Sarcomas are tumors of mesenchymal origin that account for approximately 1%of human cancers. There are at least 60 dif-ferent subtypes of soft tissue sarcoma (STS). However, most tumor types are highly malignant tumors that lack an optimal therapeutic agent. Although gastrointestinal stromal tumor (GIST) responds well to imatinib, other types of STSs remain challenging because of their heterogeneous genetic and clinical features and poor prognosis. In recent years, the field of molecular targeted therapy has pro-gressed rapidly. Patients with advanced disease can receive individualized treatment to improve their quality of life. This review focus-es on the targeted therapies that have been evaluated for advanced non-GIST STS. Other promising novel therapeutic agents that are currently in the early phases of investigation are also presented.

Objective To investigate the effects of Tongxinluo,a Chinese medicine,on neurological deficits,neuron apoptosis and the expression of nerve growth factor(NGF) and brain derived neurotrophic factor(BDNF) after cerebral ischemia in diabetic rats.Methods Wistar diabetic rats(n=36) were subjected to middle cerebral artery occlusion and randomly divided into 2 groups:control group(n=18) and Tongxinluo group(n=18).Tongxinluo group received Tongxinluo 1.0 g/kg·d after cerebral ischemia.Neurological severity scores,TUNEL staining and immunohistological assessments were performed to evaluate the effects.Results Compared with the control,the neurological score significantly improved(P<0.05),the expression of NGF and BDNF increased(P<0.05),and cell apoptosis decreased(P<0.05) in the tongxinluo group.Conclusion Tongxinluo can improve the neurological function through inhibition of neuron apoptosis and increasing the expression of NGF and BDNF after cerebral ischemia in diabetic rats.

Objective:To investigate effects of viola on macrophage TOLL-like receptor expression ,and tentatively explore the partial mechanism of viola intervention on macrophage function.Methods: Using viola water decoction lavage intervention in clean grade SD rats of conventional preparation containing serum ,In a certain concentration coculture with mouse peritoneal macrophages in 96-well plates.After 24 hours,cell phagocytosis activity was determined by neutral red uptake assay ,changes in expression levels of TLR-1,TLR-2,TLR-3,TLR-4,TLR-5 mRNAs were determined by RT-PCR.Results:Compared with the same concentration of normal serum group :(1 ) viola-containing serum group macrophage activity was significantly increased ( P<0.01 );( 2 ) Within certain concentration,viola containing serum group with increased or decreased expression levels of TLR -1,TLR-2,TLR-3 mRNA(P<0.05 or P<0.01 ) ,the expression level of TLR-4 was not significantly altered in each group ( P>0.05 ) ,and the expression level of TLR-5 was significantly increased in each group ( P<0.01 ).Conclusion:Viola-containing serum has obvious promoting effect on macrophage phag-ocytosis,the mechanism of which may be related to that this drug regulates and controls part of macrophage TOLL -like receptor expres-sion.

Objective:To evaluate the accuracy and feasibility of sentinel lymph node biopsy (SLNB) marked by 99Tcm-IT-Ritux-imab and to discuss the clinical value of the method in diagnosis and treatment of cutaneous melanoma. Methods:A total of 67 patients with cutaneous malignant melanoma received 99Tcm-IT-Rituximab-tagged SLNB from March 2008 to March 2012. Lymphoscintigra-phy was conducted 30 min to 1 h after intra-dermal injection of 99Tcm-IT-Rituximab. Subsequently, the surgery of SLNB was carried out using gamma probe. The detection and positive rates of SLNB were counted. The relationship between the status and the clinical features of the sentinel lymph node (SLN) was analyzed, such as the T stage, ulceration, age, gender, and location. The influence of SLN status on overall survival (OS) and disease-free survival (DFS) was evaluated. Results:SLNs were detected in all the 67 patients by SPECT and gamma detector, with detection rate of 100%. Fifteen patients had SLN metastasis, and the positive rate was 22.4%. Chi-square indicates that SLN metastasis is associated with age, T stage, and ulceration (P<0.05). A total of 63 patients were followed up for 24-69 months, and the median follow up time was 43 months. Kaplan-Meier survival analysis shows that both OS and DFS in the SLN-negative group are better than those in the SLN-positive group (OS:93.9%vs. 57.1%, P<0.01;DFS:79.6%versus 28.6%, P<0.01). Cox-regression multiple factors analysis suggests that both SLN status and T stage are independent factors that affect the DFS of malignant melanoma. Conclusion:SLNB assisted by 99Tcm-IT-Rituximab can well reflect the state of lymph node metastasis and is es-sential for accurate staging, prognosis judging, and treatment guiding. Its operation procedure is simple with high accuracy, and the im-aging status is stable. Therefore, it is convenient and feasible as a means of SLNB.

OBJECTIVE: To evaluate the advantage of Gukangling Decoction (GKLD), a compound traditional Chinese herbal medicine, combined with technetium [(99)Tc] methylene diphosphonate injection ((99)Tc-MDP) in treating osteoporosis in rabbits. METHODS: A rabbit model of osteoporosis was established by intramuscular injection of dexamethasone (DX). Fifty-six rabbits were divided into 8 groups: Group A, B, C, D, E, F, G and H. Rabbits in groups A and B were intramuscularly injected normal saline as normal control, groups C and D were untreated groups, rabbits in group E were treated by (99)-MDP, rabbits in group F were treated by aminodiphosphate, rabbits in group G were treated by GKLD, and rabbits in group H were treated by (99)-MDP and GKLD. Rabbits in groups A and C were executed to demonstrate the establishment of the rabbit model of osteoporosis at the 8th week of experiment. Rabbits in the other six groups were executed after 16-week experiment (8-week treatment), and then bone structure and cell shape were observed by electron microscope, X-ray, CT and emission computed tomography (ECT). Bone density, biomechanical parameters, the levels of bone specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured too. RESULTS: After 8-week of intramuscular injection of DX, the bone trabecula in group A were regular and showed normal configuration, while the bone trabecula in group C were sparse, ruptured and showed damaged form. The bone density and biomechanical parameters in group A were higher than those in group C, indicating that the rabbit model of osteoporosis was established successfully. At the 9th week of experiment, the results of cell pathology in group D showed that the bone trabeculas were sparse, ruptured, defected or had hollow section, but the bone trabeculas in group B were regular and dense. The bone trabeculas in groups H and E were restored, and were thicker than those in group D. The bone quality in groups H and E was better than group D significantly, the bone quality in group F was better than group G, and the bone quality in group G was better than group D slightly. CONCLUSION: GKLD combined with (99)-MDP had superiority in treating osteoporosis of rabbits as compared with the respective single therapy.

Objective:Cancer stem cells (CSCs) are resistant to chemotherapy. Our study aimed to investigate the stem cell-like proper-ties of doxorubicin-resistant osteosarcoma cell line 143B and its correlation with Notch signaling. Methods:We generated doxorubicin-resistant osteosarcoma cells by treating them with 2μm doxorubicin. Stem cell-like properties such as morphology change, Stro-1/CD117 double positive ratio, stem cell-related gene expression, sphere formation efficiency, and EMT character were assessed on day 5 after doxorubicin withdrawal. Notch receptor and its target genes were examined using qPCR and Western blot analysis. The stem cell-like properties of doxorubicin-resistant osteosarcoma cells were assessed when pretreated with Notch inhibitor or vehicle. The an-ti-tumor effect of Notch inhibitor was tested using a xenograft model. Results:Doxorubicin-resistant osteosarcoma cells were enriched in Stro-1+/CD117+cells, which showed obvious increased expression of stem cell-related genes, and exhibited enhanced spheroid for-mation and evident mesenchymal characteristics unlike doxorubicin-sensitive cells. qPCR and Western blot assays showed that Notch intracellular domain 1 (NICD1) and target genes Hes1 and Hey1 were upregulated in doxorubicin-resistant osteosarcoma stem cells compared with those in vehicle cells. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signaling en-hanced chemo-sensitivity and inhibited doxorubicin-enriched osteosarcoma stem cell activity in vitro. Finally, the Notch inhibitor pre-vented tumor growth in mice xenograft models. Conclusion: Doxorubicin induced the enrichment of osteosarcoma stem-like cells through Notch signaling, and inactivation of Notch could be useful for overcoming drug resistance and eliminating osteosarcoma.

Objective To measure the organ weights , blood physiological and biochemical parameters , and immune cells of BALB/cA-nu mice .Methods BALB/cA-nu mice at five and ten weeks of age were selected , and the organ weights , blood physiological and biochemical parameters were observed .The percentages of CD 3+, CD4+, CD8+, CD19+, B220+, NK1.1+, and CD11b+were detected by FCM in BALB/cA-nu mice at six weeks of age in terms of its T, B lymphocyte cells and NK cell activity .Results At the same age, the weights of the body , liver, and kidney in male mice are significantly higher than females .The HGB、MCH、HCT in male mice are significantly higher than females (P <0.05).The weights of the lung, liver, and kidney, and the parameters of TP、GLOB、CHO、TBIL、UN are significantly lower at five weeks of age comparing with ten weeks (P <0.05).The BALB/cA-nu mice lacks T cells(0.18 ±0.06)%、CD4+T cells(0.26 ±0.08)%、CD8+T cells(0.13 ±0.04)%、The percentage of B cells is CD19+B cells (30.10 ±2.74)% and B220 +B cells(30.55 ±2.77)%.The percentage of NK cells is (1.35 ±0.29)%, and the percentage of granulocytes is (47.90 ±5.48)%.The BALB/cA-nu mice lack T cells and the group of cells .Conclusion The study suggests that the organ weights , blood physiological and biochemical parameters are affected by age and gender in BALB/cA-nu mice that lack T cells immune function .The studied parameters of BALB/cA-nu mice are similar with the same strain in other countries .

Objective:To investigate the effects of Huang-Lian-Jie-Du-Decotion containing serum for the autophagy of RAM264.7 macrophages ,and to explore its possible anti-atherosclerosis mechanism .Methods:The SD rats were intervened with large , middle and small dose Huang-Lian-Jie-Du-Decotion to prepare containing drug serum .Cell proliferation was tested by MTT assay .The gene and protein expressions of Beclin 1, mTOR was assessed by fluorescent quantitative PCR and Western blot method .Results:Compared with the normal serum group ,Huang-Lian-Jie-Du-Decotion containing serum enhanced expression of the mRNA and protein level of Beclin1,and decreased the expression of mTOR and p-mTOR(P<0.05 or P<0.01).Conclusion:Huang-Lian-Jie-Du-Decotion containing serum could regulate the expressions of Beclin 1 and mTOR.These might be one of the mechanisms for preventing atheroscle-rosis.

Objective:To explore the outcome of soft tissue sarcoma (STS) on patients with soft tissue metastasis. Methods:We ana-lyzed 25 STS patients with soft tissue metastasis primarily localized on extremity and trunk. The study was conducted from June 2010 to June 2016 by retrospective analysis of the clinical and pathological characteristics of the patients. The assessed endpoints were overall survival. Results:Six patients (24%) had synchronous soft tissue metastasis, and 19 patients (76%) had metachronous metasta-sis. The average time for primary tumor recession of metastatic lesions was 45.3 months. Metastases were most common in parts of the trunk in 18 patients (72%), followed by the head and neck in 5 patients (20%). Eleven patients (44%) with lung metastasis had poor prognosis. Conclusion:STS occurred more rarely in soft tissue metastasis than in pulmonary metastasis. Neoadjuvant chemotherapy and surgical treatment were the major therapies employed. Targeted therapy as a new treatment rendered good results.

Objective To measure the organ weights , physiological and biochemical parameters and immune cells of NOD/SCID mice.Methods Mice at five and ten weeks of age were selected .The organ weights, blood physiological and biochemical parameters were observed .The percentages of CD 3+, CD4+, CD8+, CD19+, B220+, NK1.1+, and CD11b+were checked by FCM in NOD/SCID mice at six week of age in terms of its T , B lymphocyte function and NK cell activity.Results Among the same sex group of NOD/SCID mice, the weights of kidney, liver, heart and lung, and the blood physiological indexes of RBC , HGB, HCT, MCV, MCH, RDW, and the blood biochemical indexes of TP , ALB, ALP, CHO, TBIL show significant difference between 5 and 10 weeks.At the same age, HCT, GLOB, A/G, CHO, TG, TBIL and the UN are significantly different between male and female NOD /SCID mice.NOD/SCID mice lack T cells (0.37 ±0.26)%、CD4+T cells (0.35 ±0.13)%、CD8 +T cells (0.47 ±0.10)%、CD19+B cells (0.13 ± 0.05)%、B220+B cells (1.20 ±0.44)%.The percentage of NK cells is (6.90 ±0.82)%, and the percentage of granulocytes is (47.88 ±15.54)%.Conclusions The study indicates that NOD/SCID mice show the deficiency of T , B and NK cells function .The organ weights , blood physiological and biochemical parameters are affected by age and gender . The studied parameters of NOD/SCID mice are similar with the same strain in other countries .