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Sample records for controls bone metastasis

  1. Osthole inhibits bone metastasis of breast cancer

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    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...

  2. Colorectal cancer presenting as bone metastasis

    Directory of Open Access Journals (Sweden)

    M C Suresh Babu

    2017-01-01

    Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

  3. Study of bone metastasis of cervical carcinoma by bone scintigraphy

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    Okamura, Shinsuke; Okamoto, Yoshiaki; Maeda, Takayoshi; Sano, Takashi; Ueki, Minoru; Sugimoto, Osamu; Sakata, Tsunehiko; Yamasaki, Kouichi; Akagi, Hiroaki

    1985-04-01

    In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate. Of 172 post-operative cases, 20.8% (11/53) of those with lymph node metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymph node metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymphnode metastases. The 28 bone metastasis cases included 10 cases with multiple bone metastases and 5 with only a single bone metastasis. Most bone metastases were seen in the lumbar vertebrae and the pelvic bone. Post-operative cases had more distant metastases than non-operative cases. On diagnosis of bone metastases and 17 of the 28 patients had pain, 6 of the remaining 11 patients developing pain thereafter. (J.P.N.).

  4. Bone metastasis target redox-responsive micell for the treatment of lung cancer bone metastasis and anti-bone resorption.

    Science.gov (United States)

    Ye, Wei-Liang; Zhao, Yi-Pu; Cheng, Ying; Liu, Dao-Zhou; Cui, Han; Liu, Miao; Zhang, Bang-Le; Mei, Qi-Bing; Zhou, Si-Yuan

    2018-01-16

    In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis.

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

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

    2009-08-15

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

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

    International Nuclear Information System (INIS)

    Carrafiello, Gianpaolo; Lagana, Domenico; Ianniello, Andrea; Nicotera, Paolo; Fontana, Federico; Dizonno, Massimiliano; Cuffari, Salvatore; Fugazzola, Carlo

    2009-01-01

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

  7. Molecular mechanism and potential targets for bone metastasis

    International Nuclear Information System (INIS)

    Iguchi, Haruo

    2007-01-01

    The incidence of bone metastasis has been increasing in all cancers in recent years. Bone metastasis is associated with substantial morbidity, including bone pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the management of bone metastasis in patients is a clinically significant issue. In the process of bone metastasis, the primary mechanism responsible for bone destruction is cancer cell-mediated stimulation of osteoclastic bone resorption, which results in osteolysis and release of various growth factors from the bone matrix. These growth factors are prerequisites for successful colonization and subsequent invasive growth of cancer cells in bone, which is called a 'vicious cycle.' Thus, it is important to elucidate what molecules are involved in this step of bone destruction, and the understanding of these molecular mechanisms could lead to develop molecular-target therapies for bone metastasis. Bisphosphonates introduced in the treatment for bone metastasis have been shown to reduce skeletal morbidity. In Japan, the most potent bisphosphonate, zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical trial of humanized anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Denosumab) against bone metastasis is under way as a global study. These new agents, which are targeted to osteoclasts, are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and/or hormone therapy. (author)

  8. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

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

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    Yibin Kang

    2016-06-01

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

  10. Clinical outcome for patients of solitary bone only metastasis.

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    Hosaka, Seiichi; Katagiri, Hirohisa; Honda, Yosuke; Wasa, Junji; Murata, Hideki; Takahashi, Mitsuru

    2016-03-01

    Solitary bone only metastasis (SBOM) is a rare condition in which metastasis is limited to a single skeletal lesion originating from a previously treated or controllable primary lesion. The study objective was to evaluate the clinical features and survival regarding this rare condition and to clarify its treatment strategy. A total of 1453 patients with bone metastasis registered in our hospital database were enrolled. To assess the primary and/or metastatic lesion we used plain X-ray images, CT, MRI and FDG-PET scans as well as bone scans. Among the patients, only 27 (1.8%) had SBOM. The primary cancers responsible for SBOM were lung in seven patients, breast in five, kidney in four, prostate in two, uterus in two and other types in seven. Treatment of SBOM involved resection in four patients, radiotherapy only in 17, radiotherapy in combination with zoledronate in six and chemotherapy with zoledronate in one. Local recurrence did not develop in the four cases treated with resection. However, in-field recurrence was found in 4 of 22 (18%) patients who underwent radiotherapy. All three patients who received >40 Gy did not develop in-field recurrence. The overall and event free survival rates at 5 years were 63% and 41%, respectively. Solitary bone only metastasis should be treated with wide resection or long-course radiotherapy at doses 40-50 Gy to achieve long lasting local tumor control. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  11. Paget's disease of bone resembling bone metastasis from gastric cancer.

    Science.gov (United States)

    Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

    2011-08-01

    A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

  12. The Role of Extracellular Vesicles in Bone Metastasis

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    Michela Rossi

    2018-04-01

    Full Text Available Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed, it was shown that extracellular vesicles, including exosomes and microvesicles, released from tumor cells can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the proliferation of tumor cells. The inhibition of EV-mediated crosstalk between cancer and bone cells could represent a new therapeutic target for bone metastasis.

  13. The value of combined examination of serum CYFRA21-1 levels and bone scan in the diagnosis of bone metastasis in lung cancer

    International Nuclear Information System (INIS)

    Yu Jing; Wang Junhong; Zhengping

    2007-01-01

    Objective: To explore the value of combined examination of serum tumor markers CYFRA21-1 and bone scan in the diagnosis of bone metastasis in lung cancer. Methods: Bone scan and serum CYFRA21-1 levels (with CLIA) determination were performed in 138 patients with lung cancer and 56 patients with benign lung diseases. Results: The serum level of CYFRA21-1 were significantly higher in patients with bone metastasis than those in patients without bone metastasis. The levels were also higher in patients without bone metastasis than those in controls. Most patients with bone metastasis had positive results in bone scan (97.4%), only 2 of the 78 had negative bone scan but positive with CT or MRI. A few patients without bone metastasis and controls had positive bone scan results, caused by previous operation or injury. Conclusion: The combined detection of CYFRA21-1 and bone scan were valuable in the diagnosis of bone metastasis of lung cancer. (authors)

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

    International Nuclear Information System (INIS)

    Miyoshi, Hidenao; Otsuka, Nobuaki; Sone, Teruki; Nagai, Kiyohisa; Tamada, Tsutomu; Mimura, Hiroaki; Yanagimoto, Shinichi; Tomomitsu, Tatsushi; Fukunaga, Masao

    1999-01-01

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

  15. Functions and Epigenetic Regulation of Wwox in Bone Metastasis from Breast Carcinoma: Comparison with Primary Tumors

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    Paola Maroni

    2017-01-01

    Full Text Available Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox. The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1 affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma. In hypoxic-bone metastatic cells, Wwox enhances HIF-1α stabilization, phosphorylation, and nuclear translocation. Consistently, in bone-metastasis specimens Wwox localizes in cytosolic/perinuclear area, while TAZ (transcriptional co-activator with PDZ-binding motif and HIF-1α co-localize in nuclei, playing specific regulatory mechanisms: TAZ is a co-factor of HIF-1, and Wwox regulates HIF-1 activity by controlling HIF-1α. In vitro, DNA methylation affects Wwox-protein synthesis; hypoxia decreases Wwox-protein level; hepatocyte growth factor (HGF phosphorylates Wwox driving its nuclear shuttle, and counteracting a Twist program important for the epithelial phenotype and metastasis colonization. In agreement, in 1833-xenograft mice under DNA-methyltransferase blockade with decitabine, Wwox increases in nuclei/cytosol counteracting bone metastasis with prolongation of the survival. However, Wwox seems relevant for the autophagic process which sustains metastasis, enhancing more Beclin-1 than p62 protein levels, and p62 accumulates under decitabine consistent with adaptability of metastasis to therapy. In conclusion, Wwox methylation as a bone-metastasis therapeutic target would depend on autophagy conditions, and epigenetic mechanisms regulating Wwox may influence the phenotype of bone metastasis.

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

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    Krishnangshu Bhanja Choudhury

    2011-01-01

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

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

    African Journals Online (AJOL)

    Background: Hyoid bone chondrosarcoma is a very rare condition. This study presents a case report of low-grade chondrosarcoma of hyoid bone with cervical nodal metastasis. The study also presents preoperative radiological investigations, pathological examination and the follow-up of the case. Case presentation: A 42 ...

  18. Bone scintigraphy for metastasis detection in canine osteosarcoma

    International Nuclear Information System (INIS)

    Forrest, L.J.; Thrall, D.E.

    1994-01-01

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

  19. Protocadherin-7 induces bone metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-05

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

  20. Protocadherin-7 induces bone metastasis of breast cancer

    International Nuclear Information System (INIS)

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Sun, Xuan; Cao, Xu-Chen

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  2. Diagnosis of bone metastasis from thyroid carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  3. A study of bone metastasis of cervical carcinoma by bone scintigraphy

    International Nuclear Information System (INIS)

    Okamura, Shinsuke; Okamoto, Yoshiaki; Maeda, Takayoshi; Sano, Takashi; Ueki, Minoru; Sugimoto, Osamu; Sakata, Tsunehiko; Yamasaki, Kouichi; Akagi, Hiroaki

    1985-01-01

    In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate (p<0.05). Of 172 post-operative cases, 20.8% (11/53) of those with lymphnode metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymphnode metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymphnode metastases. The 28 bone metastasis cases included 10 cases with multiple bone metastases and 5 with only a single bone metastasis. Most bone metastases were seen in the lumbar vertebrae and the pelvic bone. Post-operative cases had more distant metastases than non-operative cases. On diagnosis of bone metastases and 17 of the 28 patients had pain, 6 of the remaining 11 patients developing pain thereafter. (J.P.N.)

  4. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

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

    2017-01-01

    OBJECTIVE: In the 10 most common primary types with bone metastases, we aimed to examine survival, further stratifying on bone metastases only or with additional synchronous metastases. METHODS: We included all patients aged 18 years and older with incident hospital diagnosis of solid cancer...... 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...... 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...

  5. Malignant Giant Cell Tumour of Bone with Axillary Metastasis

    African Journals Online (AJOL)

    2002-06-06

    Jun 6, 2002 ... SUMMARY. Giant Cell Tumour of bone is a typically benign and solitary tumour. However, multiple lesions have been described and 5-10% of lesions may be malignant. We present a case of a malignant giant cell tumour of the distal radius with metastasis to the ipsilateral axilla (an uncommon location).

  6. The usefulness of bone marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Morita, Rikushi

    1985-01-01

    A combination study of bone and bone marrow scintigraphy was performed on 25 pts with prostatic cancer, and, in order to study the usefulness in the diagnosis of bone metastasis, the findings of 2 scintigraphies were compared with those of skeletal roentgenography. Out of the 18 cases with the hot spots of sup(99m)Tc-MDP in the lower lumbar spine or/and the pelvic bone, 8 showed normal bone marrow scintigrams which were eventually proved to have degenerative changes of the spine accompanied by aging. On the other hand, nine cases of the ten, who had accumulation defects on the bone marrow scintigrams were finally proved having bone metastasis. All six cases with extensive bone metastases shown by bone scintigraphy with sup(99m)Tc-MDP, demonstrated multiple accumulation defects on bone marrow scintigraphy with sup(99m)Tc-sulfur colloid. In conclusion, bone marrow scintigraphy was thought to be helpful in distinguishing the metastatic lesions from the benign spinal degenerative changes in the cases with suspicions bone involvement and in evaluating equivocal lesions in the pelvis. Therefore, it was shown that, in the detection and diagnosis of bone metastasis from prostatic cancer, bone scintigraphy alone was insufficient, and that combination with bone marrow scintigraphy was found to be useful. (author)

  7. 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

  8. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

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

    2017-01-01

    %, 11% to 14%). The risk of mortality was increased for the majority of cancer types among patients with bone and synchronous metastases compared with bone only (adjusted relative risk 1.29-1.57), except for cervix, ovarian and bladder cancer. CONCLUSIONS: While patients with bone metastases after most......OBJECTIVE: In the 10 most common primary types with bone metastases, we aimed to examine survival, further stratifying on bone metastases only or with additional synchronous metastases. METHODS: We included all patients aged 18 years and older with incident hospital diagnosis of solid cancer...... 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...

  9. 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.

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

    International Nuclear Information System (INIS)

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

    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 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

  11. 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.

  12. 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.

  13. Role of Tumor-Derived Chemokines in Osteolytic Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Salvatore J. Coniglio

    2018-06-01

    Full Text Available Metastasis is the primary cause of mortality and morbidity in cancer patients. The bone marrow is a common destination for many malignant cancers, including breast carcinoma (BC, prostate carcinoma, multiple myeloma, lung carcinoma, uterine cancer, thyroid cancer, bladder cancer, and neuroblastoma. The molecular mechanism by which metastatic cancer are able to recognize, infiltrate, and colonize bone are still unclear. Chemokines are small soluble proteins which under normal physiological conditions mediate chemotactic trafficking of leukocytes to specific tissues in the body. In the context of metastasis, the best characterized role for the chemokine system is in the regulation of primary tumor growth, survival, invasion, and homing to specific secondary sites. However, there is ample evidence that metastatic tumors exploit chemokines to modulate the metastatic niche within bone which ultimately results in osteolytic bone disease. In this review, we examine the role of chemokines in metastatic tumor growth within bone. In particular, the chemokines CCL2, CCL3, IL-8/CXCL8, and CXCL12 are consistently involved in promoting osteoclastogenesis and tumor growth. We will also evaluate the suitability of chemokines as targets for chemotherapy with the use of neutralizing antibodies and chemokine receptor-specific antagonists.

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

    International Nuclear Information System (INIS)

    Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C.; Garcia Garc'ia, T.; Azagra Ros, P.; Maruenda Paulino, J.I.; Ferrer Albiach, C.

    1999-01-01

    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.) [de

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  16. Therapeutic effects of strontium-89 combined with endocrine therapy for treatment of bone metastasis in patients with prostate cancer

    International Nuclear Information System (INIS)

    Guo Deming

    2009-01-01

    Objective: To evaluate the effects of strontium-89 ( 89 Sr) combined with endocrine therapy for the treatment of bone metastasis in patients with advanced prostate cancer. Methods: 45 cases of prostate cancer with bone metastasis were randomly divided into 2 groups: patients in study group (23 cases) were given 89 Sr combined with endocrine therapy while patients in control group (22 cases) were given endocrine therapy only. The effect on pain relief, the serum PSA level, hemogram and biochemical indicators of hepatic and renal function were observed. Results: The pain degree was not statistically significant between two groups before treatment (P>0.05) and was statistically significant after treatment (P 89 Sr radionuclide combined with endocrine therapy was more effective than endocrine therapy alone in relief of the pain from bone metastasis and reduction of metastasis size in patients with advaced prostatic cancer. (authors)

  17. Diagnosis of bone metastasis from thyroid carcinoma: a multidisciplinary approach

    International Nuclear Information System (INIS)

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

    2015-01-01

    Sarcomas are rare tumors originating from soft tissue or bone. Diagnosis and treatment of sarcomas should be performed at specialized sarcoma centers, where patients are evaluated at a multidisciplinary tumor conference. We present a case where sarcoma was suspected from magnetic resonance imaging (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-evaluation of previous pathology and a thorough patient history enabled a final diagnosis

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  19. Detection of bone metastasis of prostate cancer. Comparison of whole-body MRI and bone scintigraphy

    International Nuclear Information System (INIS)

    Ketelsen, D.; Roethke, M.; Aschoff, P.; Lichy, M.P.; Claussen, C.D.; Schlemmer, H.P.; Merseburger, A.S.; Reimold, M.

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Taher Rajabi

    2014-01-01

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

  1. A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone

    National Research Council Canada - National Science Library

    Che, Mingxin; Nie, Daotai

    2005-01-01

    Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil...

  2. A Tissue Engineering Approach to Study the Progression of Breast Tumor Metastasis in Bone

    National Research Council Canada - National Science Library

    Che, Mingxin; Nie, Daotai

    2006-01-01

    Most patients dying of breast cancer suffer painful bone metastasis. It is our hypothesis that the invasive growth and progression of breast metastatic lesions in bone requires the participation of various constituents from "soil...

  3. MR imaging of bone marrow metastasis in patients with neuroblastoma. Comparison between mass-screened cases and clinically detected cases

    International Nuclear Information System (INIS)

    Kanegawa, Kimio; Akasaka, Yoshinori; Kawasaki, Ryuta; Nishiyama, Shoji; Mabuchi, Osamu; Muraji, Toshihiro

    1999-01-01

    Seventy-six patients with neuroblastoma who underwent bone marrow MRI were divided into two groups: the first group consisted of patients detected by mass screening (M group, n=55), and the second group of patients detected clinically (non-M group, n=21). Bone marrow metastasis was morphologically classified into two types, nodular type and diffuse type. We studied the incidence of bone marrow metastasis, relationship between the patterns of bone marrow metastasis and the presence of bone metastasis, and morphological changes of bone marrow metastasis after chemotherapy. In M group, the incidence of bone marrow metastasis was 7.3% (4 patients) and the patterns of bone marrow metastases were all nodular type not accompanied with bone metastasis and disappeared after chemotherapy. In non-M group, the incidence of bone marrow metastasis was 52.4% (11 patients). Bone marrow metastases had both patterns of metastasis. Forty-five per cent of diffuse type of bone marrow metastasis were accompanied with bone metastasis. All bone marrow metastases disappeared after chemotherapy, but in one of 11, there was recurrence of bone marrow metastasis. (author)

  4. Patterns of Intraosseous Recurrence After Stereotactic Body Radiation Therapy for Coxal Bone Metastasis.

    Science.gov (United States)

    Ito, Kei; Shimizuguchi, Takuya; Nihei, Keiji; Furuya, Tomohisa; Ogawa, Hiroaki; Tanaka, Hiroshi; Sasai, Keisuke; Karasawa, Katsuyuki

    2018-01-01

    To analyze the detailed pattern of intraosseous failure after stereotactic body radiation therapy (SBRT) for coxal bone metastasis. Patients treated with SBRT to coxal bone metastasis were identified by retrospective chart review. The SBRT doses were 30 Gy or 35 Gy in 5 fractions. A margin of 5 to 10 mm was added to the gross tumor volume to create the clinical target volume. We evaluated the presence or absence of intraosseous recurrence using magnetic resonance imaging. Intraosseous recurrences were assessed as "in-field" or "marginal/out-of-field." In addition, we measured the distance between the center of the recurrent tumor and the nearest edge of the initial bone metastasis in cases of marginal/out-of-field recurrence. Seventeen patients treated for 17 coxal bone metastases were included. Median age was 64 years (range, 48-79 years). Coxal lesions involved the ilium in 14 cases, pubis in 3, and ischium in 4 (3 lesions crossed over multiple regions). Patients most commonly had renal cell carcinoma (29.4%), followed by lung, hepatic cell, and colorectal cancers (23.5%, 11.8%, and 11.8%, respectively). Median follow-up after SBRT was 13 months (range, 2-44 months). Among all 17 cases, 7 cases developed 8 intraosseous recurrences, including in-field recurrence in 1 case and marginal/out-of-field recurrences in 7 cases. Median time to intraosseous recurrence was 10 months (range, 2-35 months). Among 7 cases with marginal/out-of-field recurrence, mean distance to the center of the recurrent tumor from the nearest edge of the initial bone metastasis was 34 mm (range, 15-55 mm). Most recurrences were observed out-of-field in the same coxal bone. These results suggest that defining the optimal clinical target volume in SBRT for coxal bone metastasis to obtain sufficient local tumor control is difficult. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    Na1 8F bone positron emission tomography (bone PET) is a new imaging modality which is useful for the evaluation of bone diseases. Here, we compared the diagnostic accuracies between bone PET and bone scan for the detection of bone metastasis (BM). Sixteen cancer patients (M:F = 10:6, mean age = 60 ± 12 years) who underwent both bone PET and bone scan were analyzed. Bone PET was conducted 30 minutes after the injection of 370 MBq Na1 8F , and a bone scan was performed 3 hours after the injection of 1295 MBq 9 9mT c-hydroxymethylene diphosphonate. In the patient-based analysis (8 patients with BM and 8 without BM), the sensitivities of bone PET (100% 8/8) and bone scan (87.5% = 7/8) were not significantly different (p > 0.05), whereas the specificity of bone PET (87.5% = 7/8) was significantly greater than that of the bone scan (25% = 2/8) (p 8F bone PET is more accurate than bone scan for BM evaluation.

  6. 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.

  7. Bone metastasis pattern in initial metastatic breast cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Xiong Z

    2018-02-01

    Full Text Available Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%. Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of

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

    International Nuclear Information System (INIS)

    Bevilacqua, E.; Frankenberger, C.A.; Rosner, M.R.

    2012-01-01

    In the past decade cancer research has recognized the importance of tumor stroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression have not been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated 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 bioinformatics 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

  9. Pulmonary metastasis in osteosarcoma in bone scintigraphy: 2 case reports poster

    International Nuclear Information System (INIS)

    Grobocopatel, D.; Silva, N.J.; Hunsche, A.; Fernandes, D.D.; Berdichevski, E.H.; Cembrani, L.; Anselmi, C.E.; Anselmi, O.E.

    2004-01-01

    Full text: Osteosarcoma is considered the most common malignant primary bone tumour in children and adolescents. The lungs are the common sites of metastasis, which, if present, are associated with poor prognosis. Imaging workup includes x-ray, computed tomography, nuclear resonance imaging and bone scintigraphy in order to diagnose, help to choose appropriate treatment and prognosticate this disease. Chemotherapy is used to increase survival rate and to control the occurrence of lung metastasis. CASE 1: ELWS, male, 6 years old. The patient had a left knee trauma followed by increase in size and pain over 15 days. Knee x-ray showed a voluminous lesion and densely calcified tissue in the left knee, with soft tissue involvement. Chest x-ray showed multiple nodular dense lesions diffusely involving the lungs. Left knee MRI showed a neoplasm involving the distal epiphysis of the femur with extension from the bone marrow to the trochanteric region. Biopsy diagnosed small cell osteosarcoma. Chest computed tomography showed multiple opacities in the parenchyma of both lungs, most with calcification, predominantly in the cortical region. Bone scintigraphy showed intense uptake of the radiopharmaceutical in the distal half of the left femur and focal areas of increased uptake in the skull, left humerus, right scapula, thoracic soft tissue (mostly in the right side, in the same place as the pulmonary metastasis seen in the chest computed tomography), 12th thoracic vertebra, 4th lumbar vertebra and in the pelvis. CASE 2: ACD, male 20 years old. The patient presented pain and increase in size of the right knee starting 5 months ago. Right knee x-ray: insufflating bony lesion in the proximal epiphysis of the right tibia compatible with osteosarcoma; increase in volume in soft tissue around the knee. Right knee MRI: voluminous expansive osteoblastic lesion hypointense in T1 and heterogeneous in T2, diffusely enhanced by the use of gadolinium-DTPA; the lesion involved almost

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

    Science.gov (United States)

    Meng, X Y; Song, S T

    2017-03-23

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

  11. The value of combined examination of serum CA15-3, CEA level and whole body bone scan in the diagnosis of bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Lu Baoshi; Gao Yufang

    2011-01-01

    Objective: To explore the value of combined examination of serum tumormarkers carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA) and whole body bone scan in the diagnosis of bone metastasis in breast cancer. Methods: Whole body bone scan and serum CA15-3 and CEA levels with a electrochemical luminescence assay were performed in 97 patients with breast cancer (46 cases with bone metastasis and 51 cases without bone metastasis) and 45 patients with benign breast diseases. As for the negative cases who had significant pains in bones, CT or MRI was performed to make sure. Results: The serum level of CA15-3 and CEA were significantly higher in patients with bone metastasis than those in patients without bone metastasis and the benign lesions. The positive predicting values were 76.09% and 80.43%. Most patients with bone metastasis had positive results in bone scan (95.65%), only 2 cases had negative results (4.35%), which is positive by CT or MRI Seven. Seven patients without bone metastasis and Three patients with the benign lesions had positive results in bone scan, that may be caused by previous operation or injury. The combined determination of CA15-3, CEA and whole body bone scan had a better performance in sensitivity, specificity and accuracy than each single way. Conclusion: The combined determination of CA 15-3, CEA and whole body bone scan were valuable in the diagnosis of bone metastasis in breast cancer. (authors)

  12. Clinical eveluation of metastasis from carcinoma of the prostate by bone scintiscanning

    International Nuclear Information System (INIS)

    Okada, Kiyoki; Igarashi, Jotaro; Nogaki, Joji; Kinoshita, Masayuki; Kishimoto, Takashi

    1981-01-01

    Eighty radioisotopic bone scintiscans in conjunction with radiographic skeletal survey were carried out in 47 patients with prostatic carcinoma encountered over the past 6 years. Five patients were excluded because of false positive bone scan. None of the patients was found with false negative bone scan irrespective of the presence of osteolytic lesions. In 21 of the remaining 42 cases (40.0%), increased information on bone metastasis was obtained by the bone scan. A positive bone scan was interpreted at 156 sites, of which 67 (42.9%) were negative on bone survey. Bone scan was superior to bone survey for detecting metastatic sites of the sternum, cervical and thoracic spine, ribs, scapula and skull. Serial bone scans in some cases demonstrated an objective response of the metastasis following hormonal treatment. At the time of bone scan, 22 of 47 cases (46.8%) showed an abnormal renal image, which represented the degree of bone metastasis as well as that of renal function. Thus, bone scan represents a useful tool for detecting metastatic lesions from prostatic carcinoma and for assessing the response to treatment. (author)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 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 2 solution (containing 1.4 mg Ca and 5nCi 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 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 41 Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 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.

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

    Directory of Open Access Journals (Sweden)

    Fatma Uçar

    2011-12-01

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

  15. Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

    National Research Council Canada - National Science Library

    Donahue, Henry

    2001-01-01

    .... We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2...

  16. 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.

  17. The diagnostic value of PSA, cPSA and bone scintigraphy for early skeletal metastasis of prostate cancer

    International Nuclear Information System (INIS)

    Xue Zhongguang

    2007-01-01

    Objective: To evaluate the value of prostate specific antigen (PSA), complexed prostate specific antigen (cPSA) and bone scintigraphic imaging in diagnosis of early skeletal metastasis of prostate cancer. Methods: 152 patients (74 with prostate cancer, 78 with benign prostate disease) and 90 controls were examined for the serum concentrations of PSA and cPSA. At the same time, the 74 patients with PCa were examined with bone scintigraphy. The cPSA/PSA ratio was calculated. Results: Serum PSA, cPSA levels and cPSA/PSA ratio of patients with prostate cancer were significantly higher than those in benign prostate patients and controls. In addition, the serum PSA, cPSA levels and cPSA/PSA ratio in prostate cancer patients with skeletal metastasis were remarkably higher than those in patients without skeletal metastasis, and the differences were significant (P 20 μg/L, cPSA>10 μg/L, cPSA/PSA>0.80, there is a high probability that skeletal metastasis of prostate cancer would be present and bone scintigraphy should be performed. (authors)

  18. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

    Science.gov (United States)

    Campbell, J Preston; Karolak, Matthew R; Ma, Yun; Perrien, Daniel S; Masood-Campbell, S Kathryn; Penner, Niki L; Munoz, Steve A; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A; Elefteriou, Florent

    2012-07-01

    Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

  19. Prospective study of bone metastasis from prostate cancer: comparison between large field diffusion-weighted imaging and bone scintigraphy

    International Nuclear Information System (INIS)

    Wang Xiaoying; Zhang Chunyan; Jiang Xuexiang

    2009-01-01

    Objective: To evaluate the large field diffusion weighted imaging (DWI) (from head vertex to lower leg) in detection of bone metastases from prostate cancer. Methods: One hundred and sixty- six consecutive patients who were suspected of prostate cancer received pelvic MRI and large field diffusion weighted imaging examination. Forty-nine of them underwent bone scintigraphy within one month of the examination of large field DWI. The images were double-blindly evaluated without the knowledge of the pathology result. Conventional MR T 1 and fat saturation T 2 weighted images were taken as standard for the diagnosis of bone metastasis. The sensitivity, specificity, and area under curve between large field DWI and bone scintigraphy were compared with McNemar test. Five patients with bone metastases exceeding 10 per patient were excluded in the lesion-by-lesion analysis. Results: Ten of the 49 patients were diagnosed as bone metastases. The diagnosis of bone metastasis were made in 15 patients by large field DWI and in 17 patients by bone scintigraphy. With patient number as study units (n=49), the diagnostic sensitivity of bone metastases with large field DWI and bone metastases were both 100% (10/10), and specificity were 87.2% (34/39) vs. 82.1% (32/39), respectively. ROC study showed the area under curve (AUC) of large field DWI and bone scintigraphy were 0.936 vs. 0.910, respectively. Totally 68 abnormal foci were identified from large field DWI and/or bone scintigraphy in 44 patients (while 5 patients with bone metastases exceeding 10 foci per patient were excluded), 20 of them were diagnosed as foci of bone metastasis. The diagnosis of bone metastases was made in 23 foci by large field DWI and in 34 by bone scintigraphy. With lesion numbers as study units (n=68), the diagnostic sensitivity of large field DWI and bone scintigraphy were both 90.0% (18/20), and specificity were 89.6% (43/48) vs. 66.7% (32/48), respectively. ROC study showed the area under curve of

  20. The effect of radiation therapy for bone metastasis in urinary organ cancer

    International Nuclear Information System (INIS)

    Chikazawa, Ippei; Inoue, Shinya; Nakazawa, Yusuke

    2016-01-01

    Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer. (author)

  1. 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.)

  2. Clinical characteristics and outcome of bone-only metastasis in inflammatory and noninflammatory breast cancers.

    Science.gov (United States)

    Kai, Megumi; Kogawa, Takahiro; Liu, Diane D; Fouad, Tamer M; Kai, Kazuharu; Niikura, Naoki; Hsu, Limin; Willey, Jie S; Theriault, Richard L; Valero, Vicente; Ueno, Naoto T

    2015-02-01

    Inflammatory breast cancer is a rare and aggressive presentation of breast cancer. Bone is a common metastatic site in breast cancer, and bone-only metastatic disease is clinically considered to have a better prognosis than visceral metastasis. However, bone-only metastasis in IBC (bone-only IBC) has not been compared with bone-only metastasis in non-IBC (bone-only non-IBC) in terms of clinical features and outcome. Because of the intrinsically aggressive nature of IBC, we hypothesized that bone-only IBC has a poorer prognosis than does bone-only non-IBC. We retrospectively identified patients with stage III primary diagnosed breast cancer who, between January 1997 and December 2012, had a first recurrence located only in the bone. Among the 197 patients that we defined as a study cohort, 50 patients had IBC and 147 patients had non-IBC. Progression-free survival (PFS) and overall survival (OS) from the date of recurrence were estimated using the Kaplan-Meier method, and patient characteristic groups were compared using the log-rank test. OS did not differ significantly between the 2 groups (P = .2467), but a shorter PFS was seen in patients with bone-only IBC than in patients with bone-only non-IBC (P = .0357). Among patients with estrogen receptor (ER)-positive disease, a much shorter PFS was seen in bone-only IBC than in bone-only non-IBC (P = .0159). Bone-only IBC has a poorer prognosis than does bone-only non-IBC, particularly in those with ER-positive tumors. We might need to consider more aggressive intervention (e.g., chemotherapy) for IBC patients with ER-positive bone-only metastatic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Chirion, Cristina; Stanescu, D.A.; Draganescu, Sandina; Ion, Virginia

    2004-01-01

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

  4. Skin metastasis from conventional giant cell tumor of bone: conceptual significance

    International Nuclear Information System (INIS)

    Tyler, W.; Barrett, T.; Frassica, F.; McCarthy, E.

    2002-01-01

    A conventional giant cell tumor of the proximal femur recurred twice locally and developed pulmonary nodules. The lung lesions were felt to be an example of ''benign'' metastases. Eight months after the initial presentation, the patient developed a single skin nodule on the contralateral leg. Histologic features of the skin nodule showed conventional giant cell tumor identical to the bone lesion. This nodule is a manifestation of arterial metastasis typical of any malignant tumor and seemingly contradicts the concept of ''benign '' metastasis. (orig.)

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

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi

    1994-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-06-01

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

  7. High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor.

    Science.gov (United States)

    Joeckel, Elke; Haber, Tobias; Prawitt, Dirk; Junker, Kerstin; Hampel, Christian; Thüroff, Joachim W; Roos, Frederik C; Brenner, Walburgis

    2014-02-28

    The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 μM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.

  8. [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.

  9. 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

  10. 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

  11. Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice

    OpenAIRE

    Campbell, J. Preston; Karolak, Matthew R.; Ma, Yun; Perrien, Daniel S.; Masood-Campbell, S. Kathryn; Penner, Niki L.; Munoz, Steve A.; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A.; Elefteriou, Florent

    2012-01-01

    Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depr...

  12. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

    Directory of Open Access Journals (Sweden)

    J Preston Campbell

    2012-07-01

    Full Text Available Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

  13. 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.

  14. Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F FDG PET/CT and 99mTc HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation

    International Nuclear Information System (INIS)

    Seo, Hyo Jung; Choi, Yun Jung; Kim, Hyun Jeong; Jeong, Youg Hyu; Cho, Arthur; Lee, Jae Hoon; Yun, Mijin; Choi, Hye Jin; Lee, Jong Doo; Kang, Won Jun

    2011-01-01

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

  15. Advances in the biology of bone metastasis: how the skeleton affects tumor behavior.

    Science.gov (United States)

    Sterling, Julie A; Edwards, James R; Martin, T John; Mundy, Gregory R

    2011-01-01

    It is increasingly evident that the microenvironment of bone can influence the cancer phenotype in many ways that favor growth in bone. The ability of cancer cells to adhere to bone matrix and to promote osteoclast formation are key requirements for the establishment and growth of bone metastases. Several cytokine products of breast cancers (e.g. PTHrP, IL-11, IL-8) have been shown to act upon host cells of the bone microenvironment to promote osteoclast formation, allowing for excessive bone resorption. The increased release of matrix-derived growth factors, especially TGF-β, acts back upon the tumor to facilitate further tumor expansion and enhance cytokine production, and also upon osteoblasts to suppress bone formation. This provides a self-perpetuating cycle of bone loss and tumor growth within the skeleton. Other contributing factors favoring tumor metastasis and colonization in bone include the unique structure and stiffness of skeletal tissue, along with the diverse cellular composition of the marrow environment (e.g. bone cells, stromal fibroblasts, immune cells), any of which can contribute to the phenotypic changes that can take place in metastatic deposits that favor their survival. Additionally, it is also apparent that breast cancer cells begin to express different bone specific proteins as well as proteins important for normal breast development and lactation that allow them to grow in bone and stimulate bone destruction. Taken together, these continually emerging areas of study suggest new potential pathways important in the pathogenesis of bone metastasis and potential areas for targeting therapeutics. Copyright © 2010. Published by Elsevier Inc.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...... 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 ...

  17. Clinical value of SPECT/CT imaging in the diagnosis of bone metastasis

    International Nuclear Information System (INIS)

    Wang Xinhua; Zhao Yanping; Lu Haijian; Dong Zhanfei

    2010-01-01

    Objective: To evaluate the clinical value of 99 Tc m -methylene diphosphonic acid (MDP) SPECT/CT imaging for the diagnosis of bone metastasis. Methods: Patients suspected for bone metastasis and with bone pain of unknown origin were included in this study (n=237). All cases underwent SPECT and CT imaging at 180 min after 99 Tc m -MDP injection. Diagnosis was confirmed by pathology (n=21), more than 2 kinds of radiologieal imaging (MRI, CT, X-ray) (n=106), and clinical follow up in 2 years (n=110). χ 2 -test was used to compare the results of planar and SPECT/CT imaging using SAS 6.12 software. Results: In 237 patients, planar imaging of 142 cases matched the final diagnosis in which 72 had benign lesions and 70 had bone metastases. The definite coincidence rate was 95.30% (142/149). SPECT/CT imaging of 224 cases matched the final diagnosis in which 104 had benign lesions and 120 cases diagnosed as bone metastases. The coincidence and definite coincidence rates were 94.51% (224/237), and 99.48% (192/193). Difference in the definite coincidence rate between planar and SPECT/CT imaging was statistically significant (χ 2 = 5.37, P=0.024). Conclusion: SPECT/CT imaging is valuable for accurate localization of osseous pathology and for improvement of diagnosing bone metastasis. (authors)

  18. Clinicopathological features and prognostic evaluation of bone metastasis in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Anqi Luo

    2017-01-01

    Conclusions: Tumor Stage III-IV, multiple BMs, or coexistence of visceral metastasis were associated with poor prognosis for OS in TNBC patients with BM. These associations may contribute to prevention, early detection, and goal-directed treatment of bone metastatic TNBC.

  19. Bone scan and serum CA 15-3 in bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Mendoza, G.; Cano, R.; Morales, R.; Guzman, C.

    1996-01-01

    CA 15-3 is a tumor marker useful in evolution control of breast cancer, being the serum levels trend the most important parameter. The purpose of this study was to report our experience and show the concordance of bone scan and CA 15-3 in patients with breast cancer attending the Breast and Bone Department of INEN from June to December 1993. One hundred patients had serum CA 15-3 quantification between June and December of 1993 in Nuclear Medicine Center (Peruvian Institute of Nuclear Energy and National Institute of Neoplasic Diseases). We selected 52 patients which simultaneously had a bone scan performed. Patients age ranged from 21 to 67 years (media of 44,57 years). 99m Tc methylenediphosphonate produced by IPEN was the radiopharmaceutical employed. A GE AZS-400 gamma camera was utilized to obtain the bone scans. Ca 15-5 quantification was performed with ELSA-CA 15-3 (CIS bio France) IRMA kit. Bone scan and CA 15-3 media of 17,06 U/ml (DS 15,4). Eight patients had a positive bone scan with a CA 15-3 media of 41,6 U/ml (SD 23,0). CA 15-3 levels ranged between 4,6 and 96,0 U/ml in the first group and 10,1 U/ml to 75,0 U/ml in the second group. Using a cut-off point of 30 U/ml the sensitivity of CA 15-3 was 62,5% and the specificity 93,2% respectively. Mean CA 15-3 values of the negative and positive bone scan groups were significantly different (p=0,0361). The high negative predictive value of CA 15-3 may help to establish which patients will benefit from bone scan procedure. (authors) 42 refs., 2 tabs

  20. Multiple bone metastasis of medulloblastoma; a case report

    International Nuclear Information System (INIS)

    Oh, Jae Cheon; Lee, Seoung Ro; Kim, Yong Soo; Park, Dong Woo; Joo, Kyung Bin; Hahm, Chang Kok

    1996-01-01

    Medulloblastoma is one of the most undifferentiated primitive neuroectodermal tumors and represents about 30% of all posterior fossa tumors in children. Disseminated medulloblastoma, mainly involving cerebral surfaces, ventricles and the subarachnoid space can, in 50% of patients, be identified on intial imaging studies. One third of these lesions metastasize to an extracranial sity, primarily to bone. Osseous metastases, which occur mainly after craniectomy are typically lytic, but osteoblastic lesions also may occur. We experienced the case of a 14 year-old female patient with multiple bone metastases of medulloblastoma after craniectomy. Bone metastatic lesions were present in the right femur and thoracic spine and were osteoblastic or osteolytic

  1. Urinary hydroxyproline excretion as a marker of bone metastasis in prostatic cancer, 2

    International Nuclear Information System (INIS)

    Nemoto, Shin-ichi; Rinsho, Kenji

    1984-01-01

    In 25 patients with prostatic cancer confirmed histologically, 24 patients had bone metastasis on the whole body bone scintigraphy. The extent of bone metastasis was estimated quantitatively by the computerized digitizer. At the same time, the number of the metastatic lesions was counted. The correlations between the area of metastatic lesions on the sup(99m)Tc-MDP bone scintigrams and ESR, LDH, total acid phosphatase, prostatic acid phosphatase, ALP and urinary hydroxyproline/creatinine levels were further investigated. The number of the metastatic lesions was also investigated with the same tumor markers. The results are as follows: 1) The extent of the metastatic lesions was showed more accurately by the area measured with the computerized digitalizer than by the number of metastatic lesions. 2) The correlation between the area of metastatic lesions and serum ALP levels was relatively high (γ = 0.75). But almost all were within normal limits. 3) As for the relation between the area of the metastatic lesions and the urinary hydroxyproline/creatinine levels, the correlation was high (γ = 0.78). And the hydroxyproline/creatinine levels were almost over the upper limit. Therefore, the urinary hydroxyproline/creatinine was considered as a good marker of the extent of bone metastasis. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

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

  3. Three-dimensional trabecular bone architecture of the lumbar spine in bone metastasis from prostate cancer: comparison with degenerative sclerosis

    International Nuclear Information System (INIS)

    Tamada, Tsutomu; Sone, Teruki; Imai, Shigeki; Kajihara, Yasumasa; Fukunaga, Masao; Jo, Yoshimasa

    2005-01-01

    Prostate cancer frequently metastasizes to bone, inducing osteosclerotic lesions. The objective of this study was to clarify the three-dimensional (3D) trabecular bone microstructure in bone metastasis from prostate cancer by comparison with normal and degenerative sclerotic bone lesions, using microcomputed tomography (micro-CT). A total of 32 cancellous bone samples were excised from the lumbar spine of six autopsy patients: 15 metastatic samples (one patient), eight degenerative sclerotic samples (four patients) and the rest from normal sites (three patients). The samples were serially scanned cross-sectionally by micro-CT with a pixel size of 23.20 μm, slice thickness of 18.56 μm, and image matrix of 512 x 512. Each image data set consisted of 250 consecutive slices. The volumes of interest (96 x 96 x 120 voxels) were defined in the original image sets and 3D indices of the trabecular microstructure were determined. The trabecular thickness (Tb.Th) in degenerative sclerotic lesions was significantly higher than that in normal sites, whereas no significant difference was observed in trabecular number (Tb.N). By contrast, in metastatic lesions, the Tb.N was significantly higher with increased bone volume fraction (BV/TV) than in normal sites, and no significant difference was found in Tb.Th. The characteristics of the trabecular surface in the metastatic samples showed concave structural elements with an increase in BV/TV, indicating osteolysis of the trabecular bone. In 3D reconstructed images, increased trabecular bone with an irregular surface was observed in samples from metastatic sites, which were uniformly sclerotic on soft X-ray radiographs. These results support, through 3D morphological features, the strong bone resorption effect in bone metastasis from prostate cancer. (orig.)

  4. 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

    2018-03-01

    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.

  5. 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.

  6. Bone metastasis of undifferentiated pulmonary adenocarcinoma in a cat

    International Nuclear Information System (INIS)

    Jensen, H.E.; Arnbjerg, J.

    1986-01-01

    In the cat, metastases from primary lung tumors (PLT) to distal bones have been described by Moore & Middleton (differentiated adenocarcinoma) and Pool et al. (squamous cell carcinoma) (16 22). This paper describes the radiological and pathological findings in a cat with metastatic undifferentiated papillary adenocarcinoma. The involvement of the toes was the initial sign leading to veterinary consultation

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

    International Nuclear Information System (INIS)

    Liu Baoping; Mao Ronghu; Han Xingmin

    2008-01-01

    Objective: 99 Tc m -4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime (HL91), a new type of hypoxic agents, accumulates in tumor hypoxic tissue specifically. The aim of this study was to evaluate the value of 99 Tc m -HL91 imaging in the diagnosis of bone metastasis. Methods: Nine- teen cases with bone metastasis (without any treatment) and 8 cases with benign lesions underwent SPECT imaging at 4 h after injection of 740 MBq of 99 Tc m -HL91 along with 99 Tc m -methylene diphosphonic acid (MDP) imaging. Regions of interest (ROIs) were drawn in tumor tissue and contralateral normal tissue respectively, and the radioactivity ratios of tumor-to-normal (T/N) were calculated. The t-test was used for data analysis with SPSS 11.0. Results: There were visible uptake of 99 Tc m -HL91 in 79 out of 85 focuses in 19 patients of bone metastasis; however, there was no obvious uptake of 99 Tc m -HL91 in 12 focuses of 8 patients of benign lesions. Significant difference existed between the T/N values of malignant (1.877 ± 0.288) and benign lesions [(0.735 ± 0.236); t=13.065, P 0.05). Conclusion: The results indicated that 99 Tc m -HL91 was useful in diagnosing the malignant and benign bone lesions. (authors)

  8. The relationship between biological marker factors and the bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Xiong Lingjing; Liang Changhua; Li Xinhui; Deng Haoyu; Hu Shuo; Duan Huaxin

    2003-01-01

    Objective: To investigate the relationship between biological marker factors and the bone metastasis in breast cancer to instruct the follow-up of breast cancer patients. Methods: One hundred and fifteen breast cancer patients proved by histological examination after surgery were involved. To detect nm23 protein, C-erbB-2 protein, estrogen receptor (ER), progestogen receptor (PR) expression of their excised breast cancer tissue, immunohistochemical procedures were used. The relationship between biological marker factors and the bone metastasis in breast cancer was analyzed. All patients were examined by radioisotope whole body bone imaging during the follow-up. Results: The results were that the clinical staging, the status of axillary lymph nodes, the expression of nm23 protein, C-erbB-2 protein, ER were related to the bone metastasis in breast cancer, while the age, the mode of operation and the expression of PR were not. Conclusion: Colligating analysis of clinical, pathological status and biological marker factors is very important for the prediction of the prognosis and the direction of the follow-up in breast cancer patients after surgery

  9. Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

    Science.gov (United States)

    Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

    2017-01-01

    Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

  10. 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.

  11. 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

  12. Th-MYCN Mice with Caspase-8 Deficiency Develop Advanced Neuroblastoma with Bone Marrow Metastasis

    OpenAIRE

    Teitz, Tal; Inoue, Madoka; Valentine, Marcus B.; Zhu, Kejin; Rehg, Jerold E.; Zhao, Wei; Finkelstein, David; Wang, Yong-Dong; Johnson, Melissa D.; Calabrese, Christopher; Rubinstein, Marcelo; Hakem, Razqallah; Weiss, William A.; Lahti, Jill M.

    2016-01-01

    Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow (BM). Advances in therapy and understanding of the metastatic process have been limited due in part, to the lack of animal models harboring BM disease. The widely employed transgenic model, the Th-MYCN mouse, exhibits limited metastasis to this site. Here we establish th...

  13. Anemia and thrombocytopenia as initial symptoms of occult breast cancer with bone marrow metastasis

    OpenAIRE

    Liu, Lulu; Zhang, Jingjing; Chen, Mingtai; Ren, Saisai; Liu, Haihui; Zhang, Hao

    2017-01-01

    Abstract Rationale: Occult breast cancer (OBC) is a rare type of breast cancer without any symptoms in the breast and is often presented with initial symptoms of axillary lymph node metastasis or other metastases. The low incidence rates of OBC make it a great challenge to diagnose and cure. Patient concerns: Our case was a 58-year-old female affected by dizziness and fatigue for nearly a month. Blood tests revealed anemia and thrombocytopenia, and pathological results of a bone marrow biopsy...

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

    Science.gov (United States)

    2016-10-01

    6. Products 4 Publications: The paper entitled “CXCL14 is a Marker of Prostate Cancer Bone Metastasis: A Pro-Metastatic Chemokine with CXCR4...overnight, followed by one-hour incubation with 2 mg/ml of bovine serum albumin (BSA). Cells were plated and grown to confluency. Thereafter, a...ARCaPM and PC-3, at 80% confluence, were serum-starved in medium supplemented with 0.1% bovine serum albumin (Probumin, Celliance) for 8 hours

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-23

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

  16. Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

    Directory of Open Access Journals (Sweden)

    Diego Andres Adrianzen Herrera

    2018-04-01

    Full Text Available The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  18. The clinical value of "9"9Tc"m-MDP whole body bone imaging in diagnosing bone metastasis of lung cancer

    International Nuclear Information System (INIS)

    Zhao Yigang; Gou Zhengxing

    2016-01-01

    Objective: To discuss the clinical value of whole body bone imaging on lung cancer bone metastases diagnosis, so as to evaluate the staging of lung cancer patients. Methods: A total of 113 cases of patients diagnosed with lung cancer received whole body imaging, alkaline phosphatase and blood calcium examination. Bone metastasis probability of lung cancer was assessed based on different pathological types. Accuracy rates of bone metastases was compared by whole body bone imaging and suspicious bone metastasis factors (Including one or several items in ostalgia, alkaline phosphatase rising and hypercalcemia). Results The occurrence rate of lung cancer bone metastasis is 36.7%, and the bone metastasis occurrence rate of adenocarcinoma of lung is higher than that of squamous cell lung carcinoma (P < 0.01). Whole body Imaging diagnose of lung cancer bone metastases had sensitivity (92.7%), specificity (83.2%) and accuracy (85.7%). Conclusion: "9"9Tc"m-MDP whole body imaging is a highly sensitive tool to review whole body bone. Lung cancer patients are recommended to receive routine whole body bone imaging. (authors)

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

    International Nuclear Information System (INIS)

    KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh

    2012-01-01

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

  20. ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography for the evaluation of bone metastasis in patients with gastric cancer.

    Science.gov (United States)

    Ma, Dae Won; Kim, Jie-Hyun; Jeon, Tae Joo; Lee, Yong Chan; Yun, Mijin; Youn, Young Hoon; Park, Hyojin; Lee, Sang In

    2013-09-01

    The roles of positron emission tomography and bone scanning in identifying bone metastasis in gastric cancer are unclear. We compared the usefulness of positron emission tomography-computed tomography and scanning in detecting bone metastasis in gastric cancer. Data from 1485 patients diagnosed with gastric cancer who had undergone positron emission tomography-computed tomography and scanning were reviewed. Of 170 enrolled patients who were suspected of bone metastasis in either positron emission tomography or scanning, 81.2% were confirmed to have bone metastasis. The sensitivity, specificity, and accuracy were 93.5%, 25.0%, and 80.6%, respectively, for positron emission tomography and 93.5%, 37.5%, and 82.9%, respectively, for scanning. 87.7% of patients with bone metastasis showed positive findings on two modalities. 15.0% of solitary bone metastases were positive on positron emission tomography only. Positron emission tomography was superior to scanning for the detection of synchronous bone metastasis, but the two modalities were similar for the detection of metachronous bone metastasis. The concordance rate of response assessment after treatment between two modalities was moderate. Positron emission tomography-computed tomography may be more effective for the diagnosis of bone metastasis in the initial staging workup. Conversely, bone scanning and positron emission tomography-computed tomography may be similarly effective for the detection of metachronous bone metastasis. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Oligometastatic state predicts a favorable outcome for renal cell carcinoma patients with bone metastasis under the treatment of sunitinib.

    Science.gov (United States)

    Lu, Xiaolin; Gu, Weijie; Zhang, Hailiang; Zhu, Yao; Shi, Guohai; Ye, Dingwei

    2016-05-03

    The aim of the study was to investigate whether RCC patients with oligometastatic state of bone metastasis treated with sunitinib had a favorable clinical outcome. 22 patients were classified into oligometastatic state of bone metastasis with a median OS of 30.1 months (95%CI: 26.3 to 33.8 months). The 45 patients with non-oligometastatic state had a median OS of 12.7 months (95%CI: 9.43 to 16.0 months). Kaplan-Meier analysis showed significant difference between them (Log Rank test p<0.001). When we set patients with only multiple bone (at least 5 sites) metastases as a single group, there was still significant difference between oligometastatic state group and non-oligometastatic state groups. In multivariate Cox proportion hazard ratio analysis, metastatic states (p=0.012), MSKCC score (p=0.002), ECOG (p=0.001) and lymph nodes metastasis (p=0.000) were significantly associated with prognosis. The integration of metastatic state into the MSKCC risk model improved the c-index from 0.651 to 0.752. 67 patients from Fudan University Shanghai Cancer Center with bone metastatic RCC were divided into 2 metastatic states. One included those with oligometastatic state of bone metastasis with less than 5 sites of bone metastasis. The other involved those patients with multiple bone metastases (at least 5 sites) or together with other sites of metastasis. Then patients with only multiple bone (at least 5 sites) metastases were set into a single group. RCC patients with oligometastatic state of bone metastasis treated with sunitinib had a favorable clinical outcome.

  2. 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.

  3. "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.

  4. The usefulness of measurement of whole body count in assessing bone marrow metastasis in cancer patients with increased periarticular bone uptake on follow-up bone scan: a comparison with bone marrow scan

    International Nuclear Information System (INIS)

    Jin, Seong Chan; Choi, Yun Young; Cho, Suk Shin

    2003-01-01

    Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung canner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases

  5. Correlative study of SPECT bone scan, serum tPSA and fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis

    International Nuclear Information System (INIS)

    Xu Haiqing; Duan Jun

    2011-01-01

    Objective: To study the rules and characteristics of SPECT bone scan, serum TPSA, fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis. Methods: Nuclear medicine SPECT bone scan as the gold standard, retrospective analysis of the in vitro radioimmunoassay in 107 patients with prostate cancer serum PSA (prostate specific antigen) levels, serum fPSA/tPSA ratio and whole body bone imaging studies and pathological classification. Results: 107 patients with prostate cancer : 49 patients had bone metastases, accounting for 45.8% (49/107), in which groups of different pathological comparison between the incidence of bone metastasis significantly, the lower the degree of differentiation, the more the incidence of bone metastases high; with elevated levels of tPSA, the incidence of bone metastasis increased significantly; serum tPSA 4 - 40 ng/ml, the use of fPSA/tPSA ratio may improve the diagnostic specificity of prostate cancer. Conclusion: Patients with bone metastases of prostate cancer incidence and degree of differentiation of prostate cancer, serum PSA levels and fPSA/tPSA ratio of a certain relationship. The lower degree of differentiation,the higher the incidence of bone metastasis. (authors)

  6. 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.

  7. CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.

    Science.gov (United States)

    Dondossola, Eleonora; Rangel, Roberto; Guzman-Rojas, Liliana; Barbu, Elena M; Hosoya, Hitomi; St John, Lisa S; Molldrem, Jeffrey J; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2013-12-17

    Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  9. Exceptional bone metastasis of basal cell carcinoma in Gorlin-Goltz syndrome.

    Science.gov (United States)

    Lamon, Tatiana; Gerard, Stephane; Meyer, Nicolas; Losfeld, Benjamin; Abellan van Kan, Gabor; Balardy, Laurent; Vellas, Bruno

    2010-01-01

    Basal cell carcinoma (BCC), the most prevalent form of cancer worldwide, is a malignant skin neoplasm. It is locally invasive, with an exceptional incidence of reported metastasis. It can also be part of the Gorlin-Goltz syndrome, an autosomal dominant genetic disorder with high penetrance and variable expressivity, which is principally characterized by cutaneous BCC, odontogenic keratocysts, palmar and/or plantar pits, and falx cerebri calcification. We report the exceptional clinical observation of a 54-year-old man presenting bone metastasis from BCC in Gorlin-Goltz syndrome. Less than 300 cases of metastatic BCC have been reported in the literature. The present case is the second associated with Gorlin-Goltz syndrome. Copyright 2009 S. Karger AG, Basel.

  10. Potential Role of CD68 in Breast Cancer Bone Metastasis

    Science.gov (United States)

    2013-01-01

    May 2005 – May 2006: Participated in research on the risk factors of Salmonella in poultry farms and processing plants. EDUCATIONAL ACTIVITIES...as one of two students from a pool of 135 students. Dairy Farm Research Assistant: Dairy Research Center, Mississippi State University. May 2005...418-ML-005) were obtained from R&D Systems (Minneapolis, MN). Neutralizing anti-human IL-11 antibody (AB-218-NA) and normal goat IgG control

  11. Application of semiquantitative analysis of whole body bone imaging on distal femoral metaphysis osseous metastasis of neuroblastoma

    International Nuclear Information System (INIS)

    Liu Yang; Wang Huixiang; Zhou Tao

    2012-01-01

    Objective: To evaluate the value of semiquantitative analysis of whole body bone imaging on distal femoral metaphysis osseous metastasis of neuroblastoma. Methods: Twenty-nine patients with confirmed neuroblastoma by pathological reports were divided into group of metastasis and group of no metastasis by bone marrow slides, X-ray, CT, MRI or clinical follow-up. Whole body bone imaging was performed pre-or postoperation. All cases were analysed by two methods: (1) Semi-quantitative analysis: Regions of interest on bilateral distal femoral metaphysic and middle of femoral were drawn, and their average counts were measured. The ratio of radioactivity of distal femoral metaphysic to middle of femoral was calculated; (2) Visual analysis:Bilateral distal femoral metaphysic metastasis were diagnosed by visual analysis according to whole body bone imaging. The differences between this two methods were compared. Results: There were differences of the ratio of radioactivity of distal femoral metaphysic to middle of femoral between group of metastasis and group of no metastasis (t =8.334, P<0.01), and there was no significant difference between t the two methods (χ 2 =0.68, P>0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of semiquantitative analysis in detecting osseous metastasis were 90.5% , 95.7% , 94.4% , 86.4% and 97.1% , while visual analysis were 81% , 100% , 95.6% , 100% and 94.5% . Conclusions: Radionuclide whole body bone imaging was of great importance in diagnosis of osseous metastasis of neuroblastoma. The diagnostic accuracy was improved by combination of visual analysis and semi-quantitative analysis. (authors)

  12. The usefulness of bone-marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Sone, Teruki; Yoneda, Masaya; Tomomitsu, Tatsushi; Yanagimoto, Shinichi; Muranaka, Akira; Morita, Rikushi; Saito, Noriaki; Tanaka, Hiroyoshi

    1985-01-01

    We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose sup(99m)Tc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients, were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by sup(99m)Tc-MDP bone scintigraphy, sup(99m)Tc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis. (orig.)

  13. Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

    Science.gov (United States)

    Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kitano, Atsuko; Sasada, Shinsuke; Shimomura, Akihiko; Noguchi, Emi; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Fujiwara, Yasuhiro; Tamura, Kenji

    2017-11-01

    Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

  14. An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

    Science.gov (United States)

    Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

    2016-11-22

    One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

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

    International Nuclear Information System (INIS)

    Fan Guanglei; Wan Renming; Peng Mingya; Luan Yufen; Zhao Jun; Liu Jianwen; Xu Longbao

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Yokomizo, Akira; Koga, Hirofumi; Shinohara, Nobuo

    2010-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  18. Comparison of whole body MR diffusion weighted imaging and skeletal scintigraphy in detecting bone metastasis

    International Nuclear Information System (INIS)

    Xu Xian; Ma Lin; Zhang Jinshan; Cai Youquan; Cheng Liuquan; Guo Xinggao; Xu Baixuan

    2008-01-01

    Objective: To evaluate the application of whole body MR diffusion weighted imaging (DWI) in the detection of bone metastasis using skeletal scintigraphy as the reference. Methods: Forty-two healthy volunteers and 38 patients with malignant tumors were enrolled in our study. All the patients received MR examination and skeletal scintigraphy within one week. MR examination was performed on GE signa 3.0T MR scanner using a build-in body coil. The skeletal system was divided into eight regions and the images of the whole body MR DWI and skeletal scintigraphy were reviewed to compare the two modalities patient by patient and region by region. The images were reviewed separately by two radiologists and two nuclear medicine physicians, who were blinded to the results of another imaging modality. Results: A total of 169 metastatic lesions in 69 regions of 30 patients were detected by whole body MR DWI while 156 lesions in 68 regions of 29 patients were identified by skeletal scintigraphy. There were two cases negative in scintigraphy but positive in whole body MR DWI and one case positive in scintigraphy only. There were eight lesions negative in scintigraphy but positive in whole body MR DWI, mainly located in the spine, pelvis and femur. Seven lesions were only detected by scintigraphy, mainly located in the skull, sternum, clavicle and scapula. Conclusion: The whole body MR DWI reveals excellent consistency with skeletal scintigraphy regarding bone metastasis, and the two modalities are complementary for each other. (authors)

  19. Functions of Tenascin-C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2017-10-01

    AWARD  NUMBER:          W81XWH-16-1-0523 TITLE:  Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer Bone Metastasis...Prostat Prostate Cancer  Bone Metastasis   5a.  CONTRACT  NUMBER   Functions of Tenascin- C and Integrin alpha9beta1 in Mediating Prostate Cancer...SUPPLEMENTARY  NOTES 14. ABSTRACT The purpose of this work is to dissect mechanisms responsible for interactions between integrin a9b1 and tenascin- C that are

  20. Clinical utility of Gd-DTPA subtraction MR imaging for spinal bone metastasis

    International Nuclear Information System (INIS)

    Ando, Keiichi; Murakami, Masao; Kuroda, Yasumasa

    1993-01-01

    Based on reports that Gd-DTPA contributes to the detection of tumors, we used it in 31 cases (97 lesions) of spinal bone metastases. The result was that Gd-DTPA increased the intensity of tumors and the surrounding bone marrow to almost the same level in 53%. To show the metastases clearly, an existing subtraction command system was utilized. The technique included the pixel-by-pixel method, to obtain a Gd-DTPA T1-weighted image (T1WI) subtracted by the original T1WI. The detectability of the subtraction image was improved up to 96%, but was less than the original T1WI (99%). Because of the different imaging rationale between two methods, a means to assess the quality of diagnosis must be proposed. To check the normal background, the same kind of postprocessing was performed in 21 patients without malignancy. Gd-DTPA prefusion was highest in the paravertebral veins, moderate in muscles and epidural fat, and lowest in the spinal cord, intervertebral disk and bone cortex. Gd-DTPA enhanced subtraction MR imaging provides a new diagnostic tool to detect and to assess bone metastasis. (author)

  1. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

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

    International Nuclear Information System (INIS)

    Hayashi, Shinya; Hoshi, Hiroaki

    2000-01-01

    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

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

    International Nuclear Information System (INIS)

    Aoki, Jun; Koyama, Yoshinori; Morita, Hideo; Takahashi, Ayako; Nakajima, Takahito; Yagi, Akiko; Arai, Kiyokazu; Shinozaki, Tetsuya; Watanabe, Hideomi

    2005-01-01

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

  4. Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray.

    Science.gov (United States)

    Cosphiadi, Irawan; Atmakusumah, Tubagus D; Siregar, Nurjati C; Muthalib, Abdul; Harahap, Alida; Mansyur, Muchtarruddin

    2018-03-08

    Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study. Immunohistochemistry and gene expression analysis was performed on 81 formalin-fixed paraffin-embedded samples. Data were collected through medical records, and gene expression of 200 selected genes compiled from 6 previous studies was performed using NanoString nCounter. Genetic expression profiles showed that 22 genes were significantly differentially expressed between breast cancer patients with metastasis in bone and other organs (BM+) and non-BM, whereas subjects with only BM showed 17 significantly differentially expressed genes. The following genes were associated with an increasing incidence of BM in the BM+ group: estrogen receptor 1 (ESR1), GATA binding protein 3 (GATA3), and melanophilin with an area under the curve (AUC) of 0.804. In the BM group, the following genes were associated with an increasing incidence of BM: ESR1, progesterone receptor, B-cell lymphoma 2, Rab escort protein, N-acetyltransferase 1, GATA3, annexin A9, and chromosome 9 open reading frame 116. ESR1 and GATA3 showed an increased strength of association with an AUC of 0.928. A combination of the identified 3 genes in BM+ and 8 genes in BM showed better prediction than did each individual gene, and this combination can be used as a training set. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Alison Gartland

    2016-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

  8. EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF.

    Science.gov (United States)

    Chen, Yanke; Gou, Xingchun; Kong, Derek Kai; Wang, Xiaofei; Wang, Jianhui; Chen, Zeming; Huang, Chen; Zhou, Jiangbing

    2015-10-20

    EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.

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

    International Nuclear Information System (INIS)

    Kong, Weidong; Zhang-Salomons, Jina; Hanna, Timothy P.; Mackillop, William J.

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Sosnoski, D.M.; Krishnan, V.; Mastro, A.M.; Kraemer, W.J.; Dunn-Lewis, C.

    2012-01-01

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

  12. 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.

  13. 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

  14. Imaging Findings of Pelvic Tumor Thrombosis Extending from Sacral Bone Metastasis of Adrenocortical Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenichiro Ishida

    2012-01-01

    Full Text Available We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with 18F-fluorodeoxyglucose and single-photon emission computed tomography with 131I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.

  15. F-18 Sodium Fluoride Positron Emission Tomography/Computed Tomography for Detection of Thyroid Cancer Bone Metastasis Compared with Bone Scintigraphy.

    Science.gov (United States)

    Lee, Hyunjong; Lee, Won Woo; Park, So Yeon; Kim, Sang Eun

    2016-01-01

    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 0.05). Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-15

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

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

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

  19. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  20. BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.

    Science.gov (United States)

    Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan

    2014-03-01

    Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease.

  1. Application of Measurements of Serum CA15-3 and B-AKP in Diagnosis of Bone Metastasis in Patients with Post-operative Mammary Cancer

    International Nuclear Information System (INIS)

    Liu Yan; Zhang Xia; Yuan Shiqiang

    2010-01-01

    To evaluate the diagnosis value of serum CA15-3 and B-AKP measurements in diagnosis of bone metastasis images in patients with post-operative mammary cancer, retrospective study on the bone scan images and serum CA15-3 and bone alkaline phosphatase (B-AKP) levels were performed in 92 patients with confirmed post-operative mammary gland cancer. The results showed that the serum levels of CA15-3 and B-AKP were increased step by step significantly along with the advancement of bone metastatic grading from M0 to M3 (P<0.01). The serum levels of CA15-3 and B-AKP were positively correlated with the number of bone metastasis. The positive rate of bone metastasis was 63.2% with serum CA15-3 more than 25U/mL; and the negative predictive value of bone metastasis was 94.5% with serum CA15-3 less than 25U/mL. The positive rate of bone metastasis was 59.6% with serum B-AKP levels more than 20U/L; and the negative predictive value of bone metastasis was 73.5% with serum B-AKP levels less than 20U/L. The negative predictive value of bone metastasis was 100% with serum CA15-3 less than 25U/mL and serum B-AKP levels less than 20U/L. The combined measurement of the serum CA15-3 and B-AKP levels would play an important role in diagnosis of bone scan images in patients with post-operative mammary cancer. (authors)

  2. Central and peripheral nervous systems: master controllers in cancer metastasis.

    Science.gov (United States)

    Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

    2013-12-01

    Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

  3. 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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  5. Clinical application of determination of serum ICTP and PINP contents in cancer patients with bone metastasis for diagnosis and treatment

    International Nuclear Information System (INIS)

    Zhou Haizhong; Li Bin; Zhu Yaling

    2004-01-01

    Objective: To study the clinical usefulness of determination of serum carboxy terminal telepeptide type I collagen (ICTP) and aminoterminal prepeptide type I procollagen (PINP) in cancer patients with bone metastasis for diagnosis and treatment. Methods: Serum ICTP and PINP contents were measured with RIA in 115 patients and 30 controls. These patients consisted of : 1) Group A, less than 6 metastatic foci, n=47 2) Group B, 6-20 foci, n=42 3) Group C, over 20 foci, n=26. A second measurement of these markers was done in 35 of the 115 patients after comprehensive treatment. Results: The Serum ICTP and PINP contents in the patients were significantly higher than those in the controls (p<0.01). The contents increased steadily from Group A to Group C, with significant differences between those in successive groups (p<0.01 or p<0.05). Levels of the two markers correlated well to the number of foci (r=0.68, p<0.01; r=0.52, p<0.01). In the 35 treated patients, the levels dropped significantly (p<0.01, p<0.05 respectively). Conclusion: Both ICTP and PINP level determinations could reflect the clinical status of metastatic size and treatment effect (ICTP more sensitive)

  6. A case report of a thyroid papillary cancer that manifested leukocytosis and hypercalcemia after radiotherapy for bone metastasis

    International Nuclear Information System (INIS)

    Kobayashi, Hisataka; Endo, Keigo; Nishimura, Kazumasa; Kasagi, Kanji; Yamamoto, Itsuo; Konishi, Junji; Abe, Mitsuyuki; Shimizu, Yoshihiko.

    1989-01-01

    Bone metastasis from a thyroid papillary cancer of a 59-year-old woman had been successfully treated with radiotherapy (6,000 rad) and iodine-131 (120 mCi). One year later, the patient developed leukocytosis (maximum 143,000/mm 3 ) and hypercalcemia (16.0 mg/dl). A colony stimulating factor (CSF) was detectable in her plasma, and nude mice that had been given metastatic tissues sinilarly developed leukocytosis and hypercalcemia. Leukocytosis and hypercalcemia seemed to have been caused by the CSF produced in the bone metastasized tissues of this thyroid cancer. (author)

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

    International Nuclear Information System (INIS)

    Silva, M.A. da; Suzuki, M.F.; Rogero, J.R.; Okazaki, K.; Guimaraes, M.I.C.C.; Buchpiguel, C.A.

    2002-01-01

    The 153 Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of 153 Sm-EDTMP at cellular level. The present study was conducted with the aim of evaluating the cytogenetic effects of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique. For that, the blood samples were collected before and one hour after the endovenous administrations of 153 Sm-EDTMP (mean activity of 42.53 ± 5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before 153 Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with 153 Sm-EDTMP, did not influence these parameters. The obtained data showed that the therapy with 153 Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes one hour after its administration in patients, although, theoretically, a long term stochastic effect cannot be disregarded. (author)

  8. Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression.

    Directory of Open Access Journals (Sweden)

    Limin eZhu

    2013-09-01

    Full Text Available The two most common primary bone malignancies, osteosarcoma and Ewing sarcoma, are both aggressive, highly metastatic cancers that most often strike teens, though both can be found in younger children and adults. Despite distinct origins and pathogenesis, both diseases share several mechanisms of progression and metastasis, including neovascularization, invasion, anoikis resistance, chemoresistance and evasion of the immune response. Some of these processes are well-studies in more common carcinoma models, and the observation from adult diseases may be readily applied to pediatric bone sarcomas. Neovascularization, which includes angiogenesis and vasculogenesis, is a clear example of a process that is likely to be similar between carcinomas and sarcomas, since the responding cells are the same in each case. Chemoresistance mechanisms also may be similar between other cancers and the bone sarcomas. Since osteosarcoma and Ewing sarcoma are mesenchymal in origin, the process of epithelial-to-mesenchymal transformation is largely absent in bone sarcomas, necessitating different approaches to study progression and metastasis in these diseases. One process that is less well-studied in bone sarcomas is dormancy, which allows micrometastatic disease to remain viable but not growing in distant sites – typically the lungs – for months or years before renewing growth to become overt metastatic disease. By understanding the basic biology of these processes, novel therapeutic strategies may be developed that could improve survival in children with osteosarcoma or Ewing sarcoma.

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

    Directory of Open Access Journals (Sweden)

    Ferreira DS

    2016-08-01

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

  10. The ratio of free to total serum prostate specific antigen in 412 patients with prostate cancer and analysis of bone metastasis

    International Nuclear Information System (INIS)

    Cai Jinlai; Dong Li; Pan Fangfang; Gao Zheng; Xu Meihua; Shen Wei

    2012-01-01

    Objective: To analyze the characteristics of the ratio of serum free prostate specific antigen (FPSA) to total prostate specific antigen (TPSA) and bone metastases in patients with prostate cancer (Pca). Methods: 412 patients with prostate cancer were enrolled in this study. The preoperative serum FPSA and TPSA levels in patients were measured and SPECT imaging with 99m Tc-MDP were carried out. The patients were further divided into 2 groups according to whether they were found with bone metastases. Results: The result showed that 25.5% of patients (105/412) were found without any bone metastasis, and 74.5% of them(307/412) were with bone metastasis. Among the 307 cases of Pca patients with bone metastases, total 2907 metastatic lesions were found. 97.5% of the metastasis showed a 'hot zone' sign, 2.5% of them showed a 'cold zone' sign. The serum levels of TPSA, FPSA and F/T in patients with bone metastasis were 97.9±59.4μg/L, 10.2±8.1μg/L, 0.09±0.04, respectively. The serum levels of TPSA, FPSA and F/T in patients without bone metastasis were 24.8±23.0μg/L, 4.4±3.4μg/L, 0.12±0.05, respectively. There was significantly different in TPSA, FPSA and F/T between two groups (P<0.01). The TPSA in patients was positively correlated with bone metastasis (r=-0.487, P<0.05). There was positively correlation between the ratio of F/T and bone metastasis (r=-0.641, P<0.05). Conclusion: The prostate patients with F/T<0.15 were highly suspected to have bone metastasis. The SPECT bone scan was recommended in these patients when necessary. The bone metastasis predication sites were pelvis, vertebrae and ribs, most of the type of bone metastases were ossification. (authors)

  11. Primary neuroendocrine carcinoma of breast with liver and bone metastasis detected with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography

    International Nuclear Information System (INIS)

    Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshak; Shibu, Deepu; Radhakrishnan, Edathuruthy Kalarikal; Shinto, Ajit Sugunan

    2014-01-01

    Cases of primary neuroendocrine carcinoma (NEC) of the breast have been reported, though rare. We report the case of a 45-year-old woman presented with jaundice and evaluated to have liver metastasis from neuroendocrine origin. She underwent whole body positron emission tomography/computed tomography, which showed left breast lesion and bone metastasis. Fine-needle aspiration (FNA) of breast revealed a NEC. A diagnosis of a primary NEC of the breast was rendered with hepatic and bone metastasis. She was treated with peptide receptor radionuclide therapy and is on follow-up

  12. Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer.

    Science.gov (United States)

    Al-Ogaili, Zeyad; Troedson, Russell

    2016-02-01

    The aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC). CT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed. Osseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis). Osseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC. © 2015 The Royal Australian and New Zealand College of Radiologists.

  13. Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Al-Ogaili, Zeyad; Troedson, Russell

    2016-01-01

    The aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC). CT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed.Osseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis). Osseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC.

  14. Regional control of melanoma neck node metastasis after selective neck dissection with or without adjuvant radiotherapy

    NARCIS (Netherlands)

    Hamming-Vrieze, Olga; Balm, Alfons J. M.; Heemsbergen, Wilma D.; Hooft van Huysduynen, Thijs; Rasch, Coen R. N.

    2009-01-01

    OBJECTIVE: To examine the effect of adjuvant radiotherapy on regional control of melanoma neck node metastasis. DESIGN: A single-institution retrospective study. SETTING: Tertiary care cancer center. PATIENTS: The study included 64 patients with melanoma neck node metastasis who were treated with

  15. Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope

    Directory of Open Access Journals (Sweden)

    Chelakkot G Prameela

    2018-01-01

    Full Text Available Head and neck malignancies have always been challenging for the clinician, both with regards to locoregional control and distant metastasis. Aggressive approaches translate to an acceptable locoregional control, but distant failures pose a dilemma. Newer, sophisticated, imaging modalities have helped in early diagnosis of solitary metastasis, and in turn have opened up an array of interventional procedures, which to some extent improve the disease-free survival and quality of life, as was seen in the present case of locoregionally controlled advanced hypopharyngeal malignancy who presented with solitary distant metastasis. Still, diligent care needs to be taken not to aggravate the scenario with these interventions.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Mathieu Paul Rodero

    2013-06-01

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

  18. MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.

    Science.gov (United States)

    Wu, Zhiqiang; Wang, Ting; Fang, Meng; Huang, Wending; Sun, Zhengwang; Xiao, Jianru; Yan, Wangjun

    2018-04-06

    Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. In addition, up-regulation of MFAP5 increased the expression of MMP2 and MMP9 and activated the ERK signaling pathway. Conversely, inhibition of MFAP5 suppressed the expression of MMP2, MMP9, p-FAK, p-Erk1/2 and p-cJun. These findings may provide a better understanding about the mechanism of breast cancer and suggest that MFAP5 may be a potential prognostic biomarker and therapeutic target for breast cancer, especially for bone metastasis of breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

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

    International Nuclear Information System (INIS)

    Andresen, R.; Luedtke, C.W.; Kamusella, P.; Wissgott, C.; Radmer, S.; Schober, H.C.

    2014-01-01

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

  1. 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

  2. Controlled release pharmaceutical composition useful for the treatment of diseases and conditions affecting metabolism and/or structural integrity of cartilage and/or bone in male comprises strontium salt

    DEFF Research Database (Denmark)

    2004-01-01

    , hyperparathyroidism, periarticular erosions in rheumatoid arthritis, osteodystrophy, myositis ossificans, Bechterew's disease, osteolytic lesions produced by bone metastasis, bone pain due to bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone...

  3. 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)

  4. Differentially expressed and survival-related proteins of lung adenocarcinoma with bone metastasis.

    Science.gov (United States)

    Yang, Mengdi; Sun, Yi; Sun, Jing; Wang, Zhiyu; Zhou, Yiyi; Yao, Guangyu; Gu, Yifeng; Zhang, Huizhen; Zhao, Hui

    2018-04-01

    Despite recent advances in targeted and immune-based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two-dimensional gel electrophoresis (2-DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan-Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry (IHC) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD. Lastly, the results were analyzed with respect to clinical features and patient's follow-up. We identified a number of matched proteins from 2-DE. High expression of enolase 1 (ENO1) (HR = 1.67, logrank P = 1.9E-05), ribosomal protein lateral stalk subunit P2 (RPLP2) (HR = 1.77, logrank P = 2.9e-06), and NME/NM23 nucleoside diphosphate kinase 2 (NME1-NME2) (HR = 2.65, logrank P = 3.9E-15) was all significantly associated with poor survival (P < 0.05). Further, ENO1 was upregulated (P = 0.0004) and calcyphosine (CAPS1) was downregulated (P = 5.34E-07) in TCGA LUAD RNA-seq expression data. IHC revealed that prominent ENO1 staining (OR = 7.5, P = 0.034) and low levels of CAPS1 (OR = 0.01, P < 0.0001) staining were associated with BM incidence. Finally, we found that LUAD patients with high expression of ENO1 and RPLP2 had worse overall survival. This is the first instance where the genes ENO1, RPLP2, NME1-NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Nakamura S

    2017-02-01

    Full Text Available Sho Nakamura, Tadahisa Fukui, Shuhei Suzuki, Hiroyuki Takeda, Kaname Watanabe, Takashi Yoshioka Department of Clinical Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan Abstract: Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow. Disease control was achieved for 10.8 months following chemotherapy with a modified FOLFOX6 regimen combined with an anti-EGFR antibody. He died of cancer 22.7 and 16.6 months after disease onset and first-line chemotherapy, respectively. This case shows that early tumor shrinkage and deepness of response to the anti-EGFR antibody were observed even in a patient with bone marrow metastasis. Anti-EGFR antibody therapy should therefore be considered even when a patient’s medical condition appears to be poor owing to bone marrow metastasis. Moreover, tumors that are likely to be sensitive to chemotherapy, such as RAS-wildtype colorectal cancers, can be considered for anti-EGFR antibody therapy even if the patient is considered unfit for chemotherapy. Keywords: colorectal cancer, anti-epidermal growth factor receptor antibody, molecular targeted therapies, disseminated intravascular coagulation, standard of care

  6. 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

  7. Regulation of tumor progression and metastasis by bone marrow-derived microenvironments

    DEFF Research Database (Denmark)

    El Rayes, Tina; Gao, Dingcheng; Altorki, Nasser K.

    2017-01-01

    Activating mutations in driver oncogenes and loss-of-function mutations in tumor suppressor genes contribute to tumor progression and metastasis. Accordingly, therapies targeting key tumor cell-intrinsic signaling pathways are being used in clinical trials, and some have met FDA approval. However...

  8. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

    Science.gov (United States)

    Smith, Matthew R; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

    2013-10-20

    Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.

  9. Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

    Directory of Open Access Journals (Sweden)

    Tzong-Tyng Hung

    Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

  10. Use of 153Sm-EDTMP in the treatment of painful bone metastasis (Tunis experience about 80 cases)

    International Nuclear Information System (INIS)

    Mhiri, A.; Hassad, R.; Ben Slimene, M.F.; Sellem, A.; Hammami, H.; Mahersi, M.

    2006-01-01

    Metabolic radiotherapy is a good therapeutic alternative presently proposed for the treatment of disseminated painful bone metastasis. 153 Sm-EDTMP (Quadramet is the radiopharmaceutical used in Tunisia for this indication since October 2001. We are presenting here the results of a 40-month multicentric and retrospective study carried out on 80 patients receiving this new therapy for painful bone metastasis related with various primary carcinoma. All patients received a dose of thirty seven mega-becquerel per kilogram of weight and per treatment (37 MBq/kg/treatment). Our aim was to evaluate four parameters: therapeutic efficiency, factors influencing the response to the treatment, treatment toxicity and sources of treatment failure. A positive response on pain was obtained for 82.5% of cases. This response was complete for 33.9% of them. The average duration of the antalgic protection for each injection was three months, with limits varying from 3 weeks to 12 months. The response was not influenced by the primary type, nor by the number of metastatic lesions, the previously received therapy other than chemotherapy or the general state of the patient prior to treatment. The results obtained after multiple treatments show that the therapies could be repeated with comparable results to those of the first treatment. The only toxicity was of haematological order: It was often mild and reversible with an average complete recovery after 8 weeks. Conclusion: the therapeutic efficiency of Quadramet is at least equivalent to the other therapeutical means, with nearly no side effects. Its early introduction in the management of metastatic patients would allow them to better benefit from its efficiency, simplicity and low toxicity and therefore enjoy a better quality of life. The difficulties we are facing are mainly related to coordination logistic issues during the drug imports and incidentally a lack of awareness and information of the physicians in charge. (author)

  11. Incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis.

    Science.gov (United States)

    Yerram, Prakirthi; Kansagra, Shraddha; Abdelghany, Osama

    2017-04-01

    Background Denosumab therapy is commonly used for the prevention of skeletal-related events in patients with bone metastasis. However, a common side effect of denosumab is hypocalcemia. Objective The aim of the study is to determine the incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis and evaluate risk factors for developing hypocalcemia. Methods This was a retrospective medication use evaluation reviewing the incidence of hypocalcemia in patients receiving outpatient denosumab for prevention of skeletal-related events at Yale-New Haven Hospital. Additionally, various risk factors were reviewed to determine their risk of developing hypocalcemia. Results As per Common Terminology Criteria for Adverse Events v4.03, of the 106 patients included in the study population, 37 (35%) patients had an incidence of hypocalcemia within 30 days of denosumab administration. Fourteen patients (13.2%) had an incidence of grade 1, 13 patients (12.3%) had an incidence of grade 2 hypocalcemia, and 7 patients (6.6%) had an incidence of grade 3 hypocalcemia. Grade 4 hypocalcemia occurred in three (2.8%) patients. Calcium supplementation did not decrease the risk of developing hypocalcemia. Patients who had one or more episodes of acute kidney insufficiency were at a higher risk of developing hypocalcemia (odds ratio = 7.5 (95% confidence interval = 1.8-36.3), p = 0.001). Conclusion This study found that the overall incidence of hypocalcemia and severe hypocalcemia was higher than reported in clinical trials. Additionally, calcium supplementation did not have an effect on incidence of hypocalcemia, while patients who experienced acute kidney insufficiency while on denosumab had a higher likelihood of developing hypocalcemia.

  12. Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model

    National Research Council Canada - National Science Library

    Anderson, Robin

    2001-01-01

    .... We have developed a murine model of breast cancer that actively mimics the human disease. After implantation of tumor cells into the mammary gland, a primary tumour develops and subsequently metastasises to the lymph nodes, lung and bone...

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

    Directory of Open Access Journals (Sweden)

    Caroline Wilson

    2016-09-01

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

  14. 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

  15. Evaluation of genotoxic and cytotoxic effects of 153 Sm-EDTMP in peripheral blood lymphocytes of bone metastasis patients

    International Nuclear Information System (INIS)

    Suzuki, Miriam Fussae

    2003-01-01

    In this study the cellular damage in peripheral lymphocytes after exposure to 153 Sm-EDTMP (Samarium-153 ethylene-diamine-tetramietylene-phosphonate) was determined using the technique of micronuclei analysis and differential coloration. 153 Sm-EDTMP is a radiopharmaceutical used for pain relief in patients with bone metastases. The analysis of the frequency of micronuclei in patient blood samples obtained one hour after endovenous administration of radiopharmaceutical (41 MBq/kg) showed no statistical difference in relation to basal values in binucleated cells. However the analysis of damage distribution in mononucleated cells, showed that the patients without previous radiotherapy treatment presented a significant increase in the frequency of cells with one micronucleus and in those who had taken previous radiotherapy treatment, in cells with two or more micronuclei. The in vitro experiments conducted with the exposition of total blood to three radiation concentrations of 153 Sm-EDTMP (0.370, 0.555 and 1.110 MBq/mL) during one hour showed an increase in the frequency of micronuclei and necrotic and apoptotic cells with increasing radiation dose. Dose-response curves for healthy donors and patients with bone metastasis without previous radiotherapy treatment were constructed. The comparison of the curves showed that patients presented higher radiosensitivity, either micronuclei or dead cell (necrotic or apoptotic) percentages, than healthy donors. (author)

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

    Directory of Open Access Journals (Sweden)

    Shuai Huang

    2016-07-01

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

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

    Science.gov (United States)

    2010-04-01

    I. Glass reinforced hydroxyapatite for hard tissue surgery—part II: in vitro evaluation of bone cell growth and function. Biomaterials 2001;22:2817...24. [72] Cerroni L, Filocamo R, Fabbri M, Piconi C, Caropreso S, Condo SG. Growth of osteoblast-like cells on porous hydroxyapatite ceramics: an in...unappreciated role for bone-forming cells in host defense and disease progression. Immunol Res 30:291–308. doi: 10.1385/ IR :30:3:291 35. Fritz EA, Glant TT

  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. Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG PET/CT imaging

    International Nuclear Information System (INIS)

    Su, Ming Gang; Tian, Rong; Fan, Qiu Ping; Tian, Ye; Li, Fang Lan; Li, Lin; Kuang, An Ren; Miller, John Howard

    2011-01-01

    Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT imaging to allow identification of this abnormality. Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was performed in 9 patients. Standard uptake value (SUV) for each lesion, on early and delayed imaging, was calculated. Lesions were confirmed in 6 patients by biopsy. The PET images correlated with MDCT to establish the imaging characteristics. Solitary lesions were found in 4 patients, two lesions in 1 patient, and in 6 patients there were multiple bone lesions. The SUV early ranged from 1.23 to 9.64 with an average of 3.76 ± 2.40. The SUV delayed ranged from 1.76 to 11.42 with an average of 4.51 ± 3.07. The SUV delayed decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased significantly (11% to 39%) in 3. There was a negative correlation between SUVs and age, as well as the number of affected bones. In our study, FDB had wide skeletal distribution with variability of 18F-FDG uptake and CT appearance. SUV in the delayed stage was seen to either decrease or increase on dual-time 18F-FDG PET scanning. It is very important to recognize the characteristics of this skeletal dysplasia to allow differentiation from skeletal metastasis. (orig.)

  20. Radionuclide bone imaging in suspected skeletal metastasis: does it contribute to diagnosis or treatment ?

    International Nuclear Information System (INIS)

    Reddy, K.G.; Subbarao, K.; Kumaresan, K.; Murthy, V.S.; Kishore, L.T.

    1988-01-01

    A retrospective analysis of 47 patients with suspected bone metastases is performed to evaluate the role of bone scan in diagnosis or treatment and to compare radionuclide images with radiographs. Scan revealed solitary lesions in 27.7 per cent, multiple lesions in 44.7 per cent and was normal in 10.6 per cent of patients studied. In 11 patients the scan was +ve and x-ray was -ve and scan was false negative in one patient. Role of bone scan is evaluated by a scoring method. Scan contributed to correct diagnosis in 25.5 per cent, altered the management in 21.3 per cent of patients. However, scan by itself did not contribute to final management in 48.6 per cent of patients. Scan had misled the diagnosis because of false positive result in 4.3 per cent of patients. It is highlighted that though bone scan is non-specific, it has contributed considerably to the management of majority of patients. (author). 10 refs., 3 tabs., 4 figs

  1. 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

  2. Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis.

    Science.gov (United States)

    Sieh, Shirly; Taubenberger, Anna V; Lehman, Melanie L; Clements, Judith A; Nelson, Colleen C; Hutmacher, Dietmar W

    2014-06-01

    As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

  4. Biomimetic materials for controlling bone cell responses.

    Science.gov (United States)

    Drevelle, Olivier; Faucheux, Nathalie

    2013-01-01

    Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks, such as pain and morbidity at both donor and acceptor sites, the limited quantity of material available, and frequently its inappropriate shape. Researchers have therefore developed alternative strategies that involve biomaterials to fill bone defects. These biomaterials must be biocompatible and interact with the surrounding bone tissue to allow their colonization by bone cells and blood vessels. The latest generation biomaterials are not inert; they control cell responses like adhesion, proliferation and differentiation. These biomaterials are called biomimetic materials. This review focuses on the development of third generation materials. We first briefly describe the bone tissue with its cells and matrix, and then how bone cells interact with the extracellular matrix. The next section covers the materials currently used to repair bone defects. Finally, we describe the strategies employed to modify the surface of materials, such as coating with hydroxyapatite and grafting biomolecules.

  5. 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

    metastasis enhancers and 1 GFP as an internal control). Each ORF is associated with a unique nucleic acid “ barcode ” sequence and is identified by...for this screen because BC3-p53KD cells have not yet metastasized robustly to the lungs at this point. Genomic DNA (gDNA) is isolated and submitted...have already identified a potential functional enhancer of metastasis (Fig. 16). The barcode sequence associated with SMOC2 is enriched in lung

  6. Course of Quality of Life After Radiation Therapy for Painful Bone Metastases: A Detailed Analysis From the Dutch Bone Metastasis Study

    International Nuclear Information System (INIS)

    Westhoff, Paulien G.; Verdam, Mathilde G.E.; Oort, Frans J.; Jobsen, Jan J.; Vulpen, Marco van; Leer, Jan Willem H.; Marijnen, Corrie A.M.; Graeff, Alexander de; Linden, Yvette M. van der

    2016-01-01

    Purpose: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. Patients and Methods: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. Results: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (−0.11 to −0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. Conclusion: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.

  7. Course of Quality of Life After Radiation Therapy for Painful Bone Metastases: A Detailed Analysis From the Dutch Bone Metastasis Study

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Department of Radiotherapy, Radboud University Medical Center, Nijmegen (Netherlands); Verdam, Mathilde G.E. [Department of Medical Psychology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Oort, Frans J. [Research Institute of Child Development and Education, Department of Medical Psychology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, Radboud University Medical Center, Nijmegen (Netherlands); Marijnen, Corrie A.M. [Department of Radiotherapy, Leiden University Medical Center, Leiden (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Linden, Yvette M. van der [Department of Radiotherapy, Leiden University Medical Center, Leiden (Netherlands)

    2016-08-01

    Purpose: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. Patients and Methods: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. Results: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (−0.11 to −0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. Conclusion: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.

  8. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-15

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

  10. 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.

  11. Salivary gland carcinomas: prognostic factors for local control and distant metastasis, the role of radiotherapy

    International Nuclear Information System (INIS)

    Terhaard, C.H.J.; Lubsen, H.; Tweel, I. van der; Hilgers, F.J.M.; Eijkenboom, W.M.H.; Marres, H.A.M.; Tjho-Heslinga, R.E.; Jong, J.M.A. de; Roodenburg, J.L.N.

    1997-01-01

    +radiotherapy: RR 7.0). Bone invasion was the only independent histopathological factor for local control. In the primary radiotherapy group a clear dose-response relationship was shown between 60 and 70 Gy (resp. 0% and 55% 5 yr local control). Actuarial distant metastatic free survival after 8 yr was 64%. Independent prognostic factors were: I: T-stage (T 2 vs T 1 : RR3.0, T 3 vs T 1 : RR3.9, T 4 vs T 1 : RR 10.4), II: N-stage (N+ vs N 0 : RR 3.1) and III: histologic type (acinic cell ca. vs adenoid cystic ca.: RR 0.39, mucoepidermoid ca. vs adenoid cystic ca.: RR 0.29). Conclusion: Multivariate analysis showed that, in patients with salivary gland carcinoma, postoperative radiotherapy independently improved local control. However, small tumors of the oral cavity, when radically resected, may be treated with surgery alone. Histologic type was an independent factor for distant metastasis, but not for local control. In patients treated by primary radiotherapy with curative intent, a local control rate of 55% may be reached using a tumor dose of 70 Gy/ 5 times 2 Gy weekly

  12. Single photon emission computed tomography/spiral computed tomography fusion imaging for the diagnosis of bone metastasis in patients with known cancer

    International Nuclear Information System (INIS)

    Zhao, Zhen; Li, Lin; Li, Fanglan; Zhao, Lixia

    2010-01-01

    To evaluate single photon emission computed tomography (SPECT)/spiral computed tomography (CT) fusion imaging for the diagnosis of bone metastasis in patients with known cancer and to compare the diagnostic efficacy of SPECT/CT fusion imaging with that of SPECT alone and with SPECT + CT. One hundred forty-one bone lesions of 125 cancer patients (with nonspecific bone findings on bone scintigraphy) were investigated in the study. SPECT, CT, and SPECT/CT fusion images were acquired simultaneously. All images were interpreted independently by two experienced nuclear medicine physicians. In cases of discrepancy, consensus was obtained by a joint reading. The final diagnosis was based on biopsy proof and radiologic follow-up over at least 1 year. The final diagnosis revealed 63 malignant bone lesions and 78 benign lesions. The diagnostic sensitivity of SPECT, SPECT + CT, and SPECT/CT fusion imaging for malignant lesions was 82.5%, 93.7%, and 98.4%, respectively. Specificity was 66.7%, 80.8%, and 93.6%, respectively. Accuracy was 73.8%, 86.5%, and 95.7%, respectively. The specificity and accuracy of SPECT/CT fusion imaging for the diagnosis malignant bone lesions were significantly higher than those of SPECT alone and of SPECT + CT (P 2 = 9.855, P = 0.002). The numbers of equivocal lesions were 37, 18, and 5 for SPECT, SPECT + CT, and SPECT/CT fusion imaging, respectively, and 29.7% (11/37), 27.8% (5/18), and 20.0% (1/5) of lesions were confirmed to be malignant by radiologic follow-up over at least 1 year. SPECT/spiral CT is particularly valuable for the diagnosis of bone metastasis in patients with known cancer by providing precise anatomic localization and detailed morphologic characteristics. (orig.)

  13. 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.

  14. Bone metastasis: review and critical analysis of random allocation trials of local field treatment

    International Nuclear Information System (INIS)

    Ratanatharathorn, Vaneerat; Powers, William E.; Moss, William T.; Perez, Carlos A.

    1999-01-01

    Purpose: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. Methods and Materials: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. Results: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment. All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is 'informative' (the processes of loss relate to the outcome) and not acceptable since it

  15. Rapid recurrence and bilateral lungs, multiple bone metastasis of malignant solitary fibrous tumor of the right occipital lobe: report of a case and review.

    Science.gov (United States)

    Wu, Zhengrong; Yang, Hongjun; Weng, Desheng; Ding, Yanqing

    2015-07-09

    Intracranial malignant solitary fibrous tumor (MSFT) is extremely rare. The authors report a case of MSFT of the right occipital lobe with a rapid recurrence and bilateral lung, multiple bone metastasis. The patient was a 25-year-old male presenting with headache, nausea and visual disturbances without obvious cause. Three times right-side occipital craniotomies were performed and two times postoperative conformal radiotherapy were administered within one year. 4 months after the third time of right-side occipital craniotomy, the patient felt right chest pain and neck pain. Positron emission tomography/computed tomography (PET/CT) showed tumor recurrence of the right occipital lobe and bilateral lung metastasis, multiple bone metastasis including: vertebrae, libs, the left iliac wing, sacrum, the right ischium and upper parts of both femurs. Ultrasound guided puncture biopsy of left-side back of the neck and CT guided puncture biopsy of the third lumbar vertebra were performed. General sample showed grayish white or grayish red with irregular shape. Histopathologically, the tumor was composed of areas of alternating hypercellularity and hypocellularity with spindle-shaped cells, which arranged as fascicular, storiform pattern or patternless pattern, with intervening irregular eosinophilic collagen bundles. Some areas showed hemangiopericytoma-like perivascular pattern and perivascular hyalinization. Tumor cells were pleomorphic with mitotic counts of more than 4 per 10 high power fields and showed coagulative necrosis. Immunohistochemically, tumor cells were diffusely positive for vimentin and CD99, focal positive for CD34, bcl-2 and Actin. Ki-67 labelling index was more than 40%. The final pathological diagnosis was MSFT of the right occipital lobe, metastatic MSFT of left-side back of the neck and the third lumbar vertebra. The MSFT of the right occipital lobe with recurrence and bilateral lung, multiple bone metastasis is extremely rare. Although intracranial

  16. 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.

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

    International Nuclear Information System (INIS)

    Treglia, Giorgio; Luca, Giovanella; Barbara, Muoio; Carmelo, Caldarella

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Ambrosini, Valentina; Nanni, Cristina; Castellucci, Paolo; Allegri, Vincenzo; Montini, Giancarlo; Franchi, Roberto; Zompatori, Maurizio; Campana, Davide; Tomassetti, Paola; Rubello, Domenico; Fanti, Stefano

    2010-01-01

    To retrospectively evaluate the sensitivity, specificity and accuracy of 68 Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET). From among patients with NET who underwent 68 Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings. PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there were no false

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

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Karsenty, Gerard

    2003-01-01

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

  20. Hypoxia inducible factor-1 is activated by transcriptional co-activator with PDZ-binding motif (TAZ) versus WWdomain-containing oxidoreductase (WWOX) in hypoxic microenvironment of bone metastasis from breast cancer.

    Science.gov (United States)

    Bendinelli, Paola; Maroni, Paola; Matteucci, Emanuela; Luzzati, Alessandro; Perrucchini, Giuseppe; Desiderio, Maria Alfonsina

    2013-07-01

    The hypoxic microenvironment of bone marrow favours the bone metastasis process. Hypoxia inducible factor (HIF)-1α is hallmark for hypoxia, correlating with poor prognosis and radio/chemotherapy resistance of primary-breast carcinoma. For bone metastasis, the molecular mechanisms involved in HIF-1α expression and HIF-1 (α/β heterodimer)-transcription factor activity are scarcely known. We studied the role played by HIF-1 in the cross-talk between neoplastic and supportive-microenvironmental cells. Also, WWdomain-containing oxidoreductase (Wwox) and transcriptional co-activator with PDZ-binding motif (TAZ) were taken into consideration evaluating whether these Hippo-pathway effectors affect bone-metastatic phenotype through HIF-1 activity. Considering bone-metastasis specimens, nuclear HIF-1α-TAZ co-localisation occurred in neoplastic and supportive cells, such as fibroblasts and endotheliocytes. Based on these data, the functional importance was verified using 1833-bone metastatic clone under hypoxia: nuclear HIF-1α and TAZ expression increased and co-immunoprecipitated, activating HIF-1-DNA binding and transactivation. In contrast, Wwox localised at perinuclear level in neoplastic cells of bone metastasis, being almost absent in supportive cells, and Wwox-protein expression diminished in hypoxic-1833 cells. Thus, TAZ regulation of HIF-1 activity might be important for bone-secondary growth, participating in metastasis-stroma cross-talk. Further, TAZ and HIF-1α-protein levels seemed correlated. In fact, blocking cyclooxygenase-2 with NS398 in hypoxic-1833 cells, not only HIF-1α decreased but also molecular-mechanism(s) upstream of the Hippo pathway were triggered: LATS-dependent TAZ phosphorylation seemed responsible for TAZ nucleus/cytoplasm translocation and degradation. In the 1833-xenograft model, NS398 largely prevented the outgrowth of bone-metastatic cells, probably related to remarkable-extracellular matrix assembly. We gained clinical insight into

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

    International Nuclear Information System (INIS)

    Liu Ningbo; Ma Li; Zhou Wei; Pang Qingsong; Hu Man; Shi Fang; Fu Zheng; Li Minghuan; Yang Guoren; Yu Jinming

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jeannine Missbach-Guentner

    2007-09-01

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

  3. 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.

  4. 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.

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

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

    2014-01-17

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

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

    International Nuclear Information System (INIS)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-01

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

  7. Frameless stereotactic radiosurgery of a solitary liver metastasis using active breathing control and stereotactic ultrasound

    International Nuclear Information System (INIS)

    Boda-Heggemann, J.; Walter, C.; Mai, S.; Dobler, B.; Wenz, F.; Lohr, F.; Dinter, D.

    2006-01-01

    Background and purpose: radiosurgery of liver metastases is effective but a technical challenge due to respiration-induced movement. The authors report on the initial experience of the combination of active breathing control (ABC registered ) with stereotactic ultrasound (B-mode acquisition and targeting [BAT registered ]) for frameless radiosurgery. Patient and methods: a patient with a solitary, inoperable liver metastasis from cholangiocellular carcinoma is presented. ABC registered was used for tumor/liver immobilization. Tumor/liver position was controlled and corrected using ultrasound (BAT registered ). The tumor was irradiated with a single dose of 24 Gy. Results: using ABC registered , the motion of the tumor was significantly reduced and the overall positioning error was registered allowed a rapid localization of the lesion during breath hold which could be performed without difficulties for 20 s. Overall treatment time was acceptable (30 min). Conclusion: frameless stereotactic radiotherapy with the combination of ABC registered and BAT registered allows the delivery of high single doses to targets accessible to ultrasound with high precision comparable to a frame-based approach. (orig.)

  8. Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

    Science.gov (United States)

    Doré, M; Martin, S; Delpon, G; Clément, K; Campion, L; Thillays, F

    2017-02-01

    To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Shimo

    2011-02-01

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

  10. The role of glycosylation in breast cancer metastasis and cancer control

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    Alexandra eKölbl

    2015-10-01

    Full Text Available AbstractGlycosylation and its correlation to the formation of remote metastasis in breast cancer had been an important scientific topic in the last 25 years. With the development of new analytical techniques new insights were gained on the mechanisms underlying metastasis formation and the role of aberrant glycosylation within. Mucin-1 and Galectin were recognized as key players in glycosylation. Interestingly, aberrant carbohydrate structures seem to support the development of brain metastasis in breast cancer patients, as changes in glycosylation structures facilitate an overcoming of blood-brain barrier. Changes in the gene expression of glycosyltransferases are the leading cause for a modification of carbohydrate chains, so that also altered gene expression plays a role for glycosylation. In consequence, glycosylation and changes within can be useful for cancer diagnosis, determination of tumour stage and prognosis, but can as well be targets for therapeutic strategies. Thus, further research on this topic would worth wile for cancer combating.

  11. Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer

    Science.gov (United States)

    Rajput, Ashwani; Teggart, Carol A.; Brattain, Lisa E.; Weber, Hannah R.; Chowdhury, Aparajita; Brattain, Michael G.

    2011-01-01

    Background Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. Methodology/Principal Findings Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival. Conclusion/Significance This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors. PMID:21559296

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

    Directory of Open Access Journals (Sweden)

    Sanjib Chowdhury

    2011-05-01

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

  13. Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Denisa; Plachý, Jiří; Kosla, Jan; Trejbalová, Kateřina; Čermák, Vladimír; Hejnar, Jiří

    2013-01-01

    Roč. 11, č. 10 (2013), s. 1235-1247 ISSN 1541-7786 R&D Projects: GA MŠk(CZ) LC06061 Institutional support: RVO:68378050 Keywords : homeobox gene * metastasis * HOPX Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.502, year: 2013

  14. 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

    Energy Technology Data Exchange (ETDEWEB)

    Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshakh; Shinto, Ajit Sugunan, E-mail: dr.kamaleshwar@gmail.com [Department of Nuclear Medicine and PET/CT, Kovai Medical Centre and Hospital Limited, Coimbatore (India); Madhavan, Devdas [Department of Urology, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital Limited, Coimbatore (India)

    2013-10-15

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

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

    International Nuclear Information System (INIS)

    Chen, L; Chen, X; Wang, B; Gupta, R; Ma, C

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Richhariya A

    2012-02-01

    Full Text Available Akshara Richhariya1, Yi Qian2, Yufan Zhao2, Karen Chung11Amgen Inc, Global Health Economics, Thousand Oaks, CA, USA; 2Amgen Inc, Global Biostatistical Sciences, Thousand Oaks, CA, USAPurpose: Intravenous (IV zoledronic acid (ZA is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in patients with bone metastases secondary to breast or prostate cancer (BC or PC in the clinic setting.Methods: Eligible BC or PC patients with bone metastases scheduled to receive IV ZA were observed at seven US-based oncology clinics. Trained observers recorded the time for preinfusion tasks, ZA drug preparation, intravenous infusion, and follow-up activities.Results: Data are reported for 39 patients (BC: 24; PC: 15. Mean administration time was 69 (standard deviation [SD] 42 minutes for all patients combined, 72 (SD 47 minutes for BC, and 65 (SD 33 minutes for PC. Activity times were comparable between tumor types. Mean time for preinfusion tasks (eg, assessment of vital signs, blood draw and ZA preparation were 12 (SD 20 minutes and 2 (SD 1 minutes, respectively. Mean time required for intravenous infusion (ZA infusion and hydration, when provided and follow-up activities were 54 (SD 31 minutes and 2 (SD 1 minutes, respectively.Conclusion: Infusion time was the greatest time commitment associated with IV ZA administration, representing 78% of the total time on average. Time for preinfusion activities varied substantially. Overall, the mean time for ZA administration represents a notable time burden for healthcare providers and patients.Keywords: time and motion, bisphosphonates, zoledronic acid, intravenous administration

  19. [A case of group G Streptococcus sepsis, chest wall abscess, and vertebral osteomyelitis mimicking a primary lung cancer with bone metastasis].

    Science.gov (United States)

    Hayashi, Yumeko; Ishii, Yoshiki; Arai, Ryo; Obara, Kazuki; Kamada, Aya; Takizawa, Hidenori; Hase, Isano; Mashio, Kazuki; Yamada, Issei; Takemasa, Akihiro; Sugiyama, Kumiya; Fukushima, Yasutsugu; Fukuda, Takeshi

    2007-01-01

    A 73-year-old woman who had been followed in our department of gynecology because of ovarian cancer since 2002, was admitted with liver dysfunction and complaining of back pain and light precordial chest pain. The chest radiograph on admission revealed a tumor in her left upper lung field, and chest CT revealed a tumor adjacent to the chest wall and mediastinum. FDG-positron emission tomography (PET) showed abnormal uptake in the tumor and Th6/7, and the subaortic lymph nodes. On the basis of these findings, primary lung cancer with bone metastasis was suspected. She had a high grade fever on admission, and blood cultures were positive for group G streptococcus. The treatment with intravenous penicillin was started. Percutaneous biopsy of the tumor in her left chest showed an abscess wall in the chest wall, but no evidence of malignancy. Transbronchial lung biopsy and CT-guided biopsy also showed no malignant cells. Since the tumor decreased in size and back pain improved gradually by only antibiotic treatment, a diagnosis of sepsis of group G streptococcus, chest wall abscess, and vertebral osteomyelitis was made. She was treated with intravenous penicillin for 4 weeks and oral amoxicillin for another 4 weeks. After 60 days of antibiotic treatment, the tumor vanished.

  20. Nasopharyngeal carcinoma with pericardial metastasis

    Directory of Open Access Journals (Sweden)

    Shang-Wen Chen

    2011-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Sarah A. Hansen

    2016-10-01

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

  2. Dual-controlled release system of drugs for bone regeneration.

    Science.gov (United States)

    Kim, Yang-Hee; Tabata, Yasuhiko

    2015-11-01

    Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Hypophyseal metastasis

    International Nuclear Information System (INIS)

    Yanes Quesada, Miguel Angel; Yanes Quesada, Marelys; Lopez Arbolay, Omar; Lima Perez, Mayte; Hernandez Yero, Arturo

    2009-01-01

    Metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. We describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. (Author)

  4. Gut metastasis from breast carcinoma.

    Science.gov (United States)

    Al-Qahtani, Mohammed S

    2007-10-01

    Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone, and the brain. Metastases to the gastrointestinal tract are rare with patients presenting with small-bowel perforation, intestinal obstruction, and gastrointestinal bleeding. Here we report a case of a Saudi female presenting with invasive lobular carcinoma and ileo-cecal junction metastasis.

  5. Gut metastasis from breast carcinoma

    International Nuclear Information System (INIS)

    Al-Qahtani, Mohammad S.

    2007-01-01

    Breast cancer is the second most common malignancy in women. Common sites of metastases include the liver, lung, bone and the brain. Metastases to the gastrointestinal tract are with patients presenting with small-bowel perforation, intestinal obstruction and gastrointestinal bleeding. Here we report a case of Saudi female presenting with invasive lobular carcinoma and i leo-junction metastasis. (author)

  6. Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

    International Nuclear Information System (INIS)

    Kuroda, Isao

    2014-01-01

    Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

  7. Bone metastases in breast cancer and its risk factor

    International Nuclear Information System (INIS)

    Tanaka, Shigeko; Matsumura, Yasumasa; Tanaka, Masahiro

    1991-01-01

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

  8. Multiple levels of epigenetic control for bone biology and pathology.

    Science.gov (United States)

    Montecino, Martin; Stein, Gary; Stein, Janet; Zaidi, Kaleem; Aguilar, Rodrigo

    2015-12-01

    Multiple dimensions of epigenetic control contribute to regulation of gene expression that governs bone biology and pathology. Once confined to DNA methylation and a limited number of post-translational modifications of histone proteins, the definition of epigenetic mechanisms is expanding to include contributions of non-coding RNAs and mitotic bookmarking, a mechanism for retaining phenotype identity during cell proliferation. Together these different levels of epigenetic control of physiological processes and their perturbations that are associated with compromised gene expression during the onset and progression of disease, have contributed to an unprecedented understanding of the activities (operation) of the genomic landscape. Here, we address general concepts that explain the contribution of epigenetic control to the dynamic regulation of gene expression during eukaryotic transcription. This article is part of a Special Issue entitled Epigenetics and Bone. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Romeeta Trehan

    2015-01-01

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

  10. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    Science.gov (United States)

    Kuranishi, Fumito; Ohno, Tadao

    2013-06-04

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

  11. 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.

  12. Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer

    NARCIS (Netherlands)

    Vlems, F. A.; Diepstra, J. H. S.; Punt, C. J. A.; Ligtenberg, M. J. L.; Cornelissen, I. M. H. A.; van Krieken, J. H. J. M.; Wobbes, T.; van Muijen, G. N. P.; Ruers, T. J. M.

    2003-01-01

    In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated

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

    Science.gov (United States)

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

    2017-06-01

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

  14. A case of central diabetes insipidus that was caused by pituitary metastasis of lung adenocarcinoma and was controlled by radiation therapy

    International Nuclear Information System (INIS)

    Izumi, Yusuke; Masuda, Takeshi; Nabeshima, Shinji

    2017-01-01

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

  15. Process based analysis of manually controlled drilling processes for bone

    Science.gov (United States)

    Teicher, Uwe; Achour, Anas Ben; Nestler, Andreas; Brosius, Alexander; Lauer, Günter

    2018-05-01

    The machining operation drilling is part of the standard repertoire for medical applications. This machining cycle, which is usually a multi-stage process, generates the geometric element for the subsequent integration of implants, which are screwed into the bone in subsequent processes. In addition to the form, shape and position of the generated drill hole, it is also necessary to use a technology that ensures an operation with minimal damage. A surface damaged by excessive mechanical and thermal energy input shows a deterioration in the healing capacity of implants and represents a structure with complications for inflammatory reactions. The resulting loads are influenced by the material properties of the bone, the used technology and the tool properties. An important aspect of the process analysis is the fact that machining of bone is in most of the cases a manual process that depends mainly on the skills of the operator. This includes, among other things, the machining time for the production of a drill hole, since manual drilling is a force-controlled process. Experimental work was carried out on the bone of a porcine mandible in order to investigate the interrelation of the applied load during drilling. It can be shown that the load application can be subdivided according to the working feed direction. The entire drilling process thus consists of several time domains, which can be divided into the geometry-generating feed motion and a retraction movement of the tool. It has been shown that the removal of the tool from the drill hole has a significant influence on the mechanical load input. This fact is proven in detail by a new evaluation methodology. The causes of this characteristic can also be identified, as well as possible ways of reducing the load input.

  16. Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

    Science.gov (United States)

    2015-12-01

    extensive and painful metastasis of the bone. We proposed compare the impact of exosomes derived from advanced stage prostate cancer on bone stromal cells...The revised report including additional figures, tables, and text, is attached below. 1. INTRODUCTION Bone metastasis is a painful and often lethal...protein interacting protein 2 X*** BG PABPC1 poly (A) binding protein, cytoplasmic 1 X X Inf X PABPC3 poly (A) binding protein, cytoplasmic 3 X

  17. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    International Nuclear Information System (INIS)

    Lee, Chul Min; Lee, Seung Hun; Bae, Ji Yoon

    2015-01-01

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

  18. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-15

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

  19. Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

    Directory of Open Access Journals (Sweden)

    Alison B. Shupp

    2018-06-01

    Full Text Available The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

  20. High-risk factors of parotid lymph node metastasis in nasopharyngeal carcinoma: a case-control study

    International Nuclear Information System (INIS)

    Wang, Hong-zhi; Cao, Cai-neng; Luo, Jing-wei; Yi, Jun-lin; Huang, Xiao-dong; Zhang, Shi-ping; Wang, Kai; Qu, Yuan; Xiao, Jian-ping; Li, Su-yan; Gao, Li; Xu, Guo-zhen

    2016-01-01

    Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma. This was a 1:2 case-control study. All patients in this study were newly diagnosed NPC with N2-3 classification from January 2005 to December 2012. Cases were 22 sides with ipsilateral PLNM. Controls were 44 patients who were randomly selected from N2-3 disease in database. 20/1096 (1.82 %) NPC patients were found PLNM. Sum of the longest diameter for multiple lymph nodes (SLD) in level II was larger in case group than that in control group (6.0 cm vs. 3.6 cm, p = 0.003). Level II lymph node necrosis, level Va/b involvement, and rare neck areas involvement were more common in case group (p = 0.016, p = 0.034, and p < 0.001, respectively). RPN, level III, and level IV metastases showed no significant difference between the two groups. Multivariate analysis in logistic regression showed that only SLD ≥5 cm in II area (OR = 4.11, p = 0.030) and rare neck areas involvement (OR = 3.95, p = 0.045) were associated with PLNM in NPC patients. PLNM was an uncommon event in NPC patients. SLD ≥5 cm in level II and involvement in rare-neck areas may be potentially high-risk factors for PLNM. Sparing parotid in IMRT was not recommended for NPC patients with high risks of PLNM

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  3. Internal targeted radiotherapy for bone metastasis: what about underlying physiopathology; Radiotherapie interne vectorisee (metabolique) des metastases osseuses: quid de la physiopathologie sous-jacente?

    Energy Technology Data Exchange (ETDEWEB)

    Vuillez, J.Ph. [Centre Hospitalier Universitaire, Hopital Michallon, Service de Biophysique et Medecine Nucleaire, 38 - Grenoble (France); Laval, G. [Centre Hospitalier Universitaire, Hopital Michallon, Unite de Recherche et de Soutien en Soins Palliatifs, 38 - Grenoble (France)

    2006-03-15

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

  4. Utility of the dimercapto succinic acid pentavalent (99m Tc- DMSA V) in the diagnostic of secondary bone leisure at metastasis of diverse primary tumours. Preliminary study

    International Nuclear Information System (INIS)

    Ortega L, N.; Pichardo R, P.A.; Marquez H, A.

    2005-01-01

    The more used method in the diagnosis of secondary bone lesions to become cancerous it is by means of having derived of phosphates like it is the 99m Tc- MDP. The reason of acquiring searching with the radiopharmaceutical 99m Tc- DMSA V is with the purpose to find other bone lesions that are not visualized with the gammagraphy with diphosphonate and therefore to increase the specificity of the study. (Author)

  5. Preoperative radiotherapy for resectable rectal cancer: improved local control is prognostic for distant metastasis occurrence and survival

    International Nuclear Information System (INIS)

    Zlotecki, Robert A.; Mendenhall, William M.; Copeland, Edward M.; Vauthey, Jean-Nicholas; Marsh, Robert D.; McCarley, Dean L.; Million, Rodney R.

    1996-01-01

    Purpose/Objective: To evaluate the effect of preoperative external beam radiotherapy (RT) on local control (LC), distant metastasis (DM), survival, and perioperative complications in a 15-year single-institution experience. Disease and treatment variables potentially prognostic for local-regional control and survival were evaluated, and the importance of LC as a determinant of DM and survival was also examined. Materials and Methods: Two hundred ten patients with potentially resectable cancers of the rectum were treated with preoperative external beam RT at a single institution between 1975 and 1990. Excluded were patients with 'fixed' unresectable tumors and those treated with palliative intent only. All patients were treated with megavoltage RT to minimum tumor doses of 30 Gy using multiple-field techniques. Preoperative chemotherapy was not used. Surgical resection was performed 3-5 weeks after completion of RT. Abdominoperineal resection was performed in 175 cases, low anterior resection in 25 cases, and other surgical procedures in 10 cases. Pathologic tumor staging was by the Astler-Coller modification of the Dukes system. Minimum follow-up was 5 years. Survival analysis was performed using the Kaplan-Meier method, with univariate and multivariate analysis of disease and treatment variables for prognostic significance. Results: No treatment-specific variables were predictive for LC, DM, absolute survival, or cause-specific survival. Disease-specific variables prognostic for LC were deep tumor infiltration or 'tethering' on digital rectal exam and Dukes pathologic stage. Ten-year LC rates were 91% for freely mobile tumors vs. 82% for tethered lesions (p=.009). LC rates for Dukes A, B, and C stage tumors were 100%, 91%, and 73%, respectively (p=.02). Variables prognostic for DM were tumor length, annular involvement, LC, and Dukes pathologic stage. Absolute survival at 5 and 10 years was 57% and 36%, respectively. Variables prognostic for absolute survival were

  6. Evaluation of genotoxic and cytotoxic effects of {sup 153} Sm-EDTMP in peripheral blood lymphocytes of bone metastasis patients; Avaliacao dos efeitos genotoxico e citotoxico do {sup 153} Sm-EDTMP em linfocitos perifericos de pacientes com metastase ossea

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Miriam Fussae

    2003-07-01

    In this study the cellular damage in peripheral lymphocytes after exposure to {sup 153} Sm-EDTMP (Samarium-153 ethylene-diamine-tetramietylene-phosphonate) was determined using the technique of micronuclei analysis and differential coloration.{sup 153} Sm-EDTMP is a radiopharmaceutical used for pain relief in patients with bone metastases. The analysis of the frequency of micronuclei in patient blood samples obtained one hour after endovenous administration of radiopharmaceutical (41 MBq/kg) showed no statistical difference in relation to basal values in binucleated cells. However the analysis of damage distribution in mononucleated cells, showed that the patients without previous radiotherapy treatment presented a significant increase in the frequency of cells with one micronucleus and in those who had taken previous radiotherapy treatment, in cells with two or more micronuclei. The in vitro experiments conducted with the exposition of total blood to three radiation concentrations of {sup 153} Sm-EDTMP (0.370, 0.555 and 1.110 MBq/mL) during one hour showed an increase in the frequency of micronuclei and necrotic and apoptotic cells with increasing radiation dose. Dose-response curves for healthy donors and patients with bone metastasis without previous radiotherapy treatment were constructed. The comparison of the curves showed that patients presented higher radiosensitivity, either micronuclei or dead cell (necrotic or apoptotic) percentages, than healthy donors. (author)

  7. Bone metastases from hepatocellular carcinoma; Literature review, radiological features and personal experience. Metastasi ossee di epatocarcinomi; Revisione della letteratura, quadri radiologici e casistica personale

    Energy Technology Data Exchange (ETDEWEB)

    Borghetti, M; Benelli, G; Bonardi, R; Reduzzi, L; Iori, M [Ospedale Maggiore, Crema (Italy). Serv. di Radiologia

    1991-01-01

    Prognosis of patients affected with hepatocellular carcinoma (HCC) has been improved by the modern imaging techniques allowing an early diagnosis and by the value of the therapeutic protocols employed. Staging has also become more and more important. Bone metastases from HCC are reportedly rare. The authors observed a 5.5 incidence in 90 cases of hepatocarcinoma. The metastases were demonstrated by radiography, CT, and nyclear scintigraphy, in patients with skeletal pain. The plain film appearance of skeletal metastases from Hcc was osteolytic in all cases; no surrounding sclerosis was seen. CT scans demonstrated the destructive nature of these lesions, which were associated with bulky soft-tissue masses. Metastases exhibited increased radiotracer ({sup 99m}Tc-MDP) uptake at bone scintigraphy. The authors believe that bone scintigraphy should be included in the staging protocols of the HCCs which need a potentially curative therapy. 28 refs.

  8. Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis

    Science.gov (United States)

    Chiou, Aaron E.; Loh, Hyun Chae; Lynch, Maureen; Seo, Bo Ri; Song, Young Hye; Hoerth, Rebecca; Bortel, Emely L.; Willie, Bettina M.; Duda, Georg N.; Masic, Admir; Wagermaier, Wolfgang; Fratzl, Peter; Fischbach, Claudia

    2017-01-01

    Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with the mineralized bone extracellular matrix. Bone mineral is largely composed of hydroxyapatite (HA) nanocrystals with physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether bone regions typically targeted by metastatic breast cancer feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis with large-area Raman imaging, backscattered electron microscopy, histopathology, and microcomputed tomography to characterize HA in mouse models of advanced breast cancer in relevant skeletal locations. The proximal tibial metaphysis served as a common metastatic site in our studies; we identified that in disease-free bones this skeletal region contained smaller and less-oriented HA nanocrystals relative to ones that constitute the diaphysis. We further observed that osteolytic bone metastasis led to a decrease in HA nanocrystal size and perfection in remnant metaphyseal trabecular bone. Interestingly, in a model of localized breast cancer, metaphyseal HA nanocrystals were also smaller and less perfect than in corresponding bone in disease-free controls. Collectively, these results suggest that skeletal sites prone to tumor cell dissemination contain less-mature HA (i.e., smaller, less-perfect, and less-oriented crystals) and that primary tumors can further increase HA immaturity even before secondary tumor formation, mimicking alterations present during tibial metastasis. Engineered tumor models recapitulating these spatiotemporal dynamics will permit assessing the functional relevance of the detected changes to the progression and treatment of breast cancer bone metastasis. PMID:28923958

  9. Design of complex bone internal structure using topology optimization with perimeter control.

    Science.gov (United States)

    Park, Jaejong; Sutradhar, Alok; Shah, Jami J; Paulino, Glaucio H

    2018-03-01

    Large facial bone loss usually requires patient-specific bone implants to restore the structural integrity and functionality that also affects the appearance of each patient. Titanium alloys (e.g., Ti-6Al-4V) are typically used in the interfacial porous coatings between the implant and the surrounding bone to promote stability. There exists a property mismatch between the two that in general leads to complications such as stress-shielding. This biomechanical discrepancy is a hurdle in the design of bone replacements. To alleviate the mismatch, the internal structure of the bone replacements should match that of the bone. Topology optimization has proven to be a good technique for designing bone replacements. However, the complex internal structure of the bone is difficult to mimic using conventional topology optimization methods without additional restrictions. In this work, the complex bone internal structure is recovered using a perimeter control based topology optimization approach. By restricting the solution space by means of the perimeter, the intricate design complexity of bones can be achieved. Three different bone regions with well-known physiological loadings are selected to illustrate the method. Additionally, we found that the target perimeter value and the pattern of the initial distribution play a vital role in obtaining the natural curvatures in the bone internal structures as well as avoiding excessive island patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Humeral Metastasis in a case of Squamous Cell Carcinoma - a ...

    African Journals Online (AJOL)

    A rare case of squamous cell carcinoma with metastasis to distal acral skeleton – humerus within two months of diagnosis of the primary is being reported. The metastasis to the bones from carcinoma cervix is uncommon especially in the distal appendicular skeleton. A 47 years female came with spontaneous fracture of ...

  11. Combination of prostate specific antigen and pathological stage regarding to gleason score to predict bone metastasis of newly diagnosed prostate cancer

    International Nuclear Information System (INIS)

    Wang Zhen; Zhou Liquan; Gao Jiangping; Shi Lixin; Zhao Xiaoyi; Hong Baofa

    2004-01-01

    To determine the value of tumor grade and serum prostate-specific antigen in predicting skeletal metastases in untreated prostate cancer, the results of bone scans were related retrospectively to levels of serum PSA and tumor Grade based on pathologyical examination in 202 patients with prostate cancer newly diagnosed. Skeletal metastases were present in 7% of patients with serum PSA 100 μg/L. Bone scans are omitted likely in a man newly diagnosed with prostate cancer who has no suggestive clinical features, a serum PSA 100 μg/L. (authors)

  12. Skeletal metastasis in primary carcinoma of the liver | Schweitzer ...

    African Journals Online (AJOL)

    Abstract. Two cases of hepatoma metastasizing to bone are reported. A ttention is drawn to the fact that although skeletal metastasis in hepatoma is uncommon, it may be the initial ;presentafion of the tumour.

  13. Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

    International Nuclear Information System (INIS)

    Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik

    2008-01-01

    Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses

  14. Microenvironment Determinants of Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  15. External Beam Radiotherapy in Metastatic Bone Pain from Solid ...

    African Journals Online (AJOL)

    Key Words: Bone, metastasis, radiotherapy, pain, control randomized ... described the efficacy of external beam radiotherapy in pain .... life of patients with multiple myeloma. Eur. J. ... Rades D, Jeremic B, Hoskin PJ: The Role of ... randomised multicenter trial on single fraction ... "The subjective experience of acute pain. An.

  16. Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

    Science.gov (United States)

    Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

    2017-11-01

    The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

  17. 68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml

    DEFF Research Database (Denmark)

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

    2017-01-01

    /computed tomography ((68)Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on (68)Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (.../ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with (18)F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, (68)Ga-PSMA PET/CT is promising for the restaging of patients...... with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics....

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Reactive Astrocytes in Brain Metastasis

    Directory of Open Access Journals (Sweden)

    David Wasilewski

    2017-12-01

    Full Text Available Brain metastasis, the secondary growth of malignant cells within the central nervous system (CNS, exceeds the incidence of primary brain tumors (i.e., gliomas by tenfold and are seemingly on the rise owing to the emergence of novel targeted therapies that are more effective in controlling extracranial disease relatively to intracranial lesions. Despite the fact that metastasis to the brain poses a unmet clinical problem, with afflicted patients carrying significant morbidity and a fatal prognosis, our knowledge as to how metastatic cells manage to adapt to the tissue environment of the CNS remains limited. Answering this question could pave the way for novel and more specific therapeutic modalities in brain metastasis by targeting the specific makeup of the brain metastatic niche. In regard to this, astrocytes have emerged as the major host cell type that cancer cells encounter and interact with during brain metastasis formation. Similarly to other CNS disorders, astrocytes become reactive and respond to the presence of cancer cells by changing their phenotype and significantly influencing the outcome of disseminated cancer cells within the CNS. Here, we summarize the current knowledge on the contribution of reactive astrocytes in brain metastasis by focusing on the signaling pathways and types of interactions that play a crucial part in the communication with cancer cells and how these could be translated into innovative therapies.

  20. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

  1. 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.

  2. Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity

    International Nuclear Information System (INIS)

    Iwasaki, Ryotaro; Ninomiya, Ken; Miyamoto, Kana; Suzuki, Toru; Sato, Yuiko

    2008-01-01

    The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.

  3. The level of serum tumor makers and bone metastases of lung cancer correlation

    International Nuclear Information System (INIS)

    Li Li; Jin Jianhua

    2014-01-01

    Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. "9"9"mTc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ"2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by "9"9"mTc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of "9"9"mTc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence

  4. Cytogenetic analysis of {sup 153} Sm-EDTMP in peripheral lymphocytes from patients with bone cancer metastasis; Analise citogenetica do {sup 153} Sm-EDTMP em linfocitos perifericos de pacientes com cancer osseo matastatico

    Energy Technology Data Exchange (ETDEWEB)

    Silva, M.A. da; Suzuki, M.F.; Rogero, J.R.; Okazaki, K. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil); Guimaraes, M.I.C.C.; Buchpiguel, C.A. [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Centro de Medicina Nuclear

    2002-07-01

    The {sup 153} Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of {sup 153} Sm-EDTMP at cellular level. The present study was conducted with the aim of evaluating the cytogenetic effects of {sup 153} Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique. For that, the blood samples were collected before and one hour after the endovenous administrations of {sup 153} Sm-EDTMP (mean activity of 42.53 {+-} 5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before{sup 153} Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with {sup 153} Sm-EDTMP, did not influence these parameters. The obtained data showed that the therapy with {sup 153} Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes one hour after its administration in patients, although, theoretically, a long term stochastic effect cannot be disregarded. (author)

  5. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part. Copyright © 2015 Wiley Periodicals, Inc.

  6. The Multiple Roles of Exosomes in Metastasis

    Science.gov (United States)

    WEIDLE, H. ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWEN; RÜGER, RÜDIGER

    2016-01-01

    Exosomes are important contributors to cell−cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes. PMID:28031234

  7. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  8. Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

    Science.gov (United States)

    2011-04-01

    of rhBMP-2 in patients.8 Both the physical properties and pharmacokinetics of the FR +BMP scaffold are believed to contribute to its superior...scaffolds investigated in this study exhibit these key physical properties.28 Further, the observation of re- generated bone grown in direct contact with...Amit, Y., Arbel, R., Aro, H., Atar , D., Bishay, M., Borner, M.G., Chiron, P., Choong, P., Cinats, J., Courtenay, B., Fei- bel, R., Geulette, B., Gravel

  9. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  10. Spinal Metastasis Of Wilm's Tumuor: An Unusual Occurrence ...

    African Journals Online (AJOL)

    Background: Metastasis of the Wilm's tumor is usually to surrounding tissue, the lungs and the liver. Rarely is there spread to bone, bone-marrow, spinal canal and other tissues, but this unusual mode of spread sometimes occurs. Objectives: To report a case of Wilm's tumuor complicated by spastic paraplegia consequent to ...

  11. Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report

    Directory of Open Access Journals (Sweden)

    Takashi Tokita

    2018-05-01

    Full Text Available We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment. Keywords: Melanoma, Urethral neoplasm, Inguinal lymphadenectomy, Nivolumab

  12. Characterization of controlled bone defects using 2D and 3D ultrasound imaging techniques

    Energy Technology Data Exchange (ETDEWEB)

    Parmar, Biren J; Longsine, Whitney; Han, Arum; Righetti, Raffaella [Department of Electrical and Computer Engineering, Dwight Look College of Engineering, Texas A and M University, College Station, TX (United States); Sabonghy, Eric P [OneOrtho Orthopedic Surgery Clinic, Houston, TX (United States); Tasciotti, Ennio; Ferrari, Mauro [Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX (United States); Weiner, Bradley K, E-mail: righetti@ece.tamu.ed [Division of Spinal Surgery, Department of Orthopaedic Surgery, Methodist Hospital, Houston, TX 77030 (United States)

    2010-08-21

    Ultrasound is emerging as an attractive alternative modality to standard x-ray and CT methods for bone assessment applications. As of today, however, there is a lack of systematic studies that investigate the performance of diagnostic ultrasound techniques in bone imaging applications. This study aims at understanding the performance limitations of new ultrasound techniques for imaging bones in controlled experiments in vitro. Experiments are performed on samples of mammalian and non-mammalian bones with controlled defects with size ranging from 400 {mu}m to 5 mm. Ultrasound findings are statistically compared with those obtained from the same samples using standard x-ray imaging modalities and optical microscopy. The results of this study demonstrate that it is feasible to use diagnostic ultrasound imaging techniques to assess sub-millimeter bone defects in real time and with high accuracy and precision. These results also demonstrate that ultrasound imaging techniques perform comparably better than x-ray imaging and optical imaging methods, in the assessment of a wide range of controlled defects both in mammalian and non-mammalian bones. In the future, ultrasound imaging techniques might provide a cost-effective, real-time, safe and portable diagnostic tool for bone imaging applications.

  13. BEYOND GLYCEMIC CONTROL IN DIABETES MELLITUS: EFFECTS OF INCRETIN-BASED THERAPY ON BONE METABOLISM

    Directory of Open Access Journals (Sweden)

    ELENA eCECCARELLI

    2013-06-01

    Full Text Available Diabetes mellitus (DM and osteoporosis (OP are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM and in type 2 (T2DM diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density (BMD. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g. tiazolidinediones, insulin may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e. GLP-1 receptor agonists and DPP-4 inhibitors is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells.Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

  14. The behaviour of fatigue-induced microdamage in compact bone samples from control and ovariectomised sheep.

    Science.gov (United States)

    Kennedy, Oran D; Brennan, Orlaith; Mauer, Peter; O'Brien, Fergal J; Rackard, Susan M; Taylor, David; Lee, T Clive

    2008-01-01

    This study investigates the effect of microdamage on bone quality in osteoporosis using an ovariectomised (OVX) sheep model of osteoporosis. Thirty-four sheep were divided into an OVX group (n=16) and a control group (n=18). Fluorochromes were administered intravenously at 3 monthly intervals after surgery to label bone turnover. After sacrifice, beams were removed from the metatarsal and tested in three-point bending. Following failure, microcracks were identified and quantified in terms of region, location and interaction with osteons. Number of cycles to failure (Nf) was lower in the OVX group relative to controls by approximately 7%. Crack density (CrDn) was higher in the OVX group compared to controls. CrDn was 2.5 and 3.5 times greater in the compressive region compared to tensile in control and OVX bone respectively. Combined results from both groups showed that 91% of cracks remained in interstitial bone, approximately 8% of cracks penetrated unlabelled osteons and less than 1% penetrated into labelled osteons. All cases of labelled osteon penetration occurred in controls. Crack surface density (CrSDn), was 25% higher in the control group compared to OVX. It is known that crack behaviour on meeting microstructural features such as osteons will depend on crack length. We have shown that osteon age also affects crack propagation. Long cracks penetrated unlabelled osteons but not labelled ones. Some cracks in the control group did penetrate labelled osteons. This may be due the fact that control bone is more highly mineralized. CrSDn was increased by 25% in the control group compared to OVX. Further study of these fracture mechanisms will help determine the effect of microdamage on bone quality and how this contributes to bone fragility.

  15. Pulmonary Metastasis from Pseudomyxoma Peritonei

    Directory of Open Access Journals (Sweden)

    Toshiyuki Kitai

    2012-01-01

    Full Text Available Pseudomyxoma peritonei (PMP is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.

  16. Factors controlling the engraftment of transplanted dog bone marrow cells

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Klapwyk, W.M.; Heidt, P.J.; Hogeweg, B.; Zurcher, C.; Bekkum, D.W. van

    1982-01-01

    The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrme was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility comples (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rateof hemopoietic recovery correlated with the number of BM cells given. Approximtely 2 x 10 7 autologous and 1 x 10 8 MHC identical BM cells.kg -1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterine inertia in female dogs after 7.5 GY TBI. Fertility in males or females was not changed by radiation. An increase of pancreas fibrosis was noted in dogs receiving fractions of 6.0 Gy TBI. (author)

  17. Cells at risk for the production of bone tumors in man: an electron microscope study of the endosteal surface of control bone and bone from a human radium case

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Henning, C.B.

    1979-01-01

    The endosteal cells of bone from a radium dial worker are documented for the first time by electron microscopy. Fresh samples of bone and tumor tissue from the femur were made available as a result of amputation for a fibrosarcoma in the region of the right knee joint. Bone was examined from a site proximal to the tumor where no invasion of tumor tissue was evident. The patient, who was exposed at age 16 in 1918, died in 1978 with a terminal body burden, calculated to be 1.2 μCi, 226 Ra. A sample of bone, also obtained at amputation from an unirradiated control patient, age 65, was examined from the same site in the femur. A comparison of the bone bone-marrow interface from the two patients showed that, unlike the control bone where cells were seen close to bone mineral, an intervening fibrotic layer was interposed between the marrow cells and the bone mineral in the radium bone. This layer varied in thickness up to 50 μm and was usually acellular, although cell remnants and occasionally cells, which appeared viable, were seen. Autoradiographs of sections of bone adjacent to those used for the electron microscope studies are being evaluated

  18. Radionuclide bone image in growing and stable bone island

    International Nuclear Information System (INIS)

    Go, R.T.; El-Khoury, G.Y.; Iowa Univ., Iowa City; Wehbe, M.A.

    1980-01-01

    A normal radionuclide bone image can facilitate distinction between a bone island and significant pathologic processes, especially an osteoblastic metastasis. This distinction becomes more crucial when growth is detected in an isolated sclerotic bone lesion or if a relatively large sclerotic lesion is detected de novo in patients with a known neoplasm. This report presents three patients with isolated bone islands: two with interval growth, the other with a relatively large stable lesion; all showing a normal radionuclide bone image. (orig.) [de

  19. Cavitary pulmonar metastasis

    International Nuclear Information System (INIS)

    Marchiori, E.; Matushita, J.P.K.; Azevedo, C.M. de

    1984-01-01

    Seven cases of cavitary lung metastasis, four from head and neck neoplasma, two from uterine carcinoma and one from hepatoma are reported. The physiopathology and the most common sites of this kind of lesion are discussed. The rarity of the solitary excavated metastasis from hepatoma, not reported previously in the literature reviewed, is emphasized. (Author) [pt

  20. Humeral Metastasis from Cervical Cancer: A Rare Case Report

    OpenAIRE

    Sonia Chhabra; KanikaTaneja; Megha Ralli; Sunita Singh; Aditi Arora; Sohrab Arora; Pansi Gupta

    2015-01-01

    Long bone metastasis in cervical cancer is a rare presentation generally seen in the lumbar column or ribs. The reported rates of bone metastases are between 15%-29%. It is associated with poor prognosis. Bone scan and magnetic resonance imaging are useful techniques for diagnosis. In this case report, a 32-year old female with a previous history of cervical carcinoma FIGO stage IIIA presented with severe pain and swelling in her right humerus. X-ray and magnetic resonance imag...

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

    International Nuclear Information System (INIS)

    Imamura, Akihiko; Hoshi, Hiroaki; Jinnouchi, Seishi; Samejima, Masahiko; Watanabe, Katsushi

    1988-01-01

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

  2. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  3. Glycemic control and alveolar bone loss progression in type 2 diabetes.

    Science.gov (United States)

    Taylor, G W; Burt, B A; Becker, M P; Genco, R J; Shlossman, M

    1998-07-01

    This study tested the hypothesis that the risk for alveolar bone loss is greater, and bone loss progression more severe, for subjects with poorly controlled (PC) type 2 diabetes mellitus (type 2 DM) compared to those without type 2 DM or with better controlled (BC) type 2 DM. The PC group had glycosylated hemoglobin (HbA1) > or = 9%; the BC group had HbA1 or = 75% were used to identify the worst bone score (WBS) in the dentition. Change in worst bone score at follow-up, the outcome, was specified on a 4-category ordinal scale as no change, or a 1-, 2-, 3-, or 4-category increase over baseline WBS (WBS1). Poorly controlled diabetes, age, calculus, time to follow-up examination, and WBS1 were statistically significant explanatory variables in ordinal logistic regression models. Poorly controlled type 2 DM was positively associated with greater risk for a change in bone score (compared to subjects without type 2 DM) when the covariates were included in the model. The cumulative odds ratio (COR) at each threshold of the ordered response was 11.4 (95% CI = 2.5, 53.3). When contrasted with subjects with BC type 2 DM, the COR for those in the PC group was 5.3 (95% CI = 0.8, 53.3). The COR for subjects with BC type 2 DM was 2.2 (95% CI = 0.7, 6.5), when contrasted to those without type 2 DM. These results suggest that poorer glycemic control leads to both an increased risk for alveolar bone loss and more severe progression over those without type 2 DM, and that there may be a gradient, with the risk for bone loss progression for those with better controlled type 2 DM intermediate to the other 2 groups.

  4. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    Science.gov (United States)

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-05

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

  5. The Role of Extracellular Vesicles in Metastasis

    Science.gov (United States)

    2017-10-01

    transferred via ESVs to osteoblasts. These bone cells represent the most common tissue target for breast cancer metastasis, and we will mimic ESV...separation of beads will result in good separation of bead-complexed exosomes and microvesicles. Furthermore, we show that we can use the same device to...proteins for 3 common exosome tetraspanin markers (CD9, CD63, and CD81) [Andreu & Yanez-Mo 2014] in tandem (pLLNL-exo-GFP) in order to both increase

  6. Strontium-89 therapy and subarachnoid phenol block successfully eliminated intractable pain of metastasis in the patient with advanced urachal carcinoma

    International Nuclear Information System (INIS)

    Arakawa, Yasuhiro; Inoue, Daisuke; Sakuyama, Toshikazu; Nagasaki, Eijiro; Aiba, Keisuke

    2011-01-01

    We report a case of a 39-year-old man with intractable multifocal pain caused by metastatic urachal carcinoma to the bone. The patient underwent a partial cystectomy in May 2008, and lung metastasis occurred 9 months after the surgery. He then received salvage chemotherapy, but developed metastasis to the liver, brain, and bone. He was hospitalized due to a shoulder pain, a lower back pain, buttocks pain, numbness in both legs, and drop foot in right leg. MRI revealed metastases to the spine, and lumbar spinal canal stenosis with cauda equina compression. Even a combination of fentanyl-patch, oral acetaminophen, gabapentin and paroxetine was not effective for pain control. Strontium-89 therapy and subarachnoid phenol block successfully eliminated intractable pain. The patient could be discharged from hospital and received a palliative care at home for a short period of time. (author)

  7. Gastric metastasis of triple negative invasive lobular carcinoma

    OpenAIRE

    Caglayan Geredeli; Osman Dogru; Ethem Omeroglu; Farise Yilmaz; Faruk Cicekci

    2015-01-01

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis o...

  8. Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

    Science.gov (United States)

    Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

    2012-01-01

    The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

  9. Bone health in patients with epilepsy: A community-based pilot nested case–control study

    Directory of Open Access Journals (Sweden)

    Shweta Singla

    2017-01-01

    Full Text Available Background: Antiepileptic drugs (AEDs adversely affect bone health and there are reports describing association of alternations of bone and mineral metabolism in epileptic patients. Objectives: This study was undertaken to evaluate the bone profile (bone mineral parameters and bone mineral density [BMD] of patients with epilepsy and compare them to their age-, gender-, and socioeconomic status-matched healthy controls in a community. Materials and Methods: This was a nested case–control study conducted in fifty individuals, which included 25 cases (age above 18 years and on AEDs for at least 3 years for which 25 controls were selected from the same community. Bone mineral parameters (serum calcium, proteins, phosphorous, alkaline phosphate, parathyroid hormone, and Vitamin D and BMD were measured. Results: There was significant hypocalcemia (P = 0.003, hypoproteinemia (P = 0.014, hyperparathyroidism (P = 0.048, and increased levels of serum alkaline phosphatase (P = 0.019 in cases as compared to controls. The difference was insignificant in the serum levels of Vitamin D and phosphorous among both the groups. Vitamin D was significantly low in female patients as compared to males (P = 0.043. There was no significant difference in BMD at the lumbar spine and femur neck among both the groups. Mean duration of epilepsy was longest in patients with osteoporosis (23.6 years, and increasing duration of epilepsy was associated with reduction in age- and sex-corrected total BMD mean Z-score anteroposterior spine. There was negative correlation between cumulative drug load and T-score of patients with epilepsy. Conclusion: Patients on long-term AED treatment have altered bone profile as evident from biochemical parameters and reduced BMD. There is a need for more extensive research and that too on a larger sample size.

  10. Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study

    DEFF Research Database (Denmark)

    Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Mosekilde, Leif

    2012-01-01

    In a controlled cohort study, bone mineral density (BMD) was measured in 153 women pre-pregnancy; during pregnancy; and 0.5, 4, 9, and 19 months postpartum. Seventy-five age-matched controls, without pregnancy plans, were followed in parallel. Pregnancy and breastfeeding cause a reversible bone...... in fat mass differed according to breastfeeding status with a slower decline in women who continued breastfeeding. Calcium and vitamin D intake was not associated with BMD changes. CONCLUSION: Pregnancy and breastfeeding cause a reversible bone loss. At 19 months postpartum, BMD has returned to pre-pregnancy...... loss, which, initially, is most pronounced at trabecular sites but also involves cortical sites during prolonged breastfeeding. INTRODUCTION: Conflicting results have been reported on effects of pregnancy and breastfeeding on BMD and body composition (BC). In a controlled cohort study, we elucidate...

  11. A brief instrument to measure health-related quality of life in patients with bone metastasis: validation of the German version of Bone Metastases Quality-of-Life-10 (BOMET-QoL-10).

    Science.gov (United States)

    Marschner, Norbert; Wilke, Jochen; Reschke, Daniel; Kaiser, Florian; Schmoor, Claudia; Grugel, Renate; Boller, Emil

    2018-06-06

    This prospective, epidemiologic study was designed to translate the original Spanish Bone Metastases Quality-of-Life-10 (BOMET-QoL-10) questionnaire and undertake a validation of the translated German version of BOMET-QoL-10 in Germany to assess health-related quality of life (HRQoL) in patients with bone metastases (BM). The translation process included forward and backward translations, and a linguistic validation. Patients aged ≥18 years with histological confirmation of cancer, diagnosed with BM, life expectancy ≥6 months, and fluency in German were eligible for this study (enrolled consecutively in 33 outpatient centers in Germany). Patients were given the German version of BOMET-QoL-10 together with European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and EORTC QLQ-BM22 questionnaires at inclusion, 6 weeks, 3 months, and 6 months after inclusion. A debriefing questionnaire was administered at inclusion to determine patient acceptability and understanding. Data include 364 patients with BM (median age: 68 years; female sex: 71.7%). The BOMET-QoL-10 is brief and clear (median completion time: 5 minutes; >90% of patients completed the questionnaire without assistance). The BOMET-QoL-10 forms only one overall scale. All 10 items showed a substantial correlation with the first factor (factor loading, range: 0.58 - 0.86). BOMET-QoL-10 exhibits high internal consistency and reproducibility (Cronbach's alpha: 0.91; intra-class correlation coefficient: 0.76). BOMET-QoL-10 showed significant correlations (range: 0.69 - 0.79) both with EORTC QLQ-C30 and EORTC QLQ-BM22 within the functioning (physical, social, interference) and symptom (fatigue, pain) scales, displayed significant sensitivity to change in EORTC QLQ-BM22 scores, and proved potential ability to detect change in HRQoL in patients with different disease status. There was a high proportion of females in our study which might represent a limitation. The

  12. Influence of controlled immediate loading and implant design on peri-implant bone formation.

    Science.gov (United States)

    Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

    2007-02-01

    Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (pimplant contact occurred was the highest for SL and significantly different from SU (pimplant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

  13. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Zhang, L.; Wang, H.; Liang, S.; Ma, C.

    2015-01-01

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  14. Imaging Primary Prostate Cancer and Bone Metastasis

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2004-01-01

    ... and androgen independent prostate cancer xenografted mice. Specific Aims: (1) Design, synthesize, and characterize positrori emitting bombesin analogs, labeled with copper-64 or fluorine-I 8; (2...

  15. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2018-03-01

    E) ELISA for total CXCL1 and CXCL5 levels in supernatants of MΦs alone or cocultured with RM1(HA) or PC3(HA). (F) Transcriptional activ- ity cell...marrow macrophages (Fig- ure 1D). ELISA evaluation for CXCL1 and CXCL5 proteins in the coculture media for apoptotic cancer cells (Figure 1E) confirmed... ELISA analysis of total pro- tein lysates from VEH- (n = 10) and AP-treated (n = 11) tumor vossicles. (G) Graphs depicting the correlation between

  16. Study on the serum levels of relevant cytokines IL-β, IL-6, IL-8 and tumor markers CEA, CA15-3, PRL in breast cancer patients with bone metastatic lesions shown on SPECT radio-nuclide bone scan

    International Nuclear Information System (INIS)

    Zhu Bao

    2009-01-01

    Objective: To explore the correlationship between SPECT radionuclide bone scan and serum levels of three tumor markers as well as three cytokines in patients with breast cancer. Methods: Serum levels of IL-1β, IL-6, IL-8, CEA, CA15-3(with RIA) and PRL(with CLIA) were determined in 1)20 breast cancer patients with definite bone metastatic lesions shown on radio-nuclide bone scan 2) 20 breast cancer patients without bone metastasis 3) 30 patients with benign breast disorders and 4) 35 controls. Results: The serum tumor markers levels in patients osseous metastasis were significantly higher than those in the other three groups (P 0.05). The serum levels of IL-6, IL-8, IL-1β in patients with osseous metastasis were also significantly higher than those in other groups(P<0.05). Conclusion: Over expression of CEA, CA15-3 and PRL as well as IL-6, IL-8, IL-1β were related with osseous metastasis from breast cancer. Determination of the levels of these six parameters would be helpful for dynamic monitoring of the extent of metastasis. (authors)

  17. Nanofibrous yet injectable polycaprolactone-collagen bone tissue scaffold with osteoprogenitor cells and controlled release of bone morphogenetic protein-2

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, Gayathri; Bialorucki, Callan [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Yildirim-Ayan, Eda, E-mail: eda.yildirimayan@utoledo.edu [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614 (United States)

    2015-06-01

    In this work, we developed a nanofibrous, yet injectable orthobiologic tissue scaffold that is capable of hosting osteoprogenitor cells and controlling kinetic release profile of the encapsulated pro-osteogenic factor without diminishing its bioactivity over 21 days. This innovative injectable scaffold was synthesized by incorporating electrospun and subsequently O{sub 2} plasma-functionalized polycaprolactone (PCL) nanofibers within the collagen type-I solution along with MC3T3-E1 cells (pre-osteoblasts) and bone morphogenetic protein-2 (BMP2). Through changing the PCL nanofiber concentration within the injectable scaffolds, we were able to tailor the mechanical strength, protein retention capacity, bioactivity preservation, and osteoinductive potential of the scaffolds. The nanofibrous internal structure of the scaffold allowed us to use a low dose of BMP2 (200 ng/ml) to achieve osteoblastic differentiation in in vitro culture. The osteogenesis capacity of the injectable scaffolds were evaluated though measuring MC3T3-E1 cell proliferation, ALP activity, matrix mineralization, and early- and late-osteoblast specific gene expression profiles over 21 days. The results demonstrated that the nanofibrous injectable scaffold provides not only an osteoinductive environment for osteoprogenitor cells to differentiate, but also a suitable biomechanical and biochemical environment to act as a reservoir for osteogenic factors with controlled release profile. - Highlights: • Injectable nanofibrous scaffold with osteoprogenitor cells and BMP2 was synthesized. • PCL nanofiber concentration within collagen scaffold affected the BMP2 retention and bioactivity. • Optimal PCL concentration was identified for mechanical stability, injectability, and osteogenic activity. • Scaffolds exhibited long-term osteoinductive capacity for bone repair and regeneration.

  18. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

    Directory of Open Access Journals (Sweden)

    Fu YC

    2015-12-01

    Full Text Available Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid microspheres (SIM/PLGA that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration

  19. Instrument for bone mineral measurement using a microprocessor as the control and arithmetic element

    International Nuclear Information System (INIS)

    Alberi, J.L.; Hardy, W.H. II.

    1975-11-01

    A self-contained instrument for the determination of bone mineral content by photon absorptometry is described. A high-resolution detection system allows measurements to be made at up to 16 photon energies. Control and arithmetic functions are performed by a microprocessor. Analysis capability and limitations are discussed

  20. Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.

    Science.gov (United States)

    Xu, Tao-Tao; Jin, Hong-Ting; Tong, Pei-Jian

    2018-04-12

    As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen defifi ciency as a pathological condition has a negative effect on the skeleton of body, specififi cally the disorder of bone homeostasis. Present studies indicate that Shen defifi ciency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue (osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

  1. Comparison of Bone Mineral Density in Thalassemia Major Patients with Healthy Controls

    Directory of Open Access Journals (Sweden)

    Mahesh Chand Meena

    2015-01-01

    Full Text Available Chronic hemoglobinopathies like thalassemia are associated with many osteopathies like osteoporosis. Methods. This observational study was carried out to compare the bone mineral density (BMD in transfusion dependent thalassemics with that of healthy controls. Thirty-two thalassemia patients, aged 2–18 years, and 32 age and sex matched controls were studied. The bone mineral concentration (BMC and BMD were assessed at lumbar spine, distal radius, and neck of femur. Biochemical parameters like serum calcium and vitamin D levels were also assessed. Results. The BMC of neck of femur was significantly low in cases in comparison to controls. We also observed significantly lower BMD at the lumbar spine in cases in comparison to controls. A significantly positive correlation was observed between serum calcium levels and BMD at neck of femur. Conclusion. Hence, low serum calcium may be used as a predictor of low BMD especially in populations where incidence of hypovitaminosis D is very high.

  2. The fate of allogenic radiation sterilized bone grafts controlled by the electron spin resonance spectrometry

    International Nuclear Information System (INIS)

    Ostrowski, K.; Dziedzic-Goclawska, A.

    1981-01-01

    The normal fate of bone grafts is their resorption and substitution by the own host's bone tissue. This phenomenon described as creeping substitution process was controlled using biopsies from the grafted region in allogenic experimental system. Electron spin resonance (ESR) spectrometry was used for independent evaluation of resorption and substitution processes. The measurements were based on the process of induction in the hydroxyapatite (HA) crystals of bone mineral of stable paramagnetic centers which can be detected by ESR spectrometry. The loss of total amount of spins connected with the paramagnetic centers expressed in percent describes the kinetics of resorption. The changes in the concentration of spins due to the ''dilution'' of spins implanted with the graft by the nonirradiated ingrowing host's own bone describe the kinetics of the substitution process. Allogenic bone of calvaria was grafted orthotopically into rabbits after lyophilization and radiation sterilization with a dose of 3.5 Mrads. The process of graft's rebuilding was evaluated using the described ESR method. The application of the described technique in the human clinic is possible. (author)

  3. Quality control and quality standards for the production of bone allografts in China

    International Nuclear Information System (INIS)

    Sun Shiquan; Li Youchen

    1999-01-01

    There is a rapid progress of tissue banking especially Bone Banking in China, In order to strengthen the control on medical devices, Ministry of Public Health (MPH) issued the 'Regulation on Supervision of Critical Medical Devices, MPH Decree No. 54' in 1997. The SPTB was requested to submit new application for the approval of production and providing of tissue allografts. The needed documents are clinical reports, package insert, quality standards of product, Quality System Regulation (QSR) and audit report. Quality System Regulation document adopted the GMP standard for medical devices of FDA, US (21 CFR 620-1997). SPTB will amend the existed Quality Manual to suit the requirement of QSR. Referring to the AATB Standards, SPTB established 'Technical Standards' for Tissue Banking and was approved by the local government, which will be the supplement of the submitted QSR document. Considering the need of market control, MPH requested to submit a 'Quality Standard of Product' and the method of inspection. SPTB has completed such standards for final inspection of bone products, which includes the test for residual water, microbiology, bone species, colour and structure. In addition, the Tissue Bank has completed standards for in process inspection, which includes residual blood, radiation sterilization, initial bioburden, package leakage and biomechanics. In-process inspection is important for the control of non-conforming final products to assure the safety and efficacy of bone grafts. Methods of in process inspection and final inspection are described and discussed in this paper

  4. Criteria for palliation of bone metastases - Clinical applications

    International Nuclear Information System (INIS)

    2008-02-01

    -steroidal anti-inflammatory drugs, is the first option in most patients, progressing to stronger opioids as the intensity of pain rises. These drugs produce unwanted side effects such as nausea, sedation, and constipation. Local external radiotherapy or surgery can be used for localized metastatic disease and hemibody radiotherapy might be suitable for patients with disease extending to one region of the body. In patients with widespread painful bone involvement, bone-seeking radiopharmaceuticals provide a promising pain-control strategy. This TECDOC should be seen as a guide and useful resource both for researchers and practitioners alike in both radiation oncology and nuclear medicine fields. The IAEA has put special emphasis on the issue of bone metastasis in the research field of cancer. Recent coordinated research projects have shown that it is an important issue to be addressed through clinical trials setting the best need of developing countries

  5. Criteria for palliation of bone metastases - Clinical applications

    International Nuclear Information System (INIS)

    2007-04-01

    -steroidal anti-inflammatory drugs, is the first option in most patients, progressing to stronger opioids as the intensity of pain rises. These drugs produce unwanted side effects such as nausea, sedation, and constipation. Local external radiotherapy or surgery can be used for localized metastatic disease and hemibody radiotherapy might be suitable for patients with disease extending to one region of the body. In patients with widespread painful bone involvement, bone-seeking radiopharmaceuticals provide a promising pain-control strategy. This TECDOC should be seen as a guide and useful resource both for researchers and practitioners alike in both radiation oncology and nuclear medicine fields. The IAEA has put special emphasis on the issue of bone metastasis in the research field of cancer. Recent coordinated research projects have shown that it is an important issue to be addressed through clinical trials setting the best need of developing countries

  6. Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study.

    Science.gov (United States)

    Constantin, Tina; Tangpricha, Vin; Shah, Reshma; Oyesiku, Nelson M; Ioachimescu, Octavian C; Ritchie, James; Ioachimescu, Adriana G

    2017-07-01

    Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. To evaluate calcium and bone metabolism in active and treated acromegaly. We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent. Copyright © 2017 Endocrine Society

  7. Green tea polyphenols and Tai Chi for bone health: Designing a placebo-controlled randomized trial

    Directory of Open Access Journals (Sweden)

    Chyu Ming-Chien

    2009-09-01

    model of repeated measurements with random effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. Discussion We present the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women. Trial registration ClinicalTrials.gov identifier: NCT00625391

  8. Effect of controlled early implant loading on bone healing and bone mass in guinea pigs, as assessed by micro-CT and histology.

    NARCIS (Netherlands)

    Smet, E. De; Jaecques, S.V.; Wevers, M.; Jansen, J.A.; Jacobs, R.; Sloten, J. van der; Naert, I.E.

    2006-01-01

    Without controlled loading, the failure of early loaded oral implants is higher than in delayed loading, unless loading regimens can be identified that stimulate bone formation. The purpose of this study was to investigate whether controlled early loading optimizes osseointegration. Six series of

  9. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  10. [Cranial metastasis of thyroid follicular carcinoma. Report of a case].

    Science.gov (United States)

    Calderón-Garcidueñas, A L; González-Schaffinni, M A; Farías-García, R; Rey-Laborde, R

    2001-01-01

    Thyroid follicular carcinoma is able to produce metastatic lesions before the vanishing of the primary lesion. We present a case of a woman with a lytic, solitary, asymptomatic parietal bone lesion of 2 years of evolution. Autopsy revealed a thyroid gland with two small cystic areas and renal metastasis. Thyroid carcinoma should be included in the differential diagnosis in cases of lytic bone lesions with long evolution in patients 60 years of age or older.

  11. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    Science.gov (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  12. 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

    pad of immunocompromised mice, express epithelial cell markers, and make milk proteins and lipids [51,52]. BRMS1 is a metastasis suppressor that, by...Invi- trogen), and 0.02 mmol/L of non-essential amino acids (Mediatech, Manassas, VA). Neither antibiotics nor anti-mycotics were used. All cell lines

  13. Iris metastasis in small-cell lung carcinoma

    NARCIS (Netherlands)

    Roenhorst, Anke W. J.; van den Bergh, Alphons C. M.; van Putten, John W. G.; Smit, Egbert F.

    2007-01-01

    Small-cell lung cancer (SCLC) is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic treatment, until now treatments have failed to control or cure this disease in most patients. Here, we describe a patient with SCLC in which symptoms caused by iris metastasis

  14. 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 ...

  15. Lung Metastasis Mimicking Fingertip Infection

    Science.gov (United States)

    Soylemez, Salih; Demiroglu, Murat; Yayla, Mehmet Ali; Ozkan, Korhan; Alpan, Bugra; Ozger, Harzem

    2015-01-01

    Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient's pain during his terminal period, saves the functions of the limb, and increases life comfort. PMID:26236517

  16. Lung Metastasis Mimicking Fingertip Infection

    Directory of Open Access Journals (Sweden)

    Salih Soylemez

    2015-01-01

    Full Text Available Metastasis fingers (acral metastasis are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient’s pain during his terminal period, saves the functions of the limb, and increases life comfort.

  17. Assessment of lumbar trabecular bone density by means of single energy quantitative CT in hospital control children and bone metabolic disorders, 1

    International Nuclear Information System (INIS)

    Nakano, Kazutoshi; Miyamoto, Akie; Imai, Kaoru; Mochizuki, Yumiko; Hayashi, Kitami; Mitsuishi, Yoichi; Fukuyama, Yukio; Kohno, Atsushi; Shigeta, Teiko

    1990-01-01

    We studied the 3rd lumbar vertebral trabecular bone mineral density in 59 cross-sectional pictures of quantitative computed tomography (QCT) with CaCO 3 phantom for 28 hospital control children and 30 cases of suspected bone metabolic disorders. The QCT value of bone mineral density of control children showed neither age dependency nor sexual difference before puberty: for males was 221.8±30.2 mg CaCO 3 /cm 3 (Mean±SD) under 4 years, 218.1±39.7 at 5∼9 years and 217.2±30.9 at 10∼15 years; and for females 220.9±18.3 under 4 years and 240.0±29.4 at 5∼9 years. The QCT values of bone mineral density in bed-ridden patients, children receiving glucocorticoids, and children receiving anticonvulsants were significantly lower than that in control children (p<0.005). The QCT value of bone mineral density of bed-ridden patients was significantly lower than that of children receiving glucocorticoids and of children receiving anticonvulsants (p<0.05, p<0.005 respectively). Our study confirmed that single energy quantitative CT was very useful in pediatric clinical application. (author)

  18. Assessment of lumbar trabecular bone density by means of single energy quantitative CT in hospital control children and bone metabolic disorders, 1

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Kazutoshi; Miyamoto, Akie; Imai, Kaoru; Mochizuki, Yumiko; Hayashi, Kitami; Mitsuishi, Yoichi; Fukuyama, Yukio; Kohno, Atsushi; Shigeta, Teiko (Tokyo Women' s Medical Coll. (Japan))

    1990-03-01

    We studied the 3rd lumbar vertebral trabecular bone mineral density in 59 cross-sectional pictures of quantitative computed tomography (QCT) with CaCO{sub 3} phantom for 28 hospital control children and 30 cases of suspected bone metabolic disorders. The QCT value of bone mineral density of control children showed neither age dependency nor sexual difference before puberty: for males was 221.8{plus minus}30.2 mg CaCO{sub 3}/cm{sup 3} (Mean{plus minus}SD) under 4 years, 218.1{plus minus}39.7 at 5{approx}9 years and 217.2{plus minus}30.9 at 10{approx}15 years; and for females 220.9{plus minus}18.3 under 4 years and 240.0{plus minus}29.4 at 5{approx}9 years. The QCT values of bone mineral density in bed-ridden patients, children receiving glucocorticoids, and children receiving anticonvulsants were significantly lower than that in control children (p<0.005). The QCT value of bone mineral density of bed-ridden patients was significantly lower than that of children receiving glucocorticoids and of children receiving anticonvulsants (p<0.05, p<0.005 respectively). Our study confirmed that single energy quantitative CT was very useful in pediatric clinical application. (author).

  19. Comparison of the effectiveness of two different bone substitute materials for socket preservation after tooth extraction: a controlled clinical study.

    Science.gov (United States)

    Shakibaie-M, Behnam

    2013-01-01

    The aim of this study was to compare the effectiveness of two bone substitute materials for socket preservation after tooth extraction. Extraction sockets in 10 patients were filled with either inorganic bovine bone material (Bio-Oss) or with synthetic material consisting of hydroxyapatite and silicon dioxide (NanoBone). Extraction sockets without filling served as the control. The results demonstrate the effectiveness of the presented protocol for socket preservation and that the choice of a suitable bone substitute material is crucial. The dimensions of the alveolar ridge were significantly better preserved with Bio-Oss than with NanoBone or without treatment. Bio-Oss treatment resulted in better bone quality and quantity for successful implant placement.

  20. Pancreatic Metastasis in a Child Suffering with Treated Stage 4 Neuroblastoma

    International Nuclear Information System (INIS)

    Kim, Eun Young; Yoo, So Young; Kim, Ji Hye; Sung, Ki Woong

    2008-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and its metastasis to distant organs such as bone, bone marrow and liver is well documented. However, pancreatic metastasis of neuroblastoma has not yet been reported in the medical literature. We report here on a 4-year old boy who had a metastatic relapse in his pancreas, combined with pancreatitis, after remission of stage 4 neuroblastoma. In conclusion, we present here a very rare case of neuroblastoma that metastasized to the pancreas in a 4- year-old boy. Pancreatic metastasis should be taken into consideration for those patients who are found to have pancreatic nodules concurrent with neuroblastoma

  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. Application of bone scintigraphy

    International Nuclear Information System (INIS)

    Rondain, J.E.S.

    1996-01-01

    Bone scanning has varied applications, particularly in the file of oncology. It is used in the diagnosis and follow-up of patients with cancers that metastatize to the bones (breast, prostate CA), also in primary bone cancers, infections of the bones and joints. In early stages of primary breast CA (stage I and II), the incidence of unsuspected bone metastasis is only 1-5%. On the other hand, bone scans serve as a baseline study if bone mets occur at some later stage. In patients with stage II and III breast CA, the conversion from normal to abnormal bone scans is 15% and 17%, respectively, clearly in favor of a baseline bone scan. For prostate CA, bone scanning should be used in conjunction with PSA level determination. In advanced disease, a bone scan will define the extent of the metastases, show problematic lesions in weight-bearing bones, and even allow us to evaluate response to therapy in follow-up bone scans. In patients with lung CA, a positive bone scan will make surgery of the primary lesion inappropriate. For other cancers, a bone scan maybe used if there are other signs, whether clinical or chemical, indicating bone involvement. In patients with GIT, liver, skin, brain or bladder CA, routine bone scanning may be considered superfluous. For patients with suspected infection, a 3-phase bone scan is more desirable. In patients with septic arthritis, the bones of each side of the joint take up the radiopharmaceutical while in patients with cellulitis without bony involvement, only the first two phases (dynamic and bloodpool images) will be abnormal. Bone scanning is also used in avascular lesions such as Legg-calve-Perthes disease where one will see reduced uptake of Tc99m MDP. The advent of SPECT imaging has greatly increased the sensitivity in diagnosing AVN. (author)

  3. Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study.

    Directory of Open Access Journals (Sweden)

    Karen N Borschmann

    Full Text Available Immobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans.To investigate the skeletal effect of middle cerebral artery occlusion (MCAo stroke in rats and examine its utility as a model of human post-stroke bone loss.Twenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV measured by Micro-CT (10.5 micron istropic voxel size at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and foot-faults and physical activity (cage monitoring were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX were assessed at baseline, and days 7 and 27.No effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046 at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9 and total volume (6.4%, IQR 1.2, 7.6 were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals.MCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.

  4. Metabolic control and bone health in adolescents with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Mohan Subburaman

    2011-10-01

    Full Text Available Abstract Background Adults with type 1 diabetes (T1D have decreased bone mineral density (BMD and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers. Methods Cross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27 or Results There were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA for vitamin D or calcium. Conclusions These data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

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

    International Nuclear Information System (INIS)

    Li Fenghu; Lu Bing; Fu Heyi; Han Lei; Li Qingsong; Li Huiqin

    2012-01-01

    Objective: To investigate the clinical metastasis features and the possibility of 3 dimensional radiotherapy of stage IV non-small cell lung cancer (NSCLC). Methods: The clinical materials of 546 patients with stage IV NSCLC and the relationship b T and N stage and metastasis were retrospectively analyzed. Results In 546 patients with stage IV NSCLC, the number with bone metastasis was 294, the number with brain metastasis was 167, the number with lung metastasis was 137, the number with liver metastasis was 79, the number with adrenal gland metastasis was 66, 37 with lymph node metastasis, 35 with subcutaneous metastasis and 10 with other organ metastasis. The number with single organ metastasis was 379 (69.4%) ,in which 37.7% with bone metastasis, 19.8% with brain metastasis, 16.9% with lung metastasis, 7.4% with liver metastasis, 7.4% with adrenal gland metastasis, 4.5% with lymph node metastasis, 5.5% with subcutaneous metastasis and 0.8% with other organ metastasis. The bone metastasis probability of T 3+4 patient was similar with T 1+2 (69.4%, 30.6%, χ 2 = 7.65, P = 0.067), but N 2+3 patient was more than N 0+1 (69.7%, 30.3%, χ 2 = 7.89, P = 0.044). The brain metastasis probability of T 3+4 patient was more than T 1+2 (70.7%, 29.3%, χ 2 = 10.64, P = 0.018), but N 2+3 patient was similar with N 0+1 (54.5%, 45.5%, χ 2 = 7.14, P = 0.079), and N 1+3+3 patient was more than N 0 (86.8%, 13.2%, χ 2 = 10.26, P = 0.024). Conclusions: In 546 patients with stage IV NSCLC, the most common metastatic organ is bone, the second is brain, the third is lung, the forth is liver, followed by adrenal gland; single organ metastasis is more common than multiple organ metastasis. The later the T stage is, the more severe is the metastasis. Through 3 dimensional radiotherapy, not only the quality of life of some stage IV patients is improved, but also the survival time was prolonged observably. (authors)

  6. A case-control study assessing bone mineral density in severe haemophilia A in the UK.

    Science.gov (United States)

    Wells, A J; McLaughlin, P; Simmonds, J V; Prouse, P J; Prelevic, G; Gill, S; Chowdary, P

    2015-01-01

    It has been shown that bone mineral density (BMD) may be lower in patients with haemophilia (PWH). A comparison to control subjects is required to thoroughly assess current BMD in PWH in the UK. The objective of this study was to test the hypothesis that BMD is lower in PWH than in controls, and in patients with more severely affected joints or lower activity levels. In this case-control study, 37 patients with severe haemophilia A were recruited from two haemophilia centres in the UK. A group of 37 age, gender and ethnicity-matched control participants were recruited. All participants had a bone density scan, a musculoskeletal assessment, a blood test for vitamin D and completed a functional activity questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than expected for age. No control participants had osteoporosis, 3% had osteopenia and 14% had BMD lower than expected for age. Ninety one per cent of case participants and 92% of control participants had reduced 25(OH)D levels. Case participants had significantly lower BMD than control participants, and case participants with more severely affected joints, lower activity levels, HIV, history of hepatitis C or lower BMI had significantly lower BMD. Patients with severe haemophilia have a higher risk of low BMD than men without haemophilia. Patients with more severely affected joints and lower activity levels have lower BMD. It remains unclear whether patients with low BMD reached adequate peak bone mass. Low vitamin D may be present in the majority of PWH. © 2014 John Wiley & Sons Ltd.

  7. Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Verena Schwetz

    2017-04-01

    Full Text Available Bone turnover markers (BTMs are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP, osteocalcin (OC, C-terminal telopeptide (CTX, and procollagen type 1 N-terminal propeptide (P1NP. This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT performed at the Medical University of Graz, Austria (2011–2014. Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE 0.013, 95% CI −0.029 to 0.056 µg/L; p = 0.533, CTX (MTE 0.024, 95% CI −0.163 to 0.210 ng/mL, p = 0.802, OC (MTE 0.020, 95% CI −0.062 to 0.103 ng/mL, p = 0.626, or P1NP (MTE −0.021, 95% CI −0.099 to 0.057 ng/mL, p = 0.597. Analyzing patients with 25(OHD levels <50 nmol/L separately (n = 74 left results largely unchanged. In hypertensive patients with low 25(OHD levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.

  8. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Directory of Open Access Journals (Sweden)

    Shellese A. Cannonier

    2015-08-01

    Full Text Available Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung, directly invade into bone (head and neck or originate from the bone (melanoma, chondrosarcoma where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  9. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Energy Technology Data Exchange (ETDEWEB)

    Cannonier, Shellese A.; Sterling, Julie A., E-mail: Julie.sterling@vanderbilt.edu [Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37235 (United States); Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University, Nashville, TN 372335 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN 37235 (United States)

    2015-08-26

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  10. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    International Nuclear Information System (INIS)

    Cannonier, Shellese A.; Sterling, Julie A.

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors

  11. Bone scanning in the evaluation of lung cancer

    International Nuclear Information System (INIS)

    Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk

    1994-01-01

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

  12. Bone scanning in the evaluation of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-05-15

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

  13. Staging Lung Cancer: Metastasis.

    Science.gov (United States)

    Shroff, Girish S; Viswanathan, Chitra; Carter, Brett W; Benveniste, Marcelo F; Truong, Mylene T; Sabloff, Bradley S

    2018-05-01

    The updated eighth edition of the tumor, node, metastasis (TNM) classification for lung cancer includes revisions to T and M descriptors. In terms of the M descriptor, the classification of intrathoracic metastatic disease as M1a is unchanged from TNM-7. Extrathoracic metastatic disease, which was classified as M1b in TNM-7, is now subdivided into M1b (single metastasis, single organ) and M1c (multiple metastases in one or multiple organs) descriptors. In this article, the rationale for changes in the M descriptors, the utility of preoperative staging with PET/computed tomography, and the treatment options available for patients with oligometastatic disease are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

    International Nuclear Information System (INIS)

    Vadas, M.A.

    1982-01-01

    A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F 1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR→F 1 were high responders and EO-LR→F 1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy

  15. Autogenous bone versus deproteinised bovine bone matrix in 1-stage lateral sinus floor elevation in the severely atrophied maxilla: a randomised controlled trial.

    Science.gov (United States)

    Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Rotundo, Roberto; Nieri, Michele

    2013-01-01

    To compare 100% deproteinised bovine bone matrix (DBBM) grafts (test group) with 100% autogenous bone (AB) grafts (control group) for lateral maxillary sinus floor elevation in a parallel group, superiority, randomised controlled trial. Patients with 1 to 3 mm of residual bone height below the maxillary sinus were randomised for sinus floor elevation with DBBM and AB grafts and simultaneous implant placement. Randomisation was computer generated with allocation concealment by sealed envelopes and the radiographic examiner was blinded to group assignment. The abutment connection was performed 8 months after surgery and insertion of the provisional prostheses was performed 9 months after surgery. Outcome variables were implant failures, prosthetic failures, complications, chair time, postoperative pain and radiographic bone level 6 months after loading. Forty patients were randomised: 20 (32 implants) to the DBBM group and 20 (27 implants) to the AB group. One patient from the AB group dropped out. Two implant failures occurred in the DBBM group and no implant failure occurred in the AB group (P = 0.4872). All of the planned prostheses could be delivered. One complication occurred in the DBBM group and 2 in the AB group (P = 0.6050). Chair time was shorter for the DBBM group, with a difference of 27.3 minutes (P = 0.0428). Pain difference measured with a visual analogue scale for 6 days post-surgery was 0.2 in favour of the DBBM group (P = 0.6838). The difference in vertical bone height was 0.0 mm (95% CI -1.1, 1.1; P = 0.9703) and the difference in marginal bone level was 0.3 in favour of AB (95% CI -0.3, 0.9; P = 0.3220). No differences apart from chair time were observed when comparing DBBM and AB grafts with simultaneous implant placement in sinus elevation.

  16. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  17. Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial.

    Science.gov (United States)

    Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Pagliaro, Umberto; Raffaelli, Eugenia; Nieri, Michele

    2015-01-01

    The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure β-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were

  18. 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

  19. Modelling the temperature evolution of bone under high intensity focused ultrasound

    Science.gov (United States)

    ten Eikelder, H. M. M.; Bošnački, D.; Elevelt, A.; Donato, K.; Di Tullio, A.; Breuer, B. J. T.; van Wijk, J. H.; van Dijk, E. V. M.; Modena, D.; Yeo, S. Y.; Grüll, H.

    2016-02-01

    Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR

  20. Modelling the temperature evolution of bone under high intensity focused ultrasound

    International Nuclear Information System (INIS)

    Ten Eikelder, H M M; Bošnački, D; Breuer, B J T; Van Wijk, J H; Van Dijk, E V M; Modena, D; Yeo, S Y; Grüll, H; Elevelt, A; Donato, K; Di Tullio, A

    2016-01-01

    Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR

  1. Clinical analysis of bone scanning in solitary lesion

    International Nuclear Information System (INIS)

    Zhu Jun; Zhu Ruisen; Zhu Jifang

    2002-01-01

    A rational analysis procedure for solitary lesions on whole bone scanning was offered. This study was undertaken to analyze retrospectively solitary lesions which obtained final diagnose through the following aspects: (1) diagnosis of bone metastasis, (2) the incidence of bone metastasis in different tumor, (3) the most possible lesion sites indicating bone metastasis, (4) morphological analysis of solitary lesions. The results are: (1) The incidence of solitary lesions in 2465 cases on whole bone scanning is 15.3%. (2) The rate of bone metastasis is 24.8% in 282 patients with primary malignancy. The rate of bone metastasis of 6.3% in 64 patients without primary malignancy, and the total diagnostic rate of bone metastasis is 21.4% in 346 patients. (3) In patients with primary malignancy, the incidence of bone metastasis of solitary lesions is as follows respectively; bronchi cancer 36.1%(22/61); breast cancer 23.8%(20/84); prostate gland 17.2%(5/29); other urinary system cancer 22.2%(4/18); G.I. system cancer 16.9%(10/59); others 29.0%(9/31). There is no significant difference in different cancer. (4) In patients without primary malignancy, 93.7%(60/64) of solitary lesions are benign. (5) From anatomical point of view, the authors found the diagnostic rate of bone metastasis is as follow: 30% in spine; 34.2% in pelvis; 36.4% in skull; 10.8% in other bones. There are significant differences in four groups. It is concluded that: (1) The diagnostic rate of bone metastasis in solitary lesions is 21.4%. (2) The most possible solitary lesions indicating osseous tumor spread are at spine, pelvic and skull. (3) Special attention to 'cold' and streak like lesions should be paid. (4) A clinical analysis procedure for diagnosis of solitary lesions has been summarized out here

  2. A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Alper Nesip Manav

    2014-01-01

    Full Text Available Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung, and gastrointestinal tract for metastatic testicular cancers. Metastasis of urothelial carcinoma (UC to the testis is extremely rare. Two-thirds of upper tract urothelial carcinoma (UTUC is of invasive stage at diagnosis and metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a rare case of metastatic UTUC to the testis which has not been reported before, except one case in the literature. Testicular metastasis of UC should be considered in patients with hematuria and testicular swelling.

  3. Fast and automatic depth control of iterative bone ablation based on optical coherence tomography data

    Science.gov (United States)

    Fuchs, Alexander; Pengel, Steffen; Bergmeier, Jan; Kahrs, Lüder A.; Ortmaier, Tobias

    2015-07-01

    Laser surgery is an established clinical procedure in dental applications, soft tissue ablation, and ophthalmology. The presented experimental set-up for closed-loop control of laser bone ablation addresses a feedback system and enables safe ablation towards anatomical structures that usually would have high risk of damage. This study is based on combined working volumes of optical coherence tomography (OCT) and Er:YAG cutting laser. High level of automation in fast image data processing and tissue treatment enables reproducible results and shortens the time in the operating room. For registration of the two coordinate systems a cross-like incision is ablated with the Er:YAG laser and segmented with OCT in three distances. The resulting Er:YAG coordinate system is reconstructed. A parameter list defines multiple sets of laser parameters including discrete and specific ablation rates as ablation model. The control algorithm uses this model to plan corrective laser paths for each set of laser parameters and dynamically adapts the distance of the laser focus. With this iterative control cycle consisting of image processing, path planning, ablation, and moistening of tissue the target geometry and desired depth are approximated until no further corrective laser paths can be set. The achieved depth stays within the tolerances of the parameter set with the smallest ablation rate. Specimen trials with fresh porcine bone have been conducted to prove the functionality of the developed concept. Flat bottom surfaces and sharp edges of the outline without visual signs of thermal damage verify the feasibility of automated, OCT controlled laser bone ablation with minimal process time.

  4. Rapid restoration of bone mass after surgical management of hyperthyroidism: A prospective case control study in Southern India.

    Science.gov (United States)

    Karunakaran, Poongkodi; Maharajan, Chandrasekaran; Mohamed, Kamaludeen N; Rachamadugu, Suresh V

    2016-03-01

    The rate and the extent of bone remineralization at cancellous versus cortical sites after treatment of hyperthyroidism is unclear. Few studies have examined the effect of operative management of hyperthyroidism on recovery of bone mass. To evaluate prospectively the bone mineral density (BMD), bone mineral content (BMC), and bone areal size at the spine, hip, and forearm before and after total thyroidectomy. A prospective case control observational study from August 2011 to July 2014 in a single center. This study evaluated 40 overt hyperthyroid patients and 31 age-matched euthyroid controls who were operative candidates. Bone indices were measured at baseline and 6-month postoperatively using dual energy x-ray absorptiometry. Serum levels of alkaline phosphatase and 25-hydroxy vitamin D3 (25OHD) were assessed. Baseline BMD of hyperthyroid subjects at the spine, hip, and forearm were less than euthyroid controls (P = .001) with concomitant increases in serum alkaline phosphatase (mean ± SD, 143 ± 72 vs 72 ± 23 IU/L control; P hyperthyroid patients, posttreatment BMD expressed as g/cm(2) were 0.97 ± 0.12 (vs pretreatment 0.91 ± 0.14; P = .001) at the spine, 0.87 ± 0.12 (vs pretreatment 0.80 ± 0.13; P = .001) at the hip, and 0.67 ± 0.09 (vs pretreatment 0.64 ± 0.11; P = .191) at the forearm. The percent change in BMD was greatest at spine (8.3%) followed by the hip (7.6%) and forearm (3.0%). Operative management with total thyroidectomy improved the bone loss associated with hyperthyroidism as early as 6 months postoperatively at the hip and spine despite concomitant vitamin D deficiency. Delayed recovery of bone indices at the forearm, a cortical bone, requires further long-term evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Utility of the dimercapto succinic acid pentavalent ({sup 99m} Tc- DMSA V) in the diagnostic of secondary bone leisure at metastasis of diverse primary tumours. Preliminary study; Utilidad del acido dimercapto succinico pentavalente ({sup 99m} Tc-DMSA V) en el diagnostico de lesiones oseas secundarias a metastasis de diversos tumores primarios. Estudio preliminar

    Energy Technology Data Exchange (ETDEWEB)

    Ortega L, N [Hospital de Especialidades ' Dr. Antonio Fraga Mouret' Centro Medico Nacional ' La Raza' , IMSS Mexico D.F. (Mexico); Pichardo R, P A [Medico Nuclear adscrito al servicio de Medicina Nuclear del Hospital de Oncologia, Centro Medico Nacional Siglo XXI, IMSS, Mexico D.F. (Mexico); Marquez H, A [Departamento de Medicina Nuclear, IMSS, Mexico D.F. (Mexico)

    2005-07-01

    The more used method in the diagnosis of secondary bone lesions to become cancerous it is by means of having derived of phosphates like it is the {sup 99m}Tc- MDP. The reason of acquiring searching with the radiopharmaceutical {sup 99m}Tc- DMSA V is with the purpose to find other bone lesions that are not visualized with the gammagraphy with diphosphonate and therefore to increase the specificity of the study. (Author)

  6. Bone scintigraphy as a process control with hemi-alloarthroplasty of the hip joint

    International Nuclear Information System (INIS)

    Shaltout, E.E.D.

    1983-01-01

    For the diagnostic of prosthesis complications in the treatment of femur fractures near the hip joint ('intermediate prostheses') 216 skeletal scintigrams with 99mTc MDP were made of 143 patients from 1977 to 1982, partially retrospective and partially prospective. The evaluation of the photoscan was achieved visually and photodensitometrically and divided into 10 intensity levels with the following results: 1. Increased activity concentration in the acetabulum is pathological (activated arthrosis); 2. Increased activity concentration-temporary or also continuous - in the trochanter region is pathological (loosening process); 3. Non-pathological metabolic activity as a result of the bone healing process may last longer than 1 year postoperatively; 4. Heterotopic ossification, non-fixed bone fragments and pseudoarthrosis cause continuous or newly appearing concentrations; 5. Skeletal scintigraphy is an important supplement to radiological diagnostic and a sensitive method for the recognition of metabolic activities in bone. It is recommended for progress control after hemi-alloarthrosculpture of the hip joint. (orig./TRV) [de

  7. The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

    Science.gov (United States)

    DeWoody, Yssa

    1996-01-01

    The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques required to perform certain motor tasks can be recovered through a kinematic analysis, it remains a difficult problem to determine the actual forces produced by each muscle that resulted in these torques. As a consequence, few studies have focused on the role of individual muscles in the development of stress in the bone. This study takes a control theoretic approach to the problem. A seven-link, eight degrees of freedom model of the body is controlled by various muscle groups on each leg to simulate gait. The simulations incorporate Hill-type models of muscles with activation and contraction dynamics controlled through neural inputs. This direct approach allows one to know the exact muscle forces exerted by each musculotendon throughout the gait cycle as well the joint torques and reaction forces at the ankle and knee. Stress and strain computed by finite element analysis on skeletal members will be related to these derived loading conditions. Thus the role of musculoskeletal dynamics and neuromuscular control in the stress development of the tibia during gait can be analyzed.

  8. Bone mineral density in children with acute leukemia and its associated factors in Iran: a case-control study.

    Science.gov (United States)

    Bordbar, Mohammad Reza; Haghpanah, Sezaneh; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar; Saki, Forough

    2016-12-01

    Acute leukemia is the most common malignancy in children. We showed that low bone mass is prevalent among children with leukemia, especially in femur. Serum calcium, exercise, chemotherapy protocol, and radiotherapy are the main contributing factors. We suggest that early diagnosis and treatment of this problem could improve bone health in them. Acute leukemia is the most common malignancy in children and has been reported to be associated with low bone mass. Due to lack of sufficient data about the bone mineral density of children with leukemia in the Middle East, and inconsistencies between possible associated factors contributing to decreasing bone density in these children, we aimed to conduct a case-control study in Iran. This case-control study was conducted on 60 children with acute leukemia and 60 age- and sex-matched healthy controls. Anthropometric data, sun exposure, puberty, physical activity, and mineral biochemical parameters were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). Data analysis was done by SPSS software v. 21. Serum calcium was higher in the control group (P = 0.012) while serum phosphorous, alkaline phosphatase, and serum 25(OH)D 3 were higher in children with leukemia with P values of 0.04, 0.002, and 0.036, respectively. Sun exposure and physical activity were more in healthy controls (P values children with leukemia, especially in the femoral neck. Serum calcium, physical activity, chemotherapy protocol, and radiotherapy are the main contributing factors.

  9. Tongue metastasis mimicking an abscess.

    Science.gov (United States)

    Mavili, Ertuğrul; Oztürk, Mustafa; Yücel, Tuba; Yüce, Imdat; Cağli, Sedat

    2010-03-01

    Primary tumors metastasizing to the oral cavity are extremely rare. Lung is one of the most common primary sources of metastases to the tongue. Although the incidence of lung cancer is increasing, tongue metastasis as the initial presentation of the tumor remains uncommon. Due to the rarity of tongue metastasis, little is known about its imaging findings. Herein we report the magnetic resonance imaging and clinical findings of a lingual metastasis, mimicking an abscess, from a primary lung cancer.

  10. 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.

  11. Artificial Bone and Teeth through Controlled Ice Growth in Colloidal Suspensions

    International Nuclear Information System (INIS)

    Tomsia, Antoni P.; Saiz, Eduardo; Deville, Sylvain

    2007-01-01

    The formation of regular patterns is a common feature of many solidification processes involving cast materials. We describe here how regular patterns can be obtained in porous alumina and hydroxyapatite (HAP) by controlling the freezing of ceramic slurries followed by subsequent ice sublimation and sintering, leading to multilayered porous ceramic structures with homogeneous and well-defined architecture. These porous materials can be infiltrated with a second phase of choice to yield biomimetic nacre-like composites with improved mechanical properties, which could be used for artificial bone and teeth applications. Proper control of the solidification patterns provides powerful means of control over the final functional properties. We discuss the relationships between the experimental results, ice growth fundamentals, the physics of ice and the interaction between inert particles and the solidification front during directional freezing

  12. Unusual metastasis of left colon cancer: considerations on two cases.

    Science.gov (United States)

    Gubitosi, Adelmo; Moccia, Giancarlo; Malinconico, Francesca Antonella; Gilio, Francesco; Iside, Giovanni; Califano, Umberto G A; Foroni, Fabrizio; Ruggiero, Roberto; Docimo, Giovanni; Parmeggiani, Domenico; Agresti, Massimo

    2009-04-01

    Usually, left colon cancer metastasis concerns liver, abdominal lymph nodes and lungs. Other localizations are quite rare occurrences. In spite of this, some uncommon metastasis sites are reported in literature, such as: peritoneum, ovaries, uterus, kidney testis, bones, thyroid, oral cavity and central nervous system. We report two cases of unusual localizations of left colon cancer metastasis localization, one into the retroperitoneal space and the other at the left axillary lynphnodes and between liver and pancreas. In the first reported case the diffusion pathway may have been the lymphatic mesocolic vessels, partially left in place from the previous surgery. In the second case the alleged metastatic lane may have been through the periumbilical lymph nodes to the parasternal lymph nodes and then to the internal mammary ones, finally reaching the axillary limph nodes.

  13. Diagnosis and treatment of brain metastasis

    International Nuclear Information System (INIS)

    Sajama, Carlos; Lorenzoni, Jose; Tagle, Patricio

    2008-01-01

    Cerebral metastasis occur in 20 to 30 percent of patients with systemic cancer and are the most common type of intracranial tumor. The median survival of untreated patients is one month with a slightly longer survival in those treated with steroids. Patients treated with whole brain radiation therapy survive between 3 to 6 months. In selected cases survival can increase to 10 to 12 months with combination of surgery and radiotherapy or stereotactic radiosurgery alone or associated to radiotherapy. Most brain metastasis arise from lung, breast and melanomas. The most important criteria for selecting patients who will benefit from surgery or stereotactic radiosurgery are a Karnofsky score of 70 or more, systemic control of the cancer and absence of leptomeningeal involvement. Surgery is indicated in patients with a single lesion located in an accessible zone and stereotactic radiosurgery is indicated for lesions up to 3 cm of diameter, and in patients with up to 3 or 4 metastasis, no matter their location. The survival benefit of chemotherapy in brain metastasis has not been demonstrated

  14. S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical applications

    International Nuclear Information System (INIS)

    Parashar, Surabhi; Cheishvili, David; Arakelian, Ani; Hussain, Zahid; Tanvir, Imrana; Khan, Haseeb Ahmed; Szyf, Moshe; Rabbani, Shafaat A

    2015-01-01

    Osteosarcoma (OS) is an aggressive and highly metastatic form of primary bone cancer affecting young children and adults. Previous studies have shown that hypomethylation of critical genes is driving metastasis. Here, we examine whether hypermethylation treatment can block OS growth and pulmonary metastasis. Human OS cells LM-7 and MG-63 were treated with the ubiquitous methyl donor S-adenosylmethionine (SAM) or its inactive analog S-adenosylhomocystine (SAH) as control. Treatment with SAM resulted in a dose-dependent inhibition of tumor cell proliferation, invasion, cell migration, and cell cycle characteristics. Inoculation of cells treated with 150 μmol/L SAM for 6 days into tibia or via intravenous route into Fox Chase severe combined immune deficient (SCID) mice resulted in the development of significantly smaller skeletal lesions and a marked reduction in pulmonary metastasis as compared to control groups. Epigenome wide association studies (EWAS) showed differential methylation of several genes involved in OS progression and prominent signaling pathways implicated in bone formation, wound healing, and tumor progression in SAM-treated LM-7 cells. Real-time polymerase chain reaction (qPCR) analysis confirmed that SAM treatment blocked the expression of several prometastatic genes and additional genes identified by EWAS analysis. Immunohistochemical analysis of normal human bone and tissue array from OS patients showed significantly high levels of expression of one of the identified gene platelet-derived growth factor alpha (PDGFA). These studies provide a possible mechanism for the role of DNA demethylation in the development and metastasis of OS to provide a rationale for the use of hypermethylation therapy for OS patients and identify new targets for monitoring OS development and progression

  15. Bone marrow stromal cell therapy for ischemic stroke: A meta-analysis of randomized control animal trials.

    Science.gov (United States)

    Wu, Qing; Wang, Yuexiang; Demaerschalk, Bart M; Ghimire, Saruna; Wellik, Kay E; Qu, Wenchun

    2017-04-01

    Background Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. Aims The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. Methods Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies. Primary outcomes were total infarction volume and modified Neurological Severity Score. Multiple prespecified sensitivity analyses and subgroup analyses were conducted. Random effects models were used for meta-analysis. Results Thirty-three randomized animal trials were included with a total of 796 animals. The median quality score was 6 (interquartile range, 5-7). Bone marrow stromal cell therapy decreased total infarction volume (standardized mean difference, 0.897; 95% confidence interval, 0.553-1.241; P animals treated with bone marrow stromal cell and controls was 2.47 (95% confidence interval, 1.84-3.11; P animal studies. Conclusions Bone marrow stromal cell therapy significantly decreased total infarction volume and increased neural functional recovery in randomized controlled animal models of ischemic stroke.

  16. Vulvar Metastasis from Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2015-01-01

    Full Text Available Vulvar metastasis of urothelial carcinoma of the bladder is a very rare entity; few cases are reported in the English literature. In this paper, we describe the clinical and pathological characteristics, evolution, and treatment of a patient with vulvar metastasis of urothelial carcinoma of the bladder followed by a brief review of the reported cases in the literature.

  17. Percutaneous radiofrequency ablation for a recurrent metastasis after resection of liver metastases from an ileal clear-cell sarcoma: Long-term local tumor control.

    Science.gov (United States)

    Seo, Jung Wook

    2017-12-01

    Clear-cell sarcomas (CCSs) in the gastrointestinal tract are extremely rare and aggressive tumors. We present the first case of a CCS arising in the ileum and metastasizing to the liver; our patient was a 60-year-old man. After the resection of the CCS and the liver metastases, a new liver metastasis developed, which was treated via percutaneous radiofrequency ablation only. At the 5-year follow-up, the ablated region was stable without local tumor progression. Percutaneous radiofrequency ablation is a viable local treatment option for recurrent metastases from an ileal CCS if they are detected when small and at an early stage in follow-up studies.

  18. Enhancement of osteogenesis and biodegradation control by brushite coating on Mg-Nd-Zn-Zr alloy for mandibular bone repair.

    Science.gov (United States)

    Guan, Xingmin; Xiong, Meiping; Zeng, Feiyue; Xu, Bin; Yang, Lingdi; Guo, Han; Niu, Jialin; Zhang, Jian; Chen, Chenxin; Pei, Jia; Huang, Hua; Yuan, Guangyin

    2014-12-10

    To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.

  19. Estrogen-Related Receptors and the control of bone cell fate.

    Science.gov (United States)

    Carnesecchi, Julie; Vanacker, Jean-Marc

    2016-09-05

    Bone loss is naturally occurring in aging males and females and exacerbated in the latter after menopause, altogether leading to cumulative skeleton fragility and increased fracture risk. Two types of therapeutic strategies can be envisioned to counteract age- or menopause-associated bone loss, aiming at either reducing bone resorption exerted by osteoclasts or, alternatively, promoting bone formation by osteoblasts. We here summarize data suggesting that inhibition of the Estrogen-Related Receptors α and/or γ could promote bone formation and compensate for bone loss induced by ageing or estrogen-deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Cigarette smoking and risk of lung metastasis from esophageal cancer.

    Science.gov (United States)

    Abrams, Julian A; Lee, Paul C; Port, Jeffrey L; Altorki, Nasser K; Neugut, Alfred I

    2008-10-01

    Whereas extensive research has explored the effect of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer. We conducted a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association. We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39 of 53) were ever smokers, versus 47.8% (144 of 301) of patients without lung metastases [P=0.001; summary odds ratio (OR), 2.52; 95% confidence interval (95% CI), 1.17-5.45; stratified by histology]. Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR, 1.89; 95% CI, 0.80-4.46). Upper esophageal subsite (OR, 4.71; 95% CI, 1.20-18.5), but not histology (squamous OR 0.65,95% CI 0.27-1.60), was associated with lung metastasis. Compared with the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR, 2.35; 95% CI, 1.11-4.97). There was no association between liver metastasis and smoking (OR, 0.88; 95% CI, 0.42-1.83). Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship seems to be site specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome.

  1. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.

    2008-01-01

    OBJECTIVE: Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS). DESIGN AND SETTING: We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital. PATIENTS......, sex hormones, and body composition. CONCLUSION: Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss Udgivelsesdato: 2008/5...

  2. Iris metastasis of gastric adenocarcinoma.

    Science.gov (United States)

    Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, U Emrah; Cosar, C Banu; Ozkiris, Abdullah

    2016-03-08

    Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis. A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy. Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.

  3. Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

    International Nuclear Information System (INIS)

    Matsuno, Akira; Murakami, Mineko; Hoya, Katsumi; Yamada, Shoko M.; Miyamoto, Shinya; Yamada, So; Son, Jae-Hyun; Nishido, Hajime; Ide, Fuyuaki; Nagashima, Hiroshi; Sugaya, Mutsumi; Hirohata, Toshio; Mizutani, Akiko; Okinaga, Hiroko; Ishii, Yudo; Tahara, Shigeyuki; Teramoto, Akira; Osamura, R. Yoshiyuki; Yamazaki, Kazuto; Ishida, Yasuo

    2013-01-01

    Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma

  4. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; McGee-Lawrence, Meghan E.; Weivoda, Megan M.; Poston, Daniel D.; Dudakovic, Amel; Xu, Ming; Tchkonia, Tamar; Kirkland, James L.; van Wijnen, Andre J.; Oursler, Merry Jo; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)–expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes exhibited increased expression of cytokine and matrix-degrading genes (Il-6, Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and Col10a1). Histone acetylation increased at and near genes that had increased expression. The acetylation and activation of nuclear factor κB (NF-κB) were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling promoted autocrine activation of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and NF-κB pathways to suppress chondrocyte maturation, as well as paracrine activation of osteoclasts and bone resorption. Blockade of interleukin-6 (IL-6)–JAK–STAT signaling, NF-κB signaling, and bromodomain extraterminal proteins, which recognize acetylated lysines and promote transcriptional elongation, significantly reduced Il-6 and Mmp13 expression in HDAC3-deficient chondrocytes and secondary activation in osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial expression of tissue-remodeling genes and inflammatory responses in chondrocytes to ensure proper endochondral ossification during development. PMID

  5. Vertical Ridge Augmentation of the Atrophic Posterior Mandible with Sandwich Technique: Bone Block from the Chin Area versus Corticocancellous Bone Block Allograft—Clinical and Histological Prospective Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Luigi Laino

    2014-01-01

    Full Text Available The aim of the present study is to compare the histological aspects of bone formation in atrophic posterior mandibles augmented by autologous bone block from chin area with corticocancellous bone block allograft used as inlays with the sandwich technique. Materials and Methods. Sixteen patients with bilateral partial edentulism in the posterior mandible were selected. The residual bone height, preliminarily measured by computed tomography scans, ranged between 5 and 7 mm from the inferior alveolar nerve. All patients required regeneration procedure with autologous bone block from chin area (control group versus bone block allograft Puros (Zimmer Dental, 1900 Aston Avenue, Carlsbad, CA, USA (test group. Histological and histomorphometric samples were collected at the time of implant positioning in order to analyze the percentage of newly formed bone, the residual graft material, and marrow spaces/soft tissue. Results. No statistically significant differences between the two groups were found regarding the percentage of newly formed bone. The percentage of residual grafted material was significantly higher in the test group, whilst the percentage of marrow spaces was higher in control group. Conclusions. In conclusion, both procedures supported good results, although the use of bone blocks allograft was less invasive and preferable than harvesting bone from the mental symphysis.

  6. Papillary carcinoma thyroid, metastasis to cheek: First ever reported case in literature

    Directory of Open Access Journals (Sweden)

    Aiffa Aiman

    2014-01-01

    Full Text Available Papillary thyroid carcinoma (PTC metastasis to distant organs is rare and mainly includes lung and bone. Metastasis affecting oral and maxillofacial region is extremely rare. We describe a case of PTC metastasis to cheek. The patient presented with a painless swelling of the left cheek with a history of total thyroidectomy for papillary carcinoma thyroid 5 years back. Cheek metastasis from papillary carcinoma thyroid is extremely rare. To the best of our knowledge, this is the first recorded instance of cheek metastasis from PTC. Common malignancies can metastasize to unusual sites and although infrequent, may be the presenting feature. The successful management of such cases may be achieved by a multidisciplinary approach.

  7. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin [Dept. of Radiology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of); Noh, Song Mi; Jung, Woo Hee [Dept. of Diagnostic Pathology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  8. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    International Nuclear Information System (INIS)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin; Noh, Song Mi; Jung, Woo Hee

    2011-01-01

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  9. Design of polymer-biopolymer-hydroxyapatite biomaterials for bone tissue engineering: Through molecular control of interfaces

    Science.gov (United States)

    Verma, Devendra

    In this dissertation, novel biomaterials are designed for bone biomaterials and bone tissue engineering applications. Novel biomaterials of hydroxyapatite with synthetic and natural polymers have been fabricated using a combination of processing routes. Initially, we investigated hydroxyapatite-polycaprolactone-polyacrylic acid composites and observed that minimal interfacial interactions between polymer and mineral led to inadequate improvement in the mechanical properties. Bioactivity experiments on these composites showed that the presence of functional groups, such as carboxylate groups, influence bioactivity of the composites. We have developed and investigated composites of hydroxyapatite with chitosan and polygalacturonic acid (PgA). Chitosan and PgA are biocompatible, biodegradable, and also electrostatically complementary to each other. This strategy led to significant improvement in mechanical properties of new composites. The nanostructure analysis using atomic force microscopy revealed a multilevel organization in these composites. Enhancement in mechanical response was attributed to stronger interfaces due to strong electrostatic interaction between oppositely charged chitosan and PgA. Further analysis using the Rietveld method showed that biopolymers have marked impact on hydroxyapatite crystal growth and also on its crystal structure. Significant changes were observed in the lattice parameters of hydroxyapatite synthesized by following biomineralization method (organics mediated mineralization). For scaffold preparation, chitosan and PgA were mixed first, and then, nano-hydroxyapatite was added. Oppositely charged polyelectrolytes, such as chitosan and PgA, spontaneously form complex upon mixing. The poly-electrolyte complex exists as nano-sized particles. Chitosan/PgA scaffolds with and without hydroxyapatite were prepared by the freeze drying method. By controlling the rate of cooling and concentration, we have produced both fibrous and sheet

  10. The study of the precision and accuracy of quality control in DXA bone mineral densitometry

    International Nuclear Information System (INIS)

    Gong Jian; Xu Hao

    2005-01-01

    Objective: To study the precision and accuracy of quality control (QC) in dual-energy X-ray absorptiometry (DXA) bone mineral densitometry so as to raise the reliability and necessity of the results. Methods: 1) Short-term precision trial: 30 people and 30 SD male rats were chosen, and a precision trail was performed. Each people was scanned twice and reposited in next study. The precision and the least significant change (LSC) of each examinated region were calculated. The short-term precision trail of the rats was performed in the similar way. 2) Accuracy trial: measured the body phantom supplied by factor daily, and compared the results with real value, then calculated the accuracy and correction factor. A Shewhart chart was set up based on average values. Results: 1) People's coefficient of variation (CV) and LSC in the lumbar and proximal femur were 0.7%-2.2% and 0.018-0.048 g/cm 2 . Rats' whole body short-term precision was 0.9%. 2) The average accuracy of DXA densitometer was -0.81%, the correction factor was 0.992. The average bone mineral density measured in successive 25 d was 1.244 g/cm 2 , the standard deviation (SD) was 0.008. Conclusion: The precision and accuracy trail can help to get the information about the working state of the instrument and to analyze the measured results, and can effectively raise the reliability of the measure. (authors)

  11. Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials.

    Science.gov (United States)

    Hind, K; Burrows, M

    2007-01-01

    Osteoporosis is a serious skeletal disease and as there is currently no cure, there is a large emphasis on its prevention, including the optimisation of peak bone mass. There is increasing evidence that regular weight-bearing exercise is an effective strategy for enhancing bone status during growth. This systematic review evaluates randomised and non-randomised controlled trials to date, on the effects of exercise on bone mineral accrual in children and adolescents. An online search of Medline and the Cochrane database enabled the identification of studies. Those that met the inclusion criteria were included in the review and graded according to risk for bias. Twenty-two trials were reviewed. Nine were conducted in prepubertal children (Tanner I), 8 in early pubertal (Tanner II-III) and 5 in pubertal (Tanner IV-V). Sample sizes ranged from n=10 to 65 per group. Exercise interventions included games, dance, resistance training and jumping exercises, ranging in duration from 3 to 48 months. Approximately half of the trials (n=10) included ground reaction force (GRF) data (2 to 9 times body weight). All trials in early pubertal children, 6 in pre pubertal and 2 in pubertal children, reported positive effects of exercise on bone (P<0.05). Mean increases in bone parameters over 6 months were 0.9-4.9% in prepubertal, 1.1-5.5% in early pubertal and 0.3-1.9% in pubertal exercisers compared to controls (P<0.05). Although weight-bearing exercise appears to enhance bone mineral accrual in children, particularly during early puberty; it remains unclear as to what constitutes the optimal exercise programme. Many studies to date have a high risk for bias and only a few have a low risk. Major limitations concerned selection procedures, compliance rates and control of variables. More well designed and controlled investigations are needed. Furthermore, the specific exercise intervention that will provide the optimal stimulus for peak bone mineral accretion is unclear. Future

  12. Evaluation of Tumor Viability for Primary and Bone Metastases in Metastatic Castration-Resistant Prostate Cancer Using Whole-Body Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Hiromichi Iwamura

    2018-01-01

    Full Text Available In contrast to bone scan and computed tomography (CT, which depend on osteoblastic response to detect bone metastasis, whole-body magnetic resonance imaging (WB-MRI may be able to directly detect viable tumors. A 75-year-old male who had progressive metastatic prostate cancer during primary androgen deprivation therapy was referred to our hospital. Although bone scan and CT showed multiple bone metastases, WB-MRI suggested nonviable bone metastasis and viable tumor of the primary lesion. Prostate needle biopsy demonstrated viable prostate cancer cells from 10 of 12 cores. In contrast, CT-guided needle biopsy from bone metastasis of the lumbar vertebra revealed no malignant cells. Based on these findings, we reasoned that viable tumor cells inducing disease progression may primarily exist in the primary lesions and not in the metastatic lesions, and combined prostate radiotherapy and systemic hormonal therapy resulted in successful clinical response and disease control. The use of WB-MRI to detect viable disease lesions may enable us to design optimal treatment strategies for patients with metastatic castration-resistant prostate cancer.

  13. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  14. Ampullary carcinoma with cutaneous metastasis

    Directory of Open Access Journals (Sweden)

    I-Ting Liu

    2016-06-01

    Full Text Available Carcinoma of the ampulla of Vater is a rare gastrointestinal tumor. Additionally, cutaneous metastasis from such an internal malignancy is also uncommon. We reported the case of a 55-year-old man afflicted with ampullary carcinoma with cutaneous metastasis. The patient did not undergo the standard Whipple procedure but received chemotherapy due to apparent left neck lymph node metastasis noted by initial PET/CT imaging. The skin metastasis presented as a left neck infiltrating purpuric lesion, which was confirmed by skin biopsy approximately one year after the patient's disease was first diagnosed. Thereafter, the patient received further chemotherapy pursuant to his course of medical management. Skin metastasis usually represents a poor patient prognosis. In these cases, treatment of cutaneous metastasis typically includes systemic chemotherapy and local management such as radiation therapy or tumor excision. And when choosing a chemotherapy regimen for the ampullary cancer, the histological subtypes (intestinal or pancreatobiliary should be comprehensively considered. In our review of the literature, the intestinal type seems to have less distant lymph node metastasis, advanced local invasion, as well as recurrence than pancreatobiliary type of ampullary cancer.

  15. Skeletal metastasis: The effect on immature skeleton

    International Nuclear Information System (INIS)

    Ogden, J.A.; Ogden, D.A.

    1982-01-01

    The unique opportunity to study the entire appendicular skeleton of a child who died from metastatic angiosarcoma allowed detailed assessment of radiographically evident involvement. Virtually every portion of the appendicular skeleton had evidence of metastatic disease. However, the extent of involvement was extremely variable, especially when contralateral regions were assessed. The most likely region of metastasis, the metaphysis, is normally a fenestrated cortex of woven bone in the young child, rather than a well demarcated cortex formed by osteon (lamellar) bone, as it is in the adult. The pattern of destruction is such that less extensive areas may be involved before becoming radiographically evident, and trabecular bone involvement may be evident even without cortical damage. The metaphyseal metastatic spread supports the concept of arterial hematogeneous dissemination, comparable to osteomyelitis in the child. Pathologic metaphyseal fractures involved both proximal humeri; the fracture also extended along a portion of the methaphyseal-physeal interface in one humerus. In one distal femur the physis readily separated from the metaphysis; this was a nondisplaced type 1 growth mechanism injury. (orig.)

  16. Comparing the effects of chlorhexidine and persica on alveolar bone healing following tooth extraction in rats, a randomised controlled trial.

    Science.gov (United States)

    Dorri, Mojtaba; Shahrabi, Shokufeh; Navabazam, Alireza

    2012-02-01

    Chlorhexidine is broadly prescribed by clinicians for treating extraction socket wounds; however, studies have reported adverse effects for chlorhexidine. Persica, a herbal antibacterial agent, could be an alternative for chlorhexidine. The aim of this randomised controlled trial was to investigate the effects of persica and chlorhexidine on alveolar bone healing following tooth extraction in rats. Eighteen Wistar rats were randomly allocated to three study groups: 0.2% chlorhexidine, 10% persica and controls (tap water). The rats were mouth-rinsed for 14 days. On day 8, the mandibular right first molars of all the rats were extracted. On day 21, the rats were euthanized and histological slides of their extraction sockets were prepared. The amount of new bone formation and the number of inflammatory cells in the extraction socket for each rat were recorded. Data were analysed using linear regression and Mann-Whitney tests. There was no significant difference between the control group and the intervention groups in terms of new bone formation and inflammatory cell count. The mean new bone formation was significantly higher in the persica group than in the chlorhexidine group. There was a significant association between new bone formation and inflammatory cell count in the entire sample. In conclusion, there were no significant differences between rinsing with tap water and rinsing with 0.2% chlorhexidine and 10% persica in enhancing extraction socket wound healing in rats. Extraction socket wound healing in rats was better enhanced with 10% persica than 0.2% chlorhexidine.

  17. Scintigraphic control of bone-fracture healing under ultrasonic stimulation: An animal experimental study

    International Nuclear Information System (INIS)

    Klug, W.; Franke, W.G.; Knoch, H.G.

    1986-01-01

    In a model of closed lower-leg fracture in rabbits and of secondary bone-fracture healing, scintigraphic control until biological healing was performed. Biological fracture healing was assumed for a region of interest (ROI)-activity ratio close to 1.0. After application of sup(99m)Tc-HEDP, 151 examinations were performed. ROI activity increased significantly until day 14 p.i. and reached the maximum value (Q=6.44) on day 14 postfracture. Sixty-one lower leg fractures were treated by ultrasound from days 14-28 postfractures. These stimulated fractures were biologically healed on day 168 postfracture. The fractures that were not treated by ultrasound could not be detected by scanning after day 203 postfracture. (orig.)

  18. Partnership for fragility bone fracture care provision and prevention program (P4Bones: study protocol for a secondary fracture prevention pragmatic controlled trial

    Directory of Open Access Journals (Sweden)

    Gaboury Isabelle

    2013-01-01

    Full Text Available Abstract Background Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs. Methods/design This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers. The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants’ perceptions of care integration, expectations and satisfaction with the program; and participants’ compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated

  19. [Effectiveness of conventional diagnostic radiology and nuclear medicine in the treatment of pain from bone metastases].

    Science.gov (United States)

    Genovese, Eugenio Annibale; Mallardo, Vania; Vaccaro, Andrea; Santagata, Mario; Raucci, Antonio; D'Agosto, Gianfranco; Fontanarosa, Antonio; Schillirò, Francesco

    2013-01-01

    Bone is one of the most common metastasis sites from solid tumors. Bone pain due to metastatic neoplastic growth is due to tumor infiltration and expansion of bone membranes. Treatment of acute and chronic pain represents one of the greatest problems in clinical oncology, requiring a multidisciplinary approach. This review focuses on the effectiveness of conventional diagnostic radiology and nuclear medicine for the detection, management and treatment of pain from bone metastasis.

  20. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  1. Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature

    International Nuclear Information System (INIS)

    Moon, Kyung-Sub; Jung, Shin; Lee, Kyung-Hwa; Hwang, Eu Chang; Kim, In-Young

    2011-01-01

    Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC. A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis. To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities

  2. Bone induction through controlled release of novel BMP-2-related peptide from PTMC11-F127-PTMC11 hydrogels

    International Nuclear Information System (INIS)

    Tang Shuo; Li Jingfeng; Teng Yu; Guo Xiaodong; Zhao Jingjing; Xu Shuyun; Quan Daping

    2012-01-01

    Bone morphogenetic protein 2 (BMP-2) is the most powerful osteogenic factor; its effectiveness in enhancing osteoblastic activation has been confirmed both in vitro and in vivo. We developed a novel peptide (designated P24) derived from the ‘knuckle’ epitope of BMP-2 and found it also had osteogenic bioactivity to some extent. The main objective of this study was to develop a controlled release system based on poly(trimethylene carbonate)–F127–poly(trimethylene carbonate) (PTMC 11 -F127-PTMC 11 ) hydrogels for the P24 peptide, to promote bone formation. By varying the copolymer concentrations, we demonstrated that P24/PTMC 11 -F127-PTMC 11 hydrogels were an efficient system for the sustained release of P24 over 21–35 days. The P24-loaded hydrogels elevated alkaline phosphatase activity and promoted the expression of osteocalcin mRNA in bone marrow stromal cells (BMSCs) in vitro. Radiographic and histological examination showed that P24-loaded hydrogels could induce more effective ectopic bone formation in vivo than P24-free hydrogels. These results indicate that the PTMC 11 -F127-PTMC 11 hydrogel is a suitable carrier for the controlled release of P24, and is a promising injectable biomaterial for the induction of bone regeneration. (paper)

  3. Palliative surgery for acetabular metastasis with pathological central dislocation of the hip joint after radiation therapy. A case report

    International Nuclear Information System (INIS)

    Hoshi, Manabu; Takada, Jun; Oebisu, Naoto; Nakamura, Hiroaki; Taguchi, Susumu; Takami, Masatsugu

    2012-01-01

    Orthopedic surgery for bone metastases is mainly a palliative treatment. Pathological central dislocation of the hip joint secondary to osteonecrosis of acetabular metastasis after radiation therapy brings severe suffering to cancer patients. We performed minimally invasive palliative surgery for an elderly woman, and excellent pain relief was achieved. An 80-year-old female suffering from right hip pain was referred to our hospital. She had undergone surgery for lung cancer 5 years previously and her right acetabulum was subsequently affected by metastasis. With the aim of controlling the metastasis, radiation therapy was performed. Two years later, pathological central dislocation of the hip joint occurred with sudden onset of severe pain, and she was unable to maintain a sitting position and became bedridden. After she was referred to our hospital, we created an intentional pseudarthrosis in the femoral neck for palliation. After the surgery, excellent pain relief and remarkably improved mobility were achieved during her limited remaining lifetime. In this report, we introduce a novel method of producing a pseudarthrosis in the femoral neck for pathological dislocation. This procedure is a minimally invasive treatment and an alternative option for palliative surgery for pathological dislocation of the hip joint due to osteonecrosis after radiation therapy. (author)

  4. Cutaneous metastasis in anorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Krishnendra Varma

    2015-01-01

    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  5. Periacetabular Bone Mineral Density Changes After Resurfacing Hip Arthroplasty Versus Conventional Total Hip Arthroplasty. A Randomized Controlled DEXA Study

    NARCIS (Netherlands)

    Smolders, J.M.H.; Pakvis, D.F.; Hendrickx, B.W.; Verdonschot, Nicolaas Jacobus Joseph; van Susante, J.L.C.

    2013-01-01

    A randomized controlled trial was performed to evaluate acetabular bone mineral density (BMD) changes after hip resurfacing (RHA) versus an established conventional total hip arthroplasty (THA). A total of 71 patients were allocated randomly to receive either an RHA press-fit cobalt–chromium cup (n

  6. Navigation and Image Injection for Control of Bone Removal and Osteotomy Planes in Spine Surgery.

    Science.gov (United States)

    Kosterhon, Michael; Gutenberg, Angelika; Kantelhardt, Sven Rainer; Archavlis, Elefterios; Giese, Alf

    2017-04-01

    In contrast to cranial interventions, neuronavigation in spinal surgery is used in few applications, not tapping into its full technological potential. We have developed a method to preoperatively create virtual resection planes and volumes for spinal osteotomies and export 3-D operation plans to a navigation system controlling intraoperative visualization using a surgical microscope's head-up display. The method was developed using a Sawbone ® model of the lumbar spine, demonstrating feasibility with high precision. Computer tomographic and magnetic resonance image data were imported into Amira ® , a 3-D visualization software. Resection planes were positioned, and resection volumes representing intraoperative bone removal were defined. Fused to the original Digital Imaging and Communications in Medicine data, the osteotomy planes were exported to the cranial version of a Brainlab ® navigation system. A navigated surgical microscope with video connection to the navigation system allowed intraoperative image injection to visualize the preplanned resection planes. The workflow was applied to a patient presenting with a congenital hemivertebra of the thoracolumbar spine. Dorsal instrumentation with pedicle screws and rods was followed by resection of the deformed vertebra guided by the in-view image injection of the preplanned resection planes into the optical path of a surgical microscope. Postoperatively, the patient showed no neurological deficits, and the spine was found to be restored in near physiological posture. The intraoperative visualization of resection planes in a microscope's head-up display was found to assist the surgeon during the resection of a complex-shaped bone wedge and may help to further increase accuracy and patient safety. Copyright © 2017 by the Congress of Neurological Surgeons

  7. [The related factors of head and neck mocosal melanoma with lymph node metastasis].

    Science.gov (United States)

    Yin, G F; Guo, W; Chen, X H; Huang, Z G

    2017-12-05

    Objective: To investigate the related factors of mucosal melanoma of head and neck with lymph node metastasis for early diagnosis and further treatments. Method: A retrospective analysis of 117 cases of head and neck mucosal malignant melanoma patients which received surgical treatment was performed. Eleven cases of patients with pathologically confirmed lymph node metastasis and 33 cases without lymph node metastasis (1∶3) were randomly selected to analyze. The related factors of lymph node metastasis of head and neck mucosal melanoma patients including age, gender, whether the existence of recurrence, bone invasion, lesion location were analyzed. The single factor and logistic regression analysis were performed, P difference was statistically significant. Result: The lymph node metastasis rate of head and neck mucosal melanoma was 9.40%(11/117), the single factor analysis showed that there were 3 factors to be associated with lymph node metastasis, which was recurrence ( P =0.0000), bone invasion ( P =0.001), primary position ( P =0.007). Recurrence ( P =0.021) was a risk factor for lymph node metastasis according to the Logistic regression analysis, and the impact of bone invasion ( P =0.487) and primary location ( P =0.367) remained to be further explored. Conclusion: The patients of head and neck mucosal melanoma with the presence of recurrent usually accompanied by a further progression of the disease, such as lymph node metastasis, so for recurrent patients should pay special attention to the situation of lymph node and choose the reasonable treatment. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  8. Unipedal standing exercise and hip bone mineral density in postmenopausal women: a randomized controlled trial.

    Science.gov (United States)

    Sakai, Akinori; Oshige, Toshihisa; Zenke, Yukichi; Yamanaka, Yoshiaki; Nagaishi, Hitoshi; Nakamura, Toshitaka

    2010-01-01

    The aim of this study was to test the effect of unipedal standing exercise on bone mineral density (BMD) of the hip in postmenopausal women. Japanese postmenopausal women (n = 94) were assigned at random to an exercise or control group (no exercise). The 6-month exercise program consisted of standing on a single foot for 1 min per leg 3 times per day. BMD of the hip was measured by dual-energy X-ray absorptiometry. There was no significant difference in age and baseline hip BMD between the exercise group (n = 49) and control group (n = 45). Exercise did not improve hip BMD compared with the control group. Stepwise regression analysis identified old age as a significant determinant (p = 0.034) of increased hip total BMD at 6 months after exercise. In 31 participants aged >/=70 years, the exercise group (n = 20) showed significant increase in the values of hip BMD at the areas of total (p = 0.008), intertrochanteric (p = 0.023), and Ward's triangle (p = 0.032). The same parameters were decreased in the control group (n = 11). The percent changes in hip BMD of the exercise group were not significantly different from those of the control group either in the participants with low baseline hip total BMD ( or =80% of the young adult mean). In conclusion, unipedal standing exercise for 6 months did not improve hip BMD in Japanese postmenopausal women. Effect of exercise on hip total BMD was age dependent. In participants aged > or =70 years, the exercise significantly increased hip total BMD.

  9. Stereotactic radiosurgery for brain metastasis: Pitie-Salpetriere Hospital experience

    International Nuclear Information System (INIS)

    Feuvret, L.; Germain, I.; Cornu, P.; Boisserie, G.; Dormont, D.; Hardiman, C.; Tep, B.; Faillot, T.; Duffau, H.; Simon, J.M.; Dendale, R.; Delattre, J.Y.; Poisson, M.; Marsault, C.; Philippon, J.; Fohanno, D.; Baillet, F.; Mazeron, J.J.

    1998-01-01

    Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. From january 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm 3 . The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Sixty-five metastasis were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm. (authors)

  10. Alpha-enolase (ENO1 controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis

    Directory of Open Access Journals (Sweden)

    Moitza Principe

    2017-01-01

    Full Text Available Abstract Background We have previously shown that in pancreatic ductal adenocarcinoma (PDA cells, the glycolytic enzyme alpha-enolase (ENO1 also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We therefore investigated the effect of ENO1 silencing on the modulation of cell morphology, adhesion to matrix substrates, cell invasiveness, and metastatic ability. Methods The membrane and cytoskeleton modifications that occurred in ENO1-silenced (shENO1 PDA cells were investigated by a combination of confocal microscopy and atomic force microscopy (AFM. The effect of ENO1 silencing was then evaluated by phenotypic and functional experiments to identify the role of ENO1 in adhesion, migration, and invasion, as well as in senescence and apoptosis. The experimental results were then validated in a mouse model. Results We observed a significant increase in the roughness of the cell membrane due to ENO1 silencing, a feature associated with an impaired ability to migrate and invade, along with a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alpha v/beta 3 integrin in shENO1 PDA cells. These changes impaired the ability of shENO1 cells to adhere to Collagen I and IV and Fibronectin and caused an increase in RGD-independent adhesion to vitronectin (VN via urokinase plasminogen activator receptor (uPAR. Binding of uPAR to VN triggers integrin-mediated signals, which result in ERK1-2 and RAC activation, accumulation of ROS, and senescence. In shENO1 cancer cells, the use of an anti-uPAR antibody caused significant reduction of ROS production and senescence. Overall, a decrease of in vitro and in vivo cell

  11. Long-Term Tumor Control despite Late Pseudoprogression on 18F-FDG-PET following Extremely Hypofractionated Stereotactic Radiotherapy for Retropharyngeal Lymph Node Metastasis from Esthesioneuroblastoma

    Directory of Open Access Journals (Sweden)

    Kazuhiro Ohtakara

    2014-08-01

    Full Text Available 18F-FDG-PET is a valuable adjunct to conventional imaging for evaluating treatment response following stereotactic body radiotherapy (SBRT for head and neck malignancies (HNM. The effect of treatment-related inflammation is generally deemed negligible after 12 weeks following conventionally fractionated radiotherapy. Herein, we describe an unusual case showing pseudoprogression on 18F-FDG-PET 2 years after SBRT for retropharyngeal lymph node metastasis (RPLNm from esthesioneuroblastoma. A 36-year-old man presented with right RPLNm 32 months after the diagnosis of esthesioneuroblastoma associated with ectopic adrenocorticotropic hormone production. The RPLNm was treated with SBRT in 2 fractions over 8 days using dynamic conformal arcs with concomitant chemotherapy with cisplatin and etoposide. Although follow-up MRI showed sustained lesion regression, the early/delayed maximum standardized uptake (SUVmax values on dual-time-point 18F-FDG-PET obtained 1 and 2 years after SBRT were 7.7/8.3 and 8.5/10.1, respectively, suggesting local progression. Despite no subsequent focal or systemic treatment, the SUVmax values gradually decreased thereafter over a period of 4 years (3.3/3.4 at 76 months. MRI obtained 7 years after SBRT revealed sustained tumor regression. No obvious relevant toxicities have occurred. Thus, caution should be exercised in the interpretation of the SUVmax change following ablative irradiation for HNM.

  12. Quantification of B16 Melanoma Cells in Lungs Using Triplex Q-PCR - A New Approach to Evaluate Melanoma Cell Metastasis and Tumor Control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Pedersen, Sara R; Lindkvist, Annika

    2014-01-01

    of survival once the tumor has metastasized. In the present study, we have developed a new assay for quantitative analysis of B16 melanoma metastasis in the lungs. We have used a triplex Q-PCR to determine the expression of the melanoma genes GP100/Pmel and tyrosinase-related protein 2 (TRP-2), and found...... that B16.F10gp cells were detectable in the lungs as early as 2 hours after intravenous challenge with ≥10(4) tumor cells. When investigating the gene expression as a function of time, we observed a gradual decrease from 2-24 hours post tumor challenge followed by an increase of approximately 2 log10...... the outgrowth of subcutaneous melanomas. Results obtained using Q-PCR were compared to conventional counting of metastatic foci under a dissection microscope. A marked reduction in gene expression was observed in the lungs after vaccination with both vectors; however, Ad-Ii-GP showed the highest protection...

  13. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

    2013-09-08

    Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple

  14. 9 CFR 318.24 - Product prepared using advanced meat/bone separation machinery; process control.

    Science.gov (United States)

    2010-01-01

    ... exiting the AMR system for bone solids, bone marrow, spinal cord, and DRG as prescribed in paragraph (c)(1..., or the product that exits the AMR system contains spinal cord. (v) DRG. The product that exits the AMR system contains DRG. (2) If product that may not be labeled or used as “meat” under this section...

  15. Adenocarcinoma of urethra presenting metastasis to eyes: a case report

    International Nuclear Information System (INIS)

    Lages, Rafael Bandeira; Sousa, Rodrigo Beserra; Santos, Lina Gomes dos; Vieira, Sabas Carlos; Tavares, Marilia Buenos Aires Cabral

    2010-01-01

    Primary urethral carcinoma is extremely rare, accounting for less than 1% of all female genitourinary tract cancers. To the best of our knowledge, this patient is the first reported case of primary urethral carcinoma presenting metastasis to eyes. The diagnosis of metastasis involving the choroids should be suspected in patient with history of carcinoma and a decreased visual acuity or any other visual symptom. Case presentation: A 43-year-old woman underwent a total hysterectomy, cystectomy and bilateral pelvic lymphadenectomy due a primary adenocarcinoma of the proximal urethra. Adjuvant pelvic radiotherapy and six cycles of chemotherapy using cisplatin were performed. The patient made follow-up with no evidence of oncologic disease. However, nine months later, the patient reported visual alterations. Ophthalmoloscopic examination showed choroid lesions in both eyes that were compatible with metastatic choroids tumor and nuclear magnetic resonance suggested bilateral retinal metastasis and left meningioma parasagittal in parietal region. She was undergoing a new palliative chemotherapy, but the disease developed and there were metastasis to bone four months later. The patient died fourteen months after the surgery. (author)

  16. Adenocarcinoma of urethra presenting metastasis to eyes: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lages, Rafael Bandeira; Sousa, Rodrigo Beserra; Santos, Lina Gomes dos; Vieira, Sabas Carlos, E-mail: rafaelblages@gmail.co [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil); Tavares, Marilia Buenos Aires Cabral [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Hospital Universitario Walter Cantidio; Valenca, Rodrigo Jose de Vasconcelos [Hospital Sao Marcos (HSM), Teresina, PI (Brazil)

    2010-07-01

    Primary urethral carcinoma is extremely rare, accounting for less than 1% of all female genitourinary tract cancers. To the best of our knowledge, this patient is the first reported case of primary urethral carcinoma presenting metastasis to eyes. The diagnosis of metastasis involving the choroids should be suspected in patient with history of carcinoma and a decreased visual acuity or any other visual symptom. Case presentation: A 43-year-old woman underwent a total hysterectomy, cystectomy and bilateral pelvic lymphadenectomy due a primary adenocarcinoma of the proximal urethra. Adjuvant pelvic radiotherapy and six cycles of chemotherapy using cisplatin were performed. The patient made follow-up with no evidence of oncologic disease. However, nine months later, the patient reported visual alterations. Ophthalmoloscopic examination showed choroid lesions in both eyes that were compatible with metastatic choroids tumor and nuclear magnetic resonance suggested bilateral retinal metastasis and left meningioma parasagittal in parietal region. She was undergoing a new palliative chemotherapy, but the disease developed and there were metastasis to bone four months later. The patient died fourteen months after the surgery. (author)

  17. Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer.

    Science.gov (United States)

    Lin, Song-Chang; Lee, Yu-Chen; Yu, Guoyu; Cheng, Chien-Jui; Zhou, Xin; Chu, Khoi; Murshed, Monzur; Le, Nhat-Tu; Baseler, Laura; Abe, Jun-Ichi; Fujiwara, Keigi; deCrombrugghe, Benoit; Logothetis, Christopher J; Gallick, Gary E; Yu-Lee, Li-Yuan; Maity, Sankar N; Lin, Sue-Hwa

    2017-06-05

    Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells. BMP4 overexpression in non-osteogenic C4-2b PCa cells led to ectopic bone formation under subcutaneous implantation. Tumor-induced bone was reduced in trigenic mice (Tie2 cre /Osx f/f /SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osx f/f /SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

    Science.gov (United States)

    Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

    2018-01-01

    No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

  19. Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

    Directory of Open Access Journals (Sweden)

    Fumito Kuranishi

    2018-01-01

    Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

  20. Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

    2007-01-01

    Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

  1. Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study.

    Science.gov (United States)

    Cadossi, Matteo; Buda, Roberto Emanuele; Ramponi, Laura; Sambri, Andrea; Natali, Simone; Giannini, Sandro

    2014-10-01

    Osteochondral lesions of the talus (OLT) frequently occur after ankle sprains in young patients participating in sports activities. These injuries may lead to chronic pain, joint swelling, and finally osteoarthritis, therefore, surgical repair is frequently needed. A collagen scaffold seeded with bone marrow-derived cells (BMDCs) harvested from patient's iliac crest and implanted into the OLT through a single arthroscopic procedure has been recently proposed as an effective treatment option. Nevertheless, BMDCs, embedded in an inflammatory environment, tend to differentiate toward a fibroblast phenotype with a consequential loss of mechanical characteristics. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been shown to promote anabolic chondrocyte activity, stimulate proteoglycan synthesis, and reduce the release of the most relevant pro-inflammatory cytokines. The aim of this randomized controlled trial was to evaluate the effects of PEMFs on clinical outcome in patients who underwent BMDCs transplantation for OLT. Thirty patients affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 hours per day for 60 days starting within 3 days after operation) or control group. Clinical outcome was evaluated with (American Orthopaedic Foot and Ankle Society) AOFAS score, Visual Analog Scale (VAS), and Short Form-36 (SF-36). Significantly higher AOFAS score was recorded in the experimental group both at 6 or 12 months follow-up. At 60 days and 6 and 12 months follow-up, significant lower pain was observed in the experimental group. No significant difference was found in SF-36 between groups. A superior clinical outcome was found in the experimental group with more than 10 points higher AOFAS score at final follow-up. Biophysical stimulation started soon after surgery aided patient recovery leading to pain control and a better clinical outcome

  2. Application and Effect of Mobiletype-Bone Health Intervention in Korean Young Adult Women with Low Bone Mass: A Randomized Control Trial

    Directory of Open Access Journals (Sweden)

    Young-Joo Park, PhD, RN

    2017-03-01

    Conclusion: Although both experimental groups exhibited positive outcomes in regards to the promotion of bone health, this study did not show an additional effect of the mobile application on self-management ability for the promotion of bone health. Nonetheless, the SbFb application is very meaningful as it is the first application developed with the aim of improving women's bone health.

  3. Nodal metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    The biological behavior and hence the prognosis of thyroid cancer (TC) depends among other factors on the extent of spread of the disease outside the thyroid bed. This effect is controversial, especially for nodal metastasis of well differentiated thyroid carcinoma (WDC). Nodal metastasis at the time of initial diagnosis behaves differently depending on the histology, age of the patient, presence of extrathyroidal extension, and the sex of the individual. The type of the surgery, administration of 131 I and thyroxin suppression also to some extent influence the rate of recurrence and mortality. Experience has shown that it is not as innocuous as a small intrathyroidal tumor without any invasion outside the thyroid bed and due consideration should be accorded to the management strategies for handling patients with nodal metastasis

  4. Intracardiac metastasis originated from chondrosarcoma.

    Science.gov (United States)

    Maurea, Nicola; Ragone, Gianluca; Coppola, Carmela; Caronna, Antonietta; Tocchetti, Carlo G; Agozzino, Lucio; Apice, Gaetano; Iaffaioli, Rosario V

    2017-05-01

    Primary cardiac tumors are extremely rare. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer. Cardiac metastasis of chondrosarcoma is absolutely not frequent. In the recent literature, a cardiac metastasis from chondrosarcoma has never been described. We report the case of an 18-year-old man with a diagnosis of cardiac metastasis that originated from a left scapular chondrosarcoma. Chondrosarcoma is a skeletal tumor with various grades of malignancy, rapidly evolving, and with a strong tendency to metastasize, with low responsiveness to chemotherapy. The onset of characteristic systemic symptoms in the late stage of the disease led to the diagnosis of a mass localized in the right atrium. Management and differential diagnosis of infective heart lesions were also very complex in a rapidly evolving life-threatening condition.

  5. A Case of Patella Metastasis of Papillary Thyroid Carcinoma

    International Nuclear Information System (INIS)

    Han, Eun Ji; Choi, Woo Hee; Chung, Yong An; Sohn, Hyung Sun; Kang, Chang Suk

    2009-01-01

    A 73-year-old man presented with a chief complaint of progressive left knee pain for two months. He had a history of total thyroidectomy and central lymph node dissection due to papillary thyroid carcinoma three months ago. MRI images revealed a solid mass in the left patella. A solid mass demonstrated low signal on T1 weighed image, and high signal on T2 weighed image. And whole body bone scan showed focal photon defect in same lesion of left patella. The histologic result of left knee lesion was adenocarcinoma, consistent with metastatic papillary thyroid carcinoma. Although patellar metastasis of papillary thyroid carcinoma is very rare, when knee pain and radiologic abnormality are noted, differential diagnosis of metastasis is necessary

  6. Spinal metastasis of medulloblastoma in adults: A case report

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2014-01-01

    Full Text Available Introduction. Medulloblastoma is a primitive neuro-ectodermal malignant tumor most commonly seen in childhood and rarely and uncommonly in adult age. Treatment consists of surgery followed by radiotherapy. In the case of a relapse there is no overall accepted treatment. Tumor metastasis can be seen along the neural axis, lymph nodes, soft tissues, bones and distant organs. Case Outline. In this paper we present a 45-year-old female patient with a thoraco-spinal extramedullary metastatic medulloblastoma and progressive neurological deterioration seen 11 months after the first operation and description of magnetic resonance and intraoperative finding. Conclusion. Although rare, the presence of metastasis is a poor prognostic factor. The treatment options for patients with metastases are limited and their prognosis continues to remain poor.

  7. Anorexia Nervosa and Bone

    Science.gov (United States)

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure and reduced bone strength, all of which contribute to increased fracture risk., Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising addition concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiologic estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. PMID:24898127

  8. What Is Breast in the Bone?

    Science.gov (United States)

    Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

    2016-10-22

    The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

  9. Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

    2017-09-06

    The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P system (P skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

  10. The Roles of the Bone Marrow Microenvironment in Controlling Tumor Dormancy

    Science.gov (United States)

    2017-10-01

    commonly metastasizes to bone with consequent bone pain , pathological fractures, ver- tebrae compressions, and hypercalcemia, this process is...treat potential progression of hepatitis C-related fibrosis reduced circulating TGF-beta and IL-6.92 Abdominal pain , rash, and nausea were seen in a...jpi.12380. 240. Pariente R, Pariente JA, Rodríguez AB, Espino J. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced

  11. Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

    1983-07-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

  12. Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study

    Science.gov (United States)

    Heavy alcohol drinking adversely affects vitamin D status and bone health. However, data from randomized, placebo-controlled trials (RCTs) on the effects of low to moderate alcohol consumption on vitamin D status and bone health in humans is unavailable. The objective of this cross-over RCT was to e...

  13. Cisplatin Induces Up-Regulation of KAI1, a Metastasis Suppressor ...

    African Journals Online (AJOL)

    HP

    including breast, testicular, ovarian, cervical, prostate, head and neck, ..... Vertebral bone metastasis in breast cancer: a case report. Rom J Morphol Embryol 2011; 52: 897-. 905. ... KAI1/CD82 on the β1 integrin maturation in highly migratory ...

  14. Intracranial Dural Metastasis of Ewing's Sarcoma: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eung Yeop; Lee, Seung Koo; Kim, Dong Joon; Kim, Jin Na; Lee, Kyu Sung; Jung, Woo Hee; Kim, Dong Ik [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2008-02-15

    Ewing's sarcoma is a malignant bone tumor that can occur anywhere in the body, but it is most commonly observed in the long bones of the arms and legs, the pelvis and in the chest. The predominant sites of metastasis include the lung (38%), bone (including the spine; 31%), and the bone marrow (11%). Metastasis of Ewing's sarcoma to the central nervous system (CNS) is relatively rare, and most of the previous reports have demonstrated involvement of the bony calvarium or brain parenchyma. We describe here the imaging findings of dural metastasis of Ewing's sarcoma, and these imaging findings have not been previously reported on in the medical literature. In conclusion, dural metastasis of Ewing's sarcoma is very rare and its imaging characteristics are similar to those of a primary tumor, which mimic the findings of a schwannoma or meningioma. Despite its rarity, secondary Ewing's sarcoma may be included in the differential diagnosis of extra-axial dural masses.

  15. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  16. Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation.

    Science.gov (United States)

    Wei, Wei; Shary, Judith R; Garrett-Mayer, Elizabeth; Anderson, Betsy; Forestieri, Nina E; Hollis, Bruce W; Wagner, Carol L

    2017-12-01

    Background: Little is known about bone mineral density (BMD) during pregnancy. Advances in technology with lower radiation emissions by dual-energy X-ray absorptiometry instruments now permit the safe measurement of BMD during pregnancy. Objective: We evaluated maternal BMD during pregnancy as a function of vitamin D status in women of diverse racial/ethnic backgrounds. Design: A total of 301 women who underwent BMD measurements at 12-20 wk of gestation and again at 0-14 wk postpartum were included in this analysis. Women were a subset of subjects who were recruited for a randomized, controlled, double-blind trial of vitamin D supplementation in pregnancy (400, 2000, or 4000 IU/d). Results: Treatment had no significant effect on changes in BMD that occurred between 12-20 wk of gestation and 0-14 wk postpartum. Similarly, changes in spine and femoral neck bone mineral contents (BMCs) were not significantly different in the treatment groups. In addition, vitamin D inadequacy (serum 25-hydroxyvitamin D concentration, averaged across pregnancy, vitamin D supplementation on bone health and suggest that race/ethnicity and BMI play an important role in pregnancy bone health. This trial was registered at clinicaltrials.gov as NCT00292591. © 2017 American Society for Nutrition.

  17. Cutaneous metastasis of bilateral renal cell carcinoma.

    Science.gov (United States)

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  18. Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

    1997-01-01

    Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

  19. Bone metastases from gastric cancer

    International Nuclear Information System (INIS)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

    1983-01-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

  20. Metastasis genetics, epigenetics, and the tumor microenvironment

    Science.gov (United States)

    KISS1 is a member of a family of genes known as metastasis suppressors, defined by their ability to block metastasis without blocking primary tumor development and growth. KISS1 re-expression in multiple metastatic cell lines of diverse cellular origin suppresses metastasis; yet, still allows comple...

  1. The yerba mate intake has a neutral effect on bone: A case-control study in postmenopausal women.

    Science.gov (United States)

    da Veiga, Denise T A; Bringhenti, Raísa; Bolignon, Aline A; Tatsh, Etiane; Moresco, Rafael N; Comim, Fabio V; Premaor, Melissa O

    2018-01-01

    Nutritional factors have been associated with osteoporosis and fractures. The intake of coffee may increase the risk of fracture whereas the intake of black and green tea is associated with its reduction. Recently, consumption of yerba mate was associated with increased bone mineral density in postmenopausal women. Nonetheless, its influence on fracture is not known. The aim of this study was to evaluate the effect of yerba mate tea intake on fractures, bone markers, calcium homeostasis, and oxidative stress in postmenopausal women. A case-control study was carried out in South Brazil, 46 women with fractures and 49 controls completed the study. There was no significant difference between the frequency of fractures in women who drank mate tea and women who did not (48.3% vs. 48.5%, p = .99). Moreover, there was no significant difference concerning the serum levels of total calcium, phosphorus, PTH, vitamin D, P1NP, and CTX in the subjects with the history of yerba mate use when compared to controls. Higher serum levels of NOx were found in women who drank the yerba mate infusion. In conclusion, the yerba mate intake is not associated with fracture, and it appears to have a neutral effect on the bone metabolism. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Skeletal metastases in pancreatic carcinoma: study by isotopic bone scanning

    Energy Technology Data Exchange (ETDEWEB)

    Hatfield, D R; Deland, F H; Maruyama, Y

    1976-01-01

    A review of the literature of 2,155 reported patients with primary carcinoma of the pancreas, revealed 110 cases or 5 percent to have skeletal metastasis by radiographic or autopsy study. A study conducted over a 2 year period disclosed that 1 case of skeletal metastasis was detected by bone scanning in 16 patients with pancreatic carcinoma. This indicates a minimum skeletal metastasis rate of 6 percent. We feel these percentages are low and can be further defined by the more routine employment of the bone scan to evaluate patients with carcinoma of the pancreas. The true figure may be much higher, perhaps as high as 20 percent.

  3. CT manifestation of peritoneal metastasis

    International Nuclear Information System (INIS)

    Cha, Soon Joo; Kang, Eun Young; Suh, Won Hyuck

    1989-01-01

    Peritoneal metastasis is frequent mode of dissemination of intraabdominal malignancies. Radiologic diagnosis of peritoneal metastasis has relied on indirect evidence on a barium UGI series and small bowel examination. With the advent of CT scanning, CT is capable of direct imaging of peritoneum. The sensitivity of CT in detecting peritoneal metastasis and CT manifestation of peritoneal metastatic lesions had reported occasionally, but rarely in Korea. So, authors illustrated the CT manifestation of peritoneal metastatic lesions in 32 cases of macroscopically proven cases in laparoscopy or laparotomy in Korea University Hae Wha Hospital during recent 4 years. The results are as follows. 1. Of total 32 cases, 18 cases were male and 14 cases were female. Age incidence was the most common in 6th decade. 2. The most common type of malignancy that cause peritoneal metastasis was the stomach cancer and next common type of malignancies were pancreas cancer in men and ovarian cancer in women. 3. Of total 32 cases of peritoneal metastasis which was confirmed by laparoscopy or laparotomy macroscopically, 23 cases (72%) were detected peritoneal thickening and/or omental pathology by CT, and the remaining 9 cases (28%) were not detected by CT. 4. Ascites was present in 19 cases (59%). 5. Parietal peritoneal thickening was present in 16 cases (50%) by CT and sheetlike pattern was the most common findings. The patterns of peritoneal thickening was relatively nonspecific and was not correlated with primary tumor type. 6. Tumor involvement of greater omentum by CT was present in 19 cases (59%). There were 7 cases of smudged appearance pattern, 6 cases of nodular pattern, 6 cases of omental cake pattern and no cystic mass pattern. The patterns of omental pathology was relatively nonspecific and was nor correlated with primary tumor type

  4. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

    Science.gov (United States)

    Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Bassil, Darina; El Ferkh, Karim; El-Hajj Fuleihan, Ghada

    2017-07-01

    The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p 76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  5. A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation.

    Science.gov (United States)

    Smerud, K T; Dolgos, S; Olsen, I C; Åsberg, A; Sagedal, S; Reisæter, A V; Midtvedt, K; Pfeffer, P; Ueland, T; Godang, K; Bollerslev, J; Hartmann, A

    2012-12-01

    The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Magnetic resonance guided focused ultrasound surgery (MRgFUS) of bone metastases: From primary pain palliation to local tumor control

    Science.gov (United States)

    Napoli, A.; Leonardi, A.; Andrani, F.; Boni, F.; Anzidei, M.; Catalano, C.

    2017-03-01

    Purpose: To evaluate the clinical performance of MRgFUS in primary pain palliation of painful bone metastases and in local tumor control. Materials and Methods: We enrolled 26 consecutive patients (female/male 12/14; age: 64.7±7.5yrs) with painful bone metastases. Before and 3 months after MRgFUS treatment pain severity and pain interference scores were assessed according to Brief Pain Inventory-Quality of Life (BPI-QoL) criteria and patients underwent both CT and MRI. Local tumor control was evaluated according to lesion size, density and perfusion at CT, dynamic contrast enhancement at MRI (Discovery 750HD, GE; Gd-Bopta, Bracco) and metabolic activity at PET or scintigraphy. Patients were classified as responders or non-responders. Results: No treatment-related adverse events were recorded during the study. As statistically significant difference between baseline and follow-up values for both pain severity and pain interference scores was observed (p<0.05). Increased bone density was observed in 9/26 (34.6%) patients. Non-Perfused Volume values ranged between 20% and 92%. There was no difference in NPV values between responders and non-responders (46.7±24.2% [25 - 90 %] vs. 45±24.9% [20 - 93 %]; p=0.7). In 6 patients (5 prostate and 1 breast primary cancer) there was nearly absence of metabolic activity after treatment (mean SUV=1.2). Conclusion: MRgFUS can be safely and effectively used as the primary treatment for pain palliation in patients with painful bone metastases; moreover our experience demonstrated also a potential role for the MRgFUS in local tumor control.

  7. Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy.

    Science.gov (United States)

    Hart, Nicolas H; Newton, Robert U; Spry, Nigel A; Taaffe, Dennis R; Chambers, Suzanne K; Feeney, Kynan T; Joseph, David J; Redfern, Andrew D; Ferguson, Tom; Galvão, Daniel A

    2017-05-30

    Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine-paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety of a combined modular multimodal exercise programme with spinal isometric training in advanced prostate cancer patients with sclerotic bone metastases and (2) examine whether targeted and supervised exercise can suppress sclerotic tumour growth and activity in spinal metastases in humans. A single-blinded, two-armed, randomised, controlled and explorative phase I clinical trial combining spinal isometric training with a modular multimodal exercise programme in 40 men with advanced prostate cancer and stable sclerotic spinal metastases. Participants will be randomly assigned to (1) the exercise intervention or (2) usual medical care. The intervention arm will receive a 3-month, supervised and individually tailored modular multimodal exercise programme with spinal isometric training. Primary endpoints (feasibility and safety) and secondary endpoints (tumour morphology; biomarker activity; anthropometry; musculoskeletal health; adiposity; physical function; quality of life; anxiety; distress; fatigue; insomnia; physical activity levels) will be measured at baseline and following the intervention. Statistical analyses will include descriptive characteristics, t-tests, effect sizes and two-way (group × time) repeated-measures analysis of variance (or analysis of

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

    Directory of Open Access Journals (Sweden)

    Juliana Dreyer da Silva de Menezes

    2013-09-01

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

  9. Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

    International Nuclear Information System (INIS)

    Saber, M.M.; Shouman, T.

    2003-01-01

    To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

  10. Experimental study of chemical embolus therapy combined with radiotherapy for VX2 bone tumors

    International Nuclear Information System (INIS)

    Yamaguchi, Hiroshi; Mochizuki, Kazuo; Ishii, Yoshiaki

    2000-01-01

    We conducted an experimental study, using a combination of coarse crystal cisplatin and radiotherapy for bone tumors, to evaluate the possibility of the clinical application of chemical embolus therapy in the field of orthopedic surgery. Experimental femoral bone tumors were produced, in rabbits, using VX2 carcinoma. The rabbits were allocated to five groups: untreated control, embolus, chemical embolus, irradiation alone, and chemical embolus and irradiation combination. These therapies were evaluated comparatively, in terms of local antitumor effects (including body weight, X-ray findings, angiography, and histopathology) and in terms of inhibition of pulmonary metastasis. Local antitumor effects, as evaluated by all parameters, except for body weight, were significantly greater for the chemical and irradiation combination group than for the chemical embolus, irradiation alone, untreated control, and embolus groups. There was no significant difference in the inhibition of pulmonary metastasis among the chemical embolus and irradiation combination, chemical embolus, and irradiation alone groups. These findings demonstrated the synergistic effect of the combination of chemical embolus therapy and radiotherapy. In this study, however, no significant difference was found between the chemical embolus therapy alone and the combination therapy groups in the inhibitory effect on pulmonary tumor metastasis, suggesting the need to conduct combination therapy repeatedly in the clinical setting. (author)

  11. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

  12. Rare Case of Duodenal Metastasis From Pulmonary Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zain Memon DO

    2017-10-01

    Full Text Available Pulmonary squamous cell carcinoma is the second most common non–small cell malignancy of the lung. It commonly metastasizes to the adrenal glands, bone, liver, brain, and kidneys. Most occurrences of metastatic squamous cell carcinoma involving the gastrointestinal tract originate from primary lung tumors. Metastasis to the duodenum, however, is exceedingly rare, with very few cases of stomach or duodenal involvement described in the literature. We report the case of a patient with stage IV pulmonary squamous cell carcinoma metastasizing to the duodenum with an uncommon presentation to add to the paucity of literature available regarding this rare finding.

  13. Chronic obstructive pulmonary disease and low bone mass: A case-control study

    Directory of Open Access Journals (Sweden)

    Rakesh K Gupta

    2014-01-01

    Full Text Available Background and Objective: Low bone mass (osteopenia and osteoporosis is one of the effects associated with chronic obstructive pulmonary disease (COPD. There is very little data from Saudi Arabia on COPD and low bone mass. This retrospective study was done to assess the prevalence of osteoporosis and osteopenia in COPD patients attending King Fahd Hospital of the University (KFHU, Alkhobar. Patients and Methods: After obtaining the ethical approval from the research committee, all patients seen between at the King Fahd Hospital of the University between January 2010 and December 2012 were included. The inclusion criteria included a follow up of a minimum 2 years, and the Medical Records should have the details of forced expiratory volume in one second (FEV 1 , blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry (DEXA scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5 and osteoporosis of <-2.5 as per the WHO definition of osteopenia and osteoporosis. Results: Seventy-three patients were being followed in the clinics and 49 patients satisfied the inclusion criteria. The average age was 60.6 ± 10.47 years; males were 43 and females 6. Three (6.1% were normal and the remaining 46 (93.9% were with low bone mass. Thirty-two (65.3% were osteoporotic and 14 (28.57% were osteopenic. The average duration of COPD was 4.5 ± 6.2 years. Majority (n = 36, 73.4% of patients were in the Global Initiative for COPD (GOLD class II and III. FEV 1 was significantly lower in the patients with low bone mass 1.66 ± 0.60 versus 3.61 ± 0.58 (P < 0.001. Conclusions: Our study shows that over 90% of Saudi Arabian patients with COPD suffer from osteopenia and osteoporosis and unfortunately they remain under-diagnosed and undertreated.

  14. Three-axial strain controlled testing applied to bone specimens from the proximal tibial epiphysis

    DEFF Research Database (Denmark)

    Linde, F.; Pongsoipetch, B.; Frich, Lars Henrik

    1990-01-01

    Reproducibility of the determination of Young's modulus and energy absorption along the three axes of trabecular bone cubes was analysed by non-destructive compression to 0.5% strain using different testing protocols. These protocols included testing with and without pre-conditioning to a viscoel......Reproducibility of the determination of Young's modulus and energy absorption along the three axes of trabecular bone cubes was analysed by non-destructive compression to 0.5% strain using different testing protocols. These protocols included testing with and without pre...

  15. The ventralizing activity of Radar, a maternally expressed bone morphogenetic protein, reveals complex bone morphogenetic protein interactions controlling dorso-ventral patterning in zebrafish.

    Science.gov (United States)

    Goutel, C; Kishimoto, Y; Schulte-Merker, S; Rosa, F

    2000-12-01

    In Xenopus and zebrafish, BMP2, 4 and 7 have been implicated, after the onset of zygotic expression, in inducing and maintaining ventro-lateral cell fate during early development. We provide evidence here that a maternally expressed bone morphogenetic protein (BMP), Radar, may control early ventral specification in zebrafish. We show that Radar ventralizes zebrafish embryos and induces the early expression of bmp2b and bmp4. The analysis of Radar overexpression in both swirl/bmp2b mutants and embryos expressing truncated BMP receptors shows that Radar-induced ventralization is dependent on functional BMP2/4 pathways, and may initially rely on an Alk6-related signaling pathway. Finally, we show that while radar-injected swirl embryos still exhibit a strongly dorsalized phenotype, the overexpression of Radar into swirl/bmp2b mutant embryos restores ventral marker expression, including bmp4 expression. Our results suggest that a complex regulation of different BMP pathways controls dorso-ventral (DV) patterning from early cleavage stages until somitogenesis.

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

    International Nuclear Information System (INIS)

    Roth, Eira S; Fetzer, David T; Barron, Bruce J; Joseph, Usha A; Gayed, Isis W; Wan, David Q

    2009-01-01

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

  17. Fundamental differences in axial and appendicular bone density in stress fractured and uninjured Royal Marine recruits--a matched case-control study.

    Science.gov (United States)

    Davey, Trish; Lanham-New, Susan A; Shaw, Anneliese M; Cobley, Rosalyn; Allsopp, Adrian J; Hajjawi, Mark O R; Arnett, Timothy R; Taylor, Pat; Cooper, Cyrus; Fallowfield, Joanne L

    2015-04-01

    Stress fracture is a common overuse injury within military training, resulting in significant economic losses to the military worldwide. Studies to date have failed to fully identify the bone density and bone structural differences between stress fractured personnel and controls due to inadequate adjustment for key confounding factors; namely age, body size and physical fitness; and poor sample size. The aim of this study was to investigate bone differences between male Royal Marine recruits who suffered a stress fracture during the 32 weeks of training and uninjured control recruits, matched for age, body weight, height and aerobic fitness. A total of 1090 recruits were followed through training and 78 recruits suffered at least one stress fracture. Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN) and whole body (WB) using Dual X-ray Absorptiometry in 62 matched pairs; tibial bone parameters were measured using peripheral Quantitative Computer Tomography in 51 matched pairs. Serum C-terminal peptide concentration was measured as a marker of bone resorption at baseline, week-15 and week-32. ANCOVA was used to determine differences between stress fractured recruits and controls. BMD at the LS, WB and FN sites was consistently lower in the stress fracture group (Pstress fracture recruits and controls were evident in all slices of the tibia, with the most prominent differences seen at the 38% tibial slice. There was a negative correlation between the bone cross-sectional area and BMD at the 38% tibial slice. There was no difference in serum CTx concentration between stress fracture recruits and matched controls at any stage of training. These results show evidence of fundamental differences in bone mass and structure in stress fracture recruits, and provide useful data on bone risk factor profiles for stress fracture within a healthy military population. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  18. The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens

    Directory of Open Access Journals (Sweden)

    Branden A. Smeester

    2013-01-01

    Full Text Available Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3 beginning at postimplantation day 3 (PID 3. Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7, starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA’s potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

  19. Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Melina Bezerra Loureiro

    2018-04-01

    Full Text Available ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD of patients with type 1 Diabetes mellitus (T1DM. We also assessed the association between osteoprotegerin (OPG genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05. For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.

  20. Laser vs bur for bone cutting in impacted mandibular third molar surgery: A randomized controlled trial.

    Science.gov (United States)

    Passi, Deepak; Pal, Uma Shankar; Mohammad, Shadab; Singh, Rakesh Kumar; Mehrotra, Divya; Singh, Geeta; Kumar, Manoj; Chellappa, Arul A L; Gupta, Chandan

    2013-01-01

    The aim of this study was to assess the feasibility of Er: YAG laser in bone cutting for removal of impacted lower third molar teeth and compare its outcomes with that of surgical bur. The study comprised 40 subjects requiring removal of impacted mandibular third molar, randomly categorized into two equal groups of 20 each, who had their impacted third molar removed either using Er: YAG laser or surgical bur as per their group, using standard methodology of extraction of impacted teeth. Clinical parameters like pain, bleeding, time taken for bone cutting, postoperative swelling, trismus, wound healing and complications were compared for both groups. Clinical parameters like pain, bleeding and swelling were lower in laser group than bur group, although the difference was statistically not significant. However, postoperative swelling showed significant difference in the two groups. Laser group required almost double the time taken for bone cutting with bur. Trismus persisted for a longer period in laser group. Wound healing and complications were assessed clinically and there was no significant difference in both the groups. Based on the results of our study, the possibility of bone cutting using lasers is pursued, the osteotomy is easily performed and the technique is better suited to minimally invasive surgical procedures. The use of Er: YAG laser may be considered as an alternative tool to surgical bur, specially in anxious patients.

  1. Impact of the new international association for the study of lung cancer staging system in non-small cell lung cancer: With comparison to the union for international cancer control 6th tumor, node, metastasis edition

    International Nuclear Information System (INIS)

    Lee, Myung Jae; Lee, So Won; Shim, Sung Shine; Ryu, Yon Ju; Kim, Yoo Kyung

    2014-01-01

    To investigate the impact of the proposed International Association for the Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM) system on staging and outcome of non small cell lung cancer (NSCLC). With a total of 501 NSCLC patients with staging according to Union for International Cancer Control (UICC), 6th TNM (TNM-6) were reclassified according to the IASLC proposed TNM staging (TNM-7). The impact of TNM-7 in comparison with TNM-6 was evaluated at three levels: change in substage, staging, and outcome. The outcome measure was to compare the stage-specific overall survival of NSCLC between the two groups of patients. A total of 214 (42.7%) patients had changed TNM staging, and 101 (20.2%) patients had changed stage groupings in TNM-7 compared to TNM-6. Among 100 patients showing changed stage grouping, 72 (14.4%) showed upstage and 29 (5.8%) demonstrated downstage. The TNM-7 system resulted in better separation of survival curves among stage-specific NSCLC than TNM-6 system, especially in separation of stage IIA vs. IIB (p 0.023) and stage IIIB vs. IV (p < 0.001). TNM-7 for lung cancer appears to be superior in defining stage-specific survival groups than TNM-6, especially between stage IIA vs. stage IIB and stage IIIB vs. stage IV.

  2. Pericytes limit tumor cell metastasis

    DEFF Research Database (Denmark)

    Xian, Xiaojie; Håkansson, Joakim; Ståhlberg, Anders

    2006-01-01

    Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions...... the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role...... and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing...

  3. The clinical course and prognosis of patients with renal adenocarcinoma with solitary metastasis

    International Nuclear Information System (INIS)

    Kjaer, M.; Engelholm, S.A.

    1982-01-01

    The present investigation describes a series of 25 patients with solitary metastasis from a renal adenocarcinoma. Forty-eight percent of the patients had metastatic foci in bones, 24% in the lungs, and 28% in a variety of organs. Radiotherapy was the treatment for 64% of the patients, surgery for 36%. Disease control after treatment was obtained in 88% of the patients. The 5-year survival rate was 39%. Sixteen of 25 patients died after a mean survival time of 36 months; 9/25 patients are still living 28-126 months after treatment. Women survived significantly better than men. Patients with normal pre- and post-treatment erythrocyte sedimentation rate (ESR) survived significantly longer than patients with elevated ESR. A definite relationship between ESR and disease activity was demonstrated in 64% of the patients. It is concluded that solitary metastases in bones can be treated with radiotherapy; even if 64% of the patients die there is significant clinical remission to be obtained after aggressive treatment. Furthermore, ESR seems to be an important indicator of prognosis and disease activity

  4. Isotope bone scanning in operable mammary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Maylin, C [Centre Hospitalier Universitaire, 94 - Creteil (France); Vilcoq, J R; Schlienger, P; Calle, R [Institut du Radium, 75 - Paris (France)

    1977-01-01

    In the pre-treatment work-up in breast carcinoma cases, the bone scan findings could be of major interest. If the presence of occult metastases is discovered management may be modified accordingly. In a group involving 78 cases of breast carcinoma, classified as primary, operable, in three cases only scintigraphy revealed bone metastases before they produced clinical and radiological signs. In two of them there was agreement, in one disagreement over the findings. Moreover, in 5 cases a bone metastasis was revealed and immediately confirmed on a complete bone assessment.

  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. Metastasis of Lung Adenocarcinoma to the Gingiva: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    M. Rajini Kanth

    2015-05-01

    Full Text Available Metastatic tumors account for 1% of all oral malignancies. Metastasis to jaw bones is common, particularly in the mandible, rare in the oral soft tissues, and account for only 0.1% of oral malignancies. The majority of metastatic cases (70% reported in the literature have primary tumors located in the lung, breast, kidney, and colon. Metastasis is a biological complex process that involves detachment from the surrounding cells, regulation of cell motility, invasion, survival, proliferation, and evasion of the immune system. Clinical presentation of metastatic tumors is variable, which may create diagnostic dilemma or may lead to erroneous diagnosis. Metastatic tumors clinically mimic as dental infections. Metastasis to the oral soft tissue from lung cancer, especially gingiva is a rare condition. Metastasis to the gingiva can affect the oral function, speech, and nutrition. Most of the cases in the literature reported that lesion presented in oral soft tissues before the diagnosis of primary tumors. Here we report a case of 62-year-old male patient with metastasis from lung to the gingiva, where the metastasis was detected before primary tumor.

  7. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

    International Nuclear Information System (INIS)

    Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

    2014-01-01

    Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

  8. Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones.

    Science.gov (United States)

    Sugiyama, Toshihiro; Price, Joanna S; Lanyon, Lance E

    2010-02-01

    In order to validate whether bones' functional adaptation to mechanical loading is a local phenomenon, we randomly assigned 21 female C57BL/6 mice at 19 weeks of age to one of three equal numbered groups. All groups were treated with isoflurane anesthesia three times a week for 2 weeks (approximately 7 min/day). During each anaesthetic period, the right tibiae/fibulae in the DYNAMIC+STATIC group were subjected to a peak dynamic load of 11.5 N (40 cycles with 10-s intervals between cycles) superimposed upon a static "pre-load" of 2.0 N. This total load of 13.5 N engendered peak longitudinal strains of approximately 1400 microstrain on the medial surface of the tibia at a middle/proximal site. The right tibiae/fibulae in the STATIC group received the static "pre-load" alone while the NOLOAD group received no artificial loading. After 2 weeks, the animals were sacrificed and both tibiae, fibulae, femora, ulnae and radii analyzed by three-dimensional high-resolution (5 mum) micro-computed tomography (microCT). In the DYNAMIC+STATIC group, the proximal trabecular percent bone volume and cortical bone volume at the proximal and middle levels of the right tibiae as well as the cortical bone volume at the middle level of the right fibulae were markedly greater than the left. In contrast, the left bones in the DYNAMIC+STATIC group showed no differences compared to the left or right bones in the NOLOAD or STATIC group. These microCT data were confirmed by two-dimensional examination of fluorochrome labels in bone sections which showed the predominantly woven nature of the new bone formed in the loaded bones. We conclude that the adaptive response in both cortical and trabecular regions of bones subjected to short periods of dynamic loading, even when this response is sufficiently vigorous to stimulate woven bone formation, is confined to the loaded bones and does not involve changes in other bones that are adjacent, contra-lateral or remote to them. (c) 2009 Elsevier Inc

  9. Improving temporal bone dissection using self-directed virtual reality simulation: results of a randomized blinded control trial.

    Science.gov (United States)

    Zhao, Yi Chen; Kennedy, Gregor; Yukawa, Kumiko; Pyman, Brian; O'Leary, Stephen

    2011-03-01

    A significant benefit of virtual reality (VR) simulation is the ability to provide self-direct learning for trainees. This study aims to determine whether there are any differences in performance of cadaver temporal bone dissections between novices who received traditional teaching methods and those who received unsupervised self-directed learning in a VR temporal bone simulator. Randomized blinded control trial. Royal Victorian Eye and Ear Hospital. Twenty novice trainees. After receiving an hour lecture, participants were randomized into 2 groups to receive an additional 2 hours of training via traditional teaching methods or self-directed learning using a VR simulator with automated guidance. The simulation environment presented participants with structured training tasks, which were accompanied by real-time computer-generated feedback as well as real operative videos and photos. After the training, trainees were asked to perform a cortical mastoidectomy on a cadaveric temporal bone. The dissection was videotaped and assessed by 3 otologists blinded to participants' teaching group. The overall performance scores of the simulator-based training group were significantly higher than those of the traditional training group (67% vs 29%; P < .001), with an intraclass correlation coefficient of 0.93, indicating excellent interrater reliability. Using other assessments of performance, such as injury size, the VR simulator-based training group also performed better than the traditional group. This study indicates that self-directed learning on VR simulators can be used to improve performance on cadaver dissection in novice trainees compared with traditional teaching methods alone.

  10. Isolated Asymptomatic Metastasis in the Myocardium: A Rare Scenario in Case of Carcinoma Penis

    Directory of Open Access Journals (Sweden)

    Santosh Kumar

    2015-01-01

    Full Text Available Penile cancer is a common malignancy in developing countries. It commonly metastasizes to the lymph nodes, lung, liver, and bones. Myocardial metastasis is rare. A 40-year-old male patient presented with ulcerative growth over glans penis. Histologic evaluation of the biopsy sample diagnosed the lesion as squamous cell cancer. Assessment of the stage of the disease revealed cardiac metastasis. Patient received six cycles of chemotherapy. He partially responded, but later succumbed to cardiac failure due to pericardial and pleural effusion.

  11. Colonic Metastasis with Anemia Leading to a Diagnosis of Primary Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Vasa Jevremovic

    2016-01-01

    Full Text Available Metastasis occurs with 50% of lung carcinomas, most commonly to lymph nodes, adrenal glands, liver, bone, and brain. It is extremely rare for lung cancer to present with symptoms of a gastrointestinal metastasis and even more so pertaining to the colon. To the best of our knowledge, only 12 such cases have been reported in the literature. We describe a case of a 71-year-old female presenting with refractory iron deficiency anemia that was found to have a lesion in the transverse colon. Pathology revealed adenocarcinoma of the lung and a subsequent lung lesion was discovered in a retrograde fashion.

  12. Isolated splenic metastasis of colon cancer: a case report and literature review

    OpenAIRE

    Rosa, Nisalda; Martins, Sandra; Lamelas, Javier

    2012-01-01

    Colorectal cancer (CRC) is a leading cause of death in the elderly and about 20% of these patients present metastasis at diagnosis, most often in the liver. Other common metastatic sites include: lung, bone and brain. Isolated splenic metastases are rare, and they are usually a sign of widespread disease. The authors report a case of the rare occurrence of synchronous isolated splenic metastasis, diagnosed by computed tomography in the preoperative staging of a patient with CRC.O câncer color...

  13. Extraosseus enrichments in bone scintigraphy

    International Nuclear Information System (INIS)

    Jochens, R.; Schumacher, T.; Amthauer, H.; Wolter, M.; Stock, W.; Stroszczynski, C.; Moersler, J.P.; Eichstaedt, H.

    1996-01-01

    Extraosseus enrichments are common findings in bone scintigraphy. Main causes are artifacts by skin or cloth contamination, paravenous and subcutaneous injection. Physical examination, removal of cloths, skin cleaning or further images in differing projections lead to the correct diagnosis artefact or extraosseous enrichments. Further on, extraosseous enrichments are seen in physiological variants. In different diseases extraosseous enrichments are common, especially in urinary tract, liver and extremities. Further diagnostics, e.g. conventional radiologic procedures, sonography and CT scans, have to be performed. In individual cases side results in bone scintigraphy lead to formerly unknown diagnosis, further diagnostic procedure is influenced decisively. Own cases show for example a cerebral apoplectic insult, formerly unknown liver metastasis or metastasis in extraosseous Ewings's sarcoma. (orig.) [de

  14. Analysis of metastasis of melanoma-bearing hamsters in thermal neutron capture therapy

    International Nuclear Information System (INIS)

    Ueda, Masataka; Mishima, Yutaka; Ichihashi, Masamitsu

    1985-01-01

    Melanoma-bearing hamsters were divided into three groups: the MG I was treated with both 10 B 1 -para-boronophenylalanine.HCl ( 10 B 1 -BPA) and neutron capture therapy (NCT); the MG II was treated with NCT alone; and the control group (MG III). The most satisfactory effect on regression was seen in the MG I. When the opposite site to the transplanted tumor site was exposed to thermal neutrons, no enhanced effect on metastasis was seen. Tumor cells of MG I and MG II were transplanted subcutaneously 24 hr after NCT into normal hamsters (MG It and MG IIt), and their growth and metastasis abilities were examined. MG It cells possessed neither growth nor metastasis ability; while MG IIt cells showed normal growth and metastasis abilities. Lethal effects on tumor cells seemed to occur in the MG I at 24 hr after NCT, suggesting no effects of NCT on the metastasis ability of tumor cells. Metastasis was seen in 2 of 8 animals in the MG III; however, inhibitory effects on tumor cells were the same as those in the other groups MG I and MG II. When the cells were exposed to 100 rad and 300 rad of gamma rays to assess effects of gamma rays during NCT, neither tumor growth nor lung metastasis was affected. When the tumor was excised with 5 mm margin, relapse occurred in a high incidence. There was no difference in lung metastasis between NCT and gamma irradiation. (Namekawa, K.)

  15. Malignant transformation of a unicameral bone cyst in a cat.

    Science.gov (United States)

    Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

    2016-04-01

    A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis.

  16. Vitamin D Supplementation in Elderly Black Women Does Not Prevent Bone Loss, a Randomized Controlled Trial.

    Science.gov (United States)

    Aloia, John F; Fazzari, Melissa; Islam, Shahidul; Mikhail, Mageda; Katumuluwa, Subhashini; Dhaliwal, Ruban; Stolberg, Alexandra; Usera, Gianina; Ragolia, Louis

    2018-06-15

    Black Americans have lower levels of serum 25(OH)D but superior bone health compared to white Americans. There is controversy over whether they should be screened for vitamin D deficiency and have higher vitamin D requirements than recommended by the Institute of Medicine (IOM). The purpose of this trial was to determine whether Vitamin D supplementation in elderly black women prevents bone loss. 260 healthy black American women, 60 years of age and older were recruited to take part in a two arm, double-dummy 3 year RCT of vitamin D 3 vs. placebo. The study was conducted in an ambulatory clinical research center. Vitamin D 3 dose was adjusted to maintain serum 25(OH)D above 75 nmol/L. Bone mineral density (BMD) and serum were measured for [parathyroid hormone (PTH), C-terminal crosslink telopeptide (CTX) and bone specific alkaline phosphatase (BSAP) every 6 months. Baseline serum 25(OH)D 3 was 54.8 ± 16.8 nmol/L. There was no group xtime interaction effect for any BMD measurement. For all BMD measurements, except for total body and spine, there was a statistically significant negative effect of time (P D above 75 nmol/L is comparable to the rate of loss with serum 25(OH)D at the RDA of 50 nmol/L. Black Americans should have the same exposure to vitamin D as white Americans. The trial was registered at clinical trials.gov: NCT01153568. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Endocrine control of bone and calcium metabolism. Vol. 8A - Formal sessions and abstracts

    International Nuclear Information System (INIS)

    Cohn, D.V.; Fujita, Takuo; Potts, J.T. Jr.; Talmage, R.V.

    1984-01-01

    This book contains papers of a conference about hormonal regulation of calcium metabolism. The pathophysiology and treatment of disorders of mineral metabolism is described in several chapters. A separate chapter is devoted to bone composition, development and remodelling. The same for the physiology of skeletal tissue. The other chapters deal with the secretion, metabolism and action of parathormone, vitamin D, calcitonin and new recognized calcium factors. refs.; figs.; tabs

  18. Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

    Science.gov (United States)

    Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

    2010-11-01

    Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

  19. Utilization of fish bone as adsorbent of Fe3+ ion by controllable removal of its carbonaceous component

    Science.gov (United States)

    Nurhadi, M.; Kusumawardani, R.; Widiyowati, I. I.; Wirhanuddin; Nur, H.

    2018-05-01

    The performance of fish bone to adsorb Fe3+ ion in solution was studied. Powdered fish bone and carbonized fish bone were used as adsorbent. All absorbents were characterized by X-ray diffraction (XRD), IR spectroscopy, nitrogen adsorption, scanning electron microscopy (SEM) and TG analysis. Powdered fish bone and carbonized fish bone were effective as adsorbent for removing Fe3+ ion in solution. The metal adsorptions of Fe3+ ion were 94 and 98% for powdered fish bone and fish bone which carbonized at 400 and 500 °C.

  20. Disp1 regulates growth of mammalian long bones through the control of Ihh distribution.

    Science.gov (United States)

    Tsiairis, Charisios D; McMahon, Andrew