CXCR4 has long been considered as the unique receptor of CXCL12,and CXCL12/CXCR4 axis plays a prominent role in tumorigenesis.However,a novel receptor for CXCL12,named CXCR7,has been recently identified and also plays an important role in tumorigenesis.This review summarized current studies regarding the functions of CXCR4 and CXCR7 in cancer and the recent therapeutic approaches that target these receptors or their ligands.

Objective To explore the relationship between the expression of P53 protein and the radiosensitivity in patients with advanced maxillary squamous cell carcinoma.Methods An immunohistochomical method wag used to detect the expression of P53 protein in patients with advanced maxillary squamous cell carcinoma.The follow up time was 2 years.The local recurrence of the patients having been treated with radical surgery and affiliated radiotheraphy were analyzed.Results The overexpression of P53 protein in 26 cages was 65.4% (17/26).In the P53 overexpression group,the local recurrence after systiem therapy wag occurred in one case within 6 months,6 cages between 7～12 months.3 cages between 13～18 months and 2 cases between 19～24 months.In the P53 low expression group,there were no recurrence within 6 and 12 months and one case ocurred within 18 months.5 cages between 19～24 months.The difference of recurrence within 18 months after system therapy between the expression of P53 Wag statistically significant(P＜0.05),but it Wag not significant for those within 24 months(P＞0.05).Conclusions The expression of P53 protein Wag correlated with the radiosensitivity in patient with advaneed maxillary squamous cell carciaoma,especially for the resid.rod cells in mitosis phase.The affiliated radiotherapy after radical surgery Wag limited effect.

@@

OBJECTIVE: To identify long-term outcomes and safety of transplantation of autologous peripheral blood stem cells (PBSC) for treating dilated cardiomyopathy.METHODS: A total of 38 cases with dilated cardiomyopathy received treatment at the Department of Cardiology, Guangdong General Hospital of Chinese People's Armed Police Forces, were selected, including 26 males and 12 females, aged 42-72 years, mean aged 56 years. Based on given standard therapy, 38 patients divided randomly into the transplantation group (n=20) and the control group (n=18). Patients in the transplantation group were received recombinant human granulocyte colony-stimulating factor (rhG-CSF) 300 ug/d once per day for 5 days to mobilize stem cells. At day 6, PBSC were collected with blood-cells separator and were transplanted through intracoroary way. The routine medication was performed in the control group. Blood routine test, hepatic function, renal function, glucose, triglyeride (TG), cholesterol, low density cholesterol (C-LDL), high density cholest- erol (C-HDL), uric acid (UA), creatine kinase (CK), isoenzyme of creatine kinase (CK-MB) and high sensitive C-reactive protein (hsCRP) were measured before and at months 6 and 12 after transplantation. All patients also received ultrasonic echocardiography, ECG Holter monitor and six-minute-walk test before and at 12 and 24 months after the procedure. Survival rate and incidence rate of heart incidents were compared. The study end-point was death from any cause. RESULTS: All patients received a 12-24 month follow-up with mean (18±6) months. One patient in the transplantation group received mitral valve replacement. One patient of the transplantation group and 2 of the control group died due to refractory heart failure. The blood routine test and biochemical indicators of the transplantation group had no significant differences among 6 months and 12 months after transplantation compared with control and pre-transplantation (P > 0.05). Six-minute-walking distance in the transplantation group significantly increased at 12 months after transplantation than pre-transplantation level, which was also higher than that of control patients (P < 0.05). The left ventricular ejection fraction (LVEF) was increased (P < 0.01). The left ventricular diastolic diameter (LVDd) decreased significantly in the transplantation group (P < 0.01). In the control group, improvement in LVEF and LVDd were observed, but there was no significant difference (P > 0.05). After 24 months of follow-up, the above-mentioned indexes had not improved in the transplantation group without significant differences. No malignant arrhythmias and severe side effects could be observed around transplantation and during 24 months follow-up. Survival was similar between the two groups during 24 months follow. CONCLUSION: Transplantation of mobilized autologous PBSC might be a safe and effective method for the treatment of dilated cardiomyopathy, which may improve the ventricular systolic function in a short-term, however, the long-term effects still uncertain.

Objective To investigate the clinical features, effective treatment, survival and prognostic factors of second primary tongue squamous cell carcinoma (SPTSCC) after nasopharyngeal carcinoma (NPC) radiotherapy. Methods The clinical data of 35 cases with SPTSCC after NPC radiotherapy were analyzed retrospectively. Kaplan-Meier method, Log-Rank test and COX proportional hazard mode was performed for statistical analysis. Results 3-year and 5-year overall survival rates were 55 % and 47 %, respectively, lymph node metastasis rate was 5.71 %. Univariate analysis indicated that gender (χ2 = 8.89, P = 0.00), T classification (χ2= 5.58, P= 0.02), clinical stage (χ2 = 8.51, P= 0.04) and treatment methods (χ2 = 29.37, P = 0.00) were important factors of prognosis. Multivariate analysis showed that treatment methods (P = 0.00) and T classification (P = 0.03) were independent prognostic factors. Operative treatment group had better prognosis than the non-operative treatment group, the difference was statistically significant (P <0.05), male patients in the risk of SPTSCC was higher than the female patients, and the incidence of SPTSCC was increased along with extension of the time after NPC radiotherapy. Conclusion The rate of the lymph node metastasis is lower for SPTSCC after NPC radiotherapy and treatment patterns and T stage are independent prognostic factors. Long-term follow-up after NPC radiotherapy is necessary to the early diagnosis of SPTSCC, so that to give surgery or combined therapy with surgery in order to achieve a good effect.

Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20⁺ B-cell non-Hodgkin’s lymphoma (NHL). Methods: Nine patients with CD20⁺ B-cell NHL received dose-escalating IBI301 infusions (250 mg/m², n=3; 375 mg/m², n=3; 500 mg/m², n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m², 375 mg/m², 500 mg/m² dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19⁺, CD20⁺ B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m² group, 14 events of AE in 375 mg/m² group and 20 events of AE in 500 mg/m² group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20⁺ and CD19⁺ B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration Chinadrugtrials, CTR20140762.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*