metastasis, followed by chemotherapy (before and after the surgery and radiotherapy two years ago. Following complementary examinations a malignant bone lesion in particular osteosarcoma was suspected. According to this evidence, possibility of early diagnosis of malignant tumors is very important for dentists and maxillofacial surgeons. Symptoms such as paresthesia of the lip and chin is very helpful in differential diagnosis of metastatic lesions from other similar clinical cases especially in patients with history of malignancies which minimize surgical and mental injuries and increase life expectancy of patients.

  16. Ureteral metastasis of occult breast cancer.

    Science.gov (United States)

    Hudolin, T; Nola, N; Milas, I; Nola, M; Juretic, A

    2004-12-01

    We report the case of a 59-year-old woman who presented with right flank pain and fever. Diagnostic investigations revealed stenosis of the right ureter extending over about 1cm. Since a double-J prosthesis could not be passed through it, a percutaneous nephrostomy was constructed and surgical exploration and excision of the stenotic ureteral segment were then carried out. Histopathological analysis of the segment removed showed diffuse infiltration with epithelial tumor cells. On immunohistochemistry, these cells were found to be positive for cytokeratin and for estrogen and progesterone receptors. No primary cancer and no additional metastases were detected. Eleven months later a primary tumor with a metastasis in the left supraclavicular region was found in the patient's right breast.

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

    Science.gov (United States)

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

    2016-02-18

    Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. PRAME is critical for breast cancer growth and metastasis.

    Science.gov (United States)

    Sun, Zhengwang; Wu, Zhipeng; Zhang, Fenglin; Guo, Qunfeng; Li, Lin; Li, Kun; Chen, Hui; Zhao, Juan; Song, Dianwen; Huang, Quan; Li, Lei; Xiao, Jianru

    2016-12-05

    Breast cancer is the most common cause of cancer death in women and ranks second among cancer deaths. Metastasis is the main cause of death in breast cancer patients. However, the mechanisms underlying the invasion and metastasis of breast cancer cells remain largely elusive. Here we report that the protein PRAME, a tumor-associated antigen isolated from a melanoma, plays a role in preventing the proliferation and metastasis of breast cancer cells. Knocking down of PRAME promotes breast cancer cell proliferation and inhibits apoptosis. In addition, inhibition of PRAME promotes the invasion of breast cancer cells. To further examine the role of PRAME in vivo, we utilized mouse model and found the volume and the weight of tumors was markedly increased after PRAME was knocked down. This study demonstrates that PRAME functions as a tumor suppressor in breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. [Construction and improvement of animal models with different positional osseous metastasis of prostate cancer in vivo].

    Science.gov (United States)

    Bi, Y X; Xiao, M H; Zhang, N N; Li, X Y; Mao, X P; Zhang, K; Zhang, Z R; Zhao, L Y

    2017-08-18

    To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo. Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively. The change of mouse activity, tumor formation, tumor size and survival time were observed respectively. And the femur tissue and spinal tissue were obtained from the mice after death. The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue. The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days. There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05). As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection. At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells ( at least 2 weeks longer). The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study. At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells. The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal

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

    Science.gov (United States)

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

    2016-11-01

    As lung cancer is the most common malignancy worldwide and high mortalities are the result of metastasis, novel information surpassing the treatment strategies and therapeutic agents focusing on cancer dissemination are of interest. Lung cancer metastasis involves increased motility, survival in circulation and ability to form new tumors. Metastatic cells increase their aggressive features by utilizing several mechanisms to overcome hindrances of metastasis, including epithelial to mesenchymal transition (EMT), increased in cellular survival and migratory signals. Sufficient amounts of natural product-derived compounds have been shown to have promising anti-metastasis activities by suppressing key molecular features upholding such cell aggressiveness. The knowledge regarding molecular mechanisms rendering cell dissemination together with the anti-metastasis information of natural product-derived compounds may lead to development of novel therapeutic strategies. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Cell lineage determinants as regulators of breast cancer metastasis.

    Science.gov (United States)

    Lu, Wei; Kang, Yibin

    2016-12-01

    The mammary epithelium is organized in a hierarchy of mammary stem cells (MaSCs), progenitors, and differentiated cells. The development and homeostasis of mammary gland are tightly controlled by a complex network of cell lineage regulators. These determinants of cellular hierarchy are frequently deregulated in breast tumor cells and closely associated with cancer progression and metastasis. They also contribute to the diversity of breast cancer subtypes and their distinct metastatic patterns. Cell fate regulators that normally promote stem/progenitor activities can serve as drivers for epithelial-mesenchymal transition and metastasis whereas regulators that promote terminal differentiation generally suppress metastasis. In this review, we discuss how some of the key factors function in normal mammary lineage determination and how these processes are hijacked by tumor cells to enhance metastasis. Understanding the molecular connections between normal development and cancer metastasis will enable the development of more specific and effective therapeutic approaches targeting metastatic tumor cells.

  2. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniele Santini

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

  5. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

    Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

  6. BRMS1 Suppresses Breast Cancer Metastasis to Bone via Its Regulation of microRNA-125b and Downstream Attenuation of TNF-Alpha and HER2 Signaling Pathways

    Science.gov (United States)

    2014-04-01

    April 2014 TYPE OF REPORT: Annual Summary PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort...Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY...related transcrip- tion factor; SRF, serum response factor; BRMS1, breast cancer metastasis suppressor 1; CTC, circulating tumor cells; DTC , dissemi

  7. Exploring the management of bone metastasis according to the Roy Adaptation Model.

    Science.gov (United States)

    Maxwell, T; Givant, E; Kowalski, M O

    2001-08-01

    To explore bone metastasis using Roy's Adaptation Model as a conceptual framework. Published articles, conference abstracts, recent texts, and prescribing information. Bone metastasis has a significant impact on the patient's ability to maintain physical and psychosocial functions. Primary (self), secondary (family and occupation), and tertiary (community) roles, as identified by the Roy Adaptation Model, may be impaired as a result of bone metastasis. Patient education is a nursing intervention that frequently is used, as it allows an individual to interpret an aversive event and take action, thus promoting adaptation to illness. Medications for the underlying disease, bone metastasis, pain, and other symptoms warrant consideration. Active interventions, such as relaxation therapy, guided imagery, music, meditation, and therapeutic touch, also promote adaptation. Bone is a common and potentially debilitating site of metastasis. The presence of bone metastasis indicates progressive and, almost always, incurable disease. Patient adaptation can be enhanced through the proper use of palliative therapies and other nursing measures. Oncology nurses can assist in the physical and psychosocial adaptation of patients with bone metastasis through assessment, patient education, and symptom management.

  8. Vaginal metastasis of pancreatic cancer | Benhayoune | Pan African ...

    African Journals Online (AJOL)

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of ...

  9. Hypoxia-inducible factor 1 and breast cancer metastasis.

    Science.gov (United States)

    Liu, Zhao-Ji; Semenza, Gregg L; Zhang, Hua-Feng

    2015-01-01

    Accumulating evidence has shown that the hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating breast cancer progression and metastasis. The effects of hypoxia-inducible factor 1 (HIF-1), a master regulator of the hypoxic response, have been extensively studied during these processes. In this review, we focus on the roles of HIF-1 in regulating breast cancer cell metastasis, specifically its effects on multiple key steps of metastasis, such as epithelial-mesenchymal transition (EMT), invasion, extravasation, and metastatic niche formation. We also discuss the roles of HIF-1-regulated non-coding RNAs in breast cancer metastasis, and therapeutic opportunities for breast cancer through targeting the HIF-1 pathway.

  10. Rare localisation of breast cancer metastasis to thyroid gland

    Directory of Open Access Journals (Sweden)

    Kolarević Daniela

    2012-01-01

    Full Text Available Introduction. Metastases to the thyroid gland are very rare. They are usually seen in malignant melanoma, kidney, breast cancer and lung cancer. Case report. We presented a 54- years-old female patient with breast cancer diagnosed in 2002. The adequate surgical procedure was done and the tumor and axillary lymph nodes were removed. The patient also received adjuvant postoperative chemotherapy. After seven years of a disease free period, the first relapse of the disease was detected as thyroid gland tumor with axillary lymphadenopathy. The patient had a good response to systemic treatment so the surgical removal of thyroid gland and enlarged lymph nodes was performed. Histopathological analysis confirmed metastasis with breast cancer origin. Radical mastectomy was also preformed. Second relapse of the disease was detected 10 months later, while the patient was on hormonal therapy. It was manifested as the appearance of bone and skin metastases, pleural effusion and lymphadenopathy. Conclusion. This case report emphasized the importance of detailed examination of any new onset of thyroid swelling in a patient with previous history of malignancy.

  11. Rare localisation of breast cancer metastasis to thyroid gland.

    Science.gov (United States)

    Kolarević, Daniela; Tomasević, Zorica; Marković, Ivan; Zegarac, Milan; Pupić, Gordana

    2012-12-01

    Metastases to the thyroid gland are very rare. They are usually seen in malignant melanoma, kidney, breast cancer and lung cancer. We presented a 54-years-old female patient with breast cancer diagnosed in 2002. The adequate surgical procedure was done and the tumor and axillary lymph nodes were removed. The patient also received adjuvant postoperative chemotherapy. After seven years of a disease free period, the first relapse of the disease was detected as thyroid gland tumor with axillary lymphadenopathy. The patient had a good response to systemic treatment so the surgical removal of thyroid gland and enlarged lymph nodes was performed. Histopathological analysis confirmed metastasis with breast cancer origin. Radical mastectomy was also preformed. Second relapse of the disease was detected 10 months later, while the patient was on hormonal therapy. It was manifested as the appearance of bone and skin metastases, pleural effusion and lymphadenopathy. This case report emphasized the importance of detailed examination of any new onset of thyroid swelling in a patient with previous history of malignancy.

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

    Science.gov (United States)

    Paschall, Amy V; Liu, Kebin

    2016-08-14

    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.

  13. Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Howard Li

    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPARγ inhibits growth of cancer cells including non-small cell lung cancer (NSCLC. Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγ(flox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Mac(neg, or control PPARγ(flox/flox mice. In both models, mice receiving PPARγ-Mac(neg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells.

  14. Cancer metastasis: Mechanisms of inhibition by melatonin.

    Science.gov (United States)

    Su, Shih-Chi; Hsieh, Ming-Ju; Yang, Wei-En; Chung, Wen-Hung; Reiter, Russel J; Yang, Shun-Fa

    2017-01-01

    Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage, is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site. In reference to melatonin, the vast majority of investigations have focused on tumor development and progression at the primary site. Recently, however, interest has shifted toward the role of melatonin on tumor metastases. In this review, we highlight current advances in understanding the molecular mechanisms by which melatonin counteracts tumor metastases, including experimental and clinical observations; emphasis is placed on the impact of both cancer and non-neoplastic cells within the tumor microenvironment. Due to the broad range of melatonin's actions, the mechanisms underlying its ability to interfere with metastases are numerous. These include modulation of cell-cell and cell-matrix interaction, extracellular matrix remodeling by matrix metalloproteinases, cytoskeleton reorganization, epithelial-mesenchymal transition, and angiogenesis. The evidence discussed herein will serve as a solid foundation for urging basic and clinical studies on the use of melatonin to understand and control metastatic diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. 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.

  16. RSK2 phosphorylates T-bet to attenuate colon cancer metastasis and growth.

    Science.gov (United States)

    Yao, Ke; Peng, Cong; Zhang, Yuwen; Zykova, Tatyana A; Lee, Mee-Hyun; Lee, Sung-Young; Rao, Enyu; Chen, Hanyong; Ryu, Joohyun; Wang, Lei; Zhang, Yi; Gao, Ge; He, Wei; Ma, Wei-Ya; Liu, Kangdong; Bode, Ann M; Dong, Ziming; Li, Bing; Dong, Zigang

    2017-11-13

    Metastasis is a major cause of cancer-related deaths. Approximately 80% of patients with colorectal cancer develop liver metastasis and 20% develop lung metastasis. We found that at different stages of colon cancer, IFNγ secretion from peripheral blood mononuclear cells was decreased compared with healthy controls. The ribosomal S6 kinase (RSK) family of kinases has multiple cellular functions, and we examined their roles in this observed IFNγ decrease. Flow cytometry analysis of wild-type (WT) and RSK2 knockout (KO) mice revealed significantly lower levels of IFNγ in the RSK2 KO mice compared with the WT mice. Since IFNγ is a component of immunity, which contributes to protection against metastatic carcinomas, we conducted a colon cancer liver metastasis experiment. We found significantly greater metastasis in RSK2 KO mice compared with WT mice. Transcription factor T-bet can directly activate Ifnγ gene transcription. In vitro kinase assay results showed that RSK2 phosphorylated T-bet at serines 498 and 502. We show that phosphorylation of T-bet by RSK2 is required for IFNγ expression, because knockdown of RSK2 expression or overexpression of mutant T-bet reduces IFNγ mRNA expression. To verify the function of the phosphorylation sites, we overexpressed a constitutively active mutant T-bet (S498E/S502E) in bone marrow. Mutant T-bet restored the IFNγ mRNA levels and dramatically reduced the metastasis rate in these mice. Overall, these results indicate that phosphorylation of T-bet is required for the inhibition of colon cancer metastasis and growth through a positive regulation of RSK2/T-bet/IFNγ signaling. Published under the PNAS license.

  17. [A Case of Difficult-to-Diagnose Carcinomatous Meningitis Caused by Prostate Cancer Metastasis].

    Science.gov (United States)

    Shinohara, Masatake; Kiba, Keisuke; Yamada, Atsushi; Hatakeyama, Kinta; Mita, Yasunobu; Saka, Toshihisa; Hirao, Yoshihik

    2016-05-01

    A 66-year-old man was referred to our hospital because of right leg pain. Computed tomography (CT) revealed multiple osteolytic changes. His serum prostate-specific antigen (PSA) level was increased to 77.83 ng/ml at the time of hospitalization. A prostate biopsy was performed, and histological examination results indicated poorly differentiated adenocarcinoma. Under the diagnosis of multiple bone metastasis of prostate cancer, androgen deprivation therapy was started. However, 1 month later, the patient was confused and lost appetite. Brain CT image demonstrated brain metastasis, and magnetic resonance image showed hydrocephalus. Although the patient underwent ventricular drainage because of a depressed level of consciousness, he died of primary disease complicated by pneumonia 3 months after the first visit. Perioperative cerebrospinal fluid cytological examination revealed adenocarcinoma cells. Therefore, a diagnosis of carcinomatous meningitis caused by prostate cancer metastasis was made.

  18. Metastasis on bone scan with low prostate specific antigen (≤20 ng/ml) and Gleason's score (<8) in newly diagnosed Pakistani males with prostate cancer: should we follow Western guidelines?

    Science.gov (United States)

    Zaman, Maseeh Uz; Fatima, Nosheen; Sajjad, Zafar

    2011-01-01

    To find out diagnostic correlation of prostate specific antigen (PSA) and Gleason' s score (GS) with bone metastasis (BM) in newly diagnosed prostate cancer (PC) patients in Pakistan. This retrospective study included 204 newly diagnosed PC patients who were referred for BS for staging. The mean age, mean PSA and incidence of BM on BS were 71±09 years, 111.0±58.5 ng/ml and 67/204 (33%), respectively. The mean GS of the studied population was 7±1. According to PSA levels, patients were divided into 5 groups: 10-≤20 ng/ml (4/204), >20-≤50 ng/ml (22/204), >50-≤100 (25/204) and >100 ng/ml (38/204). The incidence of positive BS (%) for BM and mean GS (score ±SD) for each group were 14%, 7±1; 10%, 6±1; 32%, 7±1; 56%, 8∓1 and 82%, 8±1 respectively (significant p value). PSA and GS were statistically significant predictors of BM on BS and their predictive value was additive (p6 was more sensitive (88.9%) and less specific (56.2%) for diagnosing BM. (1) There is an overall increased incidence of BM in newly diagnosed patients with PC and even at serum PSA level≤20 ng/ml and GS<8; (2) PSA and GS are independent predictors for BM but age is not; (3) in view of possible aggressive behavior of PC in local population, one must be careful in adopting Western guidelines for using BS in newly diagnosed Asian males with PC having PSA≤20 ng/ml and GS <8.

  19. Bone scanning--who needs it among patients with newly diagnosed prostate cancer?

    Science.gov (United States)

    Hirobe, Megumi; Takahashi, Atsushi; Hisasue, Shin-Ichi; Kitamura, Hiroshi; Kunishima, Yasuharu; Masumori, Naoya; Iwasawa, Akihiko; Fujimori, Kenji; Hasegawa, Tadashi; Tsukamoto, Taiji

    2007-10-01

    We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.

  20. 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.

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-15

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

  3. Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases.

    Science.gov (United States)

    Gao, Dongwei; Li, Sha

    2013-12-01

    Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire new traits to adapt to foreign milieu during the course of evolving into a new tumor in second organs. These comparisons also provided new information on understanding mechanism of vascular metastasis, organ-specific metastasis, and tumor dormancy. The collective results suggest a new hypothesis, biological resonance (bio-resonance) model. The hypothesis has two aspects. One is that primary cancer and matched metastasis have a common progenitor. The other is that both ancestors of primary cancer cells and metastatic cancer cells are under similar microenvironments and receive similar or same signals. When their interactions reach a status similar to primary cancer, metastasis will occur. Compared with previous hypotheses, the bio-resonance hypothesis seems to be more applicable for cancer metastasis to explain how, when and where metastasis occurs. Thus, it has important implications for individual prediction, prevention and treatment of cancer metastasis.

  4. 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.

  5. Breast cancer metastasis to thyroid: a retrospective analysis | Zhou ...

    African Journals Online (AJOL)

    Background: Breast cancers metastasizing to thyroid gland are relatively uncommon in clinical practice. Objective: Retrospective analysis of data from breast cancer patients with thyroid metastasis (TM). Methods: The US suspected, fine-needle aspiration cytology (FNAC) confirmed TM in breast cancer patients, treated ...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Secondary metastatic cancer remains the single biggest cause of mortality and morbidity across most solid tumors. In breast cancer, 100% of deaths are attributed to metastasis. At present, there are no "cures" for secondary metastatic cancer of any form and there is an urgent unmet clinical need ...

  7. Panax notoginseng saponins (PNS) inhibits breast cancer metastasis.

    Science.gov (United States)

    Wang, Peiwei; Cui, Jingang; Du, Xiaoye; Yang, Qinbo; Jia, Chenglin; Xiong, Minqi; Yu, Xintong; Li, Li; Wang, Wenjian; Chen, Yu; Zhang, Teng

    2014-07-03

    Panax notoginseng (Burkill) F.H. Chen (Araliaceae) has been extensively used as a therapeutic agent to treat a variety of diseases. Panax notoginseng saponins (PNS) consist of major therapeutically active components of Panax notoginseng. PNS inhibit the growth of a variety of tumor cells in vitro and in vivo. The aim of the study is to investigate the effects and underlying mechanisms of PNS on breast cancer metastasis. 4T1 cell, a highly metastatic mouse breast carcinoma cell line, was utilized for in vitro and in vivo assays. In vitro assays were first performed to examine the effects of PNS on 4T1 cell viability, migration and invasion, respectively. Real-time PCR analyses were also performed to examine the effects of PNS on the expression of genes associated with tumor metastasis. The effect of PNS on 4T1 tumor cell metastasis was further assessed in spontaneous and experimental metastasis models in vivo. PNS treatment exhibited a dose-dependent effect on impairing 4T1 cell viability in vitro. However, when examined at a lower dose that did not affect cell viability, the migration and invasion of 4T1 cell was remarkably inhibited in vitro. Meanwhile, PNS treatment led to upregulated expression of genes known to inhibit metastasis and downregulated expression of genes promoting metastasis in cultured 4T1 cells. These results suggested a selective effect of PNS on 4T1 migration and invasion. This hypothesis was further addressed in 4T1 metastasis models in vivo. The results showed that the lung metastasis was significantly inhibited by PNS treatment in both spontaneous and experimental metastasis models. Taken together, our results demonstrated an inhibitory effect of PNS on 4T1 tumor metastasis, warranting further evaluation of PNS as a therapeutic agent for treating breast cancer metastasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. ASSESSMENT OF PROGNOSTIC FACTORS CONSIDERING THE VOLUME OF SKELETAL METASTASIS IN PATIENTS WITH DISSEMINATED PROSTATE CANCER

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    N. E. Kosyh

    2017-01-01

    Full Text Available Purpose. To determine the correlation between prognostic factors (age, differentiation grade assessed using the Gleason scoring system, serum prostate specific antigen, prostate volume, and serum testosterone and the volume of skeletal metastasis expressed as bone metastasis index (BMI in patients with disseminated prostate cancer (DPC. Material and methods. We conducted a retrospective analysis of 157 patients with initially diagnosed DPC treated at the Khabarovsk Regional Cancer Center from 2003 to 2013. Bone metastases were revealed in all patients. The volume of skeletal metastasis was measured using a novel automated computeraided diagnosis system devised by the specialists of Computer Center of the Russian Academy of Sciences. Results. The patients were divided into four groups. Group1: BMI≤1 % and Gleason score≤5; group 2: BMI ≤1 % and Gleason Score≥3; group 3: BMI>1 % and Gleason score≤5; group 4: BMI>1 % and Gleason score>5. The median survival time was 48 months in group 1 patients, 36.5 months in group 2, 33 months in group 3 and 20 months in group 4 patients. Both log-rank and Wilcoxon tests demonstrated a statistically significant difference in survival curves between the groups 1 and 3, and between the groups 2 and 4. There was also a difference in differentiation grade assessed by the Gleason score system between these two pairs of groups. Correlation of other prognostic factors, such as age, serum prostate specific antigen, prostate volume, and serum testosterone with the volume of skeletal metastasis demonstrated that BMI predominantly influenced the survival of prostate cancer patients. Conclusion. The assessment of prognostic factors allowed the patients’ groups with the worst prognosis to be identified. The bone metastasis index and differentiation grade of the tumor appeared to be independent predictors of high death risk in patients with disseminated prostate cancer.

  9. SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

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    Sh. Hashemzadeh M. Safari

    2004-11-01

    Full Text Available Although splenic metastasis is fairly common in disseminated cancer, solitary splenic metastasis in the absence of diffuse dissemination is rare. We report a case of 44 year-old man who developed isolated splenic metastasis of colon cancer. The patient had undergone right sided hemicolectomy for colon cancer in 1988. In 2001, he underwent reoperation because of local recurrence of tumor in the anastomotic site. The patient was admitted to our hospital on Sep 2003 with abdominal pain. Chest X-ray was normal. Abdominal CT scan showed a large cystic lesion in the spleen. Splenectomy was performed for the patient. The spleen was enlarged, firm and irregular. Histological examination showed metastatic mucinous adenocarcinoma. Based on this case, we recommend that clinicians consider possibility of metastasis in cystic lesions of spleen, especially in patients with a history of a malignant disease.

  10. A case of rectal cancer with sternal metastasis as initial presentation.

    Science.gov (United States)

    Choi, J H; Kim, S J; Oh, J Y; Ryu, S R; Shim, K S; Kim, K H; Baek, S Y; Choi, H Y; Lee, S W; Kim, M J

    1995-08-01

    Colorectal cancer with bone metastasis as initial manifestation is a very rare event. We have reported a case of rectal cancer presenting with sternal metastasis. A 30 year-old man was evaluated due to pain in the sternal area with a bulging mass. History and physical examination did not suggest any specific disease. A radionuclide bone scan revealed increased uptake in the sternal area, right 6th rib, and sacrum. Microscopic examination of a biopsy specimen from the sternum showed metastatic adenocarcinoma. A barium enema and CT scan of the pelvis suggested carcinoma of the upper rectum. Adenocarcinoma of the rectosigmoid junction area was demonstrated by colonoscopic examination with biopsy. He received palliative transverse colostomy for obstruction without further treatment.

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

    Science.gov (United States)

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

    2016-10-01

    Dysregulation of microRNAs is involved in the initiation and progression of several human cancers, including breast cancer, as strong evidence of miRNAs acting as oncogenes or tumour suppressor genes has been found. This study was performed to investigate the biological functions of microRNA-421 (miR-421) in breast cancer and the underlying mechanisms. The expression level of miR-421 was detected in 50 pairs of surgical specimens and human breast cancer cell lines. The results showed that miR-421 is downregulated in breast cancer tissues and metastatic cell lines. In addition, the decrease in miR-421 levels was significantly associated with lymph node metastasis, recurrence/metastasis, or pTNM stage. Functions of miR-421 in cell migration and invasion were assessed through its silencing and overexpression. The results showed that miR-421 knockdown promotes invasion and metastasis in MCF-7 cells and its overexpression suppresses invasion and metastasis in MDA-MB-231 cells. The specific target genes of miR-421 were predicted by TargetScan algorithm and determined by dual luciferase reporter assay, quantitative reverse transcriptase PCR, and western blot analysis. miR-421 could suppress luciferase activity of the reporter containing 3'-untranslated region of metastasis associated 1 (MTA1), a potent oncogene. miR-421 overexpression or knockdown had no effect on the mRNA expression of MTA1, but it could modulate MTA1 protein level. Furthermore, MTA1 knockdown receded the effect of miR-421 inhibitor on invasion and metastasis of MCF-7 cells, and its overexpression receded the effect of miR-421 on invasion and metastasis of MDA-MB-231 cells. Our findings clearly demonstrate that miR-421 suppresses breast cancer metastasis by directly inhibiting MTA1 expression. The present study provides a new insight into the tumour suppressor roles of miR-421 and suggests that miR-421/MTA1 pathway is a putative therapeutic target in breast cancer. Copyright © 2016 Elsevier Masson SAS

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

    Science.gov (United States)

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

    2016-01-01

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

  13. 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.

  14. Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis.

    Science.gov (United States)

    Agarwal, E; Robb, C M; Smith, L M; Brattain, M G; Wang, J; Black, J D; Chowdhury, S

    2017-06-01

    Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.

  15. 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

  16. Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis

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    Thaiz F. Borin

    2017-12-01

    Full Text Available Metastatic breast cancer (BC (also referred to as stage IV spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4 family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE, an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.

  17. 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.

  18. Metformin inhibits the development and metastasis of ovarian cancer.

    Science.gov (United States)

    Wu, Buchu; Li, Shu; Sheng, Lili; Zhu, Jing; Gu, Liying; Shen, Haoran; La, Duanduan; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-09-01

    The aim of this study was to investigate the role of metformin in the regulation of development and metastasis of ovarian carcinoma cell lines in vitro and ovarian cancer in a nude mouse model in vivo. The effects of metformin on the ability of two high-metastatic potential human ovarian cancer cell lines (SKOV3 and HO8910-PM) to adhere, invade and migrate in vitro were observed by means of a cell adhesion test, cell invasion test and cell migration test. The size and number of the inoculated and metastatic tumours in vivo in a nude mouse were determined following intraperitoneal injection of metformin. Furthermore, the extent of angiogenesis (vWF) and macrophage infiltration in the tumour were determined. Proliferation, migration, invasion and adhesion of ovarian cancer cells were significantly inhibited (Pmetformin inhibited hepatic, intestinal and lung metastasis (Pmetformin inhibits the development and metastasis of ovarian cancer by reducing cellular-ECM interactions, neovascularisation and macrophage infiltration.

  19. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass

    OpenAIRE

    Peters, H. Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A.; Tan, Sanda A.

    2017-01-01

    Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to th...

  20. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass.

    Science.gov (United States)

    Peters, H Charles; Liu, Xiuli; Iqbal, Atif; Cunningham, Lisa A; Tan, Sanda A

    2017-01-01

    Despite improved screening modalities, 15-25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.

  1. [Predictive factors for bone metastases of prostate cancer].

    Science.gov (United States)

    Chen, Ye-Hui; Nie, Pin; Jiang, Wen; Zhao, Shi-Jia; Zhang, Zhi; Lin, Hua-Xin; Li, Miao-Yuan; Liu, Yan-Qing; Li, Peng-Hui; Zhu, Xu-Sheng

    2016-02-01

    To investigate the correlation between a diverse of clinical factors and bone metastases of prostate cancer. The clinical data of 80 patients with prostate cancer were collected and analyzed. The correlations of age, alkaline phosphotase (ALP), prostate specific antigen (PSA), erythrocyte sedimentation rate (ESR), Gleason score, and expressions of androgen receptor (AR) and Ki-67 with bone metastases were analyzed by one-way ANOVA and Logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated. Forty-five of the 80 patients (56%) were found to have bone metastasis, who had significantly older age and higher levels of ALP, PSA, ESR, Gleason score, and expressions of AR and Ki-67 than those without bone metastasis (PGleason score and AR expression as independent factors correlated with bone metastasis with OR (95% CI) of 1.005 (1.001, 1.009) (P=0.008), 5.356 (1.431, 20.039) (P=0.013), and 18.594 (2.460, 140.524) (P=0.005), respectively. The cutoff values of PSA, Gleason Score and AR were 67.1 ng/ml, 7.5, and 2.5, respectively; their sensitivities were 55.6%, 75.6%, and 84.0% for predicting bone metastasis with specificities of 97.1%, 82.9%, and 91.4%, respectively. Of the factors analyzed, PSA, Gleason score and AR expression, but not age, ALP, PSA, ESR, or Ki-67 expression, are the predictive factors of bone metastasis of prostate cancer.

  2. Sacral metastasis in a patient with endometrial cancer: case report and review of the literature.

    Science.gov (United States)

    Albareda, J; Herrera, M; Lopez Salva, A; Garcia Donas, J; Gonzalez, R

    2008-12-01

    Bone involvement in endometrial cancer has been described in less than 15% of the patients with metastatic disease. The medical literature reports 29 cases, although none involving the sacrum. We present a case of a 62-year-old woman who underwent surgery for endometrial adenocarcinoma in December 2002 (FIGO stage IB grade 1). In January 2006, the CT scan revealed a lesion on the inferior side of the sacrum. Rescue surgery, consisted of sacrectomy with en bloc excision of the metastasis. After 26 months of follow up the patient is disease-free. This case is unusual for the following reasons: the site of metastasis was the sacrum, metastasis was secondary to a tumour whose histological grade suggested a good prognosis (G1), the patient lacked clinical signs, the diagnosis was fortuitous and because of the surgical treatment pursued and its successful outcome.

  3. Is Selenium a Potential Treatment for Cancer Metastasis?

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    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.

  4. The Usefulness of Bone Biomarkers for Monitoring Treatment Disease: A Comparative Study in Osteolytic and Osteosclerotic Bone Metastasis Models

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    Marta Martín-Fernández

    2017-04-01

    Full Text Available BACKGROUND: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases. The aim of this work was to establish the correlation between tumor dispersion (bioluminescence and biochemical markers of bone turnover in two osteolytic and osteoblastic metastasis models in mice. METHODS: The A549M1 cell line that produces osteolytic metastases and the LADOB cell line extracted from a patient with a lung carcinoma and osteoblastic metastases cells were retrovirally transduced with a luciferase reporter gene for in vivo image analysis. Forty-four-week–old mice were inoculated in the left cardiac ventricle with A549M1 or LADOB cells. Twenty mouse of each group were treated with a single dose of ZA (70 μg/kg 5 days after i.c. Ten animals of each group were sacrificed at 21 and 28 days postinoculation in A549M1 and 60 and 75 days in the LADOB assay. Bioluminescence analysis was quantified 7, 14, 21 ,and 28 days postinoculation in A549M1 mice and 33, 45, 60, and 75 days after inoculation in LADOB mice. Osteocalcin (BGP, aminoterminal propeptide of procollagen I (PINP, carboxiterminal telopeptide of type I collagen (CTX, and 5b isoenzyme of tartrate-resistant acid phosphatase were measured by ELISA (IDS, UK. RESULTS: Bioluminescence imaging revealed a significant increase of tumor burden on time in both osteolytic and osteoblastic mice models. ZA administration resulted in a significant decrease in tumor burden at 21 and 28 days in the A549M1 animals and 60 and 70 days postinoculation in the LADOB line. Biomarkers levels were significantly increased in the untreated group at every point in the osteolytic model. In the osteoblastic model, 2 months after

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

    Directory of Open Access Journals (Sweden)

    Shunfang YANG

    2011-02-01

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

  6. 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.

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

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    Paola Bendinelli

    2016-05-01

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

  8. Risk of skeletal related events among elderly prostate cancer patients by site of metastasis at diagnosis.

    Science.gov (United States)

    Hussain, Arif; Aly, Abdalla; Daniel Mullins, C; Qian, Yi; Arellano, Jorge; Onukwugha, Eberechukwu

    2016-11-01

    The purpose of this study was to estimate the risk of developing skeletal-related events (SREs) based on site of metastasis at diagnosis and identify other predictors of developing SREs among metastatic prostate cancer patients. We conducted a retrospective cohort study using linked SEER (Surveillance, Epidemiology, and End Results) and Medicare data and identified men over the age of 65 with incident metastatic prostate cancer diagnosed during 2005-2009. SREs included radiation (RAD), pathological fractures (PF), bone surgery (BS), and spinal cord compression (SCC). The association between site of metastasis at diagnosis and SRE was examined using a Cox proportional hazards model that accounts for death as a competing risk. Among 4404 men (median age: 79 years) with incident metastatic prostate cancer, 44% experienced SREs at a median of 9.6 months post diagnosis. Compared to bone metastasis only, our model showed that patients were significantly less likely to develop SREs if they had LN-only metastasis at diagnosis (Sub-Hazard Ratio [SHR] 0.56; 95% Confidence Interval [CI]: 0.43-0.72) or unknown site of metastasis (SHR: 0.79; CI: 0.64-0.97). Other predictors of reduced SRE risk were age 80+ years (SHR: 0.83; CI: 0.75-0.91), non-Hispanic Black (SHR: 0.77; CI: 0.65-0.90), or being diagnosed in year 2009 (SHR: 0.85; CI: 0.72-0.99). Patients were significantly more likely to develop SREs if they received androgen deprivation therapy (SHR: 1.73; CI: 1.48-2.02) or had Gleason score 8-10 disease (SHR: 0.79; CI: 0.64-0.97). Compared to patients who present with bone metastasis only at diagnosis, patients presenting with other metastatic sites have similar risk of developing SREs, with the exception of those presenting with lymph node only metastasis who have a significantly reduced risk of SREs. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

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

  11. Diagnostic value of urinary N-telopeptide of type I collagen in prostate cancer. Comparison with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Fukumitsu, Nobuyoshi; Yanada, Shuuichi; Hatano, Takashi; Igarashi, Hiroshi; Nakada, Jojiro [Jikei Univ., Chiba (Japan). Kashiwa Hospital; Uchiyama, Mayuki; Mori, Yutaka

    1999-05-01

    The usefulness of a new biochemical marker of bone resorption, N-telopeptide of type I collagen (NTx), in the diagnosis of bone metastasis was assessed in 69 prostate cancer patients. Based on the bone scintigraphy findings, the patients were divided into a bone metastasis (+) group (n=36) and a bone metastasis (-) group (n=33). The urinary NTx level was significantly higher in the bone metastasis (+) group than in the bone metastasis (-) group (95.5{+-}18.5 nM BCE/mM Cr vs. 63.3{+-}7.9 nM BCE/mM Cr). There was a tendency for greater variability in urinary NTx levels during a 2 month-period in the bone metastasis (+) group than in the bone metastasis (-) group. The urinary NTx level of the 6 patients who were clinically staged as (4+) according to the extent of disease (EOD) grading system was 211.4{+-}96.9 nM BCE/mM Cr, and was significantly higher (p<0.05) than in the (-) group. However, there was not a significant difference in urinary NTx levels between the (1+) to (3+) groups and the (-) group. In conclusion, measuring urinary NTx levels in useful in diagnosing bone metastasis in view of the fact that it is a simple and noninvasive procedure. While it is not as sensitive as bone scintigraphy, it may be used to supplement bone scintigraphy. (author)

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

    Science.gov (United States)

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

    2015-09-24

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

  13. 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...... 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....... This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved...

  14. 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.

  15. IL-25 blockade inhibits metastasis in breast cancer

    Directory of Open Access Journals (Sweden)

    Zhujun Jiang

    2016-12-01

    Full Text Available Abstract Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E was expressed by tumor-infiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.

  16. IL-25 blockade inhibits metastasis in breast cancer.

    Science.gov (United States)

    Jiang, Zhujun; Chen, Jingtao; Du, Xuemei; Cheng, Hang; Wang, Xiaohu; Dong, Chen

    2017-03-01

    Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.

  17. 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.

  18. Rad51 supports triple negative breast cancer metastasis

    Science.gov (United States)

    Wiegmans, Adrian P; Al-Ejeh, Fares; Chee, Nicole; Yap, Pei-Yi; Gorski, Julia J; Silva, Leonard Da; Bolderson, Emma; Chenevix-Trench, Georgia; Anderson, Robin; Simpson, Peter T; Lakhani, Sunil R; Khanna, Kum Kum

    2014-01-01

    In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months. PMID:24811120

  19. Testicular Metastasis of Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Ayumu Kusaka

    2014-09-01

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

  20. 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.

  1. Imaging Primary Prostate Cancer and Bone Metastasis

    Science.gov (United States)

    2007-04-01

    frozen in a dry ice and isopropyl alcohol bath for 2 min. The bodies were then embedded in a 4% carboxymethyl cellulose (Aldrich) water mixture using a...anionic charges on cell membranes . Recently, a cross-bridged ligand tetraazamacrocycle 4,11-bis(carboxymethoxymethyl)-1,4,8,11-tetraazabicyclo (6.6.2

  2. Detection of cancer before distant metastasis

    NARCIS (Netherlands)

    Coumans, Frank A. W.; Siesling, Sabine; Terstappen, Leon W. M. M.

    2013-01-01

    Background: 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

  3. When to perform bone scintigraphy in patients with newly diagnosed prostate cancer? a retrospective study.

    Science.gov (United States)

    Lin, Yiwei; Mao, Qiqi; Chen, Bin; Wang, Liujiang; Liu, Ben; Zheng, Xiangyi; Xie, Liping

    2017-06-12

    To determine when a bone scintigraphy investigation is appropriate in patients with newly diagnosed prostate cancer (PCa). We retrospectively reviewed 703 newly diagnosed PCa patients who were referred for bone scintigraphy. The association between age, prostate specific antigen (PSA), Gleason score (GS) and bone scintigraphy result were investigated by series of crude or stratified analysis. Overall, 15.08% (106/703) patients had bone metastases. PSA and GS between positive bone scan group and negative bone scan group were significantly different, while age was not. The incidence of bone metastasis in patient with PSA bone scan. Patients with PSA ≥ 20 ng/ml or GS ≥ 8 were in higher risk of bone metastasis, bone scintigraphy was recommended. But a bone scintigraphy is of limited value in PCa patients with PSA ≤ 20 ng/ml and GS ≤ 7.

  4. SKI-606 (Bosutinib) blocks prostate cancer invasion, growth, and metastasis in vitro and in vivo through regulation of genes involved in cancer growth and skeletal metastasis.

    Science.gov (United States)

    Rabbani, Shafaat A; Valentino, Maria-Luisa; Arakelian, Ani; Ali, Suhad; Boschelli, Frank

    2010-05-01

    In the current study, we have examined the efficacy of a Src/Abl kinase inhibitor SKI-606 (Bosutinib) for its effect on prostate cancer growth and skeletal metastasis. Treatment of highly invasive human prostate cancer cells PC-3 and DU-145 with different doses of SKI-606 decreased Src activation, cell proliferation, migration, and invasion as determined by Matrigel Boyden chamber invasion assay. For in vivo studies, PC-3 cells were inoculated through s.c. or i.t. route into male BALB/c nu/nu or Fox Chase severe combined immunodeficient mice, respectively. Experimental animals treated with SKI-606 developed tumors of a significantly smaller volume and a significant decrease (50%) in experimental skeletal lesion area. A marked increase (32%) in bone volume to tumor volume ratio was also seen by micro-computed tomography analysis of tibias from control and experimental groups of animals. Western blot analysis showed the ability of SKI-606 to significantly decrease the phosphorylation of signaling molecules (AKT, mitogen-activated protein kinase, focal adhesion kinase) and the expression of tumor progression-associated genes uPAR, MMP-2, MMP-9, N-cadherin, fibronectin, BMP-2 (bone morphogenetic protein 2), BMP-6 (bone morphogenetic protein 6), IL-8 (interleukin 8), and TGF-beta (transforming growth factor beta) in prostate cancer cells. SKI-606 is currently in clinical trials for breast cancer and chronic myelogenous leukemia. Results from these studies provide convincing evidence for evaluating its efficacy in prostate cancer patients.

  5. Ubc9 promotes invasion and metastasis of lung cancer cells.

    Science.gov (United States)

    Li, Hui; Niu, Huiyan; Peng, Yang; Wang, Jiahe; He, Ping

    2013-04-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. The mortality is high mainly due to the lack of known effective screening procedures; there is a high tendency for early spread and systemic therapies do not cure metastatic disease. Thus, it is important to investigate the molecular mechanism(s) of lung cancer development and, specifically, to identify an effective method by which to inhibit the invasion and metastasis of lung cancer. Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays a key role in tumorigenesis. Whether Ubc9 is involved in the invasion and metastasis of lung cancer remains unknown. Herein, we report that Ubc9 exhibits an important role in lung cancer invasion and metastasis. We first investigated the biological effect of Ubc9 on lung cancer by cloning the Ubc9 gene into a eukaryotic expression plasmid and stably expressing it in the human small cell lung cancer cell line NCI-H446 in order to observe any biological changes. We further analyzed the effect of Ubc9 in an in vivo experiment, injecting NCI-H446 cells stably overexpressing Ubc9 into nude mice and analyzing their metastatic ability. Our results demonstrated that Ubc9 is expressed at higher levels in primary lung cancer tissue and metastatic nodules as compared to premalignant and/or normal tissue. Furthermore, we demonstrated that upregulation of Ubc9 expression promotes migration and invasion. Ubc9 likely plays an important role in cancer progression by promoting invasion and metastasis in lung cancer.

  6. Endothelial Cells as Precursors for Osteoblasts in the Metastatic Prostate Cancer Bone

    Directory of Open Access Journals (Sweden)

    Ana E. Paiva

    2017-11-01

    Full Text Available Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer–induced osteogenesis in vivo. Deciphering the osteoblasts origin in the bone microenvironment may result in the development of promising new molecular targets for prostate cancer therapy.

  7. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

    Science.gov (United States)

    Li, J; Gu, D; Lee, S S-Y; Song, B; Bandyopadhyay, S; Chen, S; Konieczny, S F; Ratliff, T L; Liu, X; Xie, J; Cheng, J-X

    2016-01-01

    Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By using label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification. PMID:27132508

  8. 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.

  9. Claudin-2 Promotes Breast Cancer Liver Metastasis by Facilitating Tumor Cell Interactions with Hepatocytes

    Science.gov (United States)

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

    2012-01-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes. PMID:22645303

  10. Anal metastasis originating from colorectal cancer: Report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Min; Lim, Joon Seok; Choi, Jin Young; Park, Mi Suk; Kim, Myeong Jin [Dept. of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Taek; Kim, Ho Guen [Dept. of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    Anal metastasis from colorectal cancer rarely occurs, but it severely impairs the patient's quality of life, often requiring wide resection including the anal sphincter with permanent colostomy. This lesion can be misdiagnosed as a perianal fistula or an abscess, and it can be overlooked at the time of surgery because it is not included in the routine surgical extent of low anterior resection. We report two rare cases of anal metastasis from colorectal cancer. In both cases, perianal nodules with an internal solid portion were detected on preoperative rectal magnetic resonance imaging and additional local excisions of the anal lesions were performed during the process of treatment. Anal metastasis was pathologically confirmed by histology and immunohistochemical staining.

  11. Zebrafish xenograft models of cancer and metastasis for drug discovery.

    Science.gov (United States)

    Brown, Hannah K; Schiavone, Kristina; Tazzyman, Simon; Heymann, Dominique; Chico, Timothy Ja

    2017-04-01

    Patients with metastatic cancer suffer the highest rate of cancer-related death, but existing animal models of metastasis have disadvantages that limit our ability to understand this process. The zebrafish is increasingly used for cancer modelling, particularly xenografting of human cancer cell lines, and drug discovery, and may provide novel scientific and therapeutic insights. However, this model system remains underexploited. Areas covered: The authors discuss the advantages and disadvantages of the zebrafish xenograft model for the study of cancer, metastasis and drug discovery. They summarise previous work investigating the metastatic cascade, such as tumour-induced angiogenesis, intravasation, extravasation, dissemination and homing, invasion at secondary sites, assessing metastatic potential and evaluation of cancer stem cells in zebrafish. Expert opinion: The practical advantages of zebrafish for basic biological study and drug discovery are indisputable. However, their ability to sufficiently reproduce and predict the behaviour of human cancer and metastasis remains unproven. For this to be resolved, novel mechanisms must to be discovered in zebrafish that are subsequently validated in humans, and for therapeutic interventions that modulate cancer favourably in zebrafish to successfully translate to human clinical studies. In the meantime, more work is required to establish the most informative methods in zebrafish.

  12. 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.

    2013-01-01

    Do cancer cells escape their confinement of their original habitat in the primary tumor or are they forced out by ecological changes in their home niche? Describing metastasis in terms of a simple one-way migration of cells from the primary to 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 utilized by social scientists, however, the application of the diaspora concept to metastasis may yield new biological insights as well as therapeutic paradigms. The diaspora paradigm takes into account and models several variables: 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. Ecological scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies. For example, ecological 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 ecological 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

  13. AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective

    Science.gov (United States)

    Talmadge, James E; Fidler, Isaiah J

    2014-01-01

    Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy. PMID:20610625

  14. Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis.

    Science.gov (United States)

    Roe, Jae-Seok; Hwang, Chang-Il; Somerville, Tim D D; Milazzo, Joseph P; Lee, Eun Jung; Da Silva, Brandon; Maiorino, Laura; Tiriac, Hervé; Young, C Megan; Miyabayashi, Koji; Filippini, Dea; Creighton, Brianna; Burkhart, Richard A; Buscaglia, Jonathan M; Kim, Edward J; Grem, Jean L; Lazenby, Audrey J; Grunkemeyer, James A; Hollingsworth, Michael A; Grandgenett, Paul M; Egeblad, Mikala; Park, Youngkyu; Tuveson, David A; Vakoc, Christopher R

    2017-08-24

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. In this context, FOXA1-dependent enhancer reprogramming activates a transcriptional program of embryonic foregut endoderm. Collectively, our study implicates enhancer reprogramming, FOXA1 upregulation, and a retrograde developmental transition in PDA metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Breast Cancer Metastasis Suppressor 1 Up-regulates miR-146, Which Suppresses Breast Cancer Metastasis

    Science.gov (United States)

    Hurst, Douglas R.; Edmonds, Mick D.; Scott, Gary K.; Benz, Christopher C.; Vaidya, Kedar S.; Welch, Danny R.

    2009-01-01

    Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that differentially regulates expression of multiple genes, leading to suppression of metastasis without blocking orthotopic tumor growth in multiple human and murine cancer cells of diverse origins. We hypothesized that miR-146 may be involved in the ability of BRMS1 to supress metastasis because miR-146 expression is altered by BRMS1 and because BRMS1 and miR-146 are both associated with decreased signaling through the nuclear factor-κB pathway. BRMS1 significantly up-regulates miR-146a by 6- to 60-fold in metastatic MDA-MB-231 and MDA-MB-435 cells, respectively, and miR-146b by 40-fold in MDA-MB-435 as measured by real-time quantitative reverse transcription-PCR. Transduction of miR-146a or miR-146b into MDA-MB-231 down-regulated expression of epidermal growth factor receptor, inhibited invasion and migration in vitro, and suppressed experimental lung metastasis by 69% and 84%, respectively (mean ± SE: empty vector = 39 ± 6, miR-146a = 12 ± 1, miR-146b = 6 ± 1). These results further support the recent notion that modulating the levels of miR-146a or miR-146b could have a therapeutic potential to suppress breast cancer metastasis. PMID:19190326

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

    DEFF Research Database (Denmark)

    Josa, Valeria; Krzystanek, Marcin; Vass, Tamas

    2015-01-01

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

  17. Retrobulbar Metastasis Of Prostate Cancer: A Case Report | Oranusi ...

    African Journals Online (AJOL)

    A case of retrobulbar metastasis of prostate cancer in a 58years old man without lower urinary tract symptoms is reported. He presented with a two months history of protrusion of the right eye, diplopia and pain in the eye. Digital rectal examination revealed a mildly enlarged prostate that was hard in consistency and nodular ...

  18. Cutaneous metastasis reveling lung cancer | Elfatoiki | Pan African ...

    African Journals Online (AJOL)

    Pan African Medical Journal. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 20, No 1 (2015) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Cutaneous metastasis reveling lung cancer. FZ Elfatoiki, F Hali. Abstract.

  19. Focal adhesion kinase signaling in metastasis and breast cancer treatment

    NARCIS (Netherlands)

    Nimwegen, Maria Jannetje van

    2007-01-01

    In order to form a distant metastasis, a cancer cell has to migrate out of the primary tumor, intravasate into a blood or a lymphatic vessel, subsequently survive in the absence of cell-cell and cell-matrix interactions, extravasate the blood or lymphatic vessel, migrate through the target organ and

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  1. Cancer cell metastasis; perspectives from the focal adhesion

    Directory of Open Access Journals (Sweden)

    Lefteris C Zacharia

    2015-10-01

    Full Text Available In almost all cancers, most patients die from metastatic disease and not from the actual primary tumor. That is why addressing the problem of metastasis is of utmost importance for the successful treatment and improved survival of cancer patients. Metastasis is a complex process that ultimately leads to cancer cells spreading from the tumor to distant sites of the body. During this process, cancer cells tend to lose contact with the extracellular matrix (ECM and neighboring cells within the primary tumor, and are thus able to invade surrounding tissues. Hence, ECM, and the ECM-associated adhesion proteins play a critical role in the metastatic process. This review will focus on recent literature regarding interesting and novel molecules at the cell-ECM adhesion sites, namely migfilin, mitogen-inducible gene-2 (Mig-2 and Ras suppressor-1 (RSU-1, that are also critically involved in cancer cell metastasis, emphasizing on data from experiments performed in vitro in breast cancer and hepatocellular carcinoma cell lines as well as human breast cancer tissue samples.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. [Paget's disease mimicking metastatic prostate cancer on bone scan image : a case report].

    Science.gov (United States)

    Fukushi, Ken; Koie, Takuya; Yamamoto, Hayato; Okamoto, Akiko; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

    2013-04-01

    A 61-year-old man was referred to our hospital complaining of elevated serum prostate-specific antigen (PSA) (5.1 ng/ml). Histopathologic diagnosis with trans-rectal prostate biopsy specimen was adenocarcinoma, Gleason score 4+5 = 9. Bone scintigraphy revealed an abnormal uptake on left coxal bone. The patient was diagnosed with prostate cancer with bone metastasis. He received androgen deprivation therapy for two years. Serum PSA decreased to an undetected level. However, the abnormal activity of left coxal bone lesion was not changed on bone scintigraphy. Coxal bone biopsy was performed. The bone lesion was histopathologically diagnosed as Paget's disease of bone.

  4. Naringenin reduces lung metastasis in a breast cancer resection model

    OpenAIRE

    Qin, Lei; Jin, Lingtao; Lu, Linlin; Lu, Xiaoyan; Zhang, Chunling; Zhang, Fayun; Liang, Wei

    2011-01-01

    Metastasis is the main cause of death in cancer patients. To improve the outcomes of patients undergoing a surgery, new adjuvant therapies that can effectively inhibit metastases have to be developed. Studies have shown that flavonoid naringenin, a natural product that is mainly present in grapes and citrus, may contribute to cancer prevention. It has many advantages compared to traditional chemotherapeutic drugs, such as low toxicity. To determine whether naringenin can also inhibit metastas...

  5. IMPLANTATION METASTASIS OF LARYNGEAL CANCER AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY

    OpenAIRE

    Guz, A. O.; A. S. Zakharov; A. V. Garev

    2017-01-01

    Squamous cell head and neck carcinoma is frequently associated with dysphagia. An adequate enteral nutrition is the key to successful treatment and rehabilitation of these patients. Percutaneous endoscopic gastrostomy is the preferred route of feeding and nutritional support in head and neck cancer patients with dysphagia. We report a rare case of implantation metastasis of laryngeal cancer following percutaneous endoscopic gastrostomy. Our experience in treating this complication has been de...

  6. Bone-Targeted Agents for the Management of Breast Cancer Patients with Bone Metastases

    Directory of Open Access Journals (Sweden)

    Demetrios Simos

    2013-08-01

    Full Text Available Despite advances in adjuvant therapy for breast cancer, bone remains the most common site of recurrence. The goal of therapy for these patients is palliative and focused on maximizing the duration and quality of their life, while concurrently minimizing any disease or treatment-related complications. Bone metastases predispose patients to reduced survival, pain, impaired quality of life and the development of skeletal-related events. With an increased understanding of the pathophysiology of bone metastasis, effective treatments for their management have evolved and are now in widespread clinical use. This article will discuss the pathogenesis of bone metastases and review the key clinical evidence for the efficacy and safety of currently available systemic bone-targeted therapies in breast cancer patients with an emphasis on bisphosphonates and the receptor activator of nuclear factor kappa B ligand (RANKL inhibitors. We will also discuss novel strategies and therapies currently in development.

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

    Science.gov (United States)

    Molania, Ramyar; Mahjoubi, Frouzandeh; Mirzaei, Rezvan; Khatami, Saeed-Reza; Mahjoubi, Bahar

    2014-01-01

    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. PMID:26317029

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

    Directory of Open Access Journals (Sweden)

    Ramyar Molania

    2014-01-01

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

  9. Association of proteasomal activity with metastasis in luminal breast cancer

    Science.gov (United States)

    Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

    2017-09-01

    Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

  10. EGFR and HER2 signaling in breast cancer brain metastasis

    Science.gov (United States)

    Sirkisoon, Sherona R.; Carpenter, Richard L.; Rimkus, Tadas; Miller, Lance; Metheny-Barlow, Linda; Lo, Hui-Wen

    2016-01-01

    Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis. PMID:26709660

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

    African Journals Online (AJOL)

    The mass was 5.5 cm 7.5 cm and mobile with deglutition. Conclusions: Although the tumor was low grade, it showed cervical lymph node metastasis months after its surgical excision. This shows the importance of scheduled CT scan of the neck during follow-up of these cases. Keywords: Hyoid chondrosarcoma; Radiology; ...

  12. Movers and shakers: cell cytoskeleton in cancer metastasis.

    Science.gov (United States)

    Fife, C M; McCarroll, J A; Kavallaris, M

    2014-12-01

    Metastasis is responsible for the greatest number of cancer deaths. Metastatic disease, or the movement of cancer cells from one site to another, is a complex process requiring dramatic remodelling of the cell cytoskeleton. The various components of the cytoskeleton, actin (microfilaments), microtubules (MTs) and intermediate filaments, are highly integrated and their functions are well orchestrated in normal cells. In contrast, mutations and abnormal expression of cytoskeletal and cytoskeletal-associated proteins play an important role in the ability of cancer cells to resist chemotherapy and metastasize. Studies on the role of actin and its interacting partners have highlighted key signalling pathways, such as the Rho GTPases, and downstream effector proteins that, through the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An emerging role for MTs in tumour cell metastasis is being unravelled and there is increasing interest in the crosstalk between key MT interacting proteins and the actin cytoskeleton, which may provide novel treatment avenues for metastatic disease. Improved understanding of how the cytoskeleton and its interacting partners influence tumour cell migration and metastasis has led to the development of novel therapeutics against aggressive and metastatic disease. This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24. © 2014 The British Pharmacological Society.

  13. Colorectal cancer lung metastasis treatment with polymer-drug nanoparticles.

    Science.gov (United States)

    Rychahou, Piotr; Bae, Younsoo; Reichel, Derek; Zaytseva, Yekaterina Y; Lee, Eun Y; Napier, Dana; Weiss, Heidi L; Roller, Nick; Frohman, Heather; Le, Anh-Thu; Mark Evers, B

    2018-02-05

    Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis. Copyright © 2018. Published by Elsevier B.V.

  14. Non-migratory tumorigenic intrinsic cancer stem cells ensure breast cancer metastasis by generation of CXCR4(+) migrating cancer stem cells.

    Science.gov (United States)

    Mukherjee, S; Manna, A; Bhattacharjee, P; Mazumdar, M; Saha, S; Chakraborty, S; Guha, D; Adhikary, A; Jana, D; Gorain, M; Mukherjee, S A; Kundu, G C; Sarkar, D K; Das, T

    2016-09-15

    Although the role of metastatic cancer stem cells (mCSCs) in tumor progression has been well documented, our study reveals a hitherto unidentified role of tumorigenic intrinsic CSCs (iCSCs) in breast cancer metastasis. We show that unlike highly migratory mCSCs residing in the breast tumor disseminating/peripheral regions, iCSCs populate the inner mass of the tumor and are non-migratory. However iCSCs, via paracrine signaling, induce conversion of non-stem cancer cells to CSCs that (i) are identical to the previously reported mCSCs, and (ii) in contrast to iCSCs, express chemokine receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), which is crucial for their metastatic potential. These mCSCs also demonstrate high in vivo tumorigenicity. Physical non-participation of iCSCs in metastasis is further validated in vivo, where only mCSCs are found to exist in the metastatic sites, lymph nodes and bone marrow, whereas the primary tumor retains both iCSCs and mCSCs. However, iCSCs ensure metastasis since their presence is crucial for deliverance of highly metastatic CXCR4(+) mCSCs to the migrating fraction of cells. Cumulatively, these results unveil a novel role of iCSCs in breast cancer metastasis as parental regulators of CXCR4(+) mCSCs, and highlight the therapeutic requisite of targeting iCSCs, but not CXCR4(+) mCSCs, to restrain breast cancer metastasis from the root by inhibiting the generation of mCSCs from iCSCs. Considering the pivotal role of iCSCs in tumor metastasis, the possibility of metastasis to be a 'stem cell phenomena' is suggested.

  15. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis

    OpenAIRE

    Pollari, Sirkku; Kakonen, Sanna-Maria; Edgren, Henrik; Wolf, Maija; Kohonen, Pekka; Sara, Henri; Guise, Theresa,; Nees, Matthias; Kallioniemi, Olli

    2010-01-01

    Abstract Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, an understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidences for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic...

  16. FOXC2 promotes colorectal cancer metastasis by directly targeting MET.

    Science.gov (United States)

    Cui, Y-M; Jiao, H-L; Ye, Y-P; Chen, C-M; Wang, J-X; Tang, N; Li, T-T; Lin, J; Qi, L; Wu, P; Wang, S-Y; He, M-R; Liang, L; Bian, X-W; Liao, W-T; Ding, Y-Q

    2015-08-13

    Metastasis is the major cause of death in colorectal cancer (CRC). Although multiple genes have been identified to be responsible for the development of CRC, the molecular changes that enable CRC cells to undergo early local invasion and to form distant metastatic colonies still remain largely unknown. Herein, we investigated the role of Forkhead box protein C2 (FOXC2) and explored the underlying mechanisms in invasion and metastasis of CRC. We show that both high FOXC2 expression and nuclear localization of FOXC2 are significantly correlated with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis) stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted local invasion and distant metastasis in an orthotopic mouse metastatic model of CRC. Microarray analysis revealed that overexpression of FOXC2 increased the proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and chromatin immunoprecipitation assays revealed that FOXC2 directly associated with MET promoter to increase the transcriptional activity of MET. Inhibition of MET attenuates the invasive phenotype and metastatic potential of FOXC2-overexpressing CRC cells, indicating that MET is a major mediator of FOXC2-promoted metastasis. In addition, FOXC2 expression was positively correlated with MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET expression, highlighting FOXC2 as a potential therapeutic target for preventing or reducing metastasis in CRC.

  17. [Robo1 expression in non-small cell lung cancer and its brain metastasis].

    Science.gov (United States)

    Li, Xiao-xia; Jin, Ling; Sun, Zeng-feng; Gu, Feng; Li, Wen-liang; Ma, Yong-jie

    2013-03-01

    To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis. SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test. The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.

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

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

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

  19. Intratumor heterogeneity predicts metastasis of triple-negative breast cancer.

    Science.gov (United States)

    Yang, Fang; Wang, Yucai; Li, Quan; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhu, Aiyu; Li, Yan; Zhang, Wenwen; Wang, Yanru; Xie, Hui; Gustafsson, Jan-Åke; Wang, Shui; Guan, Xiaoxiang

    2017-09-01

    Even with the identical clinicopathological features, the ability for metastasis is vastly different among triple-negative breast cancer (TNBC) patients. Intratumor heterogeneity (ITH), which is common in breast cancer, may be a key mechanism leading to the tumor progression. In this study, we studied whether a quantitative genetic definition of ITH can predict clinical outcomes in patients with TNBC. We quantified ITH by calculating Shannon index, a measure of diversity in a population, based on Myc, epidermal growth factor receptor/centromeric probe 7 (EGFR/CEP7) and cyclin D1/centromeric probe 11 (CCND1/CEP11) copy number variations (CNVs) in 300 cells at three different locations of a tumor. Among 75 TNBC patients, those who developed metastasis had significantly higher ITH, that is Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs. Higher Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs were significantly associated with the development of metastasis and were predictive of significantly worse metastasis-free survival (MFS). Regional heterogeneity, defined as the difference in copy numbers of Myc, EGFR or CCND1 at different locations, was found in 52 patients. However, the presence of regional heterogeneity did not correlate with metastasis or MFS. Our findings demonstrate that higher ITH of EGFR/CEP7 and CCND1/CEP11 CNVs is predictive of metastasis and is associated with significantly worse MFS in TNBC patients, suggesting that ITH is a very promising novel prognostic factor in TNBC. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. 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.

  1. A Case of Suspected Breast Cancer Metastasis to Brachial Plexus Detected by Magnetic Resonance Neurography

    Directory of Open Access Journals (Sweden)

    Atsushi Mizuma

    2016-07-01

    Full Text Available Metastasis of breast cancer is often detected through a long-term course and difficult to diagnose. We report a case of brachial plexopathy suspected to be the initial lesion of breast cancer metastasis, which was only detected by magnetic resonance (MR neurography. A 61-year-old woman was admitted to our hospital within 2 years after operation for breast cancer because of progressive dysesthesia and motor weakness initially in the upper limb on the affected side and subsequently on the contralateral side. Enhanced computed tomography, axillary lymph node echo, gallium scintigraphy, and short tau inversion recovery MR images showed no abnormalities. MR neurography revealed a swollen region in the left brachial plexus. We suspected neuralgic amyotrophy and initiated treatment with intravenous immunoglobulin therapy and steroid therapy. However, there was no improvement, and the progression of motor weakness in the bilateral lower limbs appeared over 4 years. Concomitant elevation of carbohydrate antigen 15-3 level (58.9 U/ml led us to suspect breast cancer metastasis, which was associated with the worsening of neurological findings, although gallium scintigraphy and bone scintigraphy showed no inflammatory and metastatic lesions. Swelling of the cauda equina in enhanced lumbar MR imaging and abnormal accumulation at the brachial plexus and cervical spinal cord in positron-emission tomography were newly detected contrary to the normal findings on the gallium scintigraphy, which suggested cerebrospinal fluid seeding. We suspected breast cancer metastasis about the initial brachial plexopathy based on the clinical course. MR neurography may be a helpful tool to detect metastatic lesion, especially in nerve roots.

  2. Implications of para-aortic lymph node metastasis in patients with endometrial cancer without pelvic lymph node metastasis.

    Science.gov (United States)

    Todo, Yukiharu; Takeshita, Sho; Okamoto, Kazuhira; Yamashiro, Katsushige; Kato, Hidenori

    2017-09-01

    The aim of this study was to confirm the incidence and implications of a lymphatic spread pattern involving para-aortic lymph node (PAN) metastasis in the absence of pelvic lymph node (PLN) metastasis in patients with endometrial cancer. We carried out a retrospective chart review of 380 patients with endometrial cancer treated by surgery including PLN dissection and PAN dissection at Hokkaido Cancer Center between 2003 and 2016. We determined the probability of PAN metastasis in patients without PLN metastasis and investigated survival outcomes of PLN-PAN+ patients. The median numbers of PLN and PAN removed at surgery were 41 (range: 11-107) and 16 (range: 1-65), respectively. Sixty-four patients (16.8%) had lymph node metastasis, including 39 (10.3%) with PAN metastasis. The most frequent lymphatic spread pattern was PLN+PAN+ (7.9%), followed by PLN+PAN- (6.6%), and PLN-PAN+ (2.4%). The probability of PAN metastasis in patients without PLN metastasis was 2.8% (9/325). The 5-year overall survival rates were 96.5% in PLN-PAN-, 77.6% in PLN+PAN-, 63.4% in PLN+PAN+, and 53.6% in PLN-PAN+ patients. The likelihood of PAN metastasis in endometrial cancer patients without PLN metastasis is not negligible, and the prognosis of PLN-PAN+ is likely to be poor. The implications of a PLN-PAN+ lymphatic spread pattern should thus be taken into consideration when determining patient management strategies.

  3. 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

    2015-08-21

    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.

  4. Is tail vein injection a relevant breast cancer lung metastasis model?

    National Research Council Canada - National Science Library

    Rashid, Omar M; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine I; Schaum, Julia C; Yamada, Akimitsu; Aoyagi, Tomoyoshi; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2013-01-01

    TWO MOST COMMONLY USED ANIMAL MODELS FOR STUDYING BREAST CANCER LUNG METASTASIS ARE: lung metastasis after orthotopic implantation of cells into the mammary gland, and lung implantations produced after tail vein (TV) injection of cells...

  5. Colorectal Cancer Metastasis to the Thymus Gland: Rare Presentation of Colorectal Cancer as Anterior Mediastinal Mass

    Directory of Open Access Journals (Sweden)

    H. Charles Peters

    2017-01-01

    Full Text Available Despite improved screening modalities, 15–25% of newly diagnosed colorectal cancers are metastatic at the time of diagnosis. The vast majority of these cases present as hepatic metastasis; however, 22% present with concomitant extrahepatic disease. The thymus gland is an uncommon site of metastasis for any primary malignancy, particularly, colorectal cancer given its vascular and lymphatic drainage. This case report details our experience with a rare case of colorectal cancer metastasis to the thymus gland presenting as a symptomatic mediastinal mass.

  6. Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.

    Science.gov (United States)

    Okada, Yoshiyuki; Sonoshita, Masahiro; Kakizaki, Fumihiko; Aoyama, Naoki; Itatani, Yoshiro; Uegaki, Masayuki; Sakamoto, Hiromasa; Kobayashi, Takashi; Inoue, Takahiro; Kamba, Tomomi; Suzuki, Akira; Ogawa, Osamu; Taketo, M Mark

    2017-04-01

    A major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples. We then performed overexpression and knockdown of AES in human PCa cell lines LNCaP, DU145 and PC3, and determined the effects on proliferation, invasion and metastasis in culture and in a xenograft model. We also compared the PCa phenotypes of Aes/Pten compound knockout mice with those of Pten simple knockout mice. Expression levels of AES were inversely correlated with clinical stages of human PCa. Exogenous expression of AES suppressed the growth of LNCaP cells, whereas the AES knockdown promoted it. We also found that AES suppressed transcriptional activities of androgen receptor and Notch signaling. Notably, AES overexpression in AR-defective DU145 and PC3 cells reduced invasion and metastasis to lymph nodes and bones without affecting proliferation in culture. Consistently, prostate epithelium-specific inactivation of Aes in Ptenflox/flox mice increased expression of Snail and MMP9, and accelerated growth, invasion and lymph node metastasis of the mouse prostate tumor. These results suggest that AES plays an important role in controlling tumor growth and metastasis of PCa by regulating both AR and Notch signaling pathways. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. 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)

  8. Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

    Science.gov (United States)

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

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

  9. Wnt Signaling in Prostate Cancer Bone Metastases

    Science.gov (United States)

    2016-11-01

    Pten, Estrous Cycle MCB - 11 THE EFFECT OF HDACI (AR-42) ON CANINE PROSTATE CANCER METASTASIS. S. Elshafae1, N. Kohart1, L... canine prostate cancer overexpressing Dkk-1 was used in this study to investigate how enhanced Wnt/JNK signaling could alter tumor growth, metastasis and...metastatic phenotype of prostate cancer. Ace-1-Dkk-1, a canine prostate cancer overexpressing human Dkk-1, previously developed in our lab was used in

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  11. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

    Science.gov (United States)

    Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

    2015-04-15

    RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

  12. Application of bone scans for prostate cancer staging: Which guideline shows better result?

    Science.gov (United States)

    Chong, Ari; Hwang, Insang; Ha, Jung-min; Yu, Seong Hyeon; Hwang, Eu Chang; Yu, Ho Song; Kim, Sun Ouck; Jung, Seung-Il; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung

    2014-01-01

    Introduction: We evaluated the accuracy of current guidelines by analyzing bone scan results and clinical parameters of patients with prostate cancer to determine the optimal guideline for predicting bone metastasis. Methods: We retrospectively analyzed patients who were diagnosed with prostate cancer and who underwent a bone scan. Bone metastasis was confirmed by bone scan results with clinical and radiological follow-up. Serum prostate-specific antigen, Gleason score, percent of positive biopsy core, clinical staging and bone scan results were analyzed. We analyzed diagnostic performance in predicting bone metastasis of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA), and the National Comprehensive Cancer Network (NCCN) guidelines as well as Briganti’s classification and regression tree (CART). We also compared the percent of positive biopsy core between patients with and without bone metastases. Results: A total 167 of 806 patients had bone metastases. Receiver operating curve analysis revealed that the AUA and EAU guidelines were better for detecting bone metastases than were Briganti’s CART and NCCN. No significant difference was observed between AUA and EAU guidelines. Patients with bone metastases had a higher percent positive core than did patients without metastasis (the cut-off value >55.6). Conclusion: The EAU and AUA guidelines showed better results than did Briganti’s CART and NCCN for predicting bone metastasis in the enrolled patients. A bone scan is strongly recommended for patients who have a higher percent positive core and who meet the EAU and AUA guidelines. PMID:25210554

  13. Clinical significance of lymph node metastasis in gastric cancer

    Science.gov (United States)

    Deng, Jing-Yu; Liang, Han

    2014-01-01

    Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development...... lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes. RESULTS: Although GAGE proteins were strongly upregulated in the highly metastatic clone (CL16) compared to non-metastatic (NM2C5), weakly metastatic (M4A4......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  15. IMPLANTATION METASTASIS OF LARYNGEAL CANCER AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY

    Directory of Open Access Journals (Sweden)

    A. O. Guz

    2017-01-01

    Full Text Available Squamous cell head and neck carcinoma is frequently associated with dysphagia. An adequate enteral nutrition is the key to successful treatment and rehabilitation of these patients. Percutaneous endoscopic gastrostomy is the preferred route of feeding and nutritional support in head and neck cancer patients with dysphagia. We report a rare case of implantation metastasis of laryngeal cancer following percutaneous endoscopic gastrostomy. Our experience in treating this complication has been described. Percutaneous endoscopic gastrostomy is a less-invasive procedure than open gastrostomy. Percutaneous endoscopic gastrostomy can be accompanied by severe complications such as implantation metastasis at gastrostomy site. Careful monitoring can provide early detection of this complication and early treatment. 

  16. Pathology-confirmed granuloma mimicking liver metastasis of breast cancer.

    Science.gov (United States)

    Li, Ting; Fan, Minhao; Shui, Ruohong; Hu, Silong; Zhang, Yunyan; Hu, Xichun

    2014-03-24

    For patients with breast cancer, obtaining tissue samples from liver lesion becomes more and more important for both differential diagnosis and subsequent treatment. However, the procedure is not considered as mandatory routine and is not frequently performed. We here reported about a patient with breast cancer history and a solitary liver metastasis that was clinically diagnosed by both magnetic resonance imaging (MRI) and position emission tomography - computed tomography (PET-CT). However, pathologic diagnosis after partial hepatectomy (between sections VII and VIII) revealed multifocal granulomas. The case further addresses the importance of core needle biopsy, or surgical biopsy, for obtainment of a histological diagnosis, especially in the presence of a solitary lesion, even when the lesion has a typical medical imaging supporting metastasis, and uptake of radioactive 18F-fluorodeoxyglucose (18F-FDG) by PET-CT.

  17. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNF?-TGF?-EGFR

    OpenAIRE

    Lau, T-S; Chan, L K-Y; Wong, E C-H; Hui, C W-C; Sneddon, K; Cheung, T-H; Yim, S-F; Lee, J H-S; Yeung, C S-Y; Chung, T K-H; Kwong, J.

    2017-01-01

    Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-?) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor ...

  18. 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.

  19. Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis.

    Science.gov (United States)

    Narkhede, Akshay A; Shevde, Lalita A; Rao, Shreyas S

    2017-09-15

    The progression of breast cancer from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at specific organ sites is known to play a key role in influencing the ultimate fate of metastatic cells; yet microenvironmental mediated-molecular mechanisms underlying organ specific metastasis in breast cancer are not well understood. This review discusses biomimetic strategies employed to recapitulate metastatic organ microenvironments, particularly, bone, liver, lung and brain to elucidate the mechanisms dictating metastatic breast cancer cell homing and colonization. These biomimetic strategies include in vitro techniques such as biomaterial-based co-culturing techniques, microfluidics, organ-mimetic chips, bioreactor technologies, and decellularized matrices as well as cutting edge in vivo techniques to better understand the interactions between metastatic breast cancer cells and the stroma at the metastatic site. The advantages and disadvantages of these systems are discussed. In addition, how creation of biomimetic models will impact breast cancer metastasis research and their broad utility is explored. © 2017 UICC.

  20. Exosomal tetraspanins mediate cancer metastasis by altering host microenvironment.

    Science.gov (United States)

    Lu, Jun; Li, Jun; Liu, Shuo; Wang, Teng; Ianni, Alessandro; Bober, Eva; Braun, Thomas; Xiang, Rong; Yue, Shijing

    2017-09-22

    The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion. The exosomal tetraspanin network is a molecular scaffold connecting various proteins for signaling transduction. The complex of tetraspanin-integrin determines the recruiting cancer exosomes to pre-metastatic sites. Tetraspanin is a key element for the target cell selection of exosomes uptake that may lead to the reprogramming of target cells. Reprogrammed target cells assist pre-metastatic niche formation. Previous reviews have described the biogenesis, secretion and intercellular interaction of exosomes in various tumors. However, there is a lack of reviews on the topic of exosomal tetraspanin in the context of cancer. In this review, we will describe the main characteristics of exosomal tetraspanin in cancer cells. We will also discuss how the cancer exosomal tetraspanin alters extracellular environment and regulates cancer metastasis.

  1. Raman spectroscopy for cancer detection and characterization in metastasis models

    Science.gov (United States)

    Koga, Shigehiro; Oshima, Yusuke; Sato, Mitsunori; Ishimaru, Kei; Yoshida, Motohira; Yamamoto, Yuji; Matsuno, Yusuke; Watanabe, Yuji

    2017-02-01

    Raman spectroscopy provides a wealth of diagnostic information to the surgeon with in situ cancer detection and label-free histopathology in clinical practice. Raman spectroscopy is a developing optical technique which can analyze biological tissues with light scattering. The difference in frequencies between the incident light and the scattering light are called Raman shifts, which correspond to the vibrational energy of the molecular bonds. Raman spectrum gives information about the molecular structure and composition in biological specimens. We had been previously reported that Raman spectroscopy could distinguish various histological types of human lung cancer cells from normal cells in vitro. However, to identify and detect cancer diagnostic biomarkers in vivo on Raman spectroscopy is still challenging, because malignancy can be characterized not only by the cancer cells but also by the environmental factors including immune cells, stroma cells, secretion vesicles and extracellular matrix. Here we investigate morphological and molecular dynamics in both cancer cells and their environment in xenograft models and spontaneous metastasis models using Raman spectroscopy combined with fluorescence microscopy and photoluminescence imaging. We are also constructing a custom-designed Raman spectral imaging system for both in vitro and in vivo assay of tumor tissues to reveal the metastasis process and to evaluate therapeutic effects of anti-cancer drugs and their drug delivery toward the clinical application of the technique.

  2. CCR1-mediated accumulation of myeloid cells in the liver microenvironment promoting mouse colon cancer metastasis.

    Science.gov (United States)

    Hirai, Hideyo; Fujishita, Teruaki; Kurimoto, Kazuki; Miyachi, Hitoshi; Kitano, Satsuki; Inamoto, Susumu; Itatani, Yoshiro; Saitou, Mitinori; Maekawa, Taira; Taketo, M Mark

    2014-12-01

    To understand colon cancer metastasis, we earlier analyzed a mouse model that developed liver metastasis of cancer cells disseminated from the spleen. We suggested that CCR1(+) bone marrow (BM)-derived cells are recruited to the microenvironment of disseminated colon cancer cells, and produce metalloproteinases MMP9 and MMP2, helping metastatic colonization. In the present study, we have examined these myeloid cells expressing CCR1 and/or MMPs in detail. To this end, we have established bacterial artificial chromosome (BAC)-based transgenic mouse lines in which membrane-targeted Venus fluorescent protein (mVenus) was expressed under the control of Ccr1 gene promoter. Then, myeloid cells obtained from the BM and liver metastatic foci were analyzed by the combination of flow cytometry and cytology/immunohistochemistry, in situ RNA hybridization, or quantitative RT-PCR. We have found four distinct types of myeloid cells recruited to the metastatic foci; neutrophils, eosinophils, monocytes and fibrocytes. These cell types exhibited distinct expression patterns for CCR1, MMP2 and MMP9. Namely, neutrophils found in the early phase of cancer cell dissemination expressed CCR1 exclusively and MMP9 preferentially, whereas fibrocytes accumulated in later phase expressed MMP2 exclusively. Either genetic inactivation of Ccr1 or antibody-mediated neutrophil depletion reduced subsequent recruitment of fibrocytes. The recruitment of CCR1(+) neutrophils in early phase of colon cancer dissemination appears to cause that of fibrocytes in late phase. These results implicate the key role of CCR1 in colon cancer metastasis in this mouse model, and explain why both MMP9 and MMP2 are essential as genetically demonstrated previously. The results also suggest relevant mechanisms in humans.

  3. 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

  4. Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Distant metastasis of primary neoplasms is the main factor that limits the success of antineoplastic therapy. It can be regarded as an early or late event in the neoplastic process, and varies considerably with tumor type. The metastatic potential of a given tumor greatly influences prognosis. Tumor metastasis is not a single neoplastic event, rather, it involves several major steps: invasion of cells from the primary tumor into tissue, and penetration of blood and lymph vessels; release of tumor cell emboli into the circulation; arrest of the emboli in capillary beds of distant organs; invasion of the wall of the arresting vessel, infiltration into adjacent tissue, and multiplication; and growth of vascularized stroma into the new tumor as proliferating tumor cells invade the distant organ. Lodgement and invasion are complex events that are not fully defined. Arrest and lodgement appears to require a thromboembolic event in which the metastatic embolis (1 cell) contacts vascular endothelium and adheres to the wall with thrombis formation following aggregation of platelets and fibrin to the tumor cell(s). Invasion may involve: formation of collagenases by tumor cells; mechanical disruption; chemotactic factors. Metastatic patterns depend on the route of metastasis, tumor type, and target organ (favored soil). In general, carcinomas metastasize via lymphatics and sarcomas via hematogenous routes. Others, melanoma, mast cell tumors, etc., show mixed patterns. This knowledge is important when one is attempting to prognostically stage a tumor, especially when thoracic radiographs are negative. The question of enlarged regional lymph nodes will be discussed in lecture relative to specific tumor types. 4 refs., 1 tab.

  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. Metastasis of breast cancer to renal cancer: report of a rare case.

    Science.gov (United States)

    Huo, Zhijun; Gao, Yongsheng; Yu, Zhiyong; Zuo, Wenshu; Zhang, Yanfang

    2015-01-01

    Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.

  7. 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.

  8. Cancer as a Proinflammatory Environment: Metastasis and Cachexia

    Science.gov (United States)

    Inácio Pinto, Nelson; Carnier, June; Oyama, Lila M.; Otoch, Jose Pinhata; Alcântara, Paulo Sergio; Tokeshi, Flavio; Nascimento, Claudia M.

    2015-01-01

    The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines. PMID:26508818

  9. Skeletal-related events due to bone metastases from differentiated thyroid cancer.

    Science.gov (United States)

    Farooki, Azeez; Leung, Vivien; Tala, Hernan; Tuttle, R Michael

    2012-07-01

    In oncology, the clinical impact of metastatic bone disease is conveyed via a composite end point termed skeletal-related events (SRE), which encompasses spinal cord compression, pathological fracture, a need for external beam radiation or surgery to bone, and hypercalcemia of malignancy. An appreciation for the high incidence of SRE in other advanced cancers involving the bone has led to the approval of potent antiresorptive agents because they delay the time to the first SRE and decrease the incidence of SRE. The risk and rate of SRE after diagnosis of bone metastasis have not been described in thyroid cancer; antiresorptive agents are not routinely used. This was a retrospective review of 245 differentiated thyroid cancer patients with bone metastases identified as part of routine clinical care at Memorial Sloan-Kettering Cancer Center between 1960 and 2011. The occurrence of SRE was recorded from the initial diagnosis of bone metastasis until final follow-up or death. Seventy-eight percent of patients (192 of 245) either presented with or developed at least one SRE after the diagnosis of metastatic bone disease. The median time from identification of bone metastasis to first SRE was 5 months (excluding the 97 patients in whom first SRE occurred at the time of the bone metastasis diagnosis). Of the patients who sustained an initial SRE, 65% (120 of 192) went on to sustain a second SRE at a median of 10.7 months after the first event. SRE were frequently multiple; 39% (74 of 192) sustained three or more discrete SRE. Thyroid cancer bone metastases identified as part of routine clinical follow-up frequently cause significant and recurrent morbidity. The incidence of SRE and median time to first SRE in metastatic thyroid cancer to bone are similar to those reported in other solid tumors. Prospective clinical trials to assess the efficacy of antiresorptive agents in this population are needed.

  10. 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.

  11. 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.

  12. Adenoid Cystic Carcinoma of the Buccal Mucosa with Rare Delayed Frontal Bone Metastasis: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Dalirsani

    2016-10-01

    Full Text Available Adenoid cystic carcinoma (AdCC is a malignant neoplasm, which accounts for 5-10% of all salivary gland tumors (1. About 50% of these tumors originate from intraoral minor salivary glands usually in the hard palate (1. Three clinically obvious characteristics of AdCC include slow growth rate, perineural invasion and high incidence of distant metastasis (1. The most commonly-affected sites of distant metastasis are bone, liver and brain, followed by lungs (2. Lymph node metastases are rare;  The most common sites  involved by hematogenous spread are lungs (2.  This is a report about a patient with a rare form of AdCC on buccal mucosa with an unusual metastasis to the frontal region after a two-year follow up.

  13. Metastasis Dormancy in Estrogen Receptor-Positive Breast Cancer

    Science.gov (United States)

    Zhang, Xiang H.-F.; Giuliano, Mario; Trivedi, Meghana V.; Schiff, Rachel; Kent Osborne, C.

    2013-01-01

    About 20-40% of breast cancer patients eventually develop recurrences in distant organs, which are often not detected until years to decades after the primary tumor diagnosis. This phenomenon is especially pronounced in ER+ breast cancer, suggesting that ER+ cancer cells may stay dormant for a protracted period of time, despite adjuvant therapies. Multiple mechanisms have been proposed to explain how cancer cells survive and remain in dormancy , and how they become reactivated and exit dormancy. These mechanisms include angiogenic switch, immunosurveillance, and interaction with extracellular matrix (ECM) and stromal cells. How to eradicate or suppress these dormant cancer cells remains a major clinical issue because of the lack of knowledge about the biological and clinical nature of these cells. Herein, we review the clinical manifestation of metastasis dormancy in ER+ tumors, the current biological insights of tumor dormancy obtained from various experimental models, and the clinical challenges to predict, detect, and treat dormant metastases. We also discuss future research directions toward a better understanding of the biological mechanisms and clinical management of ER+ dormant metastasis. PMID:24298069

  14. Identification of intramural metastasis in esophageal cancer using multiphoton microscopy

    Science.gov (United States)

    Xu, Jian; Kang, Deyong; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, jiangbo; Chen, Jianxin

    2017-02-01

    Intramural metastasis (IM) of esophageal cancer is defined as metastasis from a primary lesion to the esophageal wall without intraepithelial cancer extension. Esophageal cancer with IM is more common and such cases indicate a poor prognosis. In esophageal surgery, if curative resection is possible, the complete removal of both primary tumor and associated IMs is required. Therefore, accurate diagnosis of IMs in esophageal cancer prior to surgery is of particular importance. Multiphoton microscopy (MPM) with subcellular resolution is well-suited for deep tissue imaging since many endogenous fluorophores of fresh biological tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Here, a study to identify IM in fresh tissue section using MPM is reported. In this study, the morphological and spectral differences between IM and surrounding tissue are described. These results show that MPM has the ability to accurately identify IM in esophageal tissues. With improvement of the penetration depth of MPM and the development of multiphton microendoscope, MPM may be a promising imaging technique for preoperative diagnosis of IMs in esophageal cancer in the future.

  15. Targeting Neuromimicry in Prostate Cancer Metastasis

    Science.gov (United States)

    2016-10-01

    validate MAOA/NRP1- manipulated PCa cells with stable labeling of fluorescence protein and Luc for subsequently visualizing MAOA/NRP1-mediated PCa-nerve...prostate cancer cells which were further subjected to stable labeling of fluorescence protein and luciferase for subsequent visualization of MAOA...followed by genetic manipulation of MAOA and NRP1 expression by either plasmid-based overexpression or shRNA-mediated silencing. Months 1-4 Dr. Wu

  16. Lysyl oxidase in cancer inhibition and metastasis.

    Science.gov (United States)

    Johnston, Kathryn A; Lopez, Karlo M

    2018-01-05

    Lysyl oxidase is an extracellular matrix, copper - dependent amine oxidase that catalyzes a key enzymatic step in the crosslinking of collagen and elastin. The enzyme is synthesized as a propeptide that is cleaved by procollagen - C - proteinase into two distinct parts: the mature form and the LOX propeptide. The mature enzyme plays a key role in modifying the extracellular matrix and as a result has been implicated in playing a role in the formation of cancer "niches" where tumors will develop and eventually metastasize. On the other hand, the LOX propeptide has been shown to have an inhibitory effect in the development of cancer tumors. New approaches are being developed to test the use of small molecule inhibitors on LOX; however, the lack of a crystal structure has hampered these efforts as it is extremely difficult to design selective inhibitors without knowing what the target receptor looks like. In this mini review we discuss the lysyl oxidase enzyme and its role several types of cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. 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.

  18. Metastasis Suppressor Gene Inactivates Actin-Based Mechanism of Tumor Cell Motility | Center for Cancer Research

    Science.gov (United States)

    Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with other proteins.

  19. TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model.

    Science.gov (United States)

    Fritsche, Hendrik; Heilmann, Thorsten; Tower, Robert J; Hauser, Charlotte; von Au, Anja; El-Sheikh, Doaa; Campbell, Graeme M; Alp, Göhkan; Schewe, Denis; Hübner, Sebastian; Tiwari, Sanjay; Kownatzki, Daniel; Boretius, Susann; Adam, Dieter; Jonat, Walter; Becker, Thomas; Glüer, Claus C; Zöller, Margot; Kalthoff, Holger; Schem, Christian; Trauzold, Anna

    2015-04-20

    Despite improvements in detection, surgical approaches and systemic therapies, breast cancer remains typically incurable once distant metastases occur. High expression of TRAIL-R2 was found to be associated with poor prognostic parameters in breast cancer patients, suggesting an oncogenic function of this receptor. In the present study, we aimed to determine the impact of TRAIL-R2 on breast cancer metastasis. Using an osteotropic variant of MDA-MB-231 breast cancer cells, we examine the effects of TRAIL-R2 knockdown in vitro and in vivo. Strikingly, in addition to the reduced levels of the proliferation-promoting factor HMGA2 and corresponding inhibition of cell proliferation, knockdown of TRAIL-R2 increased the levels of E-Cadherin and decreased migration. In vivo, these cells were strongly impaired in their ability to form bone metastases after intracardiac injection. Evaluating possible underlying mechanisms revealed a strong downregulation of CXCR4, the receptor for the chemokine SDF-1 important for homing of cancers cells to the bone. In accordance, cell migration towards SDF-1 was significantly impaired by TRAIL-R2 knockdown. Conversely, overexpression of TRAIL-R2 upregulated CXCR4 levels and enhanced SDF-1-directed migration. We therefore postulate that inhibition of TRAIL-R2 expression could represent a promising therapeutic strategy leading to an effective impairment of breast cancer cell capability to form skeletal metastases.

  20. The Role of chemokine receptor CXCR4 in breast cancer metastasis

    National Research Council Canada - National Science Library

    Mukherjee, Debarati; Zhao, Jihe

    2013-01-01

    .... Recent advances in the field of cancer biology has pointed to the critical role that CXCR4 receptor and its ligand CXCL12 play in the metastasis of various types of cancer, including breast cancer...

  1. [Bilateral adrenal hemorrhage due to adrenal metastasis of lung cancer].

    Science.gov (United States)

    Tamura, Keita; Furuse, Hiroshi; Sugiyama, Takayuki; Kato, Taiki; Suzuki, Takahisa; Kai, Fumitake; Nagata, Masao; Otsuka, Atsushi; Takayama, Tatsuya; Ishii, Yasuo; Mugiya, Soichi; Ozono, Seiichiro

    2013-01-01

    A 58-year-old man presented with nausea and left flank pain. The patient was referred to our hospital based on clear detection of anemia and computed tomography findings of bilateral adrenal tumors with hemorrhage and a mass in the apex of the left lung. Right adrenal artery embolization had no effect on enlargement of the right adrenal hematoma or advanced anemia. Right adrenalectomy was then performed in an attempt to control hemorrhaging and make a definitive diagnosis, and the patient's anemia improved following the operation. Histopathological diagnosis suggested adrenal metastasis of lung adenocarcinoma, which was subsequently diagnosed given similarities in transbronchial biopsy findings to those in the right adrenal gland. Adrenal hemorrhage due to metastasis of lung cancer is an extremely rare condition; indeed, to our knowledge, the present case is only the 26th reported worldwide. However, prognosis for this mortal condition may be improved should patients receive adrenalectomy followed by an appropriate treatment regimen.

  2. 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.

  3. Parotid gland metastasis of a breast cancer.

    Science.gov (United States)

    Perez-Fidalgo, J A; Chirivella, I; Laforga, J; Colio, J M; Blanes, M D; Baydal, R; Roselló, S; De-la-Morena, E; Lluch, A

    2007-04-01

    Parotid gland metastases from malignant tumors are extremely rare. A 61-year-old woman was diagnosed with an early breast cancer with no expression of oestrogen and progesterone receptors. Five years later the patient presented a tumour in parotid gland. After total parotidectomy, microscopic analysis of the gland demonstrated an invasive duct carcinoma (IDC) with positive expression of oestrogen receptor. The patient was treated with chemotherapy followed by complementary local radiotherapy. Diagnosis of a metastasic tumour in parotid gland poses a challenge. In our case an immunohistochemical study of oestrogen receptor was fundamental to establish a diagnosis.

  4. Esophageal Metastasis From Occult Lung Cancer

    Directory of Open Access Journals (Sweden)

    Po-Kuei Hsu

    2010-06-01

    Full Text Available A 66-year-old man with dysphagia was found to have a poorly differentiated esophageal carcinoma by incision biopsy. Following esophagectomy, reconstruction with a gastric tube was performed. Pathological examination and immunohisto-chemistry showed infiltration of adenocarcinoma cells with positive thyroid transcription factor 1-staining in the submucosal layer, which indicated metastatic esophageal carcinoma. Although no pulmonary lesion could be visualized by imaging or bronchoscopy, pulmonary origin was highly suspected as a result of positive thyroid transcription factor 1-staining. To the best of our knowledge, this is the first reported case of metastatic esophageal carcinoma from occult lung cancer (AJCC TNM stage TX.

  5. Diagnosis of Cardiac Metastasis from Endometrial Cancer by F-18 FDG-PET/CT.

    Science.gov (United States)

    Liu, T; Khan, S; Behr, S; Aparici, C Mari

    2014-09-01

    We report a case of a 59-year-old woman with right ventricular metastasis of undifferentiated endometrial cancer. Cardiac metastasis from endometrial cancer is a very rare finding. The case demonstrates that undifferentiated endometrial cancer is capable of metastasizing, presumably through a hematogenous route, to unexpected distant organs. These unexpected sites should not be undermined in the restaging and surveillance of these patients.

  6. Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Mi, Fei; Gong, Liansheng

    2017-08-31

    Mesenchymal stem cells (MSCs) interact with tumor cells and regulate tumorigenesis and metastasis. As one of the important components of the tumor microenvironment, MSC-secreted cytokines play a critical role in cancer development. However, whether and how bone marrow MSCs (BMSCs) and their secreted cytokines participate in hepatocellular carcinoma (HCC) progression, still remains largely unknown. In the present study, we first measured the concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM). Next, we assessed the changes of invasion ability in response to treatment of BMSC-CM or recombinant IL-6 in two human HCC cell lines Bel-7404 and HepG2. Then we analyzed the level of key components of the IL-6 signal pathway, including IL-6 receptor and signal transducer (i.e. IL-6R and gp130), a transcription factor STAT3 (signal transducer and activator of transcription 3), as well as its target genes BCL2, CCND1, MCL1 and MMP2, in BMSC-CM or recombinant IL-6 treated Bel-7404 and HepG2 cells. Results showed that a considerable amount of IL-6 was secreted by BMSCs, and BMSC-CM markedly elevated Bel-7404 cell invasion rate and stimulated the signal transduction of IL-6/STAT3 pathway. Neutralizing the secreted IL-6 bioactivity by the anti-IL-6 antibody diminished the invasion-promoting effect and down-regulated IL-6/STAT3 pathway of BMSC-CM treated Bel-7404 cells. In conclusion, we found that BMSCs may activate the IL-6/STAT3 signaling pathway and promote cell invasion in Bel-7404 cells, suggesting that this protumor effect should be seriously considered before clinical application of MSC-mediated cancer therapy. © 2017 The Author(s).

  7. Genomic Evolution of Breast Cancer Metastasis and Relapse.

    Science.gov (United States)

    Yates, Lucy R; Knappskog, Stian; Wedge, David; Farmery, James H R; Gonzalez, Santiago; Martincorena, Inigo; Alexandrov, Ludmil B; Van Loo, Peter; Haugland, Hans Kristian; Lilleng, Peer Kaare; Gundem, Gunes; Gerstung, Moritz; Pappaemmanuil, Elli; Gazinska, Patrycja; Bhosle, Shriram G; Jones, David; Raine, Keiran; Mudie, Laura; Latimer, Calli; Sawyer, Elinor; Desmedt, Christine; Sotiriou, Christos; Stratton, Michael R; Sieuwerts, Anieta M; Lynch, Andy G; Martens, John W; Richardson, Andrea L; Tutt, Andrew; Lønning, Per Eystein; Campbell, Peter J

    2017-08-14

    Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Signaling pathways in breast cancer metastasis - novel insights from functional genomics

    Science.gov (United States)

    2011-01-01

    The advent of genomic profiling technology has brought about revolutionary changes in our understanding of breast cancer metastasis. Gene expression analyses of primary tumors have been used to predict metastatic propensity with high accuracy. Animal models of metastasis additionally offer a platform to experimentally dissect components of the metastasis genetic program. Recent integrated studies have synergized clinical bioinformatic analyses with advanced experimental methodology and begun to uncover the identities and dynamics of signaling programs driving breast cancer metastasis. Such functional genomics studies hold great promise for understanding the genetic basis of metastasis and improving therapeutics for advanced diseases. PMID:21457525

  9. A Rare Tumor with a Very Rare Initial Presentation: Thymic Carcinoma as Bone Marrow Metastasis

    Directory of Open Access Journals (Sweden)

    Sonam Sharma

    2017-01-01

    Full Text Available Tumors of thymus gland are rare and account for 0.2% to 1.5% of all the neoplasms. They constitute a heterogeneous group that has an unknown etiology and a complex as well as varied biology. This has led to difficulty in their histological classification and in predicting their prognostic and survival markers. Among them, thymic carcinoma is the most aggressive thymic epithelial tumor exhibiting cytological malignant features and a diversity of clinicopathological characteristics that can cause diagnostic dilemmas, misdiagnosis, and therapeutic challenge. We herein describe a case of a 60-year-old man who while undergoing evaluation for the cause of pancytopenia was discovered having bone marrow metastasis from an asymptomatic thymic carcinoma. Bone marrow metastasis is an extremely rare initial presentation of thymic carcinoma with only few cases reported in the literature.

  10. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia.

    Science.gov (United States)

    Aljafar, Hadeel M; Alsuhibani, Sari S; Alahmari, Mohammad S; Alzahrani, Musaed A

    2015-10-01

    Otologic manifestations in chronic lymphocytic leukemia (CLL) are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhagic bullae on the posterior segment of tympanic membrane. Left sided facial paralysis developed on the third day of admission. Full recovery of facial paralysis is achieved by 10 days course of corticotherapy. Histological examination of middle ear tissue biopsy showed infiltration by monotonous small lymphoid cells, showing round nuclei, condensed chromatin suggestive of CLL. Although rare, unusual otologic manifestations should raise the suspicion of a temporal bone metastasis as a sign of relapsing CLL.

  11. Which metastasis management allows long-term survival of synchronous solitary M1b non-small cell lung cancer?

    Science.gov (United States)

    Mordant, Pierre; Arame, Alex; De Dominicis, Florence; Pricopi, Ciprian; Foucault, Christophe; Dujon, Antoine; Le Pimpec-Barthes, Françoise; Riquet, Marc

    2012-03-01

    OBJECTIVES; Patients with extrathoracic synchronous solitary metastasis and non-small cell lung cancer (NSCLC) are rare. The effectiveness of both tumour sites resection is difficult to evaluate because of the high variability among clinical studies. We reviewed our experience regarding the management and prognosis of these patients. The charts of 4668 patients who underwent lung cancer surgery from 1983 to 2006 were retrospectively reviewed. We analysed the epidemiology, treatment, pathology and prognostic characteristics of those with extrathoracic synchronous solitary metastasis amenable to lung cancer surgery on a curative intend. There were 94 patients (sex ratio M/F 3.2/1, mean age 56 years). Surgery included pneumonectomy (n = 27), lobectomy (n = 65) and exploratory thoracotomy (n = 2). Pathology revealed adenocarcinomas (n = 57), squamous cell carcinoma (n = 20), large cell carcinoma (n = 14) and other NSCLC histology (n = 3). Lymphatic extension was N0 (n = 46), N1 (n = 17) and N2 (n = 31). Metastasis involved the brain (n = 57), adrenal gland (n = 12), bone (n = 14), liver (n = 5) and skin (n = 6). Sixty-nine metastases were resected. Five-year survival rate was 16% (median 13 months). Induction therapy, adenocarcinoma, N0 staging and lobectomy were criteria of better prognosis, but metastasis resection was not. These results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve long-term survival in the case of lung resection with or without metastasis resection. This pattern may reflect a specific tumour biology whose solitary metastasis benefits both from surgical or non-surgical treatment.

  12. Naringenin reduces lung metastasis in a breast cancer resection model.

    Science.gov (United States)

    Qin, Lei; Jin, Lingtao; Lu, Linlin; Lu, Xiaoyan; Zhang, Chunling; Zhang, Fayun; Liang, Wei

    2011-06-01

    Metastasis is the main cause of death in cancer patients. To improve the outcomes of patients undergoing a surgery, new adjuvant therapies that can effectively inhibit metastases have to be developed. Studies have shown that flavonoid naringenin, a natural product that is mainly present in grapes and citrus, may contribute to cancer prevention. It has many advantages compared to traditional chemotherapeutic drugs, such as low toxicity. To determine whether naringenin can also inhibit metastases, a breast cancer resection model that mimics clinical situations was established. We found that orally administered naringenin significantly decreased the number of metastatic tumor cells in the lung and extended the life span of tumor resected mice. Flow cytometry analysis revealed that T cells displayed enhanced antitumor activity in naringenin treated mice, with an increased proportion of IFN-γ and IL-2 expressing T cells. In vitro studies further demonstrated that relief of immunosuppression caused by regulatory T cells might be the fundamental mechanism of metastasis inhibition by naringenin. These results indicate that orally administered naringenin can inhibit the outgrowth of metastases after surgery via regulating host immunity. Thus, naringenin can be an ideal surgical adjuvant therapy for breast cancer patients.

  13. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Regulation of microRNAs in Cancer Metastasis

    Science.gov (United States)

    Bouyssou, Juliette M.C.; Manier, Salomon; Huynh, Daisy; Issa, Samar; Roccaro, Aldo M.; Ghobrial, Irene M.

    2014-01-01

    Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process. PMID:24569228

  15. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia

    OpenAIRE

    Aljafar, Hadeel M.; Alsuhibani, Sari S.; Alahmari, Mohammad S.; Alzahrani, Musaed A.

    2015-01-01

    Otologic manifestations in chronic lymphocytic leukemia (CLL) are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhag...

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

    Directory of Open Access Journals (Sweden)

    Janet M Pavese

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

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

    Directory of Open Access Journals (Sweden)

    Ramandeep Rattan

    2012-01-01

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

  18. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis.

    Science.gov (United States)

    Cooperberg, Matthew R; Broering, Jeanette M; Carroll, Peter R

    2009-06-16

    Although many tools for the assessment of prostate cancer risk have been published, most are designed to predict only biochemical recurrence, usually after a single specified treatment. We assessed the accuracy of the Cancer of the Prostate Risk Assessment (CAPRA) score, which was validated previously to predict pathological and biochemical outcomes after radical prostatectomy, to predict metastases, prostate cancer-specific mortality, and all-cause mortality. We studied 10 627 men with clinically localized prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor registry, who underwent primary radical prostatectomy, radiation therapy (external beam or interstitial), androgen deprivation monotherapy, or watchful waiting/active surveillance, and had at least 6 months of follow-up after treatment. CAPRA scores were calculated at diagnosis from the prostate-specific antigen level, Gleason score, percentage of biopsy cores that were positive for cancer, clinical tumor stage, and age at diagnosis. Survival was studied with Kaplan-Meier analyses. Associations between increasing CAPRA scores and bone metastasis, cancer-specific mortality, and all-cause mortality were examined by use of proportional hazards regression, with adjustment for primary treatment; for all-cause mortality, the analysis also included adjustment for age and comorbidity. Accuracy of the CAPRA score was assessed with the concordance (c)-index. Among the 10 627 patients, 311 (2.9%) men developed bone metastases, 251 (2.4%) died of prostate cancer, and 1582 (14.9%) died of other causes. Each single-point increase in the CAPRA score was associated with increased bone metastases (hazard ratio [HR] for bone metastases = 1.47, 95% confidence interval [CI] = 1.39 to 1.56), cancer-specific mortality (HR for prostate cancer death = 1.39, 95% CI = 1.31 to 1.48), and all-cause mortality (HR for death = 1.13, 95% CI = 1.10 to 1.16). The CAPRA score was accurate for predicting metastases

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

    Science.gov (United States)

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

    2017-01-01

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

  20. 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.

  1. 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.

  2. Use of bone scan during initial prostate cancer workup, downstream procedures, and associated Medicare costs.

    Science.gov (United States)

    Falchook, Aaron D; Salloum, Ramzi G; Hendrix, Laura H; Chen, Ronald C

    2014-06-01

    For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  4. Isolated breast metastasis from gastric cancer in a male patient.

    Science.gov (United States)

    Kubo, Hirokazu; Shimizu, Tetsuya; Sekido, Hitoshi; Matsuda, Goro; Takeda, Kazuhisa; Watanabe, Akira; Sakamoto, Risa; Yamamoto, Yuji; Toyoda, Junya; Niino, Hitoshi

    2018-01-04

    A 72-year-old man underwent total gastrectomy for gastric cancer (por2, T3, N2, Stage IIIA). Eleven courses of postoperative chemotherapy with TS-1 (tegafur/gimeracil/oteracil) were administered. Five months after surgery, the serum carcinoembryonic antigen value was slightly elevated. However, computed tomography did not reveal any metastatic lesions in other organs. Two years after surgery, the patient felt a mass in the left mammary. A 2-cm tumor was palpable in the central portion of the breast. Ultrasonography revealed a hypoechoic tumor, which was Class 3 on aspiration biopsy cytological examination. No mass was detected on positron emission tomography-computed tomography. The mammary gland tumor increased in size to 3 cm, and a core needle biopsy procedure was performed. Histological examination findings revealed breast metastasis of gastric cancer. No other recurrence was found, and radical mastectomy was performed 2 years and 5 months after gastrectomy. Immunohistological analysis of the resected material confirmed breast metastasis of the gastric cancer. Two courses of TS-1 + cisplatin were administered, but this treatment was subsequently terminated because the patient experienced Grade 3 diarrhea and neutropenia. Three years and 1 month after the gastrectomy, the tumor recurred in the pelvic area. Chemotherapy and radiation therapy were performed, but the patient's overall condition became progressively worse, and he died 3 years and 9 months after gastrectomy.

  5. Epigenetic regulator RBP2 is critical for breast cancer progression and metastasis

    Science.gov (United States)

    Cao, Jian; Liu, Zongzhi; Cheung, William K.C.; Zhao, Minghui; Chen, Sophia Y.; Chan, Siew Wee; Booth, Carmen J.; Nguyen, Don X.; Yan, Qin

    2014-01-01

    Summary Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that epigenetic aberrations contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene expression datasets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes. In addition, RBP2 loss suppresses tumor formation in the MMTV-neu transgenic mice. These results suggest that therapeutically targeting RBP2 is a potential strategy to inhibit tumor progression and metastasis. PMID:24582965

  6. "Hidden" bone metastasis from thyroid carcinoma: a clinical note.

    Science.gov (United States)

    Sioka, C; Skarulis, M C; Tulloch-Reid, M K; Heiss, J D; Reynolds, J C

    2014-01-01

    The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  7. CD47 Promotes Tumor Invasion and Metastasis in Non-small Cell Lung Cancer

    OpenAIRE

    Hui Zhao; Jianxin Wang; Xiaodan Kong; Encheng Li; Yuanbin Liu; Xiaohui Du; Zhijie Kang; Ying Tang; Yanbin Kuang; Zhihui Yang; Youwen Zhou; Qi Wang

    2016-01-01

    CD47 is overexpressed in many human cancers, its level positively correlates with tumor invasion and metastasis. However, it is largely unknown whether CD47 overexpression drives metastasis and how CD47 lead to tumor metastasis in non-small cell lung cancer (NSCLC). In this study, we analyzed NSCLC specimens and cell lines, and revealed that CD47 is expressed at a higher level than in tumor-free control samples. Furthermore, increased CD47 expression correlated with clinical staging, lymph no...

  8. Sacrum colon-rectal cancer metastasis: microwave ablation for palliative pain treatment.

    Science.gov (United States)

    Maiettini, Daniele; De Angelis, Verena; Graziosi, Luigina; Rebonato, Stefania; Falcinelli, Lorenzo; Metro, Giulio; Rebonato, Alberto

    2016-12-01

    Local treatment of bone metastasis (BM) remains controversial in colon-rectum carcinoma for pain control. A patient developed a sacrum BM 4years after a left colectomy for an adenocarcinoma. Metastasis was treated in one session of CT-guided microwave ablation showing good pain control immediately after and on follow-up at four months.

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

    Directory of Open Access Journals (Sweden)

    Hervé Nyangoga

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

  10. Unravelling site-specific breast cancer metastasis : A microRNA expression profiling study

    NARCIS (Netherlands)

    Schrijver, Willemijne A M E; van Diest, Paul J.; Moelans, Cathy B.

    2017-01-01

    Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a sitespecific pattern of metastases formation. In this study,

  11. SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis.

    Science.gov (United States)

    Tang, Xiaolong; Shi, Lei; Xie, Ni; Liu, Zuojun; Qian, Minxian; Meng, Fanbiao; Xu, Qingyang; Zhou, Mingyan; Cao, Xinyue; Zhu, Wei-Guo; Liu, Baohua

    2017-08-22

    Distant metastasis is the main cause of breast cancer-related death; however, effective therapeutic strategies targeting metastasis are still scarce. This is largely attributable to the spatiotemporal intratumor heterogeneity during metastasis. Here we show that protein deacetylase SIRT7 is significantly downregulated in breast cancer lung metastases in human and mice, and predicts metastasis-free survival. SIRT7 deficiency promotes breast cancer cell metastasis, while temporal expression of Sirt7 inhibits metastasis in polyomavirus middle T antigen breast cancer model. Mechanistically, SIRT7 deacetylates and promotes SMAD4 degradation mediated by β-TrCP1, and SIRT7 deficiency activates transforming growth factor-β signaling and enhances epithelial-to-mesenchymal transition. Significantly, resveratrol activates SIRT7 deacetylase activity, inhibits breast cancer lung metastases, and increases survival. Our data highlight SIRT7 as a modulator of transforming growth factor-β signaling and suppressor of breast cancer metastasis, meanwhile providing an effective anti-metastatic therapeutic strategy.Metastatic disease is the major reason for breast cancer-related deaths; therefore, a better understanding of this process and its players is needed. Here the authors report the role of SIRT7 in inhibiting SMAD4-mediated breast cancer metastasis providing a possible therapeutic avenue.

  12. Nanoparticles target early-stage breast cancer metastasis in vivo

    Science.gov (United States)

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-01

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

  14. Suppression of Breast Cancer Metastasis Using Stapled Peptides Targeting the WASF Regulatory Complex

    Directory of Open Access Journals (Sweden)

    John K Cowell

    2017-06-01

    Full Text Available The WASF3 gene facilitates the metastatic phenotype, and its inactivation leads to suppression of invasion and metastasis regardless of the genetic background of the cancer cell. This reliance on WASF3 to facilitate metastasis suggests that targeting its function could serve as an effective strategy to suppress metastasis. WASF3 stability and function are regulated by the WASF Regulatory Complex (WRC of proteins, particularly CYFIP1 and NCKAP1. Knockdown of these proteins in vitro leads to disruption of the WRC and suppression of invasion. We have used mouse xenograft models of breast cancer metastasis to assess whether targeting the WRC complex suppresses metastasis in vivo. Stapled peptides targeting the WASF3-CYFIP1 interface (WAHM1 and the CYFIP1-NCKAP1 interface (WANT3 suppress the development of lung and liver metastases. Targeting these critical protein-protein interactions, therefore, could potentially be developed into a therapeutic strategy to control cancer cell invasion and metastasis.

  15. 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.

  16. SMARCAD1 knockdown uncovers its role in breast cancer cell migration, invasion, and metastasis.

    Science.gov (United States)

    Al Kubaisy, Elham; Arafat, Kholoud; De Wever, Olivier; Hassan, Ahmed H; Attoub, Samir

    2016-09-01

    Breast cancer is the most common cancer seen in women worldwide and breast cancer patients are at high risk of recurrence in the form of metastatic disease. Identification of genes associated with invasion and metastasis is crucial in order to develop novel anti-metastasis targeted therapy. It has been demonstrated that the DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested to play a role in genetic instability. However, its involvement in cancer migration, invasion, and metastasis has never been explored. Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of SMARCAD1 knockdown on the migration, invasion, and metastasis potential of the breast cancer cells MDA-MB-231 and T47D. We observed that SMARCAD1 knockdown in the invasive breast cancer cells MDA-MB-231, unlike in the non-invasive breast cancer cells T47D, was associated with an increased cell-cell adhesion and a significant decrease in cell migration, invasion, and metastasis due at least in part to a strong inhibition of STAT3 phosphorylation. These results indicate that SMARCAD1 is involved in breast cancer metastasis and can be a promising target for metastatic breast cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Yu-Wen Chen

    2007-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  19. In vitro and in vivo toxicity of 5-FdU-alendronate, a novel cytotoxic bone-seeking duplex drug against bone metastasis.

    Science.gov (United States)

    Schott, Sarah; Vallet, Sonia; Tower, Robert J; Noor, Seema; Tiwari, Sanjay; Schem, Christian; Busch, Christian

    2015-08-01

    Bone remains one of the most common anatomic sites for cancer metastases, and the limited therapeutic options aggravate cancer-related morbidity and mortality in multiple malignancies. The covalent conjugation of the amino-bisphosphonate alendronate (ale) with the antimetabolite 5-fluoro-2'-desoxyuridine (5-FdU) results in N(4)-(butyl-(4-hydroxy-4-phosphono)phosphate)-5-fluoro-2'-desoxyuridine (5-FdU-alendronat, 5-FdU-ale), an effective, novel bone-targeting duplex drug directed against skeletal cancer manifestations. In vitro cytotoxicity of ale, 5-FdU or 5-FdU-ale was measured with Alamar Blue and MUH cell viability assays in 14 malignant melanoma, multiple myeloma, bone marrow-derived stromal cell and osteoblast-like cell lines. In vivo toxicity was evaluated using the chicken embryo assay and evaluation of nephrotoxicity and the systemic toxicity in Balb/c nude mice. The effect of 5-FdU-ale on osteoclast was evaluated with Balb/c nude mice in a metastatic breast cancer mouse model. A cell line-specific, dose-related cytotoxicity was observed for 5-FdU-ale in all cancer cell lines tested, which was significantly less toxic than 5-FdU alone when compared to the benign osteoblasts or stromal cells. The embryotoxicity of 5-FdU-ale was significantly less than that of the parental drugs alendronate or 5-FdU. 5-FdU-ale showed no signs of unwanted side effects, weight loss or nephrotoxicity in mice. In a bone metastasis mouse model, 5-FdU-ale reduced the number of tumor-associated osteoclasts. The coupling of an amino-bisphosphonate with an antimetabolite via an N-alkyl-bonding offers a new strategy for the preparation of amino-bisphosphonates conjugates with a cancer cell-specific, efficacious cytotoxic bone-targeting potential along with a reduced systemic toxicity. The innovative duplex drug 5-FdU-ale therefore warrants further clinical investigation.

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

    Science.gov (United States)

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

    2016-02-01

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

  1. 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.|info:eu-repo/dai/nl/075281775; 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.

  2. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay.

    Science.gov (United States)

    Baccelli, Irène; Schneeweiss, Andreas; Riethdorf, Sabine; Stenzinger, Albrecht; Schillert, Anja; Vogel, Vanessa; Klein, Corinna; Saini, Massimo; Bäuerle, Tobias; Wallwiener, Markus; Holland-Letz, Tim; Höfner, Thomas; Sprick, Martin; Scharpff, Martina; Marmé, Frederik; Sinn, Hans Peter; Pantel, Klaus; Weichert, Wilko; Trumpp, Andreas

    2013-06-01

    It has been hypothesized that carcinoma metastasis is initiated by a subpopulation of circulating tumor cells (CTCs) found in the blood of patients. However, although the presence of CTCs is an indicator of poor prognosis in several carcinoma entities, the existence and phenotype of metastasis-initiating cells (MICs) among CTCs has not been experimentally demonstrated. Here we developed a xenograft assay and used it to show that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice. These MIC-containing CTC populations expressed EPCAM, CD44, CD47 and MET. In a small cohort of patients with metastases, the number of EPCAM(+)CD44(+)CD47(+)MET(+) CTCs, but not of bulk EPCAM(+) CTCs, correlated with lower overall survival and increased number of metastasic sites. These data describe functional circulating MICs and associated markers, which may aid the design of better tools to diagnose and treat metastatic breast cancer.

  3. BMI1 and H-RAS Cooperate to Drive Breast Cancer Metastasis | Center for Cancer Research

    Science.gov (United States)

    There have been significant improvements in the diagnosis of breast cancer at early stages of the disease. However, even when patients are identified early, there is a 30 percent chance of recurrence after apparently successful treatment of the initial tumor. The major cause of death for breast cancer patients is metastasis of the tumor to other organs but, unfortunately, the mechanisms of metastatic progression and cancer recurrence are poorly understood.

  4. [Occult lymph node metastasis in the middle and lower third rectal cancer after neoadjuvant radiotherapy].

    Science.gov (United States)

    Wang, Hong-wei; Yao, Yun-feng; Li, Ming; Gu, Jin

    2010-03-01

    To investigate the occult lymph node metastasis in the middle and lower third rectal cancer after neoadjuvant radiotherapy. From June 2003 to December 2006, 74 rectal cancer patients received neoadjuvant radiotherapy (30 Gy/10 f/2 w, CACA-CRC-001) and underwent total mesorectal excision (TME) two weeks later. Fat clearance technique was used in all the samples. Occult lymph node metastasis was detected in the mesorectum using the anti-CK antibody. In total 1883 retrieved lymph nodes, 172 metastasis lymph nodes were harvested by HE examination with the mean diameter [(4.9+/-2.6) mm] being larger than that (2.7+/-1.4) mm of the 1711 negative nodes (Poccult metastasis was found in 40 lymph nodes (2.33%) from 24 patients. Most of these nodes were less than 5 mm (90.0%) with a mean diameter of (3.2+/-1.2)mm, smaller than those of HE-positive metastasis nodes (POccult metastasis was found in 23.1% (9/39) of HE-negative patients. Occult metastasis incidence was higher in patients with HE-positive nodes (42.8%,Poccult metastasis with tumor differentiation, age, or surgical procedures was found. There was no significant difference in recurrence-free survival between ypN(0) patients with and without occult metastasis (P=0.157). It is not necessary to include occult lymph node metastasis in the TNM staging in patients with ypN(0) rectal cancer.

  5. Unusual jaw metastasis from squamous cell lung cancer in heavy smoker: Two case reports and review of the literature.

    Science.gov (United States)

    Pezzuto, Aldo; Morrone, Michelangelo; Mici, Elidon

    2017-05-01

    Jaw metastasis is a very rare condition associated with lung cancer evolution. In this paper we present two cases of patients who underwent different approach.Lung cancer is the leading cause of cancer related death worldwide. Survival depends on the staging and biology of tumor. Smoking may affect the prognosis. There are herein reported the cases of two patients affected by squamous cell lung cancer with spread to mandibular bone. In the first case a computed tomography (CT scan) showed a large mass located in upper right lung , then bronchoscopy was performed with biopsies and the histology revealed a squamous cell carcinoma P63+ and TTF-. In the second case upper right lung mass with metastases to mediastinal bilateral lymph nodes was found at CT scan. A bronchial biopsy revealed a squamous cell carcinoma p63 positive and TTF-1 negative. The first, a 65-years old man, current heavy smoker who quit and relapsed, at initial stage of IIa (T2aN1M0), after initial neo-adjuvant chemotherapy underwent lung lobectomy and lymph nodes resection. Three months later a metastasis located on mandibular bone was found out. The second case, a 68-years old female heavy smoker, at initial stage IIIb not available for surgery because of involvement of bilateral lymph nodes, underwent first line course chemotherapy with cisplatin and vinorelbine and second line with erlotinib. The first patient underwent hyperthermia and radiotherapy but a sepsis developed and patients died. In the second case, after two months from the beginning of II line the patient developed a jaw metastasis and underwent surgery with resection of hemi-mandible, but soon after she died because of pulmonary embolism. These cases highlight the poor prognosis of patients current smokers affected by squamous cell lung cancer. The jaw bone localization is very rare and different approach could be applied.

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

    Science.gov (United States)

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

    2016-01-01

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

  7. The Clinicopathological Factors Associated with Disease Progression in Luminal A Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A Single Center in China.

    Science.gov (United States)

    Ye, Jingming; Wang, Wenjun; Xin, Ling; Owen, Sioned; Xu, Ling; Duan, Xuening; Cheng, Yuanjia; Zhang, Hong; Zhang, Shuang; Li, Ting; Liu, Yinhua

    2017-08-01

    This study investigated the clinicopathological factors associated with outcomes in patients with Luminal A breast cancer. Retrospective analysis of the association of clinicopathological factors and breast cancer outcome in 421 patients with newly-diagnosed Luminal-A breast cancer that were enrolled from January 2008 to December 2014. Clinicopathological data were analyzed to validate the relationship with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to analyze the value of clinicopathological factors (tumor size, node status and lymphovascular invasion), and subsequent Cox regression analysis revealed significant prognostic factors. With a median of 61 months follow-up, the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate regression analysis showed that clinical anatomic stage, tumor size, status of lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413 patients with stage I-III breast cancer, 14 presented with metastasis (3.4%) during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time after metastasis was 20.4 months. Of all the sites of distant metastasis, liver metastasis was the only factor that affected survival time after metastasis (χ2=6.263, p=0.012). Patients with Luminal A breast cancer have excellent outcomes. Liver metastasis is an important factor compressing the survival time after distant metastasis presents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Rapid-prototype endoprosthesis for palliative reconstruction of an upper extremity after resection of bone metastasis.

    Science.gov (United States)

    Pruksakorn, Dumnoensun; Chantarapanich, Nattapon; Arpornchayanon, Olarn; Leerapun, Taninit; Sitthiseripratip, Kriskrai; Vatanapatimakul, Natapoom

    2015-03-01

    To present a rapid-prototype (RP) endoprosthesis replacement after tumor resection in patients with bone metastasis of the upper extremity. The short-term complications and functional outcomes were evaluated as well as the survival of patients and endoprosthesis. Bone metastasis patients who required bone resection and endoprosthesis replacement were enrolled and consented before operation. Custom-made endoprosthesis was fabricated from polymethyl methacrylate assisted by RP technology. After surgery was performed, patients were followed up daily until discharge and monthly until 6 months postoperatively for immediate post-operative complications and for signs of endoprosthesis failure. The functional outcome was evaluated 6 months postoperatively by the Musculoskeletal Tumor Society score (MTSS) and the Mankin score. Thereafter, patients' survival and arm condition were monitored every 3 months. Sixteen cases participated on this study. There were nine proximal-, four total- and two distal humerus, and one proximal ulna replacement. The median follow-up period was 486 days. The mean MTSS was 55 % and the Mankin score was good in 64 % and fair in 36 % of the patients. Glenohumeral subluxation was observed in 23 % of the patients; however, a stable shoulder was achieved in all cases. There were no prosthesis failure or systemic breakage. An RP endoprosthesis may have significant advantages when the entire humerus needs to be replaced, or periarticular sites are involved. This technique offers custom-made endoprosthesis with enough durability, and in a relatively short production time at reasonable costs which are suitable for palliative reconstruction.

  9. Unexpected Bone Metastases from Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Sandra Gibiezaite

    2015-01-01

    Full Text Available Objective. To present a complicated case of differentiated thyroid carcinoma (DTC with metastases to the skull that was evident on I-131 whole body scan (WBS but negative on other imaging modalities in a low risk patient. Methods. We will discuss clinical course, imaging, pathological findings, and treatment of the patient with skull metastasis from DTC. Pertinent literature on imaging and pathology findings as well as radioactive iodine (RAI treatment impact on quality of life and survival in patients with bone metastases from DTC will be reviewed. Results. The patient is a 37-year-old woman with a diagnosis of DTC who had focal areas of increased uptake in the head on WBS with no correlative findings on CT and MRI. Initially, false positive findings were suspected since patient had a low risk for developing metastases. However, the persistent findings on post-RAI treatment WBS, following two courses of treatment, were highly concerning for metastatic bone disease. WBC performed 6 months following the second RAI treatment revealed resolution of the findings. Conclusions. False positive findings in WBS are frequent and may be due to contamination, perspiration, or folliculitis of the scalp as well as benign lesions such as meningioma, hematoma, cavernous angioma, and metallic sutures. However, metastatic disease should always be considered even if the patient has low risk of distant metastatic disease and correlative images do not support the diagnosis. RAI therapy appears to improve the survival rates and quality of life of thyroid cancer patients with bone metastases based on retrospective studies.

  10. Do all patients with newly diagnosed prostate cancer need staging radionuclide bone scan? A retrospective study.

    Science.gov (United States)

    Al-Ghazo, Mohammed A; Ghalayini, Ibrahim F; Al-Azab, Rami S; Bani-Hani, Ibrahim; Barham, Alaa; Haddad, Yazan

    2010-01-01

    Define a group of patients with newly diagnosed prostate cancer, whose risk of bone metastasis is low enough to omit a bone scan staging study. From 2003 to 2009, the medical records of patients who were newly diagnosed with prostate cancer were retrospectively reviewed. The data collected included: age, digital rectal examination, serum prostate specific antigen (PSA), Gleason score, clinical T stage, and bone isotope scan. Patients were divided into two groups according to the results of bone isotope scan; positive group and negative group. A univariate and multivariate binary logistic regression was used to analyze the results. Of the 106 patients, 98 had a complete data collection and were entered into the study. The median age of the patients was 70.5 years and patients with a positive bone scan was 74 years, significantly higher than for patients with negative scans (69 years) (p=0.02). Bone metastasis was detected in 39 cases (39.7%). In all patients with clinical T1-2 stage, a Gleason score of bone isotope scans were negative. In univariate analysis, PSA (>20 ng/mL) and Gleason score (>7) were independently predictive of positive bone scan, while clinical stage was not. Staging bone scans can be omitted in patients with a PSA level of ≤20 ng/mL, and Gleason scoreGleason score and PSA, a larger proportion of patients with prostate cancer could avoid a staging bone scan.

  11. CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages

    Science.gov (United States)

    Kitamura, Takanori; Qian, Bin-Zhi; Soong, Daniel; Cassetta, Luca; Noy, Roy; Sugano, Gaël; Kato, Yu; Li, Jiufeng

    2015-01-01

    Pulmonary metastasis of breast cancer cells is promoted by a distinct population of macrophages, metastasis-associated macrophages (MAMs), which originate from inflammatory monocytes (IMs) recruited by the CC-chemokine ligand 2 (CCL2). We demonstrate here that, through activation of the CCL2 receptor CCR2, the recruited MAMs secrete another chemokine ligand CCL3. Genetic deletion of CCL3 or its receptor CCR1 in macrophages reduces the number of lung metastasis foci, as well as the number of MAMs accumulated in tumor-challenged lung in mice. Adoptive transfer of WT IMs increases the reduced number of lung metastasis foci in Ccl3 deficient mice. Mechanistically, Ccr1 deficiency prevents MAM retention in the lung by reducing MAM–cancer cell interactions. These findings collectively indicate that the CCL2-triggered chemokine cascade in macrophages promotes metastatic seeding of breast cancer cells thereby amplifying the pathology already extant in the system. These data suggest that inhibition of CCR1, the distal part of this signaling relay, may have a therapeutic impact in metastatic disease with lower toxicity than blocking upstream targets. PMID:26056232

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

    Science.gov (United States)

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

    2015-05-01

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

  13. Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer

    Directory of Open Access Journals (Sweden)

    Wen-Bo Jin

    2013-01-01

    Full Text Available Objective: The purpose of this study is to analyze a single institution experience with pleuropneumonectomy for pleural metastasis and malignant pleural effusion in primary lung cancer. Materials and Methods: From August 1978 to August 2011, 66 consecutive patients with lung cancer underwent pleuropneumonectomy. Patients were followed-up after the operation. The quality-of-life and the survival time were recorded. Results: All the 66 patients were successfully operated on, including 38 patients in early years (1978-1993 and 28 patients in recent years (1994-2