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In the previous study, we had showed the expression of CD133+ CD54+ CD44+ cellular subpopulation of circulating tumor cells ( CTCs) was significantly associated with liver metastasis of colorectal cancer ( CRC). This study aimed to explore whether this subpopulation of CTCs have a prognostic value in CRC patients. Flow cytometry was used to detect the expression of cellular subpopulations of CTCs with CD133, CD54, and CD44 in 152 CRC patients, between December 2013 and October 2014. The impact of clinicopathological factors and the expression of cellular subpopulations of CTCs on overall survival were then analyzed. CRC patients with liver metastases who underwent resection of the primary tumor accompanied by surgical treatment for metastasis had a better survival than other patients ( P < 0.001). The liver metastatic CRC patients with high expression of CD133+ CD54+ ( P < 0.001), CD133− CD54+ ( P = 0.004), and CD133+ CD44+ CD54+ ( P = 0.003) cellular subpopulations of CTCs had a worse survival than those patients with low expression. Multivariable survival analyses identified carcinoembryonic antigen levels (hazard ratio [ HR] = 3.056; 95% confidence interval [ CI] = 1.354-6.897; P = 0.007), treatment strategy ( HR = 0.212; 95% CI = 0.056-0.808; P = 0.023), and CD133+ CD44+ CD54+ cellular subpopulation of CTCs ( HR = 6.459; 95% CI = 1.461-28.558; P = 0.014) as independent prognostic factors for CRC patients with liver metastasis. CD133+ CD44+ CD54+ cellular subpopulation of CTCs has a prognostic value in CRC patients with liver metastasis, especially in the survival of CRC patients with liver metastasis who did not undergo surgical treatment for metastasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. RESULTS: Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower ( P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Ethyl pyruvate (EP) was reported to have an ameliorating effect on a variety of systemic inflammation reactions, including acute lung injury. However, the protective effect of EP on RILI has not been explored. Materials/Methods RILI was induced by a single thoracic irradiation of 16 Gy X-rays in C57BL/6 mice. Mice were divided into four groups: control, radiation, 100 mg/kg EP, and 200 mg/kg dexamethasone. Inflammation and fibrosis grade of lung tissue were scored by H&E and Masson's trichrome staining. Cytokines include IL-1β, IL-6, TNF-α, GM-CSF, M-CSF, TGF-β1, and HMGB1 were measured after irradiation. Colony formation assay was performed to determine the protective effect of EP in RAW264.7 and HBE cells. The effect of EP on HMGB1 was also explored in vitro. Result The cytoplasm of bronchial epithelium cells in mice was positive-stained of HMGB1 accompanying with an increase of HMGB1, IL-6, IL-1β, GM-CSF, M-CSF, TNF-α, and TGF-β1 after irradiation. EP prescription significantly reduced pulmonary inflammation infiltration of RILI, along with a decrease of HMGB1, IL-6, IL-1β, and GM-CSF at 4 weeks after irradiation. Furthermore, EP decreased radiation-induced collagen deposition at 20 weeks after irradiation. Pro-fibrotic cytokines including TGF-β1 and HMGB1 in irradiated lung tissue and plasma obviously decreased in EP administration group in the later stage. In vitro, EP administration protected HBE cells from radiation injury. EP also rescued radiation-induced release but not translocation of HMGB1 in RAW264.7 and HBE cells. Conclusion EP treatment ameliorates RILI, including radiation-induced fibrosis in mice. The inhibition of production and release of pro-inflammatory or fibrotic cytokines, especially HMGB1, may partly attribute to its attenuating RILI effect. [ABSTRACT FROM AUTHOR]