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Objective:To evaluate the clinical value of the New England spinal metastasis score (NESMS) in predicting the prognosis of patients with spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:The data of 179 patients with spinal metastases from January 2008 to December 2018 were retrospectively collected. There were 108 males (60.3%) and 71 females (39.7%) with an average age of 59.79±10.88 years old (range 27-84 years). The patient demographic characteristics, primary tumor type, spinal metastases and segments, vertebral pathological fractures, neurological Frankel classification, physical function status, Karnofsky performance scale (KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS), modified Bauer score, NESMS score, Tomita score and modified Tokuhashi score were collected. The clinical value of NESMS score, Tomita score and modified Tokuhashi score in predicting the survival of patients with spinal metastases were compared. The independent factors affecting survival in these patients were analyzed by Cox proportional hazards regression model.Results:Among the 179 patients, the peak incidence of spinal metastases was in the age group of 61-75 years (45.3%, 81/179) of all patients. Lung cancer was the most common primary tumor (46.9%, 84/179). 40.8% (73/179) of patients had multi-segment metastasisand thoracic spine was the most common site with single-site metastasis (26.3%, 47/179). 28.5% (51/179) of the patients had visceral metastases and 52.0% (93/179) of the patients had extraspinal bone metastases. 31.3% (56/179) of the patients had pathological fractures of the involved vertebral bodies.114 patients received surgical treatment (63.4%). The mortality rates in 3-months, 6-months and 1-year were 22.4% (40/179), 51.4% (92/179) and 77.1% (138/179), respectively. The median survival time of patients with NESMS score of 0-3 was 3, 4, 8, and 10 months respectively with the mean survival time was 3.60±2.10, 6.77±3.39, 9.69±5.71 and 10.53±6.25 months. The 1-year mortality rates were 100% (13/13), 87.5% (42/48), 71.6% (63/88) and 66.7% (20/30) respectively. The consistency of NESMS score, Tomita score and modified Tokuhashi score in predicting survival of all patients was 0.63, 0.58 and 0.55, respectively. For patients with spinal metastases, the NESMS score was better than the Tomita score and modified Tokuhashi score in predicting survival at 3-months (AUC=1.00, 0.63, 0.42) and 6-months (AUC=0.71, 0.63, 0.45). But the accuracy of Tomita score was best in predicting survival at 1-year (AUC=0.66, 0.61, 0.38). Multivariate Cox proportional hazards regression model analysis showed that growth rate of primary tumor, neurological function Frankel score, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases ( P<0.05). Conclusion:The consistency and accuracy of NESMS score in predicting survival of patients with spinal metastases are better than Tomita score and modified Tokuhashi score, especially in predicting 3- and 6-month survival. The growth rate of primary tumor, Frankel classification, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases.
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Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.
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Objective:To observe the expression characteristics of small ubiquitin-like modified protein (SUMO) pathway members in osteosarcomaby using molecular biology methods, and provide theoretical basis for targeted therapy based on protein SUMO modification.Methods:Eighteen fresh osteosarcoma tissue samples surgically resected at Tianjin Cancer Hospital from January 2017 to June 2019 were collected. Western blot and immunohistochemical methods were used to detect the protein expressions of SUMO1, SAE1, Ubc9, and SENP1, which are core members of SUMO pathway, in the cancerous and adjacent tissue. Taking osteosarcoma cell line 143B as the research object, three targeted treatment regimens were designed and grouped as follows: control group, nonsense group, siR-SUMO1 group, siR-Ubc9 group, and SENP1 group. Western blot was used to verify the efficiency of gene transfection, the positive expression rate of EdU was detected by cell proliferation detection kit, the ability of cell migration and invasion was measured by scratch test and Transwell invasion test, and the apoptosis rate was detected by flow cytometry. Bone marrow mesenchymal stem cells (BMSCs) were used to evaluate the side effects of three treatment regimens.Results:Results from Western blot and immunohistochemistry showed that the protein expression levels of SUMO1, SAE1, andUbc9 in osteosarcoma tissues were significantly higher than those in adjacent tissues ( P<0.05), but SENP1 was significantly lower than in adjacent tissues. The experimental results based on 143B osteosarcoma cells showed that the siR-SUMO1 group, siR-Ubc9 group, and SENP1 group can significantly inhibit the activation of SUMO pathway in osteosarcoma cells, showing lower tumor cell proliferation ( P<0.05), slower cell migration and invasion capacity ( P<0.05), and higher apoptotic rate ( P<0.05), than the control group and nonsense group; however, experimental results based on BMSCs showed that the siR-SUMO1 group and siR-Ubc9 group can significantly inhibit the proliferation of BMSCs, induce apoptosis, and show great therapeutic side effects, but the SENP1 group has almost no effect on the proliferation and apoptosis of BMSCs ( P>0.05). Conclusion:The SUMO pathway is abnormally activated in osteosarcoma. Exogenous supplementation or endogenous activation of SENP1 is one of the alternatives for targeted osteosarcoma treatment.
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Objective Based on lung cancer center database,we analyzed the clinical characteristics of lung patients with bone metastases.The relationship between bone metastases,skeletal-related events,survival time and different pathological subtypes of lung cancer were also evaluated in this study.Methods A total of 861 patients with lung cancer were studied from May 2010 to April 2012 at Tianjin Medical University Cancer Institute and Hospital.As to follow-up situation,patients' survival status and treatment information were collected by telephone follow-up and (or) examinationsin outpatient.The clinical characteristics,skeletal-related events and survival of bone metastaticpatients with different pathological types of lung cancer were analyzed.Logistic regression analysis was used to identify risk factors for bone metastases.The relationship between histological subtypes and the incidence of bone metastases was evaluated using Odds Ratios (ORs).The chi-square test was used to compare the proportion of bone metastases,synchronous bone metastases and SREs among different histological subtypes patients.The overall survivals was evaluated using the Kaplan Meier.Results A total of 861 patients with lung cancerwere enrolled in this study,including 293 cases with bone metastases.The average follow-up of our population was 14.2 months and the last follow-up time was September 2017.Among different pathological types of lung cancer,adenocarcinoma (39.14％,173/442) has the highest incidence of bone metastases,followed by other types (29.91％,35/117),squamous cell carcinoma (29.47％,56/190) and SCLC (25.89％,29/112).Spine (59.73％,175/293) was the most common location site of the bone metastases,followed by the ribs (49.15％,144/293),pelvis (20.48％,60/293),femur (16.38％,48/293) and sternal (16.38％,48/293).Lung adenocarcinoma was a risk factor for bonemetastases (P=0.002).In ORs analyze,adenocarcinoma patients were more likely to develop bone metastases [OR=1.60,95％CI (1.21～2.13)].In our cohort,58.36％of patients with lung cancer had skeletal related events.Among various types of skeletal related events of patients with bone metastases,the most common one was radiotherapy for bone metastases (51.88％,152/293),followed by pathological fractures (15.02％,44/293),spinal cord compression (6.48％,19/293),bone instability requiring surgery (4.78％,14/293) and hypercalcemia (1.71％,5/293).There was no significant difference between different types of skeletal related events.The median survival time of the patients with bone metastases was 11.5 months.There was no significant difference in survival between adenocarcinoma patients and non-adenocarcinoma patients (P=0.111).Conclusion This study suggested that the incidence of bone metastasis in lung adenocarcinoma was 39.14％ and lung adenocarcinoma was a risk factor for bone metastases,which supported early screening and monitoring of bone metastasis in the patients.
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Objective To investigate the relationship of serum cholinesterase(CHE) level with the severity and prognosis in patients with acute cerebral infarction. Methods A total of 325 patients with acute cerebral infarction were recruited as patients group,and another 101 healthy sub?jects were selected as control group. Velocity method was employed to detect the level of serum CHE. Patients with acute cerebral infarction were then divided into different groups according to the infarcts diameter and the modified Rankin scale(mRS)at 1 year post stroke. The collected data were analyzed statistically. Results The level of serum CHE in small and medium area infarction group was higher than control group(P<0.01);the level of serum CHE in large area infarction group was lower than control group(P<0.01);the level of serum CHE was negatively correlated with infarct size,NIHSS and the mRS score(r=-0.302,-0.232,-0.455,P<0.001). The level of CHE,age,NIHSS and infarcts diameter was identified as independent influence factors for prognosis of acute cerebral infarction. Conclusion Early phase of serum CHE level is closely related with the infarct size and illness severity index in patients with acute cerebral infarction,which could be an independent factor affecting the prognosis of cere?bral infarction.
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Objective:Prostate cancer frequently metastasizes to the spine. In this study, we investigate the prognostic factors as-sociated with survival in patients with prostate cancer accompanied by spinal metastases at their preliminary diagnosis. Methods:Clin-ical data of 49 patients who were diagnosed with spinal metastasis from prostate cancer between January 2005 and December 2010 were analyzed. Variables including alkaline phosphatase (ALP), previous skeletal-related event, Gleason score, prostate-specific anti-gen (PSA) nadir, and time to castration resistance were obtained. Moreover, the relationship between these variables and overall sur-vival (OS) was analyzed. Survival analysis was performed by using Kaplan-Meier curves. Furthermore, the differences among the OS rates were assessed by using the log rank test. The variables were statistically significant in the univariate analysis (P<0.05) and were included in the multivariate model. Results:The average follow-up time was 64.1 months among the 49 patients. By the end of the follow-up, 41 of these patients were dead;the mean survival was 27 months. The 1-, 3-, and 5-year survival rate was 81.6%, 40.8%, and 20.4%, respectively. Univariate analysis identified that 6 variables were statistically significant prognostic factors of OS:with or without chemotherapy, ALP, previous skeletal-related event, Gleason score, PSA nadir, and time to castration resistance. The multivari-ate analysis showed that the time to castration resistance of ≥19 months and the addition of chemotherapy after disease progression are independent prognostic factors for a high OS. Conclusion:With or without chemotherapy and the time to castration resistance are the independent prognostic factors associated with survival in patients with prostate cancer accompanied by spinal metastases at first diagnosis.
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Objective:To investigate the clinical features, treatment strategies, and relative prognostic factors in 66 patients with solitary plasmacytoma (SP). Methods:The data of 644 patients, who were diagnosed with pathologically proven plasmacytoma in Tianjin Medical University Cancer Institute and Hospital between June 2000 and October 2012, were collected. Sixty-six of these patients (10.25%) were evaluated as SP, including 45 solitary bone plasmacytoma (SBP) and 21 extramedullary plasmacytoma (EMP). Results:SBP and EMP were the two clinical subsets of SP revealing the location of the lesion. SBP mostly occurred in the axial skeleton, whereas EMP was most frequently observed in the upper respiratory tract. The differences among tumor size, serum M-protein, and serumβ2-microglobulin exhibited statistical significance. Conclusion:Large tumor size (≥5 cm), positive serum M-protein, and serumβ2-microglobulin were the factors that affected the prognosis of SBP patients. Radiotherapy and serumβ2-microglobulin>3.5 mg/L were the favorable prognostic factors for EMP patients.
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Objective To performed microarray-based comparative genomic hybridization (aCGH) detection and carried out pathway analysis to gain a systemic view on the pathway alterations of the genetically altered genes in human osteosarcoma.Methods aCGH experiments were carried on 10 fresh osteosarcoma samples to obtain recurrent copy number change pattern,then the samples were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify the altered pathways in the osteosarcoma.To validate the aberrations of these key pathways,the alterations of VEGF pathway were selected to confirm by the methods of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded (FFPE) osteosarcoma archival tissues.Results The KEEG analysis of aCGH data identified 33 genetically altered pathways in osteosarcomas.Among them 20 pathways were identified genetic amplifications,such as VEGF and mTOR signaling pathways.Thirteen pathways were genetic deletions,such as Wnt and Hedgehog signaling pathways.The genetic aberrations of cell-cell-matrix pathway such as CAMs,Adherens junction and Tight junction pathways implied the genetically alterations of these pathways which are associated with the tumor invasion and metastasis.Validation the aberrations of VEGF pathway showed that VEGFA gene was significantly amplified.The positive protein expression of VEGFA had a significant association with microvessel density (MVD).Conclusion There are genetic aberrations which involved the component genes of VEGF,mTOR,CAMs,Adherens junction,Wnt,Hedgehog and other 26 signaling pathways.The alterations of these pathways which are significantly associated with tumor invasion,metastasis and progression suggest that the genetic aberrations of these key pathways might contribute to the tumorigenesis and progression in human osteosarcoma,and provide molecular genetic evidence for targeted therapy.
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Objective To investigate the safety and efficacy of surgery in 121 patients with spinal metastases.Methotds A retrospective analysis of clinical data from April 2009 to March 2013 was performed in 121 patients with spinal metastases.From 37 to 65 years,69 males and 42 females with mean age of 55.6 years.Primary tumor origin:Lung 35(28.9％),Breast 26(21.4％),Renal 17 (14.0％),Prostate 20 (16.5％),Thyroid 14 (11.6％),Liver 2 (1.7％),Colon 1 (0.8％),other 6 (5.0％).All patients received surgery.Follow-up and survival time were analyzed.In preoperation and postoperative 3 month,pain levels were assessed by visual analogue scale (VAS),neurologic deficit was evaluated by Frankel Grade and functional impairment was classified by Karnofsky Score.The quality of the life was assessed by EORTC QLQ-C30 questionnaire.Survival analysis was evaluated by Kaplan-meier.Results The period of follow-up ranged from 5 to 35 months with the average of 15.9 months.The mean survival was 14.5 months.1-year survival was 53.5％.2-year survival was 36.5％.In patients with lung cancer,the mean survival was 8.5months.1-year survival was 14.3％.2-year survival was 11.4％.In patients with breast cancer,the mean survival was 31 months.1-year survival was 57.7％.2-year survival was 46.2％.In preoperation and postoperative 3 month,the VAS showed statistical significance (t=21.6,P＜0.01) ;Post-operatively,80.3％ of all patients had functionally useful Frankel Grade D or E compared with 43.5％ pre-operatively.KPS score (80-100) percentage was 75.6％ postoperatively compared with 33.4％ preoperatively.In 1month postoperatively,35 of 75 patients who were sphincteric dysfunction preoperatively were improved.The EORTC QLQ-C30score was 83.39±7.23 in preoperation and 51.34±14.27 in postoperaion.The quality of life was impoved significantly (t=12.6,P＜0.01).Conclusion Surgical treatment was effective in improving quality of life by providing better pain control,enabling patients to regain or maintain mobility,and offering improved sphincter control.In all patients,the number of patents with spinal metastases from breast and lung cancer is higher.Compared with spinal metastases from breast cancer,the proportion of lung cancer origin received surgery is higher.
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Mesenchymal to epithelial transition (MET), whereby mesenchymal cells become more epithelial like in phenotype, was observed to occur during normal development and in cancers. Numerous investigations have been conducted on MET in carcino-mas. In addition, accumulating evidence also suggests the critical function of MET in sarcomas. Integrated analyses reveal that MET may be an important biological and clinical process in sarcomas, and transcription factors such as Slug may also perform central func-tions in epithelial differentiation in several sarcomas such as leiomyo-sarcoma and synovial sarcoma. Given the scarcity of investiga-tions and evidence, several important issues about MET, such as its molecular markers, signaling mechanisms, micro RNA regulations, and clinical significance, need to be clarified. In this article, we review several important questions about MET in sarcomas, including molecular markers, signaling mechanisms, regulation by miRNAs, and therapeutic implications.
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Objective:To investigate the safety and efficacy of laminectomy combined with vertebroplasty in spinal metastases from rapid-growth tumors. Methods:Clinical data of 23 patients with spinal metastases of lung cancer, who were admitted to the Cancer Hospital from July 2008 to May 2012, were retrospectively analyzed. Thirteen male and ten female patients, with an age range from 40 years to 65 years and a mean age of 51.5, were examined. All patients received posterior laminectomy to relieve spinal cord compression. Afterward, vertebroplasty combined with radiofrequency ablation was conducted, followed by the internal fixation of vertebrae (instrumental fixation). Operation time, blood loss, and bone cement leakage rate were analyzed. One month before and after the operation, pain measurement was conducted using visual analog scale (VAS) and neurologic deficit (spinal cord injury) by Frankel Grade. Functional impairment was classified by Karnofsky performance status (KPS) score. Quality of life was assessed by the European Organization for Research and Treatment questionnaire (EORTC QLQ-C30). Results:The mean operation time was 163±87.36 min. Blood boss was 430±130.35 mL. Bone cement leakage rate was 21.7%. One month before and after surgery, the VAS showed statistical significance (t=25.6, P<0.01). After surgery, 78.3%of all patients exhibited functionally satisfactory Frankel Grade D or E, compared with 43.5%of patients before the operation. KPS score (80 to 100) percentage was 69.6%after surgery compared with 34.8%before surgery. One month after the operation, remission of various degrees was seen in 10 of 18 patients who had sphincteric dysfunction before surgery (55.6%). The EORTC QLQ-C30 score was 85.39±8.99 before and 52.78±15.17 after operation. The quality of life improved significantly (t=11.6, P<0.01). Conclusion:Posterior laminectomy and vertebroplasty combined with radiofrequency ablation for spinal metastases from lung cancer is safe and effective. The treatment can improve pain, function, and life quality of patients with lung cancer spinal metastases.
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The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, maintenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehensively studied, yet a great deal of new evidence indicates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the targeted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications.
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Animals , Humans , Antineoplastic Agents , Pharmacology , Therapeutic Uses , Apoptosis , Caspases , Metabolism , Cytochromes c , Metabolism , Inhibitor of Apoptosis Proteins , Metabolism , Membrane Potential, Mitochondrial , Mitochondria , Metabolism , Neoplasms , Drug Therapy , Metabolism , Pathology , Proto-Oncogene Proteins c-bcl-2 , MetabolismABSTRACT
We retrospectively analyzed the clinical data of 17 patients with esophageal perforation and rupture from August 2007 to December 2011.Among them,there were spontaneous esophageal rupture (n =6),esophageal perforation caused by foreign bodies (n =8) and iatrogenic injury (n =3).Family members gave up treatment because of critical illness (n =2),conservative treatment was offered for surgical intolerance (n =1) and all others (n =14) underwent operation (thoractomy,n =13 ; neck incision,n =1).One patient with conservative treatment and another two surgical cases died.The other 12 cases recovered.Therefore individualized treatment is essential for the patients with esophageal perforation and rupture.
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ObjectiveTo investigate the safety and efficacy of combined treatment with subtotal corpectomy and radiofrequency ablation(RFA) for spinal metastases. MethodsFrom April 2009 to March 2010, 29 patients with spinal metastases who received subtotal corpectomy were analyzed. Sixteen patients (7 men and 9 women) with an average of 57.8 years having received subtotal corpectomy alone were selected for comparison (the subtotal corpectomy group). Thirteen patients (7 men and 6 women) with an average of 58.3 years having received subtotal corpectomy combined with RFA were chosen as subjects of this study (the RFA combination group). There were no significant differences between the two groups with respect to the patient's age, gender, and Tomita type. Pain levels pre-and post-procedure were assessed by the visual analogue scale(VAS), and neurologic deficit were evaluated by the Frankel scale. ResultsThe VAS in RFA combination group were 8.88±0.36, 3.76±0.33, 3.35±0.38 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in subtotal corpectomy group were 8.96±0.39, 3.81 ±0.48, 3.41 ±0.42 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in both groups showed statistical significance at each time point, there was no statistically difference between the two groups. The operate time in RFA combination group and subtotal corpectomy group were(216.54±113.77) min and(302.50±80.44)min, respectively. The blood loss of the two groups were (1084.62±539.82)ml and (1625.00±724.34)ml, respectively. The recurrent rate of the two groups were 30.8％ and 75.0％, respectively. The RFA combination group were lower in operate time, blood loss and recurrent rates than subtotal corpectomy group. Conclusion Compared with the subtotal corpectomy, the RFA combination can reduce the blood loss, operation time, and the recurrent rates.
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ObjectiveTo study the mechanism of myocardial dielectric property changes in radio frequency during hypothermic preservation and explore myocardial viability evaluative method. Methods Hybrid young pigs (20-30 kg) were used in the experiment. Heart arrest was induced with GIK solution. According to preservative temperature, the animals were divided into three groups: group A (4 ℃),group B (15 ℃) and group C (25 C). The heart was preserved in saline for 12,6 and 4 h respectively. Myocardial dielectric properties and ATP content were tested every 5 and 30 min during hypothermic preservation respectively. The relationship between tanoδm and ATP content was analyzed. ResultsTanδm of three groups was decreased significantly at the beginning, most slightly in group A and most obviously in group C. There was no significant difference in Tanδm between group B and group C with group A at 1 h,but there was obvious difference at 2,3 and 4 h (P＜0. 05,P＜0. 05,P＜0. 01 ). There was correlation between tanδm and ATP in the three groups. ConclusionTanδm in three groups is dropped with preservation time and temperature, and tanδm had a correlation with ATP content. Detection of myocardial dielectric property in radio frequency is a kind of quick, accurate and noninvasive method.
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Objective To detect the different expression of Runx2 in dedifferentiated chondrosarcoma and conventional chondrosarcoma, and to investigate the role of Runx2 in the occurrence and development of dedifferentiated chondrosarcoma. Methods Dedifferentiated chondrosarcoma cell line NDCS-1 and normal chondrosarcoma cell line SW1353 were cultured, then mRNA and total cellular protein were extracted.RT-PCR Western blotting, and immunocytochemistry were used to detect the expression of Runx2.Immunohistochemistry was used to test Runx2's expression in the dedifferentiated chondrosarcoma specim ens that confirmed by pathology. Results Runx2 was high expression in dedifferentiated chondrosarcoma cell line and high-grade component of dedifferentiated chondrosarcoma tissues. Conclusion The high expression of Runx2 in dedifferentiated chondrosarcoma is involved in the occurrence and development of dedifferentiated chondrosarcoma.
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Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2～q21.3,6q16～q25.3,9p24.2～q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicine:apomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.
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Objective: To investigate the differential expression of Sox9 in conventional chondrosarcoma,dedifferentiated chondrosarcoma and normal cartilage. Methods: We reported 12 cases of chondrosarcomas,which were initially diagnosed as chondrosarcomas(6 cases of conventional chondrosarcoma and 6 cases of dedifferentiated chondrosarcoma)at Peking University People's Hospital between January 2003 and January 2007.We used genechip method to identify difierentially expressed genes involved in conventional chondrosarcoma,dedifferentiated chondrosarcoma and in normal cartilage(6 cases)and found thousands of differentially expressed genes after extensive statistical analysis.With Sox9 which played crucial roles in the process of both differentiation and maturation of chondrocyte as a candidate,we used Real-time PCR,Westem blot and immunohistochemistry to confirm the results found by gene chip. Results: DNA microarray results showed that Sox9 was up-regulated about 1.6 times in conventional chondrosarcoma compared with that in normal cartilage.But in dedifferentiated chondrosarcoma,the expression level of Sox9 was significantly down-regulated,0.082 times of that in normal cartilage.Real-time PCR results showed that the expression levels of Sox9 mRNA in conventional chondrosarcomas and dedifferentiated chondrosarcomas were 1.68±0.119 and 0.088±0.017,respectively.Sox9 protein level was significantly higher in humen conventional chondrosarcomas than that in normal cartilage.Sox9 protein level in dedifferentiated chondrosarcomas was significantly lower than that in normal cartilage tissue.All of the 6 cases of conventional chondrosarcomas showed diffuse and strong staining of Sox9.However,Only scattered staining was observed in dedifferentiated chondrosarcomas. Conclusion: Compared with that in normal cartilage,Sox9 expression is up-regulated in conventional chondrosarcomas and down-regulated in dedifferentiated chondrosarcomas.Decrease of Sox9 expression in dedifferentiated chondrosarcoma is correlated with poor survival,indicating that Sox9 may serve as a molecular prognostic marker for chondrosarcomas and disease progression.
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Objective:To investigate the killing effect of nanoliposome encapsulated cisplatin(NLE-CDDP) on human osteosarcoma cell line Saos-2 and explore the distribution of platinum(Pt) in tumor-bearing mice.Methods: Saos-2 cells were cultured at different concentrations of NLE-CDDP.MTT assay,inverted microscopic observation and flow cytometry assay(FCM)were used to observe the antiproli-ferative effect of NLE-CDDP on the human osteosarcoma cells.Antitumor effect of NLE-CDDP was determined using the xenografts models of human osteosarcoma cell Saos-2 in nude mice.The Pt concentration in the tissues of tumor-transplanted mice was determined by atomic spectrophotometer.Results: When treated at different concentrations of NLE-CDDP for 24-96 hours,the survival rate of Saos-2 cells decreased significantly(P
