The effect of cell cycle synchronisation on glucose metabolism in cancer cells is not known. We assessed how cell cycle synchronisation by thiazolidinediones (TZDs) can affect glucose uptake by cancer cells and investigated the anti-cancer effect of combination therapy with TZDs and 2-deoxy-glucose (2-DG) in colon cancer cells and in mouse xenograft models. Troglitazone (58.1 ± 2.0 vs 48.6 ± 1.3%, p = 0.002) or pioglitazone (82.9 ± 1.9 vs 61.6 ± 3.4%, p < 0.001) induced cell cycle arrest in SW480 cells at G1 phase. Western blot analysis showed the degradation of cyclin D1 and CDK4, and an increase in the expression levels of p21 and p27 after TZDs treatment. Withdrawal of troglitazone treatment induced significant increase in cellular 3 H-DG uptake (141.5% ± 12.9% of controls) and membrane GLUT1 expression levels (146.3% of controls) by 24 h; 1 mM 2-DG treatment alone decreased cell survival by 5.8% as compared with the controls.; however, combination therapy enhanced the anti-tumour effects to 34.6% or 20.3% as compared with control cells. In vivo, each combination treatment group showed significant anti-tumour effects unlike the 2-DG alone group. Cell cycle synchronisation using TZDs induced cellular glucose uptake, which significantly enhanced the therapeutic effect of 2-DG in colon cancer.The reprogramming of energy metabolism has recently been recognised as a hallmark of cancer 1 . Understanding metabolic differences between normal cells and cancer cells can provide opportunities for both cancer imaging and therapy. Imaging glycolytic shifts in tumours using 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET), which has been widely used in clinical oncology, is a notable example. To treat cancers by targeting tumour metabolism, 2-deoxyglucose (2-DG) inhibits glycolysis, depletes intracellular adenosine triphosphate, and induces autophagy in cancer cells 2 . However, as high concentrations of 2-DG are needed to inhibit the glycolytic metabolism of cancer cells 2,3 , approaches that can enhance the efficacy of 2-DG treatment are crucial.Until now, a lot of agents that can modulate cell cycle in cancer cells have been used or are under development for cancer therapy 4 . However, few studies have examined the effect of cell cycle synchronisation on glucose metabolism in cancer cells. We have previously reported that cell cycle arrest at G1 by T-type calcium channel blocker, mibefradil, induced a subsequent increase in cell population in S phase after drug removal, and increased glucose uptake s in breast cancer cells, which enhanced the therapeutic effects of 2-DG 5 .Peroxisome proliferator activated receptor-γ (PPARγ) is widely expressed in various tumours and cell lines, thus this receptor has become a target for developing new anticancer drugs that can take advantage of the antiproliferative effects mediated through PPAR. Thiazolidinediones (TZDs), such as troglitazone, pioglitazone, ciglitazone, and rosiglitazone are well-known PPARγ ligands. TZDs have been reported to exert anti-tumour effects,...

This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 269 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy (mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 78 patients were analyzed. Tissue eosinophilia was significantly associated with age and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, in patients with non-eosinophilic CRSwNP, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.

Background and Objective: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response of the lung to noxious particles or gases. Cigarette smoking is the major risk factor for the development of COPD. This study evaluated the levels of cyclophilin B in sputa from patients with COPD and COPD with acute exacerbation (AECOPD). Materials and Methods: Two-dimensional electrophoresis was used for differential display proteomics. Western blotting was used to identify and quantify cyclophilin B in sputum from subjects with AECOPD and COPD. Results: Forty-nine protein spots differed in relative intensity between the AECOPD (n = 6) and COPD (n = 6) subjects. Twenty proteins showed increased expression in the sputum of AECOPD subjects, and 29 proteins were present at lower levels in AECOPD sputum compared with COPD sputum. One of these proteins was associated with cyclophilin B. Cyclophilin B concentrations were lower in sputum from subjects with COPD (n = 4) versus AECOPD (n = 4). Conclusion: The sputum proteomic analysis suggests that changes in various proteins are associated with the development of AECOPD.

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This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 296 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy(mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 58 patients were analyzed. Tissue eosinophilia was significantly associated with age, and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients in patients with non-eosinophilic CRSwNP. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.