AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients.
METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS).
RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and AFP levels correlated with both OS and DFS.
CONCLUSION: Preoperative fibrinogen levels can serve as an independent prognostic marker to evaluate patient response to colon cancer treatment.
Fibrinogen; Colon cancer; Clinicopathological parameters; Relationship; Prognosis
AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.
METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ2 tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.
RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m2 (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m2 (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).
CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.
Apurinic endonuclease 1; Base excision repair; Single nucleotide polymorphisms; Colorectal cancer; X-ray repair cross-complementing groups
We report the full genome sequence of an isolate of bovine enterovirus type B from China. The virus (BEV-BJ001) was isolated from Beijing, China, from fecal swabs of cattle suffering from severe diarrhea. This genome sequence will give useful insight for future molecular epidemiological studies in China.
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence, which imposes a substantial public health problem. The heritability of AD is estimated at 60–80% forecasting the potential use of genetic biomarkers for risk stratification in the future. Several large scale genome-wide association studies using high frequency variants identified 10 loci accountable for only a fraction of the estimated heritability. To find the missing heritability, systematic assessment of various mutational mechanisms needs to be performed. This copy number variation (CNV) genome-wide association study with age at onset (AAO) of AD identified 5 CNV regions that may contribute to the heritability of AAO of AD. Two CNV events are intragenic causing a deletion in CPNE4. In addition, to further study the mutational load at the 10 known susceptibility loci, CNVs overlapping with these loci were also catalogued. We identified rare small events overlapping CR1 and BIN1 in AD and normal controls with opposite CNV dosage. The CR1 events are consistent with previous reports. Larger scale studies with deeper genotyping specifically addressing CNV are needed to evaluate the significance of these findings.
Age at onset; Alzheimer’s disease; copy number variation
Evenly separated crystalline CuIn0.8Ga0.2Se2 (CIGS) nanoparticles are deposited on ITO-glass substrate by pulsed laser deposition. Such CIGS layers are introduced between conjugated polymer layers and ITO-glass substrates for enhancing light absorbance of polymer solar cells. The P3HT:PCBM absorbance between 300 and 650 nm is enhanced obviously due to the introduction of CIGS nanoparticles. The current density-voltage curves of a P3HT:PCBM/CIGS solar cell demonstrate that the short-circuit current density is improved from 0.77 to 1.20 mA/cm2. The photoluminescence spectra show that the excitons in the polymer are obviously quenched, suggesting that the charge transfer between the P3HT:PCBM and CIGS occurred. The results reveal that the CIGS nanoparticles may exhibit the localized surface plasmon resonance effect just as metallic nanostructures.
61.46. + w; 61.41.e; 81.15.Fg; 81.07.b
CuIn0.8Ga0.2Se2 nanoparticles; P3HT:PCBM; Pulsed laser deposition; Absorption; Polymer solar cells; Photoluminescence
Since the end of the 1990s, the incidence of hemorrhagic fever with renal syndrome (HFRS) has been increasing dramatically in Changchun, northeastern China. However, it is unknown which, and how, underlying risk factors have been involved in the reemergence of the disease.
Data on HFRS cases at the county scale were collected from 1998 to 2012. Data on livestock husbandry including the numbers of large animals (cattle, horses, donkeys and mules), sheep, and deer, and on climatic and land cover variables were also collected. Epidemiological features, including the spatial, temporal and human patterns of disease were characterized. The potential factors related to spatial heterogeneity and temporal trends were analyzed using standard and time-series Poisson regression analysis, respectively.
Annual incidence varied among the 10 counties. Shuangyang County in southeastern Changchun had the highest number of cases (1,525 cases; 35.9% of all cases), but its population only accounted for 5.6% of the total population. Based on seasonal pattern in HFRS incidence, two epidemic phases were identified. One was a single epidemic peak at the end of each year from 1988 to 1997 and the other consisted of dual epidemic peaks at both the end and the beginning of each year from 1998 to the end of the study period. HFRS incidence was higher in males compared to females, and most of the HFRS cases occurred in peasant populations. The results of the Poisson regression analysis indicated that the spatial distribution and the increasing incidence of HFRS were significantly associated with livestock husbandry and climate factors, particularly with deer cultivation.
Our results indicate that the re-emergence of HFRS in Changchun has been accompanied by changing seasonal patterns over the past 25 years. Integrated measures focusing on areas related to local livestock husbandry could be helpful for the prevention and control of HFRS.
To explore whether the presence of a Y chromosome AZFc microdeletion confers any adverse effect on the outcomes of intracytoplasmic sperm injection (ICSI) with fresh ejaculated sperm.
A total of 143 oligozoospermia patients with Y chromosome AZFc microdeletion in ICSI cycles in a five-year period were studied. Infertile men with normal Y chromosome in ICSI at the same time-frame were used as controls matched to the study group for age of female, female’s body mass index, male’s age, infertility duration and number of oocytes retrieved. Retrospective case–control study was used.
There were no significant differences between groups in clinical outcomes of endometrial thickness, transferred embryos, good embryo rates, implantation rates, biochemical pregnancy rates, clinical pregnancy rates, ectopic pregnancy rates, miscarriage rates, preterm birth rates, the ratio of male and female babies, newborn body height, newborn weight, low birth weight and birth defects (P > 0.05). Patients with Y chromosome AZFc microdeletion had a lower fertilization rate (61.8 % vs. 67.8 %, P < 0.05) and higher cleaved embryo rate (94.0 % vs. 88.1 %, P < 0.05).
ICSI clinical outcomes for oligozoospermic patients with Y chromosome AZFc microdeletion are basically comparable to that of infertile patients with normal Y chromosomes. The results of ICSI were not affected by the AZFc deletion. Preimplantation genetic diagnosis (PGD) before ICSI for Y chromosome AZFc microdeletion may not be a justifiable regular procedure if the couples didn’t care the vertical transmission of Y chromosome deletion.
Y chromosome microdeletion; AZF; ICSI; Male infertility; Clinical outcome; PGD
This study aims to compare the protein composition of high-density lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls by proteomic methods.
HDL has been reported to exert pro-atherogenic properties in CHD patients. Accumulating evidence indicates that HDL composition, rather than the HDL-C level, determines its functions. The changes in HDL composition involved in the conversion of anti-atherogenic to pro-atherogenic properties in CHD patients are currently unknown.
Methods and Results
iTRAQ combined with nanoLC-MS/MS was performed to obtain a differential expression profile of the HDL pooled samples of the male age-matched CHD patients and controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12 were differentially expressed between the CHD patients and the controls, including five up-regulated proteins and seven down-regulated proteins. Using GO analysis, we determined that the up-regulated proteins were mostly involved in inflammatory reactions, displaying a potential pro-atherogenic profile. In contrast, the down-regulated proteins were mostly involved in lipid metabolism processes, displaying anti-atherogenic properties. To confirm the proteomic results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA, in the same population as the proteomic analysis, as well as another independent population (n = 120/group). Consistent with the proteomic results, the amount of SAA was significantly increased, and apoC-I was significantly decreased in the HDL particles of CHD patients compared with those of controls (P<0.05).
Our study shows that the HDL proteome changes to a pro-atherogenic profile in CHD patients, which might compromise the protective effects of HDL. Proteomic analysis of HDL composition may provide more relevant information regarding their functional properties than steady-state HDL-C levels.
Despite the use of modern immunochemotherapy regimens, a significant proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a new prognostic factor in relapsed or primary refractory DLBCL.
We retrospectively analyzed 163 patients who have been diagnosed with relapsed or primary refractory DLBCL. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors for OS and PFS.
On univariate and multivariate analysis performed with factors included in the saaIPI, early relapse, prior exposure to rituximab and autologous stem-cell transplantation (ASCT), the ALC/AMC ratio at the time of first relapse remained an independent predictor of PFS and OS (PFS: P < 0.001; OS: P < 0.001). Patients with lower ALC/AMC ratio (<2.0) had lower overall response rate, 1-year PFS and 2-year OS rate compared with those with higher ALC/AMC ratio (≥2.0). Moreover, the ALC/AMC ratio can provide additional prognostic information when superimposed on the saaIPI.
Lower ALC/AMC ratio at the time of first relapse is a adverse prognostic factor for OS and PFS in relapsed or primary refractory DLBCL, and leads to the identification of high-risk patients otherwise classified as low/intermediate risk by the saaIPI alone.
Absolute lymphocyte count/absolute monocyte count ratio; Diffuse large B-cell lymphoma; Relapse; SaaIPI; Survival
We used molecular methods to identify Rickettsia raoultii infections in 2 persons in China. These persons had localized rashes around sites of tick bites. R. raoultii DNA was detected in 4% of Dermacentor silvarum ticks collected in the same area of China and in 1 feeding tick detached from 1 patient.
Rickettsia raoultii; rickettsia; human infections; ticks; Dermacentor silvarum; vector-borne infections; China
Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer.
Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models.
miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin.
Our data demonstrate that miR-181a expression is associated with CRC liver metastasis and survival. miR-181a has strong tumor-promoting effects through inhibiting the expression of WIF-1, and its potential role in promoting epithelial-mesenchymal transition.
miR-181a; Colorectal cancer; Liver metastasis; WIF-1
In our previous study, the upregulation of adipophilin in lung adenocarcinoma were identified compared with normal lung tissues by quantitative proteomics. In this study, our aim was to verify the result from quantitative proteomics, further investigate the relationship between adipophilin expression and clinicopathologic factors of lung cancer patients. The expression levels of adipophilin were examined in 10 pairs of lung adenocarcinoma and normal lung tissues using western blotting and the expression and cellular distribution of adipophilin were determined by IHC in 62 formalin-fixed and paraffin embedded primary lung cancer specimens. Adipophilin expression was significantly higher in lung adenocarcinoma specimens than in normal tissues and lung squamous cell carcinomas (P<0.05). There were no significant difference of adipophilin expression between lung squamous cell carcinomas and normal lung tissues. The expression of adipophilin in lung cancer did not correlate with any clinicopathologic factors such as lymph node metastasis, patients’ age, gender, tumor size, grade, and TNM stage. In Conclusion, Adipophilin was upregulated in lung adenocarcinoma, suggesting that adipophilin play an important role in tumorigenesis of lung adenocarcinoma and may serve as a potential marker for lung adenocarcinoma.
Adipophilin; lung cancer; western blotting; immunohistochemistry
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality, and is characterized by high potential for metastasis and recurrence. The outcome of it is still poor due to lacking of targeted therapeutic strategies. There is an urgent need to find new therapeutic targets for interventions against HCC metastasis and recurrence. In the present study, we found cytohesin-3, a member of the cytohesin family, was upregulated in HCC tissues, and its expression was negatively correlated with the overall survival and relapse-free survival of HCC patients. Further clinicopathological correlation analysis revealed that cytohesin-3 expression was related with tumor size and vascular invasion. And in vitro studies revealed that knock-down of cytohesin-3 suppressed HCC cells proliferation and migration. These results suggest that cytohesin-3 may act as a novel prognostic factor of HCC, and it might also be useful to exploit targeted therapeutic drugs against HCC growth and metastasis.
Cytohesin-3; hepatocellular carcinoma; prognosis; cell proliferation; vascular invasion
Early-stage endometrial carcinoma (EC) patients have a high cure rate; however, those with high-risk factors may have poor prognosis. Thus, there is an urgent need for searching for new prognostic molecules to more accurately predict survival of patients. We detected the Rictor mRNA expression level in 30 fresh EC tissue and 17 normal endometrial tissue samples with real-time quantitative RT-PCR and Rictor protein expression level in 134 (test cohort) and 115 (validation cohort) paraffin tissue samples by immunohistochemistry, analyzed the correlation between variables and overall survival (OS) using Cox proportional hazards regression, compared the prognostic accuracy of Rictor with other clinicopathological risk factors by logistic regression. The results showed that Rictor mRNA expression of EC is higher than that of normal endometrium; Rictor protein expression level was closely correlated with FIGO stage, grade and vascular invasion in both cohorts; a univariate analysis showed that the pathological type, stage, grade, vascular invasion, lymphatic metastasis and Rictor were predictors of OS in both cohorts; furthermore, multivariate Cox proportional hazards regression analysis indicated that vascular invasion and Rictor were independent prognostic factors for EC in both cohorts; an ROX curve comparison showed that the area under the curve (AUC) for Rictor combined with other clinicopathological prognostic factors was higher than any individual factor or other clinicopathological prognostic factors’ combination. Based on the above data, we concluded that Rictor is an independent prognostic factor for EC. It combined with other clinicopathological risk factors was a stronger prognostic model than individual risk factor or their combination.
Rictor; prognosis; endometrial carcinoma
AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.
METHODS: In total, 19 patients were enrolled in this study, of which 12 received PEG-IFNα-2a 67.5 μg 1 time/wk (Group 1) and 7 received standard interferon α-2b subcutaneously 1.5 × 106 U 3 times/wk (Group 2). The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3. All patients were prospectively followed after the completion of therapy. The efficacy and tolerability of the treatment were evaluated based on the sustained virological response (SVR) and treatment-related drop-out rate.
RESULTS: In Group 1, 11 of the 12 patients completed the treatment. Early virological response (EVR) and sustained virological response (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment-related adverse events (nausea and depression). In this group, the drop-out rate was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia was the most frequent side effect and was observed in 10/19 patients (55.5%), but could be effectively managed with erythropoietin.
CONCLUSION: Low-dose interferon monotherapy, either with PEG-IFNα-2a or standard interferon α-2b, is an effective treatment option for hemodialysis patients with chronic hepatitis C.
Chronic hepatitis C; End-stage renal disease; Hemodialysis; Hepatitis C virus; Peginterferon
Chlorpyrifos is a widely used insecticide in recent years, and it will produce adverse effects on soil when applied on crops or mixed with soil. In this study, nested polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) were combined to explore the bacterial and fungal community successions in soil treated with 5 and 20 mg/kg of chlorpyrifos. Furthermore, isolates capable of efficiently decomposing chlorpyrifos were molecular-typed using enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Under the experimental conditions, degradation of chlorpyrifos in soil was interpreted with the first-order kinetics, and the half-lives of chlorpyrifos at 5 and 20 mg/kg doses were calculated to be 8.25 and 8.29 d, respectively. DGGE fingerprint and principal component analysis (PCA) indicated that the composition of the fungal community was obviously changed with the chlorpyrifos treatment, and that samples of chlorpyrifos treatment were significantly separated from those of the control from the beginning to the end. While for the bacterial community, chlorpyrifos-treated soil samples were apparently different in the first 30 d and recovered to a similar level of the control up until 60 d, and the distance in the PCA between the chlorpyrifos-treated samples and the control was getting shorter through time and was finally clustered into one group. Together, our results demonstrated that the application of chlorpyrifos could affect the fungal community structure in a quick and lasting way, while only affecting the bacterial community in a temporary way. Finally, nine typical ERIC types of chlorpyrifos-degrading isolates were screened.
Denaturing gradient gel electrophoresis (DGGE); Bacterial community; Fungal community; Chlorpyrifos-degrading isolates; Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR)
Valtrate is a principle compound isolated from Valeriana jatamansi Jones, which is a Traditional Chinese Medicine used to treat various mood disorders. The aim of the present study was to investigate the anxiolytic effects of valtrate in rats. The animals were orally administered valtrate (5, 10, and 20 g/kg daily) for 10 days and exposed to open field test (OFT) and elevated plus-maze (EPM). Then the corticosterone levels in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). The valtrate (10 mg/kg, p.o.) exhibited the anxiolytic effect in rats by increasing the time and entry percentage into the open arms in the EPM and the number of central entries in the OFT. Valtrate (10 mg/kg, p.o.) significantly reduced the corticosterone level in the rat serum. Taken together, these results suggest that the valtrate has anxiolytic activity in behavioral models that might be mediated via the function of hypothalamus-pituitary-adrenal axis.
We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p <.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.
Prostate cancer; microRNA; biochemical progression; miR-103; miR-125b; miR-222; cancer epigenetics
Background. The molecular work-up of thyroid nodules from fine needle aspiration samples has given clinicians a new level of diagnostic information. The aim of the present study was to evaluate the utility of molecular analysis in thyroid fine needle aspiration samples from a Chinese population. Methods. Specimens were collected from thyroid nodules by fine needle aspiration. Cytology diagnosis and genes analysis were performed and correlated with histology outcome. Results. A total of 83 patients with thyroid nodules were enrolled, including 20 benign lesions and 63 papillary carcinomas. BRAF and RAS mutations and RET/PTC gene rearrangements were found in 65.1%, 0%, and 1.6% of papillary carcinomas, respectively. No gene alterations were found in benign lesions. The combination of BRAF testing and cytology improved the accuracy of cytology from 69.9% to 89.2% (P < 0.05). Moreover, BRAF testing confirmed 82.4% of papillary carcinomas with suspicious cytology and identified 33.3% of papillary carcinomas with atypia cytology. Conclusions. Of the three candidate markers, BRAF testing showed diagnostic utility in fine needle aspiration. Combining BRAF testing with cytology improves the accuracy of fine needle biopsy. Those who have positive BRAF and malignant or suspicious malignant cytology can undergo thyroidectomy without a frozen section.
Saprotrophy on plant biomass is a recently developed nutrition strategy for Trichoderma. However, the physiology and evolution of this new nutrition strategy is still elusive. We report the deep sequencing and analysis of the genome of Trichoderma longibrachiatum, an efficient cellulase producer. The 31.7-Mb genome, smallest among the sequenced Trichoderma species, encodes fewer nutrition-related genes than saprotrophic T. reesei (Tr), including glycoside hydrolases and nonribosomal peptide synthetase–polyketide synthase. Homology and phylogenetic analyses suggest that a large number of nutrition-related genes, including GH18 chitinases, β-1,3/1,6-glucanases, cellulolytic enzymes, and hemicellulolytic enzymes, were lost in the common ancestor of T. longibrachiatum (Tl) and Tr. dN/dS (ω) calculation indicates that all the nutrition-related genes analyzed are under purifying selection. Cellulolytic enzymes, the key enzymes for saprotrophy on plant biomass, are under stronger purifying selection pressure in Tl and Tr than in mycoparasitic species, suggesting that development of the nutrition strategy of saprotrophy on plant biomass has increased the selection pressure. In addition, aspartic proteases, serine proteases, and metalloproteases are subject to stronger purifying selection pressure in Tl and Tr, suggesting that these enzymes may also play important roles in the nutrition. This study provides insights into the physiology and evolution of the nutrition strategy of Trichoderma.
Trichoderma longibrachiatum; cellulolytic enzymes; carbohydrate-active enzymes; proteases; purifying selection; dN/dS
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder frequently accompanied by obesity and by insulin resistance, and patients with this syndrome suffer from infertility and poor pregnancy outcome. Disturbances in plasma amino acid (AA) metabolism have been implicated in women with PCOS. However, direct evidence on follicular AA metabolic profiles in PCOS patients and their relationship with pregnancy outcome is sparse.
We conducted a prospective study in 63 PCOS patients and 48 controls in the Division of Reproductive Center, Peking University Third Hospital. Follicular AA levels were measured by the liquid chromatography-tandem mass spectrometric method, and the results were analyzed based on different grouping criteria.
The levels of aromatic amino acid (AAA) increased in PCOS patients independent of obesity (P < 0.05), whereas the levels of branched-chain amino acid (BCAA), glutamic acid, phenylalanine, alanine, and arginine increased with body mass index irrespective of the PCOS status (all P < 0.05). In addition, compared with non insulin resistant-PCOS patients and controls, insulin resistant-PCOS group had higher levels of leucine, valine and glutamic acid (all P < 0.05). In PCOS group, aspartic acid and serine levels were elevated in pregnant patients compared with the non-pregnant subjects (both P < 0.05). Moreover, the levels of BCAA and valine were higher in the non-pregnant group than in the pregnant group (both P < 0.05). The pregnancy rate (45.00%) of subjects with elevated BCAA level was significantly lower than that (66.67%) in control subjects (P = 0.036) at a BCAA cutoff value of 239.10 μM, while the abortion rate was much higher (33.33% versus 2.78%, P = 0.004).
Both PCOS and obesity were accompanied by follicular AA metabolic disturbances, with obesity exerting a more pronounced effect on AA metabolic profiles. The disruptions in specific AAs in the follicular fluid might account for the inferior pregnancy outcome in obese patients and increased risk of abortion in PCOS patients.
PCOS; Amino acid; Obesity; Follicular fluid
Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies.
Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested.
MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months.
MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.
MK-2206; AKT inhibitor; Protein serine-threonine kinase; Phase 1; Chemotherapy; Combination therapy; Solid tumors
The objective of this study was to evaluate the effect of overexpression of epidermal growth factor receptor (EGFR) on the expression of epithelial cell markers (E-cadherin and α-catenin) and mesenchymal cell markers (N-cadherin and vimentin) in endometrial carcinoma.
The expression of all 4 markers was evaluated in EGFR overexpressing Ishikawa cells, control Ishikawa cells, and KLE cells using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The expression of these 4 markers was also determined in cancerous tissues of patients with endometrial carcinoma using immunohistochemical staining.
Ishikawa cells transfected with EGFR showed decreased expression of E-cadherin and α-catenin and increased expression of N-cadherin and vimentin compared with control Ishikawa cells (p<0.01 for all). The expression of N-cadherin and vimentin was higher and the expression of E-cadherin and α-catenin was lower in stage II-III than stage I and in grade II-III than grade I endometrial carcinoma tissue (p<0.01 for all).
Decreased expression of epithelial markers (E-cadherin and α-catenin) and increased expression of mesenchymal markers (N-cadherin and vimentin) were observed in human endometrial carcinoma tissue. These findings correlate with high EGFR expression in cultured endometrial carcinoma cells.
Endometrial carcinoma cells; Epidermal growth factor receptor; Epithelial-mesenchymal transition
The goal of this study is to determine the effects of Insulin-Transferrin-Selenium (ITS) on proliferation of auricular chondrocytes and formation of engineered cartilage in vitro. Pig auricular monolayer chondrocytes and chondrocyte pellets were cultured in media containing 1% ITS at different concentrations of fetal bovine serum (FBS, 10%, 6%, 2%, 0%), or 10% FBS alone as a control for four weeks. Parameters including cell proliferation in monolayer, wet weight, collagen type I/II/X (Col I, II, X) and glycosaminoglycan (GAG) expression, GAG content of pellets and gene expression associated with cartilage formation/dedifferentiation (lost cartilage phenotype)/hypertrophy within the chondrocyte pellets were assessed. The results showed that chondrocytes proliferation rates increased when FBS concentrations increased (2%, 6%, 10% FBS) in ITS supplemented groups. In addition, 1% ITS plus 10% FBS significantly promoted cell proliferation than 10% FBS alone. No chondrocytes grew in ITS alone medium. 1% ITS plus 10% FBS enhanced cartilage formation in terms of size, wet weight, cartilage specific matrices, and homogeneity, compared to 10% FBS alone group. Furthermore, ITS prevented engineered cartilage from dedifferentiation (i.e., higher index of Col II/Col I mRNA expression and expression of aggrecan) and hypertrophy (i.e., lower mRNA expression of Col X and MMP13). In conclusion, our results indicated that ITS efficiently enhanced auricular chondrocytes proliferation, retained chondrogenic phenotypes, and promoted engineered cartilage formation when combined with FBS, which is potentially used as key supplementation in auricular chondrocytes and engineered cartilage culture.
insulin-transferrin-selenium; auricular chondrocyte; dedifferentiation; hypertrophy; serum; engineered cartilage
Angiotensin II (AngII) contributes to the pathogenesis of hypertension and other cardiovascular diseases. AngII induces a pro-oxidative, pro-inflammatory, and pro-thrombogenic phenotype in vascular endothelial cells. Although the peptide promotes the recruitment of leukocytes and platelets and induces oxidative stress in the microvasculature, it remains unclear whether and how the blood cell recruitment is linked to the production of reactive oxygen species (ROS). In this study, we addressed the contributions of AngII type-1 receptors (AT1r), and gp91phox to the recruitment of leukocytes and platelets and ROS production in venules during chronic (2 wks) infusion of AngII in wild type (WT) and mutant mice. Intravital video microscopy was used to measure the adhesion and emigration of leukocytes, the adhesion of fluorescently labeled platelets, and dihydrorhodamine oxidation (a measure of oxidative stress) in cremaster muscle post-capillary venules. In WT mice, AngII infusion induced a time-dependent increase in the adhesion of leukocytes and platelets and enhanced ROS production in venules. These changes in blood cell adhesion and ROS production were not observed in AT1r−/− mice, in AT1r−/− bone marrow chimeras (blood cells deficient in AT1r), gp91phox−/−, gp91phox−/− chimeras (blood cells or endothelial cells deficient in gp91phox) and in WT mice rendered granulocytopenic via i.p injection of anti-mouse Gr-1 antibody. Thrombocytopenic WT mice (platelets depleted by i.p. injection of rabbit anti-mouse thrombocyte antiserum) responded similar to WT mice. These findings implicate leukocyte-associated AT1r and gp91phox in the induction of the pro-oxidative, proinflammatory and prothrombogenic phenotype assumed by microvessels that are chronically exposed to elevated AngII.
Angiotensin II; neutrophils; oxidative stress; blood vessels; microcirculation