Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma.

Stress-induced phosphoprotein 1 (STIP1) is an adaptor protein that bridges between HSP70 and HSP90 folding and a secretory protein which regulates malignant cell growth. However, the role of STIP1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found high expression of STIP1 in tumors was associated with worse overall survival (41.3 vs 62.7 months, P < 0.001) in 231 HCC patients. STIP1 was overexpressed in HCC tissues compared to adjacent non-tumor liver tissue (64.9% vs 4.0% P < 0.001), and serum STIP1 levels of HCC patients were elevated compared to healthy controls (P < 0.001). Mechanistically, STIP1 promoted HCC growth through PI3K-AKT-dependent anti-apoptotic pathway. STIP1 mediated cell growth in an autocrine fashion, which could be suppressed either by neutralizing extracellular STIP1 or by knocking down intracellular STIP1. In xenograft mouse model, knockdown of STIP1 significantly reduced tumor growth (P < 0.001). In conclusion, STIP1 is upregulated in HCC and associated with poor clinical prognosis. Blocking STIP1 activity suppresses HCC cell growth, providing the rationale for STIP1 as a potential therapeutic target in HCC.

[Effect of benazepril on the VEGF and MVD in the remnant kidney of 5/6 subtotal nephrectomized rats].

OBJECTIVE: To explore the effect of benazepril (one of angiotesin converting enzymes) on the expression of vascular endothelial growth factor (VEGF) and the change of microvessel density (MVD) in the remnant kidney of rats that undergone 5/6 subtotal nephrectomy (STNx). METHODS: The male Sprague-Dawley (SD) rats were performed 5/6 nephrectomy to produce chronic renal failure, and randomly divided into a model group (STNx group), a STNx combined with benazepril group (Benazepril group), and a sham group that served as normal controls. Pathological changes of the remnant kidney were evaluated at the 8th week after gastric gavage. Immunohistochemistry Methods were used to examine the expression of VEGF and MVD in the remnant kidney, and the correlation was determined between VEGF, MVD and glomerulosclerosis index (GSI), tubulointerstitial score (TIS), BUN, and creatinine (Cr). RESULTS: UP, BUN, Cr, GSI, and TIS significantly decreased in the benazepirl group (P<0.05); and the expression of VEGF and MVD significant increased (P<0.05). The expression of VEGF was positively related to MVD (P<0.05), and there was negative correlation between VEGF, MVD and GSI, TIS, BUN, Cr (P<0.05). CONCLUSION: The decrease of the expression of VEGF and MVD in the remnant kidney may be involved in the progressive remnant kidney fibrosis and renal function. Benazepril can significantly relieve the remnant kidney fibrosis and protect the renal function by increasing the expression of VEGF and MVD in the remnant kidney.

[Intrathecal administration of HSV-I amplicon vector-mediated HPPE gene therapy of nocicepion in rats with formalin pain].

OBJECTIVE: To investigate the antinociceptive effect of intrathecal administration of HSV-I amplicon vector-mediated HPPE. METHODS: Sprague Dawley rats (290+/-30) g were randomly divided into pHSVIRES-HPPE-LacZ (SHPZ) group, pHSVIRES-LacZ (SHZ) group, and saline group (NS), and 3 d, 1 week, 2 weeks, 3 weeks, 4 weeks, and 5 weeks group,which were anesthetized with 10% chlroral hydrate 300- 350 mg/kg. A microspinal catheter was inserted into the lumbar subarachnoid space. Rats were intrathecally delivered with recombinant HSV-I amplicon vector SHPZ, SHZ or NS. The HPPE expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and radioimmune assay. Formalin 50 microL (5%) was injected into the left hindpaw, pain intensity scoring (PIS) was used to assess the antinociceptive effect. RESULTS: After in vivo transferring,neurocyte demonstrated strong positive signals with X-gal immunohistochemical staining. RT-PCR and L-enkephalin radioimmune assay found that the neural cells transferred foreign gene (HPPE) had effective expression. Intrathecal delivery of SHPZ showed antinociceptive effects on formalin induced pain for 5 weeks compared with SHZ. CONCLUSION: This amplicon virus can transfer HPPE into rat central nerve system neural cells and express efficiently, suggesting SHPZ is satisfactory treatment for gene therapy for chronic pain. Intrathecal delivery SHPZ demonstrated antinociceptive effects on formalin induced pain.

[Hypofibrinogenemia caused by hemocoagulase after endoscopic sinus surgery: a case report].

A 61 year-old male patient, plasma fibrinogen level was 2.98 g/L, endoscopic sinus surgery was performed under general anesthesia for polypoid of uncinate process with mycotic maxillary sinusitis. Hemocoagulase were given in pre- and post-operative for treatment. The patient was found postoperative drain blood continuously since 3 days after surgery, when the dose of hemocoagulase reach 26 KU, and fibrinogen determined in Plasma was 0.48 g/L. Coagulation returned to normal and nasal bleeding stopped after discontinuation of the hemocoagulase and supplement with fibrinogen.

[The value of cyclooxygenase-2 to predict the effect of radiotherapy in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the relation between the expression of COX-2 protein and the effect of radiotherapy, estimate the value of COX-2 in predicting the effect of radiotherapy in patients with nasopharyngeal carcinoma,provide theoretical basement for establishing characteristic project of treatment and raising curative effect and life quantity. METHOD: The expression of COX-2 protein was examined in 30 radiosensitive and 30 radioresistant poorly differentiated NPC by immunohistochemical staining (SP method) before radiotherapy. The relation between the expression of COX-2 and the effect of radiotherapy was analyzed. RESULT: The positive rate of COX-2 protein expression was 61. 67% in NPC tissues, there was statistical difference( P <0. 01) of the positive rate between the 86. 67 % of 30 radioresistant and 36. 67 % of radiosensitive NPC tissues. The intensity of COX-2 protein expressions showed statistical difference( P <0. 05),too. Based on the expression of COX-2, the effect of radiotherapy, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, false positive and false negative were predicted as follows: 86. 67Y, 63. 33% ,75. 00%, 70. 27% ,82. 61% ,36. 67% and 13. 33 , respectively. CONCLUSION: COX-2 expression may serve as a marker in predicting the response to radiotherapy in NPC. According to the expression of COX-2, the sound treatment scheme can be selected.

[Blood vessel multiply and significance of expression of Cox-2, VEGF in pterygium].

OBJECTIVE: To investigate the role of cyclooxygenases-2 (Cox-2) and vascular endothelial growth factor (VEGF) in the occurrence and development of human pterygium. METHODS: The immunohistochemical elivision method was used to examine the expressions of Cox-2 and VEGF in 30 cases of pterygium and 15 cases with normal conjunctiva. RESULTS: The positive rate of Cox-2 was 42.8% in resting stage, 84.6% in active stage, 90.0% in recurrent pterygium and 6.6% in normal conjunctiva. The positive rate of VEGF was 57.1% in resting stage, 69.2% in active stage, 100.0% in recurrent pterygium and 13.3% in the normal conjunctiva. There was significant difference in the expressions of Cox-2 and VEGF between the pterygium and normal conjunctiva (P < 0.05, P < 0.001). CONCLUSIONS: There are high Cox-2 and VEGF expressions in pterygium, which suggests that there is abnormal blood vessel multiply in pterygium, and the Cox-2 and VEGF plays an important role in the incidence and development of pterygium. Specific Cox-2 and VEGF inhibitor become a new target for the therapy of pterygium. Specific Cox-2 and VEGF inhibitor become a new target for the therapy of pterygium.