A Direct Drive Parallel Plane Piezoelectric Needle Positioning Robot for MRI Guided Intraspinal Injection.

Recent developments in the field of cellular therapeutics have indicated the potential of stem cell injections directly to the spinal cord. Injections require either open surgery or a Magnetic Resonance Imaging (MRI) guided injection. Needle positioning during MRI imaging is a significant hurdle to direct spinal injection, as the small target region and interlaminar space require high positioning accuracy. OBJECTIVE: To improve both the procedure time and positioning accuracy, an MRI guided robotic needle positioning system is developed. METHODS: The robot uses linear piezoelectric motors to directly drive a parallel plane positioning mechanism. Feedback is provided through MRI during the orientation procedure. Both accuracy and repeatability of the robot are characterized. RESULTS: This system is found to be capable of repeatability below 51 µm. Needle endpoint error is limited by imaging modality, but is validated to 156 µm. CONCLUSION: The reported robot and MRI image feedback system is capable of repeatable and accurate needle guide positioning. SIGNIFICANCE: This high accuracy will result in a significant improvement to the workflow of spinal injection procedures.

[Clinical effect of Nd:YAG laser combined with total glucosides of paeony for the treatment of erosive oral lichen planus].

PURPOSE: To investigate the clinical effect of Nd:YAG laser combined with total glucosides of paeony (TGP) taken orally for the treatment of erosive oral lichen planus (OLP). METHODS: Sixty patients who were diagnosed as erosive OLP with clinical symptoms were divided into experimental group (n=28) and control group (n=32) using a random number table. All patients received TGP while the patients in the experimental group were given Nd:YAG laser irradiation. The clinical effects were evaluated 3 months after treatment. The data were analyzed using SPSS 17.0 software package. RESULTS: Three months later, the average VAS score and sign score had improved significantly to (1.36±1.39) and (2.32±1.56) in the experimental group. The same tendency was observed in the control group and at the time point no significant difference was observed between the experimental group and the control group. The effectiveness of the experimental group was significantly higher than the control group (82.1% vs 53.1%). CONCLUSIONS: Nd: YAG laser combined with TGP can improve the efficacy of erosive OLP. The regime is safe and effective, which is worth of wide clinical application.

Pharmacokinetics and safety of cyclophosphamide and docetaxel in a hemodialysis patient with early stage breast cancer: a case report.

BACKGROUND: Standardized chemotherapy used in cancer patients with severe kidney insufficiency is ineffective. Although there are some pharmacokinetic studies on cyclophosphamide in kidney insufficiency patients, to the best of our knowledge, the pharmacokinetics and safety of combination of cyclophosphamide and docetaxel as postoperative chemotherapy in a patient with early stage breast cancer undergoing hemodialysis is unclear thus far. CASE PRESENTATION: The patient received regular TC regimen (cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2). She underwent hemodialysis 48 h after chemotherapy. Blood samples at multiple time-points were collected for determination of plasma levels of cyclophosphamide and docetaxel. Pharmacokinetic analyses indicated that compared with the reference data, the in vivo half-life (66.96 h) and drug exposure (150%) of cyclophosphamide significantly increased; however, pharmacokinetic parameters of docetaxel was unaffected. Patient developed grade I thrombocytopenia and grade III leukopenia without any other severe adverse reactions. In total, four cycles of treatment were completed. After the chemotherapy, the patient received tamoxifen as endocrine therapy for one and a half years. No recurrence was reported. CONCLUSION: These results suggest that the standard TC regimen is mostly safe and could be used as postoperative adjuvant chemotherapy for hemodialysis patients with early stage breast cancer.

MiR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression.

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.

Combining bevacizumab and panitumumab with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as second-line treatment in patients with metastatic colorectal cancer.

Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3-4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC.

Resveratrol attenuates renal hypertrophy in early-stage diabetes by activating AMPK.

BACKGROUND: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms. METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot. RESULTS: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.