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Objective: To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC). Methods: Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison. Results: Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Conclusion: Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients' OS and PFS, enabling timely prognostic assessment.
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OBJECTIVE: To investigate the value of the left lateral decubitus position in laparoscopic right posterior lobe tumor resection. PATIENTS AND METHODS: The clinical data of patients who underwent laparoscopic right posterior lobectomy from January 2020 to March 2023 were retrospectively collected and divided into group A (left lateral decubitus position group, n=30) and group B (conventional position group, n=35) according to different body positions. Intraoperative and postoperative data were collected and compared between the 2 groups. RESULTS: The operation time (210.43±57.56 vs. 281.97±65.89, t =5.887, P <0.05), hilar occlusion time (23.97±14.25 vs. 35.79±12.62, t =4.791, P <0.05), intraoperative blood loss (162.14±72.61 vs. 239.65±113.56, t =5.713, P <0.05), postoperative feeding time (1.13±0.36 vs. 1.57±0.67, t =3.681, P <0.05), postoperative visual analog scale score (5.16±0.89 vs. 7.42±1.31, t =3.721, P <0.05), postoperative abdominal drainage tube indwelling time (4.58±1.34 vs. 5.42±1.52, t =4.553, P <0.05), incidence rate of complications (43.33% vs. 82.86%, χ 2 =11.075, P <0.05) in group A were lower than those in group B ( P <0.05). Symptoms/side effects (32.42±3.42 vs. 27.44±3.31, t =4.331, P <0.05), and there were significant differences in social function (33.55±2.56 vs. 29.31±3.32, t =4.863, P <0.05). CONCLUSION: For right posterior lobe tumors of the liver, the left lateral decubitus position has many advantages in laparoscopic right posterior lobectomy, such as a wide field of view, simple steps, a short operation time, less bleeding, and a high postoperative quality of life. It is an effective treatment for right posterior lobe tumors of the liver and is worthy of being widely popularized.
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Laparoscopia , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Qualidade de Vida , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a kind of systemic autoimmune disease, and the joint inflammation and cartilage destruction are the major features. Some traditional Chinese medicine have been discovered to exhibit regulatory roles in the treatment of RA. Forsythiaside A (FA) as an active ingredient isolated from forsythia suspensa has been discovered to participate into the regulation of some diseases through improving inflammation. However, the regulatory effects of FA on the progression of RA keep indistinct. METHODS: IL-1ß treatment (10 ng/mL) in MH7A cells was built to mimic RA in vitro (cell) model. The cell viability was examined through CCK-8 assay. The cell proliferation was detected through Edu assay. The levels of TNF-α, IL-6, and IL-8 were evaluated through ELISA. The protein expressions were measured through western blot. The cell apoptosis was assessed through flow cytometry. The cell migration and invasion abilities were tested through Transwell assay. RESULTS: In this study, it was revealed that the cell proliferation was strengthened after IL-1ß treatment (p < .001), but this effect was reversed after FA treatment in a dose-increasing manner (p < .05). Furthermore, FA suppressed inflammation in IL-1ß-triggered MH7A cells through attenuating the levels of TNF-α, IL-6, and IL-8 (p < .05). The cell apoptosis was lessened after IL-1ß treatment (p < .001), but this effect was rescued after FA treatment (p < .05). Besides, the cell migration and invasion abilities were both increased after IL-1ß treatment (p < .001), but these changes were offset after FA treatment (p < .05). Eventually, FA retarded the JAK/STAT pathway through reducing p-JAK/JAK and p-STAT/STAT levels (p < .01). CONCLUSION: Our study manifested that FA exhibited anti-migration and anti-inflammation effects in RA in vitro model (IL-1ß-triggered MH7A cells) through regulating the JAK/STAT pathway. This work hinted that FA can be an effective drug for RA treatment.
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Artrite Reumatoide , Glicosídeos , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Janus Quinases/metabolismo , Janus Quinases/farmacologia , Janus Quinases/uso terapêutico , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/farmacologia , Fatores de Transcrição STAT/uso terapêutico , Inflamação/metabolismo , Proliferação de Células , Fibroblastos/metabolismoRESUMO
Acidic oxygen evolution reaction (OER) remains a significant challenge due to the low activity and/or poor stability of the catalysts, even with state-of-the-art catalysts such as IrO2 and RuO2. Herein, we propose a strategy to enhance both the catalytic activity and stability of IrRu oxides for acidic OER by doping non-noble metal W. The W-doped IrRu3Ox (W-IrRu3Ox) undergoes a process of W leaching and reconstruction during the OER, leading to a more uniform distribution of elements, while the electronegative nature of W influences the electronic structures of Ir and Ru in W-IrRu3Ox. The dual role of W in promoting the formation of active site Ir5+ and inhibiting the concentration of soluble Ru>4+ ions results in a synergistic enhancement of both the activity and stability of acidic OER. Remarkably, W-IrRu3Ox exhibits outstanding catalytic activity for the OER in 0.5 M H2SO4, with a high stability of more than 500 h. This work presents a novel and feasible strategy for the development of efficient and stable catalysts for acid OER, shedding light on the design of advanced electrocatalysts for energy conversion and storage applications.
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Background: Numerous researches have reported that long noncoding RNAs (lncRNAs) participate in tumor development and progression. LncRNA apolipoprotein C-I pseudogene 1 (APOC1P1), a pseudogene located in 19q13.2 between apolipoprotein C-I and apolipoprotein C-IV, is involved in a variety of diseases. However, the role of lncRNA APOC1P1 in hepatocellular carcinoma (HCC) remains unknown. Methods: Quantitative polymerase chain reaction (qPCR) was performed to examine the expression of APOC1P1, miR-106b, and PTEN (phosphatase and TENsin homolog deleted on chromosome 10) in HCC tissues, adjacent normal tissues, and specific cell lines (LO2, Bel-7407, HCCLM3, MHCC-97H, Hep G2, and Huh-7). Upregulation of APOC1P1 and downregulation of miR-106b were conducted via application of vector transfection and microRNA (miRNA) inhibitor. Bioinformatics analysis and luciferase reporter assay were used to verify the binding sites of APOC1P1, miR-106b, and PTEN. Cell proliferation and invasion were determined with Cell Counting Kit-8 (CCK-8) and Transwell experiments. Subcellular location analysis was used to determine the distribution of APOC1P1 in cells, and Western blotting was used to detect the expression of PTEN. Results: It was found that the expressions of APOC1P1 and PTEN were downregulated, while that of miR-106b was upregulated in HCC tissues and cells. Subcellular location analysis showed that APOC1P1 was localized in cytoplasm and competitively bound to miR-106b. APOC1P1 overexpression and miR-106b inhibition suppressed HCC cell proliferation and invasion. qPCR indicated the negative correlation between APOC1P1 expression and miR-106b expression in HCC tissues and a positive correlation between APOC1P1 and PTEN. Conclusions: Our findings suggested that the lncRNA APOC1P1 inhibits HCC progression by competitively binding to miR-106b, leading to elevated PTEN expression, inhibiting cell proliferation and invasion in HCC cells. These results provide new insights into the diagnosis and therapy of HCC.
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Immunotherapy is the most promising treatment for hepatocellular carcinoma (HCC). However, the immunosuppressive microenvironment and necrosis limit its therapeutic effectiveness. Carbon nanotubes (CNTs) have good tissue permeability and can penetrate tumor necrosis area. Here we constructed a Durvalumab/CNT/PEI/ aptamer-siRNA chimera (chimera/Durmab/CNT) nanoparticles for the immunotherapy of HCC. In vivo and in vitro experiments showed that aptamer-siRNA chimeras could specifically bind HCC cells and inhibit the triggering receptor expressed on myeloid cells-2 (Trem2) expression, but had no effect on Trem2 expression in normal liver and lung. Transmission electron microscope (TEM) results showed that the CNT/PEI nanoparticles were 20-30 nm in diameter and 200-350nm in length. Dense PEI attachment can be observed on CNTs. CNT/PEI nanoparticles could control the sustained release of Durvalumab for 48 hours. In vitro experimental results showed that chimera/Durmab/CNT could increase the proportion of T cells and CD8+T cells, and then promote the apoptosis of HepG2 cells, and the therapeutic effect was superior to aptamer/Durmab/CNT and Durmab/CNT. We constructed a tumor-bearing mouse model, and the results showed that chimera/Durmab/CNT significantly inhibited the growth of transplanted tumor, and the volume and proliferation was further reduced in the chimera/Durmab/CNT group compared with the aptamer/Durmab/CNT group. T cells and CD8+T cells infiltration, and HCC cell apoptosis were significantly increased in the chimera/Durmab/CNT group. In conclusion, we constructed a Durvalumab/CNT/PEI/chimera, which can effectively treat HCC by activating anti-tumor immunity.
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The ability to regulate charge separation is pivotal for obtaining high efficiency of any photoelectrode used for solar fuel production. Vacancy engineering for metal oxide semiconductor photoelectrode is a major strategy but has faced a formidable challenge in bulk charge transport because of the elusive charge self-trapping site. In this work, a new deep eutectic solvent to engineer bismuth vacancies (Bivac ) of BiVO4 photoanode is reported; the novel Bivac can remarkably increase the charge diffusion coefficient by 5.8 times (from 1.82 × 10-7 to 1.06 × 10-6 cm2 s-1 ), which boosts the charge transport efficiency. Through further loading CoBi cocatalyst to enhance charge transfer efficiency, the photocurrent density of BiVO4 photoanode with optimal Bivac concentration reaches 4.5 mA cm-2 at 1.23 V vs reversible hydrogen electrode under AM 1.5 G illumination, which is higher than that of previously reported Ovac engineered BiVO4 photoanode where the BiVO4 photoanode is synthesized by a similar procedure. This work perfects a cation defect engineering that enables the potential capability to equate the charge transport properties in different types of semiconductor materials for solar fuel conversion.
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OBJECTIVE: To investigate the expression of long non-coding RNA LINC01279 in gastric cancer and its relationship with the clinicopathological features and prognosis of gastric cancer patients. METHODS: Serum, gastric cancer and adjacent tissue samples from 90-patients with gastric-cancer treated by surgery and serum samples from 90-healthy adults were collected. The expression level of LINC01279 was analyzed by RT-PCR. The clinical baseline data of gastric cancer patients were obtained. Correlation between the expression level of LINC01279 and the clinicopathological characteristics of gastric cancer patients was assessed. RESULTS: LINC01279 was highly expressed in gastric cancer tissues and serum of gastric cancer patients (P < 0.05). The expression level of lncRNA 01279 was closely related to vascular invasion, nerve invasion, T-stage, lymph node metastasis, and advanced clinical-stage of gastric cancer (P < 0.05). The expression level was not correlated with gender, age, tumor size, location, and differentiation. There was a significant negative correlation between the expression of LINC01279 and the overall survival of gastric-cancer patients (P < 0.05). CONCLUSION: LINC01279 is highly expressed in gastric-cancer tissues and serum, which is closely related to tumor-invasion. Serum LINC01279 is a better prognostic indicator of invasive cancer than current tumor markers.
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Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Adenocarcinoma/genética , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Humanos , Metástase Linfática , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVES: The aim of the current study was to identify the long noncoding RNAs (lncRNAs) ANRIL function and molecular pathways underlying hepatocellular carcinoma progression. METHODS: ANRIL knockdown with specific siRNA, and transfected into HepG2 cells according to the protocol of Lipofectamine 2000. Cell proliferation, apoptosis, migration and metastasis were assessed with MTT assay, flow cytometry and wound healing assay, respectively. Moreover, the expression level of ANRIL, apoptosis-related genes, and the Wnt pathway-associated genes were assessed by real time-PCR and Western blot assay. KEY FINDINGS: Knocking down of ANRIL led to alleviated cell growth and increased cell apoptosis of HepG2 cells through markedly increased expression levels of Bax and Bad. In contrast, dramatically diminished the expressions of anti-apoptotic factors including Bid and Bcl-2 in comparison to the scrambled control group (si-NC). Furthermore, ANRIL silencing resulted in an inactivated Wnt/ß-catenin pathway by suppressing key genes associated with this pathway. CONCLUSIONS: Taken together, these findings imply new insights into the regulatory network of the Wnt pathway through lncRNA ANRIL that indicate ANRIL may be a therapeutic factor potential for hepatocellular carcinoma.
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Apoptose , Carcinoma Hepatocelular , Inativação Gênica , Neoplasias Hepáticas , RNA Longo não Codificante , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ensaios de Migração Celular/métodos , Proliferação de Células , Sobrevivência Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes/métodos , Genes bcl-2/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Análise de Sequência de RNA , Via de Sinalização Wnt/genética , Proteína de Morte Celular Associada a bcl/genéticaRESUMO
Designing skin decontaminating materials with outstanding therapeutic effects, adhesiveness, and suitable mechanical property has great practical significance in radionuclide-contaminated skin wound healing. Here, a physically crosslinked hydrogel is constructed via hydrogen bonding of poly acrylamide, sodium alginate (SA), and the complexing agent diethylene triamine pentaacetic acid (DTPA). The physical and chemical properties of the poly(AAm-SA-DTPA) hydrogel (PASD) are detected according to established methods. The decontaminating property and skin wound healing of the PASD are investigated to confirm multi-functions of wound dressing. The physical and chemical properties results show that the synthesis of the PASD hydrogel is effective and that DTPA is present in the hydrogel. The hydrogel also shows great mechanical and swelling properties. In vitro tests find that PASD shows significant scavenging abilities for strontium and cerium. In vivo experiments show that the PASD hydrogel can remove radioactive strontium from the skin wounds of mice, and can effectively prevent the absorption of radioactive strontium through the skin wound. Furthermore, the PASD hydrogel can effectively promote the formation of granulation tissue in a radioactive contaminated wound. Taken together, the PASD hydrogels, which has good mechanical properties and radionuclides decontamination, is expected to be used as a dressing for radionuclide-contaminated skin wound healing.
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Descontaminação/métodos , Hidrogéis , Radioisótopos/isolamento & purificação , Pele/lesões , Ferimentos e Lesões , Resinas Acrílicas/química , Alginatos/química , Animais , Animais não Endogâmicos , Ligação de Hidrogênio , Camundongos , Estresse Oxidativo , Ácido Pentético/análise , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização , Ferimentos e Lesões/metabolismoRESUMO
Solar water splitting is one of the most efficient technologies to produce H2, which is a clean and renewable energy carrier. Photoanodes for water oxidation play the determining roles in solar water splitting, while its photoelectrochemical (PEC) performance is severely limited by the hole injection efficiency at the interface of semiconductor/electrolyte. To address this problem, in this research, by employing BiVO4 as the model semiconductor for photoanodes, we develop a novel, facile, and efficient method, which simply applies K cations in the preparation process of BiVO4 photoanodes, to in situ induce a crystalline-amorphous heterophase junction by the formation of an amorphous BiVO4 layer (a-BiVO4) on the surface of the crystalline BiVO4 (c-BiVO4) film for PEC water oxidation. The K cation is the key to stimulate the formation of the heterophase, but not incorporated in the final photoelectrodes. Without sacrificing the light absorption, the in situ formed a-BiVO4 layer accelerates the kinetics of the hole transfer at the photoanode/electrolyte interface, leading to the significantly increased efficiency of the surface hole injection to water molecules. Consequently, the BiVO4 photoanode with the crystalline-amorphous heterophase junction (a-BiVO4/c-BiVO4) exhibits almost twice the photocurrent density at 1.23 V (vs reversible hydrogen electrode) for water oxidation than the bare c-BiVO4 ones. Such advantages from the crystalline-amorphous heterophase junction are still effective even when the a-BiVO4/c-BiVO4 is coated by the cocatalyst of FeOOH, reflecting its broad applications in PEC devices. We believe this study can supply an efficient and simple protocol to enhance the PEC water oxidation performance of photoanodes, and provide a new strategy for the potential large-scale application of the solar energy-conversion related devices.
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A host-guest complex self-assembled through Co2+ and cucurbit[5]uril (Co@CB[5]) is used as a supramolecular catalyst on the surface of metal oxides including porous indium tin oxide (ITO) and porous BiVO4 for efficient electrochemical and photoelectrochemical water oxidation. When immobilized on ITO, Co@CB[5] exhibited a turnover frequency (TOF) of 9.9â s-1 at overpotential η=550â mV in a pHâ 9.2 borate buffer. Meanwhile, when Co@CB[5] complex was immobilized onto the surface of BiVO4 semiconductor, the assembled Co@CB[5]/BiVO4 photoanode exhibited a low onset potential of 0.15â V (vs. RHE) and a high photocurrent of 4.8â mA cm-2 at 1.23â V (vs. RHE) under 100â mW cm-2 (AMâ 1.5) light illumination. Kinetic studies confirmed that Co@CB[5] acts as a supramolecular water oxidation catalyst, and can effectively accelerate interfacial charge transfer between BiVO4 and electrolyte. Surface charge recombination of BiVO4 can be also significantly suppressed by Co@CB[5].
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N-type silicon is a kind of semiconductor with a narrow band gap that has been reported as an outstanding light-harvesting material for photoelectrochemical (PEC) reactions. Decorating a thin catalyst layer on the n-type silicon surface can provide a direct and effective route toward PEC water oxidation. However, most of catalyst immobilization methods for reported n-type silicon photoanodes have been based on energetically demanding, time-consuming, and high-cost processes. Herein, a high-performance NiFeP alloy (NiFeP)-decorated n-type micro-pyramid silicon array (n-Si) photoanode (NiFeP/n-Si) was prepared by a fast and low-cost electroless deposition method for light-driven water oxidation reaction. The saturated photocurrent density of NiFeP/n-Si can reach up to â¼40 mA cm-2, and a photocurrent density of 15.5 mA cm-2 can be achieved at 1.23 VRHE under light illumination (100 mW cm-2, AM1.5 filter), which is one of the most promising silicon-based photoanodes to date. The kinetic studies showed that the NiFeP on the silicon photoanodes could significantly decrease the interfacial charge recombination between the n-type silicon surface and electrolyte.
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A novel flame-assisted deposition (FAD) method was used to generate and immobilize cobalt oxide (CoOx) on the surface of fluorine-doped tin oxide (FTO) and TiO2 modified hematite (TiO2/Fe2O3) for electrochemical and photoelectrochemical (PEC) water oxidation, respectively, with significant performance.
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Chemotherapy is the best choice for the vast majority of hepatocellular carcinoma patients at late stage, but few effective chemotherapy drugs are available in clinic. Licochalcone A (LicA) is a new chemotherapy drug inducing apoptosis as Bcl-2 inhibitor, but few studies report on LicAinduced autophagy. This study investigated the phenomenon and mechanisms of LicA-induced autophagy looking for a targeted combination drug. Human hepatocellular carcinoma cells (HCCs) were treated with LicA, to detect markers of autophagy and to investigate the mechanisms. In order to investigate the role of reactive oxygen species (ROS) in LicAinduced autophagy, ROS, glutathione (GSH) and O2- were measured in LicA treated HCCs, and antioxidant N-Acetyl-L-cysteine (NAC) was cotreated with LicA in HCCs, then mechanisms of ROS-induced autophagy was investigated in LicA or LicA combined with NAC treated HCCs. Finally, the LicA-induced apoptosis was detected in LicA combined with NAC treated HCCs. We first report that LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, suppression of LicA-induced ROS through antioxidant NAC can enhance LicA-induced apoptosis, promoting the function of LicA killing HCCs. LicA can activate the ULK1/Atg13 complex which is upstream of autophagy, additionally, LicA also can promote ROS generation, ROS trigger the expression level of TSC1/2 complex, PRAS40, CTMP, PP2A, PDK1 and Rubicon change, these molecules are upstream of autophagy. In conclusion, LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, LicA combined with NAC can enhance LicA-induced apoptosis. Our results may provide a novel design for clinical hepatocellular carcinoma therapy trials.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Chalconas/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the therapeutic effect and safety of high-intensity focused ultrasound (HIFU) therapy combined with gemcitabine in treating unresectable pancreatic carcinoma. METHODS: The 45 patients suffering from pancreatic carcinoma were randomized into two groups. The patients in the experimental group (n=23) received HIFU in combination with gemcitabine and those in the control group (n=22) received gemcitabine alone. The effect and clinical benefit rates in the two groups were compared. The median survival time and 6-month and 12-month survival rates were calculated by Kaplan-Meier method and log-rank test. RESULTS: The median survival time and 6-month survival rate were significantly higher in the experimental group than in the control group (8.91 months vs 5.53 months, 73.9% vs 40.9%, respectively P<0.05), but 12-month survival rate was not statistically different between the two groups (13.0% vs 4.5%, P>0.05). The clinical benefit rates in the experimental group and the control group were 69.6% and 36.3%, respectively (P<0.05). The pain remission rate in the experimental group was significantly higher than that in the control group (65.2% vs 31.8%, P<0.05). CONCLUSION: HIFU in combination with gemcitabine is better than gemcitabine alone. This combinatorial therapy may become a better and effective treatment for unresectable pancreatic carcinoma.
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BACKGROUND AND OBJECTIVES: Currently, extended resection and preoperative neoadjuvant chemotherapy are the two main modalities for improvement of the resection rate and R0 resection rate of borderline resectable pancreatic cancer. The past few years, however, have witnessed some progress in the treatment of unresectable pancreatic cancer with high intensity focused ultrasound (HIFU). The aim of this study is twofold: first, to evaluate the feasibility and safety of HIFU ablation as a preoperative adjuvant therapy for borderline resectable pancreatic cancer, and second, to conduct pathological analyses to verify the safety and effectiveness of HIFU treatment of pancreatic cancer. METHODS: From January 2011 to December 2012, 30 patients with borderline resectable pancreatic cancer underwent HIFU ablation by Haifu Model-JC200 Focused Ultrasound Tumor Therapeutic System prior to radical surgery. The effect of pre-operative HIFU ablation was evaluated by post-HIFU functional imaging results, operation time of radical surgery, blood loss volume, R0 resection rate, postoperative 1-year survival rate and Ca199 curve. Postoperative pathological specimens were obtained for histological examination. RESULTS: All 30 patients with borderline resectable pancreatic cancer had completed the treatments and follow-ups. Functional image assessment after HIFU treatment showed a mean tumor ablation rate of (61.5±24.3)%. 28 patients underwent radical resection of pancreatic cancer 7-9 days after HIFU treatment (23 cases underwent pancreaticoduodenectomy. 4 patients underwent pancreatectomy and 1 patient had total pancreatectomy). 7 patients underwent combined resection and reconstruction of portal-superior mesenteric vein (23.3%), with the resectability rate of 93.3%, the R0 resection rate of 92.7%, and the 1-year survival rate of 96.7%. The biological coagulative necrosis regions identified by the postoperative pathological examination matched well with the necrosis foci identified by post-operative functional imaging. CONCLUSION: The effectiveness of HIFU ablation of pancreatic tumors, as well as interstitial tissues within he main vascular spaces was confirmed by post-operative pathological examinations. Based on these observations, we conclude that preoperative HIFU ablation of borderline resectable pancreatic cancer can significantly improve the resection rate, R0 resection rate, and reduce the difficulty and risk of surgery. Therefore, HIFU may be a valuable pre-operative adjunct therapy for resectable pancreatic cancer. However, the safety and the efficacy on the improvement of the surgery need to established with future multicenter, randomized studies.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias Pancreáticas/cirurgia , Período Pré-Operatório , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Cuidados Paliativos , Neoplasias Pancreáticas/patologiaRESUMO
The influence of specific blocking of the Delta-like ligand 4 (DLL4)/Notch signal transduction pathway on the biological behavior of human umbilical vein endothelial cells (HUVECs) has been studied. Recombinant adeno-associated virus (rAAV) vectors expressing an active small interfering RNA (siRNA) (vector 6) targeting the DLL4 (rAAV-DLL4-short hairpin RNA [shRNA]) was used to infect HUVECs. The same cell line infected with empty plasmid (rAAV-EGFP) was used as a control. Stable transfection and expression of DLL4-mRNA in HUVECs were determined by semiquantitative RT-polymerase chain reaction (PCR). Protein expression of DLL4 was examined by western blotting. The distribution of cells in cell cycle was assessed by flow cytometry and cell growth was analyzed by MTT assay. HUVECs were seeded on type I collagen and cultured in a three-dimensional culture system to allow for tubule-like structure (TLS) formation. Compared with negative controls, semiquantitative RT-PCR and western blot analysis showed that the expression of DLL4 mRNA and protein was downregulated in stably transfected cells (p = 0.024, p = 0.033). HUVEC growth and proliferation were stimulated following infection with rAAV vectors containing active siRNA against DLL4, whereas infection with empty plasmid had no specific effect. The proliferation index of rAAV-DLL4-shRNA-infected HUVECs was 39.90% +/- 2.19% compared with 25.63% +/- 4.54% (p = 0.036) for control-treated cells. TLS formation was significantly induced in cells expressing the rAAV vector; the average length of TLS was greater than the control group (p = 0.028). Altogether, the data suggest that inhibiting the DLL4/Notch signal transduction pathway stimulated proliferation of HUVECs, thereby facilitating angiogenesis.
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Proliferação de Células , Endotélio Vascular/citologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/genética , Proteínas Adaptadoras de Transdução de Sinal , Western Blotting , Proteínas de Ligação ao Cálcio , Ciclo Celular , Células Cultivadas , Dependovirus/genética , Regulação para Baixo , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neovascularização Fisiológica , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Receptores Notch/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Veias Umbilicais/citologiaRESUMO
Vascular endothelial growth factor (VEGF) is overexpressed in colorectal cancer (CRCs) cells and plays a critical role in angiopoiesis and cell proliferation, making it a potential target for cancer therapy. We developed a system that blocks VEGF in the human colorectal cancer cell line, HCT116, using RNA interference. By transfecting CRCs with the small interfering RNA (siRNA) that targets human VEGF, we were able to establish a stable clones in which VEGF expression was significantly downregulated (p<0.01). This resulted in the decreased proliferation of HCT116 cells in vitro and suppressed the size of subcutaneous (s.c.) tumors and the microvessel density in an HCT116 s.c. nude mouse xenograft model in vivo (p<0.01). These results suggest that a strategy based on siRNA targeting of VEGF may build the foundation to the clinical management of CRC.