IntroductionStudies have demonstrated that mesenchymal stromal cells (MSCs) could reverse acute and chronic kidney injury by a paracrine or endocrine mechanism, and microvesicles (MVs) have been regarded as a crucial means of intercellular communication. In the current study, we focused on the therapeutic effects of human Wharton-Jelly MSCs derived microvesicles (hWJMSC-MVs) in renal ischemia/reperfusion injury and its potential mechanisms.MethodsMVs isolated from conditioned medium were injected intravenously in rats immediately after ischemia of the left kidney for 60 minutes. The animals were sacrificed at 24 hours, 48 hours and 2 weeks after reperfusion. The infiltration of inflammatory cells was identified by the immunostaining of CD68+ cells. ELISA was employed to determine the inflammatory factors in the kidney and serum von Willebrand Factor (VWF). Tubular cell proliferation and apoptosis were identified by immunostaining. Renal fibrosis was assessed by Masson’s tri-chrome straining and alpha-smooth muscle actin (α-SMA) staining. The CX3CL1 expression in the kidney was measured by immunostaining and Western blot, respectively. In vitro, human umbilical vein endothelial cells were treated with or without MVs for 24 or 48 hours under hypoxia injury to test the CX3CL1 by immunostaining and Western blot.ResultsAfter administration of hWJMSC-MVs in acute kidney injury (AKI) rats, renal cell apoptosis was mitigated and proliferation was enhanced, inflammation was also alleviated in the first 48 hours. MVs also could suppress the expression of CX3CL1 and decrease the number of CD68+ macrophages in the kidney. In the late period, improvement of renal function and abrogation of renal fibrosis were observed. In vitro, MVs could down-regulate the expression of CX3CL1 in human umbilical vein endothelial cells under hypoxia injury at 24 or 48 hours.ConclusionsA single administration of MVs immediately after ischemic AKI could ameliorate renal injury in both the acute and chronic stage, and the anti-inflammatory property of MVs through suppression of CX3CL1 may be a potential mechanism. This establishes a substantial foundation for future research and treatment.

Purpose: To obtain the treatment parameters of internally cooled microwave antenna and to evaluate the feasibility of ultrasound-guided percutaneous microwave ablation (MWA) for benign thyroid nodules. Materials and methods: MWAs were performed by microwave antenna (16G) in ex vivo porcine liver. The lesion diameters achieved in different groups (20, 25, and 30 W for 3, 5, 7, 10, and 12 min) were compared. The clinical study was approved by the ethics committee. Written informed consent was obtained from all patients. MWA was performed in 11 patients (male to female ratioZ1:10; mean age, 50G7 years) with 11 benign thyroid nodules. Ultrasound scan, laboratory data, and clinical symptoms were evaluated before and 1 day and 1, 3, 6, 9, and 12 months after the procedure. Results: In ex vivo study, the ablation lesion at 30 W 12 min tended to have appropriate scope and spherical shape. In clinical study, the follow-up periods ranged from 1 to 9 months. At the last followup, the largest diameter decreased from 2.9G1.0 (range, 1.6-4.1) to 1.9G0.7 (range, 0.4-3.0) cm (P!0.01), and the volume decreased from 5.30G4.88 (range, 0.89-14.81) to 2.40G2.06 (range, 0.02-6.35) ml (P!0.01). The volume reduction ratio was 45. 99G29.90 (range, 10.56-98.15) %. The cosmetic grading score was reduced from 3.20G0.79 to 2.30G0.95 (P!0.05). One patient experienced temporary nerve palsy and was recovered within 2 months after treatment. Conclusion: The internally cooled microwave antenna can yield ideal ablation lesions, and ultrasoundguided percutaneous MWA is a feasible technique for benign thyroid nodules.

Sonographically guided microwave coagulation proved to be safe and effective for the treatment of hepatocellular carcinoma. This therapy resulted in a high percentage of cases without evidence of residual tumor and satisfactory long-term results.

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The tumor suppressor p53 is a transcription factor that controls cellular growth and proliferation. p53 targets include RNA polymerase (pol) III-dependent genes encoding untranslated RNAs such as tRNA and 5S rRNA. These genes are repressed through interaction of p53 with TFIIIB, a TATA-binding protein (TBP)-containing factor. Although many studies have shown that p53 binds to TBP, the signi®cance of this interaction has remained elusive. Here we demonstrate that the TBP±p53 interaction is of functional importance for regulating RNA pol III-transcribed genes. Unlike RNA pol II-dependent promoter repression, overexpressing TBP can reverse inhibition of tRNA gene transcription by p53. p53 does not disrupt the direct interaction between the TFIIIB subunits TBP and Brf1, but prevents the association of Brf1 complexes with TFIIIC2 and RNA pol III. Using chromatin immunoprecipitation assays, we found that TFIIIB occupancy on tRNA genes markedly decreases following p53 induction, whereas binding of TFIIIC2 to these genes is unaffected. Together our results support the idea that p53 represses RNA pol III transcription through direct interactions with TBP, preventing promoter occupancy by TFIIIB.

BackgroundHepatocellular carcinoma (HCC) is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC.MethodsPubMed, the Cochrane Library, and Google Scholar were searched using the terms “bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable)”. Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS), tumor response, and toxicities.ResultsA total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial) or in combination with erlotinib (n = 4 trials), capecitabine (n = 1 trial), capecitabine+oxaliplatin (n = 1 trial), or gemcitabine+oxaliplatin (n = 1 trial). Most trials (five of eight) reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%), fatigue (12%), hypertension (10%), diarrhea (8%), and neutropenia (5%). Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12), typically due to esophageal varices.ConclusionsBevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently approved treatment for unresectable HCC. Phase III trials are warranted to comprehensively examine the efficacy and safety of bevacizumab for treatment of advanced HCC.

Compared with microwave ablation (MWA), percutaneous radiofrequency ablation (RFA) and laser ablation (LA) have been recommended as minimally invasive treatments for patients with symptomatic benign thyroid nodules (BTNs) because of the large number of clinical applications. This prospective multicenter study sought to evaluate the clinical outcomes of RFA and MWA for BTNs. In eight participating institutions, the total number of 1252 patients treated by RFA and MWA were 649 ones with 687 BTNs and 603 ones with 664 BTNs, respectively. The clinical outcomes including the nodular maximal diameter reduction ratio (MDRR), the nodular volume reduction ratio (VRR), and the incidence of complications were compared to evaluate the efficacy and safety of the two techniques. The results for the nodular MDRR and VRR in the RFA group were significantly better than those in the MWA group at 6 months and later follow-up, and the major complication rates of 4.78% and 6.63% in RFA and MWA groups showed no statistically significant differences. In conclusion, both RFA and MWA are safe and effective techniques for selected patients with symptomatic BTNs. The achieved MDRR and VRR in the RFA group were greater than those in the MWA group at 6 months and later follow-up.

In our previous study, microvesicles (MVs) released from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) retard the growth of bladder cancer cells. We would like to know if MVs have a similar effect on human renal cell carcinoma (RCC). By use of cell culture and the BALB/c nu/nu mice xeno-graft model, the influence of MVs upon the growth and aggressiveness of RCC (786-0) was assessed. Cell counting kit-8 (CCK-8) assay, incidence of tumor, tumor size, Ki-67 or TUNEL staining was used to evaluate tumor cell growth in vitro or in vivo. Flow cytometry assay (in vitro) or examination of cyclin D1 expression (in vivo) was carried out to determine the alteration of cell cycle. The aggressiveness was analyzed by Wound Healing Assay (in vitro) or MMP-2 and MMP-9 expression (in vivo). AKT/p-AKT, ERK1/2/p-ERK1/2 or HGF/c-MET expression was detected by real-time PCR or western blot. Our data demonstrated that MVs promote the growth and aggressiveness of RCC both in vitro and in vivo. In addition, MVs facilitated the progression of cell cycle from G0/1 to S. HGF expression in RCC was greatly induced by MVs, associated with activation of AKT and ERK1/2 signaling pathways. RNase pre-treatment abrogated all effects of MVs. In summary, induction of HGF synthesis via RNA transferred by MVs activating AKT and ERK1/2 signaling is one of crucial contributors to the pro-tumor effect.