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

International Nuclear Information System (INIS)

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

2009-01-01

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

Whole-body bone segmentation from MRI for PET/MRI attenuation correction using shape-based averaging

DEFF Research Database (Denmark)

Arabi, Hossein; Zaidi, H.

2016-01-01

Purpose: The authors evaluate the performance of shape-based averaging (SBA) technique for whole-body bone segmentation from MRI in the context of MRI-guided attenuation correction (MRAC) in hybrid PET/MRI. To enhance the performance of the SBA scheme, the authors propose to combine it with stati......Purpose: The authors evaluate the performance of shape-based averaging (SBA) technique for whole-body bone segmentation from MRI in the context of MRI-guided attenuation correction (MRAC) in hybrid PET/MRI. To enhance the performance of the SBA scheme, the authors propose to combine...... it with statistical atlas fusion techniques. Moreover, a fast and efficient shape comparisonbased atlas selection scheme was developed and incorporated into the SBA method. Methods: Clinical studies consisting of PET/CT and MR images of 21 patients were used to assess the performance of the SBA method. In addition...... voting (MV) atlas fusion scheme was also evaluated as a conventional and commonly used method. MRI-guided attenuation maps were generated using the different segmentation methods. Thereafter, quantitative analysis of PET attenuation correction was performed using CT-based attenuation correction...

Osthole inhibits bone metastasis of breast cancer

OpenAIRE

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

2017-01-01

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

Description and assessment of a registration-based approach to include bones for attenuation correction of whole-body PET/MRI.

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Marshall, Harry R; Patrick, John; Laidley, David; Prato, Frank S; Butler, John; Théberge, Jean; Thompson, R Terry; Stodilka, Robert Z

2013-08-01

Attenuation correction for whole-body PET/MRI is challenging. Most commercial systems compute the attenuation map from MRI using a four-tissue segmentation approach. Bones, the most electron-dense tissue, are neglected because they are difficult to segment. In this work, the authors build on this segmentation approach by adding bones using a registration technique and assessing its performance on human PET images. Twelve oncology patients were imaged with FDG PET/CT and MRI using a Turbo-FLASH pulse sequence. A database of 121 attenuation correction quality CT scans was also collected. Each patient MRI was compared to the CT database via weighted heuristic measures to find the "most similar" CT in terms of body geometry. The similar CT was aligned to the MRI with a deformable registration method. Two MRI-based attenuation maps were computed. One was a standard four-tissue segmentation (air, lung, fat, and lean tissue) using basic image processing techniques. The other was identical, except the bones from the aligned CT were added. The PET data were reconstructed with the patient's CT-based attenuation map (the silver standard) and both MRI-based attenuation maps. The relative errors of the MRI-based attenuation corrections were computed in 14 standardized volumes of interest, in lesions, and over whole tissues. The squared Pearson correlation coefficient was also calculated over whole tissues. Statistical testing was done with ANOVAs and paired t-tests. The MRI-based attenuation correction ignoring bone had relative errors ranging from -37% to -8% in volumes of interest containing bone. By including bone, the magnitude of the relative error was reduced in all cases (pbone was improved from a mean of -7.5% to 2% (pbone reduced the magnitude of relative error in three cases (pbone slightly increased relative error in lung from 7.7% to 8.0% (p=0.002), in fat from 8.5% to 9.2% (pbone from -14.6% to 1.3% (pbone was included or not. The approach to include bones in MRI

Drugs Approved for Bone Cancer

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This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation.

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Grenald, Shaness A; Doyle, Timothy M; Zhang, Hong; Slosky, Lauren M; Chen, Zhoumou; Largent-Milnes, Tally M; Spiegel, Sarah; Vanderah, Todd W; Salvemini, Daniela

2017-09-01

Metastatic bone pain is the single most common form of cancer pain and persists as a result of peripheral and central inflammatory, as well as neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P). Intriguingly, de novo sphingolipid biosynthesis was increased as shown by the elevations of dihydro-ceramides and dihydro-S1P. We next identified the S1P receptor subtype 1 (S1PR1) as a novel target for therapeutic intervention. Intrathecal or systemic administration of the competitive and functional S1PR1 antagonists, TASP0277308 and FTY720/Fingolimod, respectively, attenuated cancer-induced spontaneous flinching and guarding. Inhibiting CIBP by systemic delivery of FTY720 did not result in antinociceptive tolerance over 7 days. FTY720 administration enhanced IL-10 in the lumbar ipsilateral spinal cord of CIBP animals and intrathecal injection of an IL-10 neutralizing antibody mitigated the ability of systemic FTY720 to reverse CIBP. FTY720 treatment was not associated with alterations in bone metabolism in vivo. Studies here identify a novel mechanism to inhibit bone cancer pain by blocking the actions of the bioactive metabolites S1P and dihydro-S1P in lumbar spinal cord induced by bone cancer and support potential fast-track clinical application of the FDA-approved drug, FTY720, as a therapeutic avenue for CIBP.

Where is the place of bone scan in breast cancer?

International Nuclear Information System (INIS)

Nowferesti, G. H.; Ghavam Nasiri, M. R.; Anvari, K.

2002-01-01

Breast cancer is the most common female cancer in west and in Iran. The incidence in all over the world in year 2000 was 1050000 cases out of which 370000 were dead. General y bone is the most common site of distant. Metastases in beast cancer. Bone scan has an important place in the bone metastases and extent of bone disease and even in the staging and treatment protocol. In study done during 1 year, breast cancer patients and place of bone scan were studied. Every year more than 2000 new patients with cancer are diagnosed and treated in Khorasan state. And more than half of them are treated in Omid Hospital. In the year 2000 a study was done. 1336 new cases were admitted for treatment out of which 164 persons (13%) were breast cancer patients. 100 patients were selected randomly and different factors were studied. How many patients had bone scan and its place in breast cancer? Where is the most common metastatic place and relation with bone scan? The differential diagnosis in positive bone scans and comparing with radiography and patient's clinic were studied. Bone scan is positive in 35% of patients in stage III. Bone is the most common place for distant metastases in breast cancer in patients admitted in Omid hospital in year 2000. Clinical and para clinical study such as radiography and tumour markers were adjusted with bone scan, more in stages III and IV. 39 patients out of 100 studied patients had bone scan. 28 bone scan were adjusted radiologically. In 20 positive bone scan out of 28 patients with metastases 12 patients had bone metastases. Despite 5% positive bone scan in early stages can suggest that bone scan be taken for all patients with breast cancer as a basic step?

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...

Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

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Yardley DA

2016-05-01

Full Text Available Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. Keywords: breast cancer, bone metastases, hormone receptor-positive, bone-related complications, interventions, management and management strategies, estrogen receptor-positive

Irradiated long bone transplants in limb saving surgeries for extremity bone cancers

International Nuclear Information System (INIS)

Wang, E.HM.

1996-01-01

In the Philippines, the treatment of cancers of the limbs has always been by amputation. In recent decades, better understanding of these cancers and advances in the disciplines of cancer medicine have made the saving of these limbs almost routine in better developed countries. Surgeries entail two steps: (1) excision of the tumor and the bone from which the tumor arose, followed by (2) reconstruction of the defect resulting from the excision. Tumor implants, however, are not available locally, and are too costly for the average Filipino patient. Microvascular surgery is limited by the size of the defect it can bridge; and bone cement, not being biologic, can result in greater long term problems. Recently, the option of long bone transplants (aka large-segment allografts) to reconstruct these defects has become available locally. These bones are harvested from both cadaveric and live amputee donors after appropriate consent and medical work-up. After processing at the UP-PGH Tissue and Bone Bank, the bones are sterilized by irradiation at the PNRI(Philippine Nuclear Research Institute), and store in deep freezers until use. In the Philippines, limb saving surgery for bone cancers of the extremities using these large-segment alloografts was introduced in 1993 at the UP-PGH Musculoskeletal Tumor Unit. This paper will present the author's initial 3-year experience with 19 patients whose limbs were saved using bone transplantation. All surgeries were performed by the author and all patients have been personally followed up by the author (follow-up ranging from 6 months to 3-1/2 years). Cases will be presented to show the pre- and intraoperative processing of the irradiated bone; and the patients before and after the operations with emphasis on their improved quality of life and return to function. These results would seem to show that irradiated long bone transplants coupled with skills for limb saving surgery may make amputations a thing of the past for many of our

Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

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Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

2017-04-04

Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

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Yanju Bao

2015-01-01

Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

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Aceto, Nicola; Bardia, Aditya; Wittner, Ben S; Donaldson, Maria C; O'Keefe, Ryan; Engstrom, Amanda; Bersani, Francesca; Zheng, Yu; Comaills, Valentine; Niederhoffer, Kira; Zhu, Huili; Mackenzie, Olivia; Shioda, Toshi; Sgroi, Dennis; Kapur, Ravi; Ting, David T; Moy, Beverly; Ramaswamy, Sridhar; Toner, Mehmet; Haber, Daniel A; Maheswaran, Shyamala

2018-04-01

Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER) + breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER + breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients. Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720-7. ©2018 AACR . ©2018 American Association for Cancer Research.

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

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Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

2015-07-10

Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

International Nuclear Information System (INIS)

Brockton, Nigel T.; Gill, Stephanie J.; Laborge, Stephanie L.; Paterson, Alexander H. G.; Cook, Linda S.; Vogel, Hans J.; Shemanko, Carrie S.; Hanley, David A.; Magliocco, Anthony M.; Friedenreich, Christine M.

2015-01-01

Bone is the most common site of breast cancer distant metastasis, affecting 50–70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

Targeted Therapies for Myeloma and Metastatic Bone Cancers

Science.gov (United States)

2010-09-01

Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

Numerical and experimental study on the wave attenuation in bone--FDTD simulation of ultrasound propagation in cancellous bone.

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Nagatani, Yoshiki; Mizuno, Katsunori; Saeki, Takashi; Matsukawa, Mami; Sakaguchi, Takefumi; Hosoi, Hiroshi

2008-11-01

In cancellous bone, longitudinal waves often separate into fast and slow waves depending on the alignment of bone trabeculae in the propagation path. This interesting phenomenon becomes an effective tool for the diagnosis of osteoporosis because wave propagation behavior depends on the bone structure. Since the fast wave mainly propagates in trabeculae, this wave is considered to reflect the structure of trabeculae. For a new diagnosis method using the information of this fast wave, therefore, it is necessary to understand the generation mechanism and propagation behavior precisely. In this study, the generation process of fast wave was examined by numerical simulations using elastic finite-difference time-domain (FDTD) method and experimental measurements. As simulation models, three-dimensional X-ray computer tomography (CT) data of actual bone samples were used. Simulation and experimental results showed that the attenuation of fast wave was always higher in the early state of propagation, and they gradually decreased as the wave propagated in bone. This phenomenon is supposed to come from the complicated propagating paths of fast waves in cancellous bone.

A study on dose attenuation in bone density when TBI using diode detector and TLD

International Nuclear Information System (INIS)

Im, Hyun Sil; Lee, Jung Jin; Jang, Ahn Ki; KIm, Wan Sun

2003-01-01

Uniform dose distribution of the whole body is essential factor for the total body irradiation(TBI). In order to achieved this goal, we used to compensation filter to compensate body contour irregularity and thickness differences. But we can not compensate components of body, namely lung or bone. The purpose of this study is evaluation of dose attenuation in bone tissue when TBI using diode detectors and TLD system. The object of this study were 5 patients who undergo TBI at our hospital. Dosimetry system were diode detectors and TLD system. Treatment method was bilateral and delivered 10 MV X-ray from linear accelerator. Measurement points were head, neck, pelvis, knees and ankles. TLD used two patients and diode detectors used three patients. Results are as followed. All measured dose value were normalized skin dose. TLD dosimetry : Measured skin dose of head, neck, pelvis, knees and ankles were 92.78±3.3, 104.34±2.3, 98.03±1.4, 99.9±2.53, 98.17±0.56 respectably. Measured mid-depth dose of pelvis, knees and ankles were 86±1.82, 93.24±2.53, 91.50±2.84 respectably. There were 6.67%-11.65% dose attenuation at mid-depth in pelvis, knees and ankles. Diode detector : Measured skin dose of head, neck, pelvis, knees and ankles were 95.23±1.18, 98.33±0.6, 93.5±1.5, 87.3±1.5, 86.90±1.16 respectably. There were 4.53%-12.6% dose attenuation at mid-depth in pelvis, knees and ankles. We concluded that dose measurement with TLD or diode detector was inevitable when TBI treatment. Considered dose attenuation in bone tissue, We must have adequately deduction of compensator thickness that body portion involved bone tissue.

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...

Prevention and Treatment of Bone Metastases in Breast Cancer

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Ripamonti Carla

2013-09-01

Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

Quantitative evaluation of bone scintigraphy in prostate cancer

International Nuclear Information System (INIS)

Yamamoto, Yasushi

2017-01-01

This paper described the quantitative evaluation of bone scintigraphy that is used in the inspection of the bone-metastasis of prostate cancer. In advanced prostate cancer, bone scintigraphic examination with technetium 99m methylenediphosphonate (complex compound) is indispensable. Since bone metastasis hardly involves soft tissue, the morphological evaluation of soft tissue cancer cannot be used as a reference. Therefore, quantitative evaluation peculiar to bone scintigraphy has been developed. Following the visual evaluation that began in the 1980's, a technique considering highly integrated parts and areas of images was proposed in the 1990's. The computer-aided diagnosis (CAD) software that automated the manual analysis of the above technique was developed in the 2010's. In order to evaluate the usefulness of quantitative evaluation based on bone CAD, the authors performed bone scintigraphy for 42 patients, who were diagnosed as castration-resistant prostate cancer (CRPC) in 2004 to 2011 and received DEC therapy for 4 months. When bone CAD analysis was performed, it was found that the therapeutic effect could not be determined earlier than the judgement using the increase of PSA antigen. Recently quantitative analysis shifted from bone scintigraphy to bone SPECT (single photon emission computed tomography), and papers have also been published since the 2010s. In bone SPECT, the quantitative function of SUV (standardized uptake value) was equipped, and in the clinical use case of SUV, SUV increase was seen earlier than the increase of PSA antigen. The evidences are expected to be accumulated in the future. (A.O.)

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)

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

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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.

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

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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.

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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.

Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

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Yibin Kang

2016-06-01

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

Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

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2015-11-01

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

Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

Institute of Scientific and Technical Information of China (English)

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

2013-01-01

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

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

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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.

Risk factors and characteristics of prostate cancer bone metastases

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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

SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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A. S. Semkov

2010-01-01

Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

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A. S. Semkov

2014-08-01

Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

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Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-10-01

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units (HU ) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into HU was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of 4~mm corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

MR-based attenuation correction for PET/MRI neurological studies with continuous-valued attenuation coefficients for bone through a conversion from R2* to CT-Hounsfield units.

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Juttukonda, Meher R; Mersereau, Bryant G; Chen, Yasheng; Su, Yi; Rubin, Brian G; Benzinger, Tammie L S; Lalush, David S; An, Hongyu

2015-05-15

MR-based correction for photon attenuation in PET/MRI remains challenging, particularly for neurological applications requiring quantitation of data. Existing methods are either not sufficiently accurate or are limited by the computation time required. The goal of this study was to develop an MR-based attenuation correction method that accurately separates bone tissue from air and provides continuous-valued attenuation coefficients for bone. PET/MRI and CT datasets were obtained from 98 subjects (mean age [±SD]: 66yrs [±9.8], 57 females) using an IRB-approved protocol and with informed consent. Subjects were injected with 352±29MBq of (18)F-Florbetapir tracer, and PET acquisitions were begun either immediately or 50min after injection. CT images of the head were acquired separately using a PET/CT system. Dual echo ultrashort echo-time (UTE) images and two-point Dixon images were acquired. Regions of air were segmented via a threshold of the voxel-wise multiplicative inverse of the UTE echo 1 image. Regions of bone were segmented via a threshold of the R2* image computed from the UTE echo 1 and UTE echo 2 images. Regions of fat and soft tissue were segmented using fat and water images decomposed from the Dixon images. Air, fat, and soft tissue were assigned linear attenuation coefficients (LACs) of 0, 0.092, and 0.1cm(-1), respectively. LACs for bone were derived from a regression analysis between corresponding R2* and CT values. PET images were reconstructed using the gold standard CT method and the proposed CAR-RiDR method. The RiDR segmentation method produces mean Dice coefficient±SD across subjects of 0.75±0.05 for bone and 0.60±0.08 for air. The CAR model for bone LACs greatly improves accuracy in estimating CT values (28.2%±3.0 mean error) compared to the use of a constant CT value (46.9%±5.8, punits. From our analysis, we conclude that the proposed method closely approaches (<3% error) the gold standard CT-scaled method in PET reconstruction accuracy

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

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

2018-01-16

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

Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

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Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

2014-08-01

Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer

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Hahn, Steffen; Heusner, Till; Forsting, Michael; Antoch, Gerald (Dept. of Diagnostic and Interventional Radiology and Neuroradiology, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany)), email: steffen.hahn@uk-essen.de; Kuemmel, Sherko; Koeninger, Angelika (Dept. of Gynecology and Obstetrics, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany)); Nagarajah, James; Mueller, Stefan; Boy, Christian; Bockisch, Andreas; Stahl, Alexander (Dept. of Nuclear Medicine, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany))

2011-11-15

Background Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy. Purpose To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients. Material and Methods Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients. Results A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases. Conclusion On a lesion

Quantitative assessment of bone marrow attenuation values at MDCT: An objective tool for the detection of bone bruise related to occult sacral insufficiency fractures

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Henes, F.O.; Groth, M.; Bley, T.A.; Regier, M.; Ittrich, H.; Adam, G.; Bannas, P. [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Nuechtern, J.V. [University Medical Center Hamburg-Eppendorf, Department of Trauma, Hand and Reconstructive Surgery, Hamburg (Germany); Treszl, A. [University Medical Center Hamburg-Eppendorf, Center for Experimental Medicine, Department of Medical Biometry and Epidemiology, Hamburg (Germany)

2012-10-15

To prove the feasibility of using Hounsfield attenuation values at MDCT to detect bone bruises related to sacral insufficiency fractures. Twenty-two patients with acute sacrum trauma and no fracture findings at MDCT were included in our prospective study. Two observers independently reviewed CTs regarding visual signs of bone bruises in 132 defined regions of the sacral alae. Interobserver agreement was tested by {kappa} statistics. Subsequently, HU values were obtained in the same regions, and attenuation differences between the two sides were calculated. Validity and reliability were assessed by intraclass correlation coefficient and Bland-Altman analysis. HU differences were subjected to ROC curve analysis to determine sensitivity, specificity, PPV and NPV. MRI served as standard reference. MRI revealed 19 regions with bone bruises and associated sacral insufficiency fractures. HU measurements demonstrated good validity and reliability (r = 0.989). ROC curve analysis exhibited an ideal cutoff value of 35.7 HU density difference between affected and non-affected regions. Visual evaluation revealed moderate agreement ({kappa} = 0.48); diagnostic accuracy was inferior to objective evaluation. Assessment of differences in bone marrow density by HU measurements is an objective and reliable tool for detection of bone bruises associated with occult sacral insufficiency fractures. (orig.)

Follow-up of breast cancer by bone scintigraphy

International Nuclear Information System (INIS)

Garcia N, E.; Castro, F.; Miranda, R.; Leon, L.; Bustamante, G.; Escobar, M.

2004-01-01

Full text: Breast cancer is one of the most common cancers in women. It is the second most widespread cancer in Mexican women. Among the several methods for diagnosis and follow up of the disease, tumor markers like CA-53 have high sensitivity and specificity. Bone scan is a useful method in the detection of bone metastases. In comparison to other diagnostic modalities, bone scan is more sensitive and less expensive for detection of early bone abnormalities and hence to select an appropriate treatment for better prognosis. In our country, in about 70% of cases diagnosis of breast cancer is made when the disease is in an advanced state - states III and IV. The aim of this study was to evaluate the follow up of breast cancer by bone scans and to correlate these findings with the stage of the disease and other diagnostic modalities. The work was carried out at Mexican General Hospital. A total of 350 patients with breast tumor were included; bone scans were performed in all patients at the time of clinical diagnosis and at every 6 months for a period of 1 to 5 years using an Elscint APEX SP6 HR gamma camera coupled with ultra high resolution collimator. Scan was performed 2-3 hours after intravenous administration of 555-925 MBq of Tc-99m methyl diphosphonate. Tumor classification was made according to TNM criteria. Serum levels of alkaline phosphates, carcino-embrionic antigen (CEA) and Ca 53 were also measured on the same day. Fifty-one patients confirmed to have a diagnosis of benign breast were excluded from the study group. Of the remaining 299 patients, 89 (39%) were between 41 years to 50 years, 69 between 51 to 60 years. The clinical stage most commonly observed was stage III (n=164, 54%) followed by stage II (25%). In 59.5% of patients, scintigraphy showed bone metastasis. Four patients with bone metastases showed regression and 42 (14%) with negative scans became positive on follow up bone scans. Ninety-three patients were free of bone metastases during all

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

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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.

Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

International Nuclear Information System (INIS)

Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V.

1990-01-01

Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases

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

Study of radiation dose attenuation by skull bone in head during radiotherapy treatment using MCNP

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Menezes, Artur F.; Boia, Leonardo S.; Trombetta, Debora M.; Martins, Maximiano C.; Reis Junior, Juraci P.; Silva, Ademir X., E-mail: ademir@con.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), RJ (Brazil). Programa de Engenharia Nuclear; Batista, Delano V.S., E-mail: delano@inca.gov.b [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Dept. de Fisica Medica

2011-07-01

In this study the MCNPX code was used to investigate possible influences of the attenuation beam by the surface bone during radiotherapy treatments of the skull. The computer simulation was performed on topographic image obtained from the National Cancer Institute, in Rio de Janeiro, database of patients treated with radiotherapy. The image segmentation process were performed using the SAPDI program developed to this purpose. The segmented image conversion for the input file recognized by MCNPX code was performed by SCAN2MCNP Software. The simulation was done using 10MeV Clinac 2300C spectrum considering two opposite parallel beams, with field size 2x2 and 4x4 cm{sup 2}, incident on a slice located above the eyes, containing two row of detectors positioned on the central region with a radius of 0.03 cm and arranged perpendicular to the radiation beams. After analyze the results, the relative error values in the range of 2 at 4% for the high dose region, and 26 at 37% for the low dose area were found, respectively. These differences were attributed to the radiation field attenuation on the bone surface at the entrance of the beam. It was observed that most situations on the high dose region the beam profile, from more realistic scenarios, became smaller than the one obtained when the tomography image was considered consisting of water. However for the low dose area the profile, obtained of the realistic situation, became higher than the one which was obtained when the tomography image was considered consisting of water. The results showed significant differences between both analyzed cases which show the need to use a correction factor by the treatment planning system used in radiotherapy services when the real chemical composition of patient head is unconsidered during the patient treatment planning. (author)

Study of radiation dose attenuation by skull bone in head during radiotherapy treatment using MCNP

International Nuclear Information System (INIS)

Menezes, Artur F.; Boia, Leonardo S.; Trombetta, Debora M.; Martins, Maximiano C.; Reis Junior, Juraci P.; Silva, Ademir X.; Batista, Delano V.S.

2011-01-01

In this study the MCNPX code was used to investigate possible influences of the attenuation beam by the surface bone during radiotherapy treatments of the skull. The computer simulation was performed on topographic image obtained from the National Cancer Institute, in Rio de Janeiro, database of patients treated with radiotherapy. The image segmentation process were performed using the SAPDI program developed to this purpose. The segmented image conversion for the input file recognized by MCNPX code was performed by SCAN2MCNP Software. The simulation was done using 10MeV Clinac 2300C spectrum considering two opposite parallel beams, with field size 2x2 and 4x4 cm 2 , incident on a slice located above the eyes, containing two row of detectors positioned on the central region with a radius of 0.03 cm and arranged perpendicular to the radiation beams. After analyze the results, the relative error values in the range of 2 at 4% for the high dose region, and 26 at 37% for the low dose area were found, respectively. These differences were attributed to the radiation field attenuation on the bone surface at the entrance of the beam. It was observed that most situations on the high dose region the beam profile, from more realistic scenarios, became smaller than the one obtained when the tomography image was considered consisting of water. However for the low dose area the profile, obtained of the realistic situation, became higher than the one which was obtained when the tomography image was considered consisting of water. The results showed significant differences between both analyzed cases which show the need to use a correction factor by the treatment planning system used in radiotherapy services when the real chemical composition of patient head is unconsidered during the patient treatment planning. (author)

Multifunctional materials for bone cancer treatment

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Marques C

2014-05-01

Full Text Available Catarina Marques,1 José MF Ferreira,1 Ecaterina Andronescu,2 Denisa Ficai,2 Maria Sonmez,3 Anton Ficai21Department of Materials and Ceramics Engineering, Centre for Research in Ceramics and Composite Materials, University of Aveiro, Aveiro, Portugal; 2Faculty of Applied Chemistry and Material Science, University Politehnica of Bucharest, Bucharest, Romania; 3National Research and Development Institute for Textiles and Leather, Bucharest, RomaniaAbstract: The purpose of this review is to present the most recent findings in bone tissue engineering. Special attention is given to multifunctional materials based on collagen and collagen–hydroxyapatite composites used for skin and bone cancer treatments. The multifunctionality of these materials was obtained by adding to the base regenerative grafts proper components, such as ferrites (magnetite being the most important representative, cytostatics (cisplatin, carboplatin, vincristine, methotrexate, paclitaxel, doxorubicin, silver nanoparticles, antibiotics (anthracyclines, geldanamycin, and/or analgesics (ibuprofen, fentanyl. The suitability of complex systems for the intended applications was systematically analyzed. The developmental possibilities of multifunctional materials with regenerative and curative roles (antitumoral as well as pain management in the field of skin and bone cancer treatment are discussed. It is worth mentioning that better materials are likely to be developed by combining conventional and unconventional experimental strategies.Keywords: bone graft, cancer, collagen, magnetite, cytostatics, silver

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

Correction of quantification errors in pelvic and spinal lesions caused by ignoring higher photon attenuation of bone in [{sup 18}F]NaF PET/MR

Energy Technology Data Exchange (ETDEWEB)

Schramm, Georg, E-mail: georg.schramm@kuleuven.be; Maus, Jens; Hofheinz, Frank; Petr, Jan; Lougovski, Alexandr [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden 01328 (Germany); Beuthien-Baumann, Bettina; Oehme, Liane [Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Dresden 01307 (Germany); Platzek, Ivan [Department of Radiology, University Hospital Carl Gustav Carus, Dresden 01307 (Germany); Hoff, Jörg van den [Helmholtz-Zentrum Dresden-Rossendorf, Institute for Radiopharmaceutical Cancer Research, Dresden 01328 (Germany); Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Dresden 01307 (Germany)

2015-11-15

Purpose: MR-based attenuation correction (MRAC) in routine clinical whole-body positron emission tomography and magnetic resonance imaging (PET/MRI) is based on tissue type segmentation. Due to lack of MR signal in cortical bone and the varying signal of spongeous bone, standard whole-body segmentation-based MRAC ignores the higher attenuation of bone compared to the one of soft tissue (MRAC{sub nobone}). The authors aim to quantify and reduce the bias introduced by MRAC{sub nobone} in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [{sup 18}F]NaF. Methods: The authors reconstructed 20 PET/MR [{sup 18}F]NaF patient data sets acquired with a Philips Ingenuity TF PET/MRI. The PET raw data were reconstructed with two different attenuation images. First, the authors used the vendor-provided MRAC algorithm that ignores the higher attenuation of bone to reconstruct PET{sub nobone}. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [{sup 18}F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm{sup −1} was assigned to the segmented bone regions in the MRI-based attenuation image (MRAC{sub bone}) which was used to reconstruct PET{sub bone}. The automatic bone segmentation algorithm was validated in six PET/CT [{sup 18}F]NaF examinations. Relative SUV{sub mean} and SUV{sub max} differences between PET{sub bone} and PET{sub nobone} of 8 pelvic and 41 spinal lesions, and of other regions such as lung, liver, and bladder, were calculated. By varying the assigned bone attenuation coefficient from 0.11 to 0.13 cm{sup −1}, the authors investigated its influence on the reconstructed SUVs of the lesions. Results: The comparison of [{sup 18}F]NaF-based and CT-based bone segmentation in the six PET/CT patients showed a Dice similarity of 0.7 with a true positive rate of 0.72 and a false discovery rate of 0.33. The [{sup 18}F]NaF-based bone

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%.

Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

Directory of Open Access Journals (Sweden)

Roger von Moos

2013-08-01

Full Text Available Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.

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)

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

International Nuclear Information System (INIS)

Li Li; Jin Jianhua

2014-01-01

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

Bone morphogenetic protein signalling in colorectal cancer

NARCIS (Netherlands)

Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

2008-01-01

Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

Science.gov (United States)

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

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

Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

National Research Council Canada - National Science Library

Navone, Nora

2001-01-01

.... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

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)

Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

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Ya-Qun Zhou

2018-04-01

Full Text Available Cancer-induced bone pain (CIBP is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100 mg/kg and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200 mg/kg significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord. Keywords: Cancer-induced bone pain, Reactive oxygen species, PBN, Tempol

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

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Xiong Z

2018-02-01

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

Bone marrow radioimmune scintigraphy in the assessment of breast cancer treatment

International Nuclear Information System (INIS)

Klissarova, A.; Georgieva, Zh.; Tsekov, H.; Temelkov, T.

2004-01-01

Full text: Breast cancer is the most common cancer, affecting women in all developed countries of the world. 60 to 70% of women who die with breast cancer have bone metastases. These metastases are currently detected by means of bone scintigraphy and X-ray examinations. Serial bone scans provide significant prognostic information but the assessment of the treatment response remains a problem as the 'flare phenomena' seen shortly after treatment causes difficulty in interpretation of the bone scan. Moreover, an unchanged bone scan findings do not always indicate poor / absent response to therapy. The assessment of bone marrow regeneration in patients with breast cancer is important because it is the primary site of metastases. The aim of this study was to assess the efficacy of chemotherapy treatment in patients with breast cancer by means of radioimmuno bone marrow scintigraphy. We studied 15 patients (mean age 63 years) with advanced breast cancer (II - III stage) and bone metastases revealed by whole body bone scintigraphy and X-ray examination. All patients were treated with two courses of chemotherapy with FEC (Farmorubicin, Cyclophosphamide and 5-Fuoracil) at an interval of four weeks. After the treatment, all patients underwent bone marrow radioimmuno scintigraphy with AGMoAb BW 250/183 (Granulozyt). The AGMoAb was injected by slow intravenous injection in a dose 0.5 mg labelled with 740 Mbq of Tc-99m in a volume of 2 ml of. The images were obtained between 5 - 6 hours after the injection. Whole body scan was performed in anterior and posterior views under a gamma camera (DIACAM-Siemens) coupled with low energy collimator. Radioimmuno imaging before surgery and chemotherapy showed absence of granulopoeitic bone marrow in many areas of the skeleton coinciding with the bone metastases detected by bone scintigraphy. Radioimmuno imaging performed after chemotherapy demonstrated presence of bone marrow in 8 patients (53%) in areas where it was previously absent

Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis

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Yonghui Dong

2016-06-01

Full Text Available Previous studies showed that SDF-1α is a catabolic factor that can infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity. Inhibiting the SDF-1α/CXCR4 signalling pathway can attenuate the pathogenesis of osteoarthritis (OA. Recent studies have also shown that SDF-1α enhances chondrocyte proliferation and maturation. These results appear to be contradictory. In the current study, we used a destabilisation OA animal model to investigate the effects of SDF-1α/CXCR4 signalling in the tibial subchondral bone and the OA pathological process. Post-traumatic osteoarthritis (PTOA mice models were prepared by transecting the anterior cruciate ligament (ACLT, or a sham surgery was performed, in a total of 30 mice. Mice were treated with phosphate buffer saline (PBS or AMD3100 (an inhibitor of CXCR4 and sacrificed at 30 days post ACLT or sham surgery. Tibial subchondral bone status was quantified by micro-computed tomography (μCT. Knee-joint histology was analysed to examine the articular cartilage and joint degeneration. The levels of SDF-1α and collagen type I c-telopeptidefragments (CTX-I were quantified by ELISA. Bone marrow mononuclear cells (BMMCs were used to clarify the effects of SDF-1α on osteoclast formation and activity in vivo. μCT analysis revealed significant loss of trabecular bone from tibial subchondral bone post-ACLT, which was effectively prevented by AMD3100. AMD3100 could partially prevent bone loss and articular cartilage degeneration. Serum biomarkers revealed an increase in SDF-1α and bone resorption, which were also reduced by AMD3100. SDF-1α can promote osteoclast formation and the expression oftartrate resistant acid phosphatase (TRAP, cathepsin K (CK, and matrix metalloproteinase (MMP-9 in osteoclasts by activating the MAPK pathway, including ERK and p38, but not JNK. In conclusion, inhibition of SDF-1α/CXCR4signalling was able to prevent trabecular bone loss and attenuated cartilage

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.

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

Science.gov (United States)

Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

2015-12-01

Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Awareness, concern, and communication between physicians and patients on bone health in cancer.

Science.gov (United States)

Tripathy, Debu; Durie, Brian G M; Mautner, Beatrice; Ferenz, Krag S; Moul, Judd W

2014-06-01

This study aims to explore physician-patient communications about bone metastases and cancer treatment-induced bone loss (CTIBL). The study utilizes online survey of patients with breast cancer, prostate cancer, and multiple myeloma, and the physicians who treat them. Even though 69 and 48 % of patients with nonmetastatic breast and prostate cancer aware of treatment-induced bone loss, only 39 and 23 %, respectively, were concerned about bone loss. Yet, 62 and 71 % of oncologists treating breast and prostate cancer felt that their patients were concerned. Among patients with metastatic breast and prostate cancer, two thirds had not discussed treatment for bone metastases with their doctor; when discussed, 88 and 91 % of discussions were initiated by the doctor, usually prior to initiating treatment. Most myeloma patients (77 %) had discussed treatment options with their physicians; 99 % of hematologists reported discussing treatment of bone disease with patients. Physicians are primary sources of information to patients regarding bone health. There is a gap between what physicians assume their patients know about bone health and the patients' perceptions, presenting a need for systematic awareness and education.

Cost of palliative radiation to the bone for patients with bone metastases secondary to breast or prostate cancer

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Hess Gregory

2012-10-01

Full Text Available Abstract Background To estimate the costs (paid amounts of palliative radiation episodes of care (REOCs to the bone for patients with bone metastases secondary to breast or prostate cancer. Methods Claims-linked medical records from patients at 98 cancer treatment centers in 16 US states were analyzed. Inclusion criteria included a primary neoplasm of breast or prostate cancer with a secondary neoplasm of bone metastases; ≥2 visits to ≥1 radiation center during the study period (1 July 2008 through 31 December 2009 on or after the metastatic cancer diagnosis date; radiation therapy to ≥1 bone site; and ≥1 complete REOC as evidenced by a >30-day gap pre- and post-radiation therapy. Results The total number of REOCs was 220 for 207 breast cancer patients and 233 for 213 prostate cancer patients. In the main analysis (which excluded records with unpopulated costs the median number of fractions per a REOC for treatment of metastases was 10. Mean total radiation costs (i.e., radiation direct cost + cost of radiation-related procedures and visits per REOC were $7457 for patients with breast cancer and $7553 for patients with prostate cancer. Results were consistent in sensitivity analyses excluding patients with unpopulated costs. Conclusions In the US, current use of radiation therapy for bone metastases is relatively costly and the use of multi-fraction schedules remains prevalent.

Bone metastases from breast cancer at the time or radical mastectomy as detected by bone scan. Eight-year follow-up.

Science.gov (United States)

Sklaroff, R B; Sklaroff, D M

1976-07-01

Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.

Mechanisms of, and Adjuvants for, Bone Pain.

Science.gov (United States)

Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

2018-06-01

Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnostic performance of [18F] FDG PET-CT compared to bone scintigraphy for the detection of bone metastases in lung cancer patients

International Nuclear Information System (INIS)

RODRIGUES, Margarida; STARK, Hannes; RENDL, Gundula; RETTENBACHER, Lukas; PIRICH, Christian; DATZ, Lidwina; STUDNICKA, Michael

2016-01-01

Accurate staging of lung cancer is essential for effective patient management and selection of appropriate therapeutic strategy. The aim of this paper was to compare the value of bone scintigraphy and FDG PET-CT for detecting bone metastases in lung cancer patients and the impact of these modalities in disease staging. One hundred sixty-four lung cancer patients who had undergone both FDG PET-CT and bone scintigraphy within 14 days were included into this study. The analysis of FDG PET-CT and bone scintigraphy was carried out patient- and lesion-based. One hundred twenty-one patients were negative and 43 patients positive for bone metastases. FDG PET-CT found bone metastases in 42/43 patients and bone scintigraphy in 38/43 patients. Sensitivity, specificity and accuracy of FDG PET-CT and bone scintigraphy for detecting bone metastases were 97.7%, 100% and 99.4%, and 87.8%, 97.5% and 94.2%, respectively. FDG PET-CT identified 430 bone metastases and bone scintigraphy 246 bone metastases. Skull was the only region where bone scintigraphy identified more lesions than FDG PET-CT. Based on both scintigraphic modalities disagreement concerning disease stage was found in 3 patients. In conclusion, FDG PET-CT yielded a higher sensitivity, specificity and accuracy than bone scintigraphy for identifying bone metastases in lung cancer patients. FDG PET-CT thus can be recommended for initial staging of lung cancer patients without applying bone scintigraphy for the detection of bone metastases.

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.

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.

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.)

Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

National Research Council Canada - National Science Library

Reddi, A

2003-01-01

...? The predominant site of prostate cancer is bone. However, unlike the osteolytic lesions of breast cancer, prostate cancer causes osteoblastic osteosclerosis which leads ultimately to morbidity and mortality...

Carbenoxolone as a novel therapy for attenuation of cancer-induced bone pain

DEFF Research Database (Denmark)

Falk, Sarah

2018-01-01

to elucidate the underlying mechanisms using the two specific blockers 37,43Gap27 and 43Gap26. Compared with vehicle treatment, chronic systemic administration of 20 mg/kg or 40 mg/kg carbenoxolone caused a significantly later onset and attenuation of movement-evoked and on-going pain, assessed with limb use...... and weight-bearing respectively. In addition, the carbenoxolone-treated groups demonstrated a significant delay in time to reach the humane endpoint. Acute intrathecal administration of 37,43Gap27 significantly attenuated both limb use and weight-bearing, whereas 43Gap26 had a less pronounced effect...

Relationship of natural incidence and radiosensitivity for bone cancer in dogs

International Nuclear Information System (INIS)

Taylor, G.N.; Lloyd, R.D.; Miller, S.C.; Jee, W.S.S.

1997-01-01

A comparison of the risk coefficients for 239 Pu- or 226 Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239 Pu and 226 Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239 Pu: 226 Ra open-quotes toxicity ratiosclose quotes for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radio nuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid. 26 refs., 5 tabs

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

Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

International Nuclear Information System (INIS)

Saber, M.M.; Shouman, T.

2003-01-01

To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

Disseminated carcinomatosis of the bone marrow from pancreatic cancer: a case report

International Nuclear Information System (INIS)

Namikawa, Hiroki; Takemoto, Yasuhiko; Makuuchi, Ayako; Kobayashi, Masanori; Kinuhata, Shigeki; Morimura, Mina; Ikebe, Takashi; Tanaka, Hiromu; Shuto, Taichi

2016-01-01

Most cases of disseminated carcinomatosis of the bone marrow (DCBM) arise from gastric cancer. DCBM from pancreatic cancer is very rare. We herein present a case of DCBM from pancreatic cancer. A 57-year-old man was referred to our hospital for severe lumbago. Laboratory data indicated that he suffered from disseminated intravascular coagulation (DIC). Non-contrast abdominal computed tomography (CT) revealed multiple bone masses but no other abnormal findings. Left iliac bone marrow biopsy revealed poorly differentiated adenocarcinoma cells. Positron emission tomography (PET)-CT showed diffuse abnormal uptake in the bones and tail of the pancreas. Contrast whole-body CT showed a tumor measuring approximately 28 mm in diameter with poor enhancement in the tail of the pancreas. The patient’s final diagnosis was pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC. His DCBM was thus believed to originate from the pancreatic cancer. He succumbed to the disease approximately 2 months after admission to our hospital. We herein describe a case of pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC, which, in our case, was DCBM. Therefore, in cases of DCBM with an unknown primary tumor, pancreatic cancer should be considered during differential diagnosis

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)

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

Science.gov (United States)

Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

2017-09-01

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

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 Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

DEFF Research Database (Denmark)

Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

2017-01-01

Pain is a severe and debilitating complication of metastatic bone cancer. Current analgesics do not provide sufficient pain relief for all patients, creating a great need for new treatment options. The Src kinase, a non-receptor protein tyrosine kinase, is implicated in processes involved in cancer......-induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

Bone mineral density deficits in childhood cancer survivors: Pathophysiology, prevalence, screening, and management

Directory of Open Access Journals (Sweden)

Min Jae Kang

2013-02-01

Full Text Available As chemotherapy and other sophisticated treatment strategies evolve and the number of survivors of long-term childhood cancer grows, the long-term complications of treatment and the cancer itself are becoming ever more important. One of the most important but often neglected complications is osteoporosis and increased risk of fracture during and after cancer treatment. Acquisition of optimal peak bone mass and strength during childhood and adolescence is critical to preventing osteoporosis later in life. However, most childhood cancer patients have multiple risk factors for bone mineral loss. Cancer itself, malnutrition, decreased physical activity during treatment, chemotherapeutic agents such as steroids, and radiotherapy cause bone mineral deficit. Furthermore, complications such as growth hormone deficiency and musculoskeletal deformity have negative effects on bone metabolism. Low bone mineral density is associated with fractures, skeletal deformity, pain, and substantial financial burden not only for childhood cancer survivors but also for public health care systems. Thus, it is important to monitor bone health in these patients and minimize their risk of developing osteoporosis and fragility fractures later in life.

SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

Directory of Open Access Journals (Sweden)

S. V. Kostritsky

2014-07-01

Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

Directory of Open Access Journals (Sweden)

S. V. Kostritsky

2013-01-01

Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

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.

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

Science.gov (United States)

Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Definition of molecular determinants of prostate cancer cell bone extravasation.

Science.gov (United States)

Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

2013-01-15

Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

P2X7 receptor-deficient mice are susceptible to bone cancer pain

DEFF Research Database (Denmark)

Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat

2011-01-01

The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state...

Bone scintiscanning significance in breast cancer propaedeutics

Energy Technology Data Exchange (ETDEWEB)

de Almeida, J S; Fahel, V G; de Almeida, M R.M.; Hassan, A T; Hassan, E M.M.T. [Hospital Aristides Maltez, Salvador (Brazil). Servico de Medicina Nuclear

1977-01-01

An evaluation was performed of 139 bone scannings which were accomplished in patients with breast cancer. Bone scintigraphy was concluded to be more important than the radiological examination in this propedeutic. The increase of alkaline phosphatase was very significative too, since there was only one case in which it was increased and the bone scanning was negative and even so the liver scanning was positive. On the other hand there were cases which showed positive both bone scanning and radiological study although the alkaline phosphatase was not increase. The necessity of realizing this examination was emphazised even in initial cases, making possible to modify therapeutic shedules in time, to help patient.

The use of bone scintigraphy to establish cancer extension records: application to prostate and breast cancers

International Nuclear Information System (INIS)

Methlin, G.; Grob, J.C.; Moyses, B.; Deschler, J.M.; Ott, G.; Berthelen, B.

1975-01-01

The recent development of the technique described, especially in the systematic search for metastases was due to the introduction of stannous diphosphate complexed with sup(99m)Tc well suited to bone scintigraphy. The documents are obtained in two stages. First a whole-body scintigraph is taken by means of an omniview device fitted to a Picker dynacamera, and this scanning phase is followed immediately by static views centred mainly on abnormal or doubtful regions. The results are given for 136 breast cancers and 61 prostate cancers, two cancers particularly liable to affect the bone, and show that scintigraphy offers positive advantages over radiological investigations. These advantages are offset to some extent by the non-specific nature of the hyperfixing regions since different diseases involving changes in the bone structure can give similar images, but for breast and prostate cancers bone scintigraphy presents distinct possibilities in the search for metastases of the skeleton [fr

186Re-HEDP for metastatic bone pain in breast cancer patients

International Nuclear Information System (INIS)

Lam, Marnix G.E.H.; Rijk, Peter P. van; Klerk, John M.H. de

2004-01-01

Two-thirds of patients with metastatic cancer suffer from pain. Pain originating from skeletal metastases is the most common form of cancer-related pain. Bone pain, often exacerbated by pressure or movement, limits the patient's autonomy and social life. Pain palliation with bone-seeking radiopharmaceuticals has proven to be an effective treatment modality in patients with metastatic bone pain. These bone-seeking radiopharmaceuticals are extremely powerful in treating scattered painful bone metastases, for which external beam radiotherapy is impossible because of the large field of irradiation. 186 Re-hydroxyethylidene diphosphonate (HEDP) is a potentially useful radiopharmaceutical for this purpose, having numerous advantageous characteristics. Bone marrow toxicity is limited and reversible, which makes repetitive treatment safe. Studies have shown encouraging clinical results of palliative therapy using 186 Re-HEDP, with an overall response rate of ca. 70% in painful bone metastases. It is effective for fast palliation of painful bone metastases from various tumours and the effect tends to last longer if patients are treated early in the course of their disease. 186 Re-HEDP is at least as effective in breast cancer patients with painful bone metastases as in patients with metastatic prostate cancer. It is to be preferred to radiopharmaceuticals with a long physical half-life in this group of patients, who tend to have more extensive haematological toxicity since they have frequently been pretreated with bone marrow suppressive chemotherapy. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. (orig.)

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)

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)

Measurement of attenuation coefficients for bone, muscle, fat and water at 140, 364 and 662keV γ-ray energies

International Nuclear Information System (INIS)

Akar, A.; Baltas, H.; Cevik, U.; Korkmaz, F.; Okumusoglu, N.T.

2006-01-01

The half-value thicknesses, linear and mass attenuation coefficients of biological samples such as bone, muscle, fat and water have been measured at 140, 364 and 662keV γ-ray energies by using the ATOMLAB TM -930 medical spectrometer. The γ-rays were obtained from 99m Tc, 131 I and 137 Cs γ-ray point sources. Also theoretical calculations have been performed in order to obtain the half-value thicknesses and, mass and linear attenuation coefficients at photon energies 0.001keV-20MeV for bone, muscle and water samples. The calculated value and the experimental results of this work and the other results in literature are found to be in good agreement

Novel anti-cancer strategy in bone tumors by targeting molecular and cellular modulators of bone resorption.

Science.gov (United States)

Brounais, Bénédicte; Ruiz, Carmen; Rousseau, Julie; Lamoureux, François; Blanchard, Frédéric; Heymann, Dominique; Redini, Françoise

2008-11-01

Tumor cells alter the balanced process of bone formation and bone resorption mediated respectively by osteoblasts and osteoclasts, leading to the disruption of the normal equilibrium and resulting in a spectrum of osteolytic to osteoblastic lesions. This review will summarize research on molecules that play direct and essential roles in the differentiation and activity of osteoclasts, and the role of these molecules in bone destruction caused by cancer. Results from experimental models suggest that the Receptor Activator of NF-kB Ligand (RANKL), a member of the TNF superfamily is a common effector of bony lesions in osteolysis caused by primary and secondary bone tumors. Therefore, osteoclast represents an attractive target across a broad range of tumors that develop in bone. Elucidation of the mechanisms of RANKL interactions with its activator (RANK) and decoy (osteoprotegerin: OPG) receptors has enable the development of pharmacological inhibitors of RANKL (and of its signalling pathway) which have been recently patented, with potential for the treatment of cancer-induced bone disease. Blocking bone resorption by specific other drugs such as bisphosphonates, inhibitors of cathepsin K (the main enzyme involved in bone resorption mechanisms) or signalling pathways regulating osteoclast differentiation and activation is also a promising target for the treatment of osteolysis associated to bone tumors.

The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

International Nuclear Information System (INIS)

Tabak, Daniel

1997-01-01

This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

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)

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.

The Role of Purinergic Receptors in Cancer-Induced Bone Pain

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Sarah Falk

2012-01-01

Full Text Available Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

Bone scintiscanning significance in breast cancer propaedeutics

International Nuclear Information System (INIS)

Almeida, J.S. de; Fahel, V.G.; Almeida, M.R.M. de; Hassan, A.T.; Hassan, E.M.M.T.

1977-01-01

An evaluation was performed of 139 bone scannings which were accomplished in patients with breast cancer. Bone scintigraphy was concluded to be more important than the radiological examination in this propedeutic. The increase of alkaline phosphatase was very significative too, since there was only one case in which it was increased and the bone scanning was negative and even so the liver scanning was positive. On the other hand there were cases which showed positive both bone scanning and radiological study although the alkaline phosphatase was not increase. The necessity of realizing this examination was emphazised even in initial cases, making possible to modify therapeutic shedules in time, to help patient [pt

The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

DEFF Research Database (Denmark)

Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

2017-01-01

-induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

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).

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

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Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Liu, Jianwen, E-mail: liujian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Ni, Lei, E-mail: nilei625@yahoo.com [Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai 200025 (China)

2014-07-18

Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

International Nuclear Information System (INIS)

Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei

2014-01-01

Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer

Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

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Chiaming Fan

2011-01-01

Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

Cancer of the prostate presenting with diffuse osteolytic metastatic bone lesions: a case report

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Segamwenge Innocent Lule

2012-12-01

Full Text Available Abstract Introduction Prostate cancer is the second most common cancer in men and the fifth most common cancer worldwide. In the USA it is more common in African-American men than in Caucasian men. Prostate cancer frequently metastasizes to bone and the lesions appear osteoblastic on radiographs. Presentation with diffuse osteolytic bone lesions is rare. We describe an unusual presentation of metastatic prostate cancer with diffuse osteolytic bone lesions. Case presentation A 65-year-old Namibian man presented with anemia, thrombocytopenia and worsening back pains. In addition he had complaints of effort intolerance, palpitations, dysuria and mild symptoms of bladder outlet obstruction. On examination he was found to be anemic, had a swollen tender right shoulder joint and spine tenderness to percussion. On digital rectal examination he had asymmetrical enlargement of the prostate which felt nodular and hard with diffuse firmness in some parts. His prostate-specific antigen was greater than 100ng/mL and he had diffuse osteolytic lesions involving the right humerus, and all vertebral, femur and pelvic bones. His screen for multiple myeloma was negative and the prostate biopsy confirmed prostate cancer. Conclusion Prostate cancer rarely presents with diffuse osteolytic bone lesions and should be considered in the differential diagnosis when evaluating male patients with osteolytic bone lesions.

Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

Science.gov (United States)

Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

2012-10-01

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

Science.gov (United States)

Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

2017-02-01

The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Module for applications of bone scan in cancer patients

International Nuclear Information System (INIS)

Morales, Rosanna; Cano, Roque; Velasquez, Maria; Vasquez, Edinson; Diaz, Pepe; Vasquez, Mario; Rojas, Peter

2013-01-01

This paper reports the application of a software which enables the complete register of patient data, for delivering appropriate information in bone scan reports. Bone scan is a frequent study in Nuclear Medicine, which enables physicians to diagnose a primary bone cancer or metastases. The software was designed in order to complete data given by oncologists and constitutes an aid for the health team attending patients. (authors).

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

Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

International Nuclear Information System (INIS)

Richardson, R.B.

2007-01-01

The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 μm thick endosteum to a 50 μm peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

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

Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute

International Nuclear Information System (INIS)

Elgamal, B.M.; Rashed, R.A.; Raslan, H.N.

2011-01-01

Bone marrow necrosis; Egyptian cancer patients Abstract Background: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. Methods: study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). Results: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. Conclusion: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome

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.)

Research of bone metastases in prostate cancer: scintigraphy and radiological study

International Nuclear Information System (INIS)

Seibel, I.; Monteiro, T.S.

1981-01-01

This paper analyses the results of bone scan and radiologic study of the bones on the search of metastases of prostate cancer seen in the last two years. In 44 patients with prostatic cancer the diagnostic of metastatic disease was made by the 99m Tc scan in 52%, and by the metastatic radiologic survey in only 25%. (author)

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...

Influence of sex differences on the progression of cancer-induced bone pain

DEFF Research Database (Denmark)

Falk, Sarah; Uldall, Maria; Appel, Camilla

2013-01-01

Background: Pain caused by bone metastases has a severe impact on the quality of life for many patients with cancer. Good translational in vivo models are required to understand the molecular mechanism and develop better treatment. In the current study we evaluated the influence of sex differences...... on the progression of cancer-induced bone pain. Materials and Methods: 4T1-luc2 mammary cancer cells were introduced into the femoral cavity of female and male BALB/cJ mice. Bioluminescence tumor signal, pain-related behavior and bone degradation were monitored for 14 days. Results: Female mice demonstrated...... a significantly greater bioluminescence signal on day 2 compared to male mice and, in addition, a significant earlier onset of pain-related behavior was observed in the females. No sex difference was observed for bone degradation. Finally, a strong correlation between pain-related behavior and bone degradation...

P2X7 Receptor Function in Bone-Related Cancer

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Elena Adinolfi

2012-01-01

Full Text Available Modulation of tumor microenvironment by different mediators is central in determining neoplastic formation and progression. Among these molecules extracellular ATP is emerging as a good candidate in promoting cell growth, neovascularization, tumor-host interactions, and metastatization. This paper summarizes recent findings on expression and function of P2X7 receptor for extracellular ATP in primary and metastatic bone cancers. Search of mRNA expression microchip databases and literature analysis demonstrate a high expression of P2X7 in primary bone tumors as well as in other malignancies such as multiple myeloma, neuroblastoma, breast, and prostate cancer. Evidence that P2X7 triggers NFATc1, PI3K/Akt, ROCK, and VEGF pathways in osteoblasts promoting either primary tumor development or osteoblastic lesions is also reported. Moreover, P2X7 receptor is involved in osteoclast differentiation, RANKL expression, matrix metalloproteases and cathepsin secretion thus promoting bone resorption and osteolytic lesions. Taken together these data point to a pivotal role for the P2X7 receptor in bone cancer biology.

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

International Nuclear Information System (INIS)

Bombardieri, E.; Martinetti, A.; Castellani, M.R.; Seregni, E.; Miceli, R.; Mariani, L.

1997-01-01

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. (orig.)

Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

Directory of Open Access Journals (Sweden)

Katsuya Morita

Full Text Available Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2 protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

Radiotherapy for bone metastases from cervical cancer

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Monzen, Yoshio; Nakanishi, Kazue; Ajimu, Akira; Morikawa, Minoru; Hayashi, Kuniaki

1989-03-01

The authors have investigated 6 cases of bone metastases from cervical cancer out of a total of 90 cases of metastatic bone tumors that were irradiated for relief of associated pain at the Department of Radiology, Nagasaki University Hospital from April 1977 to March 1987. In 2 of the 6 cases, a rare, delayed recurrence with paraaortic lymph node metastases was seen. An invasion to the proasmajor muscle, iliomajor muscle was demonstrated by Computed Tomography after the initiation of therapy, so that the size of the field was modified. Computed Tomography was found useful to determine the exact field size for radiotherapy of metastatic bone tumor.

Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

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Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

2014-01-01

Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

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Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

2007-01-01

Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

SPECT-CT bone scintigraphy in cancer patients

International Nuclear Information System (INIS)

Sergieva, S; Alexandrova, A.; Nikolova, N.; Dimcheva, M.; Baichev, G.

2012-01-01

Full text: Introduction: SPECT-CT study allows the precise correlation between functional and morphological data on the same image. Methods: Whole body bone scan (WBBS) is a diagnostic modality still firmly established as a valuable tool to assess skeleton abnormalities. CT is an imaging method for characterizing destruction of the bone spongy lesions, their consolidation or calcium accumulation. This fact allows differentiation of the osteolytic metastases from the osteosclerotic and mixed lesions and also from degenerative ones. Whole body bone scan followed by SPECT-CT scanning increases the accuracy of the study and potentially accelerates the diagnosis of the patient based on a single imaging session. This is especially important in cancer patients. Results and discussion: After retrospectively review of WBBS and SPECT-CT fused images 141 bone lesions in 89 pts were analyzed The skeletal findings with previously uncertain character were classified as definitely benign, indeterminate or definitely malignant. 1. 47 (33%) of all lesions in 36 pts could be correlated with benign degenerative findings on SPECT-CT images. 5 (3%) lesions in 3 of these pts were indeterminate on the SPECT-CT images. They were localized in the area of articulation parts and corpus of the thoracic vertebra and ribs. After additional MRT examination and 6 months follow-up these changes were considered degenerative: osteopathy changes and presence of spondyloarthrosis and osteochondrosis; compression fractures due to advanced osteoporosis. These pts were with prolonged chormono/chemotherapy; chronic inflammatory disease of the coxofemoral articulation, coxarthrosis, aseptic necrosis of the femoral head and postoperative sacroiliitis; post-traumatic fractures or surgical intervention; hyperplastic degenerative lesions in the skeleton and asymmetrical pelvic bone structures due to M. Paget. 2. 41 (28,1%) single osseous metastatic spots (up to 3 foci) were scanned in 31 pts. 3. 13 (10

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

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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.

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

Bone densitometry by gamma ray attenuation measurement. Development of an apparatus for use on medullary casualties

International Nuclear Information System (INIS)

Berard, E.J.-J.

1975-01-01

We proposed to follow changes in the bone mineral content of medullary damage cases by measuring the attenuation of a monoenergetic gamma ray according to the Cameron and Sorenson technique. Apart from their high cost, existing instruments are not designed for this bedside observation of patients. Our aim was therefore to design and develop an easily portable, inexpensive apparatus. The γ radiation is supplied by a sealed 125 I source fitted with a narrow collimator. The battery-operated scintillation detector is that used to detect post-operative phlebites after injection of radio-fibrinogen. The source-detector unit can move to allow a transverse bone mineral content measurement. Data from the detector are processed electronically and the results given: - either graphically on a tracing board which gives an area proportional to the bone mineral content, - or numerically by means of an integrator computing this area and supplying the linear bone density directly. Experiments carried out in vivo showed the apparatus to be sensitive and the measurements reproducible, the results obtained being comparable with those of other authors. Using pieces of embalmed bone moreover an excellent correlation was observed between the bone mineral content obtained after incineration and the results displayed by our apparatus, which can therefore be calibrated [fr

Correlation of bone scintigraphy findings and tumor markers during follow-up prostate cancer

International Nuclear Information System (INIS)

Aizawa, Taku

1996-01-01

In the last 9 years, 217 patients with prostate cancer were treated at our department. Of these patients 153 cases treated by estrogen therapy were followed up by bone scintigraphy and tumor marker examinations (prostate specific antigen [PSA], prostate acid phosphatase [PAP], gamma-seminoprotein [γ-SM) . The correlation between changes on bone scintigrams and synchronous changes in tumor markers was evaluated retrospectively. In cases in which bone metastasis was not recognized on bone scintigrams before treatment, changes of tumor markers corresponded with subsequent changes on bone scintigrams in more than 90%. However, in cases with bone metastasis on bone scintigrams before treatment, changes of bone scintigrams and changes of tumor markers corresponded in only 55% of cases. Changes of bone scintigrams do not always correspond with changes of tumor markers. However, by taking into consideration physical examination parameters such as bone pain, in addition to changes of tumor markers, most changes on bone scintigrams can be anticipated. The reasons for lack of correspondence between changes of bone scintigrams and changes of tumor markers may be, changes of tumor markers are more rapid than the changes on bone scintigram, some poorly differentiated cancers do not have increased tumor marker levels and bone scintigrams do not demonstrate soft tissue involvement. In the follow-up of patients with prostate cancer, it is not necessary to perform bone scintigraphy regularly at 3-month intervals. Bone scintigraphy should only be performed when serum levels of tumor markers increase or bone pain appears. (author)

Clinical observation of 89Sr treatment efficacy of multiple bone metastases in breast and prostate cancer patients

International Nuclear Information System (INIS)

Yuan Chao; Li Weipeng; Hu Yongquan; Tao Jian

2010-01-01

Objective: To evaluate the efficacy of 89 Sr in treatment of multiple bone metastases of breast and prostate cancer patients. Methods: Seventy multiple bone metastases patients (30 females with breast cancer and 40 males with prostate cancer) were treated with 89 Sr. The clinical effectiveness was assessed by Karnofsky performance score and whole body bone scanning data. Results: The total pain relief rate was 79% in bone metastases of breast cancer and 85% in bone metastases of prostate cancer, respectively. There was no significant differences between the two groups (χ 2 =0.78, P>0.05). The Karnofsky score was significantly improved in both groups (t=2.46, P 89 Sr treatment was good, and the quality of life was improved in patients with multiple bone metastases breast or prostate cancer. (authors)

Fermented dairy products consumption is associated with attenuated cortical bone loss independently of total calcium, protein, and energy intakes in healthy postmenopausal women.

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Biver, E; Durosier-Izart, C; Merminod, F; Chevalley, T; van Rietbergen, B; Ferrari, S L; Rizzoli, R

2018-05-03

A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. Fermented dairy products (FDP), including yogurts, provide calcium, phosphorus, and proteins together with prebiotics and probiotics, all being potentially beneficial for bone. In this prospective cohort study, we investigated whether FDP, milk, or ripened cheese consumptions influence age-related changes of bone mineral density (BMD) and microstructure. Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency questionnaire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography, in addition to areal (a) BMD and body composition by dual-energy X-ray absorptiometry, at the same time points. At baseline, FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia. Parathyroid hormone and β-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption. In the longitudinal analysis, FDP consumption (mean of the two assessments) was associated with attenuated loss of radius total vBMD and of Ct vBMD, area, and thickness. There was no difference in aBMD and at the tibia. These associations were independent of total energy, calcium, or protein intakes. For other dairy products categories, only milk consumption was associated with lower decrease of aBMD and of failure load at the radius. In this prospective cohort of healthy postmenopausal women, age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers, not in milk

Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy.

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Zhu, Haili; Ding, Jieqiong; Wu, Ji; Liu, Tingting; Liang, Jing; Tang, Qiong; Jiao, Ming

2017-11-01

Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

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Donna M. Sosnoski

2012-01-01

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

Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells.

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Banijamali, Mahsan; Rabbani-Chadegani, Azra; Shahhoseini, Maryam

2016-07-01

Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

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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

Stage 1 Breast Cancer and Bone Mass in Older Women

National Research Council Canada - National Science Library

Schneider, Diane

2002-01-01

The specific aims of the study are 1) to assess the bone mineral density of women 65 years of age and older with breast cancer in comparison with the bone mineral density of same aged women with normal mammograms; 2...

Incidental bone scan findings in oral cavity in patients with cancer

International Nuclear Information System (INIS)

Gutierrez G, Patricia; Salvatierra R, Guillermo; Garcia, Arlene; Morales, Rosanna; Cano, Roque; Ortiz L, Jesus; Sotelo R, Silvia; Bustamante, Cesar

2007-01-01

The main aim of the present work, done in the Nuclear medicine Center IPEN-INEN, was to identify as incidental findings, increased inflammatory uptake in oral cavity in routine bone scintigraphies for neoplasic diseases control. A descriptive and retrospective study was performed studying bone scans from patients with cancer, that came to the Nuclear Medicine Center in 2003 and revising records of those who had inflammatory uptake in the oral cavity. It is concluded that, in cancer patients these findings are underestimated. Prospective research should be needed in order to determine the frequency of inflammatory oral cavity pathology detected in bone scintigraphies. (author)

Bone pain induced by metastatic cancer: pathophysiology and treatment

International Nuclear Information System (INIS)

Salas-Herrera, Isaias; Huertas-Gabert, Luis Carlos

2004-01-01

Cancer patients who develop bone metastases are an estimated 60 to 84% . Of these 79% experienced pain syndromes are difficult to manage, of which 50% die without adequate pain relief and with a poor quality of life. Therefore, it is necessary to have accessible and effective medications for the management of this condition. The pathophysiology of pain in bone is reviewed and the drugs used most frequently in the management of this type of cancer pain are described. Furthermore an algorithm of 6 steps is presented and can guide the physician when making a therapeutic decision. (author) [es

The role of purinergic receptors in cancer-induced bone pain

DEFF Research Database (Denmark)

Falk, Sarah; Uldall, Maria; Heegaard, Anne-Marie

2012-01-01

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular...

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

International Nuclear Information System (INIS)

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

1999-01-01

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

Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization

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Ke-Li Tsai

2013-06-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration.

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

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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

Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines

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Hu Shan

2012-12-01

Full Text Available Abstract Background The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP. Lipoxins (LXs, endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. Methods The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t. or intravenous (i.v. injection. The protein level of LXA4 receptor (ALX was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. Results Our results demonstrated that: 1 i.t. injection with the same dose (0.3 nmol of lipoxin A4 (LXA4, lipoxin B4 (LXB4 or aspirin-triggered-15-epi-lipoxin A4 (ATL could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2 The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3 Immunohistochemistry showed that the lipoxin receptor (ALX-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4 Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly

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.)

Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

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Saad, Fred; Eastham, James A

2010-06-01

Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

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Falchook, Aaron D. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Salloum, Ramzi G. [Department of Health Services Policy and Management, University of South Carolina, Columbia, South Carolina (United States); Hendrix, Laura H. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Chen, Ronald C., E-mail: ronald_chen@med.unc.edu [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)

2014-06-01

Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

Bone Health in Patients with Breast Cancer: Recommendations from an Evidence-Based Canadian Guideline

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Alexander H. G. Paterson

2013-12-01

Full Text Available Bone loss is common in patients with breast cancer. Bone modifying agents (BMAs, such as bisphosphonates and denosumab, have been shown to reverse or stabilize bone loss and may be useful in the primary and metastatic settings. The purpose of this review is to provide clear evidence-based strategies for the management of bone loss and its symptoms in breast cancer. A systematic review of clinical trials and meta-analyses published between 1996 and 2012 was conducted of MEDLINE and EMBASE. Reference lists were hand-searched for additional publications. Recommendations were developed based on the best available evidence. Zoledronate, pamidronate, clodronate, and denosumab are recommended for metastatic breast cancer patients; however, no one agent can be recommended over another. Zoledronate or any oral bisphosphonate and denosumab should be considered in primary breast cancer patients who are postmenopausal on aromatase inhibitor therapy and have a high risk of fracture and/or a low bone mineral density and in premenopausal primary breast cancer patients who become amenorrheic after therapy. No one agent can be recommended over another. BMAs are not currently recommended as adjuvant therapy in primary breast cancer for the purpose of improving survival, although a major Early Breast Cancer Cooperative Trialists’ Group meta-analysis is underway which may impact future practice. Adverse events can be managed with appropriate supportive care.

Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

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Tapasi Rana

Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

Bone cancer from radium: canine dose response explains data for mice and humans

International Nuclear Information System (INIS)

Raabe, O.G.; Book, S.A.; Parks, N.J.

1980-01-01

Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species

Detection of occult bone metastases of lung cancer with Fluorine-18 fluorodeoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Foo, S.S.; Ramdave, S.; Berlangieri, S.U.; Scott, A.M.

2004-01-01

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastasesin patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans. Copyright (2004) Blackwell Science Pty Ltd

PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction

International Nuclear Information System (INIS)

Samarin, Andrei; Burger, Cyrill; Crook, David W.; Burger, Irene A.; Schmid, Daniel T.; Schulthess, Gustav K. von; Kuhn, Felix P.; Wollenweber, Scott D.

2012-01-01

Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5-30.8 %) and 3.2 ± 1.7 % (range 0.2-4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4 % (range 9.9-23.5 %) and for osteolytic spine lesions, 7.2 ± 1.7 % (range 4.9-9.3 %), respectively. CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake

Tumor markers and bone scan in breast cancer patients

International Nuclear Information System (INIS)

Ugrinska, A.; Vaskova, O.; Kraleva, S.; Petrova, D.; Smickova, S.

2004-01-01

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

Result of radiation therapy of sino-nasal cancers using partial attenuation filter

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Kim, Jin Hee; Kim, Ok Bae; Choi, Tae Jin [Keimyung University College of Medicine, Daegu (Korea, Republic of)

2007-06-15

This study was to evaluate the survival and pattern of failure after radiation therapy of sino-nasal cancer using partial attenuation filer and wedged beams and to help radiotherapy planning of sino-nasal cancer. Between February 1992 and March 2003, 17 patients with sino-nasal cancers underwent radiation therapy using partial attenuation filter at Dongsan Medical Center, Keimyung university. There were 9 male and 8 female patients. Patients' age ranged from 40 to 75 years (median 59 years). There were 10 patients of maxillary sinus cancer, 7 patients of nasal cancer. The histologic type was squamous cell carcinoma in 11, adenoid cystic carcinoma in 4 and olfactory neuroblastoma in 2. The distribution of clinical stage by the AJCC system was 3 for stage II, 7 for III and 6 for IV. The five patients were treated with radiation alone and 12 patients were treated with surgery and postoperative radiation therapy. The range of total radiation dose delivered to the primary tumor was from 44 to 76 Gy (median 60 Gy). The follow-up period ranged from 3 to 173 months with median of 78 months. The overall 2 year survival rate and disease free survival rate was 76.4%. The 5 year and 10 year survival rate were 76.4% and 45.6% and the 5 year and 10 year disease free survival rate was 70.6%. The 5 year disease free survival rate by treatment modality was 91.6% for postoperative radiation group and 20% for radiation alone group, statistical significance was found by treatment modality ({rho} = 0.006). There were no differences in survival by pathology and stage. There were local failure in 5 patients (29%) but no distant failure and no severe complication required surgical intervention. Radiation therapy of sino-nasal cancer using partial attenuation filter was safe and effective. Combined modality with conservative surgery and radiation therapy was more advisable to achieve loco-regional control in sino-nasal cancer. Also we considered high precision radiation therapy with

Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

International Nuclear Information System (INIS)

Srivastava, S.C.; Meinken, G.E.; Mausner, L.F.; Atkins, H.L.

1998-01-01

The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. 5 figs

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

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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

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

Directory of Open Access Journals (Sweden)

Caroline Wilson

2016-09-01

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

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

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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

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)

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.

Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Ramdave, Shankar; Berlangieri, Salvatore U.

2004-01-01

Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans Copyright (2004) Blackwell Publishing Asia Pty Ltd

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

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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

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

International Nuclear Information System (INIS)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun; Chung, Won-Yoon

2014-01-01

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

Energy Technology Data Exchange (ETDEWEB)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

2014-03-01

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases.

Science.gov (United States)

Galvão, Daniel A; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Joseph, David; Chambers, Suzanne K; Chee, Raphael; Peddle-McIntyre, Carolyn J; Hart, Nicolas H; Baumann, Freerk T; Denham, James; Baker, Michael; Newton, Robert U

2018-03-01

The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting because of concerns of fragility fracture. We examined the efficacy and safety of a modular multimodal exercise program in prostate cancer patients with bone metastases. Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 yr; body mass index, 28.7 ± 4.0 kg·m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine, 66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized to multimodal supervised aerobic, resistance, and flexibility exercises undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months. Physical function subscale of the Medical Outcomes Study Short-Form 36 was the primary end point as an indicator of patient-rated physical functioning. Secondary end points included objective measures of physical function, lower body muscle strength, body composition, and fatigue. Safety was assessed by recording the incidence and severity of any adverse events, skeletal complications, and bone pain throughout the intervention. There was a significant difference between groups for self-reported physical functioning (3.2 points; 95% confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX. However, there was no difference between groups for lean mass (P = 0.584), fat mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse events or skeletal fractures and no differences in bone pain between EX and CON (P = 0.507). Multimodal modular exercise in prostate cancer patients with bone metastases led to self-reported improvements in physical function and objectively measured lower body muscle strength with no skeletal complications or increased bone pain. ACTRN12611001158954.

Correlation between PSA, bone scan and Gleason score in patients with prostate cancer

International Nuclear Information System (INIS)

Mendoza, G.; Cano, R.; Morales, R.; Munoz, L.; Saavedra, P.; Aguilar, C.

2004-01-01

Full text: Prostate cancer is the third most common cancer among Peruvian males. Although radionuclide bone scans (BS) are frequently recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. It has been suggested that a routine bone scan is unnecessary in recently diagnosed prostate cancer if serum PSA is under 10 ng/mL. We hypothesized that Gleason score plus prostate-specific antigen (PSA), could predict for a positive bone scan (better that PSA alone), and that a low - risk group of patients could be identified in whom BS might be omitted. All patients who had both pathologic review of their prostate cancer biopsies and radionuclide BS at our institution from 1/93 to 12/95 were studied. Gleason score, PSA, and bone scan (Soloway Index) were determined in 165 patients. Bivariate analysis using chi (x2) was performed. The mean age of the 165 patients was 71.3 years, 109/165 (66.1%) had a 7-9 Gleason score and only 9/165 (5.5%) were well differentiated prostrate cancer. 82/165 (49.7%) had negative BS. When classifying patients according to their histological grade, the PSA median values were 11.8 ng/mL, 74.8 ng/mL and 116.4 ng/mL in well, median and poorly differentiated prostate cancer respectively. Using a cut off point of 10 ng/mL of PSA, the probability of having a positive BS in Gleason 7, 8 and 9 tumors were 0.109, 0.121 and 0.133 respectively. By using a cut off point of 20 ng/mL of PSA the possibility to have a positive BS in Gleason 7, 8 and 9 tumours were 0.182, 0.206 and 0.224 respectively. Gleason score plus PSA were independent predictors for a positive radionuclide BS in newly diagnosed prostate cancer patients. Considering that most of our patients have Gleason 7-9, the risk of bone metastases despite PSA levels between 10 - 20 ng/mL is not negligible. In our opinion, it is important to continue including bone scan in the staging assessment of prostate cancer. (author)

Assessment on zoledronic acid use in patients with bone metastatic breast cancer

International Nuclear Information System (INIS)

Soriano Garcia, Jorge L; Batista Albuerne, Noyde; Lima Perez, Mayte

2010-01-01

The biphosphonates are the cornerstone in the bone metastases treatment. In present paper the effectiveness and safety of the zoledronic acid (ZA) use in patients with bone metastatic breast cancer (MBC)

Evaluation of follow-up bone scintigraphy for assessing the effects of hormone and chemotherapy of bone metastases from prostatic cancer

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Nobuaki; Ito, Yasuhiko; Morita, Rikushi; Yoneda, Masaya; Muranaka, Akira [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1983-08-01

To assess the clinical usefulness of bone scintigraphy for the osseous metastases of prostatic cancer after treatment, we attempted the correlative studies on laboratory data (TAP, PAP, ALP, and LDH) and scintigraphy. In 77 patients with prostatic cancer, bone scintigraphies were performed with sup(99m)Tc-phosphorous compounds to detect bone metastases. In 34 cases (44 %) bone metastases were detected. In 21 patients out of them, we assessed the effects of hormone and chemotherapy for bone metastases using serial bone scintigraphy. In 19 cases (24.7 %) of the bone scintigraphy showed equivocal results. Of 21 patients with bone metastases, 15 patients showed improvement on scintigram after hormone or chemotherapy. In much improved group (5 patients) and moderately improved group (5 patients), TAP and PAP levels were low and stable. On the other hand, in slightly improved group (5 patients) which showed partially effective on scintigram after treatment, serum TAP and PAP level were unstable. Some cases in the group of which the 1st scintigrams showed normal were turned to positive on scintigram, while TAP, PAP, ALP and LDH level were not elevated. Therefore, follow-up bone scintigraphies have value in evaluating the disease extent in patients with prostatic carcinoma.

Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

Science.gov (United States)

Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

2010-01-01

The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

DEFF Research Database (Denmark)

Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

2008-01-01

BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in ...... experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. CONCLUSION: Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient....

Can tumour marker assays be a guide in the prescription of bone scan for breast and lung cancers?

Energy Technology Data Exchange (ETDEWEB)

Buffaz, P.-D.; Gauchez, A.S.; Caravel, J.P.; Vuillez, J.P.; Cura, C.; Agnius-Delord, C.; Fagret, D. [Service de Medecine Nucleaire, Centre Hospitalier Universitaire de Grenoble (France)

1999-01-01

Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy. (orig.) With 3 figs., 21 refs.

Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

National Research Council Canada - National Science Library

Reddi, A. H

2005-01-01

.... Unfortunately over 40,000 patients succumbed to this horrendous cancer. Death is preceded by a characteristic triad of diffuse osteoblastic-osteosclerotic skeletal metastases, bone pain and pathologic fractures...

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

International Nuclear Information System (INIS)

Yahara, Jyunro

2003-01-01

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

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

k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

International Nuclear Information System (INIS)

Hu, Lingzhi; Traughber, Melanie; Su, Kuan-Hao; Pereira, Gisele C.; Grover, Anu; Traughber, Bryan; Muzic, Raymond F. Jr.

2014-01-01

Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstrating the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2 ∗ = 1/T2 ∗ , was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2 ∗ of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2 ∗ of human skull was measured as 0.2–0.3 ms −1 depending on the specific region, which is more than ten times greater than the R2 ∗ of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction in brain. High-quality, bone

Value of bone scintigraphy for pre-, postoperative assessment and follow-up study of breast cancer

International Nuclear Information System (INIS)

Lee, Hae Giu; Park, Jeong Mi; Chung, Soo Kyo; Kim, Choon Yul; Bahk, Yong Whee

1985-01-01

Early detection of neoplastic disease and metastatic spread is very important. Carcinoma of the breast is known to readily metastasize to the bone. The use of Tc-99m-phosphate as bone imaging agent has been shown to demonstrate early evidence of bone metastasis well before radiographic evidence is visualized and as thus become a very useful technique for establishing and monitoring the bony metastatic element of breast cancer. In this study, serial bone imaging studies were performed to monitor the management of 84 breast cancer patients before and after mastectomy and biopsy. We attempted to analyse bone scans of breast cancer and to correlate the scan findings with the clinical stage, status of lymph nodes, distant metastasis, bone pain, and laboratory data. The following useful patterns were emerged: 1. Positive bone scan rate was definitely higher in clinical stage III and IV (42, 57%) than in stage I and II (4, 18%) in initial studies. However, no correlation between positive bone scan rate and clinical stage was found in follow up studies. 2. Positive bone scan rate was high in both groups with locally advanced tumor (T3 and T4) and distant metastasis. 3. No correlation between positive bone scan and status of lymph node involvement was noted. 4. Positive bone scan rate was also very high in patients with bone pain and abnormal laboratory data

Chromosomal aberration in peripheral lymphocytes and doses to the active bone marrow in radiotherapy of prostate cancer

International Nuclear Information System (INIS)

Gershkevitsh, E.; Trott, K.R.

2002-01-01

Purpose: Radiotherapy plays an important role in the management of prostate cancer. Epidemiological data indicate a small but significant risk of radiation-induced leukemia after radiotherapy which might be related to the high mean bone marrow dose associated with radiotherapy of prostate cancer. The purpose of the study was to investigate the relation between the mean bone marrow dose and unstable chromosome aberrations in peripheral blood lymphocytes in patients undergoing conformal radiotherapy for prostate cancer as a possible indicator of risk. Endometrial cancer patients were also included for comparison. Patients and Methods: Nine patients, six with prostate cancer (60-73 years old) and three with endometrial cancer (61-81 years old) treated with radiotherapy were included in the study. The non-bony spaces inside the pelvic bones were outlined on every CT slice using the treatment planning system and mean doses to the bone marrow calculated. Blood samples of the patients were obtained at different times before, during and at the end of treatment. Lymphocytes were cultured in the usual way and metaphases scored for dicentric aberrations. Results: 46 samples from nine patients were obtained. The mean number of metaphases analyzed per sample was 180 with a range from 52 to 435. The mean bone marrow doses for prostate cancer patients ranged from 2.8 to 4.2 Gy and for endometrial cancer patients from 12.8 to 14.8 Gy. The aberration yield increased with the planning target volume and the mean bone marrow dose. Conclusion: The yield of dicentric aberrations for prostate cancer patients correlated closely with the mean bone marrow dose albeit the induction of dicentrics occurred in mature T lymphocytes most of which were probably in transit through the irradiated volumes. Therefore, the observed relationship between dicentrics and mean bone marrow doses are indirect. (orig.) [de

Integrated PET/MR breast cancer imaging: Attenuation correction and implementation of a 16-channel RF coil

Energy Technology Data Exchange (ETDEWEB)

Oehmigen, Mark, E-mail: mark.oehmigen@uni-due.de; Lindemann, Maike E. [High Field and Hybrid MR Imaging, University Hospital Essen, Essen 45147 (Germany); Lanz, Titus [Rapid Biomedical GmbH, Rimpar 97222 (Germany); Kinner, Sonja [Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen 45147 (Germany); Quick, Harald H. [High Field and Hybrid MR Imaging, University Hospital Essen, Essen 45147, Germany and Erwin L. Hahn Institute for MR Imaging, University Duisburg-Essen, Essen 45141 (Germany)

2016-08-15

Purpose: This study aims to develop, implement, and evaluate a 16-channel radiofrequency (RF) coil for integrated positron emission tomography/magnetic resonance (PET/MR) imaging of breast cancer. The RF coil is designed for optimized MR imaging performance and PET transparency and attenuation correction (AC) is applied for accurate PET quantification. Methods: A 16-channel breast array RF coil was designed for integrated PET/MR hybrid imaging of breast cancer lesions. The RF coil features a lightweight rigid design and is positioned with a spacer at a defined position on the patient table of an integrated PET/MR system. Attenuation correction is performed by generating and applying a dedicated 3D CT-based template attenuation map. Reposition accuracy of the RF coil on the system patient table while using the positioning frame was tested in repeated measurements using MR-visible markers. The MR, PET, and PET/MR imaging performances were systematically evaluated using modular breast phantoms. Attenuation correction of the RF coil was evaluated with difference measurements of the active breast phantoms filled with radiotracer in the PET detector with and without the RF coil in place, serving as a standard of reference measurement. The overall PET/MR imaging performance and PET quantification accuracy of the new 16-channel RF coil and its AC were then evaluated in first clinical examinations on ten patients with local breast cancer. Results: The RF breast array coil provides excellent signal-to-noise ratio and signal homogeneity across the volume of the breast phantoms in MR imaging and visualizes small structures in the phantoms down to 0.4 mm in plane. Difference measurements with PET revealed a global loss and thus attenuation of counts by 13% (mean value across the whole phantom volume) when the RF coil is placed in the PET detector. Local attenuation ranging from 0% in the middle of the phantoms up to 24% was detected in the peripheral regions of the phantoms at

Current role of bone scan with phosphonates in the follow-up of breast cancer

International Nuclear Information System (INIS)

Maffioli, Lorenzo; Florimonte, Luigia; Pagani, Luca; Butti, Ivana; Roca, Isabel

2004-01-01

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. (orig.)

Super bone scans on bone scintigraphy in patients with metastatic bone tumor

International Nuclear Information System (INIS)

Morita, Koichi; Fukunaga, Masao; Otsuka, Nobuaki

1988-01-01

Eight patients with malignant tumor (3 with gastric cancer, 4 with prostatic cancer, 1 with transitional cell carcinoma), which showed diffusely increased uptake of 99m Tc labelled phosphorous compound in axial skeleton (''Super Bone Scan'') on bone scintigraphy were clinically studied. No relationship with its histological type of the tumor was recognized. All cases revealed extremely high serum ALP concentration, which might reflect increased osteoblastic activity. Furthermore, on bone roentgenograms all cases showed predominantly osteosclerotic change in the metastatic bones, while some did locally osteolytic change. In three cases with gastric cancer, although they had diffuse skeletal metastases, two had no evidence of liver metastases. Thus, it seemed that clinical study of patients with ''Super Bone Scan'' was interesting to evaluate the mechanism of accumulation of 99m Tc labelled phosphorous compound to bone and bone metabolism, and the pathophysiology in the pathway of bone metastases. (author)

Bone scan in breast cancer patients with mastectomy and breast reconstruction with a myocutaneous TRAM flap

International Nuclear Information System (INIS)

Morales, Rosanna; Cano, Roque; Delgado, Ricardo; Munive, Carlos

2014-01-01

Objectives: To report findings in bone scans for breast cancer patients with mastectomy and breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM). Material and Methods: Inclusion criteria were: confirmed breast cancer, mastectomy, breast reconstruction with TRAM flap and bone scan performed after TRAM. Exclusion criteria were: Absence of bone scan image, breast reconstruction by other approaches. Results: Absence of uptake in TRAM flap in six patients, diminished uptake in skin near TRAM, with peripheral increased uptake in three and increased uptake in TRAM flap, in a patient with cancer recurrence, confirmed by biopsy. Conclusions: Bone scans in breast cancer patients with mastectomy and TRAM flap can have different imaging presentations, procedure details diminish reporting errors. TRAM flap may present fat necrosis areas, which should be differentiated from recurrence in bone scans. Additional imaging and biopsy will be needed to diagnose this finding. (authors).

CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

International Nuclear Information System (INIS)

Oue, Erika; Lee, Ji-Won; Sakamoto, Kei; Iimura, Tadahiro; Aoki, Kazuhiro; Kayamori, Kou; Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo; Yamaguchi, Akira

2012-01-01

Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

Energy Technology Data Exchange (ETDEWEB)

Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

2012-08-03

Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

Influence of Simultaneous Targeting of the Bone Morphogenetic Protein Pathway and RANK-RANKL Axis in Osteolytic Prostate Cancer Lesion in Bone

Science.gov (United States)

Virk, Mandeep S.; Petrigliano, Frank A.; Liu, Nancy Q.; Chatziioannou, Arion F.; Stout, David; Kang, Christine O.; Dougall, William C.; Lieberman, Jay R.

2009-01-01

Metastasis to bone is the leading cause of morbidity and mortality in advanced prostate cancer patients. Considering the complex reciprocal interactions between the tumor cells and the bone microenvironment, there is increasing interest in developing combination therapies targeting both the tumor growth and the bone microenvironment. In this study, we investigated the effect of simultaneous blockade of BMP pathway and RANK-RANKL axis in an osteolytic prostate cancer lesion in bone. We used a retroviral vector encoding noggin (Retronoggin) to antagonize the effect of BMPs and RANK: Fc, which is a recombinant RANKL antagonist was used to inhibit RANK-RANKL axis. The tumor growth and bone loss were evaluated using plain radiographs, hind limb tumor measurements, micro PET-CT (18F- fluorodeoxyglucose [FDG] and 18F-fluoride tracer), and histology. Tibias implanted with PC-3 cells developed pure osteolytic lesions at 2 weeks with progressive increase in cortical bone destruction at successive time points. Tibias implanted with PC-3 cells over expressing noggin (Retronoggin) resulted in reduced tumor size and decreased bone loss compared to the implanted tibias in untreated control animals. RANK: Fc administration inhibited the formation of osteoclasts, delayed the development of osteolytic lesions, decreased bone loss and reduced tumor size in tibias implanted with PC-3 cells. The combination therapy with RANK: Fc and noggin over expression effectively delayed the radiographic development of osteolytic lesions, and decreased the bone loss and tumor burden compared to implanted tibias treated with noggin over expression alone. Furthermore, the animals treated with the combination strategy exhibited decreased bone loss (micro CT) and lower tumor burden (FDG micro PET) compared to animals treated with RANK: Fc alone. Combined blockade of RANK-RANKL axis and BMP pathway resulted in reduced tumor burden and decreased bone loss compared to inhibition of either individual

Maintaining bone health in prostate cancer throughout the disease continuum.

Science.gov (United States)

Saad, Fred; Eastham, James

2010-06-01

Prostate cancer (PC) is the most prevalent malignancy in men, with 604,506 new cases diagnosed yearly worldwide. Maintaining bone health is important during all stages of PC, including patients who experience bone loss from androgen-deprivation therapy and patients who develop bone metastases. Patients with bone metastases often experience severe bone pain and are at increased risk for potentially debilitating skeletal-related events. Bisphosphonates are a well-established treatment option for patients with bone metastases from solid tumors and bone lesions from multiple myeloma. Zoledronic acid (ZOL) is the only bisphosphonate (BP) that has been extensively studied in patients with castration-recurrent PC and is indicated for treating patients with bone metastases from PC in conjunction with standard antineoplastic therapy. This review will examine the breadth of evidence supporting a role for ZOL and emerging therapies in managing patients with PC throughout the disease continuum. 2010 Elsevier Inc. 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)

Vitamin D, Breast Cancer, and Bone Health

Science.gov (United States)

2011-05-01

vitamin D and bone from David Feldman, MD and from David Karpf, MD. I am thankful for Department of Defense, Breast Cancer Research Program for...Clin Nutr. Jul 2008;88(1):133-139. 3. Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite

Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

Science.gov (United States)

Caglar, M; Kupik, O; Karabulut, E; Høilund-Carlsen, P F

2016-01-01

To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Bone density as a marker for local response to radiotherapy of spinal bone metastases in women with breast cancer: a retrospective analysis

International Nuclear Information System (INIS)

Foerster, Robert; Eisele, Christian; Bruckner, Thomas; Bostel, Tilman; Schlampp, Ingmar; Wolf, Robert; Debus, Juergen; Rief, Harald

2015-01-01

We designed this study to quantify the effects of radiotherapy (RT) on bone density as a local response in spinal bone metastases of women with breast cancer and, secondly, to establish bone density as an accurate and reproducible marker for assessment of local response to RT in spinal bone metastases. We retrospectively assessed 135 osteolytic spinal metastases in 115 women with metastatic breast cancer treated at our department between January 2000 and January 2012. Primary endpoint was to compare bone density in the bone metastases before, 3 months after and 6 months after RT. Bone density was measured in Hounsfield units (HU) in computed tomography scans. We calculated mean values in HU and the standard deviation (SD) as a measurement of bone density before, 3 months and 6 months after RT. T-test was used for statistical analysis of difference in bone density as well as for univariate analysis of prognostic factors for difference in bone density 3 and 6 months after RT. Mean bone density was 194.8 HU ± SD 123.0 at baseline. Bone density increased significantly by a mean of 145.8 HU ± SD 139.4 after 3 months (p = .0001) and by 250.3 HU ± SD 147.1 after 6 months (p < .0001). Women receiving bisphosphonates showed a tendency towards higher increase in bone density in the metastases after 3 months (152.6 HU ± SD 141.9 vs. 76.0 HU ± SD 86.1; p = .069) and pathological fractures before RT were associated with a significantly higher increase in bone density after 3 months (202.3 HU ± SD 161.9 vs. 130.3 HU ± SD 129.2; p = .013). Concomitant chemotherapy (ChT) or endocrine therapy (ET), hormone receptor status, performance score, applied overall RT dose and prescription of a surgical corset did not correlate with a difference in bone density after RT. Bone density measurement in HU is a practicable and reproducible method for assessment of local RT response in osteolytic metastases in breast cancer. Our analysis demonstrated an excellent local response within

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 ...

Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

Science.gov (United States)

Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

2018-01-21

Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

Detection of bone marrow involvement in patients with cancer

International Nuclear Information System (INIS)

Federico, M.; Silingardi, V.; Wright, R.M.

1989-01-01

Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is alredy the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow

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.

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment

OpenAIRE

Schwartz, Boris; Benadjaoud, Mohamed Amine; Clero, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Munzer, Martine; Tan Dat N'Guyen; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne

2014-01-01

International audience; : Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated be...

How MMPs Impact Bone Responses to Metastatic Prostate Cancer

Science.gov (United States)

2011-04-30

bone metabolism. J Biol Chem 2006;281:33814–24. 28. Wilson TJ, Nannuru KC, Singh RK. Cathepsin G-mediated activation of pro-matrix metalloproteinase 9...male mice. Nat Genet 2003;35:252–7. [47] Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, et al. MMP-7 promotes prostate cancer-induced...described (15). A luciferase tagged 4T1 mammary tumor cell line (16) was kindly provided by Dr. Swati Biswas of Vanderbilt Center for Bone Biology. All

Scanning usefulness for bone metastases diagnosis in the breast cancer follow-up

International Nuclear Information System (INIS)

Guillen, G.; Martinez, P.; Garcia, F.; Tres, A.

1988-01-01

It is studied the incidence of osseus metastases and the usefulness of 179 bone scanning realized in the diagnosis and follow-up (average: 23,6 months) of 87 patients operated by breast cancer. It is obvious the scan sensitivity and its unspecificity (15,08% phase-positives). In 13 (14,9%) patients who showed them, during the follow-up, scan was pathological at the moment of the osseus metastases diagnosis or a bit later; there were other clinical data or abnormal analytical ones of suspicion in 77% of them. The time average of appearance is 27 months after surgery. We concluded that the bone scan in the follow-up of breast cancer will be realized only when clinical or analytical suspicion of bone metastases. (Author)

Accuracy and precision in the in vivo determination of bone minerals content using the attenuation of a continuous x-ray spectrum

International Nuclear Information System (INIS)

Jonson, R.; Roos, B.; Hansson, T.; Mattsson, S.

1986-01-01

An x-ray technique using a highly stabilized generator and a germanium detector for the in vivo determination of bone mineral content in the lumbar vertebra has been described previously from the authors laboratory. This technique estimates the bone mineral content in presence of fat and lean soft tissue in the path of the x-ray beam. The present investigation was undertaken in vitro to determine the accuracy, precision and long term reproducibility of the technique. The ash density of 12 human bone specimens was determined on the basis of ash weight and total volume measurements of each specimen. The result was compared with the measured bone mineral content. The deviation between the result of the attenuation measurements and the weight/volume measurements was (4 +/- 0.9%). The precision of the method as measured in vitro has been determined to be between +/- 1.6% (high bone mineral content) and +/- 2.6% (low bone mineral content) by repeated measurements on a new type of bone mineral phantom. The results show that the technique described gives an accuracy and a precision which is of the same order of magnitude as the technique using dual photon energy absorptiometry

Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

International Nuclear Information System (INIS)

Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama; Arndt, Jan-Willem; Zwinderman, Aeilko H.; Bril, Herman; Papapoulos, Socrates E.; Hamdy, Neveen A.T.

2004-01-01

In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

Science.gov (United States)

Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

2015-06-01

Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.

Science.gov (United States)

Xu, Wen Wen; Li, Bin; Guan, Xin Yuan; Chung, Sookja K; Wang, Yang; Yip, Yim Ling; Law, Simon Y K; Chan, Kin Tak; Lee, Nikki P Y; Chan, Kwok Wah; Xu, Li Yan; Li, En Min; Tsao, Sai Wah; He, Qing-Yu; Cheung, Annie L M

2017-02-10

Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

Comparison of bone mineral density in young patients with breast cancer and healthy women

Directory of Open Access Journals (Sweden)

Sousan Kolahi

2014-05-01

Full Text Available BACKGROUND: Almost 1 in 8 women will have breast cancer during their lifetime. Several risk factors were identified; however, 70% of females with breast cancer have no risk factors. Many risk factors are associated with sex steroid hormones. Some studies have been focused on identification of the indices of cumulative exposures to estrogen during the patients’ life. One of these indicators is bone mineral density (BMD. Our aim was the comparison of BMD in young patients with and without breast cancer, and finding a relationship between breast cancer and bone density. METHODS: In this case-control study, 120 people were enrolled; 40 patients with breast cancer and 80 normal healthy persons as control group. Measurement of BMD was performed in both groups and compared. RESULTS: Both groups were matched in age, weight, age at menarche, age at first marriage and first pregnancy, number of pregnancies over 32 weeks and lactation period, and taking supplemental calcium and vitamin D. However, there was a significant difference between the two groups in terms of estrogen intake, family history of breast cancer, and history of breast masses (P = 0.03, P = 0.03, P ≤ 0.01, respectively. A significant difference was found between BMD, bone mineral content (BMC, and t-scores of lumbar spine of the two groups; they were higher in the control group (P = 0.08, P ≤ 0.01, P = 0.06, respectively. CONCLUSIONS: This study shows that bone mineral density of young patients with breast cancer is not higher than normal similar age females; thus, BMD is not directly a risk factor for breast cancer.

Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

Science.gov (United States)

Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F; Kirkpatrick, Charles J; Sader, Robert A

2013-07-01

The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

In-vitro studies with 188Re-HEDP, a clinically used bone pain palliating agent, on bone cancer cells

International Nuclear Information System (INIS)

Sharma, Rohit; Kumar, Chandan; Mallia, Madhava B.; Banerjee, Sharmila; Kameswaran, Mythili

2017-01-01

Rhenium-188 is an attractive radioisotope for a wide variety of radiotherapy applications. 188 Re-HEDP (HEDPhydroxyethylidene- 1,1-diphosphonic acid) is one such, clinically useful, radiopharmaceutical for palliation of bone pain due to osseous metastasis. Herein, our aim was to study the uptake and retention of 188 Re-HEDP in mineralized bone and to assess its cellular toxicity, along with its underlying mechanism in human osteocarcinoma (MG-63 and Soas-2) cell lines. 188 Re-HEDP uptake was found to be significantly higher in mineralized bone. The 188 Re-HEDP complex also induces G2-M cell cycle arrest and thus contributing to apoptosis and cellular toxicity in bone cancer cells. (author)

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

Science.gov (United States)

Schwartz, Boris; Benadjaoud, Mohamed Amine; Cléro, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cécile; Oberlin, Odile; Veres, Cristina; Pacquement, Hélène; Munzer, Martine; N'guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Hawkins, Mike; Winter, David; Lefkopoulos, Dimitri; Chavaudra, Jean; Rubino, Carole; Diallo, Ibrahima; Bénichou, Jacques; de Vathaire, Florent

2014-05-01

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

Science.gov (United States)

Hui, Susanta K; Arentsen, Luke; Sueblinvong, Thanasak; Brown, Keenan; Bolan, Pat; Ghebre, Rahel G; Downs, Levi; Shanley, Ryan; Hansen, Karen E; Minenko, Anne G; Takhashi, Yutaka; Yagi, Masashi; Zhang, Yan; Geller, Melissa; Reynolds, Margaret; Lee, Chung K; Blaes, Anne H; Allen, Sharon; Zobel, Bruno Beomonte; Le, Chap; Froelich, Jerry; Rosen, Clifford; Yee, Douglas

2015-04-01

Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and

P2X7 receptor-mediated analgesia in cancer-induced bone pain

DEFF Research Database (Denmark)

Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit

2015-01-01

Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique for ca...

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.

Bone tumor

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-17

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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.)

Bone Cancer—Patient Version

Science.gov (United States)

Bone cancer is rare and includes several types. Some bone cancers, including osteosarcoma and Ewing sarcoma, are seen most often in children and young adults. Start here to find information on bone cancer treatment, research, and statistics.

Module for applications of bone scan in cancer patients; Modulo para solicitudes de gammagrafia osea en pacientes con cancer

Energy Technology Data Exchange (ETDEWEB)

Morales, Rosanna; Cano, Roque; Velasquez, Maria [Centro de Medicina Nuclear, Instituto Peruano de Energia Nuclear, Lima (Peru); Vasquez, Edinson; Diaz, Pepe; Vasquez, Mario; Rojas, Peter [Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos 2520, Surquillo, Lima (Peru)

2013-07-01

This paper reports the application of a software which enables the complete register of patient data, for delivering appropriate information in bone scan reports. Bone scan is a frequent study in Nuclear Medicine, which enables physicians to diagnose a primary bone cancer or metastases. The software was designed in order to complete data given by oncologists and constitutes an aid for the health team attending patients. (authors).

The status of nuclear medicine techniques in the diagnosis of bone metastases in breast cancer

International Nuclear Information System (INIS)

Makaiova, I.; Kausitz, J.; Hupka, S.; Vivodova, M.

1989-01-01

Experience is presented with the diagnosis of bone metastases in patients with breast cancer using bone scintigraphy with 99m TC phosphonate and radioimmunological determination of carcinoembryonic antigen (CEA) and tissue polypeptic antigen (TPA). In a group of 395 patients, there was agreement between tumor markers (CEA, TPA) and the results of bone scintigraphy in 331 cases (84%) - negative in 193 cases (49%) and positive (i.e., in terms of bone scintigraphy results and the presence of at least one tumor marker) in 138 cases (35%). On the basis of this agreement between bone scintigraphy and CEA and TPA levels, the following algorithm is recommended in monitoring patients with breast cancer: a) follow-up of tumor markers at several month intervals and in case of an increase in their levels the patient should be referred to further examination using imaging techniques including bone scintigraphy. (author). 1 fig., 1 tab., 23 refs

Using Micro-CT Derived Bone Microarchitecture to Analyze Bone Stiffness - A Case Study on Osteoporosis Rat Bone

Directory of Open Access Journals (Sweden)

Yuchin eWu

2015-05-01

Full Text Available Micro-computed tomography images can be used to quantitatively represent bone geometry through a range of computed attenuation-based parameters. Nonetheless, those parameters remain indirect indices of bone micro-architectural strength and require further computational tools to interpret bone structural stiffness and potential for mechanical failure. Finite element analysis (FEA can be applied to measure trabecular bone stiffness and potentially predict the location of structural failure in preclinical animal models of osteoporosis, although that procedure from image segmentation of micro-CT derived bone geometry to FEA is often challenging and computationally expensive, resulting in failure of the model to build. Notably, the selection of resolution and threshold for bone segmentation are key steps that greatly affect computational complexity and validity. In the following study, we evaluated an approach whereby Micro-CT derived greyscale attenuation and segmentation data guided the selection of trabecular bone for analysis by FEA. We further correlated those FEA results to both two and three dimensional bone microarchitecture from sham and ovariectomized (OVX rats (n=10/group. A virtual cylinder of vertebral trabecular bone 40% in length from the caudal side was selected for FEA because micro-CT based image analysis indicated the largest differences in microarchitecture between the two groups resided there. Bone stiffness was calculated using FEA and statistically correlated with the three dimensional values of bone volume/tissue volume, bone mineral density, fractal dimension, trabecular separation and trabecular bone pattern factor. Our method simplified the process for the assessment of trabecular bone stiffness by FEA from Micro-CT images and highlighted the importance of bone microarchitecture in conferring significantly increased bone quality capable of resisting failure due to increased mechanical loading.

Effect of music therapy on pain behaviors in rats with bone cancer pain.

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Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

2016-01-01

To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (pMusic therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

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.

Biological Differences Between Prostate Cancer Cells that Metastasize to Bone Versus Soft Tissue Sites

National Research Council Canada - National Science Library

Pienta, Kenneth J

2004-01-01

.... Comparisons were made between patients as well as within the same patient. No consistent differences were found between bone and soft tissue sites that could explain the predilection of prostate cancer cells to metastasize to bone...

Targeting a novel bone degradation pathway in primary bone cancer by inactivation of the collagen receptor uPARAP/Endo180

DEFF Research Database (Denmark)

Engelholm, Lars H; Carlsen Melander, Eva Maria; Hald, Andreas

2016-01-01

metastases of carcinoma origin. This opened the possibility that sarcoma cells might directly mediate bone degeneration. To examine this question, we utilized a syngeneic, osteolytic bone tumour model with transplanted NCTC-2472 sarcoma cells in mice. When analysed in vitro, these cells were capable......In osteosarcoma, a primary mesenchymal bone cancer occurring predominantly in younger patients, invasive tumour growth leads to extensive bone destruction. This process is insufficiently understood, cannot be efficiently counteracted and calls for novel means of treatment. The endocytic collagen...... receptor, uPARAP/Endo180, is expressed on various mesenchymal cell types and is involved in bone matrix turnover during normal bone growth. Human osteosarcoma specimens showed strong expression of this receptor on tumour cells, along with the collagenolytic metalloprotease, MT1-MMP. In advanced tumours...

Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications.

Science.gov (United States)

Leong, Stanley P L; Tseng, William W

2014-01-01

Cancer metastasis may be regarded as a progressive process from its inception in the primary tumor microenvironment to distant sites by way of the lymphovascular system. Although this type of tumor dissemination often occurs in an orderly fashion via the sentinel lymph node (SLN), acting as a possible gateway to the regional lymph nodes, bone marrow, and peripheral blood and ultimately to distant metastatic sites, this is not a general rule as tumor cells may enter the blood and spread to distant sites, bypassing the SLN. Methods of detecting micrometastatic cancer cells in the SLN, bone marrow, and peripheral blood of patients have been established. Patients with cancer cells in their SLN, bone marrow, or peripheral blood have worse clinical outcomes than patients with no evidence of spread to these compartments. The presence of these cells also has important biologic implications for disease progression and the clinician's understanding of the process of cancer metastasis. Further characterization of these micrometastatic cancer cells at each stage and site of metastasis is needed to design novel selective therapies for a more "personalized" treatment. © 2014 American Cancer Society, Inc.

Distribution of Proliferating Bone Marrow in Adult Cancer Patients Determined Using FLT-PET Imaging

International Nuclear Information System (INIS)

Hayman, James A.; Callahan, Jason W.; Herschtal, Alan; Everitt, Sarah; Binns, David S.; Hicks, Rod J.; Mac Manus, Michael

2011-01-01

Purpose: Given that proliferating hematopoietic stem cells are especially radiosensitive, the bone marrow is a potential organ at risk, particularly with the use of concurrent chemotherapy and radiotherapy. Existing data on bone marrow distribution have been determined from the weight and visual appearance of the marrow in cadavers. 18 F-fluoro-L-deoxythymidine concentrates in bone marrow, and we used its intensity on positron emission tomography imaging to quantify the location of the proliferating bone marrow. Methods and Materials: The 18 F-fluoro-L-deoxythymidine positron emission/computed tomography scans performed at the Peter MacCallum Cancer Centre between 2006 and 2009 on adult cancer patients were analyzed. At a minimum, the scans included the mid-skull through the proximal femurs. A software program developed at our institution was used to calculate the percentage of administered activity in 11 separately defined bony regions. Results: The study population consisted of 13 patients, 6 of whom were men. Their median age was 61 years. Of the 13 patients, 9 had lung cancer, 2 had colon cancer, and 1 each had melanoma and leiomyosarcoma; 6 had received previous, but not recent, chemotherapy. The mean percentage of proliferating bone marrow by anatomic site was 2.9% ± 2.1% at the skull, 1.9% ± 1.2% at the proximal humeri, 2.9% ± 1.3% at the sternum, 8.8% ± 4.7% at the ribs and clavicles, 3.8% ± 0.9% at the scapulas, 4.3% ± 1.6% at the cervical spine, 19.9% ± 2.6% at the thoracic spine, 16.6% ± 2.2% at the lumbar spine, 9.2% ± 2.3% at the sacrum, 25.3% ± 4.9% at the pelvis, and 4.5% ± 2.5% at the proximal femurs. Conclusion: Our modern estimates of bone marrow distribution in actual cancer patients using molecular imaging of the proliferating marrow provide updated data for optimizing normal tissue sparing during external beam radiotherapy planning.

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

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

Science.gov (United States)

Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

2017-12-01

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

Prognostic factors for survival of women with unstable spinal bone metastases from breast cancer

International Nuclear Information System (INIS)

Foerster, Robert; Bruckner, Thomas; Bostel, Tilman; Schlampp, Ingmar; Debus, Juergen; Rief, Harald

2015-01-01

Bone metastases are an important clinical issue in women with breast cancer. Particularly, unstable spinal bone metastases (SBM) are a major cause of severe morbidity and reduced quality of life (QoL) due to frequent immobilization. Radiotherapy (RT) is the major treatment modality and is capable of promoting re-ossification and improving stability. Since local therapy response is excellent, survival of these patients with unstable SBM is of high clinical importance. We therefore conducted this analysis to assess survival and to determine prognostic factors for bone survival (BS) in women with breast cancer and unstable SBM. A total population of 92 women with unstable SBM from breast cancer who were treated with RT at our department between January 2000 and January 2012 was retrospectively investigated. We calculated overall survival (OS) and BS (time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with a Cox regression model. Mean age at first diagnosis of breast cancer was 60.8 years ± SD 12.4 years. OS after 1, 2 and 5 years was 84.8, 66.3 and 50 %, respectively. BS after 1, 2 and 5 years was 62.0, 33.7 and 12 %, respectively. An age > 50 years (p < .001; HR 1.036 [CI 1.015–1.057]), the presence of a single bone metastasis (p = .002; HR 0.469 [CI 0.292–0.753]) and triple negative phenotype (p < .001; HR 1.068 [CI 0.933–1.125]) were identified as independent prognostic factors for BS. Our analysis demonstrated a short survival of women with breast cancer and unstable SBM. Age, presence of a solitary SBM and triple-negative phenotype correlated with survival. Our results may have an impact on therapeutic decisions in the future and offer a rationale for future prospective investigations

Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain.

Science.gov (United States)

Bennett, Michael I; Johnson, Mark I; Brown, Sarah R; Radford, Helen; Brown, Julia M; Searle, Robert D

2010-04-01

This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain. Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial. Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

International Nuclear Information System (INIS)

Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee

2009-01-01

This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis

Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of)

2009-08-15

This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis.

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

A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic Biomarker and Novel Therapeutic Mitochondrial Target

Science.gov (United States)

2017-10-01

goal of this application is to identify targets for the treatment of androgen receptor null castration-resistant prostate cancer in in vitro and pre...AWARD NUMBER: W81XWH-16-1-0584 TITLE : A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic...Missense Mutation in 77% of Prostate Cancer Bone Metastases: 5a. CONTRACT NUMBER A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases

PET/MR brain imaging: evaluation of clinical UTE-based attenuation correction

International Nuclear Information System (INIS)

Aasheim, Lars Birger; Karlberg, Anna; Goa, Paal Erik; Haaberg, Asta; Soerhaug, Sveinung; Fagerli, Unn-Merete; Eikenes, Live

2015-01-01

One of the greatest challenges in PET/MR imaging is that of accurate MR-based attenuation correction (AC) of the acquired PET data, which must be solved if the PET/MR modality is to reach its full potential. The aim of this study was to investigate the performance of Siemens' most recent version (VB20P) of MR-based AC of head PET data, by comparing it to CT-based AC. Methods: 18 F-FDG PET data from seven lymphoma and twelve lung cancer patients examined with a Biograph mMR PET/MR system were reconstructed with both CT-based and MR-based AC, avoiding sources of error arising when comparing PET data from different systems. The resulting images were compared quantitatively by measuring changes in mean SUV in ten different brain regions in both hemispheres, as well as the brainstem. In addition, the attenuation maps (μ maps) were compared regarding volume and localization of cranial bone. The UTE μ maps clearly overestimate the amount of bone in the neck, while slightly underestimating the amount of bone in the cranium, and the localization of bone in the cranial region also differ from the CT μ maps. In air/tissue interfaces in the sinuses and ears, the MRAC method struggles to correctly classify the different tissues. The misclassification of tissue is most likely caused by a combination of artefacts and the insufficiency of the UTE method to accurately separate bone. Quantitatively, this results in a combination of overestimation (0.5-3.6 %) and underestimation (2.7-5.2 %) of PET activity throughout the brain, depending on the proximity to the inaccurate regions. Our results indicate that the performance of the UTE method as implemented in VB20P is close to the theoretical maximum of such an MRAC method in the brain, while it does not perform satisfactorily in the neck or face/nasal area. Further improvement of the UTE MRAC or other available methods for more accurate segmentation of bone should be incorporated. (orig.)

Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

Science.gov (United States)

Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Kato, Takashi; Odawara, Soichi; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

2017-08-01

The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

The potential of shark bone powder in breast cancer inhibition (pre-clinical study in DMBA-Induced Sprague Dawly Rats)

Science.gov (United States)

Bintari, S. H.; Parman, S.; Dafip, M.

2018-03-01

Breast cancer is a malignant disease, which lead to second cause of that after cervical cancer in women. To date, lots of drugs and supplement have been developed and consumed by patients. Shark bone is one of the supplements that might inhibit the proliferation of cancer cells. The application of shark bone powder for supplementation in breast cancer cases still becomes controversy; but until now people are still many who consume as a supplement. This study aimed to prove the potency of shark bone powder in the inhibition of breast cancer proliferation and to propose the possibility of its biological mechanism. The pre-clinical experimental study used a controlled posttest controlled design with 25 white rats strains of DML-induced Sprague-Dawley strains. The cancer markers observed were p53, AgNORs, VEGF, Bcl-2, and Cas-3. The test subjects were divided into 3 groups: control group and 2 treatment groups fed modified with 60% and 90% respectively. A pre-clinical trial of shark bone powder showed that there was significant inhibition for the DMBA-induced anti proliferation and breast cell cancer (p breast cancer proliferation lies in concentration 30mg/BB/day.

Monitoring Dynamic Interactions between Breast Cancer Cells and Human Bone Tissue in a Co-Culture Model

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Contag, Christopher H.; Lie, Wen-Rong; Bammer, Marie C.; Hardy, Jonathan W.; Schmidt, Tobi L.; Maloney, William J.; King, Bonnie L.

2015-01-01

Purpose Bone is a preferential site of breast cancer metastasis and models are needed to study this process at the level of the microenvironment. We have used bioluminescence imaging (BLI) and multiplex biomarker immunoassays to monitor dynamic breast cancer cell behaviors in co-culture with human bone tissue. Procedures Femur tissue fragments harvested from hip replacement surgeries were co-cultured with luciferase-positive MDA-MB-231-fLuc cells. BLI was performed to quantify breast cell division and track migration relative to bone tissue. Breast cell colonization of bone tissues was assessed with immunohistochemistry. Biomarkers in co-culture supernatants were profiled with MILLIPLEX® immunoassays. Results BLI demonstrated increased MDA-MB-231-fLuc proliferation (pbones, and revealed breast cell migration toward bone. Immunohistochemistry illustrated MDA-MB-231-fLuc colonization of bone, and MILLIPLEX® profiles of culture supernatants suggested breast/bone crosstalk. Conclusions Breast cell behaviors that facilitate metastasis occur reproducibly in human bone tissue co-cultures and can be monitored and quantified using BLI and multiplex immunoassays. PMID:24008275

Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.

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Delk, Nikki A; Farach-Carson, Mary C

2012-04-01

Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

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

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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.

A meta-analysis of 18FDG-PET–CT, 18FDG-PET, MRI and bone scintigraphy for diagnosis of bone metastases in patients with lung cancer

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Qu Xinhua; Huang Xiaolu; Yan Weili; Wu Lianming; Dai Kerong

2012-01-01

Background and purpose: Lung cancer is the most common cause of cancer related death among both men and women worldwide. The skeleton is the most common site of cancer metastasis. Early detection is crucial for prognosis. To evaluate and compare the capability for bone metastasis assessment of [ 18 F] fluoro-2-D-glucose positron emission tomography with computed tomography ( 18 FDG-PET–CT), [ 18 F] fluoro-2-D-glucose positron emission tomography ( 18 FDG-PET), magnetic resonance imaging (MRI) and bone scintigraphy (BS) in lung cancer patients, a meta-analysis is preformed. Methods: We searched MEDLINE, OVID, EMBASE and the Cochrane Library for studies evaluating diagnosis validity of 18 FDG-PET–CT, 18 FDG-PET, MRI and BS between January 1990 and August 2010. Meta-analysis methods were used to pool sensitivity, specificity, diagnostic odd ratios (DORs) and to construct a summary receiver-operating characteristic curve (SROC). Results: A total of 17 articles (9 18 FDG-PET–CT studies, 9 18 FDG-PET studies, 6 MRI studies and 16 BS studies) that included 2940 patients who fulfilled all of the inclusion criteria were considered for inclusion in the analysis. The pooled sensitivity for the detection of bone metastasis in lung cancer using 18 FDG-PET–CT, 18 FDG-PET, MRI and BS were 0.92 (95% CI, 0.88–0.95), 0.87 (95% CI, 0.81–0.92), 0.77 (95% CI, 0.65–0.87) and 0.86 (95% CI, 0.82–0.89), respectively. The pooled specificity for the detection of bone metastasis from lung cancer using 18 FDG-PET–CT, 18 FDG-PET, MRI and BS were 0.98 (95% CI, 0.97–0.98), 0.94 (95% CI, 0.92–0.96), 0.92 (95% CI, 0.88–0.95), 0.88 (95% CI, 0.86–0.89), respectively. The pooled DORs estimates for 18 FDG-PET–CT 449.17 were significantly higher than for 18 FDG-PET (118.25, P 18 FDG-PET–CT and 18 FDG-PET were better imaging methods for diagnosing bone metastasis from lung cancer than MRI and BS. 18 FDG-PET–CT has higher diagnostic value (sensitivity, specificity and DORs

Usefulness of 18F fluoride PET/CT in breast cancer patients with osteosclerotic bone metastases

International Nuclear Information System (INIS)

Yoon, Seok Ho; Kim, Ku Sang; Kang, Seok Yun; Song, Hee Sung; Jo, Kyung Sook; Lee, Su Jin; Yoon, Joon Kee; An, Young Sil; Choi, Bong Hoi

2012-01-01

Bone metastasis is an important factor for the treatment and prognosis of breast cancer patients. Whole body bone scintigraphy (WBBS) can evaluate skeletal metastases, and 18 F FDG PET/CT seems to exhibit high specificity and accuracy in detecting bone metastases. However, there is a limitation of 18 F FDG PET in assessing sclerotic bone metastases because some lesions may be undetectable. Recent studies showed that 18 F fluoride PET/CT is more sensitive than WBBS in detecting bone metastases. This study aims to evaluate the usefulness of 18 F fluoride PET/CT by comparing it with WBBS and 18 F FDG PET/CT in breast cancer patients with osteosclerotic skeletal metastases. Nine breast cancer patients with suspected bone metastases (9 females; mean age ± SD, 55.6±10.0 years) underwent 99m Tc MDP WBBS, 18 F FDG PET/CT and 18 F fluoride PET/CT. Lesion based analysis of five regions of the skeletons(skull, vertebral column, thoracic cage, pelvic bones and long bones of extremities) and patient based analysis were performed. 18 F fluoride PET/CT, 18 F FDG PET/CT and WBBS detected 49, 20 and 25 true metastases, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of 18 F fluoride PET/CT were 94.2%, 46.3%, 57.7% and 91.2%, respectively. Most true metastatic lesions of 18 F fluoride PET/CT had osteosclerotic change (45/49, 91.8%), and only four lesions showed osteolytic change. Most lesions on 18 F FDG PET/CT also demonstrated osteosclerotic change (17/20, 85.0%) with three osteolytic lesions. All true metastatic lesions detected on WBBS and 18 F FDG PET/CT were identified on 18 F fluoride PET/CT. 18 F FDG PET/CT in detecting osteosclerotic metastatic lesions. 18 F fluoride PET/CT might be useful in evaluating osteosclerotic metastases in breast cancer patients

Increased circulating rather than spinal cytokines accompany chronic pain behaviors in experimental bone cancer and arthritis

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Line Pourtau

2014-12-01

Full Text Available Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play a part in chronic pain. Therefore, spinal cord, dorsal root ganglia and circulating cytokines were compared in murine arthritis and bone cancer models in relationship to behavioral signs of pain. Methods: Exploratory behaviors were studied after intra-articular complete Freund's adjuvant or bone intramedullary sarcoma cell injection. Nervous tissue and blood cytokine expression were determined by real-time polymerase chain reaction (PCR and multiplex immunoassays, respectively. Results: PCR analysis did not reveal any hallmark of spinal neuroinflammation in spontaneously-behaving mice with cartilage or bone lesions. However, imposed paw stimulation during joint inflammation increased spinal interleukin-1β (IL-1β expression. Spontaneous paw guarding during rearing was displayed by animals with joint inflammation and bone destruction and was accompanied by increased circulating IL-6 and monocyte chemoattractant protein-1, respectively. In addition, dorsal root ganglia were found to constitutively express receptors for this chemotactic cytokine. Conclusion: Our findings indicate that spinal neuroinflammation is not a necessary condition for chronic pain and suggest that circulating cytokine action in dorsal root ganglia may contribute to experimental joint inflammation and bone cancer pain.

Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

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Waldenstroem, Ann-Charlotte; Olsson, Caroline; Wilderaeng, Ulrica; Dunberger, Gail; Lind, Helena; Al-Abany, Massoud; Palm, Asa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

2011-01-01

Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.

What Is Breast in the Bone?

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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.

Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

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Rafiei, Shahrzad; Komarova, Svetlana V

2013-01-01

Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients

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Monroy-Cisneros, Karina; Esparza-Romero, Julián; Valencia, Mauro E.; Guevara-Torres, Alfonso G.; Méndez-Estrada, Rosa O.; Anduro-Corona, Iván; Astiazarán-García, Humberto

2016-01-01

Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm 2 in femoral neck and 0.063 g/cm 2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm 2 in femoral neck and 0.035 g/cm 2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm 2 (p = 0.003). The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status

Palliative effect of Re-186 HEDP in different cancer patients with bone metastases

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Kucuk, N.O.; Ibis, E.; Aras, G.; Soylu, A.; Baltaci, S.; Beduk, Y.; Ozalp, G.; Canakci, N.

2001-01-01

The clinical picture of bone metastases is manifested by pain and loss of mechanical stability. Standard treatment options for bone metastases include external beam radiotherapy and the use of analgesics. Due to a large number of lesions in many patients, the use of radionuclide therapy with beta emitters may be preferable. Re-186 hydroxyethydilene diphosphonate (Re-186 HEDP) is one of the radiopharmaceuticals suitable for palliative treatment of metastatic bone pain. The aim of this study was to investigate palliative and side effects of Re-186 HEDP in pts with different type of cancers. Material and method: Thirty one (17 male, 14 female) patients with cancer (10 prostate, 10 breast, 4 rectum, 5 lung, 2 nasopharynx) and bone metastases were included in the study. Therapy was started with a fixed dose of 1295 MBq of Re-186 HEDP. If necessary, the same dose was repeated at least 3 times after an interval of 10-12 weeks A total of 40 standard doses (1295 MBq Re HEDP, Mallinckrodt, Holland) were given; 6 pts received repeated doses (3 doses in 3 pts, 2 doses in 3 pts). The pts with bone marrow suppression were excluded from the study. The pain relief was assessed with ECOG and Karnofsky status index. All pts were evaluated with standard evaluation forms filled daily a maximum of 10 weeks. Results: The respond rate was found as 87.5% in pts with breast and prostate Ca, 75% in pts with rectum Ca, 50% in pts with nasopharynx Ca and 20% in pts with lung Ca. The overall response rate was 67.5%. The palliation period varied between 6 to 10 weeks. The mean palliation period was 8.1 ± 1.3 weeks. Maximal palliation effect was observed between the 3 rd and the 7 th weeks. Any serious side effects were not seen except mild haematologic toxicity. Discussion and conclusion: It is concluded that Re-186 HEDP is a highly effective agent in the palliation of metastatic bone pain in pts with prostate, breast, rectum cancer, mildly effective in pts with nasopharynx cancer, but not

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

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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

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

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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.

Development of Raman spectral markers to assess metastatic bone in breast cancer

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Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-11-01

Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

Genistein suppresses Prevotella intermedia lipopolysaccharide-induced inflammatory response in macrophages and attenuates alveolar bone loss in ligature-induced periodontitis.

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Choi, Eun-Young; Bae, Seung Han; Ha, Min Hee; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2016-02-01

Genistein is a major isoflavone subclass of flavonoids found in soybean and a potent tyrosine kinase inhibitor. The present study aimed to assess the effect of genistein on the production of proinflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen associated with different forms of periodontal disease, and to evaluate its possible influence on alveolar bone loss in ligature-induced periodontitis using micro-computed tomography (micro-CT) analysis as well. LPS was isolated from P. intermedia ATCC 25611 by using the standard hot phenol-water method. Culture supernatants were analyzed for nitric oxide (NO) and interleukin-6 (IL-6). Inducible NO synthase (iNOS) protein expression was evaluated by immunoblot analysis. Real-time PCR was carried out to measure iNOS and IL-6 mRNA expression. In addition, effect of genistein on alveolar bone loss was evaluated in a rat model of experimental periodontitis using micro-CT analysis. Genistein significantly attenuated P. intermedia LPS-induced production of iNOS-derived NO and IL-6 with attendant decrease in their mRNA expression in RAW264.7 cells. In addition, when genistein was administered to rats, decreases in alveolar bone height and bone volume fraction induced by ligature placement were significantly inhibited. Genistein administration also prevented ligature-induced alterations in the microstructural parameters of trabecular bone, including trabecular thickness, trabecular separation, bone mineral density and structure model index. While additional studies are required, we suggest that genistein could be utilized for the therapy of human periodontitis in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer patients undertaking bone scans in a department of Nuclear Medicine have significant stress related to the examination

International Nuclear Information System (INIS)

Sioka, C.; Manetou, M.; Dimakopoulos, N.; Christidi, S.; Kouraklis, G.

2005-01-01

Bone scanning is a standard screening procedure for evaluation of metastases in cancer patient. In addition to the staging procedures, bone scan is a valuable test for deciding palliative therapeutic options in selected patients. The aim of this study was to investigate if patients with cancer who were undertaking routine bone scans had any stress related to the test. We asked 83 consecutive patients with various types of cancer if they had anxiety just prior to undergoing the test. Overall, we found that 53 (64%) patients had increased anxiety related to the examination and 30 (36%) patients did not. Among the 53 patients who were anxious about the bone scan, 32 were concerned about the results of the examination, 13 worried about the effects of the radiation, 4 were anxious for both results/radiation, and 4 patients had stress but could not specify the reason. Among the 32 patients who were concerned about the results of the examination, 15 were having their first bone scans, while 17 had already undergone the procedure before. Among the 13 patients who were mainly concerned about the risks of the radiation exposure during the test, 9 were having bone scans for the first time. Out of the 4 patients who feared both the results and radiation, 3 were having bone scans for the first time and 1 had it for several times. Finally, out of the 4 patients who had anxiety about the test but could not identify the reason, 3 were having bone scans for the first time and one had the test before but was claustrophobic. Our findings indicate that most patients (64%) with cancer who underwent a routine bone scan to check for metastatic disease had intense stress related either to the results or the side effects of the examination. However, there were more patients who were concerned about the results of the test rather than the effects of radiation. Among the patients who feared the effects of radioactivity most were having the test for the first time. A previous study in a

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

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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

Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain.

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Louis Doré-Savard

2010-10-01

Full Text Available Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT. Bone metastases were visualized as early as day 8 by MRI (T(1-Gd-DTPA before pain detection. PET (Na(18F co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining. Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal and ATF3 (DRG neuronal activation, sustained by astrocyte (GFAP and microglia (Iba1 reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future.

Comparative analysis of bone mineral contents with dual-energy quantitative computed tomography

International Nuclear Information System (INIS)

Choi, T. J.; Yoon, S. M.; Kim, O. B.; Lee, S. M.; Suh, S. J.

1997-01-01

The Dual-Energy Quantitative Computed Tomography(DEQCT) was compared with bone equivalent K 2 HPO 4 standard solution and ash weight of animal cadaveric trabecular bone in the measurement of bone mineral contents(BMC). The attenuation coefficient of tissues highly depends on the radiation energy, density and effective atomic number of composition. The bone mineral content of DEQCT in this experiments was determined from empirical constants and mass attenuation coefficients of bone, fat and soft tissue equivalent solution in two photon spectra. In this experiments, the BMC of DEQCT with 80 and 120kV p X rays was compared to ash weight of animal trabecular bone. We obtained the mass attenuation coefficient of 0.2409, 0.5608 and 0.2206 in 80kV p , and 0.2046, 0.3273 and 0.1971 cm 2 /g in 120kV p X-ray spectra for water, bone and fat equivalent materials, respectively. The BMC with DEQCT was accomplished with empirical constants K 1 =0.3232, K 2 =0.2450 and mass attenuation coefficients has very closed to ash weight of animal trabecular bone. The BMC of empirical DEQCT and that of manufacturing DEQCT were correlated with ash weight as a correlation r=0.998 and r=0.996, respectively. The BMC of empirical DEQCT using the experimental mass attenuation coefficients and that of manufacture have showed very close to ash weight of animal trabecular bone. (author)

Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands.

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Giulia Falivelli

Full Text Available The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting "in trans" with ligands anchored to the surface of neighboring cells via a GPI-anchor (ephrin-As or a transmembrane segment (ephrin-Bs, which leads to receptor clustering and increased kinase activity. Additionally, soluble forms of the ephrin-A ligands released from the cell surface by matrix metalloproteases can also activate EphA receptor signaling. Besides these trans interactions, recent studies have revealed that Eph receptors and ephrins coexpressed in neurons can also engage in lateral "cis" associations that attenuate receptor activation by ephrins in trans with critical functional consequences. Despite the importance of the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have not been previously investigated in cancer cells. Here we show that in cancer cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4 but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some cases ephrins that cannot activate a particular Eph receptor in trans can nevertheless inhibit its signaling ability through cis association. We also found that an EphA3 mutation identified in lung cancer enhances cis interaction with ephrin-A3. These results suggest a novel mechanism that may contribute to cancer pathogenesis by attenuating the tumor suppressing effects of Eph receptor signaling pathways activated by ephrins in trans.

Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction for PET/MR on Pediatric Patients.

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Bezrukov, Ilja; Schmidt, Holger; Gatidis, Sergios; Mantlik, Frédéric; Schäfer, Jürgen F; Schwenzer, Nina; Pichler, Bernd J

2015-07-01

Pediatric imaging is regarded as a key application for combined PET/MR imaging systems. Because existing MR-based attenuation-correction methods were not designed specifically for pediatric patients, we assessed the impact of 2 potentially influential factors: inter- and intrapatient variability of attenuation coefficients and anatomic variability. Furthermore, we evaluated the quantification accuracy of 3 methods for MR-based attenuation correction without (SEGbase) and with bone prediction using an adult and a pediatric atlas (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients. The variability of attenuation coefficients between and within pediatric (5-17 y, n = 17) and adult (27-66 y, n = 16) patient collectives was assessed on volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic variability was assessed on SEGwBONEad/pe attenuation maps by computing mean differences to CT-based attenuation maps for regions of bone tissue, lungs, and soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis. Inter- and intrapatient variability of the bias was assessed for each VOI group and method. Statistically significant differences in mean VOI Hounsfield unit values and linear attenuation coefficients between adult and pediatric collectives were found in the lungs and femur. The prediction of attenuation maps using the pediatric atlas showed a reduced error in bone tissue and better delineation of bone structure. Evaluation of PET quantification accuracy showed statistically significant mean errors in mean standardized uptake values of -14% ± 5% and -23% ± 6% in bone marrow and femur-adjacent VOIs with physiologic uptake for SEGbase, which could be reduced to 0% ± 4% and -1% ± 5% using SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all methods. Lung VOIs showed high SDs in the range of 15% for

Classification of bones from MR images in torso PET-MR imaging using a statistical shape model

International Nuclear Information System (INIS)

Reza Ay, Mohammad; Akbarzadeh, Afshin; Ahmadian, Alireza; Zaidi, Habib

2014-01-01

There have been exclusive features for hybrid PET/MRI systems in comparison with its PET/CT counterpart in terms of reduction of radiation exposure, improved soft-tissue contrast and truly simultaneous and multi-parametric imaging capabilities. However, quantitative imaging on PET/MR is challenged by attenuation of annihilation photons through their pathway. The correction for photon attenuation requires the availability of patient-specific attenuation map, which accounts for the spatial distribution of attenuation coefficients of biological tissues. However, the lack of information on electron density in the MR signal poses an inherent difficulty to the derivation of the attenuation map from MR images. In other words, the MR signal correlates with proton densities and tissue relaxation properties, rather than with electron density and, as such, it is not directly related to attenuation coefficients. In order to derive the attenuation map from MR images at 511 keV, various strategies have been proposed and implemented on prototype and commercial PET/MR systems. Segmentation-based methods generate an attenuation map by classification of T1-weighted or high resolution Dixon MR sequences followed by assignment of predefined attenuation coefficients to various tissue types. Intensity-based segmentation approaches fail to include bones in the attenuation map since the segmentation of bones from conventional MR sequences is a difficult task. Most MR-guided attenuation correction techniques ignore bones owing to the inherent difficulties associated with bone segmentation unless specialized MR sequences such as ultra-short echo (UTE) sequence are utilized. In this work, we introduce a new technique based on statistical shape modeling to segment bones and generate a four-class attenuation map. Our segmentation approach requires a torso bone shape model based on principle component analysis (PCA). A CT-based training set including clearly segmented bones of the torso region

Pain and mean absorbed dose to the pubic bone after radiotherapy among gynecological cancer survivors.

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Waldenström, Ann-Charlotte; Olsson, Caroline; Wilderäng, Ulrica; Dunberger, Gail; Lind, Helena; al-Abany, Massoud; Palm, Åsa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

2011-07-15

To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

RANKL/RANK: from bone loss to the prevention of breast cancer.

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Sigl, Verena; Jones, Laundette P; Penninger, Josef M

2016-11-01

RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the preventive strategy for BRCA1-mutation carriers includes preventive mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer. © 2016 The Authors.

β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells

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Bing Yan

2013-01-01

Full Text Available Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. β-Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs showed enhanced proliferation capacity compared to their CD44− counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro. These cells were also more superior in spheroid colony formation (in vitro and tumorigenicity (in vivo and positively associated with microvessel density (in vivo. β-Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro. β-Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. β-Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.

Incidence of bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark

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Fryzek Jon P

2011-01-01

Full Text Available Abstract Background Breast cancer (BrCa is the most commonly diagnosed cancer among women in the industrialized world. More than half of women presenting with metastatic BrCa develop bone metastases. Bone metastases increase the risk of skeletal-related events (SREs, defined as pathological fractures, spinal cord compression, bone pain requiring palliative radiotherapy, and orthopaedic surgery. Both bone metastases and SREs are associated with unfavorable prognosis and greatly affect quality of life. Few epidemiological data exist on SREs after primary diagnosis of BrCa and subsequent bone metastasis. We therefore estimated the incidence of bone metastases and SREs in newly-diagnosed BrCa patients in Denmark from 1999 through 2007. Methods We estimated the overall and annual incidence of bone metastases and SREs in newly-diagnosed breast cancer patients in Denmark from January 1, 1999 to December 31, 2007 using the Danish National Patient Registry (DNPR, which covers all Danish hospitals. We estimated the cumulative incidence of bone metastases and SREs and associated 95% confidence intervals (CI using the Kaplan-Meier method. Results Of the 35,912 BrCa patients, 178 (0.5% presented with bone metastases at the time of primary breast cancer diagnosis, and of these, 77 (43.2% developed an SRE during follow up. A total of 1,272 of 35,690 (3.6% BrCa patients without bone metastases at diagnosis developed bone metastases during a median follow-up time of 3.4 years. Among these patients, 590 (46.4% subsequently developed an SRE during a median follow-up time of 0.7 years. Incidence rates of bone metastases were highest the first year after the primary BrCa diagnosis, particularly among patients with advanced BrCa at diagnosis. Similarly, incidence rates of a first SRE was highest the first year after first diagnosis of a bone metastasis. Conclusions The high incidence of SREs following the first year after first diagnosis of a bone metastasis

32-Phosphorus for bone pain palliation due to bone metastases, its safety and efficacy in patients with advanced cancer

International Nuclear Information System (INIS)

Fettich, J.; Nair, G.; Padky, A.K.; Stare, J.; Nair, N.; Moralles, R.; Riccabona, G.; Tanumihardia, M.

2001-01-01

Bone pain due to bony metastases can seriously affect a patient's quality of life. External irradiation, narcotic drugs and polyphosphates may cause important side effects or are expensive, therefore in many patients radionuclide treatment using a single dose of beta emitting bone seeking radiopharmaceuticals has become widely accepted. Except 32-Phosphorus (32-P) all of them are expensive and difficult to obtain in certain countries. The aim of the study was to evaluate safety and efficacy of 32-P for palliation of bone pain due to bony metastases by comparing it to 89-Strontium (89-Sr), the most commonly used radiopharmaceutical for bone pain palliation in the framework of a prospective IAEA co-ordinated multicenter study. A very strict protocol for unified patient inclusion and follow up was used. 93 cancer patients with osteoblastic bony metastases were included into the study, 48 were treated by 89-Sr (150 MBq) and 45 by 32-P (450 MBq). Pain score, analgesic consumption, quality of life, and indices of bone marrow depression were monitored 2 weeks pre- and up to 4 months post treatment. Favourable response to treatment was recorded in 75% of the patients treated with 89-Sr and in 60% of those treated with 32-P (p=0,122). There was no significant difference between the duration of favourable effect for both radiopharmaceuticals. Moderate decrease of white blood cell (WBC) and platelet counts, and haemoglobin (Hb) levels was detected more often in the 32-P treated group. Although 32-P appears to be more toxic, no toxic effects requiring specific treatment were seen in either group. Due to its comparable efficacy and safety, general availability and low cost its more widespread use should be encouraged to increase quality of life and reduce cost of medical care of patients with intractable bone pain due to cancer metastases. (author)

Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

International Nuclear Information System (INIS)

Nakamura, Ryosuke; Kayamori, Kou; Oue, Erika; Sakamoto, Kei; Harada, Kiyoshi; Yamaguchi, Akira

2015-01-01

Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

Transforming growth factor-β synthesized by stromal cells and cancer cells participates in bone resorption induced by oral squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Ryosuke [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Kayamori, Kou [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Oue, Erika [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Sakamoto, Kei [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Harada, Kiyoshi [Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan)

2015-03-20

Transforming growth factor beta (TGF-β) plays a significant role in the regulation of the tumor microenvironment. To explore the role of TGF-β in oral cancer-induced bone destruction, we investigated the immunohistochemical localization of TGF-β and phosphorylated Smad2 (p-Smad2) in 12 surgical specimens of oral squamous cell carcinoma (OSCC). These studies revealed TGF-β and p-Smad2 expression in cancer cells in all tested cases. Several fibroblasts located between cancer nests and resorbing bone expressed TGF-β in 10 out of 12 cases and p-Smad2 in 11 out of 12 cases. Some osteoclasts also exhibited p ∼ Smad2 expression. The OSCC cell line, HSC3, and the bone marrow-derived fibroblastic cell line, ST2, synthesized substantial levels of TGF-β. Culture media derived from HSC3 cells could stimulate Tgf-β1 mRNA expression in ST2 cells. Recombinant TGF-β1 could stimulate osteoclast formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264 cells. TGF-β1 could upregulate the expression of p-Smad2 in RAW264 cells, and this action was suppressed by the addition of a neutralizing antibody against TGF-β or by SB431542. Transplantation of HSC3 cells onto the calvarial region of athymic mice caused bone destruction, associated with the expression of TGF-β and p-Smad2 in both cancer cells and stromal cells. The bone destruction was substantially inhibited by the administration of SB431542. The present study demonstrated that TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC-induced bone destruction. - Highlights: • Cancer cell, fibroblastic cells, and osteoclasts at bone resorbing area by oral cancer exhibited TGF-β and p-Smad2. • TGF-β1 stimulated osteoclastogenesis induced by RAKL in RAW264 cell. • Xenograft model of oral cancer-induced bone resorption was substantially inhibited by SB431542. • TGF-β synthesized by both cancer cells and stromal cells participates in the OSCC

Bone densitometry in dogs using gamma radiation

International Nuclear Information System (INIS)

Oliveira, A.L.B.; Costa, V.E.; Rezende, M.A.; Grossklauss, D.B.B.F.; Oliveira, T.B.

2010-01-01

Full text. The purpose of this work came from the possibility of joining similar methodologies for determination of density, used in different areas, and provide more precise values of bone density by analyzing the mass attenuation coefficient. For over 20 years, The Applied Physics Laboratory, Department of Physics and Biophysics, IBB- UNESP, Botucatu campus, has been working in the determination of density in different areas, using the methods of immersion and gamma radiation attenuation. The results presented have excellent precision, due to the facility in obtaining and preparing samples, coupled to the large experience in the area. This study aims to determine the bone density of samples of mongrel dogs (dogs without defined breed) by the immersion method; to determine the mass attenuation coefficient of bones samples of mongrel dogs with a gamma radiation source; to discuss and to evaluate the methodological aspects involved in the optic densitometry used nowadays, presenting its advantages and disadvantages and, finally, to examine the effect of animal weight, age and sex on bone densitometry of medium-sized dogs. For this study, we use upper limbs samples, at the joint region humerus-radio-ulnar of after death mongrel dogs, assigned by the Department of Pathology, Faculty of Animal Science and Veterinary Medicine (UNESP-Botucatu) and by the Kennel of the city of Araras, Sao Paulo. This work is performed in three stages. In the first step is determined the density by the method of immersion in water, in the second step, is obtained the mass coefficient attenuation and, finally, in the third step are discussed the implemented methods and evaluate the density bone samples to establish correlations with the age, weight and sex parameters of each group of animals. Based on this methodology , we can find the average value for the mass attenuation coefficient of gamma radiation with energy 59,6, find variations in the values of bone densitometry in the same bone

Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging

DEFF Research Database (Denmark)

Aznar, M.C.; Sersar, Rachida; Saabye, J.

2014-01-01

and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. Methods: Twenty oncology...

Clinical diagnosis of bone metastases of cervical cancer by sup(99m)Tc scintigraphy and computerized tomography

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Doi, S; Okamura, S; Ueki, M; Sugimoto, O [Osaka Medical Coll., Takatsuki (Japan)

1980-05-01

Early diagnosis of recurrence after treatment of cervical cancer has large influence on the prognosis. Local recurrence can be easily discovered by speculum inspection and palpation and also by association with cytodiagnosis and colposcopy. However, remote metastases, especially bone metastasis, though not highly frequent, have been difficult to diagnose. Therefore, we attempted the combination of computerized tomography and bone scintigraphy using sup(99m)Tc-labeled phosphate in 79 cases treated for cervical cancer at stage I to III. As a result, bone metastases was found in 16.7% of the 79 patients. Out of these 79 cases, bone metastases was considered as positive by bone scintigraphy in 15 cases (20.0%), as false positive in 9 cases (11.4%) and as negative, in 55 cases (69.6%). In 24 cases consisting of 15 positive and 9 false-negative cases of bone scintigraphy, CT was performed; 13 cases were proved positive and 11 cases, negative. Thirteen cases, proved positive by both bone scintigraphy and CT were diagnosed to surely have bone metastases. Metastases was found most frequently in the vertebral column (42.1%), and the ribs (26.3%). It was found also in the pelvis and in the femur in some cases. In the cases confirmed in operation to have metastases into the lymphatic glands, the incidence of bone metastases was higher (22.5%) than in the cases without. Metastases were discovered in many cases within 1 year after operation. From the above results, it was found that bone scintigraphy was useful for early discovery of bone metastases after treatment of cervical cancer, and that the additional application with CT would be very valuable in raising the success rate for discovery.

Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

International Nuclear Information System (INIS)

Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

2010-01-01

Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

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)

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.

The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

DEFF Research Database (Denmark)

Kamby, C; Egsmose, C; Söletormos, G

1993-01-01

Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...... bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...

MR-based attenuation correction in brain PET based on UTE sequences

Energy Technology Data Exchange (ETDEWEB)

Cabello, Jorge; Nekolla, Stephan G; Ziegler, Sibylle I [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München (Germany)

2014-07-29

Attenuation correction (AC) in brain PET/MR has recently emerged as one of the challenging tasks in the PET/MR field. It has been shown that to ignore the attenuation produced by bone can lead to errors ranging from 5-30% in regions close to bone structures. Since the information provided by the MR signal is not directly related to tissue attenuation, alternative methods have to be developed. Signal from bone tissue is difficult to measure given its short transverse relaxation time (T2). Ultrashort-echo time (UTE) pulse sequences were developed to measure signal from tissues with short T2. A combination of two consecutive UTE echoes has been used in several works to measure signal from bone tissue. The first echo is able to measure signal from bone tissue in addition to soft tissue, while the second echo contains most of the soft tissue contained in the first echo but not bone. In this work we extract the attenuation information from the difference between the logarithm of two images obtained after applying two consecutive UTE pulse sequences using the mMR scanner (Siemens Healthcare). Subsequently, image processing techniques are applied to reduce the noise and extract air cavities within the head. The resulting image is converted to linear attenuation coefficients, generating what is known as µ-map, to be used during reconstruction. For comparison purposes PET/CT scans of the same patients were acquired prior to the PET/MR scan. Additional µ-maps obtained for comparison were extracted from a Dixon sequence (used in clinical routine) and an additional µ-map calculated by the scanner based on UTE pulse sequences. Preliminary quantitative results measured in the cerebellum, using the value obtained with CT-based AC as reference, show differences of 34% without AC, 13% using the Dixon-based and UTE-based provided by the scanner, and 0.8% with the AC strategy presented here.

[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.

Effect of Thyrotropin Suppression Therapy on Bone in Thyroid Cancer Patients.

Science.gov (United States)

Papaleontiou, Maria; Hawley, Sarah T; Haymart, Megan R

2016-02-01

The thyroid cancer incidence is rising. Despite current guidelines, controversy exists regarding the degree and duration of thyrotropin suppression therapy. Also, its potential skeletal effects remain a concern to physicians caring for thyroid cancer patients. We conducted a review of published data to evaluate existing studies focusing on the skeletal effects of thyrotropin suppression therapy in thyroid cancer patients. A systematic search of the PubMed, Ovid/Medline, and Cochrane Central Register of Controlled Trials databases was conducted. The retained studies were evaluated for methodological quality, and the study populations were categorized into premenopausal women, postmenopausal women, and men. Twenty-five pertinent studies were included. Seven studies were longitudinal and 18 were cross-sectional. Of the 25 included studies, 13 were assigned an excellent methodological quality score. Three of 5 longitudinal studies and 3 of 13 cross-sectional studies reported decreased bone mineral density (BMD) in premenopausal women; 2 of 4 longitudinal studies and 5 of 13 cross-sectional studies reported decreased BMD in postmenopausal women. The remaining studies showed no effect on BMD. The only longitudinal study of men showed bone mass loss; however, cross-sectional studies of men did not demonstrate a similar effect. Studies to date have yielded conflicting results on the skeletal effects of thyrotropin suppression therapy and a knowledge gap remains, especially for older adults and men. Existing data should be cautiously interpreted because of the variable quality and heterogeneity. Identifying groups at risk of adverse effects from thyrotropin suppression therapy will be instrumental to providing focused and tailored thyroid cancer treatment. The standard treatment for thyroid cancer includes total thyroidectomy with or without radioactive iodine ablation, often followed by thyrotropin suppression therapy. Despite current guidelines, controversy exists

Technetium 99m pyrophosphate bone scintigraphy in the exploration of breast cancer bone metastases (analysis of 311 examinations)

International Nuclear Information System (INIS)

Bonichon, Francoise.

1976-01-01

Sodium pyrophosphate was chosen for its ease of application and the quality of the images it gives. The aim of this study, in the context of breast cancer exploration, is to examine: - its reliability for the detection of bone metastases, - the correlation of its results with other factors. The first part reviews the properties of sup(99m)Tc-labelled sodium pyrophosphate and the current hypotheses on the mechanism of its bone fixation, essential for an understanding of the image formation mechanism and for the interpretation of anomalies. Part two gives an analysis of 311 examinations carried out on 223 patients, obtained by the use of a coded file and modern data processing methods. The following are dealt with in turn: - material and methods, - the results themselves and especially their reliability for the whole skeleton and for one bone at a time, - discussion and comparison with published data. Sup(99m)Tc pyrophosphate bone scintigraphy is a simple examination easy to interpret and allows the whole skeleton to be explored. Abnormal scintigraphic images are: - seldom hypofixing lacunae, - usually 'hyperfixing centres' which point to a perilesional bone reaction and depend on: vascular factors, the affinity of technetium for the immature collagen fibres of the forming bone matrix, the affinity of pyrophosphate for the bone mineral substance [fr

Radiotherapy Results of Breast Cancer Patients with Metastatic Bone Disease

Directory of Open Access Journals (Sweden)

Ahmet Dirier

2006-01-01

Full Text Available Breast cancer patients with bone metastasis who had admitted to Dicle University Department of Radiation Oncology for palliative radiation therapy between September 2001 and December 2003 were evaluated. There were 31 patients (26 female, 5 male. Median age was 43 years (range 23-79. Histopathological subtypes were infiltrating ductal carcinoma (88%, tubulolobuler carcinoma (6% and inflammatory carcinoma (6%. Loci of bone metastasis were vertebra only in twelve patients (39%, non-vertebral bones only in 8 patients (26% and both vertebral and nonvertebral bones in 11 patients (35%. Two patients had refused radiotherapy. Radiation doses were 3000 cGy with 10 fractions in 15 patients, 2000 cGy with 5 fractions in 6 patients and 800 cGy single fraction in eight patients. Complete palliation of pain was achieved in 18 patients (62% and partial palliation was achieved in 11 patients (38%. Treatment related toxicity was grade I-II dermatitis. In conclusion; same respons rates in terms of palliation can be achieved in the three radiotherapy schedules.

Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography

International Nuclear Information System (INIS)

Pompe, Esther; Lammers, Jan-Willem J.; Jong, Pim A. de; Jong, Werner U. de; Takx, Richard A.P.; Eikendal, Anouk L.M.; Willemink, Martin J.; Mohamed Hoesein, Firdaus A.A.; Oudkerk, Matthijs; Budde, Ricardo P.J.

2016-01-01

To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT). Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low-dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis. Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 ± 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification. Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT. (orig.)

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.

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

3D printing of high-strength bioscaffolds for the synergistic treatment of bone cancer

Science.gov (United States)

Ma, Hongshi; Li, Tao; Huan, Zhiguang; Zhang, Meng; Yang, Zezheng; Wang, Jinwu; Chang, Jiang; Wu, Chengtie

2018-04-01

The challenges in bone tumor therapy are how to repair the large bone defects induced by surgery and kill all possible residual tumor cells. Compared to cancellous bone defect regeneration, cortical bone defect regeneration has a higher demand for bone substitute materials. To the best of our knowledge, there are currently few bifunctional biomaterials with an ultra-high strength for both tumor therapy and cortical bone regeneration. Here, we designed Fe-CaSiO3 composite scaffolds (30CS) via 3D printing technique. First, the 30CS composite scaffolds possessed a high compressive strength that provided sufficient mechanical support in bone cortical defects; second, synergistic photothermal and ROS therapies achieved an enhanced tumor therapeutic effect in vitro and in vivo. Finally, the presence of CaSiO3 in the composite scaffolds improved the degradation performance, stimulated the proliferation and differentiation of rBMSCs, and further promoted bone formation in vivo. Such 30CS scaffolds with a high compressive strength can function as versatile and efficient biomaterials for the future regeneration of cortical bone defects and the treatment of bone cancer.

Targeting MTA1/HIF-1alpha Signaling by Pterostilbene in Combination with Histone Deacetylase Inhibitor Attenuates Prostate Cancer Progression (Open Access)

Science.gov (United States)

2017-08-30

expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol. Cancer Ther. 6:51–60. 25...2673 Introduction Prostate cancer (PCa) is the second most common cause of cancer - related death in men in the USA because of advanced castrate...signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression Nasir A. Butt1,2, Avinash Kumar1,3

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

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

National Research Council Canada - National Science Library

Anderson, Robin

2001-01-01

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

Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790

DEFF Research Database (Denmark)

Hald, Andreas; Hansen, Rikke Rie; Thomsen, Mette W

2009-01-01

Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activit...

A Dual-Action Armed Replicating Adenovirus for the Treatment of Osteoblastic Bone Metastases of Prostate Cancer

Science.gov (United States)

2007-03-01

that bone metastases of prostate cancer have an extensive bone resorptive component mediated by osteoclasts: resorption of the bone matrix provides...enhances protection by parenteral Mycobac- 795 terium bovis BCG immunization against pulmonary tuberculosis. 796 Infection and Immunity, 74, 4634–4643. 797...oncolysis; replicating adeno- virus; TIMP-2; tumor growth ABBReviATionS MMP matrix metalloproteinase TIMP-2 tissue inhibitor of metalloproteinases-2

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

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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.

Clinical observation on strontium-89-chloride therapy in elder patients with prostate cancer for palliation of pain from bone metastases

International Nuclear Information System (INIS)

Chen Weimin; Lin Tiansheng; Wang Shen; Chen Tanying

2006-01-01

Objective: To estimate clinical curative efficacy and adverse reaction of 89 Sr-chloride therapy for palliation of pain from bone metastases in the older patients with prostate cancer. Methods: 48 cases of older patients with metastatic prostate cancer with bone pain were studied after androgen deprivation therapy, 89 Sr- chloride were administrated iv for the palliative treatment of metastatic bone pain. The curative effects in patients were investigated, including palliation of pain, change of metastatic focus, the tumor sign of PSA, and the adverse reaction. Results: After 89 Sr-chloride therapy, the total palliation rate was 89.6%, inefficiency rate was 10.4%, while metastatic focus and PSA decreased to some extent. No severe adverse reaction occurred. Conclusions: It is shown that the curative efficacy of acesodyne is evident after 89 Sr-chloride therapy in older patients suffering from bone metastase with prostate cancer. It is an effective therapeutic method for the palliation of pain from bone metastases especially to the older patients with multiple metastatases. (authors)

Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008.

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Mikhail Sokolnikov

Full Text Available Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008. The cohort of Mayak Production Association (PA workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface among 25,757 workers who were first employed in 1948-1982. During the period 1948-2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 - 0.26 when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 - 0.21 when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.

Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

Science.gov (United States)

2008-04-01

paclitaxel. British Journal of Cancer 84:1126-34; 2001. 46. Jilka, R. L., Weinstein , R. S., Bellido, T., Roberson, P., Parfitt, A. M., and Manolagas...D., and Harvey , W. J. Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans

Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis.

Science.gov (United States)

Carragee, Eugene J; Chu, Gilbert; Rohatgi, Rajat; Hurwitz, Eric L; Weiner, Bradley K; Yoon, S Tim; Comer, Garet; Kopjar, Branko

2013-09-04

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor known to have in vitro effects on the growth and invasiveness of cancer. It has been approved by the U.S. Food and Drug Administration in limited doses for single-level anterior spinal arthrodesis, but it is commonly used off-label and at high doses. The effect of rhBMP-2 on the risk of cancer has been a concern. We sought to evaluate the risk of new cancers in patients receiving high-dose rhBMP-2. We used publicly available data from a pivotal, multicenter, randomized controlled trial of patients with degenerative lumbar spine conditions who underwent a single-level instrumented posterolateral arthrodesis with either high-dose rhBMP-2 in a compression-resistant matrix (CRM) (rhBMP-2/CRM; n = 239) or autogenous bone graft (control group; n = 224). We compared the risks of new cancers in the rhBMP-2/CRM and control groups at two and five years after surgery. At two years, with 86% follow-up, there were fifteen new cancer events in eleven patients in the rhBMP-2/CRM group compared with two new cancer events in two patients in the control group treated with autogenous bone graft. The incidence rate of new cancer events per 100 person-years was 3.37 (95% confidence interval [CI], 1.89 to 5.56) in the rhBMP-2/CRM group at two years compared with 0.50 (95% CI, 0.06 to 1.80) in the control group. The incidence rate ratio was 6.75 (95% CI, 1.57 to 60.83; p = 0.0026) at two years. Calculated in terms of the number of patients with one or more cancer events two years after the surgery, the incidence rate per 100 person-years was 2.54 (95% CI, 1.27 to 4.54) in the rhBMP-2/CRM group compared with 0.50 (95% CI, 0.06 to 1.82) in the control group at two years; the incidence rate ratio was 5.04 (95% CI, 1.10 to 46.82; p = 0.0194). At five years, there was a 37% loss of follow-up, but a significantly greater incidence of cancer events was still observed in the rhBMP-2/CRM group. A high dose of 40 mg of rh

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.

Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord

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Guiqin Zhu

2016-01-01

Full Text Available Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI in rat tibia (TCI cancer pain model. Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy. Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

International Nuclear Information System (INIS)

Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

2014-01-01

Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools

Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Bostanci, Zeynep, E-mail: zbostanci@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Alam, Samina, E-mail: sra116@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); Soybel, David I., E-mail: dsoybel@hmc.psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States); Kelleher, Shannon L., E-mail: slk39@psu.edu [The Pennsylvania State University, Department of Nutritional Sciences, 209 Chandlee Lab, University Park, PA 16802 (United States); The Pennsylvania State University Milton S. Hershey Medical Center, Department of Surgery, 500 University Dr., Hershey, PA 17033 (United States); The Pennsylvania State University College of Medicine, Department of Cell and Molecular Physiology, 500 University Dr., Hershey, PA 17033 (United States)

2014-02-15

Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging

DEFF Research Database (Denmark)

Aznar, M.C.; Sersar, Rachida; Saabye, J.

2014-01-01

patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET...... and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. Methods: Twenty oncology.......3%) and lowest for spongCT (–2.2%, range: 0.0% to –13.7%). Conclusions: In PET/MR imaging using standard MR-AC PET uptake values in soft lesions and bone lesions are underestimated by about 10%. In individual patients this bias can be as high as 22%, which is significant during clinical follow-up exams. If bone...

Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

Directory of Open Access Journals (Sweden)

Gater Adam

2011-10-01

Full Text Available Abstract Background Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC. Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited. Methods To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL, semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI scale from the McGill Pain Questionnaire (MPQ, and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF was also assessed. Results Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients. Conclusions Study findings support the

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

Directory of Open Access Journals (Sweden)

Tsuyoshi Shimo

2011-02-01

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

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

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Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

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

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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.

Heme oxygenase-1 (HO-1 expression in prostate cancer cells modulates the oxidative response in bone cells.

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Mercedes Ferrando

Full Text Available Prostate cancer (PCa is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1 counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs, we demonstrated that HO-1 pharmacological induction (hemin treatment abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1 cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.

Bone X-ray absorptiometry using two energies

International Nuclear Information System (INIS)

Laval-Jeantet, A.M.; Laval-Jeantet, M.; Bloch, J.

1979-01-01

A method of X-ray absorptiometry using two energies (28 and 36 keV) as a means of determining mineralisation of a bone specimen is described. The ratio of coefficients determined at the different energies varies according to the total mineralisation of the bone studied. A model, representing a serie of bone specimens constructed to study this relationship is described. The coefficients of attenuation for a given wavelength were measured. The relation between the coefficients found at two energies for a given specimen of known mineral content was found to vary as a function of the mineralisation. It is possible to determine the coefficient of attenuation characteristic of a bone and hence its mineralisation and thickness by measurements at two different wavelengths using this function. Experimental results show this potential of the method, but also its high sensitivity to small measurements errors [fr

Zoledronic Acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer.

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Saad, Fred; Eastham, James

2010-11-01

To evaluate, in an exploratory analysis, the effect of zoledronic acid (ZOL) on skeletal-related event (SRE) incidence as determined by the bone pain levels at study entry. Bone metastases can undermine skeletal integrity long before the onset of symptoms. Treating patients before symptom onset might be more effective in preventing SREs and improving patients' quality of life. ZOL has shown significant reductions in SREs and pain compared with placebo in patients with bone metastases from advanced prostate cancer in a randomized placebo-controlled trial. Patients from a placebo-controlled, Phase III trial of men with castration-resistant prostate cancer, randomized to receive ZOL 4 mg (n = 214) or placebo (n = 208) for ≤ 24 months, were stratified by pain or no pain at baseline. Bone pain was assessed at baseline, week 3, and week 6 and at 6-week intervals thereafter. The primary endpoint was the proportion of patients with ≥ 1 SRE. ZOL significantly reduced the mean pain scores compared with placebo at 3, 9, 21, and 24 months (P ≤ .03 for each point) and reduced the annual incidence of SREs. Among patients without baseline pain, ZOL decreased the percentage of patients with ≥ 1 SRE by 39% and reduced the annual incidence of SREs by 49% compared with placebo. ZOL delayed the onset of bone pain in those patients without pain at baseline compared with placebo. ZOL reduced bone pain and SREs compared with placebo in patients with bone metastases from castration-resistant prostate cancer, irrespective of the baseline pain status, and appeared more efficacious when initiated before the onset of pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

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Beheshti, Mohsen; Rezaee, Alireza; Geinitz, Hans; Loidl, Wolfgang; Pirich, Christian; Langsteger, Werner

2016-10-01

18 F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18 F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18 F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18 F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18 F-NaF PET/CT is a highly sensitive method, but 18 F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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

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Hiromichi Iwamura

2018-01-01

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

Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

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Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

2017-01-01

Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

Correlation between bone scan findings and serum PSA level in prostate cancer patients in Bangladesh: both newly diagnosed and hormonally treated cases

International Nuclear Information System (INIS)

Yasmeen, S.; Nasreen, F.; Kabir, M.F.

2007-01-01

Full text: The objective of the current study was to determine whether pre- treatment serum prostate specific antigen (PSA) levels can identify a group with low probability of osseous metastases and safely eliminate the need for bone scan as a routine part of the staging evaluation in Bangladeshi patients with newly diagnosed prostate carcinoma. Also, to find out a cut off value for serum PSA level for predicting positive bone scan in newly diagnosed Bangladeshi prostate cancer patients and to assess the role of PSA level in hormonally treated cases. Prostate cancer most commonly metastasizes to the bone. Bone scintigraphy is one of the best methods in detecting bone metastases, assessing the progression of the disease and response to therapy. For more than 30 yrs it has been known that bone scintigraphy is more sensitive than radiographic, clinical evaluation or chemical markers such as alkaline phosphatase or acid phosphatase in detection of early osseous metastatic prostate cancer. The introduction of PSA has dramatically changed the management of prostate cancer. Serum PSA level has proven to be a useful serum marker for detection of metastatic prostate cancer and it provides the best overall correlation. It also has considerable impact on bone scanning. Of special significance is the fact that patients who have a low PSA level in previously untreated carcinoma of prostate are extremely unlikely to have positive findings on a bone scan for metastases. The picture is different in patients who has received and responded to hormonal therapy. Bone scintigraphy appears to be extremely useful in patients whose PSA level begins to rise after surgical procedure. Patients, who were on anti- androgen therapy, even though they had visible metastatic disease on bone scans, had normal level of PSA Patients and methods: A total of 390 cases were studied. Some (n=242) were newly diagnosed without having any specific treatment other than surgery. Others (n=148) were old cases

Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.

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Jung, Younghun; Decker, Ann M; Wang, Jingcheng; Lee, Eunsohl; Kana, Lulia A; Yumoto, Kenji; Cackowski, Frank C; Rhee, James; Carmeliet, Peter; Buttitta, Laura; Morgan, Todd M; Taichman, Russell S

2016-05-03

GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

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Vessella Robert L

2006-01-01

Full Text Available Abstract Background After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL, a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. Methods Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. Results ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. Conclusion In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.

Application of bone scintigraphy

International Nuclear Information System (INIS)

Rondain, J.E.S.

1996-01-01

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

Standardised uptake values from PET/CT images: comparison with conventional attenuation-corrected PET

International Nuclear Information System (INIS)

Souvatzoglou, M.; Ziegler, S.I.; Martinez, M.J.; Dzewas, G.; Schwaiger, M.; Bengel, F.; Busch, R.

2007-01-01

In PET/CT, CT-derived attenuation factors may influence standardised uptake values (SUVs) in tumour lesions and organs when compared with stand-alone PET. Therefore, we compared PET/CT-derived SUVs intra-individually in various organs and tumour lesions with stand-alone PET-derived SUVs. Thirty-five patients with known or suspected cancer were prospectively included. Sixteen patients underwent FDG PET using an ECAT HR+scanner, and subsequently a second scan using a Biograph Sensation 16PET/CT scanner. Nineteen patients were scanned in the reverse order. All images were reconstructed with an iterative algorithm (OSEM). Suspected lesions were grouped as paradiaphragmatic versus distant from the diaphragm. Mean and maximum SUVs were also calculated for brain, lung, liver, spleen and vertebral bone. The attenuation coefficients (μ values) used for correction of emission data (bone, soft tissue, lung) in the two data sets were determined. A body phantom containing six hot spheres and one cold cylinder was measured using the same protocol as in patients. Forty-six lesions were identified. There was a significant correlation of maximum and mean SUVs derived from PET and PET/CT for 14 paradiaphragmatic lesions (r=0.97 respectively; p<0.001 respectively) and for 32 lesions located distant from the diaphragm (r=0.87 and r=0.89 respectively; p<0.001 respectively). No significant differences were observed in the SUVs calculated with PET and PET/CT in the lesions or in the organs. In the phantom, radioactivity concentration in spheres calculated from PET and from PET/CT correlated significantly (r=0.99; p<0.001). SUVs of cancer lesions and normal organs were comparable between PET and PET/CT, supporting the usefulness of PET/CT-derived SUVs for quantification of tumour metabolism. (orig.)

Neurologic disturbances in case of breast cancer disseminated into cranial bones

International Nuclear Information System (INIS)

Tarasyuk, S.V.; Letyagin, V.P.

1986-01-01

The paper presents data on 52 cases of breast cancer disseminated into cranial vault bones (2 into the orbit). Metastases into the brain (2) and meninges (6) were detected in 17 cases with the aid of computerized tomography of the brain and examination of cerebrospinal fluid. The latter cases were not included into the study group. Metastases into cranial bones were identified by craniography and scanning of the skeleton. Half the patients (18 out of 35) revealed the following neurologic syndromes which were determined by the site of metastases into cranial vault bones and tumour growth pattern (into cranial cavity or soft tissues of the head): lesions in ramus primus nervi trigemini, greater occipital nerve, migraine, pseudotumorous and pseudoencephalitic syndromes. Cases of such neurologic disorders require an all-round examination including ophthalmooscopy, EEG, computerized tomography of the brain, craniography and scanning of the skeleton

Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

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Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

2011-01-01

Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

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

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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.