MiR-92a antagonized the facilitation effect of extracellular matrix protein 1 in GC metastasis through targeting its 3'UTR region.

MicroRNAs were known to play very important roles in human diseases, and have attracted great interests of research scientists in medicine, toxicology and functional foods. Gastric carcinoma (GC) remains one of the most common and lethal types of malignancy worldwide. However, the molecular mechanism of GC and the role of microRNAs in GC development remain unclear. The expression of extracellular matrix protein 1 (ECM1) is up-regulated in many cancer types, but its functional role is inconstant. In the present study, we aimed to investigate the correlation between GC development and ECM1 expression, along with its regulation by microRNAs. Immunohistochemical results showed that ECM1 was up-regulated in GC tissues and ECM1 expression level was negatively correlated with the prognosis of GC. ECM1 was found to promote gastric cancer cell metastasis in cell migration assays by facilitating the expression of proteins involved in epithelial-mesenchymal transition (EMT). MiR-92a was recognized for the first time to suppress the migration of human GC cells by directly targeting to the 3'UTR of ECM1 gene in a dual-luciferase reporter assay. These results highlighted the antagonistic roles of ECM1 and miR-92a in GC development, which may serve as a new target for gastric cancer.

Glycemic reduction alters white blood cell counts and inflammatory gene expression in diabetes.

OBJECTIVE: Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. RESEARCH DESIGN AND METHODS: This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. RESULTS: After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ±â€¯1.8 to 6.8 ±â€¯0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; krüppel-like factor 5; and IL-1. Also, circulating levels of IL-1ß and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. CONCLUSION: Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Analysis of serum undercarboxylated osteocalcin level in rats with type 2 diabetes mellitus and the correlation with cognitive impairment.

The aim of the study was to investigate the correlation between the serum undercarboxylated osteocalcin (ucOC) level and the blood biochemistry and cognitive impairment in rats with type 2 diabetes mellitus (T2DM). Sprague-Dawley (SD) rats were randomly divided into the normal control group (NC) and type 2 DM group. DM group received the high-fat and high-sugar diet combined with the intraperitoneal injection of low-dose STZ to establish the type 2 DM rat model. After 12 weeks of feeding, a Morris water maze was used to observe the rats' cognitive ability, and the levels of blood lipid, ucOC, insulin and adiponectin in the two groups were measured. The results showed that blood glucose of rats in DM group was increased significantly at 2-12 weeks (p<0.01) and the body weight was significantly increased at 4-12 weeks (p<0.01). The levels of serum triglyceride (TG), total cholesterol, low-density lipoprotein and insulin in rats in DM group were significantly increased compared with those in NC group (p<0.01) and the levels of high-density lipoprotein, adiponectin and ucOC were significantly decreased compared with those in the NC group (p<0.01). The place navigation and spatial exploration capacities of rats in DM group were significantly decreased compared with those in NC group (p<0.01). In the DM group, the place navigation and spatial exploration capacities of rats in the low ucOC group were significantly decreased compared with those in the high ucOC group (p<0.01). Additionally, single-factor correlation analysis revealed that ucOC was negatively correlated with blood glucose, TG and escape latency (p<0.01), but was positively correlated with adiponectin, residence time in target quadrant and traversing times (p<0.05 or p<0.01). In conclusion, the decreased serum ucOC level in rats with type 2 diabetes mellitus has a certain correlation with cognitive impairment.

A Risk Factor Analysis of Cognitive Impairment in Elderly Patients with Chronic Diseases in a Chinese Population.

BACKGROUND This study analyzed the risk factors of cognitive impairment (CI) in elderly patients with chronic diseases. MATERIAL AND METHODS In total of 385 elderly patients with chronic diseases were selected and assigned into CI and normal groups. The activities of daily living (ADL), global deterioration scale (GDS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), patient-generated subjective global assessment (PG-SGA), and mini nutritional assessment (MNA) were performed to analyze the differences between the 2 groups. Logistic regression analysis was conducted for risk factors of CI in elderly patients with chronic diseases. RESULTS There were differences in age, education level, type 2 diabetes mellitus, multifocal cerebral infarction, hearing, and eyesight between CI and normal groups. Patients in the CI group showed more CD4+ cells, more admission times, and higher GDS scores than the normal group. Also, MMSE and MoCA scores revealed differences in total score, directive force, attention and calculating ability, language, delayed memory, reading comprehension, writing, and visual-spatial ability between the 2 groups. The number of B and CD8+ cells, ADL, and MNA scores were protective factors, while cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age were risk factors of CI in elderly patients with chronic diseases. CONCLUSIONS Our study provides evidence that cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age are risk factors of CI in elderly patients with chronic diseases.

Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy.

OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. METHODS: Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. RESULTS: We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. CONCLUSION: A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

Cardiomyocyte-specific loss of diacylglycerol acyltransferase 1 (DGAT1) reproduces the abnormalities in lipids found in severe heart failure.

Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor α and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase Cα (PKCα), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.

Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Human epidermal growth factor receptor (EGFR) and HER2 (ErbB2) both belong to EGFR family, which are overexpressed in a significant proportion of cases of gastric cancer (GC). Various studies have evaluated the prognostic value of EGFR or HER level in GC. However, the overall test performance remains unclear. We undertook this study to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of EGFR or HER2 as a predictor of survival time in patients with GC. METHODS: Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle-Ottawa Tool. Data were collected comparing overall survival (OS) in patients with high and low EGFR or HER2 level. Studies were pooled and summary hazard ratios were calculated. RESULTS: Studies were listed twice if they provided overall survival data for both EGFR and HER2. Eight studies (seven for EGFR and eight for HER2) were included. Two distinct groups were pooled for analysis and revealed that high EGFR, HER2 levels predicted poor overall (HR = 1.66, 95% CI: 1.35-2.02) and (HR = 1.43, 95% CI: 1.09-1.88) survival. No publication bias was found. CONCLUSIONS: This meta-analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients.

Effects of phlorizin on diabetic retinopathy according to isobaric tags for relative and absolute quantification-based proteomics in db/db mice.

PURPOSE: Diabetic retinopathy (DR) is a leading cause of vision loss in working-age people. To retard the development and progression of retina lesions, effective therapeutic strategies directed toward key molecular targets are desired. Phlorizin is effective in treating diabetic complications, but little is known about functional protein changes that may mediate its actions. The aim of this study was to identify retinal proteomic alterations in db/db mice treated with phlorizin. METHODS: We used C57BLKS/J db/db mice as a type 2 diabetic animal model, while C57BLKS/J db/m mice were selected as the control. Phlorizin (20 mg/kg bodyweight /d) was administrated to db/db mice for ten weeks. Serum fasting blood glucose and advanced glycation end products were determined. Meanwhile, retina cell apoptosis was determined with terminal transferase dUTP nick end labeling. Isobaric tags for relative and absolute quantification and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify and profile retinal proteins among control, untreated diabetic, and phlorizin-treated db/db mice. The expression of glial fibrillary acidic protein was measured in retinas using western blotting analysis. RESULTS: Phlorizin treatment significantly reduced fasting blood glucose and levels of advanced glycation end products (p<0.05) and remarkably inhibited retina cell apoptosis and the expression of glial fibrillary acidic protein in the retinas of db/db mice. In addition, we identified 1,636 proteins from retina tissue in total, of which 348 proteins were differentially expressed in db/db mice compared with the controls. Only 60 proteins in the retinas of the db/db mice were found to be differentially changed following phlorizin treatment, including 33 proteins that were downregulated and 27 proteins that were upregulated. Most of these differentially changed proteins were involved in oxidative stress, apoptosis, energy metabolism, and signaling transduction. CONCLUSIONS: Our study revealed the expression of proteins differentially changed after phlorizin therapy. These proteins are most likely to participate in the development and recovery of DR. Our findings help expand understanding of the mechanism underlying the onset and progression of DR, and provide novel targets for evaluating the effects of phlorizin therapy.

Pathobiologic implications of methylation and expression status of Runx3 and CHFR genes in gastric cancer.

Runx3 and CHFR genes were defined as tumor suppressor genes in gastric cancer (GC) recently. This paper was to investigate the roles of methylation and expression status of Runx3 and CHFR genes in GC patients. Methylation-specific polymerase chain reaction (MSP) and bisulfite DNA sequencing (BSP) were used to detect methylation status of Runx3 and CHFR genes in GC patients. The expression of Runx3 and CHFR in GC patients was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical analysis. The expression of the protein and mRNA decreased remarkably in the patients with aberrant promoter methylation of Runx3 and CHFR genes. The methylation status of Runx3 and CHFR were inversely related to the tumor size, tumor invasion depth and tumor differentiation in GC patients. Moreover, the protein expression of Runx3 and CHFR were significantly correlated with tumor invasion depth and tumor differentiation, respectively. Aberrant promoter methylation of Runx3 and CHFR genes may be involved in the carcinogenesis and development of GC and may provide useful clues for the prediction of the malignant behaviors of GC.

[Effects of low-dose aspirin on primary prevention of cardiovascular events: a systematic review].

OBJECTIVE: To evaluate the effect and safety of low-dose aspirin for primary prevention of cardiovascular events. METHODS: We searched for randomized controlled trials (RCT) in the following electronic databases: MEDLINE, EMbase, the Cochrane Library (Issue 3, 2008), CBM, CNKI. Quality assessment and data extraction were conducted by two reviewers independently. All data were analyzed using Review Manager 4.2. RESULTS: Six studies (TPT, HOT, PPP, WHS, POPADAD, J-PAD) involving a total of 72,466 participants met the inclusion criteria. Meta-analysis results showed that: (1) Compared with placebo, the incidences of total cardiovascular events (RR = 0.85, 95% CI: 0.80-0.92), stroke (RR = 0.87, 95% CI: 0.77-0.98), nonfatal stroke (RR = 0.81, 95% CI: 0.70-0.95) and transient ischemic attack (RR = 0.76, 95% CI: 0.64-0.90) were significantly lower in low-dose aspirin group than those in placebo control group (all P < 0.05). (2) Nonfatal myocardial infarction (RR = 0.89, 95% CI: 0.77-1.02), death from cardiovascular causes (RR = 0.98, 95% CI: 0.86-1.13) and death from any cause (RR = 0.95, 95% CI: 0.88-1.02) were similar between the 2 groups (all P > 0.05). (3) The risk of coronary heart disease was reduced in low-dose aspirin group in the elderly (RR = 0.81, 95% CI: 0.70-0.94, P < 0.05). (4) The risk of bleeding was higher in low aspirin group compared to placebo group (RR = 1.15, 95% CI: 1.12-1.18, P < 0.01). CONCLUSIONS: Low-dose aspirin use could reduce the incidences of total cardiovascular events, stroke, nonfatal stroke and transient ischemic attack but increase the risk of bleeding, the incidence of nonfatal myocardial infarction, death from cardiovascular causes and death from any cause was not affected by low-dose aspirin use. Low-dose aspirin use was also significantly reduced the risk of coronary heart disease in the elderly.

[Effects of aging and decreased glomerular filtration rate on the prevalence of anemia in elderly population receiving body check from urban area of Hefei, China.].

OBJECTIVE: To investigate the effects of aging and the decreased glomerular filtration rate on the prevalence of anemia in elder receiving body check from urban area of Hefei, China. METHODS: A total of 4547 > 60 years subjects received healthy examination in Healthy Center of Anhui Provincial Hospital from January 2005 to December 2007 were enrolled in this study. Anemia was defined as hemoglobin < 120 g/L in men or < 110 g/L in women. RESULTS: The prevalence of anemia in the subjects was 4.40% (95%CI: 3.83% - 5.05%) and significantly increased with the aging process and the decline of estimated glomerular filtration rate (eGFR). With logistic analyses, increasing age, female, decreased eGFR were major risk factors for anemia. CONCLUSIONS: The morbidity of anemia is 4.40% in old population receiving body check from urban area of Hefei, China. Aging and the decline of eGFR are the independent risk factors of anemia.

Promoter methylation of CHFR gene in gastric carcinoma tissues detected using two methods.

BACKGROUND AND OBJECTIVE: Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation-specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer. METHODS: Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0. RESULTS: The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P < 0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age, gender, tumor size, clinical stage, Borrman type, tumor invasion depth, differentiation, and lymph node metastasis (P > 0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P > 0.05). CONCLUSIONS: Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene in gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.

Promoter methylation of p16, Runx3, DAPK and CHFR genes is frequent in gastric carcinoma.

AIMS AND BACKGROUND: Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including gastric cancer. A number of reports on methylation of various genes in gastric cancer have been published, but most of these studies focused on cancer tissues or only a single gene. In this study, we determined the promoter hypermethylation status and mRNA expression of 4 genes: p16, Runx3, DAPK and CHFR. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of p16, Runx3, DAPK and CHFR gene promoters in cancer and adjacent normal gastric mucosa specimens from 70 patients with gastric cancer, as well as normal gastric biopsy samples from 30 people without cancer serving as controls. In addition, the mRNA expression of p16, Runx3, DAPK and CHFR was investigated in 34 gastric cancer patients by RT-PCR. Bisulfite DNA sequence analysis was applied to check the positive samples detected by MSP. RESULTS: When carcinoma specimens were compared with adjacent normal gastric mucosa samples, a significant increase in promoter methylation of p16, Runx3, DAPK and CHFR was observed, while all 30 histologically normal gastric specimens were methylation free for all 4 genes. The methylation rate of the 4 genes increased from normal stomach tissue to tumor-adjacent gastric mucosa to gastric cancer tissue. Concurrent methylation in 2 or more genes was found in 22.9% of tumor-adjacent normal gastric mucosa and 75.7% of cancer tissues. No correlation was found between hypermethylation and other clinicopathological parameters such as sex, age, and tumor location. However, the frequency of DAPK and CHFR methylation in cancer tissues was significantly associated with the extent of differentiation and lymph node metastasis (P < 0.05) and the frequency of Runx3 methylation was significantly associated with tumor size (P < 0.05). Weak expression and loss of expression of the 4 genes was observed in cancer tissues and was significantly associated with promoter hypermethylation (P < 0.05). CONCLUSIONS: Promoter hypermethylation of p16, Runx3, DAPK and CHFR is frequent in gastric cancer. DAPK and CHFR promoter hypermethylation may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. Weak gene expression and loss of gene expression due to promoter hypermethylation may be a cancer-specific event.

[Chiral selectivity in differentiation of lung cancer A549 cell to vascular endothelial cells after drug resistance induced by D-or L-methotrexate enantiomers].

OBJECTIVE: To study the chiral selectivity in vascular endothelial differentiation in drug resistant lung cancer cells induced by high-dose L- or D-methotrexate (MTX) enantiomer. METHODS: Human lung cancer cells of the line A549 were co-cultured with high-dose (15 micromol/L) L- or D-MTX enantiomer so as to develop cancer cells resistant to MTX. MTT method was used to detect the drug resistant index. Flow cytometry was used to detect the expression of CD44, a transmembrane glycoprotein reflecting the migration ability of cells, CD31, a marker of vascular endothelium, and P-170 protein. Fifteen BALB/c nude mice were inoculated with the parent A549 cells, L-MTX-resistant A549 cells induced by L-MTX enantiomer, and D-MTX-resistant A549 cells induced by D-MTX enantiomer. Four weeks later the mice were killed to take out the tumor masses. Immunohistochemistry with CD34 staining was used to detect the microvascular density (MVD). RESULTS: The drug resistant index of the D-MTX induced drug resistant A549 cells was 20.1 +/- 2.3, significantly higher than that of the L-MTX-induced cells (12.4 +/- 1.2, P = 0.000). The CD44 positive rate of the D-MTX induced A549 cells was 97.0% +/- 0.9%, not significantly different from that of the L-MTX-induced A549 cells (96.7% +/- 1.4%, P = 0.544). The CD31 positive rate of the D-MTX induced A549 cells was 91.9% +/- 3.2%, significantly higher than that of the L-MTX-induced A549 cells (32.9% +/- 8.0%, P = 0.000). The P-170 protein positive rate of the parent cells was 85.5% +/- 4.6%, and the P-170 protein positive rate of the D-MTX-induced A549 cells was 87.0% +/- 8.9%, significantly higher than that of the L-MTX-induced cells (71.5% +/- 8.2%, P = 0.002). The MVD of the D-MTX-induced cells was 55.9 +/- 11.9, significantly higher than that of the L-MTX-induced cells (7.2 +/- 1.7, P = 0.000). MVD was significantly positively correlated with the CD31 level (r = 0.462, P = 0.007), and not correlated with P-170 protein and CD34 levels. CONCLUSION: The MTX enantiomers have different chiral selectivity on human lung cancer cell, D-MTX resistant cells shows a potential of differentiation from cancer cells to vascular endothelial cells. D-MTX is not be regarded just as a pollutant in the drug MTX, MTX with single enantiomer (L-MTX) should be selected clinically so as to decrease the side effects of D-MTX.

High-performance capillary electrophoretic method for the quantification of global DNA methylation: application to methotrexate-resistant cells.

Global DNA hypomethylation in tumor tissue is a common characteristic in a variety of malignancies such as breast, colon, oral, lung, and blood cancers. A rapid and sensitive method has been developed for the determination of global DNA methylation in cells. Five substances--2'-deoxycytidine (dC), 5-methyl 2'-deoxycytidine (mdC), 2'-deoxyadenosine (dA), 2'-deoxythymidine (dT), and 2'-deoxyguanosine (dG)--were completely separated by high-performance capillary electrophoresis in 10 min. Intraday coefficient of variation was less than 1%, and interday coefficient of variation was less than 2%. The minimal detection limit was 1 microM. Acquired drug resistance to methotrexate (MTX) is one of the most serious problems in cancer chemotherapy. Under optimal conditions, we analyzed global DNA methylation levels in A549 and A549/MTX cells, and only 10(5) cells are needed to obtain reliable results. The percentage of 5-methyl-2'-deoxycytidine (5-mC) was 4.80+/-0.52% in A549 cells, and this decreased to 4.20+/-0.44% in A549/MTX cells. It was considered as statistically significant. This demonstrated that the mechanisms of acquired drug resistance to MTX might be concerned with DNA methylation.

[The effect of amino acid nutritional support on serum tryptophan and melatonin in lung cancer patients receiving chemotherapy].

OBJECTIVE: To investigate the effect of amino acid parenteral nutritional (PN) support on serum tryptophan and melatonin in non-small cell lung cancer (NSCLC) patients receiving chemotherapy. METHODS: Seventy-two patients with inoperable NSCLC were divided into three groups randomly: control group, 250 ml/d amino acids PN therapy group and 500 ml/d amino acids PN therapy group. The same NP (cisplatin + vinorelbine) chemotherapy was carried out in all the three groups. During three sessions of chemotherapy,amino acids PN therapy was given to the amino acids PN therapy groups. Serum tryptophan and melatonin concentration changes were assessed before and after chemotherapy. RESULTS: After chemotherapy the concentration of MT and Try were much lower than that before chemotherapy in the three group patients (P < 0.05). But the concentration of MT and Try in the PN group patients was higher than that in control group patients. The concentration of MT and Try in the 500 ml/d amino acid parenteral nutritional support group patients were significantly higher than that in the 250 ml/d group patients, the difference was significant (P < 0.05). CONCLUSION: Amino acid parenteral nutritional support is beneficial to improve the lower concentration of serum MT and Try in NSCLC patients receiving chemotherapy, and a more significant effect can be achieved by the 500 ml/d amino acid parenteral nutritional support treatment.