• Clinical and Experimental Pediatrics
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• v.56 no.2
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• pp.60-67
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• 2013

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

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1503-1510
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• 2014

Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor ${\kappa}B$ ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

• The Korean Journal of Pain
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• v.23 no.4
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• pp.230-235
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• 2010

Background: Bone cancer pain has a disruptive effect on the cancer patient's quality of life. Although ginsenosides have been used as traditional medicine in Eastern Medicine, the effect on bone cancer pain has not been throughly studied. The aim of this study was to determine whether ginsenosides may alter the bone cancer pain at the spinal level. Methods: NCTC 2472 tumor cells ($2.5{\times}10^5$) were injected into the femur of adult male C3H/HeJ mice to evoke bone tumor and bone cancer pain. To develop bone tumor, radiologic pictures were obtained. To assess pain, the withdrawal thereshold was measured by applying a von Frey filament to the tumor cells inoculation site. The effect of intrathecal ginsenosides was investigated. Effect of ginsenosides (150, 500, $1,000{\mu}g$) was examined at 15, 30, 60, 90, 120 min after intrathecal delivery. Results: The intrafemoral injection of NCTC 2472 tumor cells induced a radiological bone tumor. The withdrawal threshold with tumor development was significantly decreased compared to the sham animals. Intrathecal ginsenosides effectively increased the withdrawal threshold in the bone cancer site. Conclusions: NCTC 2472 tumor cells injection into the mice femur caused bone tumor and bone cancer pain. Intrathecal ginsenosides attenuated the bone cancer-related pain behavior. Therefore, spinal ginsenosides may be an alternative analgesic for treating bone cancer pain.

• The Korean Journal of Nuclear Medicine
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• v.15 no.2
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• pp.1-9
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• 1981

Bone scans with $^{99m}Tc-MDP$ (methylene diphosphonate) were obtained and analysed in 574 patients with biopsy-proven malignancy, who visited Seoul National University Hospital from April, 1979 to June, 1931. Clinical staging was done in all patients without bone scan information and compared with bone scan to determine the predictive value of bone scanning. 1. Primary site of the maligancies were lung in 152, breast in 97, stomach in 43, colon in 15, esophagus in 9, liver and pancreas in 11, kidney in 14, bladder in 27, prostate in 22, thyroid in 20, skin in 11, bone in 9, head and neck in 36, ovary and uterus in 17, hematopoietic and lymphoretic ular system in 33, nervous system in 10, and others in 9 cases. Primary site was not defined in 39 cases. 2. Bone scans were positive in 186 cases (32.4%), which, included 48 cases (31.6%) of lung cancer, 27 cases (27.8%) of breast cancer, 12 cases(28%) of stomach cancer, 6 cases(40%) of colon cancer, 6 cases(43%) of kidney tumor, 4 cases(15%) of bladder cancer, 14 cases(64%) of prostate cancer, 3 cases(15%) of thyroid cancer and 66 other cases. 3. Bone scans were suspicious in 64 cases (11.2%) which included 29 cases (19.1%) of lung cancer, 10 cases (10.3%) of breast cancer, 4 cases (9.3%) of stomach cancer, one case (7%) of colon cancer, 3 cases(11%) of bladder cancer, 2 cases(10%) of thyroid cancer and 15 other cases. 4. Out of 121 cases with early stage of malignancy (which included 20 cases of lung cancer in stage I, II, 38 cases of breast cancer, 13 cases of stomach cancer, 8 cases of kidney tumor, 14 cases of thyroid cancer in stage $I{\sim}III$, and 6 cases of colon cancer, 14 cases of bladder cancer, 8 cases of prostate cancer in stage $A{\sim}C$, bone scans were positive in 5 cases (4.1%) which included 3 cases of lung cancer one case of breast cancer and one case of prostate cancer, and considered as further advanced stage. Out of 121 cases with early stage of malgnancy, bone scans were suspicious in 21 cases (17.4%) which inlcuded 9 cases of lung cancer, 4 cases of breast cancer, 2 cases of stomach cancer, one case of colon cancer, 3 cases of bladder cancer, and 2 cases of thyroid cancer. From these results, we concluded bone scan was useful in detecting bone metastasis in patients of early stage of malignancy, determining prognosis and establishing therapentic plan.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.38-45
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• 2011

Purpose: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis. Materials and Methods: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was retrospectively analyzed. Results: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis location was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the 18 cases that received a stomach cancer operation was on average $14.9{\pm}17.3$ months and the period until death after the diagnosis of bone metastasis was on average $3.8{\pm}2.6$ months. As a result of univariate survival rate analysis, the group that was treated for bone metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis. Conclusions: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the patients with bone metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8401-8404
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• 2014

Background: To determine survival times of cervical cancer patients with bone metastasis related to the effect of age at the time of cervical cancer diagnosis, we performed the retrospectively analytical study. Methods: A total of 68 cervical cancer patients with bone metastasis were treated at a single hospital, during January 1998 to December 2010. Fifty-two medical records were identified and collected, the remaining sixteen medical records were not found. Main outcome measures were patient characteristics, clinical information, duration from cervical cancer diagnosis to bone metastasis diagnosis, survival time after bone metastasis and overall survival time. Results: Among fifty-two cervical cancer patients with bone metastasis, there were 13 patients who were less than 45 years old, and 39 patients were 45 years old or more at the time of cervical cancer diagnosis. The younger group had less median overall survival than the older group, with a statistically significant difference (21 months, 95% CI 19.93-22.06; 34 months, 95% CI 23.27-44.72, p = 0.021). However, they were comparable in the duration from cervical cancer diagnosis to bone metastasis diagnosis and the survival time after bone metastasis. Conclusion: Young patients with bone metastasis aged less than 45 years old at the time of cervical cancer diagnosis have a poorer prognosis than the elderly patients. Impact: To improve survival and quality of life, more intensive and novel multimodal treatments at the time of cervical cancer diagnosis should be considered in patients less than forty-five years, who can tolerate the side effects better.

• Journal of Cancer Prevention
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• v.21 no.2
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• pp.88-94
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• 2016

Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3289-3292
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• 2013

Introduction: The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. Materials and Methods: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. Results: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was $69.2{\pm}7.3$ years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among thowse with a low PSA level less than 20ng/ml, and less than 10ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml)+1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=$2.718^x/1+2.718^x$. Conclusion: Newly diagnosed prostate cancer patients with a PSA level of 10ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3647-3652
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• 2013

Purpose: To evaluate the diagnostic value of $^{18}F$-FDG PET/CT for detection of bone metastasis in comparison with the efficacies of $^{18}F$-FDG PET/CT, CT, $^{18}F$-FDG PET and conventional planar bone scintigraphy in a series of cancer patients. Methods: Five hundred and thirty patients who underwent both $^{18}F$-FDG PET/CT and bone scintigraphy within 1 month were retrospectively analyzed. The skeletal system was classified into 10 anatomic segments and interpreted blindly and separately. For each modality, the sensitivity, specificity, accuracy, PPV and NPV were calculated and the results were statistically analyzed. Results: Bone metastases were confirmed in 117 patients with 459 positive segments. On patient-based analysis, the sensitivity, specificity, accuracy, PPV and NPV of $^{18}F$-FDG PET/CT were significantly higher than bone scintigraphy, CT and $^{18}F$-FDG PET (P<0.05). On segment-based analysis, the sensitivity of CT, bone scintigraphy, $^{18}F$-FDG PET and $^{18}F$-FDG PET/CT were 70.4%, 89.5%, 89.1% and 97.8%, respectively (P<0.05, compared with $^{18}F$-FDG PET/CT). The overall specificity and accuracy of the four modalities were 89.1%, 91.8%, 90.3%, 98.2% and 90.3%, 90.9%, 89.8%, 98.0%, respectively (P<0.05, compared with $^{18}F$-FDG PET/CT). The PPV and NPV were 89.8%, 87.6%, 85.6%, 97.2% and 85.6%, 93.2%, 92.8%, 98.6%, respectively. Three hundred and twelve lesions or segments were presented as lytic or sclerotic changes on CT images at the corresponding sites of increased $^{18}F$-FDG uptake. In lytic or mixed lesions, the sensitivity of $^{18}F$-FDG PET/CT and $^{18}F$-FDG PET were better than bone scintigraphy, while in osteoblastic lesions bone scintigraphy had a similar performance with $^{18}F$-FDG PET/CT but better than $^{18}F$-FDG PET alone. Conclusion: Our data allow the conclusion that $^{18}F$-FDG PET/CT is superior to planar bone scintigraphy, CT or $^{18}F$-FDG PET in detecting bone metastasis. $^{18}F$-FDG PET/CT may enhance our diagnosis of tumor bone metastasis and provide more information for cancer treatment.