Caveolin-1, a 21-to 24-kd protein, is the principal component of caveolae, which are special invaginated microdomains of the plasma membrane present in most mammalian cells. 1 It is well established that caveolin-1 is a tumor suppressor gene. Caveolin-1 mRNA and protein expression are frequently lost in human cancer cell lines. Re-expression of caveolin-1 in oncogenically transformed cell lines inhibits tumor cell growth and reduces tumorigenicity. [2][3][4][5][6] Several mechanisms have been proposed for caveolin-1 to function as a tumor suppressor. Caveolin-1 may exert its tumor-growth inhibition by contact inactivation of signaling molecules such as v-src, Ha-Ras, protein kinase A, PKC, and p42/44 MAP kinase within caveolae. [7][8][9][10] In addition, down-regulation of caveolin-1 in colon carcinoma cells has been shown to prevent the degradation of inducible nitric oxide synthase via the proteosome pathway, which, in turn, increases the local nitric oxide concentration to facilitate tumorigenesis. 11 Caveolin-1 can also function as a tumor metastasispromoting molecule, which is unrelated to its obvious function of cell growth inhibition. 12 Elevated expression of caveolin-1 is found to be associated with progression of prostate, colon, and breast carcinoma. 13,14 Inhibition of c-myc-induced apoptosis by caveolin-1 was recently proposed to promote progression of prostate cancer, 15 and it may serve as a prognostic indicator for these patients. 16 Nonetheless, it still remains unclear whether and how caveolin-1 can potentiate tumor progression in other types of human cancer.In the present study, we investigated the expression pattern of caveolin-1 both in a series of lung carcinoma cell lines (CLs) with varying invasive/metastatic ability 17

Cancer cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1 expression in tumor-associated macrophages is associated with cancer recurrence and poor survival of patients with NSCLC. TREM-1 and the inflammatory response may play an important role in cancer progression.

BACKGROUND: Annexin A1 (AnxA1) has been well-known as a glucocorticoid-regulated anti-inflammatory protein, and it is implicated in tumorigenesis in a tumor type-specific pattern. However, the role of AnxA1 in gastric cancer (GC) is indeterminate, and the underlying mechanism is not clear. The purpose of this study was to evaluate the prognostic significance and associated mechanism of AnxA1 in GC. METHODS: Immunohistochemical staining was employed to analyze 118 GC patients. Both AnxA1 gain-of-function and loss-of-function approaches were performed in GC cells. Western blotting and reverse-transcription polymerase chain reaction were used for assessment of the AnxA1 regulation mechanism in GC cells. An intraperitoneal inoculation model in severe combined immunodeficient mice was used for an in vivo assay. RESULTS: High AnxA1 expression was significantly associated with peritoneal metastasis (P ¼ .009) and serosal invasion (P ¼ .044). Cox multivariate analysis showed that high AnxA1 expression was an independent risk factor for poor overall survival in GC patients (P ¼ .037). AnxA1 expression positively correlated with invasiveness of human GC cells both in vitro and in vivo. AnxA1 could regulate the GC cell invasion through the formyl peptide receptor (FPR)/extracellular signalregulated kinase/integrin beta-1-binding protein pathway, and all 3 FPRs (FPR1 through FPR3) were involved in the regulation process. CONCLUSIONS: High AnxA1 expression was associated with more serosal invasion, more peritoneal metastasis, and poorer overall survival in GC patients. The current study demonstrated a novel mechanism involving FPRs, extracellular signal-regulated kinases 1

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IntroductionDry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye.MethodsTo explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin–epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated “GEH”. The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit’s model.ResultsThe synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of IL1B and IL6 in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered.ConclusionWe successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES.