Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was observed in lung adenocarcinoma tissues as compared with their normal counterparts. The lack of expression could be due to either the loss of heterozygosity (LOH) or hypermethylation of the CpG island DNA of TROP2 upstream promoter region as confirmed by bisulphite sequencing and methylation-specific (MS) polymerase chain reaction (PCR). 5-Aza-2′-deoxycytidine treatment on lung cancer cell (CL) lines, CL1-5 and A549, reversed the hypermethylation status and elevated both TROP2 mRNA and protein expression levels. Enforced expression of TROP2 in the lung CL line H1299 reduced AKT as well as ERK activation and suppressed cell proliferation and colony formation. Conversely, silencing TROP2 with shRNA transfection in the less efficiently tumour-forming cell line H322M enhanced AKT activation and increased tumour growth. Trop-2 could attenuate IGF-1R signalling-mediated AKT/β-catenin and ERK activation through a direct binding of IGF1. In conclusion, inactivation of TROP2 due to LOH or by DNA methylation may play an important role in lung cancer tumourigenicity through losing its suppressive effect on IGF-1R signalling and tumour growth.

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The pharmacist intervention program provided pharmaceutical services that improved long-term, safe control of blood sugar levels for ambulatory elderly patients with diabetes and did not increase medical expenses.

Objective Patients with RA often ask if specific foods, popularized as “inflammatory” or “anti-inflammatory,” can improve or worsen their RA. We surveyed patients regarding diet and RA symptoms. Methods We mailed a diet survey to 300 subjects in a single-center RA registry at a large academic center. Subjects were asked whether they consume each of 20 foods and whether these foods make their RA symptoms better, worse, or unchanged. Semi-annual registry data include demographics, medications, comorbidities, and disease activity scores. Fisher's exact and Wilcoxon rank-sum tests evaluated associations between subject characteristics from the most recent registry assessment and change in RA symptoms from specific foods. Results Among 217 subjects (72% response rate), 83% were female, median RA duration was 17 years (IQR 9-27), and 58% were using a biologic DMARD. Twenty-four percent of subjects reported that foods affect their RA, with 15% reporting improvement and 19% worsening. Blueberries and spinach were the foods most often reported to improve RA symptoms, while soda with sugar and desserts were most often reported to worsen RA symptoms. Younger age and noting that sleep, warm room temperature, and vitamin/mineral supplements improve RA were each associated with reporting that foods affect RA symptoms. Medication use, sex, body mass index, smoking, disease duration, disease activity scores, and self-reported RA flares were not associated with reporting that foods affect RA. Conclusion Nearly one-quarter of RA subjects with longstanding disease reported an effect of diet on their RA symptoms.

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Despite a wide range of available sources for bone repair, significant limitations persist. To bioengineer bone, we have previously transferred adenovirus-mediated human BMP-2 gene into autologous bone marrow stromal cells (MSC). We have successfully repaired large, full thickness, cranial defects using this approach. We report now the effectiveness of various hydrogels as the scaffold for this type of bone regeneration, comparing specifically alginate with Type I collagen. Cultured MSC of miniature swine were infected with BMP-2 or beta-gal adenovirus 7 days before implantation. These cells were mixed with alginate, ultrapure alginate, alginate-RGD, or type I collagen to fabricate the MSC/biomaterial constructs. The results of cranial bone regeneration were assessed by gross examination, histology, 3D CT, and biomechanical tests at 6 weeks and 3 months after implantation. We found that the BMP-2 MSC/collagen type I construct, but not the beta-gal control, effectively achieved nearly complete repair of the cranial defects. No bone regeneration was observed with the other hydrogels. Biomechanical testing showed that the new bone strength was very close and only slightly inferior to that of normal cranial bone. Controlling for the integration of stem cells and ex vivo gene transfer, the alginate scaffolds has a significant negative impact on the success of the construct. Our study demonstrates better bone regeneration by collagen type I over alginate. This may have therapeutic implications for tissue engineered bone repair.

Under real-world conditions, there is no excess risk for ONJ in osteoporosis patients >50 years old using alendronate as compared with patients using raloxifene or calcitonin.

The Ad5 E1A-deleted AdV may be the optimal starting vector in ex vivo gene therapy for benign skeletal diseases. Additionally, the use of the gelatin/tricalcium phosphate ceramic/glutaraldehyde biopolymer with AdV BMP-2 gene transfer strongly enhances the bony healing of critical-size bicortical craniofacial defects. This method can be used by modifying the delivery of constructs to malunion treatment, in regional osteoporosis therapy, and spinal fusion.