Translational research : the journal of laboratory and clinical medicine
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The Cancer Genome Atlas (TCGA) has profiled more than 10,000 samples derived from 33 types of cancer to date, with the goal of improving our understanding of the molecular basis of cancer and advancing our ability to diagnose, treat, and prevent cancer. This review focuses on lung cancer as it is the leading cause of cancer-related mortality worldwide in both men and women. ⋯ Our goal was to demonstrate the impact of TCGA on lung cancer research under 4 themes: diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools. Examples are given related to DNA mutation, copy number variation, messenger RNA, and microRNA expression along with methylation profiling.
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Preclinical studies have suggested that cytotoxic agents and radiation may partly deliver their antitumor activities by activating antitumor immune response. However, the alterations of tumor immune microenvironment including immunosuppressive molecules during chemoradiotherapy and their associations with clinical features and prognosis in rectal cancer have not been thoroughly investigated. Therefore, we investigate the densities of cluster of differentiation 8 (CD8) positive tumor-infiltrating lymphocytes (TILs), CD4+TILs, natural killer cell (NK)-TILs, myeloid-derived suppressor cells (MDSCs), transcription factor forkhead box P3 (FOXP3)+TILs, programmed death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) before and after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients to determine their predictive and prognostic effects. ⋯ Cell surface PD-L1 positive by tumor cells (1 of 62) and stroma cells (3 of 62) are very low. We may conclude that tumor immunity is activated after nCRT by increased infiltrating CD8+ and CD4+ T cells and relative stable numbers MDSC-TILs, FOXP3+TILs, and coinhibitory molecules. Pre-nCRT CD8+TILs, CD4+TILs, and MDSC-TILs are sensitive predictive marker for response to CRT, and high CD8+TILs are associated with better prognosis.
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Droplet digital polymerase chain reaction (ddPCR), which could perform thousands of PCRs on a nanoliter scale simultaneously, would be an attractive method to massive parallel sequencing for identifying and studying the significance of low-frequency rare mutations. Recent evidence has shown that the key potential mechanisms of the failure of aromatase inhibitors-based therapy involve identifying activating mutations affecting the ligand-binding domain of the ESR1 gene. Therefore, the detection of ESR1 mutations may be useful as a biomarker predicting an effect of the treatment. ⋯ Biopsy was performed in heterochrony in 8 women twice. In 8 women, 4 women had primary breast cancer and MBC specimens and 4 women had 2 specimens when treatment was failure. Four of these 8 women acquired ESR1 mutation, whereas no ESR1 mutation could be identified at first biopsy. ddPCR technique could be a promising tool for the next-generation sequencing-free precise detection of ESR1 mutations in endocrine therapy resistant cases and may assist in determining the treatment strategy.
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The phenomenon known as renal "ischemic preconditioning," whereby an initial ischemic insult induces resistance against subsequent kidney damage, has been well established in the experimental literature. However, a clinically applicable way to safely recapitulate this state has not been defined. We hypothesized that a unique combination of agents (nitrited myoglobin [N-Mgb] + tin protoporphyrin [SnPP]) can achieve these ends safely and synergistically, increasing cytoprotective proteins (eg, heme oxygenase 1 [HO-1], interleukin 10 [IL-10], and haptoglobin) in kidney cells. ⋯ Combined N-Mgb + SnPP was more protective than either agent alone (assessed in glycerol model). N-Mgb + SnPP also upregulated cytoprotective pathways in liver and induced marked protection against both hepatic ischemia-reperfusion and toxic liver damage. In conclusion, we posit that "preconditioning" with combined administration of N-Mgb + SnPP represents a promising approach for protecting against diverse forms of renal and nonrenal (hepatic) forms of tissue damage.
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The diagnostic value of tumor markers, carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 19-9, CA 125, cytokeratin fragment (CYFRA), and neuron-specific enolase (NSE) in pleural fluid to differentiate between benign and malignant pleural effusion (MPE) has not yet been clearly established. A review of English language studies using human subjects was performed. Sensitivity and specificity values of the chosen tumor markers were pooled using a random effects model to generate hierarchical summary receiver operator curves to determine the diagnostic performance of each tumor marker. ⋯ Although these tumor markers exhibit high specificity, the low sensitivity of each marker limits the diagnostic value. We conclude that tumor markers used individually are of insufficient diagnostic accuracy for clinical use. Tumor markers used in various combinations or from serum may have some potential worth further investigation.