Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study.

BACKGROUND: The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored. METHODS: We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan-Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis. RESULTS: The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients. CONCLUSIONS: The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.

Gene heterogeneity in metastasis of colorectal cancer to the lung.

Colorectal cancer (CRC) as a heterogeneous disease, is one of the most common and serious cancers with high metastases and mortality. Lung is one of the most common sites of CRC metastases with high heterogeneity between cells, pathways, or molecules. The present review will focus on potential roles of gene heterogeneity in KRAS pathway in the development of CRC metastasis to lung and clinical therapies, which would lead to better understanding of the metastatic control and benefit to the treatment of metastases. KRAS is the central relay for pathways originating at the epidermal growth factor receptor (EGFR) family. KRAS mutation exists in about 40% CRC, associated with higher cumulative incidence of CRC lung metastasis, and acts as an independent predictor of metastasis to lung. Mutations in KRAS can lead to poor response of patients to panitumumab, and inferior progression-free survival. However, most patients with KRAS wild-type tumors still do not respond, which indicates other mutations. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation was associated with lung metastases in metastatic colorectal cancer. PIK3CA mutation in exon 20 was found to be correlated with patient survival in the metastatic setting after the treatment with cetuximab and chemotherapy. The heterogeneity of KRAS pathway was found in the phosphatase and tensin homologue deleted on chromosome ten loss, disheveled binding antagonist of beta catenin 2 overexpression and increased dual-specificity protein phosphatase 4 expression of CRC lung metastasis.

Discriminating gastric cancer and gastric ulcer using human plasma amino acid metabolic profile.

Patients with gastric ulcer (GU) have a significantly higher risk of developing gastric cancer (GC), especially within 2 years after diagnosis. The main way to improve the prognosis of GC is to predict the tumorigenesis and metastasis in the early stage. The objective of this study was to demonstrate the ability of human plasma amino acid metabolic profile for discriminating GC and GU. In this study, we first used liquid chromatography-tandem mass spectrometry technique to characterize the plasma amino acid metabolism in GC and GU patients. Plasma samples were collected from 84 GC patients and 82 GU patients, and 22 amino acids were detected in each patient. Partial least squares-discriminant analysis model was performed to analyze the data of these amino acids. We observed seven differential amino acids between GC and GU. A regression analysis model was established using these seven amino acids. Finally, a panel of five differential amino acids, including glutamine, ornithine, histidine, arginine and tryptophan, was identified for discriminating GC and GU with good specificity and sensitivity. The receiver operating characteristic curve was used to evaluate diagnostic ability of the regression model and area under the curve was 0.922. In conclusion, this study demonstrated the potential values of plasma amino acid metabolic profile and metabolomic analysis technique in assisting diagnosis of GC. More studies are needed to highlight the theoretical strengths of metabolomics to understand the potential metabolic mechanisms in GC. © 2018 IUBMB Life, 70(6):553-562, 2018.

The inhibition of UDP-glucuronosyltransferases (UGTs) by tetraiodothyronine (T4) and triiodothyronine (T3).

1. UDP-glucuronosyltransferases (UGTs) are important drug-metabolizing enzymes (DMEs) catalyzing the glucuronidation elimination of various xenobiotics and endogenous substances. Endogenous substances are important regulators for the activity of various UGT isoforms. Triiodothyronine (T3) and thyroxine (T4) are important thyroid hormones essential for normal cellular differentiation and growth. The present study aims to elucidate the inhibition behavior of T3 and T4 on the activity of UGT isoforms. 2. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to screen the inhibition potential of T3 and T4 on the activity of various UGT isoforms. Initial screening results showed that T4 exerted stronger inhibition potential than T3 on the activity of various UGT isoforms at 100 µM. Inhibition kinetics was determined for the inhibition of T4 on the representative UGT isoforms, including UGT1A1, -1A3, -1A7, -1A8, -1A10 and -2B7. The results showed that T4 competitively inhibited the activity of UGT1A1, -1A3, -1A7, 1A10 and -2B7, and noncompetitively inhibited the activity of UGT1A8. The inhibition kinetic parameters were calculated to be 1.5, 2.4, 11, 9.6, 4.8 and 3.0 µM for UGT1A1, -1A3, -1A7, -1A8, -1A10 and -2B7, respectively. In silico docking method was employed to demonstrate why T4 exerted stronger inhibition than T3 towards UGT1A1. Stronger hydrogen bonds and hydrophobic interaction between T4 and activity cavity of UGT1A1 than T3 contributed to stronger inhibition of T4 towards UGT1A1. 3. In conclusion, more clinical monitoring should be given for the patients with the elevation of T4 level due to stronger inhibition of UGT isoforms-catalyzed metabolism of drugs or endogenous substances by T4.

Everolimus-inhibited multiple isoforms of UDP-glucuronosyltransferases (UGTs).

1. Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and has been clinically utilized to prevent the rejection of organ transplants. This study aims to determine the inhibition of everolimus on the activity of phase-II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). 2. The results showed that 100 µM of everolimus exerted more than 80% inhibition toward UGT1A1, UGT-1A3 and UGT-2B7. UGT1A3 and UGT2B7 were selected to elucidate the inhibition mechanism, and in silico docking showed that hydrogen bonds and hydrophobic interactions mainly contributed to the strong binding of everolimus toward the activity cavity of UGT1A3 and UGT2B7. Inhibition kinetic-type analysis using Lineweaver-Burk plot showed competitive inhibition toward all these UGT isoforms. The inhibition kinetic parameters (Ki) were calculated to be 2.3, 0.07 and 4.4 µM for the inhibition of everolimus toward UGT1A1, UGT-1A3 and UGT-2B7, respectively. 3. In vitro-in vivo extrapolation (IVIVE) showed that [I]/Ki value was calculated to be 0.004, 0.14 and 0.002 for UGT1A1, UGT-1A3 and UGT-2B7, respectively. Therefore, high DDI potential existed between everolimus and clinical drugs mainly undergoing UGT1A3-catalyzed glucuronidation.

The Significance of Single-Cell Biomedicine in Stem Cells.

Clinical application of stem cells (SCs) progresses significantly in the treatment of a large number of diseases, e.g. leukemia, respiratory diseases, kidney disease, cerebral palsy, autism, or autoimmune diseases. Of those, the population, biological phenotypes, and functions of individual SCs are mainly concerned, due to the lack of cell separation and purification processes. The single-cell technology, including microfluidic technology and single-cell genome amplification technology, is widely used to study SCs and gains some recognitions. The present review will address the importance of single-cell technologies in the recognition and heterogeneity of SCs and highlight the significance of current single-cell approaches in the understanding of SC phenotypes. We also discuss the values of single-cell studies to overcome the bottleneck in explore of biological mechanisms and reveal the therapeutic potentials of SCs in diseases, especially tumor-related diseases, as new diagnostic and therapeutic strategies.

Downregulation of MicroRNA-330 Correlates with the Radiation Sensitivity and Prognosis of Patients with Brain Metastasis from Lung Cancer.

BACKGROUND: The present study sought to explore the role of microRNA-330 (miR-330) in predicting the radiation response and prognosis of patients with brain metastasis (BM) from lung cancer (LC). METHODS: Patients with BM from LC were identified and classified into radiation-sensitive and radiation-resistant groups according to the overall survival rate, local and distant recurrence rate after conventional whole-brain radiation therapy. Quantitative realtime polymerase chain reaction (qRT-PCR) was used to detect miR-330 expression in serum. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic value of miR-330 for the radiation sensitivity of brain metastasis from LC. Related clinical factors for radiation sensitivity were assessed by logistic regression analysis, and a survival analysis was conducted using COX regression and the Kaplan-Meier method. RESULTS: MiR-330 exhibited lower expression in the radiation-sensitive group than in the radiation-resistant group. The area under the ROC curve of miR-330 for predicting radiation sensitivity was 0.898 (optimal cut-off value, 0.815), with a sensitivity of 71.7% and a specificity of 90.1%. After radiation therapy, patients with low miR-330 expression, compared to patients with high miR-330 expression, displayed a lower survival rate and a median survival time. MiR-330 expression was correlated with extracranial metastasis, maximum BM diameter, tumor-node-metastasis (TNM) stage and node (N) stage. Logistic regression and COX regression analyses revealed that extracranial metastasis, TNM stage, N stage and miR-330 expression were factors that influenced both radiation sensitivity and individual prognostic factors in patients with BM from LC. CONCLUSIONS: These findings indicate that the downregulation of miR-330 correlates with radiation sensitivity and poor prognosis in patients with BM from LC.

Rapid differentiating colorectal cancer and colorectal polyp using dried blood spot mass spectrometry metabolomic approach.

Colorectal cancer (CRC) is the third leading causes of cancer mortality, and the early-stage detection could significantly enhance survival rates. Cancer influences the important metabolic pathways and the changes in metabolite levels had been used in many studies as the potential biomarkers. This study is aimed at screening metabolite biomarkers with CRC diagnosis potentials. The direct infusion mass spectrometry (MS) metabolomic analysis based on dried blood spot was used to distinguish CRC from polyp. The target metabolites were composed of 23 amino acids and 26 acylcarnitines. The 21 metabolites in blood were selected via multivariate analysis. A regression model was established based on parameters C16, Arg, C4/C8, C5/C3, Val, Phe/Tyr, Ala, C4/C3. Tenfold cross validation (CV) method was used to test this model and showed sensitivity of 81.18% and specificity of 83.95%. The metabolomic analysis is a practicable method for CRC detection. The use of direct MS analysis in metabolite screening could be finished in several minutes and served as a higher-throughput method to distinguish CRC and polyps. © 2017 IUBMB Life, 69(5):347-354, 2017.

Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury.

Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1. ANIT also increased NF-κB/IL-6/STAT3 signaling, and in vitro luciferase reporter gene assays revealed that LPC 18:0 and LPC 18:1 can activate NF-κB in a concentration-dependent manner. Activation of PPARα through feeding mice a Wy-14,643-containing diet (0.1%) reduced ANIT-induced liver injury, as indicated by lowered ALT and AST levels, and liver histology. In conclusion, the present study demonstrated a role for the lipid-regulated NF-κB/IL-6/STAT3 axis in ANIT-induced hepatotoxicity, and that PPARα may be a potential therapeutic target for the prevention of drug-induced cholestatic liver injury.

Identification of arginine and its "Downstream" molecules as potential markers of breast cancer.

Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide. Arginine is a semiessential amino acid in humans and is essential for several biological pathways in malignant and normal cells, such as ornithine and N1, N12-diacetylspermine (DiAcSpm). This study aimed to determine the role of arginine and these downstream molecules in BC. Plasma arginine, ornithine, and arginine-to-ornithine ratio (AOR) were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine samples were measured by the colloid gold aggregation to test determination of urinary diAcSpm. A principal component analysis was performed to evaluate the results observed between breast tumor and control characteristics. Differences in individual metabolite concentrations between BC patients and controls were tested by receiver operating characteristics (ROC) analyses. Student's t tests were used to detect the differences between two groups of normally distributed variables, and Wilcoxon sign rank tests were performed for asymmetrically distributed variables. As we analyzed, BC patients had lower plasma arginine and arginine/ornithine level, and higher plasma ornithine and urinary DiAcSpm concentrations as compared with control patients (P = 0.028, 0.020, 0.002, and 0.011, respectively). And the ROC curve was drawn and the area under the curve of the metabolites was calculated to be 0.659 (P = 0.028), 0.645 (P = 0.045), 0.7233 (P = 0.002), 0.683 (P = 0.011), respectively. In addition, our analysis showed that arginine concentrations and AOR had a positive correlation with ER status, while ornithine had a negative correlation with T stage (P = 0.042, 0.023, respectively).In conclusion, arginine and these downstream molecules were biomarkers for BC. More studies are needed to highlight the theoretical strengths. © 2016 IUBMB Life, 68(10):817-822, 2016.

Association of plasma arginine with breast cancer molecular subtypes in women of Liaoning province.

Arginine is one of the human nonessential amino acids critical for the growth of human cancers. The aim of this study is to investigate the variation of arginine between breast cancer (BC) patients and benign mammary gland disease (control) patients to determine its value in predicting the risk of BC. We also explore the associations between arginine levels and breast cancer subtypes. Preoperative blood samples were obtained from 267 patients (102 BC and 165 controls) in 2015. Plasma arginine values were determined for all preoperative blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyse differences in arginine levels between BC patients and control patients and the correlations between arginine and clinicopathologic parameters in BC. The arginine levels of BC patients were significantly lower than those of control patients (5.96 [3.76-12.47] vs. 12.54 [7.14-24.94], P = 0.000). The area under the curve (AUC) for arginine was 0.721 (95% CI, 0.660-0.782, P < 0.0001). The concentration of arginine was significantly different among different molecular BC subtypes (P = 0.030). Our results suggested that plasma arginine was associated with breast cancer molecular subtypes. © 2016 IUBMB Life, 68(12):980-984, 2016.

miR-155-5p antagonizes the apoptotic effect of bufalin in triple-negative breast cancer cells.

Bufalin, a cardiotonic steroid isolated from toad venom, has been shown to kill various types of tumor cells. Our previous study showed that triple-negative breast cancer (TNBC) cells were less sensitive to bufalin than other types of breast cancer cells, but the reason for this lower sensitivity remains unclear. In this study, we showed that bufalin induced apoptosis in MDA-MB-231 and MCF-7/ADR TNBC cell lines, accompanied by increased miR-155-5p expression. Overexpression of miR-155-5p promoted proliferation and reduced bufalin-induced apoptosis of TNBC cells. In contrast, downregulation of miR-155-5p increased sensitivity to bufalin and upregulated the expression of FOXO3A. Bufalin also downregulated DNA methyltransferases 1 and 3a (DNMT1 and DNMT3a), and concurrent inhibition of DNMT1 and DNMT3a significantly increased miR-155-5p expression. These results indicate that miR-155-5p antagonizes bufalin sensitivity in TNBC cells, and that downregulation of DNMT1 and DNMT3a may be responsible for the bufalin-induced upregulation of miR-155-5p.

Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small-cell lung cancer.

OBJECTIVE: To investigate the correlation between miR-26b and non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: NSCLC tissues and normal lung tissues that were more than 7 cm adjacent from tumor were collected from 154 NSCLC patients. Additionally, 63 normal specimens from benign lung disease were selected as the control group. Real-time fluorescent quantitative PCR was used to detect miR-26b expression in tissues. RESULT: miR-26b expression in NSCLC tissues was significantly lower than in other two types of tissues. Receiver operating characteristic curve analysis showed that the area under the curve was 0.856 with sensitivity and specificity of 79.9 and 79.4%, respectively. miR-26b expression was a risk factor for poor prognosis of NSCLC. CONCLUSION: The expression of miR-26b is downregulated in NSCLC tissues, and it might be useful in the diagnosis and prognosis of NSCLC patients.

Knockdown of High Mobility Group-Box 3 (HMGB3) Expression Inhibits Proliferation, Reduces Migration, and Affects Chemosensitivity in Gastric Cancer Cells.

BACKGROUND High mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms. MATERIAL AND METHODS GC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay. Cell migration and invasion were determined by wound scratch and transwell assay. MGC803 and BGC823 cells were treated with various concentrations of oxaliplatin, cisplatin, and paclitaxel. After 24 hours of drug exposure, we performed MTT assays to investigate chemoresistance in both groups. Western blot assays were used to detect related proteins expression. RESULTS Silencing of HMGB3 inhibited cell proliferation and induced G0/G1 phase arrest of GC cells partly via modulating p53 and p21 pathways, and downregulating Bcl-2/Bax ratio. RNA interference of HMGB3 inhibited cell invasion and migration by downregulating MMP2 and MMP9. Silencing of HMGB3 enhanced sensitive to cisplatin and paclitaxel, and reduced sensitive to oxaliplatin. CONCLUSIONS These findings suggest the importance of HMGB3 in the regulation of growth, migration, and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis.

Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation.

The History of Telocyte Discovery and Understanding.

Telocytes (TCs) are identified as a peculiar cell type of interstitial cells in various organs. The typical features of TCs from the other cells are the extending cellular process as telopodes with alternation of podomeres and podoms. Before the year of 2010, TCs were considered as interstitial Cajal-like cells because of the similar morphology and immunohistochemical features with interstitial cells of Cajal which were found more than 100 years ago and considered to be pacemakers for gut motility. Subsequently, it demonstrated that TCs were not Cajal-like cells, and thus the new name "telocyte" was proposed in 2010. With the help of different techniques, e.g., transmission electron microscopy, immunohistochemistry, or omics science, TCs have been detected in various tissues and organs from different species. The pathological role of TCs in different diseases was also studied. According to observation in situ or in vitro, TCs played a vital role in mechanical support, signaling transduction, tissue renewal or repair, immune surveillance, and mechanical sensor via establishing homo- or heterogenous junctions with neighboring cells to form 3D network or release extracellular vesicles to form juxtacrine and paracrine. This review will introduce the origin, distribution, morphology, functions, omics science, methods, and interaction of TCs with other cells and provide a better understanding of the new cell type.

Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers.

It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein-protein or gene-gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed.

Aquaporins as diagnostic and therapeutic targets in cancer: how far we are?

Aquaporins (AQPs) are a family of water channel proteins distributed in various human tissues, responsible for the transport of small solutes such as glycerol, even gas and ions. The expression of AQPs has been found in more than 20 human cancer types and is significantly correlated with the severity of histological tumors and prognosis of patients with cancer. More recent evidence showed that AQPs could also play a role in tumor-associated edema, tumor cell proliferation and migration, and tumor angiogenesis in solid and hematological tumors. Inhibitors of AQPs in tumor cells and microvessels have been suggested as new therapeutic strategies. The present review overviews AQPs structures, expression variation among normal tissues and tumors, AQPs functions and roles in the development of cancer with special focuses on lung, colorectal, liver, brain and breast cancers, and potential AQPs-target inhibitors. We call the special attention to consider AQPs important as diagnostic and therapeutic biomarkers. It may be a novel anticancer therapy by the AQPs inhibition.

Effect of metformin on the proliferation and apoptosis of the renal cancer cell line 786-O and the underlying mechanisms.

PURPOSE: To investigate the effects of metformin (Met) on the proliferation and apoptosis of a renal carcinoma cell line and study the underlying mechanisms. METHODS: Renal cell carcinoma (RCC) line 786-O was cultured with media containing different concentrations of Met. The proliferation and apoptosis of 786-O cells were detected by the MTT method and flow cytometry, respectively. The invasion of 786-O cells was detected by scratch test, and the expression of pro-apoptotic proteins was determined by Western blot assay. RESULTS: The proliferation rates of 786-O cells with Met concentrations of 10, 15, and 20 mM were decreased by 62.8, 61.7, and 65.1%, respectively, with no significant difference among these concentrations (p>0.05). Twenty-four hrs after the scratch assay, the mean migration index in the control group and Met treatment group was 51.6% +/- 5.9 and 28.1% +/- 4.3, and that after 48 hrs was 92.2% +/- 6.4 and 68.0% +/- 4.9, respectively (p<0.05). At low serum concentration, the percentage of apoptotic cells in the Met treatment group (17.6%) was significantly higher (p<0.05) than that in the control group (5.2%). Met (10 mM) treatment significantly increased the expression of Caspase-3 and Bax proteins in 786-O cells (p<0.05). CONCLUSIONS: Metformin may be a potential drug of choice in the treatment of metastatic RCC.

Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer.

Lymphocytes play important roles in the balance between body defense and noxious agents involved in a number of diseases, e.g. autoimmune diseases, allergic inflammation and cancer. The proteomic analyses have been applied to identify and validate disease-associated and disease-specific biomarkers for therapeutic strategies of diseases. The proteomic profiles of lymphocytes may provide more information to understand their functions and roles in the development of diseases, although proteomic approaches in lymphocytes are still limited. The present review overviewed the proteomics-based studies on lymphocytes to headlight the proteomic profiles of lymphocytes in diseases, such as autoimmune diseases, allergic inflammation and cancer, with a special focus on lung diseases. We will explore the potential significance of diagnostic biomarkers and therapeutic targets from the current status in proteomic studies of lymphocytes and discuss the value of the currently available proteomic methodologies in the lymphocytes research.