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)

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)

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

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

Directory of Open Access Journals (Sweden)

J Preston Campbell

2012-07-01

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

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

Science.gov (United States)

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

2012-07-01

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

Molecular mechanism and potential targets for bone metastasis

International Nuclear Information System (INIS)

Iguchi, Haruo

2007-01-01

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

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.

[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.

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

Directory of Open Access Journals (Sweden)

Abdulsalam Alnajjar

2014-12-01

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

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

Science.gov (United States)

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

2011-08-01

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

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

Science.gov (United States)

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

2017-08-26

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

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

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

Science.gov (United States)

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

2016-11-22

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

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

International Nuclear Information System (INIS)

Xu Haiqing; Duan Jun

2011-01-01

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

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.

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

Science.gov (United States)

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

2015-02-01

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

The 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)

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.

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.

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

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

Directory of Open Access Journals (Sweden)

TAKURO ISODA

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

2015-08-21

Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

The Role of Extracellular Vesicles in Bone Metastasis

Directory of Open Access Journals (Sweden)

Michela Rossi

2018-04-01

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

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 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)

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

Energy Technology Data Exchange (ETDEWEB)

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

2000-10-01

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

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

Science.gov (United States)

2017-10-01

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

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

Science.gov (United States)

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

2017-01-01

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

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.

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

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...

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

International Nuclear Information System (INIS)

Wang Xiaoying; Zhang Chunyan; Jiang Xuexiang

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Mary C. Farach-Carson

2017-08-01

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

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

Directory of Open Access Journals (Sweden)

Laura Mercatali

2016-08-01

Full Text Available Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231. The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT, revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.

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

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).

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

International Nuclear Information System (INIS)

Guo Deming

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Fatma Uçar

2011-12-01

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

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

Science.gov (United States)

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

2018-03-26

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

Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

Directory of Open Access Journals (Sweden)

Donna M. Sosnoski

2012-01-01

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

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

International Nuclear Information System (INIS)

Liu Yan; Zhang Xia; Yuan Shiqiang

2010-01-01

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

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

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

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

International Nuclear Information System (INIS)

Nemoto, Shin-ichi; Rinsho, Kenji

1984-01-01

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

Case of thyroid cancer with bone metastasis greatly ameliorated by radiotherapy

Energy Technology Data Exchange (ETDEWEB)

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

1988-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Role of Tumor-Derived Chemokines in Osteolytic Bone Metastasis

Directory of Open Access Journals (Sweden)

Salvatore J. Coniglio

2018-06-01

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

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.

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.)

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

Science.gov (United States)

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

2018-04-06

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-12-15

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

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.

Risk factors and characteristics of prostate cancer bone metastases

Directory of Open Access Journals (Sweden)

Jun-ming LIN

2017-10-01

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

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)

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)

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 ...

Study of bone metastasis of cervical carcinoma by bone scintigraphy

Energy Technology Data Exchange (ETDEWEB)

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

1985-04-01

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

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

Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

Science.gov (United States)

2015-12-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-01-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

In the past decade cancer research has recognized the importance of tumor stroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression have not been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatics analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs

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

OpenAIRE

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

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Alison B. Shupp

2018-06-01

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

A study of bone metastasis of cervical carcinoma by bone scintigraphy

International Nuclear Information System (INIS)

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

1985-01-01

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

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

Science.gov (United States)

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

2018-04-01

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

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

Science.gov (United States)

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

2017-11-01

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

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

Science.gov (United States)

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

2013-11-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Science.gov (United States)

2016-10-01

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

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

Directory of Open Access Journals (Sweden)

Nakamura S

2017-02-01

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

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

Science.gov (United States)

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

2009-01-01

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

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

Science.gov (United States)

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

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

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

Directory of Open Access Journals (Sweden)

Alison Gartland

2016-09-01

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

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

Science.gov (United States)

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

2011-01-01

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

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

National Research Council Canada - National Science Library

Che, Mingxin; Nie, Daotai

2005-01-01

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

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

National Research Council Canada - National Science Library

Che, Mingxin; Nie, Daotai

2006-01-01

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

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

Directory of Open Access Journals (Sweden)

Qinghua ZHOU

2014-03-01

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

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

Science.gov (United States)

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

2013-04-01

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

Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer.

Science.gov (United States)

Lin, Song-Chang; Lee, Yu-Chen; Yu, Guoyu; Cheng, Chien-Jui; Zhou, Xin; Chu, Khoi; Murshed, Monzur; Le, Nhat-Tu; Baseler, Laura; Abe, Jun-Ichi; Fujiwara, Keigi; deCrombrugghe, Benoit; Logothetis, Christopher J; Gallick, Gary E; Yu-Lee, Li-Yuan; Maity, Sankar N; Lin, Sue-Hwa

2017-06-05

Prostate cancer (PCa) bone metastasis is frequently associated with bone-forming lesions, but the source of the osteoblastic lesions remains unclear. We show that the tumor-induced bone derives partly from tumor-associated endothelial cells that have undergone endothelial-to-osteoblast (EC-to-OSB) conversion. The tumor-associated osteoblasts in PCa bone metastasis specimens and patient-derived xenografts (PDXs) were found to co-express endothelial marker Tie-2. BMP4, identified in PDX-conditioned medium, promoted EC-to-OSB conversion of 2H11 endothelial cells. BMP4 overexpression in non-osteogenic C4-2b PCa cells led to ectopic bone formation under subcutaneous implantation. Tumor-induced bone was reduced in trigenic mice (Tie2 cre /Osx f/f /SCID) with endothelial-specific deletion of osteoblast cell-fate determinant OSX compared with bigenic mice (Osx f/f /SCID). Thus, tumor-induced EC-to-OSB conversion is one mechanism that leads to osteoblastic bone metastasis of PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Shuai Huang

2015-08-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-15

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

Clinical outcome for patients of solitary bone only metastasis.

Science.gov (United States)

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

2016-03-01

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

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

Science.gov (United States)

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

2017-01-01

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

Bone metastases from gastric cancer

International Nuclear Information System (INIS)

Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

1983-01-01

We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

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

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

Science.gov (United States)

Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

2010-11-01

Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

Energy Technology Data Exchange (ETDEWEB)

Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

1983-07-01

We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

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)

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-05-15

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

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

Directory of Open Access Journals (Sweden)

Paola Maroni

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2011-08-22

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

The 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

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.

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

Science.gov (United States)

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

2013-10-20

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

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%.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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.)

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

African Journals Online (AJOL)

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

Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

National Research Council Canada - National Science Library

Donahue, Henry

2001-01-01

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Directory of Open Access Journals (Sweden)

Gruber Helen E

2011-08-01

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

Humeral Metastasis from Cervical Cancer: A Rare Case Report

OpenAIRE

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

2015-01-01

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

Brain metastasis from colorectal cancer

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

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

2016-05-03

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

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

Directory of Open Access Journals (Sweden)

Shunfang YANG

2011-02-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Daniele Santini

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

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

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

Al-Ogaili, Zeyad; Troedson, Russell

2016-01-01

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

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

Science.gov (United States)

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

2009-04-01

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

A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis

International Nuclear Information System (INIS)

Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

2016-01-01

Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment

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.)

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.

Mandibular metastasis of adenocarcinoma from prostate cancer: case report according to epidemiology and current therapeutical trends of the advanced prostate cancer

Directory of Open Access Journals (Sweden)

Juliana Dreyer da Silva de Menezes

2013-09-01

Full Text Available Prostate cancer represents the most frequent non-cutaneous neoplasia in males. This type of neoplasia can develop peculiar patterns of evolution, presenting, in many cases, precocious relapses and metastasis. Bone metastasis in the mouth is extremely rare, and represents 1% of all malignant mouth neoplasias. The aim of the present study is to report a clinical case of bone metastasis in the mandibular region associated with a tumoral prostate adenocarcinoma, as well as to discuss connected aspects about diagnosis, prognosis and integrated treatment of this condition.

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

Science.gov (United States)

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

2017-08-01

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

Bone scintigraphy for metastasis detection in canine osteosarcoma

International Nuclear Information System (INIS)

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

1994-01-01

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

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

Science.gov (United States)

Al-Ogaili, Zeyad; Troedson, Russell

2016-02-01

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

Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis

International Nuclear Information System (INIS)

Weichhaus, Michael; Segaran, Prabu; Renaud, Ashleigh; Geerts, Dirk; Connelly, Linda

2014-01-01

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells

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

Directory of Open Access Journals (Sweden)

Anqi Luo

2017-01-01

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

Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

Science.gov (United States)

Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

2017-01-01

Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

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

Science.gov (United States)

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

2010-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

The 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...

Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

Directory of Open Access Journals (Sweden)

Tobias Bäuerle

2008-05-01

Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

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

International Nuclear Information System (INIS)

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

1999-01-01

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

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

Directory of Open Access Journals (Sweden)

Selami Ilgaz Kayılıoğlu

2014-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Isolated splenic metastasis of colon cancer: a case report and literature review

OpenAIRE

Rosa, Nisalda; Martins, Sandra; Lamelas, Javier

2012-01-01

Colorectal cancer (CRC) is a leading cause of death in the elderly and about 20% of these patients present metastasis at diagnosis, most often in the liver. Other common metastatic sites include: lung, bone and brain. Isolated splenic metastases are rare, and they are usually a sign of widespread disease. The authors report a case of the rare occurrence of synchronous isolated splenic metastasis, diagnosed by computed tomography in the preoperative staging of a patient with CRC.O câncer color...

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-10-23

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-10-15

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

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

International Nuclear Information System (INIS)

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

1999-01-01

A case of a 43-year-old man suffering from pleural mesothelioma with distant bone metastasis is reported. The results of bone scintigraphy and NMR findings allowed the diagnosis. The current case describes a hematogenous metastasis to the pelvis and vertebral column from a malignant pleural mesothelioma that was detected initally by bone scintigraphy. (orig.) [de

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-01

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

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

Science.gov (United States)

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

2013-12-17

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

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

Directory of Open Access Journals (Sweden)

Faris Shweikeh

2014-01-01

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

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

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.

Clinical analysis of bone scanning in solitary lesion

International Nuclear Information System (INIS)

Zhu Jun; Zhu Ruisen; Zhu Jifang

2002-01-01

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

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

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

Directory of Open Access Journals (Sweden)

Shuai Huang

2016-07-01

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

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

Science.gov (United States)

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

2014-02-28

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

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)

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.

AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2011-10-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-15

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

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

Directory of Open Access Journals (Sweden)

Thaiz F. Borin

2017-12-01

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

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

International Nuclear Information System (INIS)

Zhu Bao

2009-01-01

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

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

African Journals Online (AJOL)

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

Analysis of metastasis associated signal regulatory network in colorectal cancer.

Science.gov (United States)

Qi, Lu; Ding, Yanqing

2018-06-18

Metastasis is a key factor that affects the survival and prognosis of colorectal cancer patients. To elucidate molecular mechanism associated with the metastasis of colorectal cancer, genes related to the metastasis time of colorectal cancer were screened. Then, a network was constructed with this genes. Data was obtained from colorectal cancer expression profile. Molecular mechanism elucidated the time of tumor metastasis and the expression of genes related to colorectal cancer. We found that metastasis-promoting and metastasis-inhibiting networks included protein hubs of high connectivity. These protein hubs were components of organelles. Some ribosomal proteins promoted the metastasis of colorectal cancer. In some components of organelles, such as proteasomes, mitochondrial ribosome, ATP synthase, and splicing factors, the metastasis of colorectal cancer was inhibited by some sections of these organelles. After performing survival analysis of proteins in organelles, joint survival curve of proteins was constructed in ribosomal network. This joint survival curve showed metastasis was promoted in patients with colorectal cancer (P = 0.0022939). Joint survival curve of proteins was plotted against proteasomes (P = 7 e-07), mitochondrial ribosome (P = 0.0001157), ATP synthase (P = 0.0001936), and splicing factors (P = 1.35e-05). These curves indicate that metastasis of colorectal cancer can be inhibited. After analyzing proteins that bind with organelle components, we also found that some proteins were associated with the time of colorectal cancer metastasis. Hence, different cellular components play different roles in the metastasis of colorectal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

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

OpenAIRE

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

2016-01-01

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

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.

Discordant Findings of Skeletal Metastasis Between Tc99m MDP Bone Scans and F18 FDG PET/CT Imaging for Advanced Breast and Lung Cancers—Two Case Reports and Literature Review

Directory of Open Access Journals (Sweden)

Yu-Wen Chen

2007-12-01

Full Text Available Traditionally, Tc99m methyl diphosphate (MDP bone scintigraphy provides high-sensitivity detection of skeletal metastasis from breast and lung cancers in regular follow-up. Fluorodeoxyglucose (FDG positron emission tomography/computed tomography (PET/CT, based on the glucose metabolism of malignant cells, plays a role in describing rumor growth, proliferation of neoplasm and the extent of metastasis. In general, concordant findings of skeletal metastasis are seen on both types of image, especially in cases of breast and lung cancer. However, there were extremely discordant findings of skeletal metastasis between bone scans and F18 FDG PET/CT imaging in two cases among 300 consecutive F18 FDG PET/CT follow-up exams of patients with malignancies, during the past year, in our center. Both cases, one of breast cancer and one of lung cancer, had negative bone scintigraphic findings, but a diffusely high grade of F18 FDG avid marrow infiltration in the axial spine, leading to the diagnosis of stage IV disease in both cases. Owing to variant genetic aberrance of malignance, F18 FDG PET/CT reveals direct evidence of diffuse, rapid neoplasm metabolism in the bone marrow of the spine, but not of secondary osteoblastic reactions in vivo. F18 FDG PET/CT should always be employed in the follow-up of patients with malignancies.

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.)

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)

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

International Nuclear Information System (INIS)

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

2011-01-01

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

NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use.

Science.gov (United States)

McCaffrey, Gwen; Thompson, Michelle L; Majuta, Lisa; Fealk, Michelle N; Chartier, Stephane; Longo, Geraldine; Mantyh, Patrick W

2014-12-01

Studies in animals and humans show that blockade of nerve growth factor (NGF) attenuates both malignant and nonmalignant skeletal pain. While reduction of pain is important, a largely unanswered question is what other benefits NGF blockade might confer in patients with bone cancer. Using a mouse graft model of bone sarcoma, we demonstrate that early treatment with an NGF antibody reduced tumor-induced bone destruction, delayed time to bone fracture, and increased the use of the tumor-bearing limb. Consistent with animal studies in osteoarthritis and head and neck cancer, early blockade of NGF reduced weight loss in mice with bone sarcoma. In terms of the extent and time course of pain relief, NGF blockade also reduced pain 40% to 70%, depending on the metric assessed. Importantly, this analgesic effect was maintained even in animals with late-stage disease. Our results suggest that NGF blockade immediately upon detection of tumor metastasis to bone may help preserve the integrity and use, delay the time to tumor-induced bone fracture, and maintain body weight. ©2014 American Association for Cancer Research.

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

Directory of Open Access Journals (Sweden)

Hiromichi Iwamura

2018-01-01

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

Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

Energy Technology Data Exchange (ETDEWEB)

Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

2012-03-15

A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

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

Directory of Open Access Journals (Sweden)

Yi-Rang Na

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

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

Directory of Open Access Journals (Sweden)

Diego Andres Adrianzen Herrera

2018-04-01

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

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

Science.gov (United States)

Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

2015-11-01

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. ©2015 American Association for Cancer Research.

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

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

Directory of Open Access Journals (Sweden)

Limin eZhu

2013-09-01

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

Renal Metastasis from Primary Cervical Cancer: A Case Report

International Nuclear Information System (INIS)

Jeon, Seong Woo; Kim, See Hyung; Kwon, Sun Young

2013-01-01

Metastasis of malignant tumors to the kidney is clinically rare and often discovered by autopsy. Primary lymphoma and lung cancer are known that can metastasize to the kidney. Other malignant tumor metastasis to the kidney is very unusual. Primary cervical cancer metastasis to adjacent pelvic organs and lymph nodes are well known followed by abdominal solid organs such as the liver and adrenal glands. However, reported primary cervical cancer metastasis to the kidney is extremely rare and mostly appeared as bilateral multiple renal masses. We report here on a rare case of unilateral single renal metastasis from primary cervical cancer after concur- rent chemoradiotherapy.

Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

Energy Technology Data Exchange (ETDEWEB)

Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

2013-10-15

The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

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.

Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

International Nuclear Information System (INIS)

Roy, S.S.; Vadlamudi, R.K.

2012-01-01

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

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

Energy Technology Data Exchange (ETDEWEB)

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

1999-05-01

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

Molecular biology of breast cancer metastasis: Genetic regulation of human breast carcinoma metastasis

International Nuclear Information System (INIS)

Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W

2000-01-01

The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention

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

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

Science.gov (United States)

Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

2018-01-01

No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

Science.gov (United States)

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

2015-05-05

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

What Is Breast in the Bone?

Science.gov (United States)

Shemanko, Carrie S; Cong, Yingying; Forsyth, Amanda

2016-10-22

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Zhiwen Xiao

2014-01-01

Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

Remodeling of the methylation landscape in breast cancer metastasis.

Directory of Open Access Journals (Sweden)

Marsha Reyngold

Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

Wang Xinhua; Zhao Yanping; Lu Haijian; Dong Zhanfei

2010-01-01

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

Platelet "first responders" in wound response, cancer, and metastasis.

Science.gov (United States)

Menter, David G; Kopetz, Scott; Hawk, Ernest; Sood, Anil K; Loree, Jonathan M; Gresele, Paolo; Honn, Kenneth V

2017-06-01

Platelets serve as "first responders" during normal wounding and homeostasis. Arising from bone marrow stem cell lineage megakaryocytes, anucleate platelets can influence inflammation and immune regulation. Biophysically, platelets are optimized due to size and discoid morphology to distribute near vessel walls, monitor vascular integrity, and initiate quick responses to vascular lesions. Adhesion receptors linked to a highly reactive filopodia-generating cytoskeleton maximizes their vascular surface contact allowing rapid response capabilities. Functionally, platelets normally initiate rapid clotting, vasoconstriction, inflammation, and wound biology that leads to sterilization, tissue repair, and resolution. Platelets also are among the first to sense, phagocytize, decorate, or react to pathogens in the circulation. These platelet first responder properties are commandeered during chronic inflammation, cancer progression, and metastasis. Leaky or inflammatory reaction blood vessel genesis during carcinogenesis provides opportunities for platelet invasion into tumors. Cancer is thought of as a non-healing or chronic wound that can be actively aided by platelet mitogenic properties to stimulate tumor growth. This growth ultimately outstrips circulatory support leads to angiogenesis and intravasation of tumor cells into the blood stream. Circulating tumor cells reengage additional platelets, which facilitates tumor cell adhesion, arrest and extravasation, and metastasis. This process, along with the hypercoagulable states associated with malignancy, is amplified by IL6 production in tumors that stimulate liver thrombopoietin production and elevates circulating platelet numbers by thrombopoiesis in the bone marrow. These complex interactions and the "first responder" role of platelets during diverse physiologic stresses provide a useful therapeutic target that deserves further exploration.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-09-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis

Science.gov (United States)

2011-01-01

affect breast cancer metastasis with a subcutaneous mouse tumor implantation model of breast cancer metastasis. HMLE -Twist1 cells expressing shRNAs...13 4 Introduction Distant metastases are responsible for the vast majority of breast cancer deaths. This process...to migrate and invade is therefore essential to the metastatic process. The initial steps of breast cancer metastasis, local invasion and

The Role of Purinergic Receptors in Cancer-Induced Bone Pain

Directory of Open Access Journals (Sweden)

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.

Brain metastasis of breast cancer: clinical and radiologic findings

International Nuclear Information System (INIS)

An, Jin Kyung; Oh, Ki Keun; Kim, Eun Kyung; Chung, Tae Sub

2001-01-01

To analyse the clinical and radiologic findings brain metastasis of breast cancer. Sixty-one of 1399 patients in whom breast cancer was diagnosed between 1983 and 1999 were affected by brain metastasis. Among these 1399, the stage of the breast cancer, in descending order of frequency, was IIA (n=508), I (n=366), IIB (n=247), IIIA (n=189), IIIB (n=45), 0 (n=33) and IV (n=11). The stage of the 61 brain metastases, similarly ordered, was IIB (12.5%), IIA (3.9%), IIIA (3.1%), IIIB (2.2%) and I (0.8%). In all confirmed breast cancers, the age distribution, in descending order of frequency, was 40-49years (n=610), 50-59 (n=301), 30-39 (n=291), 60-69 (n=124), 20-19 (n=41), 70-79 (n=28), and 80-89 (n=4). The age distribution of brain metastasis was 20-29 (14.6%), 30-39 (7.9%), 50-59 (4.6%). 40-49 (2.6%) and 60-69 (1.6%). Imaging findings were available for 35 of the 61 patients affected by brain metastasis, and symptoms from brain among the 35, analysis of the symptoms of this metastasis, the site of the first distant metastasis to an extracranial or cranial organ, the interval from the diagnosis of breast cancer to brain metastasis, the interval from brain metastasis to death, and the difference in survival time between patients with initial and succeeding brain metastasis was undertaken. Brain CT findings were analysed in 29 cases and MRI findings in eight. The most common symptoms were headache and vomiting. Among the 35 brain metastasis patients for whom imaging findings were available, other systemic metastasis occurred in 22. Initial brain metastasis occurred in the remaining 13, and in seven of these there was also coincident organ metastasis, while six showed only brain metastasis, The most frequent intervals from the diagnosis of breast cancer to brain metastasis were 1-2 years(8/35) and 2-3years(8/35). Twenty-six of 35 patients died within one year of brain metastasis. Patients in whom this occurred later survived for longer than those in whom it occurred

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

Directory of Open Access Journals (Sweden)

Romeeta Trehan

2015-01-01

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

EHMT2 is a metastasis regulator in breast cancer.

Science.gov (United States)

Kim, Kwangho; Son, Mi-Young; Jung, Cho-Rok; Kim, Dae-Soo; Cho, Hyun-Soo

2018-02-05

Various modes of epigenetic regulation of breast cancer proliferation and metastasis have been investigated, but epigenetic mechanisms involved in breast cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone methyltransferase) was determined to be significantly overexpressed in breast cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell migration/invasion and regulated the expression of EMT-related markers (E-cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells. Therefore, our findings demonstrate functions of EHMT2 in breast cancer metastasis and suggest that targeting EHMT2 may be an effective therapeutic strategy for preventing breast cancer metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of GAGE cancer/testis antigen in metastasis

DEFF Research Database (Denmark)

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

2016-01-01

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

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

Science.gov (United States)

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Case of Urethral Metastasis from Sigmoid Colon Cancer Diagnostically and Prognostically Indicated by F 18 FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Seo, Han Seok; Kim, Eun Sil; Kim, Soyon; Im, Su Jin; Park, Yong Hyun; Lee, Ju Hyoung; Hur, So Chong [National Police Hospital, Seoul (Korea, Republic of)

2011-12-15

Urethral metastasis from colorectal cancer is rare and is known to have a poor prognosis. A 72 year old man with a history of colectomy and colostomy due to sigmoid colon cancer was admitted to the emergency room with bowel distension, rectal bleeding and urinary symptoms. Computed tomography of the abdominopelvis showed sigmoid colon cancer with multiple metastases involving the liver. Positron emission tomography with F 18 fluorodeoxyglucose (FDG) showed multiple hypermetabolic foci in the liver, penis and pubic bone, which otherwise could not be diagnosed. The lesions revealed no improvement with chemotherapy and urological surgery on follow up F 18 FDG PET/CT. We present a case of urethral metastasis of sigmoid colon cancer diagnostically and prognostically indicated by F 18 FDG PET/CT.

A Case of Urethral Metastasis from Sigmoid Colon Cancer Diagnostically and Prognostically Indicated by F 18 FDG PET/CT

International Nuclear Information System (INIS)

Seo, Han Seok; Kim, Eun Sil; Kim, Soyon; Im, Su Jin; Park, Yong Hyun; Lee, Ju Hyoung; Hur, So Chong

2011-01-01

Urethral metastasis from colorectal cancer is rare and is known to have a poor prognosis. A 72 year old man with a history of colectomy and colostomy due to sigmoid colon cancer was admitted to the emergency room with bowel distension, rectal bleeding and urinary symptoms. Computed tomography of the abdominopelvis showed sigmoid colon cancer with multiple metastases involving the liver. Positron emission tomography with F 18 fluorodeoxyglucose (FDG) showed multiple hypermetabolic foci in the liver, penis and pubic bone, which otherwise could not be diagnosed. The lesions revealed no improvement with chemotherapy and urological surgery on follow up F 18 FDG PET/CT. We present a case of urethral metastasis of sigmoid colon cancer diagnostically and prognostically indicated by F 18 FDG PET/CT.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

Directory of Open Access Journals (Sweden)

Fumito Kuranishi

2018-01-01

Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

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.

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.

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

International Nuclear Information System (INIS)

Liu Yang; Wang Huixiang; Zhou Tao

2012-01-01

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

Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

Directory of Open Access Journals (Sweden)

Ihsen Slim

2012-01-01

Full Text Available Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma. It is generally confined to the neck with or without spread to regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly include lung and bone. Metastases involving oral and maxillofacial region are extremely rare. We described a case of malar metastasis revealing a follicular variant of papillary thyroid carcinoma, presenting with pain and swelling of the left cheek in a 67-years-old female patient with an unspecified histological left lobo-isthmectomy medical history. To our knowledge, this is the first recorded instance of a malar metastasis from a follicular variant of papillary thyroid carcinoma.

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

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

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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

Inhibition of Breast Cancer Metastasis by Heregulin-Beta 1

National Research Council Canada - National Science Library

Yu, Dihua

1999-01-01

The major goal of this Idea proposal is to determine whether and how HRG-Beta1 inhibits breast cancer metastasis and to identify the functional domains that are sufficient for inhibition of breast cancer metastasis...

Investigation of the roles of exosomes in colorectal cancer liver metastasis.

Science.gov (United States)

Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

2015-05-01

The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

Genomic analyses of breast cancer progression reveal distinct routes of metastasis emergence

DEFF Research Database (Denmark)

Krøigård, Anne Bruun; Larsen, Martin Jakob; Brasch-Andersen, Charlotte

2017-01-01

receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound...... clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis....

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

Science.gov (United States)

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

2013-07-01

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

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Science.gov (United States)

Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

2018-05-01

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Testicular Metastasis of Prostate Cancer: A Case Report

Directory of Open Access Journals (Sweden)

Ayumu Kusaka

2014-09-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Evaluating human cancer cell metastasis in zebrafish

International Nuclear Information System (INIS)

Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

2013-01-01

In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-10-15

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Current status of research on microRNA associated with colorectal cancer liver metastasis

Directory of Open Access Journals (Sweden)

WANG Dongxu

2016-12-01

Full Text Available Tumor metastasis is a complicated process with multiple steps, and liver metastasis is the most common metastatic mode of colorectal cancer. Deep understanding and study of metastatic mechanism helps to find solutions for colorectal cancer liver metastasis. Recent studies have shown that microRNA are involved in tumor metastasis and recurrence, and studies on microRNA associated with colorectal cancer liver metastasis can provide new thoughts for the development and progression, diagnosis and treatment, and prognosis of the disease. This article summarizes the research advances in microRNA associated with colorectal cancer liver metastasis and reviews the biological function and molecular mechanism of microRNA, which suggests that microRNA have a vital significance in the field of tumor metastasis, especially colorectal cancer liver metastasis.

Cancer cell metastasis; perspectives from the focal adhesion

Directory of Open Access Journals (Sweden)

Lefteris C Zacharia

2015-10-01

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

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

International Nuclear Information System (INIS)

Liu Baoping; Mao Ronghu; Han Xingmin

2008-01-01

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

MRI features of meningeal metastasis from lung cancer

International Nuclear Information System (INIS)

Luo Xuemao; Long Wansheng; Jin Zhifa; Hu Maoqing; Mai Xuyu

2009-01-01

Objective: To investigate the pathway and MRI findings of meningeal metastasis original from lung cancer. Methods: 44 cases with cerebro-spinal meningeal metastasis original from lung cancer proven by clinical and pathology were retrospectively reviewed. All cases undergone plain MRI scan and Gd-DTPA enhanced MRI scan on brain and/or spine. Results: MRI plain scan indicated 28 cases with brain metastases, 3 cases with meningeal nodosity or irregularly patchy abnormal signal, 1 case with nodule in left cavernous sinus, 10 cases with abnormal signal in spine, 2 cases with abnormal signal in spinal dura mater. 34 cases with cerebro meningeal metastases were found in MRI enhancement scan. Among them, 11 cases displayed cerebral dura mater-arachnoid enhancement, 17 cases revealed cerebral pia mater-arachnoid enhancement and 6 cases with mixed typed enhancement. Osteoclasia in skull was found in 4 cases, spinal metastasis was revealed in 17 cases, and patchy abnormal enhancement in spinal dura mater was showed in 12 cases. Conclusion: Hematogenous metastasis is a main route of meningeal metastasis caused by lung cancer and enhanced MRI scan is of important diagnostic value. (authors)

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.

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)

Bone Cancer

Science.gov (United States)

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

The role of glycosylation in breast cancer metastasis and cancer control

Directory of Open Access Journals (Sweden)

Alexandra eKölbl

2015-10-01

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

99mTc-MDP bone scanning of patients with diffuse metastatic carcinoma of the axial skeleton

International Nuclear Information System (INIS)

Morita, Seiichiro; Ishibashi, Masatoshi; Takahashi, Kazuyuki; Funatsu, Kazuhiro; Yoshii, Toshiaki; Shirabe, Ichiju; Nomura, Yasushi; Ohtake, Hisashi

1990-01-01

Fifteen bone scintigrams in patients with diffuse bone metastases were reviewed because of the diffuse radionuclide accumulation in the axial skeleton. Diagnoses were gastric cancer in 6 patients, prostatic cancer in 5, breast cancer in 3, and renal pelvic tumor in one. In 5 patients with gastric cancer, one with prostatic cancer, and one with renal pelvic tumor, initial bone scintigraphy showed diffuse accumulation. In one gastric cancer patient and two breast cancer patients, the multiple bone metastases had altered the diffuse bone metastasis. All patients had no lung or liver metastasis morphologically at the course of diagnosed diffuse bone metastasis. Overall, the diffuse bone metastases were classified into two groups: diffuse symmetrical accumulation in proportion to bone marrow demonstrated in the gastric cancer, and diffuse accumulation centering the axial skeleton with asymmetrical accumulation in the rib and extremities demonstrated in cancer of the prostate. The finding of X ray films were consistent to common bone metastases in proportion to the primary tumor. Diffuse bone metastases did not show the characteristic finding. During the period from the diagnosed time to the death of patients, the patients with gastric cancer died extremely earlier in comparison to the patients with breast cancer and with prostatic cancer. (author)

Malignant Giant Cell Tumour of Bone with Axillary Metastasis

African Journals Online (AJOL)

2002-06-06

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

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...

Expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer.

Science.gov (United States)

Mikami, Koji; Hirano, Yukiko; Futami, Kitaro; Maekawa, Takafumi

2017-07-18

Mixed-type early gastric cancer (differentiated and undifferentiated components) incurs a higher risk of lymph node metastasis than pure-type early gastric cancer (only differentiated or only undifferentiated components). Therefore, we investigated the expansion of lymph node metastasis in mixed-type submucosal invasive gastric cancer in order to establish the most appropriate treatment for mixed-type cancer. We retrospectively analyzed 279 consecutive patients with submucosal invasive gastric cancer who underwent curative gastrectomy for gastric cancer between 1996 and 2015. We classified the patients into the mixed-type and pure-type groups according to histologic examination and evaluated the expansion of lymph node metastasis. The rate of lymph node metastasis was 23.7% (66/279) in the total patients, 36.4% (36/99) in the mixed-type group, and 16.6% (30/180) in the pure-type group. The significant independent risk factors for lymph node metastasis were tumor size ≥2.0 cm (P = 0.014), mixed-type gastric cancer (P mixed-type group. The rates of no. 7 lymph node metastasis in the total patients and mixed-type group were 2.9% (8/279) and 5.1% (5/99), respectively; the rates of no. 8a lymph node metastasis were 1.4% (4/279) and 4.0% (4/99), respectively. Mixed histological type is an independent risk factor for lymph node metastasis. Lymph node metastasis in mixed-type gastric cancer involves expansion to the no. 7 and no. 8a lymph nodes. Therefore, lymphadenectomy for mixed-type submucosal invasive gastric cancer requires D1+ or D2 dissection. Copyright © 2017. Published by Elsevier Taiwan.

SOLITARY SPLENIC METASTASIS OF COLON CANCER: A CASE REPORT

Directory of Open Access Journals (Sweden)

Sh. Hashemzadeh M. Safari

2004-11-01

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

Cigarette smoking and risk of lung metastasis from esophageal cancer.

Science.gov (United States)

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

2008-10-01

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

Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer.

Science.gov (United States)

Nagata, Hiroshi; Ishihara, Soichiro; Hata, Keisuke; Murono, Koji; Kaneko, Manabu; Yasuda, Koji; Otani, Kensuke; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

2017-05-01

The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.

Understanding the biology of urothelial cancer metastasis

Directory of Open Access Journals (Sweden)

Takashi Kobayashi

2016-10-01

Full Text Available Management of unresectable urothelial cancer (UC has been a clinical challenge for decades. While drug resistance is a key issue, precise understanding of biology of UC metastasis is another challenge for the improvement of treatment outcome of UC patients. Introduction of the cell biology concepts including epithelial-mesenchymal transition (EMT and cancer stemness seems to explain UC metastasis. Molecular genetics based on gene expression profiling, next generation sequencing, and explosion of non-coding RNA world has opened the door to intrinsic molecular subtyping of UC. Next steps include, based on the recently accumulated understanding, the establishment of novel disease models representing UC metastasis in various experimental platforms, particularly in vivo animal systems. Indeed, novel knowledge molecular genetics has not been fully linked to the modeling of UC metastasis. Further understanding of bladder carcinogenesis is needed particularly with regard to cell of origin related to tumor characteristics including driver gene alterations, pathological differentiations, and metastatic ability. Then we will be able to establish better disease models, which will consequently lead us to further understanding of biology and eventually the development of novel therapeutic strategies for UC metastasis.

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

Directory of Open Access Journals (Sweden)

Jamie Heimburg

2006-11-01

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

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

Directory of Open Access Journals (Sweden)

Po-Chun Chen

2017-01-01

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

Active Roles of Tumor Stroma in Breast Cancer Metastasis

International Nuclear Information System (INIS)

Khamis, Z.I.; Sang, Q.A.; Sahab, Z.J.

2012-01-01

Metastasis is the major cause of death for breast cancer patients. Tumors are heterogenous cellular entities composed of cancer cells and cells of the microenvironment in which they reside. A reciprocal dynamic interaction occurs between the tumor cells and their surrounding stroma under physiological and pathological conditions. This tumor-host communication interface mediates the escape of tumor cells at the primary site, survival of circulating cancer cells in the vasculature, and growth of metastatic cancer at secondary site. Each step of the metastatic process is accompanied by recruitment of stromal cells from the microenvironment and production of unique array of growth factors and chemokines. Stromal microenvironment may play active roles in breast cancer metastasis. Elucidating the types of cells recruited and signal pathways involved in the crosstalk between tumor cells and stromal cells will help identify novel strategies for cotargeting cancer cells and tumor stromal cells to suppress metastasis and improve patient outcome

Active Roles of Tumor Stroma in Breast Cancer Metastasis

Directory of Open Access Journals (Sweden)

Zahraa I. Khamis

2012-01-01

Full Text Available Metastasis is the major cause of death for breast cancer patients. Tumors are heterogenous cellular entities composed of cancer cells and cells of the microenvironment in which they reside. A reciprocal dynamic interaction occurs between the tumor cells and their surrounding stroma under physiological and pathological conditions. This tumor-host communication interface mediates the escape of tumor cells at the primary site, survival of circulating cancer cells in the vasculature, and growth of metastatic cancer at secondary site. Each step of the metastatic process is accompanied by recruitment of stromal cells from the microenvironment and production of unique array of growth factors and chemokines. Stromal microenvironment may play active roles in breast cancer metastasis. Elucidating the types of cells recruited and signal pathways involved in the crosstalk between tumor cells and stromal cells will help identify novel strategies for cotargeting cancer cells and tumor stromal cells to suppress metastasis and improve patient outcome.

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Gastric metastasis of triple negative invasive lobular carcinoma

OpenAIRE

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

2015-01-01

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

Pancreatic Metastasis from Prostate Cancer

Directory of Open Access Journals (Sweden)

Julian Jacob

2010-01-01

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

Angiotensin II facilitates breast cancer cell migration and metastasis.

Directory of Open Access Journals (Sweden)

Sylvie Rodrigues-Ferreira

Full Text Available Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.

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

Science.gov (United States)

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

2015-10-20

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

Blocking Breast Cancer Metastasis by Targeting RNA-Binding Protein HuR

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0730 TITLE: Blocking Breast Cancer Metastasis by Targeting RNA-Binding Protein HuR PRINCIPAL INVESTIGATOR: Danny Welch...NUMBER Blocking Breast Cancer Metastasis by Targeting RNA-Binding Protein HuR 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...increased aggressiveness in breast cancer , the primary objective of this proposal is to assess whether HuR (or analogs) prevent and/or treat metastasis and/or

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

Directory of Open Access Journals (Sweden)

Mitsuyoshi Tei

2014-01-01

CONCLUSION: This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer.

Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

Directory of Open Access Journals (Sweden)

Jian Cao

2014-03-01

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

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

Nodal metastasis in thyroid cancer

International Nuclear Information System (INIS)

Samuel, A.M.

1999-01-01

The biological behavior and hence the prognosis of thyroid cancer (TC) depends among other factors on the extent of spread of the disease outside the thyroid bed. This effect is controversial, especially for nodal metastasis of well differentiated thyroid carcinoma (WDC). Nodal metastasis at the time of initial diagnosis behaves differently depending on the histology, age of the patient, presence of extrathyroidal extension, and the sex of the individual. The type of the surgery, administration of 131 I and thyroxin suppression also to some extent influence the rate of recurrence and mortality. Experience has shown that it is not as innocuous as a small intrathyroidal tumor without any invasion outside the thyroid bed and due consideration should be accorded to the management strategies for handling patients with nodal metastasis

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Staging Lung Cancer: Metastasis.

Science.gov (United States)

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

2018-05-01

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

Samarium-153-EDTMP in the metastatic bone pain treatment

International Nuclear Information System (INIS)

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

1997-01-01

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

Metformin: An Emerging New Therapeutic Option for Targeting Cancer Stem Cells and Metastasis

Directory of Open Access Journals (Sweden)

Ramandeep Rattan

2012-01-01

Full Text Available Metastasis is an intricate process by which a small number of cancer cells from the primary tumor site undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Transition of a cancer cell from epithelial to mesenchymal phenotype is thought to be the first step in the progression of metastasis. Recently, the recognition of cancer stem cells has added to the perplexity in understanding metastasis, as studies suggest cancer stem cells to be the originators of metastasis. All current and investigative drugs have been unable to prevent or reverse metastasis, as a result of which most metastatic cancers are incurable. A potential drug that can be considered is metformin, an oral hypoglycemic drug. In this review we discuss the potential of metformin in targeting both epithelial to mesenchymal transition and cancer stem cells in combating cancer metastases.

The role of exosomes in cancer metastasis.

Science.gov (United States)

Steinbichler, Teresa Bernadette; Dudás, József; Riechelmann, Herbert; Skvortsova, Ira-Ida

2017-06-01

Exosomes are small membrane vesicles with a size ranging from 40 to 100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis. Metastasis is a complex multistep process of cancer cell invasion, survival in blood vessels, attachment to and colonization of the host organ. Exosomes influence every step of this cascade and can be targeted by oncological treatment. This review highlights the role of exosomes in the various steps of the metastatic cascade and how exosome dependent pathways can be targeted as therapeutic approach or used for liquid biopsies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Multiple Roles of Exosomes in Metastasis

Science.gov (United States)

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

2016-01-01

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

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.

An Unusual Presentation of Lung Cancer Metastasis: Perianal Abscess

OpenAIRE

Murat Kilic

2014-01-01

Lung cancer is one of the most commonly diagnosed cancers in both men and women. Although the most frequent sites of distant metastasis of lung cancers are the pleura, liver, adrenal glands, skeletal system and brain, perianal region has been rarely reported as a metastasis site. A male patient was admitted to our emergency room with a long standing perianal abscess. During abscess drainage, a mass was noticed at the base of the abscess pouch, and thus a biopsy was taken. Pathologically, it w...

Gut metastasis from breast carcinoma

International Nuclear Information System (INIS)

Al-Qahtani, Mohammad S.

2007-01-01

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

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

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.

The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis

International Nuclear Information System (INIS)

Havens, AM; Jung, Y; Sun, YX; Wang, J; Shah, RB; Bühring, HJ; Pienta, KJ; Taichman, RS

2006-01-01

The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes

Cancer metabolism and the dynamics of metastasis.

Science.gov (United States)

Dattoli, G; Guiot, C; Delsanto, P P; Ottaviani, P L; Pagnutti, S; Deisboeck, T S

2009-02-07

Cancer growth dynamics, commonly simulated with a Gompertzian model, is analyzed in the framework of a more recent and realistic model. In particular, we consider the setting of a tumor embedded in a host organ and investigate their interaction. We assume that, at least in some cases, tumor metastasis may be triggered by an 'energetic crisis', when the tumor exceeds the 'carrying capacity' of the host organ. As a consequence, dissemination of clusters of cancer cells is set in motion, with a statistical probability given by a Poisson distribution. The model, although still at a preclinical level, is fully quantitative and is applied, as an example, to the case of prostate cancer. The results confirm that, at least for the more aggressive cancers, metastasis starts very early during tumorigenesis and a quantitative link is found between the tumor's doubling time, its 'aggressiveness' and the metastatic potential.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-06-15

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

An Unusual Presentation of Lung Cancer Metastasis: Perianal Abscess

Directory of Open Access Journals (Sweden)

Murat Kilic

2014-06-01

Full Text Available Lung cancer is one of the most commonly diagnosed cancers in both men and women. Although the most frequent sites of distant metastasis of lung cancers are the pleura, liver, adrenal glands, skeletal system and brain, perianal region has been rarely reported as a metastasis site. A male patient was admitted to our emergency room with a long standing perianal abscess. During abscess drainage, a mass was noticed at the base of the abscess pouch, and thus a biopsy was taken. Pathologically, it was reported as a metastasis of squamous cell carcinoma, therefore some radiological  investigations and endoscopic procedures were performed to determine the primary focus of cancer. A pulmonary mass was revealed in PET/CT, and was considered as primary tumor. Both primary and metastatic perianal tumors can be rarely presented as an abscess formation. In this situation, a biopsy should be performed from the lesion to avoid misdiagnosis.

Chemokines: novel targets for breast cancer metastasis

Science.gov (United States)

Ali, Simi; Lazennec, Gwendal

2007-01-01

Recent studies have highlighted the possible involvement of chemokines and their receptors in breast cancer progression and metastasis. Chemokines and their receptors constitute a superfamily of signalling factors whose prognosis value in breast cancer progression remains unclear. We will examine here the expression pattern of chemokines and their receptors in mammary gland physiology and carcinogenesis. The nature of the cells producing chemokines or harboring chemokine receptors appears to be crucial in certain conditions for example, the infiltration of the primary tumor by leukocytes and angiogenesis. In addition, chemokines, their receptors and the interaction with glycosaminoglycan (GAGs) are key players in the homing of cancer cells to distant metastasis sites. Several lines of evidence, including in vitro and in vivo models, suggest that the mechanism of action of chemokines in cancer development involves the modulation of proliferation, apoptosis, invasion, leukocyte recruitment or angiogenesis. Furthermore, we will discuss the regulation of chemokine network in tumor neovascularity by decoy receptors. The reasons accounting for the deregulation of chemokines and chemokine receptors expression in breast cancer are certainly crucial for the comprehension of chemokine role in breast cancer and are in several cases linked to estrogen receptor status. The targeting of chemokines and chemokine receptors by antibodies, small molecule antagonists, viral chemokine binding proteins and heparins appears as promising tracks to develop therapeutic strategies. Thus there is significant interest in developing strategies to antagonize the chemokine function, and an opportunity to interfere with metastasis, the leading cause of death in most patients. PMID:17717637

The protein C pathway in cancer metastasis

NARCIS (Netherlands)

Spek, C. Arnold; Arruda, Valder R.

2012-01-01

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

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

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

DEFF Research Database (Denmark)

Cox, Thomas R; Rumney, Robin M H; Schoof, Erwin M

2015-01-01

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present...... morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic...

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

Directory of Open Access Journals (Sweden)

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.

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

African Journals Online (AJOL)

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

Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer.

Science.gov (United States)

Xiao, Jisheng; Duan, Xiaopin; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Li, Yaping

2013-12-01

Lung metastasis is one of the greatest challenges for breast cancer treatment. Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first designed to inhibit the lung metastasis of breast cancer effectively. DOX was non-covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE-PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug loading and excellent ability to deliver DOX to the nucleus, thereby significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore, DNX showed good histocompatibility and could improve drug accumulation in lung, as a result, markedly inhibited the lung metastasis of breast cancer. The high anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX could be a promising drug delivery system for the therapy of lung metastasis of breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contiguous spinal metastasis mimicking infectious spondylodiscitis

International Nuclear Information System (INIS)

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

2015-01-01

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

Contiguous spinal metastasis mimicking infectious spondylodiscitis

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-15

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

Preoperative diagnosis of lymph node metastasis in thoracic esophageal cancer

Energy Technology Data Exchange (ETDEWEB)

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

1996-10-01

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

Preoperative diagnosis of lymph node metastasis in thoracic esophageal cancer

International Nuclear Information System (INIS)

Eguchi, Reiki; Yamada, Akiyoshi; Ueno, Keiko; Murata, Yoko

1996-01-01

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

Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1.

Science.gov (United States)

Xie, Xiayang; Tang, Shou-Ching; Cai, Yafei; Pi, Wenhu; Deng, Libin; Wu, Guangyu; Chavanieu, Alain; Teng, Yong

2016-09-06

Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis.

A Rare Cause of Testicular Metastasis: Upper Tract Urothelial Carcinoma

Directory of Open Access Journals (Sweden)

Alper Nesip Manav

2014-01-01

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

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.

Gut metastasis from breast carcinoma.

Science.gov (United States)

Al-Qahtani, Mohammed S

2007-10-01

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

Serological Diagnosis of Liver Metastasis in Patients with Breast Cancer

International Nuclear Information System (INIS)

Cao, Rui; Wang, Li-ping

2012-01-01

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

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

Science.gov (United States)