Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortality. MicroRNAs have recently emerged as regulators of metastasis by acting on multiple signaling pathways. In this study, we found that miR-7 is significantly downregulated in highly metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function experiments showed that increased miR-7 expression significantly reduced GC cell migration and invasion, whereas decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also demonstrated that overexpression of miR-7 markedly inhibited GC metastasis. Moreover, the insulin-like growth factor-1 receptor (IGF1R) oncogene, which is often mutated or amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. Silencing of IGF1R using small interefering RNA (siRNA) recapitulated the anti-metastatic function of miR-7, whereas restoring the IGF1R expression attenuated the function of miR-7 in GC cells. Furthermore, we found that suppression of Snail by miR-7, through targeting IGF1R, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of miR-7 and IGF1R levels in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely correlated with IGF1R expression. The present study provides insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. Targeting this novel miR-7/IGF1R/Snail axis would be helpful as a therapeutic approach to block GC metastasis.

Background: Drug resistance is one of the biggest challenges in cancer therapy. temozolomide (TMZ) represents the most important chemotherapeutic option for glioma treatment. However, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioma, and the underlying mechanisms were not fully addressed. Herein, we demonstrate that the elevated expression of CD147 contributes to TMZ resistance in glioma cells, potentially through the post-translational regulation of Nrf2 expression. Methods: Cell-based assays of CD147 triggered drug resistance were performed through Edu-incorporation assay, CCK8 assay, TUNEL staining assay and flow cytometric assay. Luciferase reporter assay, protein stability related assays, co-immunoprecipitation assay were used to determine CD147 induction of Nrf2 expression through β-TrCP dependent ubiquitin system. Finally, the effect of the CD147/Nrf2 signaling on glioma progression and TMZ resistance were evaluated by functional experiments and clinical samples. Results: Based on the analysis of clinical glioma tissues, CD147 is highly expressed in glioma tissues and positively associated with tumor malignancy. Suppression of CD147 expression increased the inhibitory effect of TMZ on cell survival in both U251 and T98G cells, whereas the gain of CD147 function blocked TMZ-induced ROS production and cell death. Mechanistic study indicates that CD147 inhibited GSK3β/β-TrCP-dependent Nrf2 degradation by promoting Akt activation, and subsequently increased Nrf2-mediated anti-oxidant gene expressions. Supporting the biological significance, the reciprocal relationship between CD147 and Nrf2 was observed in glioma tissues, and associated with patient outcome. Conclusions: Our data provide the first evidence that glioma resistance to TMZ is potentially due to the activation of CD147/Nrf2 axis. CD147 promotes Nrf2 stability through the suppression of GSK3β/β-TrCP dependent Nrf2 protein degradation, which results in the ablation of TMZ induced ROS production. As such, we point out that targeting CD147/Nrf2 axis may provide a new strategy for the treatment of TMZ resistant gliomas.

Our results suggest that the urinary KIM-1 level is a sensitive and specific biomarker for the detection of early renal damage in HSP and may predict the severity of HSP and HSPN. The administration of creatine phosphate sodium (CP) may reduce urinary KIM-1 levels and thus correct the hypoxic condition of the kidney. Preconditioning with CP may also be a useful adjunct for preventing early renal damage in HSPN patients.

Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNA-binding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibroblasts resulted in a striking morphologic change: at confluency, the cells reorganized into a specific "bridge-like" pattern over the entire surface of the culture dish, and started migrating, thereby leaving circular holes in the monolayer. Thereafter, formation of cellular cords became apparent. This sequence of events was inhibited by coating the culture dishes with fibronectin and collagen IV. Retroviral transduction of Tel into MS1 endothelial cells reproduced the aggregation phenotype, but not the cellular cord formation. Tel-mutagenesis showed that both the pointed domain and the DNA-binding domain of Tel are required for the morphologic change. Other Ets family genes, Fli-1 and Ets-1 that are both endogenously expressed in endothelial cells, could not induce this morphologic change. Exogenous Tel expression is associated with transcriptional upregulation of entactin/nidogen, Smad5, Col3a1, CD44 and fibronectin, and downregulation of Col1a1 and secretory leukocyte protease inhibitor. Interestingly, Tel, Smad5, fibronectin, Col1a1 and Col3a1 all have essential roles during vascular development.

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Poster abstracts 79 different lesion types. In initial analyses, we have explored the expression of beta 3 integrin and certain other adhesion molecules.We demonstrate that the mRNA of beta 3 integrin is highly expressed in tumourgenic malignant melanomas and low or absent in compound nevi, paralleling these findings at the protein level 1 . We also demonstrate that the tetraspanin adhesion molecule CD9 is highly expressed in nevi with a low signal intensity detected in the melanoma sample. CD9 is a known marker whose function in melanomas is thought based on limited studies to inhibit metastatic potential.To confirm the mRNA expression data for these two markers as a proof of principle, we examined 20 tumourigenic malignant melanomas and 20 dermal nevi by immunohistochemistry to evaluate protein level expression of the respective markers. All of the melanomas showed expression of the integrin in more than 60% of lesion cells, whereas all of the nevi expressed the marker in less than 20% of their cells. Conversely, CD9 was expressed in more than 80% of cells in all but one nevus, and in less than 20% of cells in all of the melanomas. Our findings confirm the microarray expression profile for these two markers at the protein level, providing a proof of principle for use of expression arrays to evaluate expression profiles for interesting markers in RNA extracted from human tumours. 1. Van Belle, P.A. et al Hum. Pathol. (in press).Tel (ETV6) is an ETS transcription factor that is found fused to a variety of tyrosine kinases and transcription factors in lymphoid and myeloid leukemias and in fibrosarcoma and mesoblastic nephroma. It contains two functional domains, a pointed (PNT) protein interaction domain and a DNA binding domain (DBD).Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibroblasts resulted in a reproducible, striking morphological change: at confluency, the cells reorganized into a specific 'bridge-like' pattern over the entire surface of the culture dish, and started migrating, thereby leaving circular holes in the monolayer. Thereafter cellular cord formation became apparent. This morphological change is most reminiscent to that of endothelial cells that differentiate into tubes in vitro. This effect may relate to the role of Tel in angiogenesis: a Tel knockout study showed that early in development Tel is required for the maintenance of the cell layer surrounding the endothelial cells in the yolk sac. Electron microscopic examination of the fibroblastic cellular cords revealed that they did not contain a lumen. Retroviral transduction of endothelial cells did induce aggregation of the cells but not cellular cord or tube formation. We inhibited the Tel-induced morphological change in the fibroblasts by coating the culture dishes with high but not low concentrations of fibronectin and collagen IV. Transduction of the fibroblasts with deletion mutants or point mutants of Tel, or with MN1-Tel and VP16-Tel, showed that both the pointed domain and the DNA binding domain of...

Background In recent years, autologous fat grafting (AFG), also known as fat transfer or lipofilling, has been widely performed for periorbital rejuvenation and defect correction, although the evidence regarding its efficacy and safety is still lacking. Besides, with respect to the periorbital region, it is invariably the earliest appearance area of the facial aging phenomenon. Therefore, a systematic review and meta-analysis is needed to evaluate the efficacy and safety of this technique. Methods A literature search was performed in PubMed, Embase, and the Cochrane library databases on November 20, 2020, adhering to the PRISMA guidelines, to identify all relevant articles. Then, a data extraction and standardization process was performed to assess all outcome data. Ultimately, the data were assessed using a random effects regression model with comprehensive meta-analysis software. Results Thirty-nine studies consisting of 3 cohorts and 36 case series with a total of 4046 cases were included. Meta-analysis revealed a relatively high satisfaction rate of 90.9% (95% CI, 86.4%–94.0%). Frequent complications in 4046 patients receiving AFG were edema, chemosis, and contour irregularity, with an overall complication rate of 7.9% (95% CI, 4.8%–12.8%). Conclusion This systematic review and meta-analysis showed that AFG for rejuvenation of eyelids and periorbital area provided a high satisfaction rate and did not result in severe complications. Therefore, AFG might be performed safely for periorbital rejuvenation and reconstruction.

Introduction Corticosteroid-induced rosacea-like dermatitis (CIRD) is one of the cutaneous side effects of long and excessive application of topical corticosteroids, resembling rosacea that can present with a series of cutaneous manifestations. Most patients with CIRD undergo a variety of long-term treatments before their symptoms are relieved as there is no accepted standard therapy. We gave each of seven patients two sessions of platelet-rich plasma (PRP) mesotherapy before the routine treatment to restore their skin barrier function, and we were surprised to find that the patients’ symptoms and appearance were significantly improved without any further treatments. Here we report this unexpected finding in dealing with CIRD. Case Presentation Seven patients, one male and six female, who had history of applying topical corticosteroids on the face for more than 3 months continuously or intermittently for various reasons were diagnosed with CIRD, showing varying degrees of erythema, telangiectasia, and papules, with dry skin, pain, and burning or stinging sensation. We intended to use the restorative effect of PRP to restore the skin barrier function of the patients for further treatment such as tacrolimus ointment, intense pulsed light (IPL), or pulsed dye laser (PDL), so they were treated twice with PRP intradermal injections using a mesogun injector machine. We used the VISIA skin detector to photograph and compare the changes after the treatments. Clinical efficacy was also assessed by the Global Aesthetic Improvement Scale (GAIS). Patients’ assessments were recorded using three-point scale questionnaires. After two sessions of PRP treatment, before any further treatment, we were surprised to find that the patients' symptoms had improved significantly, as confirmed by VISIA skin detector and GAIS. All of the patients were satisfied with the outcomes, considering that mesotherapy was not painful and their appearance and symptoms had much improved. Conclusions PRP mesotherapy may mitigate sensitivity and inflammation in patients with CIRD by reducing erythema, telangiectasia, and papules. It is worth conducting large randomized controlled trials to verify its safety and efficacy in treating corticosteroid-induced rosacea-like dermatitis and maybe rosacea.