Construction and improvement of animal models with different positional osseous metastasis of prostate cancer in vivo / 北京大学学报(医学版)

Objective: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo.Methods: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively.The change of mouse activity, tumor formation, tumor size and survival time were observed respectively.And the femur tissue and spinal tissue were obtained from the mice after death.The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue.Results: The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days.There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05).As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection.At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells (at least 2 weeks longer).Conclusion: The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study.At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells.The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal model with bone metastasis can be stably reproduced by our method.These animal models can be used to explore the pathogenesis of different positional PCa bone metastasis and provide a new platform, which were more congruous to clinical process, for prevention and cure of neoplastic bone metastases.

Differentail diagnosis of metastatic small cell carcinoma of bone in needle biopsy:an analysis of 11 cases / 临床与实验病理学杂志

Purpose To investigate the diagnosis and differentail diagnosis of metastatic small cell carcinoma of bone in needle biopsy, especially for the differentail diagnosis with Ewing sarcoma of bone. Methods Clinicopathological informations of 11 cases of metastat-ic small cell carcinoma and 20 cases of Ewing sarcoma were collected, and markers for differentail diagnosis were detected in two groups by immunohistochemistry of EnVision. Results The positive rates of CD99 and FLI-1 were 27. 3% and 54. 5% in metastatic small cell carcinoma group, while the positive rate of CK was 15. 0% in Ewing sarcoma group. Patient′s age, single lesion, expression of CK, vimentin, CD99, FLI-1, CD56 were significantly different in two groups. Conclusions Metastatic small cell carcinoma and E-wing sarcoma share similar histopathologic features in needle biopsy, no single immunohistochemical marker can specifically distinguish small cell carcinoma from Ewing sarcouma. The correct diagnosis should comprehensive analyze clinicopathologic characters and a se-ries of immunohistochemical markers.

Clinical Observation of Modified Yanghe Decoction Combined with Analgesic Western Medicine in Relieving Cancerous Pain of Osseous Metastasis Patients / 广州中医药大学学报

Objective To observe the therapeutic effect of modified Yanghe Decoction combined with analgesic western medicine on relieving cancerous pain and constipation and on improving the quality of life ( QOL) of osseous metastasis patients. Methods A total of 200 patients with cancerous pain were evenly randomized into treatment group and control group in the admission order. The control group was given oral use of oxycodone hydrochloride controlled-release tablets, and the treatment group was given modified Yanghe Decoction on the basis of treatment for the control group. Twenty-one days constituted one treatment course. After one treatment course, the effect on relieving pain and constipation and on improving QOL were evaluated in both groups. Results (1) The analgesic efficiency was 95.0 % in the treatment group, and was 81.0 % in the control group, the analgesic efficiency of the treatment group was better than that of the control group ( P<0.05) . ( 2) Constipation occurred in 92 cases of the treatment group and was relieved to various degrees in 88 cases after treatment, with an efficiency of 95.7%. In the control group, constipation occurred in 91 cases, but was not relieved after treatment. The treatment group had better effect on relieving constipation than the control group (P<0.05) . (3) The total effective rate on improving QOL was 89.0% in the treatment group and was 71.0% in the control group, the difference being significant (P<0.05) . (4) Both groups had 2 cases of drug-induced mild hepatic damage, and the damage disappeared after symptomatic treatment . Conclusion Modified Yanghe Decoction combined with analgesic western medicine shows good toxicity-reducing and efficiency-enhancing effect for the treatment of cancerous pain.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm²) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm²). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo.

Effect of 153Sm-EDTMP combined with ibandranate in the treatment of osseous metastasis of lung cancer / 中国基层医药

Objective To explore the effect of 153Sm-EDTMP combined ibandranate in treatment of osseous metastasis of lung cancer.Methods 100 patients with osseous metastasis of lung cancer were randomly divided into two groups.The patients received intervenous drop infusion of 153Sm-EDTMP and ibandranate in treatment group( n =52).The patients received therapy with 153Sm-EDTMP in control group( n =48).The differentces of effect of odynolysis,locomotor activity,improvement of quality of life,recovery of osteolysis,toxical and adverse reaction between two groups were compared.Results The overall response rate 94.2％ in treatment group was significantly higher than that 64.5 ％ in control group( x2 =4.78,P ＜ 0.0.5 ) ;The activity to improve situation 82.6％ in treatment group was significantly higher than that 64.5％ in control group( x2 =4.13,P ＜ 0.05 ) ;The total effective rate of quality of life improve the situation 84.6％ in treatment group was significantly higher than that 62.5％ in control group( x2 =4.58,P ＜0.05 ) ;The side effects had no significant difference between two groups ( x2 =0.345,P ＞ 0.05).Conclusion The treatment of 153Sm-EDTMP combined with ibandranate in the treatment of osseous-metastasis of lung cancer was effective for relieving pain,improvement locomotor activity,improvement of quality of life,recovery of osteolysis.

Value of radiologic correlation and follow-up scintigraphy in detecting osseous metastasis in patients with non-specific bone scintigraphy lesions

Bone scintigraphy is highly sensitive in detecting bone metastasis but specificity is only about 50-60%. The aim of this study is to evaluate the value of radiologic correlation and followwup scintigraphy in detecting osseous metastasis in patients with equivocal bone scans. Bone scan results with non-specific interpretation of bone lesions from January to December 2007 were included. Results with no evidence of bone metastasis or metastatic bone disease were excluded from the study. Correlation with radiographs [X-ray, CT-scan, MRI] and follow-up bone scan within 6 months from the initial bone scan were reviewed. Of the 2322 bone scans, 435 have non-specific findings of bone lesions. From 435, only 228 patients have records of radiograph correlation and scintigraphic follow-up. Twenty two percent of the total population showed positive findings of bone metastasis in radiographs. The percentages of the non-specific findings determined to be negative from bone metastasis on correlation with X-ray, CT-scan, MRI and follow-up bone scan were 84%, 70%,73%, and 85%, respectively, whereas osseous metastasis revealed on radiologic correlation and follow-up scan were 76%, 30%,27%, and 75%, respectively. In conclusion, the finding of osseous metastasis in bone scan is increased when correlated with radiographs and scintigraphic follow-up.

Bone scintigragphy in pediatric patient with maxillary ameloblastic carcinoma

Presented here is a rare occurrence of ameloblastic carcinoma located in the maxilla of a pediatric patient. The patient's chief complaint is a large mass protruding from the right maxillary area diagnosed as ameloblastic carcinoma before consulting the nuclear medicine section for whole-body bone scintigraphy. Whole-body bone scintigraphy was performed with cranial SPECT imaging. The maxillary tumor appeared to have decreased radiotracer uptake with intense activity in the anterior and anteromedial aspects of the tumor. There was also a focus of uptake in the lateral border of the tumor, radiating to the angle of the right mandible. Mandibular X-ray series was also acquired, with findings that correlate with those of the bone scintigraphy.

Assessment of Bone Metastasis using Nuclear Medicine Imaging in Breast Cancer: Comparison between PET/CT and Bone Scan / 핵의학분자영상

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 18F-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: 28~78 years old, mean+/-SD=49.5+/-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+/-3.32 vs 1.45+/-0.44, p=0.000, 3.08+/-2.85 vs 0.30+/-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+/-3.12 vs 1.09+/-1.49, p=0.000, 4.76+/-3.31 vs 1.29+/-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.

Radiopharmaceuticals for the Therapy of Metastatic Bone Pain / 핵의학분자영상

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. It occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. 32P, 89SrCl, 153Sm-EDTMP, 188Re/186Re-HEDP, and 177Lu-EDTMP can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studies, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and indication/contraindication and follow-up protocol.

Retrospective analysis of ~(89)Sr metastron treating 83 cases of multiple osseous metastasis tumor / 第三军医大学学报

Objective To evaluate the therapeutic effect and side effects of 89Sr metastron on treating multiple osseous metastasis tumor. Methods The total 83 patients had been treated by intravenously injecting 89Sr metastron at a dose of 2.22 MBq/kg. Results Among 83 cases, 31.3% of them got complete remission, 37.3% moderate remission, and 18.1% slight remission. The total effective rate was 86.7%. The side effects were mild, and only white blood cells and platelets transiently fell by 20%. Conclusion Internal radiotherapy with 89Sr metastron is the good alternative in treating multiple osseous metastasis tumor.

Advances in research on the diagnosis and therapy of lung cancer with bone metastases / 中国癌症杂志

Bone metastases in advanced lung cancer patients are common and affect the life quality seriously. So early diagnosis and appropriate treatments are important. The methods of diagnosis include X-ray, CT, MRI, ECT and PET, which are different in sensitivity and specificity. The gene microarray technique is another advance for detecting micrometastasis. The gene analysis also can help understanding the biological characteristics of the primary tumor. The treatment of bone metastases in lung cancer is various, including systemic and local therapeutic means. Surgery is often used to prevent or treat the compressions and bone fractures. Radiotherapy is one of the most effective methods of pain relief. Diphosphonate provides a new convenient and effective way of alleviative treatment. In addition, supportive and symptomatic treatments should be keep in mind.

Zoledronic acid combined with single or multiple fraction radiotherapy for metastatic bone pain / 第三军医大学学报

0.05).ConclusionZoledronic acid combined with single or multiple fraction radiotherapy has similar clinical response.Zoledronic acid combined with single fraction is an efficient and cost-effective alternative to traditional multiple fraction radiotherapy for metastatic bone pain.