The expending and invasive features of tumor nests could reflect the malignant biological behaviors of breast invasive ductal carcinoma. Useful information on cancer invasiveness hidden within tumor nests could be extracted and analyzed by computer image processing and big data analysis.
Tissue microarrays from invasive ductal carcinoma (n = 202) were first stained with cytokeratin by immunohistochemical method to clearly demarcate the tumor nests. Then an expert-aided computer analysis system was developed to study the mathematical and geometrical features of the tumor nests. Computer recognition system and imaging analysis software extracted tumor nests information, and mathematical features of tumor nests were calculated. The relationship between tumor nests mathematical parameters and patients' 5-year disease free survival was studied.
There were 8 mathematical parameters extracted by expert-aided computer analysis system. Three mathematical parameters (number, circularity and total perimeter) with area under curve >0.5 and 4 mathematical parameters (average area, average perimeter, total area/total perimeter, average (area/perimeter)) with area under curve <0.5 in ROC analysis were combined into integrated parameter 1 and integrated parameter 2, respectively. Multivariate analysis showed that integrated parameter 1 (P = 0.040) was independent prognostic factor of patients' 5-year disease free survival. The hazard risk ratio of integrated parameter 1 was 1.454 (HR 95% CI [1.017–2.078]), higher than that of N stage (HR 1.396, 95% CI [1.125–1.733]) and hormone receptor status (HR 0.575, 95% CI [0.353–0.936]), but lower than that of histological grading (HR 3.370, 95% CI [1.125–5.364]) and T stage (HR 1.610, 95% CI [1.026 –2.527]).
This study indicated integrated parameter 1 of mathematical features (number, circularity and total perimeter) of tumor nests could be a useful parameter to predict the prognosis of early stage breast invasive ductal carcinoma.
The meaning of person names is determined by their associated information. This study used event related potentials to investigate the time course of integrating the newly constructed meaning of person names into discourse context. The meaning of person names was built by two-sentence descriptions of the names. Then we manipulated the congruence of person names relative to discourse context in a way that the meaning of person names either matched or did not match the previous context. ERPs elicited by the names were compared between the congruent and the incongruent conditions. We found that the incongruent names elicited a larger N400 as well as a larger P600 compared to the congruent names. The results suggest that the meaning of unknown names can be effectively constructed from short linguistic descriptions and that the established meaning can be rapidly retrieved and integrated into contexts.
Background and Purpose
Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy.
Material and Methods
Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction.
After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms.
Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.
Background & Aims
After liver injury, bone marrow-derived liver sinusoidal endothelial cell progenitor cells (BM SPCs) repopulate the sinusoid as liver sinusoidal endothelial cells (LSECs). After partial hepatectomy, BM SPCs provide hepatocyte growth factor, promote hepatocyte proliferation, and are necessary for normal liver regeneration. We examined how hepatic vascular endothelial growth factor (VEGF) regulates recruitment of BM SPC and their effects on liver injury.
Rats were given injections of dimethylnitrosamine to induce liver injury, which was assessed by histology and transaminase assays. Recruitment of SPCs was analyzed by examining BM SPC proliferation, mobilization to the circulation, engraftment in liver, and development of fenestration (differentiation).
Dimethylnitrosamine caused extensive denudation of LSEC at 24 hours, followed by centrilobular hemorrhagic necrosis at 48 hours. Proliferation of BM SPCs, number of SPCs in the bone marrow, and mobilization of BM SPCs to the circulation increased 2- to 4-fold by 24 hours after injection of dimethylnitrosamine; within 5 days, 40% of all LSEC came from engrafted BM SPC. Allogeneic resident SPCs, infused 24 hours after injection of dimethylnitrosamine, repopulated the sinusoid as LSEC and reduced liver injury. Expression of hepatic VEGF mRNA and protein increased 5-fold by 24 hours after dimethylnitrosamine injection. Knockdown of hepatic VEGF with antisense oligonucleotides completely prevented dimethylnitrosamine-induced proliferation of BM SPCs and their mobilization to the circulation, reduced their engraftment by 46%, completely prevented formation of fenestration after engraftment as LSEC, and exacerbated dimethylnitrosamine injury.
BM SPC recruitment is a repair response to dimethylnitrosamine liver injury in rats. Hepatic VEGF regulates recruitment of BM SPCs to liver and reduces this form of liver injury.
endothelial progenitor cells; toxic hepatitis; animal model; liver damage
To characterize longitudinal changes in basal blood flow (BF) of the optic nerve head (ONH) during progression of structural damage in experimental glaucoma (EG).
Unilateral elevation of IOP was induced in 15 adult rhesus macaques by laser treatment to the trabecular meshwork. Prior to and after laser, retinal nerve fiber layer thickness (RNFLT) and ONH BF were measured biweekly by spectral-domain optical coherence tomography and a laser speckle flowgraphy device (LSFG), respectively.
Average postlaser IOP was 20.2 ± 5.9 mm Hg in EG eyes and 12.3 ± 2.6 mm Hg in control eyes (P < 0.0001). Longitudinal changes in basal ONH BF were strongly associated with changes in RNFLT as EG progressed from early through moderately advanced stages of damage, with Pearson correlation coefficients ranging from 0.64 to 0.97 (average = 0.81) and an average slope of 1.0. During early stage (RNFLT loss < 10%), basal ONH BF was mildly increased (9% ± 10%, P = 0.004) relative to baseline and compared with fellow controls (P = 0.02). Basal ONH BF declined continuously throughout subsequent stages in EG eyes reaching 25.0% ± 9.6% (P < 0.0001) below baseline at the final stage studied (RNFLT loss > 40%). In fellow control eyes, there was no significant change in basal ONH BF over time (P = 0.27).
In EG based on chronic mild-to-moderate IOP elevation, a two-phase pattern of ONH BF alteration was observed. ONH BF increased during the earliest stage (while RNFLT was within 10% of baseline) followed by a linear decline that was strongly correlated with loss of RNFLT.
In a nonhuman primate experimental glaucomatous model with chronic intraocular pressure elevation, a two-phase pattern of optic nerve head blood flow alteration was observed: it increased during the earliest stage followed by a linear decline that was strongly correlated with loss of retinal nerve fiber layer thickness.
intraocular pressure; blood flow; optic nerve head; experimental glaucoma
Microbes that have gained resistance against antibiotics pose a major emerging threat to human health. New targets must be identified that will guide the development of new classes of antibiotics. The selective inhibition of key microbial enzymes that are responsible for the biosynthesis of essential metabolites can be an effective way to counter this growing threat. Aspartate semialdehyde dehydrogenases (ASADHs) produce an early branch point metabolite in a microbial biosynthetic pathway for essential amino acids and for quorum sensing molecules. In this study, molecular modeling and docking studies were performed to achieve two key objectives that are important for the identification of new selective inhibitors of ASADH. First, virtual screening of a small library of compounds was used to identify new core structures that could serve as potential inhibitors of the ASADHs. Compounds have been identified from diverse chemical classes that are predicted to bind to ASADH with high affinity. Next, molecular docking studies were used to prioritize analogs within each class for synthesis and testing against representative bacterial forms of ASADH from Streptococcus pneumoniae and Vibrio cholerae. These studies have led to new micromolar inhibitors of ASADH, demonstrating the utility of this molecular modeling and docking approach for the identification of new classes of potential enzyme inhibitors.
Aspartate semialdehyde dehydrogenase; Docking models; Virtual screening; Enzyme inhibitors; Validation
Because of the lack of sensitivity to small changes in distance by available FRET pairs (a constraint imposed by the dimensions of the enzyme), a DHFR containing two pyrene moieties was prepared to enable the observation of excimer formation. Pyren-1-ylalanine was introduced into DHFR positions 16 and 49 using an in vitro expression system in the presence of pyren-1-ylalanyl-tRNACUA. Excimer formation (λex 342 nm; λem 481 nm) was observed in the modified DHFR, which retained its catalytic competence and was studied under multiple and single turnover conditions. The excimer appeared to follow a protein conformational change after the H transfer involving the relative position and orientation of the pyrene moieties and is likely associated with product dissociation.
Routine repeat testing of critical values is a long-standing practice in many clinical laboratories; however, its usefulness and necessity remain to be empirically established and no regulatory requirements yet exist for verification of the critical value results obtained by repeat analysis.
To determine whether repeat testing of critical values is useful and necessary in a clinical chemistry laboratory.
A total of 601 chemistry critical values (potassium, n = 255; sodium, n = 132; calcium, n = 108; glucose, n = 106) obtained from 72,259 routine clinical chemistry specimens were repeat tested. The absolute value and the percentage of difference between the two testing runs were calculated for each of the four critical values and then compared with the allowable error limit put forth in the College of American Pathologists (CAP).
Among the repeat data for the 601 critical values, a total of 24 showed large differences between the initial result and the repeated result which exceeded the CAP limits for allowable error. The number and rates (%) of large differences for within and outside the analytical measurement range (AMR) were 12 (2.1%) and 12 (41.4%), respectively. For the 572 critical values within the AMR for each test category, the mean absolute difference (mmol/L) and difference(%) between the two testing runs were: potassium, 0.1 mmol/L (2.7%); sodium, 2.1 mmol/L (1.7%); calcium, 0.05 mmol/L (3.0%); glucose, 0.18 mmol/L (2.6%).
When the initial chemistry critical values are within the AMR, repeated testing does not improve accuracy and is therefore unnecessary. When the initial chemistry critical values are outside the AMR, however, the benefit of repeated testing justifies its performance and makes it necessary. Performing repeat clinical testing on a case-by-case, rather than routine, basis can improve patient care by delivering critical values more rapidly while providing savings on reagent costs associated with unnecessary repeat testing.
104 samples from 27 accessions belonging to 12 species of genus Epimedium were studied on the basis of cytology observation, POD (i.e., peroxide) isozyme, high performance liquid chromatography (i.e., HPLC) fingerprint, and interspecific hybridization. The cytology observation showed karyotypes of twelve species studied; all are 2A symmetry type of Stebbins standard and similar to each other, and except for karyotype of E. leptorrhizum which is 2n = 2x = 8m (2SAT) + 4sm, the rest are 2n = 2x = 6m (2SAT) + 6sm. Chromosomes C-banding of barrenwort species varies, with 15 to 22 bands, consisting of centromeric bands, intercalary bands, terminal bands, and middle satellite bands. Results of POD isozyme showed that the zymographs vary greatly and sixteen bands were detected in the eleven species, and each species has its own characteristic bands different from the others. Studies on the HPLC fingerprint showed that the HPLC fingerprint of different species has characteristic peaks, divided into two regions (retention time < 10 min and retention time > 10 min). Results of interspecific hybridization showed that crosses of any combination among seven species studied are successful and the rates of grain set vary greatly. Based on these results, the system and phylogeny of this genus were inferred.
The aim of this case report and minireview was to investigate the diagnosis of and therapeutic approaches for angiocentric glioma (AG) and to summarize the clinical manifestations and the pathological and imaging characteristics of the disease. Intraoperative cortical electroencephalogram (ECoG) monitoring was performed to locate the epileptic foci in a child with AG who presented with intractable epilepsy, prior to the total resection of the tumor being performed under the microscope. The clinical features, imaging characteristics, intraoperative conditions, surgical methods and pathological results were analyzed and compared with the literature. The review revealed that to date, the clinical features of the 52 reported cases of AG (including this case) have been mainly characterized by epilepsy. High T2-weighted image (WI) and fluid-attenuated inversion recovery (FLAIR) signals may be detected with magnetic resonance imaging (MRI) scanning of the cranium; however, no enhancement signals are detected by enhanced scanning. The prognosis following surgical resection is favorable. The lesions in the present case demonstrated clear boundaries with a central cystic affection accompanied by an arachnoid cyst on the left temporal pole. Pathological examination revealed that the lesion was positive for glial fibrillary acidic protein (GFAP), S-100 protein, vimentin, epithelial membrane antigen (EMA), cluster of differentiation 99 (CD99) and D2-40. The Ki-67/MIBk-1 labeling index was ~1%. In conclusion, AG exhibits characteristic features in imaging; however, its diagnosis depends on histopathological examination. The prognosis of total surgical resection is good and intraoperative ECoG may be used to assist positioning.
angiocentric glioma; intractable epilepsy; cortical; electrocorticogram
Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients.
This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles).
The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session.
The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis.
A shift from oxidative to glycolytic metabolism has been associated with skeletal muscle insulin resistance in type 2 diabetes1–5. However, whether this metabolic switch is deleterious or adaptive remains controversial6–8, in part due to limited understanding of the regulatory network that directs the metabolic and contractile specification of fast-twitch glycolytic muscle. Here we show that BAF60c, a transcriptional cofactor enriched in fast-twitch muscle, promotes a switch from oxidative to glycolytic myofiber type through Deptor-mediated AKT activation. Muscle-specific transgenic expression of BAF60c activates a program of molecular, metabolic, and contractile changes characteristic of glycolytic muscle. In addition, BAF60c is required for maintaining glycolytic capacity in adult skeletal muscle in vivo. BAF60c expression is significantly decreased in skeletal muscle from obese mice. Unexpectedly, transgenic activation of the glycolytic muscle program by BAF60c protects mice from diet-induced insulin resistance and glucose intolerance. Further mechanistic studies revealed that Deptor is induced by the BAF60c/Six4 transcriptional complex and mediates activation of AKT and glycolytic metabolism by BAF60c in a cell-autonomous manner. This work defines a fundamental mechanism underlying the specification of fast glycolytic muscle and illustrates that the oxidative to glycolytic metabolic shift in skeletal muscle is potentially adaptive and beneficial in the diabetic state.
As a practical inventory and transportation problem, it is important to synthesize several objectives for the joint replenishment and delivery (JRD) decision. In this paper, a new multiobjective stochastic JRD (MSJRD) of the one-warehouse and n-retailer systems considering the balance of service level and total cost simultaneously is proposed. The goal of this problem is to decide the reasonable replenishment interval, safety stock factor, and traveling routing. Secondly, two approaches are designed to handle this complex multi-objective optimization problem. Linear programming (LP) approach converts the multi-objective to single objective, while a multi-objective evolution algorithm (MOEA) solves a multi-objective problem directly. Thirdly, three intelligent optimization algorithms, differential evolution algorithm (DE), hybrid DE (HDE), and genetic algorithm (GA), are utilized in LP-based and MOEA-based approaches. Results of the MSJRD with LP-based and MOEA-based approaches are compared by a contrastive numerical example. To analyses the nondominated solution of MOEA, a metric is also used to measure the distribution of the last generation solution. Results show that HDE outperforms DE and GA whenever LP or MOEA is adopted.
AIM: To investigate the association between nuclear β-catenin overexpression in rectal adenocarcinoma and radioresistance.
METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of β-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of β-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between β-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance.
RESULTS: Nuclear β-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear β-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane β-catenin was expressed in favor of good TRG (≥ 3). Nuclear β-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear β-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear β-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear β-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity.
CONCLUSION: Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.
β-catenin; Rectal cancer; Preoperative radiotherapy; Radioresistance; Colorectal cancer
Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal microscopy, and electron paramagnetic resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice. These observations were consistent with an overall reduction of mitochondrial glucose oxidation. Activity of AMPK, the major energy-sensing enzyme, was reduced in kidneys from both diabetic mice and humans. Mitochondrial biogenesis, PDH activity, and mitochondrial complex activity were rescued by treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). AICAR treatment induced superoxide production and was linked with glomerular matrix and albuminuria reduction in the diabetic kidney. Furthermore, diabetic heterozygous superoxide dismutase 2 (Sod2+/–) mice had no evidence of increased renal disease, and Ampka2–/– mice had increased albuminuria that was not reduced with AICAR treatment. Reduction of mitochondrial superoxide production with rotenone was sufficient to reduce AMPK phosphorylation in mouse kidneys. Taken together, these results demonstrate that diabetic kidneys have reduced superoxide and mitochondrial biogenesis and activation of AMPK enhances superoxide production and mitochondrial function while reducing disease activity.
To test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG).
68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an ‘endpoint’ occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT.
Regardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d’) was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone.
This study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma.
miRNAs regulate gene expression and are key mediators of tumourigenesis. miR-129 has diverse effects in tumours, but its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. This article focuses on the role of miR-129-5p in LSCC. We show miR-129-5p is upregulated in primary LSCC tumours and correlated with advanced disease. Down-regulating miR-129-5p suppressed cell proliferation and migration, and caused cell cycle arrest in Hep-2 cell lines. Downregulation of miR-129-5p alone is sufficient to induce apoptosis both in vivo and in vitro. Moreover, the growth of LSCC xenograft exposed to miR-129-5p antisense oligonucleotides (ASO) in BALB/c mice was markedly inhibited. In addition, we found that miR-129-5p targeted adenomatous polyposis coli (APC) to release inhibition of Wnt signalling causing cell growth and tumourigenesis. Our results suggest miR-129-5p functions as an oncogene in LSCC by repressing APC and is a potential therapeutic target for LSCC.
Objective: To investigate whether inflammation could excessively activate platelet-derived growth factor (PDGF) signaling pathway in desoxycorticosterone (DOCA) induced salt-sensitive hypertensive rats with myocardial fibrosis (MF). Methods: A total of 30 male SD rats underwent right nephrectomy and then bred with 1% sodium chloride and 0.1% potassium chloride for 2 weeks. These animals were randomly divided into 3 groups: CON group, DOCA group and DOCA+FAS group. Systolic blood pressure (SBP) was measured once every 2 weeks; HE staining was done to observe myocardial inflammation; immunohistochemistry was done to detect expressions of monocyte-macrophage antigen (ectodermal dysplasia 1, ED-1), PDGFRα and PDGFRβ in the myocardium; real time fluorescence quantitative PCR was employed to detect the mRNA expressions of DGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFRα and PDGFRβ. Results: The SBP in DOCA group and DOCA+FAS group increased markedly when compared with CON group (P<0.01), but there was no marked difference between DOCA group and DOCA+FAS group (P>0.05). At 14 days, in DOCA group, the myocardial inflammation was obvious, ED-1 expression increased markedly, the mRNA expressions of PDGF-A, PDGF-B, PDGF-C, PDGFRα and PDGFRβ increased to different extents, protein expressions of PDGFRα and PDGFRβ also elevated markedly (P<0.01), but the PDGF-D mRNA expression remained unchanged, when compared with CON group. After treatment with fasudil (a drug with anti-inflammatory activity), myocardial inflammation was significantly attenuated, mRNA expressions of PDGF-A, PDGF-B, PDGF-C and PDGFRα as well as PDGFRα protein expression reduced dramatically (P<0.01), but the mRNA and protein expressions of PDGFRβ remained unchanged (P>0.05) when compared with DOCA group. Conclusion: In DOCA/salt induced hypertensive rats with MF, excessive activation of PDGF/PDGFR signaling pathway is involved in myocardial inflammation.
Desoxycorticosterone; platelet-derived growth factor; platelet-derived growth factor receptor; fasudil; inflammatory response
Objective: To investigate chemoresistance of human gastric cancer to chemotherapeutic drugs in vitro and explore the relationship with Bcl-2 protein expression. Methods: Single-cell suspensions were prepared from freshly excised samples of primary gastric cancer, and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. The induction of cell death was confirmed by microscopic analysis of cell morphology. Metabolic activity and the inhibitory rate (IR) of cells were evaluated by MTT assay. Expression of Bcl-2 was determined by immunohistochemistry of gastric cancer tissue samples. Results: The IRs of cancer cells exposed to different chemotherapeutic drugs varied as follows: the IRs for TAX, CDDP and 5-FU were significantly higher than those for ADM and MMC (P < 0.01). Poorly differentiated gastric cancer cells were more sensitive than well-differentiated cells (P = 0.021). The positive rate of Bcl-2 expression was 80%, and Bcl-2 expression was significantly associated with chemoresistance to 5-FU (rs = 0.265, P = 0.041), ADM (rs = 0.425, P = 0.001) and MMC (rs = 0.40, P = 0.002). Furthermore, Bcl-2 expression was strongly associated with lymph node metastasis in gastric cancer (P = 0.009). Conclusion: Overexpression of Bcl-2 may predict a loss of the efficacy of the chemotherapy drugs 5-FU, ADM and MMC in patients with gastric cancer.
Gastric cancer; Bcl-2; chemosensitivity; chemotherapeutic drugs; inhibitory rate
Issues of surfaces, e.g., inspired from beetle's back, spider silk, cactus stem, etc., become the active area of research on designing novel materials in need of human beings to acquire fresh water resource from air. However, the design of materials on surface structure is little achieved on controlling of micro-scale drop transport in a long distance. Here, we report the ability of micro-drop transport in a long distance on a bioinspired Fibers with Gradient Spindle-knots (BFGS), which are fabricated by tilt angle dip-coating method. The micro-drop of ~0.25 μL transports in distance of ~5.00 mm, with velocity of 0.10–0.22 m s−1 on BFGS. It is attributed to the multi-level cooperation of the release energy of drop coalescence along the gradient spindle-knots, in addition to capillary adhesion force and continuous difference of Laplace pressure, accordingly, water drops are driven to move fast directionally in a long distance on BFGS.
The aim of this study was to determine whether baseline C-reactive protein (CRP) levels and CRP kinetics predict the overall survival in metastatic nasopharyngeal carcinoma (mNPC) patients.
A total of 116 mNPC patients from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients.
Patients with higher values of baseline CRP (≥ 3.4 mg/L) had significantly worse survival than those with lower baseline CRP values (< 3.4 mg/L). Patients were divided into four groups according to baseline CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time during treatment; (3) patients whose CRP ≥ 3.4 mg/L and normalized at least one time during treatment; and (4) patients whose CRP ≥ 3.4 mg/L and never normalized during treatment. The patients were further assigned to non-elevated, elevated, normalized, and non-normalized CRP groups. Overall survival rates were significantly different among the four groups, with three-year survival rates of 68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non-normalized CRP groups respectively. When compared with the non-elevated group, hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated, and non-normalized groups (P < 0.001).
Baseline CRP and CRP kinetics may be useful to predict the prognosis of metastatic NPC patients treated with palliative chemotherapy and facilitate individualized treatment. A prospective study to validate this prognostic model is still needed however.
To study the clinical significance of lymph node ratio (LNR) in gastric cancer (GC), this study analyzed 613 patients with GC who underwent surgical resection. Of 613 patients with GC, 138 patients who had >15 lymph nodes (LNs) resected and radical resection were enrolled into the final study. All major clinicopathological data were entered into a central database. LNR was defined as the ratio of the number of metastatic LNs to the number of removed LNs. In order to determine the best cut-off points for LNR, the log-rank test and X-tile were used. LNR was then substituted for lymph node status (pN) in the 7th American Joint Committee on Cancer tumor-node-metastases (TNM) staging system and this was defined as the tumor-node ratio-metastases (TRM) staging system. Pearson's correlation coefficient (r) was used to study the correlations among the number of removed LNs, pN and LNR. The Kaplan-Meier survival curve was used to study the survival status, and the log-rank test and Cox proportional hazards model were used to identify the independent factors for survival. Receiver operating characteristic curve analysis was used to determine the predictive value of the parameters. By the time of last follow-up (median follow-up period, 38.3 months; range, 9.9–97.7 months), the median overall survival (OS) was 23.9 months [95% confidence interval (CI), 18.8–29.0 months]. The 1-, 2-, 3- and 5-year survival rates were 76.8, 57.2, 50.0 and 46.4%, respectively. The cut-off points were 0, 0.5 and 0.8 (R0, LNR=0; R1, LNR ≤0.5; R2, 0.5> LNR ≤0.8; and R3, LNR >0.8). Univariate and multivariate analyses revealed that both LNR and pN were independent prognostic factors for GC. LNR could better differentiate OS in patients than LN. In addition, the TRM staging system was better at predicting the clinical outcomes than the TNM staging system, and LNR was better than pN. In conclusion, LNR was a better prognosticator than pN for GC.
gastric cancer; lymph node ratio; prognosis
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction between virus and receptor provides key information on the evolutionary events that lead to the viral emergence.
We show that bat DPP4 genes have been subject to significant adaptive evolution, suggestive of a long-term arms-race between bats and MERS related CoVs. In particular, we identify three positively selected residues in DPP4 that directly interact with the viral surface glycoprotein.
Our study suggests that the evolutionary lineage leading to MERS-CoV may have circulated in bats for a substantial time period.
MERS-CoV; Bats; Arms-race; Adaptive evolution; Emergence