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Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.
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Humanos , Carcinoma Hepatocelular , China , Neoplasias Hepáticas , Prognóstico , Piruvato QuinaseRESUMO
Aim To explore the effect of endoplasmic reticulum (ER) stress-related exosomes derived from hepatocellular carcinoma (HCC) cells on the M2 polarization of macrophages via Toll-like receptor 4 (TLR4) and the underlying mechanism. Methods Western blot experiments were conducted to evaluate the GRP78 levels in HCC tissues and HCC cells with or without pre-treatment of tunicamycin and the identification of the isolated exosomes. Immunohistochemical staining was also employed to detect the expression of GRP78 in HCC tissues. Immunofluorescence was used to confirm the effective absorbance of exosomes by macrophages. Flow cytometry ( FCM ) , Western blot and CBA kit were used to detect M2 polarization-asso ciated markers and the expression of TLR4 on macrophages. Affymetrix gene chip and bioinformatics analy-sis were used to screen the differential expression of mRNA in macrophages stimulated by ER stressed-relat- ed exosomes and TLR4 expression. Results In clinical samples, GRP78 expression in liver cancer tissues was higher than that in the adjacent tissues. In cell experiments, tunicamycin (2.5 jxmol • L"1 ) treatment for 24 hours in HCC cells could significantly increase the expression of ER stress marker protein GRP78 compared with control group. Western blot showed that HCC cell-derived exosomes positively expressed exosom- al marker proteins,such as CD63,TSG101 and HSP70, and negatively expressed Calnexin. Interestingly, HSP70-enriched exosomes released by ER-stressed HCC cells were observed. Laser confocal microscopy found that exosomes could be effectively taken up by RAW264.7 macrophages. Flow cytometry and Western blot further indicated that ER stress-related exosomes could significantly up-regulate the expression of CD206, transformed growth factor-beta (TGF-p) and arginase-1 (Arg-1) in macrophages. Meanwhile, these exosomes could promote the secretion of IL-6 and IL- 10,and up-regulate the expression of TLR4 in macrophages. Conclusions ER stressed-HCC cells could promote macrophage M2 polarization by releasing HSP70-enriched exosomes and activating TLR4 signaling.
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In the process of tumor occurrence, development and metastasis, the stress environment experienced by tumor cells such as hypoxia, low glucose, acidosis, can cause tumor cells to undergo endoplasmic reticulum stress (E R S). In order to restore cell homeostasis, ERS initiates the unfolded protein response (U P R). But when ERS exceeds the survival ability of cells, it will mediate cell apoptosis. This article expounds the role of ERS in anti-tumor therapy and its research progress mainly from the two aspects of inhibition of UPR mediated promote survival pathways and induction of ERS mediated death pathways, in order to understand the relationship between ERS-related pathways and anti-tumor treatments, hoping to provide new ideas for tumor treatment.
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<p><b>BACKGROUND</b>As the clinical value of cytokeratin-19 (CK19) and thymidine kinase-1 (TK1) in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease.</p><p><b>METHODS</b>A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK19 was detected using quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival (OS) time.</p><p><b>RESULTS</b>Positive CK19 mRNA expression was detected in 74 (43.3%) of the 171 patients and positive TK1 expression was detected in 66 (68.8%) of the 96 patients. Furthermore, of the 96 patients, 36 (37.5%) were positive for both TK1 protein and CK19 mRNA, 30 (31.3%) were negative for TK1 protein, and 15 (15.6%) were negative for TK1 protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK19 mRNA expression had significantly shorter OS times than those who were negative for it (median OS 7.7 vs. 9.7 months, respectively; P = 0.02). Moreover, patients who were positive for CK19 mRNA and TK1 protein expression had shorter OS times (median OS 6.1 months) than those who were positive for CK19 mRNA and negative for TK1 protein expression (median OS 9.1 months; P = 0.028). Positive CK19 mRNA expression was significantly associated with shorter OS in the univariate analysis (P = 0.027). Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression (P = 0.024) was an independent predictor for OS in gastrointestinal cancer patients.</p><p><b>CONCLUSIONS</b>Our results suggest that positive expression of CK19 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CK19 and TK1 are possible gastrointestinal cancer biomarkers.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais , Sangue , Genética , Neoplasias Gastrointestinais , Sangue , Genética , Mortalidade , Queratina-19 , Sangue , Genética , Estudos Prospectivos , Timidina Quinase , Sangue , GenéticaRESUMO
Objective To evaluate the feasibility and safety in the treatment of liver cancer located under the diaphragm with cool-tip radiofrequency ablation(RFA)percutaneously under CT guidance.Methods 20 patients with total 25 lesions were treated by CT-guided RFA with cool-tip electrode involving the induced necroses.The postoperative efficacy was evaluated by enhanced CT or MRI.Results 72% lesions were completely necrotized(18/25),28% lesions were majorly necrotized(7/25).No severe complications occurred. Conclusion CT-RFA with cool-tip electrode is effective and safe in treating liver cancer located under the diaphragm.
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Objective To analyze the manifestation,reason,the processing method of the steel wire implantation with the sereotactic mammography to improve the accuracy of the preoperative positioning.Methods Seventy-nine cases which got the stereotactic steel wire implantation.In 96 lesions, 13 had steel wire displacement.Among them,5 cases got steel wire displacement during the sereotactic process,5 cases got steel wire displacement after the stereotactic process,2 cases got steel wire displacement during the operation,one case did not show the calcification on the postoperative radiography.Results The steel wire displacement occurred in 5 cases during the stereotactic process came from the patients and doctors respectively and the repositioning was needed.The steel wire displacement after the stereoscopic positioning was attributed to the overdose injection of local anesthesia,which led to the mismatch between the depth of Z axis of the mammary gland and the actual depth the computer given,the incorrect method for needle placement,and,neglecting whether the steel wire have got the lesion anchored when pulling out the needle set of steel wire hood,besides,these three kinds of instances above were all exaggerated by the accordion effect.For the displacement within 2 cm,the lesion can be excised toward the pathological change direction according to the position that steel wire prompted and re-place the second steel wire,putting the J-shaped steel wire into the needle hood and taking it out of the body.After repositioning,2 cases had the steel wire prolapse during operation,which resulted from the over-lifting of the steel wire.After placing the steel wire, the radiologist should give an accurate description on the depth and direction to the surgeon and the notch should be taken for incision from the steel wire head end which is proximate to skin.The postoperative specimen from one case had no calcification,which might be related to the condition that the calcification was located in the gland body,which got destruction from the surgical electrical electrotome.The excisionscope should be extended and the short term reexamination is recommended to make sure the complete excision of the calcification.Conclusion It is the gold standard method that implanting the steel wire with the stereotactic mammography to guide the surgical dissecting technique to diagnose non-palpable breast lesion(NPBL).Thorough understanding of the displacement manifestation of implanting steel wire with stereotactic technique and the treatment methods will be helpful in the surgical dissecting guidance.
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A research combined trickling filter system and active sludge aeration system was applied in the treatment of industrial wastewater from gas-generating with heavy oil. The wastewater contained both high contents of NH+4-N and mixed hydrocarbons including various PAHs. Its BOD5/COD ratio was less than 0.3 and belongs to recalcitrant, toxic wastewater. The results showed a touch-growth biofilms system was formed on the porous packing material and it played a key role in the decrease of toxicity of the influent. It could also improve the biodegradability of the wastewater.
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A pilot-scale research on purification of odorous gas emitted from wastewater treatment plant using a biofilter was conducted. The aim of this study is to check on the performance of biofilter running in various conditions and the effect of pH fluctuations on the performance of biofilter. The relation between distribution of microorganism and removal of odorous gases were also discussed here. The experimental results show that the predominant odor-causing gas can be efficiently eliminated by a biofilter inoculated with deodoring microorganism which were isolated previously. Moreover the biofilter had been proved having good tolerance to shocking loads of pollutant and can operate well in the condition of low pH.
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A laboratory scale combination process of anaerobic baffled reactor(ABR) with sequencing batch reactor(SBR) for treatment of real dyeing wastewater was studied.The effects of operational conditions were investigated.The results demonstrated that removal rates of COD,colour and aniline were 32%~95%,89%~99% and 50%~98%,respectively,the effluents of COD were 30.0 ~97.1mg/L,colour were 8 ~40 times dilution ratio,concentration of aniline were 0.20 ~0.95 mg/L,which could meet the National Discharge Criteria(GradeⅠ) under the operational conditions of HRTs of 24~36 h,organic loading rates of 0.43 ~2.46 kg COD/(m~(3)?d),the influent pH values of 6.5~8.0,ambient temperatures of 20℃~35℃ at the ABR stage and DOs of 2 mg/L,reaction times of 3~10h,settle times of 2 h at the SBR stage.
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A new species of genus shewarella Shewanellade decolorations S12, was isolated from activated sludge of a textile-printing waste-water treatment plant. In the anaerobic condition, S12 could conserve energy for growth by using Fe3 + as the terminal electron acceptor. At the optimal condition of pH8, temperature 30℃, ferric citrate 800mg/L, sodium lactate 2g/ L, yeast extract 0. 5g/ L , the cell growth increased with the raise of the amount of the Fe3+ reduction in 8k The effect of different carbon soucres, nitrogen sources, pH values and growth temperatures on the anaerobic Fe3 + reduction of Shewanella decolorations S12 was investigated. LB was favorable for Fe3 + reduction. Glucose and sodium lactate also were favorable for Fe3+ reduction. The cell growth and Fe3 + reduction increased with the raise of the amount of the yeast extract from 0 to 4g/L The amounts of the sodium lactate of 6g/ L and ferric citrate of 800mg/L were suitable for strain S12 growth and Fe3+ reduction. In the optimum initial pH value range of 6 -8 for Fe3+ reduction, strain S12 growth increased with the raise of the pH val- ue. Strain S12 could growth and reduce Fe3+ at the temperature range of 20 -40℃. The best temperature for strain S12 growth and Fe3 + reduction was 301.
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Denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16s rDNA was used to assess changes of biodiversity in a biotrickling filter used to treat waste air containing toluene. The results shown that along with gradually increase of removing capacity for toluene, microbial community structure in packing materials sampled from biotrickling filter also changed markedly over periods of experiment. Under selective pressure of toluene, the number of microbial species decreased but relative abundance of some predominant species increased,and microbial spatial location along the height of biotrickling filter tend to be identical.