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.

[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.

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

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)

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

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.

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.)

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)

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.

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

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)

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)

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)

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...

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.

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

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

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.

Clinical outcome for patients of solitary bone only metastasis.

Science.gov (United States)

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.

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)

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)

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 ...

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.

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

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.

{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.

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.

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.

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.

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.)

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.

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

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

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.

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...

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)

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.

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)

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.

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.

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.

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

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.

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

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.

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)

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.

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.

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)

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).

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)

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.

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

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)

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

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)

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

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

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.

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).

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.

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.

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...

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...

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.)

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)

Recombinant human bone morphogenetic protein induces bone formation

International Nuclear Information System (INIS)

Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

1990-01-01

The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

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.

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

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...

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.

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)

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

Directory of Open Access Journals (Sweden)

Ali Murat Tatlı

2013-01-01

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

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)

[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.

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

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 ...

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.

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.)

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

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

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.

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.

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

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

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.

Proinflammatory Adhesion Molecules Facilitate Polychlorinated Biphenyl–Mediated Enhancement of Brain Metastasis Formation

OpenAIRE

Sipos, Eszter; Chen, Lei; András, Ibolya E.; Wrobel, Jagoda; Zhang, Bei; Pu, Hong; Park, Minseon; Eum, Sung Yong; Toborek, Michal

2012-01-01

Polychlorinated biphenyls (PCBs) are environmental toxicants that cause vascular inflammation and facilitate the development of brain metastases. The crucial event in metastasis formation is adhesion of blood-borne tumor cells to the vascular endothelium, followed by their transcapillary migration. The aim of the present study was to examine the mechanisms of PCB118-induced brain metastasis formation at the blood-brain barrier level with the focus on tumor cell adhesion to the brain endotheli...

Osteoclasts secrete non-bone derived signals that induce bone formation

DEFF Research Database (Denmark)

Karsdal, Morten A; Neutzsky-Wulff, Anita V; Dziegiel, Morten Hanefeld

2008-01-01

Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption......) from human osteoclasts cultured on either bone or plastic, and tested their effects on bone nodule formation by osteoblasts. Both types of CM were shown to dose-dependently induce bone nodule formation, whereas non-conditioned osteoclast culture medium had no effects. These data show that osteoclasts...

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

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

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

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.

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.

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)

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.

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.

Impact of bone graft harvesting techniques on bone formation and graft resorption

DEFF Research Database (Denmark)

Saulacic, Nikola; Bosshardt, Dieter D; Jensen, Simon S

2015-01-01

BACKGROUND: Harvesting techniques can affect cellular parameters of autogenous bone grafts in vitro. Whether these differences translate to in vivo bone formation, however, remains unknown. OBJECTIVE: The purpose of this study was to assess the impact of different harvesting techniques on bone fo......: Transplantation of autogenous bone particles harvested with four techniques in the present model resulted in moderate differences in terms of bone formation and graft resorption.......BACKGROUND: Harvesting techniques can affect cellular parameters of autogenous bone grafts in vitro. Whether these differences translate to in vivo bone formation, however, remains unknown. OBJECTIVE: The purpose of this study was to assess the impact of different harvesting techniques on bone...... formation and graft resorption in vivo. MATERIAL AND METHODS: Four harvesting techniques were used: (i) corticocancellous blocks particulated by a bone mill; (ii) bone scraper; (iii) piezosurgery; and (iv) bone slurry collected from a filter device upon drilling. The grafts were placed into bone defects...

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

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.)

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.

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

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.

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.

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

Heterotopic new bone formation causes resorption of the inductive bone matrix

International Nuclear Information System (INIS)

Nilsson, O.S.; Persson, P.E.; Ekelund, A.

1990-01-01

The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM

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.

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

The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts.

Science.gov (United States)

Peinado, Héctor; Lavotshkin, Simon; Lyden, David

2011-04-01

Metastasis is a multistep process that requires acquisition of malignant cell phenotypes which allow tumor cells to escape from the primary tumor site. Each of the steps during metastatic progression involves co-evolution of the tumor and its microenvironment. Although tumor cells are the driving force of metastasis, new findings suggest that the host cells within the tumor microenvironment play a key role in influencing metastatic behavior. Many of these contributing cells are derived from the bone marrow; in particular, recruited bone marrow progenitor cells generate the "pre-metastatic niche" to which the tumor cells metastasize. Analysis of the molecular mechanisms involved in pre-metastatic niche formation has revealed that secreted soluble factors are key players in bone marrow cell mobilization during metastasis. In addition, membrane vesicles derived from both tumor and host cells have recently been recognized as new candidates with important roles in the promotion of tumor growth and metastasis. This review describes old ideas and presents new insights into the role of tumor and bone marrow-derived microvesicles and exosomes in pre-metastatic niche formation and metastasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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.

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

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)

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

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)

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.

Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

DEFF Research Database (Denmark)

Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

2011-01-01

Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of f...

Observation of microscopic bone structure during bone formation. Application of micro-computed tomography for evaluation of bone quality

International Nuclear Information System (INIS)

Ueno, Takaaki; Yamamoto, Hiromitsu; Mizukawa, Nobuyoshi; Mishima, Katsuaki; Takagi, Shin; Sugahara, Toshio

1998-01-01

Bone formation in the autogenous periosteum of the tibia grafted to the floor of the mouth to bridge the mandible was studied by micro-CT to assess its efficacy in evaluating bone formation in rabbits. On soft radiographs, bone formation was observed from both ends of the periosteum on day 14. The bone increased in width and extended medially; contact was made in the center on day 28. The time course of the development of bone trabeculae was well demonstrated three-dimensionally on micro-CT. Indices of bone quality such as Tb-Th, Tb.N, and BV, which reflect the growth of trabeculae, increased gradually from days 14 to 21 and more rapidly from days 21 to 28, whereas Tb. S decreased gradually after grafting. The results suggest that micro-CT is useful in evaluating bone formation three-dimensionally. (author)

Bone formation in cranial, mandibular, tibial and iliac bone grafts in rats

DEFF Research Database (Denmark)

Solheim, E; Pinholt, E M; Talsnes, O

1995-01-01

Several studies have suggested that grafts from membranous derived bone (e.g., calvarial grafts) retain their volume better than those from endochondral derived bone (e.g., iliac bone grafts). Increased osteogenesis in grafts of the former type has been offered as the explanation. However, simple...... volume measurements of the recovered grafts do not differentiate between viable and dead bone. We studied fresh syngeneic full-thickness bone grafts from calvaria, mandibula, tibia diaphysis, and iliac bone implanted in the back muscles of young Lewis rats. Bone formation in grafts recovered 3 weeks...... that the anatomical area of harvest is important regarding new bone formation in syngeneic bone grafts. However, the results do not support the contention that better maintenance of volume of calvarial grafts compared with iliac bone grafts is due to enhanced osteogenesis in the former....

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

Heterotopic bone formation following total shoulder arthroplasty

DEFF Research Database (Denmark)

Kjaersgaard-Andersen, P.; Frich, Lars Henrik; Sjøbjerg, J.O.

1989-01-01

The incidence and location of heterotopic bone formation following total shoulder arthroplasty were evaluated in 58 Neer Mark-II total shoulder replacements. One year after surgery, 45% had developed some ectopic ossification. In six shoulders (10%) the ossifications roentgenographically bridged...... the glenohumeral and/or the glenoacromial space. There was no correlation between shoulder pain and the development of ossification. Shoulders with grade III heterotopic bone formation had a limited range of active elevation compared with shoulders without or with only a milder lesion. Men and patients...... with osteoarthritis of the shoulder joint were significantly disposed to the development of heterotopic bone. Heterotopic bone formation following total shoulder arthroplasty is frequent, but disabling heterotopic ossifications seem to be rare....

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...

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

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.

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

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.

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.

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)

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.

Histological study on the new bone formation of the implanted bone allograft in sheep

International Nuclear Information System (INIS)

Li Youchen; Sun Guiying; Shi Zhancheng

1999-01-01

The purpose of this study is to compare the formation of new bone in the implanted frozen irradiated bone allograft with the fresh bone autograft. The work on animal model included resection and implantation of sheep's tibial diaphysis and intramedullary nail fixation, with total number 20. Tibias were harvested at 6, 12, and 24 months after operation. Sheep were fed with tetracycline I week before bone harvesting. Bones were examined with usual and fluorescence microscopes. The results showed that the progress of graft incorporation in allografts were generally similar to that of autografts. Capillaries penetration and callus formation extended from the host end to surround the host-graft junction in 6 months. Incorporation of new bone was nearly completed in 12 months; then the speed of new bone formation was decreased, and the implanted bone graft was almost completely substituted with non-nal bone structure in 24 months

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.

Clay-Enriched Silk Biomaterials for Bone Formation

Science.gov (United States)

Mieszawska, Aneta J.; Llamas, Jabier Gallego; Vaiana, Christopher A.; Kadakia, Madhavi P.; Naik, Rajesh R.; Kaplan, David L.

2011-01-01

The formation of silk protein/clay composite biomaterials for bone tissue formation is described. Silk fibroin serves as an organic scaffolding material offering mechanical stability suitable for bone specific uses. Clay montmorillonite (Cloisite ® Na+) and sodium silicate are sources of osteoinductive silica-rich inorganic species, analogous to bioactive bioglass-like bone repair biomaterial systems. Different clay particle-silk composite biomaterial films were compared to silk films doped with sodium silicate as controls for support of human bone marrow derived mesenchymal stem cells (hMSCs) in osteogenic culture. The cells adhered and proliferated on the silk/clay composites over two weeks. Quantitative real-time RT-PCR analysis revealed increased transcript levels for alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col I) osteogenic markers in the cells cultured on the silk/clay films in comparison to the controls. Early evidence for bone formation based on collagen deposition at the cell-biomaterial interface was also found, with more collagen observed for the silk films with higher contents of clay particles. The data suggest that the silk/clay composite systems may be useful for further study toward bone regenerative needs. PMID:21549864

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.

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.

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

Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair

Science.gov (United States)

Hinton, R.J.; Jing, Y.; Jing, J.; Feng, J.Q.

2016-01-01

The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived). PMID:27664203

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

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...

Does simvastatin stimulate bone formation in vivo?

Directory of Open Access Journals (Sweden)

Chorev Michael

2003-04-01

Full Text Available Abstract Background Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS to the known anabolic effects of PTH in an established model of ovariectomized (OVX Swiss-Webster mice. Methods Mice were ovariectomized at 12 weeks of age (T0, remained untreated for 5 weeks to allow development of osteopenia (T5, followed by treatment for 8 weeks (T13. Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT. Liquid chromatography/mass spectrometry (LC/MS was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH in the mouse serum. Results Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day compared to the OVX-vehicle treated group (p in vivo study. Conclusions While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo.

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.)

Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation

Energy Technology Data Exchange (ETDEWEB)

Severson, A.R. (Minnesota Univ., Duluth, MN (United States). Dept. of Anatomy and Cell Biology); Haut, C.F.; Firling, C.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biology); Huntley, T.E. (Minnesota Univ., Duluth, MN (United States). Dept. of Biochemistry and Molecular Biology)

1992-12-01

The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification. Thus, aluminum administration to rats appears to alter the differentiation and calcification of developing cartilage and bone in the DBM-induced bone formation model and suggests that aluminum by some mechanism alters the matrix calcification in growing bones. (orig.).

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

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)

Leptin regulates bone formation via the sympathetic nervous system

Science.gov (United States)

Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

2002-01-01

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

Functional Diversity of Fibroblast Growth Factors in Bone Formation

Directory of Open Access Journals (Sweden)

Yuichiro Takei

2015-01-01

Full Text Available The functional significance of fibroblast growth factor (FGF signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs. Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.

Aggressive Ewing's sarcoma appearing as a cold lesion on bone scan

International Nuclear Information System (INIS)

Chatti, K.; Guezguez, M.; Maha Ben Fredj, M.; Sfar, R.; Essabbah, H.; Mtaoumi, M.; Chatti, K.

2009-01-01

Ewing's sarcoma classically presents as a hot spot on bone scan as a result of increased vascularity of the tumor and new bone formation. Purpose We report and analyze an uncommon pattern of a 'cold' lesion in Ewing's sarcoma on bone scan and its pathophysiologic significance. Case report A 15-year-old boy complaining of thigh pain. CT scan evoked Ewing's sarcoma or osteitis. MRI evoked chronic osteitis. Scintigraphy showed a fairly intense and heterogeneous uptake on the femoral lesion and no abnormal uptake elsewhere. Biopsy showed none pathologic pattern. Three months later, a second biopsy concluded to Ewing's sarcoma. Bone scan showed a larger lesion with peripheral intense uptake centered by enlarged 'cold' area in the left femoral diaphysis and no evident bone metastasis. The patient underwent chemotherapy and surgery. Three months later, bone scan showed extensive skeletal metastasis. Conclusion Ewing's sarcoma appears usually as an intense lesion on bone scan. Nevertheless, decreased radiopharmaceutical uptake or 'cold' lesion may be seen in aggressive Ewing's sarcoma with lytic tumor, growth of which is very rapid and bony reaction is minimal. (authors)

Bone turnover markers and bone scintigraphy in the evaluation of skeletal metastases

International Nuclear Information System (INIS)

Chrapko, B.; Nocun, A.; Golebiewska, R.; Jankowska, H.; Zaorska-Rajca, J.

2005-01-01

The aim of this study was evaluation of the clinical usefulness of bone scintigraphy and of serum bone turnover marker levels in the assessment of skeletal metastases. We investigated 60 patients with suspected skeletal metastases. Serum level of bone-formation marker: amino- terminal propeptide of type I procollagen (PINP) and a bone-degradation marker: carboxy-terminal telopeptide of type I collagen (ICTP) were assessed with radioimmunoassays. Bone MDP- 99m- Tc scans were performed as well. Hot spots were showed in 72% of patients. According to bone scintigraphy the patients were divided in to 3 groups: Group I - without hot spots (n = 16; 26%), Group II up to 10 hot spots (n = 25; 42%) and Group III more that 10 hot spots (n = 19; 32%). Mean serum level of ICTP was significantly higher in Group II than in Group I (p < 0.05), as well as in Group III compared to Group II (p < 0.001) and in Group III compared to Group I (p < 0.001). There is only one significant relationship in PINP levels - between Groups II and III. The levels of bone pathological degradation (ICTP) and bone formation reflect the metastatic disease extent in bone. Serum ICTP level is more useful in staging metastasis. Significantly higher PINP reflects only a much disseminated process. (author)

High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

DEFF Research Database (Denmark)

Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

2015-01-01

transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

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.

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.

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.

Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation

NARCIS (Netherlands)

Croes, M.; Kruyt, M. C.; Groen, W. M.; Van Dorenmalen, K. M.A.; Dhert, W. J.A.; Öner, F. C.; Alblas, J.

2018-01-01

Interleukin 17 (IL-17) stimulates the osteogenic differentiation of progenitor cells in vitro through a synergy with bone morphogenetic protein (BMP)-2. This study investigates whether the diverse responses mediated by IL-17 in vivo also lead to enhanced BMP-2-induced bone formation. Since IL-17 is

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.)

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.

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)

Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

Science.gov (United States)

Stein, Koen; Prondvai, Edina

2014-02-01

We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

Science.gov (United States)

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

Vibration acceleration promotes bone formation in rodent models.

Directory of Open Access Journals (Sweden)

Ryohei Uchida

Full Text Available All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF mouse model and a rib fracture healing (RFH rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model or nine days (RFH model. All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT. In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model had significantly greater wet weight and were significantly larger (macroscopically and radiographically than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group, but

Glucocorticoids and inhibition of bone formation induced by skeletal unloading

International Nuclear Information System (INIS)

Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.

1988-01-01

Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

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.)

Rescuing loading induced bone formation at senescence.

Directory of Open Access Journals (Sweden)

Sundar Srinivasan

2010-09-01

Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

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.

Formation of blood clot on biomaterial implants influences bone healing.

Science.gov (United States)

Shiu, Hoi Ting; Goss, Ben; Lutton, Cameron; Crawford, Ross; Xiao, Yin

2014-12-01

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.

Science.gov (United States)

Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio

2011-01-01

Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.

Local induction of inflammation affects bone formation

NARCIS (Netherlands)

Croes, M; Kruyt, M C; Loozen, L; Kragten, A H; Yuan, H; Dhert, W J; Öner, F C; Alblas, J

2017-01-01

To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of

Spontaneous lung metastasis formation of human Merkel cell carcinoma cell lines transplanted into scid mice.

Science.gov (United States)

Knips, Jill; Czech-Sioli, Manja; Spohn, Michael; Heiland, Max; Moll, Ingrid; Grundhoff, Adam; Schumacher, Udo; Fischer, Nicole

2017-07-01

Merkel cell carcinoma (MCC) is an aggressive skin cancer entity that frequently leads to rapid death due to its high propensity to metastasize. The etiology of most MCC cases is linked to Merkel cell polyomavirus (MCPyV), a virus which is monoclonally integrated in up to 95% of tumors. While there are presently no animal models to study the role of authentic MCPyV infection on transformation, tumorigenesis or metastasis formation, xenograft mouse models employing engrafted MCC-derived cell lines (MCCL) represent a promising approach to study certain aspects of MCC pathogenesis. Here, the two MCPyV-positive MCC cell lines WaGa and MKL-1 were subcutaneously engrafted in scid mice. Engraftment of both MCC cell lines resulted in the appearance of circulating tumor cells and metastasis formation, with WaGa-engrafted mice showing a significantly shorter survival time as well as increased numbers of spontaneous lung metastases compared to MKL-1 mice. Interestingly, explanted tumors compared to parental cell lines exhibit an upregulation of MCPyV sT-Antigen expression in all tumors, with WaGa tumors showing significantly higher sT-Antigen expression than MKL-1 tumors. RNA-Seq analysis of explanted tumors and parental cell lines furthermore revealed that in the more aggressive WaGa tumors, genes involved in inflammatory response, growth factor activity and Wnt signalling pathway are significantly upregulated, suggesting that sT-Antigen is the driver of the observed differences in metastasis formation. © 2017 UICC.

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

Radiostrontium clearance and bone formation in response to simulated internal screw fixation

International Nuclear Information System (INIS)

Daum, W.J.; Simmons, D.J.; Fenster, R.; Shively, R.A.

1987-01-01

Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling

Influence of demineralized bone matrix's embryonic origin on bone formation: an experimental study in rats.

Science.gov (United States)

Stavropoulos, Andreas; Kostopoulos, Lambros; Mardas, Nicolaos; Karring, Thorkild

2003-01-01

There are results suggesting that differences regarding bone-inducing potential, in terms of amount and/or rate of bone formation, exist between demineralized bone matrices (DBMs) of different embryonic origins. The aim of the present study was to examine whether the embryonic origin of DBM affects bone formation when used as an adjunct to guided tissue regeneration (GTR). Endomembranous (EM) and endochondral (ECH) DBMs were produced from calvarial and long bones of rats, respectively. Prior to the study the osteoinductive properties of the DBMs were confirmed in six rats following intramuscular implantation. Following surgical exposure of the mandibular ramus, a rigid hemispheric Teflon capsule loosely packed with a standardized quantity of DBM was placed with its open part facing the lateral surface of the ramus in both sides of the jaw in 30 rats. In one side of the jaw, chosen at random, the capsule was filled with EM-DBM, whereas in the other side ECH-DBM was used. Groups of 10 animals were sacrificed after healing periods of 1, 2, and 4 months, and undecalcified sections of the capsules were produced and subjected to histologic analysis and computer-assisted planimetric measurements. During the experiment increasing amounts of newly formed bone were observed inside the capsules in both sides of the animals' jaws. Limited bone formation was observed in the 1- and 2-month specimens, but after 4 months of healing, the newly formed bone in the ECH-DBM grafted sides occupied 59.1% (range 45.6-74.7%) of the area created by the capsule versus 46.9% (range 23.0-64.0%) in the EM-DBM grafted sides (p =.01). It is concluded that the embryonic origin of DBM influences bone formation by GTR and that ECH-DBM is superior to EM-DBM.

Coupling of Bone Resorption and Formation in Real Time

DEFF Research Database (Denmark)

Lassen, Nicolai Ernlund; Andersen, Thomas Levin; Pløen, Gro Grunnet

2017-01-01

measurements show that the latter contribute the most to overall resorption. Of note, the density of osteoprogenitors continuously grew along the "reversal/resorption" surface, reaching at least 39 cells/mm on initiation of bone formation. This value was independent of the length of the reversal......It is well known that bone remodeling starts with a resorption event and ends with bone formation. However, what happens in between and how resorption and formation are coupled remains mostly unknown. Remodeling is achieved by so-called basic multicellular units (BMUs), which are local teams...... of osteoclasts, osteoblasts, and reversal cells recently proven identical with osteoprogenitors. Their organization within a BMU cannot be appropriately analyzed in common histology. The originality of the present study is to capture the events ranging from initiation of resorption to onset of formation...

Chinese red yeast rice (Monascus purpureus-fermented rice promotes bone formation

Directory of Open Access Journals (Sweden)

Rabie Bakr

2008-03-01

Full Text Available Abstract Background Statin can induce the gene expression of bone morphogenetic protein-2. Red yeast rice (RYR, Hongqu, i.e. rice fermented with Monascus purpureus, contains a natural form of statin. This study demonstrates the effects of RYR extract on bone formation. Methods Bone defects were created in the parietal bones of two New Zealand white rabbits. In the test animal, two defects were grafted with collagen matrix mixed with RYR extract. In the control animal, two defects were grafted with collagen matrix alone. UMR 106 cell line was used to test RYR extract in vitro. In the control group, cells were cultured for three durations (24 hours, 48 hours and 72 hours without any intervention. In the RYR group, cells were cultured for the same durations with various concentrations of RYR extract (0.001 g/ml, 0.005 g/ml and 0.01 g/ml. Bicinchoninic acid (BCA assay, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and alkaline phosphatase (ALP assay were performed to measure total protein, mitochondrial activity and bone cell formation respectively. Results The test animal showed more formation of new bone in the defects than the control animal. RYR significantly increased the optical density in the MTT assay and ALP activity in vitro. Conclusion RYR extract stimulated new bone formation in bone defects in vivo and increased bone cell formation in vitro.

Low-intensity pulsed ultrasound enhances bone formation around miniscrew implants.

Science.gov (United States)

Ganzorig, Khaliunaa; Kuroda, Shingo; Maeda, Yuichi; Mansjur, Karima; Sato, Minami; Nagata, Kumiko; Tanaka, Eiji

2015-06-01

Miniscrew implants (MSIs) are currently used to provide absolute anchorage in orthodontics; however, their initial stability is an issue of concern. Application of low-intensity pulsed ultrasound (LIPUS) can promote bone healing. Therefore, LIPUS application may stimulate bone formation around MSIs and enhance their initial stability. To investigate the effect of LIPUS exposure on bone formation after implantation of titanium (Ti) and stainless steel (SS) MSIs. MSIs made of Ti-6Al-4V and 316L SS were placed on rat tibiae and treated with LIPUS. The bone morphology around MSIs was evaluated by scanning electron microscopy and three-dimensional micro-computed tomography. MC3T3-E1 cells cultured on Ti and SS discs were treated with LIPUS, and the temporary expression of alkaline phosphatase (ALP) was examined. Bone-implant contact increased gradually from day 3 to day 14 after MSI insertion. LIPUS application increased the cortical bone density, cortical bone thickness, and cortical bone rate after implantation of Ti and SS MSIs (P<0.05). LIPUS exposure induced ALP upregulation in MC3T3-E1 cells at day 3 (P<0.05). LIPUS enhanced bone formation around Ti and SS MSIs, enhancing the initial stability of MSIs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fate of bone marrow stromal cells in a syngenic model of bone formation.

Science.gov (United States)

Boukhechba, Florian; Balaguer, Thierry; Bouvet-Gerbettaz, Sébastien; Michiels, Jean-François; Bouler, Jean-Michel; Carle, Georges F; Scimeca, Jean-Claude; Rochet, Nathalie

2011-09-01

Bone marrow stromal cells (BMSCs) have been demonstrated to induce bone formation when associated to osteoconductive biomaterials and implanted in vivo. Nevertheless, their role in bone reconstruction is not fully understood and rare studies have been conducted to follow their destiny after implantation in syngenic models. The aim of the present work was to use sensitive and quantitative methods to track donor and recipient cells after implantation of BMSCs in a syngenic model of ectopic bone formation. Using polymerase chain reaction (PCR) amplification of the Sex determining Region Y (Sry) gene and in situ hybridization of the Y chromosome in parallel to histological analysis, we have quantified within the implants the survival of the donor cells and the colonization by the recipient cells. The putative migration of the BMSCs in peripheral organs was also analyzed. We show here that grafted cells do not survive more than 3 weeks after implantation and might migrate in peripheral lymphoid organs. These cells are responsible for the attraction of host cells within the implants, leading to the centripetal colonization of the biomaterial by new bone.

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

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.

Nonlinear pattern formation in bone growth and architecture

Directory of Open Access Journals (Sweden)

Phil eSalmon

2015-01-01

Full Text Available The 3D morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatio-temporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here – chaotic nonlinear pattern formation (NPF – which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of group intelligence exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called particle swarm optimization (PSO. This theoretical model could be applicable to the behavior of osteoblasts osteoclasts and osteocytes, seeing them operating socially in response simultaneously to both global and local signals (endocrine, cytokine, mechanical resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in-silico simulation of bone modeling.What insights has NPF provided to bone biology? One example concerns the genetic disorder Juvenile Pagets Disease (JPD or Idiopathic Hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here coupling or feedback between osteoblasts and osteoclasts is the critical element.This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent consequence of the

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

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

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...

Hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma in a dog

International Nuclear Information System (INIS)

Rahal, S.C.; Mamprim, M.J.; Sequeira, J.L.; Franco, A.P.R.

2003-01-01

A 1.8-year-old female German Shepherd dog was presented with lameness, and painful non-edematous swelling of the right front limb. Swelling surrounding soft tissue and periosteal bone formation of the radius, ulna, metacarpals, without evidence of articular involvement were observed in the right front limb by radiographic examinations. Also, pulmonary tumor was observed in radiographic examination. Five months ago, the dog had developed osteosarcoma of the left distal ulna, and the treatment was cisplatin chemotherapy and limb amputation. The final diagnosis was hypertrophic osteopathy associated with pulmonary metastasis of osteosarcoma [pt

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

Science.gov (United States)

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

International Nuclear Information System (INIS)

Hirata, Eri; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro; Ménard-Moyon, Cécilia; Venturelli, Enrica; Bianco, Alberto

2013-01-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF–CNT) showed the same effect as FGF alone. In addition, FGF–CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF–CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF–CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications. (paper)

Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

Science.gov (United States)

Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

2013-11-01

Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

International Nuclear Information System (INIS)

Otsuru, Satoru; Tamai, Katsuto; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

2007-01-01

Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood

Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells.

Science.gov (United States)

Powan, Phattrakorn; Luanpitpong, Sudjit; He, Xiaoqing; Rojanasakul, Yon; Chanvorachote, Pithi

2017-11-01

The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers. Copyright © 2017 the American Physiological Society.

Spaceflight-induced vertebral bone loss in ovariectomized rats is associated with increased bone marrow adiposity and no change in bone formation

Science.gov (United States)

Keune, Jessica A; Philbrick, Kenneth A; Branscum, Adam J; Iwaniec, Urszula T; Turner, Russell T

2016-01-01

There is often a reciprocal relationship between bone marrow adipocytes and osteoblasts, suggesting that marrow adipose tissue (MAT) antagonizes osteoblast differentiation. MAT is increased in rodents during spaceflight but a causal relationship between MAT and bone loss remains unclear. In the present study, we evaluated the effects of a 14-day spaceflight on bone mass, bone resorption, bone formation, and MAT in lumbar vertebrae of ovariectomized (OVX) rats. Twelve-week-old OVX Fischer 344 rats were randomly assigned to a ground control or flight group. Following flight, histological sections of the second lumbar vertebrae (n=11/group) were stained using a technique that allowed simultaneous quantification of cells and preflight fluorochrome label. Compared with ground controls, rats flown in space had 32% lower cancellous bone area and 306% higher MAT. The increased adiposity was due to an increase in adipocyte number (224%) and size (26%). Mineral apposition rate and osteoblast turnover were unchanged during spaceflight. In contrast, resorption of a preflight fluorochrome and osteoclast-lined bone perimeter were increased (16% and 229%, respectively). The present findings indicate that cancellous bone loss in rat lumbar vertebrae during spaceflight is accompanied by increased bone resorption and MAT but no change in bone formation. These findings do not support the hypothesis that increased MAT during spaceflight reduces osteoblast activity or lifespan. However, in the context of ovarian hormone deficiency, bone formation during spaceflight was insufficient to balance increased resorption, indicating defective coupling. The results are therefore consistent with the hypothesis that during spaceflight mesenchymal stem cells are diverted to adipocytes at the expense of forming osteoblasts. PMID:28725730

[Endogenous pyrogen formation by bone marrow cells].

Science.gov (United States)

Efremov, O M; Sorokin, A V; El'kina, O A

1978-01-01

The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

Science.gov (United States)

Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

2018-01-01

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our

[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.

Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

Science.gov (United States)

Li, Feng; Wang, Xujun; Niyibizi, Christopher

2010-01-01

Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

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...

Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

Directory of Open Access Journals (Sweden)

Yi-Hsiung Lin

2017-11-01

Full Text Available The natural pure compound obtusilactone A (OA was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs. OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

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

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

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

Science.gov (United States)

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

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.

Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by 99mTc-MDP bone scintigraphy

International Nuclear Information System (INIS)

Yang Shunfang; Dong Qianggang; Yao Ming; Shi Meiping; Ye Jianding; Zhao Langxiang; Su Jianzhong; Gu Weiyong; Xie Wenhui; Wang Kankan; Du Yanzhi; Li Yao; Huang Yan

2009-01-01

Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with 99m Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with 99m Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as an

Trauma-induced heterotopic bone formation and the role of the immune system: A review.

Science.gov (United States)

Kraft, Casey T; Agarwal, Shailesh; Ranganathan, Kavitha; Wong, Victor W; Loder, Shawn; Li, John; Delano, Matthew J; Levi, Benjamin

2016-01-01

Extremity trauma, spinal cord injuries, head injuries, and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities, and joint contractures. The immune system has been increasingly implicated in this debilitating condition. This review summarizes the various roles immune cells and inflammation play in the formation of ectopic bone and highlights potential areas of future investigation and treatment. Cell types in both the innate and adaptive immune system such as neutrophils, macrophages, mast cells, B cells, and T cells have all been implicated as having a role in ectopic bone formation through various mechanisms. Many of these cell types are promising areas of therapeutic investigation for potential treatment. The immune system has also been known to also influence osteoclastogenesis, which is heavily involved in ectopic bone formation. Chronic inflammation is also known to have an inhibitory role in the formation of ectopic bone, whereas acute inflammation is necessary for ectopic bone formation.

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 ...

Callus formation in bone fractures combined with brain injury in rat

Directory of Open Access Journals (Sweden)

Yu-Ping Chen

2017-01-01

Full Text Available Objective: The objective of this study was to determine the speed of bony union and the serum levels of biomarkers in the setting of bone fractures combined with brain injury. Materials and Methods: In this study, Sprague–Dawley rats were randomized into four groups: sham, brain injury, bone fracture, and bone fracture plus brain injury groups. The serum levels of biochemical markers, namely, nerve growth factor (NGF, Wnt-3a, Dickkopf-related protein-1, receptor-activator of NF-κB ligand, and adrenocorticotropic hormone (ACTH, were measured on the days 1, 3, 7, and 14 following injury. Bony union was evaluated using radiographs every week for 6 weeks. Results: Compared with the brain injury group and bone fracture group, the radiographs of the bone fracture plus brain injury group revealed enhanced callus formations in week 2. From week 3, the callus formation did not differ significantly among the groups. The serum levels of the biomarkers varied at different time points. The serum levels of NGF on days 1 and 3, Wnt-3a on days 3 and 14, and ACTH on days 1, 3, and 7 were significantly higher in the bone fracture plus brain injury group than in the bone fracture group. Conclusions: Brain injury increases callus formation in simultaneous bone fracture. Considering the time point, early NGF, Wnt-3a, and ACTH elevation might be associated with early callus formation enhancement. The results indicate that these brain injury-induced biomarkers might play crucial role in accelerating bone healing.

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

Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

Science.gov (United States)

Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

2016-01-01

Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0 ± 2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2 ± 9.1%, control: 52.4 ± 8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7 ± 4 N, albumin 46.1 ± 11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc.

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.

Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone.

Science.gov (United States)

Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

2013-06-01

Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.

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)

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

Science.gov (United States)

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

Science.gov (United States)

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

Non-linear pattern formation in bone growth and architecture.

Science.gov (United States)

Salmon, Phil

2014-01-01

The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here - chaotic non-linear pattern formation (NPF) - which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of "group intelligence" exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called "particle swarm optimization" (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating "socially" in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or "feedback" between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent

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.

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.

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 ...

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.

Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

Science.gov (United States)

Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

2010-01-01

Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.

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.

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.

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

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)

Marginal zinc deficiency in pregnant rats impairs bone matrix formation and bone mineralization in their neonates.

Science.gov (United States)

Nagata, Masashi; Kayanoma, Megumu; Takahashi, Takeshi; Kaneko, Tetsuo; Hara, Hiroshi

2011-08-01

Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups and fed AIN-93G-based experimental diets containing 35 mg Zn/kg (Zn adequately supplied, N) or 7 mg Zn/kg (low level of Zn, L) from 14-day preconception to 20 days of gestation, that is, 1 day before normal delivery. Neonates were delivered by cesarean section. Litter size and neonate weight were not different between the two groups. However, in the L-diet-fed dam group, bone matrix formation in isolated neonatal calvaria culture was clearly impaired and was not recovered by the addition of Zn into the culture media. Additionally, serum concentration of osteocalcin, as a bone formation parameter, was lower in neonates from the L-diet-fed dam group. Impaired bone mineralization was observed with a significantly lower content of phosphorus in neonate femurs from L-diet-fed dams compared with those from N-diet-fed dams. Moreover, Zn content in the femur and calvaria of neonates from the L-diet group was lower than that of the N-diet-fed group. In the marginally Zn-deficient dams, femoral Zn content, serum concentrations of Zn, and osteocalcin were reduced when compared with control dams. We conclude that maternal Zn deficiency causes impairment of bone matrix formation and bone mineralization in neonates, implying the importance of Zn intake during pregnancy for proper bone development of offspring.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

International Nuclear Information System (INIS)

Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

2013-01-01

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH 1–34 or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and

Radiologic study of the experimentally produced bone destruction and bone formation

International Nuclear Information System (INIS)

Chei, Soon Chul; Ahn, Hyung Kyu

1988-01-01

Bone destruction was induced experimentally by the insertion of a bit of the arsenic compound into the pulp chambers of the right premolars and the artificial bone defects were produced in the periapical regions of the left premolars in 7 dogs. The serial standardized periapical radiographs using aluminum stepwedge attached to the XCP instruments and resin bite blocks were taken following insertion of arsenic compound and at 2, 4, 7, 10, 14, 17, 21, 24 and 28 days in case of bone destruction and following bone injury and weekly thereafter for a total of 14 weeks in case of bone formation . The errors of the method were determined with error estimators described by the Duinkerke. All radiographs were evaluated by the visual examination after joint evaluation by three dental radiologists and analysed with densitometer. The following results were obtained; 1. Analysis of the bone destruction process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.04 mm, S.D. for the over-all error; 0.06 mm, S.D. for the positioning error; 0.05 mm) 2) The radiographic changes were observed after 7 days in 6 cases, 4 days in 1 case and 10 days in 1 case by the visual examination. 3) Aluminum equivalent values were diminished after 2 days and the diminution of 0.58 ± 0.19 mm was demanded to be detected by the visual examination. 2. Analysis of the bone formation process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.03 mm, S.D. for the over-all error; 0.04 mm, S.D. for the positioning error; 0.04 mm) 2) The radiographic changes were observed after 2 weeks in 5 cases and 3 weeks in 2 cases by the visual examination. 3) Aluminum equivalent values were increased after 1 week and the increase of 0.45 ± 0.15 mm was demanded to be detected by the visual examination. 4) Aluminum equivalent values were increased continuously for 7 or 9 weeks but there was only extremely small

Bone scans in nasopharyngeal carcinoma: local experience

International Nuclear Information System (INIS)

Tiong, S.

2004-01-01

Introduction: Nasopharyngeal carcinoma (NPC) tops the list of malignancy in Malaysia and ranks first in male malignancy in the state of Sarawak. The majority of the NPC patients presented in the advanced stages and often with distal metastasis usually to the bones. In our local hospital is the new practice of bone scan using Tc99 started last year. Over a period of 9 months from July 2003 to March 2004, 41 NPC patients had the bone scans and our experience in these are reviewed and presented. Method: The NPC patients are selected consecutively including both new and treated patients. The scanner used is Siemen E.cam plus and Technecium (Tc99) the radio-active isotope used. The scan images are read and reported by qualified and trained Radiologists. The bone scans are requested from the ENT Specialist of the ENT department of the Hospital. The bone scan reports are checked by the ENT Specialists and the decisions made as to clinical correlation and further definitive imaging studies. Results: 41 NPC patients were included in the studies, 29 newly diagnosed and bone-canned before treatment started and 12 treated of which 3 being diagnosed having recurrent NPC. Of the 29 newly diagnosed patients, one was found true positive bone scan having increased radio-tracer uptake and confirmed Xray imagings. 3 of the treated patients had true positive bone scan with increased radio-tracer uptake and confirmed Xray imagings. Hence a total of 4 out of the 41 patients (9.8%) had bone metastasis on positive bone scans. Of the 29 newly diagnosed patients, 14 were found false positive bone scan having increased radio-tracer uptake but no confirmed X ray imagings. 4 of the treated patients had false positive bone scan with increased radio-tracer uptake but no confirmed X ray imagings. Hence a total of 18 out of the 41 patients (44%) had no bone metastasis on positive bone scans. There were 6 patients with symptoms referable to the bones' distal to the head and 2 had true positive bone

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

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%

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%.

A cellular automata model of bone formation.

Science.gov (United States)

Van Scoy, Gabrielle K; George, Estee L; Opoku Asantewaa, Flora; Kerns, Lucy; Saunders, Marnie M; Prieto-Langarica, Alicia

2017-04-01

Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone formation induced in an infant by systemic prostaglandin-E2 administration

DEFF Research Database (Denmark)

Jørgensen, H R; Svanholm, H; Høst, A

1988-01-01

We report a case of long-term systemic administration of prostaglandin E2 (PGE2) to a newborn infant with ductus-dependent congenital heart disease. After 46 days of treatment, radiography showed cortical hyperostosis of the long bones. The child died 62 days after discontinuation of prostaglandin...... treatment. Histologic examination of tubular bones showed hyperostosis presumably due to prostaglandin-induced rapid formation of primitive bone. The additional finding of extensive resorption of the outer cortical surface and bone formation at the inner surface suggested a reversible phase after...

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

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.

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

Directory of Open Access Journals (Sweden)

Qinghua ZHOU

2014-03-01

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

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.

Gut microbiota induce IGF-1 and promote bone formation and growth

Science.gov (United States)

Yan, Jing; Herzog, Jeremy W.; Tsang, Kelly; Brennan, Caitlin A.; Bower, Maureen A.; Garrett, Wendy S.; Sartor, Balfour R.; Charles, Julia F.

2016-01-01

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth. PMID:27821775

Understanding coupling between bone resorption and formation

DEFF Research Database (Denmark)

Andersen, Thomas Levin; Abdelgawad, Mohamed Essameldim; Kristensen, Helene Bjørg

2013-01-01

these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined...... histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested...

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

Science.gov (United States)

McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

2008-02-01

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

Energy Technology Data Exchange (ETDEWEB)

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O' Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

2013-10-15

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

International Nuclear Information System (INIS)

Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

2011-01-01

During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

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.

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

Science.gov (United States)

de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

2015-04-01

Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

Science.gov (United States)

Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

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)

Diagnostic accuracy of bone metastases detection in cancer patients. Comparison between bone scintigraphy and whole-body FDG-PET

International Nuclear Information System (INIS)

Fujimoto, Ryota; Higashi, Tatsuya; Nakamoto, Yuji

2006-01-01

18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has become widely available and an important oncological technique. To evaluate the influence of PET on detection of bone metastasis, we compared the diagnostic accuracy of PET and conventional bone scintigraphy (BS) in a variety of cancer patients. Consecutive ninety-five patients with various cancers, who received both PET and BS within one month, were retrospectively analyzed. A whole-body PET (from face to upper thigh) and a standard whole body BS were performed and these images were interpreted by two experienced nuclear medicine physicians with and without patient information using monitor diagnosis. Each image interpretation was performed according to 8 separate areas (skull, vertebra, upper limbs, sternum and clavicles, scapula, ribs, pelvis, and lower limbs) using a 5-point-scale (0: definitely negative, 1: probably negative, 2: equivocal, 3: probably positive, 4: definitely positive for bone metastasis). Twenty-one of 95 patients (22.1%) with 43 of 760 areas (5.7%) of bone metastases were finally confirmed. In untreated patients, 12 of 14 bone metastasis positive patients were detected by PET, while 9 of 14 were detected by BS. Three cases showed true positive in PET and false negative in BS due to osteolytic type bone metastases. In untreated cases, PET with and without clinical information showed better sensitivity than BS in patient-based diagnosis. For the purpose of treatment effect evaluation, PET showed better results because of its ability in the evaluation of rapid response of tumor cells to chemotherapy. Out of 10 cases of multiple-area metastases, 9 cases included vertebrae. There was only one solitary lesion located outside of field of view (FOV) of PET scan in the femur, but with clinical information that was no problem for PET diagnosis. Diagnostic accuracy of bone metastasis was comparable in PET and BS in the present study. In a usual clinical condition, limited FOV (from

Relationship between bone scintigraphy and tumor markers in patients with breast cancer

International Nuclear Information System (INIS)

Yildiz, M.; Oral, B.

2004-01-01

The aim of this study is to specify the precise role of bone scintigraphy and serum carcinoembryonic antigen (CEA) and breast cancer-associated antigen (CA) 15-3 assays in the monitoring of breast cancers in order to optimize their use and to determine whether it is possible to guide the prescription of bone scan by the use of CEA and CA 15-3 assays in the monitoring of breast cancer. For this purpose, from November 1997 to May 2002, 98 consecutive female breast cancer patients (median age, 52 years; range 35-77 years) underwent bone scintigraphy during follow-up. In these patients values of tumor markers were compared with the results of bone scintigraphy. Some of the patients with bone metastasis were checked repeatedly at intervals of 6 to 12 months, resulting in 49 patients with bone metastasis and 74 patients without bone metastasis being included in the study. In patients with bone metastasis, serum CEA levels were abnormal in 23/49 cases and CA 15-3 serum concentrations were elevated above the cut-off in 33/49 cases. Among patients without bone metastasis, CEA and CA 15-3 serum concentrations were normal in 50/74 and 55/74 cases respectively. The combination of the two markers improved the diagnostic sensitivity. Although serial tumor marker measurements are an efficient and cost effective method of monitoring disease progression, it does not allow prediction of the bone scan results; so it is not justifiable to reject a bone scintigraphy on the basis of these markers. (author)

Sintered porous hydroxyapatites with intrinsic osteoinductive activity: geometric induction of bone formation

CSIR Research Space (South Africa)

Ripamonti, U

1999-08-01

Full Text Available Sintered hydroxyapatites induce bone formation in adult baboons via intrinsic osteoinductivity regulated by the geometry of the substratum. Bone is thereby formed without exogenous bone morphogenetic proteins (BMPs), well-characterized inducers...

Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover.

Science.gov (United States)

Hussein, H; Dulin, J; Smanik, L; Drost, W T; Russell, D; Wellman, M; Bertone, A

2017-08-01

Our investigations evaluated the effect of VEL-0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX-1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis of plasma bone biomarkers (CTX-1 and osteocalcin), poststudy bone fluorescent labeling, and bone biopsy were performed. Bone specimens were further processed for microcomputed tomography and bone histomorphometry. Each dose of this CatKI transiently inhibited plasma CTX-1 (reflecting inhibition of bone collagen resorption) and increased bone plasma osteocalcin concentrations, with no detectable adverse effect on normal bone turnover in the face of exercise. Bone morphology, density, and formation rate were not different between control and treated group. Further investigation of CatK inhibition in abnormal bone turnover is required in animals with bone diseases. © 2016 John Wiley & Sons Ltd.

Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded allograft

Directory of Open Access Journals (Sweden)

J O Eniwumide

2007-08-01

Full Text Available Improvements to current therapeutic strategies are needed for the treatment of skeletal defects. Bone tissue engineering offers potential advantages to these strategies. In this study, ectopic bone formation in a range of scaffolds was assessed. Vital autograft and devitalised allograft served as controls and the experimental groups comprised autologous bone marrow derived stem cell seeded allograft, biphasic calcium phosphate (BCP and tricalcium phosphate (TCP, respectively. All implants were implanted in the back muscle of adult Dutch milk goats for 12 weeks. Micro-computed tomography (µCT analysis and histomorphometry was performed to evaluate and quantify ectopic bone formation. In good agreement, both µCT and histomorphometric analysis demonstrated a significant increase in bone formation by cell-seeded calcium phosphate scaffolds as compared to the autograft, allograft and cell-seeded allograft implants. An extensive resorption of the autograft, allograft and cell-seeded allograft implants was observed by histology and confirmed by histomorphometry. Cell-seeded TCP implants also showed distinct signs of degradation with histomorphometry and µCT, while the degradation of the cell-seeded BCP implants was negligible. These results indicate that cell-seeded calcium phosphate scaffolds are superior to autograft, allograft or cell-seeded allograft in terms of bone formation at ectopic implantation sites. In addition, the usefulness of µCT for the efficient and non-destructive analysis of mineralised bone and calcium phosphate scaffold was demonstrated.

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

International Nuclear Information System (INIS)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

2014-01-01

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

Energy Technology Data Exchange (ETDEWEB)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2014-01-10

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

Multi-protein delivery by nanodiamonds promotes bone formation.

Science.gov (United States)

Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

2013-11-01

Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.

Impact of skeletal unloading on bone formation: Role of systemic and local factors

Science.gov (United States)

Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

Science.gov (United States)

Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

2012-03-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

BMP9-Induced Osteogenetic Differentiation and Bone Formation of Muscle-Derived Stem Cells

Directory of Open Access Journals (Sweden)

Li Xiang

2012-01-01

Full Text Available Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9 in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture.

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

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.

[Experimental study of the effect of new bone formation on new type artificial bone composed of bioactive ceramics].

Science.gov (United States)

Zhu, Minghua; Zeng, Yi; Sun, Tao; Peng, Qiang

2005-03-15

To investigate the osteogenic potential of four kinds of new bioactive ceramics combined with bovine bone morphogenetic proteins (BMP) and to explore the feasibility of using compounds as bone substitute material. Ninety-six rats were divided into 4 groups (24 in each group). BMP was combined with hydroxyapatite (HA), tricalcium phosphate (TCP), fluoridated-HA (FHA), and collagen-HA(CHA) respectively. The left thighs of the rats implanted with HA/BMP, TCP/BMP, FHA/BMP, and CHA/BMP were used as experimental groups. The right thighs of the rats implanted with HA, TCP, CHA, and decalcified dentin matrix (DDM) were used as control groups. The rats were sacrificed 1, 3, 5 and 7 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP), phosphorus (P), and total protein (TP) measurement. The histological observation and electronic microscope scanning of the implants were also made. The cartilage growth in the 4 experimental groups and the control group implanted with DDM was observed 1 week after operation and fibrous connective tissues were observed in the other 3 control groups. 3 weeks after implantation, lamellar bone with bone marrow and positive reaction in ALP stain were observed in the 4 experimental groups. No bone formation or positive reaction in ALP stain were observed in the control groups. The amount of ALP activity, P value, and new bone formation in the experimental groups were higher than those in the control group(P < 0.05). The amount of ALP activity, P value, and new bone formation in TCP/BMP group were higher than those in HA/BMP, CHA/BMP and FHA/BMP groups (P < 0.05). There was no significant difference in TP between the BMP treatment group and the control groups. From 5th to 7th week, new bone formation, histochemistry evaluation, and the level of ALP, P, TP value were as high as those in the 3rd week. New composite artificial bone of TCP/BMP, HA/BMP, CHA/BMP, and FHA/BMP all prove to be effective, but TCP/BMP is the

The Effect of Aloe, Gelfoam, Plaster on Bone Formation in applying to the bone defect

International Nuclear Information System (INIS)

Choi, Eui Hwan; Kim, Su Gwan

1999-01-01

This study was to evaluate the effects of Aloe, Gelfoam, and Plaster of Paris on bone healing. Four experimental defects were created for placement of the three materials in the right femur of dogs. One defect served as an empty control site. The evaluation was performed at 1-, 6-, and 12-weeks by light microscopy and NIH image program. Radiographic and Histologic examinations showed new bone formation in the presence of Aloe, Gelfoam, and Plaster of Paris and similar bone healing reactions. On the basis of these findings, it was concluded that Aloe, Gelfoam, and Plaster of Paris may be adequate agents for use in bone procurement.

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.

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.

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)

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.

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...

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

Directory of Open Access Journals (Sweden)

Jamie Heimburg

2006-11-01

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

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

NARCIS (Netherlands)

Song, G.; Habibovic, Pamela; Bao, Chongyun; Hu, J.; van Blitterswijk, Clemens; Yuan, Huipin; Chen, W.; Xu, H.H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched

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.

Enhancement of bone formation in rabbits by recombinant human growth hormone

International Nuclear Information System (INIS)

Ehrnberg, A.; Brosjoe, O.; Laaftman, P.; Nilsson, O.; Stroemberg, L.

1993-01-01

We studied the effect of human recombinant growth hormone on diaphyseal bone in 40 adult rabbits. The diaphyseal periosteum of one femur in each animal was mechanically stimulated by a nylon cerclage band. The bands induced an increase in bone formation, bone mineral content, and maximum torque capacity of the diaphyseal bone at 1 and 2 months. Growth hormone enhanced the anabolic effect of the cerclage bands on bone metabolism, evidenced by a further increase in torsional strength of the femurs. (au) (32 refs.)

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.

Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

Directory of Open Access Journals (Sweden)

Mathilde Doyard

Full Text Available Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation

Directory of Open Access Journals (Sweden)

Md. Abdullah Al Mamun

Full Text Available BACKGROUND: Tridaxprocumbens flavonoids (TPFs are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2 CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2011-08-22

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

The relationship between inflammation and new bone formation in patients with ankylosing spondylitis

OpenAIRE

Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

2008-01-01

Introduction Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Methods Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondyl...

Functionalized Surface Geometries Induce: “Bone: Formation by Autoinduction”

Directory of Open Access Journals (Sweden)

Ugo Ripamonti

2018-02-01

Full Text Available The induction of tissue formation, and the allied disciplines of tissue engineering and regenerative medicine, have flooded the twenty-first century tissue biology scenario and morphed into high expectations of a fulfilling regenerative dream of molecularly generated tissues and organs in assembling human tissue factories. The grand conceptualization of deploying soluble molecular signals, first defined by Turing as forms generating substances, or morphogens, stemmed from classic last century studies that hypothesized the presence of morphogens in several mineralized and non-mineralized mammalian matrices. The realization of morphogens within mammalian matrices devised dissociative extractions and chromatographic procedures to isolate, purify, and finally reconstitute the cloned morphogens, found to be members of the transforming growth factor-β (TGF-β supergene family, with insoluble signals or substrata to induce de novo tissue induction and morphogenesis. Can we however construct macroporous bioreactors per se capable of inducing bone formation even without the exogenous applications of the osteogenic soluble molecular signals of the TGF-β supergene family? This review describes original research on coral-derived calcium phosphate-based macroporous constructs showing that the formation of bone is independent of the exogenous application of the osteogenic soluble signals of the TGF-β supergene family. Such signals are the molecular bases of the induction of bone formation. The aim of this review is to primarily describe today's hottest topic of biomaterials' science, i.e., to construct and define osteogenetic biomaterials' surfaces that per se, in its own right, do initiate the induction of bone formation. Biomaterials are often used to reconstruct osseous defects particularly in the craniofacial skeleton. Edentulism did spring titanium implants as tooth replacement strategies. No were else that titanium surfaces require functionalized

Selectins mediate small cell lung cancer systemic metastasis.

Directory of Open Access Journals (Sweden)

Franziska Heidemann

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

Skeletal blood flow: implications for bone-scan interpretation

International Nuclear Information System (INIS)

Charkes, N.D.

1980-01-01

The dispersion of the skeleton throughout the body and its complex vascular anatomy require indirect methods for the measurement of skeletal blood flow. The results of one such method, compartmental analysis of skeletal tracer kinetics, are presented. The assumptions underlying the models were tested in animals and found to be in agreement with experimental observations. Based upon the models and the experimental results, inferences concerning bone-scan interpretation can be drawn: decreased cardiac output produces low-contrast (technically poor) scans; decreased skeletal flow produces photon-deficient lesions; increase of cardiac output or of generalized systemic blood flow is undetectable 1 to 2 h after dose; increased local skeletal blood flow results from disturbance of the bone microvasculature and can occur from neurologic (sympatholytic) disorders or in association with focal abnormalities that also incite the formation of reactive bone (e.g., metastasis, fracture, etc.). Mathematical solutions of tracer kinetic data thus become relevant to bone-scan interpretation

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

Thymidine phosphorylase exerts complex effects on bone resorption and formation in myeloma.

Science.gov (United States)

Liu, Huan; Liu, Zhiqiang; Du, Juan; He, Jin; Lin, Pei; Amini, Behrang; Starbuck, Michael W; Novane, Nora; Shah, Jatin J; Davis, Richard E; Hou, Jian; Gagel, Robert F; Yang, Jing

2016-08-24

Myelomatous bone disease is characterized by the development of lytic bone lesions and a concomitant reduction in bone formation, leading to chronic bone pain and fractures. To understand the underlying mechanism, we investigated the contribution of myeloma-expressed thymidine phosphorylase (TP) to bone lesions. In osteoblast progenitors, TP up-regulated the methylation of RUNX2 and osterix, leading to decreased bone formation. In osteoclast progenitors, TP up-regulated the methylation of IRF8 and thereby enhanced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 protein), leading to increased bone resorption. TP reversibly catalyzes thymidine into thymine and 2-deoxy-d-ribose (2DDR). Myeloma-secreted 2DDR bound to integrin αVβ3/α5β1 in the progenitors, activated PI3K (phosphoinositide 3-kinase)/Akt signaling, and increased DNMT3A (DNA methyltransferase 3A) expression, resulting in hypermethylation of RUNX2, osterix, and IRF8 This study elucidates an important mechanism for myeloma-induced bone lesions, suggesting that targeting TP may be a viable approach to healing resorbed bone in patients. Because TP overexpression is common in bone-metastatic tumors, our findings could have additional mechanistic implications. Copyright © 2016, American Association for the Advancement of Science.

Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

Science.gov (United States)

Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

2012-09-01

OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

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.

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.

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.

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

OpenAIRE

McGee, Meghan E.; Maki, Aaron J.; Johnson, Steven E.; Lynne Nelson, O.; Robbins, Charles T.; Donahue, Seth W.

2007-01-01

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. ...

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

Science.gov (United States)

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

Directory of Open Access Journals (Sweden)

Takenobu Katagiri, PhD

2015-05-01

Full Text Available Bone morphogenetic protein (BMP was originally discovered by Marshall Urist a half century ago following the observation of a unique activity that induced heterotopic bone formation in skeletal muscle tissue. The molecular mechanisms underlying the induction of heterotopic bone formation in skeletal muscle by BMPs were elucidated through the purification and molecular cloning of BMPs and identification of their functional receptors and downstream effectors, as well as from genetic disorders related to BMP activity. BMPs are important regulators of not only skeletal development and regeneration but also the homeostasis of normal skeletal muscle mass. There is still much to learn about the physiology and pathology at the interface of BMPs and skeletal muscle.

The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

DEFF Research Database (Denmark)

Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

2004-01-01

, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION......Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride...

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

The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

Science.gov (United States)

Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

1985-01-01

The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Directory of Open Access Journals (Sweden)

Gu W

2013-06-01

Full Text Available Wenyi Gu,1,2 Chengtie Wu,3 Jiezhong Chen,1 Yin Xiao1 1Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia; 2Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia; 3State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China Abstract: Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically. Keywords: nanoparticles, nanostructured scaffold, cancer bone metastasis, bone diseases, target drug delivery, bone regeneration

Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

Science.gov (United States)

Hoch, Allison I; Duhr, Ralph; Di Maggio, Nunzia; Mehrkens, Arne; Jakob, Marcel; Wendt, David

2017-12-01

Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue-engineered bone formation using human bone marrow stromal cells and novel β-tricalcium phosphate

International Nuclear Information System (INIS)

Liu Guangpeng; Zhao Li; Cui Lei; Liu Wei; Cao Yilin

2007-01-01

In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel β-tricalcium phosphate (β-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous β-TCP scaffolds with pores of 300-500 μm in size were prepared by the polymeric sponge method. β-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous β-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In β-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in β-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous β-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering

Tissue-engineered bone formation using human bone marrow stromal cells and novel {beta}-tricalcium phosphate

Energy Technology Data Exchange (ETDEWEB)

Liu Guangpeng [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Zhao Li [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cui Lei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Liu Wei [National Tissue Engineering Research and Development Center, Shanghai 200235 (China); Cao Yilin [National Tissue Engineering Research and Development Center, Shanghai 200235 (China)

2007-06-01

In this study we investigated not only the cellular proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) on the novel {beta}-tricalcium phosphate ({beta}-TCP) scaffolds in vitro but also bone formation by ectopic implantation in athymic mice in vivo. The interconnected porous {beta}-TCP scaffolds with pores of 300-500 {mu}m in size were prepared by the polymeric sponge method. {beta}-TCP scaffolds with the dimension of 3 mm x 3 mm x 3 mm were combined with hBMSCs, and incubated with (+) or without (-) osteogenic medium in vitro. Cell proliferation and osteogenic differentiation on the scaffolds were evaluated by scanning electron microscopy (SEM) observation, MTT assay, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content measurement. SEM observation showed that hBMSCs attached well on the scaffolds and proliferated rapidly. No significant difference in the MTT assay could be detected between the two groups, but the ALP activity and OCN content of scaffolds (+) were much higher than those of the scaffolds (-) (p < 0.05). These results indicated that the novel porous {beta}-TCP scaffolds can support the proliferation and subsequent osteogenic differentiation of hBMSCs in vitro. After being cultured in vitro for 14 days, the scaffolds (+) and (-) were implanted into subcutaneous sites of athymic mice. In {beta}-TCP scaffolds (+), woven bone formed after 4 weeks of implantation and osteogenesis progressed with time. Furthermore, tissue-engineered bone could be found at 8 weeks, and remodeled lamellar bone was also observed at 12 weeks. However, no bone formation could be found in {beta}-TCP scaffolds (-) at each time point checked. The above findings illustrate that the novel porous {beta}-TCP scaffolds developed in this work have prominent osteoconductive activity and the potential for applications in bone tissue engineering.

The Use of Injectable Chitosan/Nanohydroxyapatite/Collagen Composites with Bone Marrow Mesenchymal Stem Cells to Promote Ectopic Bone Formation In Vivo

Directory of Open Access Journals (Sweden)

Bo Yu

2013-01-01

Full Text Available The aim of this study was to evaluate ectopic in vivo bone formation with or without rat bone mesenchymal stem cells (rBMSCs of an injectable Chitosan/Nanohydroxyapatite/Collagen (CS/nHAC composite. The CS/nHAC composites were injected subcutaneously into the backs of Wistar rats with freshly loaded rBMSCs at a density of 10×106 cells/mL, and the CS/nHAC composites without cells were used as negative controls. New bone formation, degradation of composites, and degree of calcification were evaluated by Computed Tomography (CT and three-dimensional (3D CT reconstruction. Histological evaluations were performed to further assess bone structure and extracellular matrix by HE and Masson staining. The inflammatory reactions related to osteogenesis were also investigated in the present study. In comparison with the CS/nHAC composites, this study revealed that CS/nHAC/rBMSCs composites showed relatively higher percentage of calcification, better establishment of ECM, and less degradation rate. Meanwhile, different extents of inflammatory reactions were also observed in the CS/nHAC and CS/nHAC/rBMSCs explants at 2 and 4 weeks after implantation. Altogether, CS/nHAC/rBMSCs composites are superior to CS/nHAC composites in ectopic bone formation. In conclusion, the rBMSCs-seeded CS/nHAC composites may be beneficial to enhancing ectopic bone formation in vivo.

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation.

Science.gov (United States)

Winkler, I G; Pettit, A R; Raggatt, L J; Jacobsen, R N; Forristal, C E; Barbier, V; Nowlan, B; Cisterne, A; Bendall, L J; Sims, N A; Lévesque, J-P

2012-07-01

The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Science.gov (United States)

Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

2013-01-01

Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

Effects of low‑level laser therapy on osteoblastic bone formation and ...

African Journals Online (AJOL)

were compared. Conclusion: Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing. Key words: Bio‑stimulation, laser, rapid maxillary expansion. Date of Acceptance: 12‑Jan‑2015. Address for correspondence: Dr. M Demirkol,.

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

Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis

DEFF Research Database (Denmark)

Abdallah, Basem; Ditzel, Nicholas; Kassem, Moustapha

2008-01-01

In vivo assessment of bone formation (osteogenesis) potential by isolated cells is an important method for analysis of cells and factors control ling bone formation. Currently, cell implantation mixed with hydroxyapa-tite/tricalcium phosphate in an open system (subcutaneous implantation) in immun...

Assessment of activated porous granules on implant fixation and early bone formation in sheep

Directory of Open Access Journals (Sweden)

Ming Ding

2016-04-01

Conclusion: In conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

Science.gov (United States)

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep

DEFF Research Database (Denmark)

Ding, Ming; Snoek Henriksen, Susan; Martinetti, Roberta

2017-01-01

allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while......, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016....

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...

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

Directory of Open Access Journals (Sweden)

Gruber Helen E

2011-08-01

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

Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration.

Science.gov (United States)

Spalthoff, S; Jehn, P; Zimmerer, R; Möllmann, U; Gellrich, N-C; Kokemueller, H

2015-06-01

We previously generated viable heterotopic bone in living animals and found that 3 months of intrinsic vascularization improved bone formation and matrix degeneration. In this study, we varied the pre-vascularization time to determine its effects on the kinetics of bone formation and ceramic degradation. Two 25-mm-long cylindrical β-tricalcium phosphate scaffolds were filled intraoperatively with autogenous iliac crest bone marrow and implanted in the latissimus dorsi muscle in six sheep. To examine the effect of axial perfusion, one scaffold was surgically implanted with (group C) or without (group D) a central vascular bundle. All animals were sacrificed 6 months postoperatively and histomorphometric measurements were compared to previous results. All implanted scaffolds exhibited ectopic bone growth. However, bone growth was not significantly different between the 3-month (group A, 0.191±0.097 vs. group C, 0.237±0.075; P=0.345) and 6-month (group B, 0.303±0.105 vs. group D, 0.365±0.258; P=0.549) pre-vascularization durations, regardless of vessel supply; early differences between surgically and extrinsically vascularized constructs disappeared after 6 months. Here, we describe a reliable procedure for generating ectopic bone in vivo. A 3-month pre-vascularization duration appears sufficient and ceramic degradation proceeds in accordance with bone generation, supporting the hypothesis of cell-mediated resorption. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Piezoelectricity could predict sites of formation/resorption in bone remodelling and modelling.

Science.gov (United States)

Fernández, J R; García-Aznar, J M; Martínez, R

2012-01-07

We have developed a mathematical approach for modelling the piezoelectric behaviour of bone tissue in order to evaluate the electrical surface charges in bone under different mechanical conditions. This model is able to explain how bones change their curvature, where osteoblasts or osteoclasts could detect in the periosteal/endosteal surfaces the different electrical charges promoting bone formation or resorption. This mechanism also allows to understand the BMU progression in function of the electro-mechanical bone behaviour. Copyright © 2011 Elsevier Ltd. All rights reserved.

Galectin-4 Reduces Migration and Metastasis Formation of Pancreatic Cancer Cells.

Directory of Open Access Journals (Sweden)

Ana I Belo

Full Text Available Galectin-4 (Gal-4 is a member of the galectin family of glycan binding proteins that shows a significantly higher expression in cystic tumors of the human pancreas and in pancreatic adenocarcinomas compared to normal pancreas. However, the putative function of Gal-4 in tumor progression of pancreatic cancer is still incompletely understood. In this study the role of Gal-4 in cancer progression was investigated, using a set of defined pancreatic cancer cell lines, Pa-Tu-8988S (PaTu-S and Pa-Tu-8988T (PaTu-T, as a model. These two cell lines are derived from the same liver metastasis of a human primary pancreatic adenocarcinoma, but differ in their growth characteristics and metastatic capacity. We demonstrated that Gal-4 expression is high in PaTu-S, which shows poor migratory properties, whereas much lower Gal-4 levels are observed in the highly metastatic cell line PaTu-T. In PaTu-S, Gal-4 is found in the cytoplasm, but it is also secreted and accumulates at the membrane at sites of contact with neighboring cells. Moreover, we show that Gal-4 inhibits metastasis formation by delaying migration of pancreatic cancer cells in vitro using a scratch assay, and in vivo using zebrafish (Danio rerio as an experimental model. Our data suggest that Gal-4 may act at the cell-surface of PaTu-S as an adhesion molecule to prevent release of the tumor cells, but has in addition a cytosolic function by inhibiting migration via a yet unknown mechanism.

Bone formation within a breast abscess

OpenAIRE

Mannu, Gurdeep Singh; Ahmed, Farid; Cunnick, Giles; Mungalsingh, Naren

2014-01-01

We present a rare case of osseous metaplasia in a poorly healing breast abscess. An 87-year-old woman was referred to the breast surgery clinic with a painful lump in her right breast. Initial imaging and core biopsy suggested a breast abscess. Despite several courses of antibiotics and repeated attempts at aspiration the painful lesion persisted. It was eventually surgically excised in its entirety and final histopathology showed the presence of bone formation within the abscess. The patient...

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.

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.

Directory of Open Access Journals (Sweden)

Liao Wang

Full Text Available Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA sintered at 1200°C and two biphasic calcium phosphate (BCP ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate, sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model.

Age-related new bone formation following the use of cancellous bone-block allografts for reconstruction of atrophic alveolar ridges.

Science.gov (United States)

Nissan, Joseph; Kolerman, Roni; Chaushu, Liat; Vered, Marilena; Naishlos, Sarit; Chaushu, Gavriel

2018-02-01

An age-related decrease in the number of osteogenic progenitor cells may compromise bone augmentation. Histomorphometrical assessment of age-related new bone formation, following atrophic alveolar ridge reconstruction, using cancellous bone-block allografts. Ninety-three consecutive patients (58 females and 35 males) were referred for implant-supported restoration of 122 severe atrophic alveolar ridges. Alveolar ridge deficiency locations were classified as anterior maxilla (n = 58), posterior maxilla (n= 32), and posterior mandible (n = 32). A bony deficiency of at least 3 mm horizontally and up to 3 mm vertically according to computerized tomography (CT) in the posterior mandible and anterior maxilla, served as inclusion criteria. In the posterior maxilla, a residual alveolar ridge up to 4 mm vertically according to CT served as inclusion criteria. Augmentation was performed by the use of cancellous bone-block allografts. Bone biopsies (9-month posterior maxilla, 4 months anterior maxilla and posterior mandible) of young (≤40 years) versus older (>40 years) patients were histomorphometrically evaluated. In the posterior maxilla, no statistically significant histomorphometric differences were noted. While at the anterior maxilla and posterior mandible, statistically significant more newly formed bone was found in young versus older individuals, respectively (38.6% vs 19.8%, P = 0.04 and 69% vs 31%, P = .05). New bone formation following residual alveolar ridge bone grafting is age-related. Longer bone consolidation and healing time may be recommended for older individuals. © 2017 Wiley Periodicals, Inc.

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

Science.gov (United States)

Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

2003-06-13

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

Samarium-153-EDTMP in the metastatic bone pain treatment

International Nuclear Information System (INIS)

Lins Filho, M.L.M.; Santos, A.O.; Nappi, A.P.B.; Meirelles, M.B.; Arouca, P.T.; Ramos, C.D.; Etchebehere, E.C.S.C.; Teixeira, L.C.; Netto Junior, N.R.; D'Ancona Cal; Camargo, E.E.

1997-01-01

Full text: Bone metastasis is the most reason of pain in prostate and mammary cancer patients. The Samarium-153-EDTMP has been showed as an alternative to the treatment of the metastasis bone pain. With the objective to evaluate the use of the Sm-153-EDTMP as a systemic therapy for the metastasis bone pain, 30 patients (19 male, 11 female, average age of 64,5 years) were studied. 19 patients with prostate cancer and 11 with mammary cancer. All the patients presented previous bone scintiscanning with multiple metastasis; interruption of the chemotherapy or radiotherapy for two or more weeks and leukocyte count higher than 2,000 leukocytes/mm 3 and platelets higher than 80,000/mm 3 . The patients were classified previously to the radioisotope therapy, as far the intensity of the pain in a scale from 0 to 10 is concerned. All the patients received 37 MBq/kg (1m Ci/kg) of weight of Sm-153-EDTMP by venous via. The evaluation 6 weeks after the therapy showed complete or partial pain relief in 22 patients (73,3%). Complete or partial pain relief has been obtained in 91,0% (10 in 11) of the patients with mammary cancer and in 62,2% (12 in 19) of the patients with prostate cancer. Transitory leukopenia (lower than 2,000 leukocytes/mm 3 ) and platelet count (lower than 80,000/mm 3 ) occurred in 33,3% of the patients. 8 patients (26,7%) did not responded to the therapy. The therapy with Samarium-153-EDTMP is a simple, safe and efficient method in the treatment of the bone pain caused by metastasis

Usefulness of serum bone metabolic markers for the diagnosis of differentiated thyroid cancer with bone metastases

International Nuclear Information System (INIS)

Wu Xiaohui; Lu Hankui; Gao Yunchao; Yuan Zhibin

2007-01-01

Objective: Bone metabolic markers (BMM) are biochemical substances that reflect bone resorption or formation. Some of them have been found to be useful in the diagnosis and management of bone metastases. The aim of this study was to investigate the usefulness of two bone resorption markers: bone-specific alkaline phosphatase (B-ALP) and N-terminal procollagen propeptides of type I collagen (PINP), as well as two bone formation markers: cross linked N and C terminal telepeptides of type I collagen (NTX and CTX) in the detection of bone metastasis in patients with differentiated thyroid cancer (DTC). Methods: There were sixty-three DTC patients in this study, 33 cases with clinically confirmed bone metastases and 30 cases with no bone metastases. The extents of bone metastases (or extents of the disease, EOD) were classified into four grades (0, I, II and III) according to the clinical and imaging findings including 99 Tc m -MDP, 131 I whole body scans and others. Serum BMM levels were measured by chemiluminescence immunoassay for B-ALP, radioimmunoassay for PINP, ELISA for NTX and electrochemiluminescence immunoassay for CTX. Nonparametric Mann-Whitney U test, grade correlation analysis and receiver operator characteristic (ROC) curve were applied to analyze the correlation between BMM and DTC patients with bone metastases. Results: The serum levels of B-ALP, NTX and CTX were significantly higher in DTC patients with bone metastases than those in patients with no bone metastases (all P 0.05). The serum levels of all markers were correlated with EOD grades (r s =0.371-0.558, all P<0.01). B-ALP level was found to have significant difference between EOD 0 to I (P=0.012). The diagnostic sensitivity and specificity of B-ALP for detecting DTC with bone metastases were 71.1% and 76.7% respectively by ROC curve analysis, which were higher than those of the other three markers. Conclusions: Serum BMM levels of B-ALP, NTX and CTX were useful for the evaluation of DTC with

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

Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

Directory of Open Access Journals (Sweden)

Jian Cao

2014-03-01

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

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.

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.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

Science.gov (United States)

Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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 ...

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.)

[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.

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.)

Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

DEFF Research Database (Denmark)

Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

2004-01-01

Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

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.

Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.

Science.gov (United States)

Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli

2018-03-01

Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.