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This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study. Reference: Jin-Cheng Zheng, Ke-Jie Chang, Yu-Xiang Jin, Xue-Wei Zhao, Bing Li, Meng-Hang Yang. Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling. Med Sci Monit 2019; 25:2228-2237. DOI: 10.12659/MSM.913091.
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Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots.
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Acorus , Tetraploidía , Filogenia , Diploidia , GenomaRESUMEN
INTRODUCTION: Small cell lung cancer (SCLC) is featured by a high TP53 mutant rate. Our previous research found that arsenic trioxide (As2O3) could significantly inhibit the growth and metastasis of SCLC. Studies have shown that the degradation of mutant p53 mediated by murine double minute 2 (MDM2) can be induced by As2O3, which probably contributes to the inhibition of SCLC, but the detailed mechanism is still unclear. We aimed to testify that As2O3 can inhibit the growth of SCLC cells by degrading mutant p53 protein via binding to MDM2. METHODS: CCK-8 assay, cell cycle analysis, and western blot of apoptosis markers were used to evaluate the inhibitory effect of As2O3 on NCI-H446 cells (containing mutant p53) and NCI-H1299 cells (p53 null). The effects of As2O3 on p53 and its downstream proteins were identified by western blot using mut-p53-knockdown and overexpressed cell models. MDM2-knockdown cell models were constructed, and western blot, co-IP of mut-p53, and ubiquitin were carried out to explore the mediating effect of MDM2 in As2O3 induced mut-p53 degradation. RESULTS: As2O3 inhibited proliferation and induced cell cycle arrest and apoptosis of SCLC cells in a dose- and timedependent manner. After mut-p53 knockdown or overexpressed, the inhibitory effect of As2O3 was dampened or enhanced. Additionally, As2O3-induced mut-p53 ubiquitination was significantly weakened after MDM2 knockdown. CONCLUSION: As2O3 could inhibit SCLC cells by inhibiting proliferation and inducing cell cycle arrest and apoptosis. These inhibitory effects were achieved at least in part by upregulating MDM2, which, in turn, promotes ubiquitination and degradation of mut-p53.
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Antineoplásicos , Arsenicales , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Animales , Ratones , Trióxido de Arsénico/farmacología , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Óxidos/farmacología , Óxidos/metabolismo , Óxidos/uso terapéutico , Arsenicales/farmacología , Arsenicales/metabolismo , Arsenicales/uso terapéutico , Línea Celular Tumoral , Apoptosis , Neoplasias Pulmonares/patología , Proliferación Celular , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/farmacología , Proteínas Proto-Oncogénicas c-mdm2/uso terapéuticoRESUMEN
Drug-resistant advanced lung adenocarcinoma (LUAD) is an aggressive malignancy with limited treatment options. A therapeutic strategy for drug-resistant LUAD is to target the tumor associated macrophages (TAMs), because they play an important role in tumor immune escape, progression and metastasis. In this study, we conducted in vivo and in vitro investigation of the inhibitory effect of arsenic trioxide (ATO) on polarization of TAMs educated by LUAD. We found that ATO at a concentration of 4 µM disrupted the Notch-dependent positive feedback loop between LUAD and TAMs. In this loop, ATO inhibited the expression of Jagged1 and Notch1 in LUAD and suppressed M2 polarization via down-regulating Notch-dependent paracrine of CCL2 and IL1ß. As a result, the secretion of M2-derived TGF-ß1 decreased, thus inducing inhibitions of LUAD proliferation, migration, invasion, colony formation and epithelial-mesenchymal transition. In xenograft mouse models, ATO significantly inhibited tumor growth and down-regulated infiltration of M2-like TAMs in tumor tissues. In clinical LUAD biopsy samples, high Jagged1/Notch1 expression positively correlated with tumor-infiltrated M2-like TAMs, leading to poor prognosis. In conclusion, our results identified a novel tumor immunomodulating function for ATO, which can inhibit the polarization of M2-type TAMs to exert anti-tumor effects in the tumor microenvironment. Our results demonstrated the translational potential of repurposing ATO to target TAMs for lung adenocarcinoma treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Animales , Ratones , Macrófagos Asociados a Tumores/metabolismo , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/farmacología , Macrófagos , Transducción de Señal , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Currently, the use of targeted drugs such as tyrosine kinase inhibitors (TKIs) plays an important role in clinical therapy. As the number of approved TKIs continues to increase, existing analysis methods will not be able to meet the growing needs, and will hamper the development of therapeutic drug monitoring (TDM) of TKIs. Based on LC-MS/MS technology, this study tends to develop and validate a multi-component analysis method for simultaneous determination of the concentrations of 39 TKIs in plasma. Spiked plasma was blended with isotope labelled internal standards, and injected into the LC-MS/MS system after protein precipitation by acetonitrile. Chromatographic separation was achieved using an ODS-4 column with gradient elution of formic acid/water (1:1000; v/v) and acetonitrile. Analytes detection was conducted in positive ionisation mode using MRM. The total run time was 8 min. The method validation was conducted by assessing the following parameters: selectivity, linearity and the lower limit of qualification, accuracy and precision, stability, matrix effect and recovery. The concentrations of 39 TKIs showed good linearity within the range of their respective standard curves in plasma, the accuracy of all quality control samples ranged from 85.9% to 114.1%, and the precision was lower than 13.3%. The extraction recovery ranged from 92.6% to 114.7%, and the matrix effect of plasma was lower than 11.3%. This new method was successfully developed, can be used for the determination of drug concentrations in multiple patients with different kinds of TKIs, and will therefore be suitable for TDM of 39 TKIs.
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Inhibidores de Proteínas Quinasas , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los ResultadosRESUMEN
Orchidaceae is one of the largest, most diverse families in angiosperms with significant ecological and economical values. Orchids have long fascinated scientists by their complex life histories, exquisite floral morphology and pollination syndromes that exhibit exclusive specializations, more than any other plants on Earth. These intrinsic factors together with human influences also make it a keystone group in biodiversity conservation. The advent of sequencing technologies and transgenic techniques represents a quantum leap in orchid research, enabling molecular approaches to be employed to resolve the historically interesting puzzles in orchid basic and applied biology. To date, 16 different orchid genomes covering four subfamilies (Apostasioideae, Vanilloideae, Epidendroideae, and Orchidoideae) have been released. These genome projects have given rise to massive data that greatly empowers the studies pertaining to key innovations and evolutionary mechanisms for the breadth of orchid species. The extensive exploration of transcriptomics, comparative genomics, and recent advances in gene engineering have linked important traits of orchids with a multiplicity of gene families and their regulating networks, providing great potential for genetic enhancement and improvement. In this review, we summarize the progress and achievement in fundamental research and industrialized application of orchids with a particular focus on molecular tools, and make future prospects of orchid molecular breeding and post-genomic research, providing a comprehensive assemblage of state of the art knowledge in orchid research and industrialization.
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Containing the largest number of species, the orchid family provides not only materials for studying plant evolution and environmental adaptation, but economically and culturally important ornamental plants for human society. Previously, we collected genome and transcriptome information of Dendrobium catenatum, Phalaenopsis equestris, and Apostasia shenzhenica which belong to two different subfamilies of Orchidaceae, and developed user-friendly tools to explore the orchid genetic sequences in the OrchidBase 4.0. The OrchidBase 4.0 offers the opportunity for plant science community to compare orchid genomes and transcriptomes and retrieve orchid sequences for further study.In the year 2022, two whole-genome sequences of Orchidoideae species, Platanthera zijinensis and Platanthera guangdongensis, were de novo sequenced, assembled and analyzed. In addition, systemic transcriptomes from these two species were also established. Therefore, we included these datasets to develop the new version of OrchidBase 5.0. In addition, three new functions including synteny, gene order, and miRNA information were also developed for orchid genome comparisons and miRNA characterization.OrchidBase 5.0 extended the genetic information to three orchid subfamilies (including five orchid species) and provided new tools for orchid researchers to analyze orchid genomes and transcriptomes. The online resources can be accessed at https://cosbi.ee.ncku.edu.tw/orchidbase5/.
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MicroARNs , Orchidaceae , Orden Génico , Bases del Conocimiento , MicroARNs/genética , Orchidaceae/genética , SinteníaRESUMEN
BACKGROUND: Anti-angiogenesis therapy mostly aimed at targeting vascular endothelial growth factor (VEGF) and its receptors have been widely applied to lung cancer. However, the improvement in the patient's overall survival remains dissatisfying. Previously, we demonstrated that arsenic trioxide (As2O3) exerts an anti-lung cancer effect through anti-angiogenesis, but the details of the mechanism in play remain unclear. Herein, we focused on the calcineurin-NFAT pathway, downstream of VEGF, and its endogenous inhibitor DSCR1. OBJECTIVE: To demonstrate the mechanism of As2O3 restraining lung cancer growth and metastasis by blocking the calcineurin-NFAT pathway by upregulating DSCR1. METHODS: We constructed xenografts and metastasis models based on wild-type (WT) and DSCR1 knockout (DSCR1-/-) mice, and carried out qPCR, Western blot, immunohistochemistry, in vivo imaging and calculated microvessel density to evaluate the effects of As2O3 on angiogenesis, tumor growth, metastasis, and the protein expression levels of DSCR1 and calcineurin-NFAT pathway-related molecules. RESULTS: As2O3 inhibited tumor growth and metastasis, reduced microvessel formation, and induced vascular lumen malformation in WT mice. At the protein level, As2O3 upregulated DSCR1, downregulated NFAT2 and its downstream molecules, but had no effect on calcineurin A. However, in DSCR1-/- mice, the above-mentioned effects of As2O3 were abolished. CONCLUSION: As2O3 can suppress lung cancer growth and metastasis through anti-angiogenesis effects by blocking the calcineurin-NFAT pathway by upregulating DSCR1. The results shed light on the antitumor mechanism of As2O3 and are a step forward in the identification of As2O3 as a new drug in the treatment of lung cancer.
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Antineoplásicos , Trióxido de Arsénico , Calcineurina , Neoplasias Pulmonares , Factores de Transcripción NFATC , Inhibidores de la Angiogénesis , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Trióxido de Arsénico/farmacología , Trióxido de Arsénico/uso terapéutico , Calcineurina/metabolismo , Proteínas de Unión al Calcio/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones , Proteínas Musculares/genética , Factores de Transcripción NFATC/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Reactive oxygen species (ROS), as primary intermediates formed during photocatalytic reactions, are critical for a photocatalyst to realize high activity. The major objective of this study was to investigate the regulation of ROS involved in the photocatalytic degradation process via constructing a typical metal-semiconductor hybrid heterojunction using Ag nanoparticles/anatase TiO2 as an example. Based on radical capturing, electron paramagnetic resonance, and electron spin resonance experiments, an increase in the available ROS can be achieved in the Ag/TiO2 heterojunction due to the fast separation of photogenerated carriers. In addition, due to the change in the electron transfer pathway, superoxide radicals (·O-2) are the dominant reactive species responsible for dye degradation using Ag/TiO2 rather than hydroxyl radicals (·OH) as the main free radicals in pristine TiO2. This study offers fresh insight into the regulation of ROS in photodegradation via the construction of a Ag/TiO2 heterojunction.
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BACKGROUND The inhibitory effect of arsenic trioxide (As2O3) on lung cancer has been reported in some preclinical studies. However, its effect on small cell lung cancer (SCLC) has been poorly explored. Calcineurin and its substrate, nuclear factor of activated T cells (NFAT), mediate the downstream signaling of VEGF, and is critical in the process endothelium activation and tumor metastasis. In this study, we aimed to evaluate whether As2O3 had inhibitory effects on endothelial cells activation and the metastasis of SCLC, and to explore the possible mechanisms. MATERIAL AND METHODS In vitro, human umbilical vein endothelial cells (HUVECs) were used. Cell Counting Kit-8 assay and cell migration assay were performed to determine the effect of As2O3 on HUVECs proliferation and migration. The level of calcineurin, NFAT, downstream factors for Down syndrome candidate region 1 (DSCR1), and the endogenous inhibitor of calcineurin, were evaluated by quantitative PCR and western blotting. In vivo, SCLC metastasis models were established by injecting NCI-H446 cells into tail veins of nude mice. Tumor-bearing mice were treated with As2O3 or calcineurin inhibitor for 10 days, after which tumor metastasis in target organs was evaluated. RESULTS As2O3 significantly inhibited the proliferation and migration of endothelial cells. Also, As2O3 inhibited the expression levels of calcineurin, NFAT, and the downstream target genes CXCR7 and RND1, while it upregulated the level of DSCR1. Both As2O3 and calcineurin inhibitor exhibited notable inhibitory effect on the metastasis of SCLC, without obvious side effects. CONCLUSIONS These findings suggested that As2O3 had remarkable inhibitory effects on the endothelial cell activation and SCLC metastasis, and the mechanism might be related to the blocking of calcineurin-NFAT signaling by upregulating DSCR1.
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Trióxido de Arsénico/farmacología , Factores de Transcripción NFATC/efectos de los fármacos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Animales , Trióxido de Arsénico/metabolismo , Calcineurina/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , China , Proteínas de Unión al ADN , Endotelio Vascular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intracelular/efectos de los fármacos , Masculino , Ratones , Ratones Desnudos , Proteínas Musculares/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Metástasis de la Neoplasia/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Receptores CXCR/efectos de los fármacos , Transducción de Señal , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Proteínas de Unión al GTP rho/efectos de los fármacosRESUMEN
Ultra-weak bioluminescence (UWL) is a physiological phenomenon widely existing in all the biological activities including human, animals, plants, etc., which reflects the energy metabolism of the organism. Since the last century, ultra-weak photon emission (UPE) has been applied to the study of the essence of meridians and acupoints of traditional Chinese medicine and obtained some results as the higher luminescence characteristics, but many problems remain unsolved due to the limitation of detection technology. In recent years, along with the development of bioluminescence signal acquiring system and imaging system, we are able to further explore the characteristics and biological mechanisms of UWL of acupuncture points and meridians in the human body. We proposed to study changes of ultra-weak luminous intensity of acupuncture points and meridians before and after needling stimulation, and the delayed effect of UPE phenomenon, etc., trying to reveal their regularities and essence. In this paper, the prospect of application of UPE to acupuncture research is also discussed by combining newly acquired results of some biological substances of acupoints in experimental studies.
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Terapia por Acupuntura , Meridianos , Puntos de Acupuntura , Humanos , LuminiscenciaRESUMEN
Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-ß, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As2O3. These findings suggested that anti-angiogenesis may be an underlying mechanism of As2O3 anticancer activity in lung cancer.
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Two new ursane-type triterpenoid saponins, bodiniosides M (1) and N (2), along with three known saponins, oblonganosides I (3), pseudobuxussaponin B (4) and bodinioside A (5), were isolated from the aerial parts of Elsholtzia bodinieri. The structures of compounds 1 and 2 were characterized by spectroscopic data as well as acid hydrolysis and GC analysis as 3-O-ß-D-xylopyranosyl-19α-hydroxy-23-acetoxy-urs-12(13)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1-2)-ß-D-glucopyranoside and 3-O-ß-D-glucopyranosyl-2α,19α-dihydroxy-urs-12(13)-en-28,20ß-lactone. Compounds 1 and 5 exhibited potent anti-HCV activities in vitro with a selective index of 6.53 and 4.41, respectively.
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Antivirales/aislamiento & purificación , Descubrimiento de Drogas/métodos , Lamiaceae/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Animales , Antivirales/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Estructura Molecular , Componentes Aéreos de las Plantas/química , Saponinas/farmacología , Triterpenos/farmacologíaRESUMEN
BACKGROUND: To investigate the similarities and differences of laparoscopic complete mesocolic excision (CME) to a colon resection with a D3 lymphadenectomy for the stage II/III left-sided colon carcinoma. METHODS: Patients between July 2011 and August 2014 were randomized into D3 and CME groups. Mesenteric area, log odds of positive lymph nodes (LODDS), and other operative parameters were collected and assessed. RESULTS: The average specimen sizes were 5730 ± 828 mm(2) in superior rectal artery (SRA)-preserving D3, 8145 ± 1022 mm(2) in SRA-nonpreserving D3, and 8745 ± 1039 mm(2) in the CME group; the differences were significant (P < .0001). The number of lymph nodes collected from CME specimens was larger, but the CME specimens did not contain an elevated value of LODDS or positive nodes or lymph node ratio (LNR). There were also no significant differences between recovery times of bowel function. Although it took more operation time in D3 approach, especially in SRA-preserving D3 operation, the difference was not significant. Concerning the leakage rate (P = .34) and vessel-related complications (P = .64), there were no significant differences either. CONCLUSIONS: Both standard D3 resection and CME could achieve a high quality of mesocolic plane grade for stage II/III colon cancer. The LODDS and LNR were comparable, and those were not relevant to mesenteric size.
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Colectomía , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Laparoscopía/métodos , Escisión del Ganglio Linfático , Mesocolon/cirugía , Anciano , Colectomía/efectos adversos , Colon/fisiopatología , Femenino , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Arteria Mesentérica Inferior/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Tempo Operativo , Estudios Prospectivos , Recuperación de la Función , Recto/fisiopatología , Carga TumoralRESUMEN
Mo-doped zinc oxide (ZnOâ¶Mo) films were deposited with direct current magnetron sputtering on quartz substrates at room temperature. The effects of Mo doping content on the crystal structure, surface microstructureï¼optical properties and plasmon characteristics of the ZnO films were investigated with X-ray diffraction(XRD),atomic force microscopy (AFM),Spectrophotometer and Raman spectrometer. The XRD pattern reveals that pure ZnO film exhibits good crystallization and c-axis oriented while heavy doping leads to increasing film defects. That results decline the film crystalline quality. When Mo doping content exceeds 3.93 Wt%, the ZnO films transform c-axis oriented into amorphous. The AFM pattern indicates that the surface of amorphous MZO film is extraordinarily flat. The Rq is 498 pm. The transmittance spectra reveal that all samples have an average transmittance of 80% in the visible light range. The optical band gap energy (Eg) increases from 3.28 to 3.60 eV as the Mo doping content increase. The absorbance spectrum indicates that ZnO surface plasmon resonance absorbance perk moves to short-wavelength as the Mo doping content increase. The Raman spectrum suggests that heavy Mo doping make the Raman scattering intensity decrease significantly. This paper obtains amorphous ZnO thin film by Mo doping. That broadens the application field of ZnO thin film materials. Meanwhile, we study the effect of Mo doping concentration on ZnO thin films surface plasmon, which provides important reference value for the preparation of oxidized zinc base photonic devices.
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AIM: To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer. METHODS: All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively. RESULTS: There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphological characteristics of schistosomiasis combined with rectosigmoid cancer could be found by colonoscopic examination: 46% were fungating mass polyps, 23% were congestive and ulcerative polyps, 23% were cauliflower-like masses, 8% were annular masses. Only 27% of the patients were diagnosed with rectal carcinoma preoperatively after the biopsy. Computed tomography (CT) scans showed thickened intestinal walls combined with linear and tram-track calcifications in 26 patients. CONCLUSION: Rectosigmoid carcinoma combined with schistosomiasis is associated with higher CA-125 values and early tumor stages. CA-125 and CT scans have a reasonable sensitivity for the accurate diagnosis.
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Parasitosis Intestinales/parasitología , Neoplasias del Recto/parasitología , Schistosoma/aislamiento & purificación , Neoplasias del Colon Sigmoide/parasitología , Anciano , Animales , Biopsia , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Colonoscopía , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Neoplasias del Recto/sangre , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Neoplasias del Colon Sigmoide/sangre , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/cirugía , Tomografía Computarizada por Rayos XRESUMEN
The aim of the study was to investigate the mechanism of arsenic trioxide (As2O3) in the treatment of malignant pleural effusion (MPE) caused by pleural metastasis of lung cancer. A mouse model of MPE caused by pleural metastasis of lung cancer was first established, and As2O3 was then intraperitoneally injected to treat the MPE. Mice treated with bevacizumab and bleomycin were included as positive controls, and placebo equivalents were also used as negative controls. The effects of As2O3 on MPE volume, pleural vessel density, vascular permeability, expression of angiogenic function-related factors, including vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α), as well as nuclear factor-κB (NF-κB) activity in pleural carcinomatosis, were observed. Intraperitoneal injection of As2O3 reduced the volume of MPE and decreased vascular density and permeability in pleural metastatic nodules in a dose-dependent manner. Moreover, dose-dependent decreases in VEGF and TNF-α expression in MPE, and NF-κB activity in pleural carcinomatosis, were also found after As2O3 treatment. We showed that As2O3 can down-regulate VEGF expression via inhibition of NF-κB, and decrease vascular density and permeability in pleural metastatic nodules, thereby eliciting its effects on MPE caused by pleural metastasis of lung cancer. Our results provide a foundation for an As2O3-based clinical treatment program.
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Arsenicales/farmacología , Neoplasias Pulmonares/patología , Óxidos/farmacología , Derrame Pleural Maligno/tratamiento farmacológico , Animales , Trióxido de Arsénico , Arsenicales/uso terapéutico , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Microvasos/efectos de los fármacos , Microvasos/metabolismo , FN-kappa B/metabolismo , Metástasis de la Neoplasia , Óxidos/uso terapéutico , Permeabilidad/efectos de los fármacos , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patología , Derrame Pleural Maligno/fisiopatología , Carga Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
This study investigated the impact of laparoscopic rectal cancer resection for patients with high operative risk, which was defined as American Society of Anesthesiology (ASA) grades III and IV. This study was conducted at a single center on patients undergoing rectal resection from 2006 to 2010. After screening by ASA grade III or IV, 248 patients who met the inclusion criteria were identified, involving 104 open and 144 laparoscopic rectal resections. The distribution of the Charlson Comorbidity Index was similar between the two groups. Compared with open rectal resection, laparoscopic resection had a significantly lower total complication rate (P<.0001), lower pain rate (P=.0002), and lower blood loss (P<.0001). It is notable that the two groups of patients had no significant difference in cardiac and pulmonary complication rates. Thus, these data showed that the laparoscopic group for rectal cancer could provide short-term outcomes similar to those of their open resection counterparts with high operative risk. The 5-year actuarial survival rates were 0.8361 and 0.8119 in the laparoscopic and open groups for stage I/II (difference not significant), as was the 5-year overall survival rate in stage III/IV (P=.0548). In patients with preoperative cardiovascular or pulmonary disease, the 5-year survival curves were significantly different (P=.0165 and P=.0210), respectively. The cost per patient did not differ between the two procedures. The results of this analysis demonstrate the potential advantages of laparoscopic rectal cancer resection for high-risk patients, although a randomized controlled trial should be conducted to confirm the findings of the present study.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Adulto , Anciano , China , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Arsenic trioxide (As2O3) has been used in the clinic for the treatment of acute promyelocytic 1eukemia and some solid tumors. However, its effectiveness against lung cancer has not been well demonstrated, and the underlying mechanism(s) of action remain unclear. In the present study, we found that As2O3 significantly inhibited the growth of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) xenograft tumors. It was observed to have antiangiogenic effects in xenograft models and matrigel pellets. It also significantly inhibited the expression of VEGF-A, VEGFR-2, HIF-1α, Dll4 and Notch-1 in vivo. Moreover, As2O3 also inhibited the expression of HIF-1α, VEGFR-2, Dll4, and Notch-1 in lung cancer cell lines and human umbilical vein endothelial cells. These findings suggest that As2O3 has significant anti-lung cancer activity, which may occur as a result of the antiangiogenic effects caused by the downregulation of the VEGF and Dll4-Notch signaling pathways.
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Inhibidores de la Angiogénesis/farmacología , Arsenicales/farmacología , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica , Óxidos/farmacología , Proteínas Adaptadoras Transductoras de Señales , Animales , Trióxido de Arsénico , Proteínas de Unión al Calcio , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Receptor Notch1/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Video-assisted thoracic surgery (VATS) has been recommended as more optimal surgical technique than traditional thoracotomy for lobectomy in lung cancer, but it is not well defined. Here, we compared VATS and traditional thoracotomy based on clinical data. From November 2008 to November 2010, 180 patients underwent lobectomy for non-small-cell lung cancer (NSCL) identified by computerized tomography. Of them, 83 cases were performed with VATS and 97 by thoracotomy. Clinical parameters, consisting of blood loss, operating time, number of lymph node dissection, days of pleural cavity drainage, and length of stay were recorded and evaluated with t test. No significant difference was observed between the VATS and thoracotomy groups in the average intraoperative blood loss, number of lymph node dissections, and days of pleural cavity drainage. While the average operating time in the VATS group was significantly longer than that in thoracotomy group, recurrence was only present in one case, as opposed to 7 cases in the thoracotomy group In conclusion, similar therapeutic effects were demonstrated in VATS and thoracotomy for NSCL. However, VATS lobectomy was associated with fewer complications, recurrence and shorter length of stay.