Cyclooxygenase-2 inhibitor rofecoxib prevents chondrocytes against hypertrophy via Wnt/ß-catenin pathway.

Previous reports indicated that specific cyclooxygenase-2 (COX-2) inhibitor suppresses osteoarthritis (OA). This study aimed to further explore the possible mechanism of Rofecoxib as a COX-2 inhibitor on the inhibition of chondrocyte (CH) hypertrophic development and tested the optimal treatment of Rofecoxib on CH. Basically, IL-1ß was used as a stimulus to establish a degenerated CH model. Immunofluorescence, Western blot, and RT-PCR were performed to determine the gene expression of Axin2, ß-catenin, GSK3ß, collagen X, collagen II, COX-2, PGE-2, SOX-9, Runx-2, and MMP- 13 expression. Cell Counting Kit (CCK-8) assay was used to analyze the viability of CHs. The data indicated that Rofecoxib significantly inhibited COX-2 expression and had less harmful effects on CH viability. Rofecoxib reversed the IL-1ß-induced upregulation of collagen X, COX-2, PGE-2, Runx-2, and MMP-13 expression, and promoted the viability of collagen II, SOX-9 expression of CHs. Furthermore, Rofecoxib suppressed Axin2, ß-catenin, and GSK3ß expression of the Wnt pathway, which was activated by IL-1ß or human recombinant Wnt-1 protein treatment. Therefore, Rofecoxib is an effective COX-2 inhibitor that protects CHs from hypertrophy by suppression of the Wnt/ß-catenin pathway.

Chinese medicinal herbs for influenza.

BACKGROUND: Influenza is an acute respiratory communicable disease which, during epidemics, can cause high morbidity and mortality. Traditional Chinese medicinal herbs, often administered following a particular theory, may be a potential medicine of choice. OBJECTIVES: To assess the effect of Chinese medicinal herbs in preventing and treating influenza, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2007), which includes the Cochrane Acute Respiratory Infections Review Group specialised register; MEDLINE (January 1966 to January 2007); EMBASE (January 1988 to January 2007); CBM (Chinese Biomedical Database) (January 1980 to January 2007); and the Chinese Cochrane Center's Controlled Trials Register (up to January 2007). We also searched Current Controlled Trials (www.controlled-trials.com) and the National Research Register (http://www.update-software.com/National/) for ongoing trials and reference lists of articles. For more information we telephoned and wrote to researchers in the field, as well as trial authors of studies evaluated in the review SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing traditional Chinese medicinal herbs with placebo, no treatment, or chemical drugs normally used in preventing and treating uncomplicated influenza patients. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Two studies involving 1012 participants were reviewed. The methodological quality of both studies was 'poor'. Included RCTs separately compared two medicinal herbs with two different antiviral drugs, precluding any pooling of results. 'Ganmao' capsules were found to be more effective than amantadine in decreasing influenza symptoms and speeding recovery in one study, (in which adverse reactions were mentioned in the amantadine group although no data were reported). There were no significant differences between 'E Shu You' and ribavirin in treating influenza, nor in the occurrence of adverse reaction. AUTHORS' CONCLUSIONS: The present evidence is too weak to support or reject the use of Chinese medicinal herbs for preventing and treating influenza. More RCTs with good methodological quality, larger numbers of participants and clear reporting are needed in the future. We recommend that all the clinical trials registered in the Chinese Clinical Trial Register and Chinese journals join in the Joint Statement of Establishing Chinese Clinical Trial Registration and Publishing System.

Chinese medicinal herbs for influenza.

BACKGROUND: Influenza is an acute respiratory communicable disease which can cause high morbidity and mortality in an epidemic. Traditional Chinese medicinal herbs following a particular theory may be a potential medicine of choice. OBJECTIVES: The objective of this review was to assess the therapeutic effect and adverse reaction of Traditional Chinese medicinal herbs in treating uncomplicated influenza. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2004); MEDLINE (January 1966 to October 2004); EMBASE (January 1988 to October 2004); CBM (Chinese Biomedical Database) (January 1980 to December 2003); and the Chinese Cochrane Center's Controlled Trials Register (up to December 2003). We also searched Current Controlled Trials (www.controlled-trials.com) and the National Research Register (http://www.update-software.com/National/) for ongoing trials and reference lists of articles. We wrote to researchers in the field, or authors of studies evaluated in the review for more information. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing traditional Chinese medicinal herbs with placebo, or various other Chinese medicinal herbs, or with other current regimes normally used in care or comparing drugs with herbal preparations to simple drugs in treating defined uncomplicated influenza patients. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality. MAIN RESULTS: Eleven studies with the number of participants ranged from 52 to 479. In total 2,088 participants were included in the review. As the interventions of the included studies were different from each other and most of the studies were of low quality, we did not perform a summary meta-analysis. Some of the studies showed positive results favouring Traditional Chinese medicinal herb treatment compared to antiviral or antipyretic-analgesic drugs or the combination of them. Only three studies mentioned adverse reactions but no detailed data were acquired in the included studies. Eleven studies with the number of participants ranged from 52 to 479, 2,088 in total were included. As the interventions of the included studies were different from each other and most of the studies were of low quality, we failed to perform a summary meta-analysis. Some of the studies showed positive results favouring Traditional Chinese medicinal herb treatment compared to antiviral or antipyretic-analgesic drugs or the combination of them. Only three studies mentioned adverse reactions but no detailed data was acquired in the included studies. AUTHORS' CONCLUSIONS: The small number of included studies and participants, as well as the low quality of most studies, made the evidence far from conclusive for clinical decision making, although traditional Chinese medicinal herbs as a whole seem to be comparatively or more effective compared to different chemical drugs. A certain herbal preparation could not be recommended for there was not enough evidence. More high quality randomised controlled trials (RCTs) with similar interventions are required to strengthen the evidence for the efficacy and safety of certain herbal preparation.

Immunomodulatory gene therapy with interleukin 12 and 4-1BB ligand: long- term remission of liver metastases in a mouse model.

BACKGROUND: The success of immunomodulatory cancer therapy is frequently hampered by the transient nature of the antitumor immune response. We have shown previously in a mouse model that interleukin 12 (IL-12) generates a strong natural killer (NK) cell-mediated antitumor response and reduces liver metastases induced by a colon carcinoma cell line. However, only a small percentage of the treated animals developed the cytotoxic T-lymphocytic response required for a long-term systemic antitumor immunity. 4-1BB is a co-stimulatory molecule expressed on the surface of activated T cells. Interaction of 4-1BB with its natural ligand (4-1BBL) has been shown to amplify T-cell (especially CD8+)-mediated immunity. In this study, we investigated the effects of adenovirus-mediated gene therapy delivering both IL-12 and 4-1BBL genes on mice with hepatic metastases induced by colon cancer cells. METHODS: Syngeneic BALB/c mice received intrahepatic injection of poorly immunogenic MCA26 colon cancer cells. Various combinations of replication-defective adenoviruses expressing IL-12 and 4-1BBL genes were injected into the established liver tumors. Changes in tumor size and animal survival were then monitored. All statistical tests were two-sided. RESULTS: The long-term survival rate of mice treated with the combination of IL-12 and 4-1BBL was significantly improved over that of animals in the control group (P =.0001). In vivo depletion of NK cells or CD8+ T cells completely abolished the long-term survival advantage of the IL-12 plus 4-1BBL-treated animals (P<.002). Moreover, the systemic immunity induced by this combination treatment protected these animals against a subcutaneous challenge with parental MCA26 cells. CONCLUSION: Adenovirus-mediated transfer of IL-12 and 4-1BBL genes directly into liver tumors resulted in tumor regression that required both NK and CD8+ T cells and generated a potent, long-lasting antitumor immunity.