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Objective:To explore the best treatment for local ablation of colon cancer liver metastases (CRLM) by meta-analysis.Methods:The electronic databases of PubMed, Web of Science, Embase, CNKI and the Cochrane Library were searched from the establishment to August 22, 2022, and studies that report outcomes with comparison between microwave ablation (WMA) and radiofrequency ablation (RFA) in CRLM treatment were selected by inclusion and exclusion criteria. Furthermore, the perioperative and survival data were statistically summarized and analyzed by Review Manager 5.3 software.Results:A total of 5 retrospective studies were included with a total sample size of 648 cases, including 316 cases (48.8%) in the WMA group and 332 cases (51.2%) in the RFA group. The results of meta-analysis showed that locoregional recurrence rate in WMA group was significantly lower than that in RFA group. The 1-year and 2-year disease-free survival (DFS) of the WMA group was significantly better than that of the RFA group with HR of 1.77 ( P=0.04, 95% CI: 1.04-3.02) and 1.60 ( P=0.02, 95% CI: 1.09-2.35), respectively. Conclusion:The local control rate and 1-year and 2-year DFS of WMA were superior to RFA.
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Objective:To study the regulative effect of Rhubarb dispensing granule on autophagy and gastrointestinal motility of Cajal interstitial cells in rats with chronic transit constipation (STC).Methods:A total of 75 rats were randomly divided into control group, model group, low, medium and high dose groups with 15 rats in each group. Except for the control group, the STC rat models were established by intragastric administration of compound diphenoxylate suspension. Rats in low, medium and high dose groups were given Rhubarb dispensing granule of 1, 2 and 4 g/kg by gavage respectively, while rats in control group and model group were given normal saline with the same volume by gavage, once a day for 14 consecutive days. Fecal moisture content and intestinal propulsion rate were measured. The serum levels of substance P (SP), vasoactive intestinal peptide (VIP), NO and NOS were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The c-kit level in colon tissue was detected by immunohistochemistry. The mRNA and protein levels of c-kit and Beclin1 in colon tissue were detected by PCR and Western blot.Results:Compared with the model group, the fecal moisture content, the carbon pushing distance and the intestinal pushing rate of the low, medium and high dose groups were significantly increased ( P<0.05), the serum SP level was increased ( P<0.05), the serum VIP, NO and NOS levels of the low, medium and high dose groups were decreased ( P<0.05), and the average expression score of c-kit in colon tissue of the low, medium and high dose groups was significantly increased ( P<0.05). The levels of c-kit mRNA (2.33 ± 0.35, 3.04 ± 0.17, 3.83 ± 0.23 vs. 0.61 ± 0.07) and protein (0.42 ± 0.06, 0.60 ± 0.07, 0.79 ± 0.08 vs. 0.22 ± 0.04)in colon tissue of rats in low, medium and high dose groups were increased ( P<0.05), and Beclin1 mRNA (4.17 ± 0.37, 3.35 ± 0.44, 1.05 ± 0.28 vs. 6.04 ± 0.31) and protein (0.76 ± 0.11, 0.57 ± 0.08, 0.43 ± 0.05 vs. 0.91 ± 0.06) were decreased ( P<0.05). Conclusion:Rhubarb dispensing granule could significantly increase the fecal moisture, intestinal motility rate, serum SP level and colonic tissue c-kit level, decrease serum VIP, NO, NOS level and colonic tissue Beclin1 level in rats with chronic transit constipation, and then inhibit autophagy of Cajal interstitial cells and regulate gastrointestinal motility in rats with chronic transit constipation.
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Objective@#To investigate the effect of microRNA-26a-5p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSC) and its related mechanisms.@*Methods@#hPDLSC in periodontal tissues from healthy adults and hPDLSC from periodontitis patients (PPDLSC) were isolated and cultured in vitro, respectively. The PPDLSC were divided into Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups. Group Ⅰ is control group, and the other four groups were transiently transfected with miR-NC, miR-26a-5p, antimiR-NC and antimiR-26a-5p lentiviral vectors, respectively. The osteogenic differentiation abilities of the cells in vitro were determined by alizarin red staining, alkaline phosphatase (ALP) activity assay and real-time quantitative PCR (qPCR). Totally 40 male mice (6-weeks) were equally divided into five groups with 8 mice in each group. The PPDLSCs cells (1×107/ml) in Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups, which adhered to hydroxyapatine-tricalcium phosphate (HA-TCP), were implanted into the nude mice subcutaneously and the animal models were constructed to analyze the effect of miR-26a-5p on the osteogenic differentiation of PPDLSCs in vivo. PPDLSCs were divided into A, B, C, D groups, and transfected with miR-26a-5p+Wnt5a-Wt, miR-NC+Wnt5a-Wt, miR-26a-5p+Wnt5a-Mut and miR-NC+Wnt5a-Mut in each of the above mentioned 5 groups, respectively. The luciferase activity assay was used to detect the relative luciferase in A, B, C and D groups to analyze the targeting relationship between miR-26a-5p and Wnt5a. Osteogenic differentiation related proteins expression were analyzed by western blotting.@*Results@#hPDLSC and PPDLSC were observed consistent with the characteristics of mesenchymal stem cells and had osteogenic differentiation ability in vitro. Compared with hPDLSC [(89.87±8.12)%], the osteogenic capacity of PPDLSC [(31.46±6.56)%] was significantly lower (P<0.05). The ALP activity (1.88±0.59), calcified nodules (79.88±5.92), the expression of the osteogenic differentiation markers Runt-related transcription factor 2 (Runx2) (2.40±0.70), ALP (2.10±0.60) and osteocalcin (3.00±0.90) mRNA in the PPDLSC from Group Ⅲ were significantly higher in comparison with the control group [(0.88±0.34), (29.69±2.65), (1.30±0.30), (0.09±0.25), (1.71±0.50)], while those from Group Ⅴ[(0.44±0.07), (14.83±3.05), (0.50±0.11), (0.30±0.08) and (0.80±0.17)] were significantly lower (P<0.05). In vivo studies in nude mice showed that the proportion of the osteogenic region [(34.96±5.65)%] in the miR-26a-5p group was significantly increased in comparison with the control group [(23.28±3.03)%], while in the antimiR-26a-5p group [(8.02±2.27)%] was significantly lower (P<0.05). The luciferase activity of the Group A (0.46±0.06) was significantly lower than Group B (3.46±0.45) (P<0.05). Compared with the control group, the expression levels of Wnt5a protein, calmodulin kinase Ⅱ and protein kinase C proteins in the Group Ⅲ were significantly decreased, while those in the GroupⅤ were significantly increased (P<0.05).@*Conclusions@#MicroRNA-26a-5p could promote osteogenic differentiation of PPDLSC in vivo and in vitro, and its mechanism might be inhibiting the activation of Wnt/Ca2+ signaling pathway by targeting Wnt5a.
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Objective The objective of this study was to investigate the effect of salinomycin on proliferation and autophagic flux of human melanoma M21 cells. Methods The cell survival rate was determined by MTS assay and IC50values( half inhibitory concentration)were calculated. The morphological changes of cells after salinomycin administration were observed under optical micro-scope. Flow cytometry was used to examine the apoptosis rate of M21 cells. Western blot was used to detect the expression of autophag-ic-related protein LC3B and p62 in M21 cells. The presence of autophagosomes in M21 cells after salinomycin administration was ob-served under transmission electron microscope. Western blot and immunofluorescence were used to detect the level of p62 protein and localizing changes in M21 cells. Results Salinomycin significantly inhibited proliferation of M21 cells, and the IC50values were (1. 38 ± 0. 18)μM. After salinomycin administration,the proliferation rate of M21 cells was slowed down,and obvious vacuoles ap-peared in the cells. Salinomycin could not only induce cell apoptosis,but it also increased the ratio of LC3B-Ⅱ/LC3B-Ⅰ in M21 cells. The increase and accumulation of autophagosomes were directly observed under transmission electron microscope. The level of p62 protein was slightly elevated after salinomycin treatment and gradually aggregated into the cytoplasm,indicating that autophagic flux was inhibited. Conclusion Salinomycin can inhibit the proliferation of human malignant melanoma M21 cells,and its mechanism may be related to the accumulation autophagosomes granules and inhibition of autophagic flux.
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Objective:To evaluate the efficacy and adverse reaction caused by Capecitabine compared with S-1 as maintenance treat-ments for patients with advanced gastric cancer (AGC) after first-line induction chemotherapy. Methods:A total of 130 AGC patients who did not suffer disease progression after first-line chemotherapies, including XELOX (four to six cycles), SOX (four to six cycles), and mFOLFOX6 regimen (six to eight cycles), were randomized into three groups. The Capecitabine group (Cap) received maintenance che-motherapy with Capecitabine (1 000 mg/m2 twice daily for 14 days, 21 days/cycle), while the S-1 group (S1) received S-1 (40, 50, or 60 mg according to the body surface area and orally administered twice a day for 14 days, 21 days/cycle). The control group was consid-ered as the observation group. Patients with maintenance treatments received drugs until disease progression or observation of intol-erant toxicity. Results:A total of 44, 33, and 53 patients received XELOX, SOX, and mFOLFOX6 regimens, respectively. The overall DCR was 63.1%. Among the 82 patients, 35, 28, and 19 belonged to the Cap, S1, and observation groups, respectively. The comparison be-tween the efficacy of treatments in the Cap and S1 groups did not show statistically significant differences (P=0.678). The median time of progression was 8.5 months in the Cap group and 9.0 months in the S1 group (P>0.05). Both groups showed better responses than the observation group, which demonstrated a median progression of 6.0 months (P<0.001). The median overall survivals were 14.5, 15.0, and 14.0 months in the Cap, S-1, and observation groups, respectively (P=0.188). The most common adverse effects observed among the patients with maintenance treatments included myelo-suppression, gastrointestinal reaction, fatigue, hand-foot syndrome, and stomatitis. No death occurred in relation to the therapy. Conclusion:The effectiveness of Capecitabine and S-1 as maintenance chemotherapies in AGC patients after the first-line induction chemotherapy are similar, and both can prolong the time of disease pro-gression with low toxicity.
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RT-PCR and Western blot were used to detect the LATS2 mRNA and protein level in 57 cases of oral squamous cell carcinoma (OSCC)specimens and 12 normal oral mucosa tissues.LATS2 mRNA and protein were expressed in all the normal oral mucosa samples (100%),but only 47.4% (27 /57)and 42.1% (24 /57)in OSCC samples respectively with positive correlation of both(P <0.01),and were respectively correlated with the tumor differentiation degree and lymph node metastasis(P <0.05).
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Background and purpose:EGFR-TKI (EGFR-tyrosine kinase inhibitors), represented by geiftinib and erlotinib, have exhibited signiifcant antiproliferative effects against non-small cell lung cancer (NSCLC) with low toxicity.EGFR gene mutation was discovered to be a predictive biomarker for EGFR-TKI treatment. Although the efifcacy of EGFR-TKI is limited toEGFR wild-type patients, it is still noticeable suggesting that some other mechanisms are responsible for it. The current study is aimed at evaluating the expression of phosphorylated EGFR in advanced NSCLC, investigating its relationship withEGFR mutations and EGFR-TKI efifcacy.Methods:EGFR gene mutations were detected by denaturing high performance liquid chromatography (DHPLC) in 205 stageⅢB-ⅣNSCLC patients. The expressions of phosphorylated tyrosine 1068 (pTyr1068) and 1173 (pTyr1173) were detected by immunohistochemistry.Results:The positive expressions of pTyr1068 and pTyr1173 were 80.0% (164/205) and 57.6% (95/165) respectively. None of them were related to clinical pathological characteristics (age, gender, pathological type, smoking status, disease stage).EGFR gene mutation rate was 44.9% (92/205), which was only related to smoking status (P=0.024) compared to other clinical pathological characteristics.EGFR gene mutations were poorly related to pTyr1068 expression (P<0.001) and not related to pTyr1173 expression (P=0.297). The objective response rate (ORR),disease control rate (DCR), and progressive free survival (PFS) of EGFR-TKI treatment in patients withEGFR mutations were 48.3% (43/89), 80.9% (72/89) and 8 months (95%CI: 6.11-11.42) respectively, which were signiifcantly higher than that ofEGFR wild-type patients [ORR=16.2% (17/105,P<0.001); DCR=56.2%(59/105,P<0.001); Median PFS: 2.1 months, (95%CI: 0.89-3.24;P=0.001)]. Superior ORR: DCR and PFS appeared in patients with pTyr1068 positive expression compared to negative [ORR: 37.7% (58/154)vs 5.0% (2/40,P<0.001); DCR: 74.7% (115/154)vs 40.0% (16/40,P<0.001); Median PFS: 7.0 monthsvs 1.2 months,P<0.001)]. Inversely, the patients with pTyr1173 positive expression had lower ORR, DCR and shorter PFS [ORR: 27.8% (25/90)vs 37.9%(25/66,P=0.123); DCR: 64.4% (58/90)vs 83.3% (55/66,P=0.007); Median PFS: 4.8 monthsvs 7.7 months (P=0.016)]. In subgroup ofEGFR wild-type patients, positive expression of pTyr1068 was 69.0% (69/100).EGFR wild-type patients with pTyr1068 positive expression had a prolonged PFS and elevated ORR and DCR compared to negative [median PFS: 3.6 monthsvs 1.2 months (P<0.001); ORR: 23.2%vs 3.2% (P=0.010); DCR: 69.6%vs 35.5% (P=0.001)]. Sixteen patients with pTyr1068 positive expression who responded to EGFR-TKI treatment in this subgroup had a remarkable PFS [median PFS: 15.6 months (95%CI:7.28-23.9)]. Multiple factor analysis showed that the expression of pTyr1068 was an independence predictor factor for EGFR-TKI treatment (OR=0.24, 95%CI: 0.16~0.37,P<0.001). Conclusion:Phosphorylation at Tyr1068 of EGFR might be a potential predictive factor for clinical response and survival of EGFR-TKI treatment in patients with advanced NSCLC, especially inEGFR wild-type patients.
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Objective To provide more convincing evidences and experimental data for exploring vanillin derivative BVAN08,6-bromine-5-hydroxy-4-methoxy-benzaldehyde,as a new anticancer drug,and to investigate the effect on the growth,radiosensitization of human glioma cell line U-251 and the relative mechanism.Methods The effect of BVAN08 on cell proliferation of U-251 and radiosensitivity to 60Co γ-rays (irradiation dose rate 2.3 Gy/min) were analyzed with MTT and colony-forming ability assay.Change in cellular morphology was observed by using light microscope.Change in cell cycle and apoptosis was detected with flow cytometry.The autophagy was observed by using TEM (irradiation dose rate is transmission electron microscope).DNA-PKcs protein level was detected through Western blot analysis.Results BVAN08 exhibited a dose- and time-dependent inhibition on the proliferation of U-251 cells during the concentration range of 10-100 mol/L (t = 1.83-3.07,P ＜ 0.05).IC50 at 48 h and 72 h after administration with BVAN08 were 55.3 and 52.7 mol/L,respectively.Obvious G2/M arrest was induced in U-251 cells after 4 h administration with BVAN08,and reached peak at 12 h.The G2/M population reached 63.3% in U-251 cells after 12 h administration of 60 μmol/L BVAN08 and kept increasing with the time,while both apoptosis and autophagic cell death were induced.The most effective radiosensitization time for BVAN08 treatment was 12 h before irradiation.The enhancement ratio of radiosensitivity was 3.14 for 20 μmol/L of BVAN08 12 h before 2 Gy irradiation.Conclusions BVAN08 can nduce apoptosis as well as autophygic cell death of U-251 cells,and sensitize U-251 cells.The mechanism of its radiosensitizing effect might be associated with the induction of G2/M arrest and inhibition of DNA-PKcs expression.BVAN08 seemed to be a romising radiosensitizing anticancer drug.
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Objective To construct a human phage single chain-antibody library, and to sieve out the antibody ScFv against lung cancer from the library. Methods Total RNA was abstracted from lymph node tissue of the lung cancer, and was used to amplify V_H and V_L gene by RT-PCR. V_H and V_L were joined by a DNA linker by SOE-PCR to form the single chain variable fragment ( ScFv) gene. ScFv gene was coloned into the phage vector pCANT-AB5E. Panning against lung cancer cell line A549 was performed and positive clones were chosen for soluble expression. Results A recombination phage single chain-antibody library was constructed. After 4 rounds panning, the number of eluted phages increased by 115 times. Positive reactions to A549 were detected in 7 of 10 random clones. The human ScFvs against lung cancer were produced and confirmed by SDS-PAGE and ELISA analysis. Conclusion ScFvs against lung cancer were acquired by the construction of phage single chain-antibody library. The soluble ScFvs has specificall avidity to human lung cancer cells.
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0.05).Conclusion Both PTX plus DDP and NVB plus DDP are effective to advanced breast cancer.There are no significant difference between the two groups.The two regimens can be applied to the first line chemotherapy.
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Objective To construct a human phage single chain-antibody library,and to sieve out the antibody ScFv against lung cancer from the library.Methods Total RNA was abstracted from lymph node tissue of the lung cancer,and was used to amplify VH and VL gene by RT-PCR. VH and VL were joined by a DNA linker by SOE-PCR to form the single chain variable fragment (ScFv) gene. ScFv gene was coloned into the phage vector pCANTAB5E. Panning against lung cancer cell line A549 was performed and positive clones were chosen for soluble expression.Results A recombination phage single chain-antibody library was constructed. After 4 rounds panning,the number of eluted phages increased by 115 times. Positive reactions to A549 were detected in 7 of 10 random clones. The human ScFvs against lung cancer were produced and confirmed by SDS-PAGE and ELISA analysis.Conclusion ScFvs against lung cancer were acquired by the construction of phage single chain-antibody library. The soluble ScFvs has specificall avidity to human lung cancer cells.
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Objective:To prepare EGF-coupling bovine serum albumin nano-carrier as a new way for initiative targeted drug delivery of epidermal growth factor receptor(EGFR) with broad range of expression in tumor cell. Methods:albumin nano-carrier was prepared by second phacoemulsification and solvent evaporation technology,and epidermal growth factor(EGF) was conjugated with albumin nano-carrier by chemical crosslinking reagents for EGF coupling bovine serum albumin nano-carrier. Results:The prepared nano-carrier then underwent isotope labeling,then the coupling effect of EGF and its coupling level were certified by sephadex column and polyacrylamide gel electrophoresis(SDS-PAGE). Conclusion:Success in the preparation of the smaller bovine serum albumin nano-carrier and EGF coupling bovine serium albumin nano-carrier establish the experimental foundation for further exploration of its targeting of tumor cells in vitro and distribution in vivo.
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Objective To evaluate the effects of radioimmunoimaging with 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb or combined application of both on nude mice bearing lung adenocarcinoma. Methods Animal model of nude mice bearing lung adenocarcinoma was established. The direct labeling method of 99Tcm was applied to labeling monoclonal antibodies for EGFR and CD44, and then the properties of the labeling antibodies purified by SephadexG50 Column were identified. The radio-immuno-image as well as body distribution concerning nude mice bearing lung adenocarcinoma was studied by application of 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb alone or combined application of both. Results The labeling rates of 99Tcm for EGFR-McAb and CD44-McAb were (91.5?3.8)% and (92.3?4.1)% respectively. Specific activities of the labeled antibodies were (2.8?0.3)MBq/g and (2.9?0.5)MBq/g, respectively. The rates of radiochemical purity were (96.5?2.8)% and (96.2?3.1)%, respectively. The tumor tissue had high intake of the two labeled antibodies according to radioimmunoimaging result. The radioactivity concentration of the combined application of the two labeled antibodies was obviously higher than that of the single application. The T/NT relative values measured through ROI technique were 5.58?0.46, 2.72?0.22, and 2.30?0.18, respectively. The body distribution result of the labeled antibodies and their imaging results were basically identical. Conclusion The optimal target and non-target ratios could be obtained by application of 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb alone in nude mice bearing lung adenocarcinoma. The target and non-target ratios could be enhanced through the combined application of the two antibodies.
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Objective To investigate the effect of Arsenic Trioxide(As_2O_3) combined with radiation on the apoptosis of nasopharyngeal carcinoma cells in vitro.Methods Using MTT and FCM to detect the cytotoxic and apoptosis at different As_2O_3 concentrations combined with 2Gy radiation on nasopharyngeal carcinoma cells(CNE1).Results Inhibition of cell proliferation seemed more dependent on the increase of As_2O_3 concentration.Cell survival rate was lower in the combination of As_2O_3 and radiation group than As_2O_3 alone.Conclusion As_2O_3 can enhance radiation effect obviously in nasopharyngeal carcinoma cells,especially at lower radiation dose.
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Purpose: The aim of the present study was to investigate the expression of breast cancer resistance protein (BCRP) in primary breast carcinoma and to determine whether such expression can predict survival. Methods: Expression of BCRP in 60 breast cancer patients was determined by immunohistochemistry on formalin-fixed, paraffin-embedded tumor section. The relationship between the expression of BCRP with the clinicphathological characteristics and the prognosis of breast cancer patients were also analyzed. Results: ①BCRP expression was observed in 21 of 60 (35%) cases.② BCRP expression was more frequently observed in patients with lymph node metastasis or hormone receptor (P 0. 05) .③Kaplan-Meier analyses revealed that BCRP expression associated only with disease-free survival (DFS) (P 0. 05) . ④In univariate and multivariate Cox regression analyses, tumor size, lymph node metastasis and estrogen receptor (ER) was associated with DFS and OS (P
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Objective In order to observe the dispersing form, the sustained release solid dispersion was prepared. Methods Sustained-release solid dispersion was prepared by taking ethyl cellulose as carrier. And the X-ray diffraction, differential scanning calotimetery (DSC) were used to evaluate the dispersing form of puerarin in the preparation and to study the solubility in vitro. Results The X-ray diffraction experiment showed that the puerarin was existed in molecuar and minicrystal form. DSC Experiment showed that there is no puerarin crystal in the solid dispersion. The test for stripping showed that thare was a better releasing results in the sustained-release capsula. Conclusion The sustained-release solid dispersion can disperse the puerarin highly to increase its bioavailability. The prepared capsula has a marked sustained-release effect.
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ObjectTo study the adsorptive properties of spherical activated carbon on some effective ingredients from Chinese materia medica (CMM) and to approach the application feasibility to CMM purification. Methods The spherical activated carbon with high strength has been successfully prepared by the carbonation and activation of polymeric resin. The apparent and theoretical adsorption capacities under the condition of static operation were investigated by Langmuir monolayer adsorption model. Elution by 75% alcohol was studied. Results The static adsorption capacities of the berberine hydrochloride and dioscin were 35.46 mg/g and 47.12 mg/g, and theoretical adsorption capacities were 96.16 mg/g and 102.04 mg/g, respectively. The apparent adsorption amount of rutin was 40.88% mg/g. The elution ratio were 83.71%, 91.45%, and 87.69%, respectively. Conclusion The spherical activated carbon adsorbent shows better comprehensive adsorption properties and can be used to purification.