• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.291-292
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• 2001

We report a case of malignant pericardial effusion originated from adenocarcinoma of the lung incidentally diagnosed by bone scintigraphy, prior to echocardiographic detection. A 76 year-old man with adenocarcinoma of the lung underwent Tc-99m MDP bone scintigraphy to evaluate skeletal metastasis. Anterior images of the chest of the bone scintigraphy unexpectedly showed diffuse increased activity in the region of the heart surrounded by an oval-shaped band of increased activity corresponding to the periphery of the cardiac silhouette (Fig. 1). There was no evidence of bony metastasis. Pericardial effusion was confirmed by echocardiography (Fig. 2) and malignant cells were revealed by subsequent microscopic examination of the pericardial fluid. Bone scintigraphy using Tc-99m phosphate compounds is commonly used to detect bony metastasis in cancer patients. Tc-99m phosphate compounds occasionally accumulate in extra-osseous sites, including $pleural^{1,2)},\;pericardial^{3,4)},\;and\;ascitic\;fluids^{5,6)}$. It has been reported that their accumulation in serous effusions should strongly suggest $malignancy^{1-6)}$. The exact mechanism for accumulation of Tc-99m phosphate compounds in serous effusions is unclear. Several investigators have proposed that the radiopharmaceuticals exuded directly from peripheral vessels to the serous cavity due to increased vascularity and vascular permeability, and bleeding by disruption of blood vessels due to cancerous $infiltration^{5,6)}$.

• Journal of Yeungnam Medical Science
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• v.31 no.1
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• pp.33-37
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• 2014

Acinic cell carcinoma (ACC) is an uncommon malignant tumor of the salivary glands that is difficult to diagnose. It grows slowly and shows distant metastasis rarely. We experienced a case of recurrent ACC in the parotid gland with cardiac metastasis and hypertrophic osteoarthropathy. The 29-year-old man had been suffering from severe multiple bones and joints pain for 2 months. Ten years earlier, he underwent superficial parotidectomy due to a right subauricular mass. The mass was diagnosed with ACC. After surgery, the tumor recurred twice. Then the patient was diagnosed with cardiac metastasis via positron emission tomography-computed tomography and trans-thoracic echocardiography. He also had hypertrophic osteoarthropathy with multiple bone metastasis. He was given palliative radiotherapy and conservative treatment. ACC in the parotid gland with cardiac metastasis and hypertrophic osteoarthropathy has not yet been reported in literature. From this case, it is recommended to evaluate multiple distant metastasis in the ACC of the parotid gland when joint and bone pain are present.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.937-940
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• 2012

Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software. The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone metastasis.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.3
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• pp.245-249
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• 2009

Primary sternal osteomyelitis without predisposing factors is a rare condition, and it is hardly differentiated from metastatic bone tumor especially in patient with the history of primary malignancy because osteomyelities shares frequently common findings with metastatic bone lesion on $^{18}F$-FDG PET and bone scan, Although there have been several publications of primary osteomyelitis mimicking bone metastasis in the spine or extremities, we report a case of primary sternal osteomyelitis in the patient with lung cancer, which has, to our knowledge, not been reported before.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.30-41
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• 2007

Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4369-4371
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• 2012

Aim: Metastatic tumor of bone is the most common malignancy involving bone and is an important predictor of prognosis in advanced cancers. The prognosis depends upon the primary site of origin and the extent of disease. In current study, we present the pattern and distribution of metastatic bone disease seen in the leading cancer care center of Pakistan, Shaukat Khanum Cancer Hospital & Research Center (SKMCH & RC), Lahore. Materials & Methods: All cases of bony metastatic disease were included that presented in the Pathology Department, from Jan 2005 to July 2011. Patients of all ages and both sexes were included. Primary bone tumors, lymphomas, sarcomas and other malignancies were excluded. The data were recorded and analyzed with SPSS 16.0. Results: A total of 146 cases of metastatic bone disease were included in the study. Out of the total cases, 79 were male and 67 were female. Age range 25-82 years (median 52). Hip bone was the most frequent bone involved, with femur and vertebrae as second and third in the list. The commonest bone involved in males was vertebrae with 23 cases and in females was hip bone with 22 cases. Regarding primary site, cancers of breast, prostate and gastrointestinal tract were at the top of the list with prostate and breast being the most frequent primary sites of metastasis in males and females respectively. Conclusion: Bone metastasis is an important entity to consider in the differential diagnosis whenever a bony tumor especially carcinoma present in older age. Our data are comparable with international findings and the literature available regarding the site and distribution of skeletal metastatic lesions. A slight deviation noted was more common bony metastatic lesions with ovarian primaries in females and gastrointestinal tract cancers in males in our study.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.82-84
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• 2001

An 11 kg, 7-year-old male pug dog with lameness and tumor of the 2-3rd interdigital portion of the right forelimb was referred to the Veterinary Medical Center of the Tokyo University. On the clinical examination findings, the tumor size was $3{\times}3 cm but alopecia and necrosis were not found. On the radiological findings, a bone lysis was found in the phalanges of digit II of the right forelimb but pulmonary metastasis was not found. The mass was removed with metacarpal bone. Histopathological examination of the mass revealed highly differentiated hemangiopericytoma. Two weeks after the operation, the dog was irradiated by orthovoltage radiation. The source of irradiation was 300 kV, 4mA, 4Gy and a focal spot to skin distance of 40 cm using 1.0 Cu, 1.0Al filter. The radiation therapy was performed twice a week for 5 weeks. The dog showed no recurrence and no metastasis. It was thought that the surgery and radiation therapy treatment was quite a useful method to treat a canine heman-giopericytoma.

• Kosin Medical Journal
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• v.33 no.3
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• pp.391-395
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• 2018

We report a case of a patient with locally advanced prostate cancer who had only lymph node involvement without bone metastasis on F-18 FDG PET/CT. A 62-year-old Korean male was admitted to our hospital due to dysuria. His PSA level on admission was 79.35 ng/mL. A transrectal ultrasound-guided prostate biopsy confirmed prostate cancer and his Gleason score was 10 (5+5). F-18 FDG PET/CT demonstrated a hypermetabolic mass lesion with SUVmax 7.0 in the prostate and hypermetabolism with SUVmax 4.7 of the abdominal and pelvic lymph nodes. Tc-99m HDP bone scan showed no significant bone metastasis. The patient underwent hormonal therapy for 9 months. Follow-up F-18 FDG PET/CT showed significantly reduced size and FDG uptake in the prostate and abdominal and pelvic lymph nodes. In this case, treatment monitoring with F-18 FDG PET/CT showed decreased mass size and FDG uptake in the prostate and abdominal and pelvic lymph nodes.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.79-82
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• 2009

A 73-year-old man presented with a chief complaint of progressive left knee pain for two months. He had a history of total thyroidectomy and central lymph node dissection due to papillary thyroid carcinoma three months ago. MRI images revealed a solid mass in the left patella. A solid mass demonstrated low signal on T1 weighed image, and high signal on T2 weighed image. And whole body bone scan showed focal photon defect in same lesion of left patella. The histologic result of left knee lesion was adenocarcinoma, consistent with metastatic papillary thyroid carcinoma. Although patellar metastasis of papillary thyroid carcinoma is very rare, when knee pain and radiologic abnormality are noted, differential diagnosis of metastasis is necessary.