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PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.
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Medios de Contraste , Compuestos Férricos , Hierro , Neoplasias Renales , Imagen por Resonancia Magnética , Óxidos , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Ultrasonografía/métodos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Diagnóstico Diferencial , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Natural orifice specimen extraction surgery (NOSES) is currently widely used in left-sided colorectal cancer. Some clinical comparative studies have been conducted, providing evidence of its safety and oncological benefits. However, these studies are typically characterized by small sample sizes and short postoperative follow-up periods. Consequently, in this research, the authors adopt the propensity score matching method to undertake a large-scale retrospective comparative study on NOSES colectomy for left-sided colorectal cancer, with the goal of further augmenting the body of evidence-based medical support for NOSES. METHODS: This retrospective study involved patients who underwent NOSES colectomy and conventional laparoscopic (CL) colectomy for left-sided colorectal cancer between January 2014 and April 2021. In the NOSES group, specimens were extracted through the anus with the help of a Cai tube (homemade invention: ZL201410168748.2). The patients were matched at a ratio of 1:1 according to age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, preoperative CEA. After matching, 132 patients in the NOSES group and 132 patients in the CL group were eligible for analysis. RESULTS: Compared with CL group, NOSES group was associated with decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000), less additional analgesia required (6.8 vs. 34.8%, P=0.000), faster time to passage of flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000), less wound infection (0.0 vs. 6.1%, P=0.007), and longer operative time (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). No significant differences were observed in estimated blood loss, time to resume regular diet, postoperative hospital stay, conversion to open surgery or conventional minilaparotomy, total morbidity, readmission, mortality, pathologic outcomes, and Wexner incontinence score between groups. After a median follow-up of 63.0 months, the 5-year overall survival rates were 88.3 versus 85.0% (P=0.487), disease-free survival rates were 82.9 versus 83.6% (P=0.824), and the local recurrence rates were 4.4 versus 4.0% (P=0.667) in the NOSES and CL groups, respectively. CONCLUSIONS: This study suggests that NOSES colectomy using a Cai tube for left-sided colorectal cancer is a safe and feasible option with better cosmetic results, less pain, faster recovery of gastrointestinal function, and comparable long-term clinical and oncologic outcomes to CL colectomy.
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Neoplasias Colorrectales , Laparoscopía , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Laparoscopía/efectos adversos , Laparoscopía/métodos , Dolor Postoperatorio , Neoplasias Colorrectales/cirugía , Colectomía/efectos adversos , Colectomía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The role of laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) colectomy in the treatment of left-sided colon cancer has not been well defined, and there remains confusion about how to conveniently exteriorize specimens through natural orifices. Therefore, we introduced a homemade invention, the Cai tube, to facilitate the extraction of specimens and compared the clinical outcomes of LA-NOSE with conventional laparoscopic (CL) colectomy for left-sided colon cancer. METHODS: From March 2015 to August 2017, patients with left-sided colon cancer were randomly divided into LA-NOSE and CL groups. Specimens were extracted through the anus with the help of a Cai tube (Patent Number: ZL201410168748.2) in the LA-NOSE group. The primary outcome measure was postoperative pain. Secondary outcomes were the duration of operation, postoperative recovery, surgical morbidity, pathological quality of the specimen, and long-term outcomes, including 3-year overall survival, disease-free survival, local recurrence, and overall recurrence. RESULTS: A total of 60 patients (30 per group) were recruited for this study. None of the patients required emergency conversion to conventional laparoscopic or open surgery during the operation. The postoperative maximum pain score was significantly lower in the LA-NOSE group (mean 2.5 vs. 5.1, P = 0.001), as was the additional analgesia requirement (mean 2/30 vs. 10/30, P = 0.021). Patients in the LA-NOSE group experienced a shorter first time to passage of flatus (mean 2.2 vs. 3.1 days, P = 0.026). All patients could control their defecation at 6 months after surgery. The comparison between the two groups showed no significant differences in the operative time, bleeding volume, postoperative hospital stay, surgical morbidity rates, number of lymph nodes harvested, or resection margin status. The mean follow-up was 48 months (range 7-59) and was similar in both groups. The results showed no differences in long-term outcomes between the two groups. CONCLUSION: In the treatment of left-sided colon cancer, compared with conventional laparoscopic colectomy, LA-NOSE colectomy using the Cai tube exhibited lower postoperative pain, shorter recovery of gastrointestinal function, and similar long-term outcomes. REGISTRATION NUMBER: ChiCTR-OOR-15007060 ( http://www.chictr.org.cn/ ).
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Neoplasias del Colon , Laparoscopía , Cirugía Endoscópica por Orificios Naturales , Humanos , Estudios Prospectivos , Neoplasias del Colon/cirugía , Dolor Postoperatorio/etiología , Colectomía/métodos , Laparoscopía/métodos , Resultado del Tratamiento , Cirugía Endoscópica por Orificios Naturales/métodosRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using 1H nuclear magnetic resonance (NMR). METHODS: Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls. RESULTS: Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples. CONCLUSIONS: Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.
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Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Líquido Folicular/metabolismo , Metabolómica , Espectroscopía de Resonancia Magnética , Aminoácidos/metabolismoRESUMEN
Peimine (PM), a natural product extracted from Fritillaria, has anti-inflammatory, drug resistance reversal, and other pharmacological effects. The purpose of this study was to investigate the antitumor effects and the molecular mechanisms of PM using gastric cancer MKN-45 cells. Cell counting kit-8 assays were used to evaluate the viability of gastric cancer cells after treatment with PM. The results showed that PM significantly reduced the activity of gastric cancer cells, and the effect was most obvious in MKN-45 cells. Annexin V-FITC/propidium iodide staining and flow cytometry were used to assess apoptosis of MKN-45 cells after PM treatment. Our results showed that PM-induced apoptosis of MKN-45 cells. Flow cytometry was also used to determine the mitochondrial membrane potential and reactive oxygen species (ROS) levels, and to assess PM-induced cell-cycle arrest. Additionally, Western blot was used to analyze the expression of signaling pathway proteins and the relationship between apoptosis and ROS accumulation. Our findings showed that PM destroyed the mitochondria by diminishing the mitochondrial membrane potential. In addition, PM regulated the mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3, and nuclear factor kappa-B signaling pathways by promoting the accumulation of ROS in MKN-45 cells. PM also caused cell-cycle arrest in the G2/M phase by increasing ROS accumulation. Furthermore, PM inhibited cell migration by regulating the Wnt/ß-catenin pathway. In conclusion, PM plays an anticancer role through endogenous apoptosis pathways and by inhibiting cell migration, and it has the potential to be a useful treatment for gastric cancers.
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Factor de Transcripción STAT3 , Neoplasias Gástricas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismo , FN-kappa B/metabolismo , Neoplasias Gástricas/metabolismo , Vía de Señalización Wnt , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/farmacología , Línea Celular Tumoral , ApoptosisRESUMEN
This study aimed to identify more biomarkers associated with osteosarcoma progression via lncRNA-mRNA co-expression network. Dataset GSE99671 was downloaded from GEO database. The mRNAs and lncRNAs that were differentially expressed between tumor and normal samples were screened out. Functional enrichment analysis of differentially expressed mRNAs was carried out, followed by weighted gene correlation network analysis (WGCNA). Based on the lncRNAs and mRNAs, a lncRNA-mRNA co-expression network was constructed. Total 703 mRNAs and 7 lncRNAs were differentially expressed between tumor and normal tissues. The mRNAs were significantly enriched in functions associated with inflammatory response as well as autoimmune thyroid disease and ribosome pathways. WGCNA revealed that ME2 module had a high correlation with tumor, and ST3GAL4, UCK2, PSAT1 etc. had higher connectivity degrees in this module. lncRNA-mRNA co-expression network showed that 12 mRNAs, such as PEMT, COL10A1 and GSTA1, were synergistically expressed with lncRNA TTTY14. Inflammatory response and ribosome synthesis may play important role in osteosarcoma progression. lncRNA TTTY14 may affect the development of osteosarcoma by cooperative expression with PEMT, COL10A1, GSTA1, etc. ST3GAL4, UCK2, PSAT1 as well as TTTY14 may serve as key biomarkers in osteosarcoma.
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Neoplasias Óseas , Osteosarcoma , ARN Largo no Codificante , Perfilación de la Expresión Génica , Humanos , Osteosarcoma/genética , ARN Largo no Codificante/genética , ARN Mensajero/genéticaRESUMEN
Reactive oxygen species (ROS) play both deleterious and beneficial roles in cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse origins, being its gene over-expression in solid tumors or frequent mutations in hematological malignancies. However, the role and regulatory mechanism of NPM in oxidative stress are unclear. Here, we found that NPM regulated the expression of peroxiredoxin 6 (PRDX6), a member of thiol-specific antioxidant protein family, consequently affected the level and distribution of ROS. Our data indicated that NPM knockdown caused the increase of ROS and its relocation from cytoplasm to nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co-immunoprecipitation further confirmed the interaction between PRDX6 and NPM. Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization, decreased PRDX6 and significantly upregulated ROS. These observations demonstrated that the expression and localization of NPM affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J. Cell. Biochem. 118: 4697-4707, 2017. © 2017 Wiley Periodicals, Inc.
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Antioxidantes/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Estrés Oxidativo , Peroxiredoxina VI/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Humanos , Indoles/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Proteínas Nucleares/genética , Nucleofosmina , Peroxiredoxina VI/antagonistas & inhibidores , Peroxiredoxina VI/genéticaRESUMEN
Nucleophosmin(NPM), heavily implicated in diverse solid tumors, is an important multifunctional protein mainly located in the nucleolus. Our previous study confirmed that NPM can also localize and accumulate in the cytoplasm of liver cancer cells. However, the role of cytoplasmic NPM (NPMc +) is unclear. Here, we showed that both nucleolar NPM and NPMc+ could promote cell proliferation, although the effect of NPMc+ was weaker than that of NPM. Cell adhesion ability of hepatoma cells was significantly reduced to a greater extent by NPMc+ expression. Nucleolar NPM enhanced cell migration and invasion, whereas NPMc+ impeded cell migration and invasion. The investigation of NPM interactional proteins by proteomic method demonstrated that the NPM was involved in multiple biological processes. By contrast, the interactional proteins of NPMc+ were mainly implicated in tRNA amino acylation regulation. The interactional network of NPMc+ was significantly small and simple. These results suggested that relocation of NPM altered its interactional network and consequently disturbed the primary functions, including cell proliferation, adhesion, migration, and invasion. NPM plays a promotional role in cancer and the reducing relocation may be a potential therapeutic target for hepatocellular carcinoma. J. Cell. Biochem. 118: 3225-3236, 2017. © 2017 Wiley Periodicals, Inc.
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Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Carcinoma Hepatocelular/patología , Adhesión Celular , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , Nucleofosmina , Transporte de ProteínasRESUMEN
BACKGROUND: During development, methylation permanently changes gene activity, while aberrant gene methylation is key to human tumorigenesis. Gene methylation is an epigenetic event leading to gene silencing and some tumor suppressor genes that are aberrantly methylated in both thyroid cancer and benign thyroid tumor, suggesting a role for methylation in early thyroid tumorigenesis. Specific gene methylation occurs in certain types of thyroid cancer and depends on particular signaling pathways. Most reports rely on data from varied samples that vary tremendously with respect to methylation. RESULTS: We observed that hyperplastic/malignant (H/M) thyroid tissue and benign/manligant (B/M) tissue had the most profoundly methylated loci compared to hyperplastic/benign (H/B) tissue. These loci are mapped to 863 genes (|Δß value|â>â0.15) in B/M and 1082 genes (|Δß value|â>â0.15) in H/M. After bioinformatic analysis, these genes were found to be involved in T-cell receptor signaling pathway (B/M) and Jak-Stat signaling pathways (H/M). CONCLUSION: Our study offers the most comprehensive DNA methylation data for thyroid disease to date, using 1 patient with 3 tissue types and high-resolution 450K arrays. Our data may lay the foundation for future identification of novel epigenetic targets or diagnosis of thyroid cancer.
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Metilación de ADN , Glándula Tiroides/patología , Neoplasias de la Tiroides/genética , Dermatoglifia del ADN , Exones , Regulación Neoplásica de la Expresión Génica , Humanos , Hiperplasia/genética , Quinasas Janus/genética , Regiones Promotoras Genéticas , Receptores de Antígenos de Linfocitos T/genética , Transducción de Señal , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/metabolismoRESUMEN
In this study, a Pb-Sn alloy nanowire of 80 nm in diameter and 50 microm in length is obtained by an anodic aluminum oxide nanomold and vacuum die casting method. The upper and lower ends of the prepared Pb-Sn alloy nanowire array are vapor deposited with 3 microm of copper thin film, which serves as the conductive layer of the gas sensor. Experimental results show that the sensitivities of 3 gas sensors fabricated by 3 different Sn-Pb alloy nanowire arrays, namely Sn70%-Pb 30% wt, Sn63%-Pb 37% wt and Sn50%-Pb 50% wt, for detecting a carbon monoxide concentration of 500 ppm under a working temperature of 250 degrees C, were 17.83%, 14.89% and 14.12% respectively.
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In order to solve the problem of on-site rapid detection of salbutamol residues in feed and animal products, and develop a new method of fast detection of salbutamol on the basis of the molecular imprinting technology, this article uses the salbutamol (SAL) working as template molecule, methacrylic acid (MAA) working as functional monomer. On this basis, a new type of core-shell type salbutamol molecularly imprinted polymers were prepared with colloidal gold particles as triggering core. Superficial characteristics of the MIPs and the related compounds were investigated by ultraviolet (UV) spectra and infrared (IR) spectra, Raman spectra, Scanning electron microscopy (SEM) respectively. The results indicated that a stable hydrogen bonding complex has been formed between the carboxyl groups of SAL and MA with a matching ratio of 1:1. The complex can be easily eluted by the reagent containing hydrogen bonding. The chemical binding constant K reaches -0.245 x 106 L² · mol⻲. The possible binding sites of the hydrogen bonding was formed between the hydrogen atoms of -COOH in MA and the oxygen atoms of C==O in SAL. IR and Raman spectrum showed that, compared with MA, a significant red shift of -OH absorption peak was manifested in MIPs, which proved that SAL as template molecule occurred a specific bond between MA. Red shift of stretching vibration absorption peak of C==O was also detected in the un-eluted MIPs and obvious energy loss happened, which demonstrated a possible binding sites is SAL intramolecular of C==O atom of oxygen. If the hydrogen atoms of -COOH in MA wanted to generate hydrogen bond. However, the shapes of absorption peak of other functional groups including C==C, C==O, and -OH were very similar both in MIPs and NIPs. Specific cavities were formed after the template molecules in MIPs were removed. It was proved by the adsorption experiment that the specific sites in these cavities highly match with the chemical and space structure of SAL. Besides, colloidal gold type core-shell molecularly imprinted polymers have looser surface, more cavities in the surface compared with ordinary molecularly imprinted polymers, which increased the effective area of adsorption to target molecules. So it have better performance in adsorption. Based on the principle that these cavities can specificly recognize and combine with target molecule in the test sample, and the excellent ability of colloidal gold core-shell molecularly imprinted polymers, the development of novel methods for fast determination of SAL based on the molecular imprinting technology can be expected in the near future.
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Albuterol/química , Impresión Molecular , Polímeros/química , Análisis EspectralRESUMEN
Palisaded encapsulated neuroma (PEN) is an uncommon, typically solitary, cutaneous neural neoplasm. Multiple mucocutaneous neuromas are usually seen in multiple endocrine neoplasia (MEN) 2b syndrome. Multiple cutaneous PEN in adult patients with or without features of MEN 2b are extremely rare, with only a few cases described. We report a case of multiple PEN in siblings of the same family with no apparent systemic abnormalities, and review the relevant published work to explore its clinical and pathogenic features and the relationship between multiple PEN and MEN 2b type neuroma (multiple mucocutaneous neuromas seen in MEN 2b syndrome).
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Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neuroma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Actinas/metabolismo , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Antígeno MART-1/metabolismo , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2b/sangre , Neoplasias Primarias Múltiples/sangre , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Primarias Múltiples/patología , Neuroma/sangre , Neuroma/metabolismo , Neuroma/patología , Proteínas S100/metabolismo , Hermanos , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
The observation that prolonged inflammation plays a causative role in cancer development has been well documented. However, an incremental process that leads from healthy to malignant phenotypes has not yet been described. Experimentally induced hepatocellular carcinoma is considered one of the representative laboratory models for studying this process. Hepatic exposure to viral infection or toxic reagents leads to chronic inflammation and gradual transformation into hepatocellular carcinoma. Here we present metabolomic profiles of hepatic cells at different stages during inflammation-induced cellular transformation by N-nitrosodiethylamine. Using gas chromatography-mass spectrometry, we quantitatively assessed the changes in cellular metabolites during the transformation process in hepatitis and liver cirrhosis. Further pathway analysis of the differentially expressed metabolites showed that carbohydrate metabolism and lipid metabolism were greatly altered in hepatitis and liver cirrhosis, respectively. Additionally, the enhanced inflammation in cirrhosis was associated with a shift from carbohydrate metabolism to lipid and amino acid metabolism. Among the differentially expressed metabolites found in diseased mouse livers, d-glucose and d-mannitol showed the most significant changes, highlighting them as potential early-diagnostic biomarkers of hepatocellular carcinoma development. Taken together, these investigations into the dynamic metabolic changes that occur during the precancerous stages of hepatocellular carcinoma add to and refine understanding of how chronic inflammation ultimately leads to cancer. Furthermore, the findings set the stage for identifying metabolites that may serve as early-diagnostic indicators of these unfolding events.
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Transformación Celular Neoplásica/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Metabolómica/métodos , Animales , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Transformación Celular Neoplásica/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Análisis por Conglomerados , Dietilnitrosamina , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hepatitis Animal/inducido químicamente , Hepatitis Animal/metabolismo , Humanos , Inflamación/genética , Lipopolisacáridos , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Metaboloma/efectos de los fármacos , Ratones Endogámicos C57BL , Pirrolidinas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TiocarbamatosRESUMEN
INTRODUCTIONS: Phospho-PRAS40(Thr246) (phosphorylated proline-rich Akt substrate of 40 kilodaltons at Thr246) is a biomarker for phosphatidylinositol 3-kinase (PI3K) pathway activation and AKT inhibitors sensitivity. MATERIAL AND METHODS: In this study, we immunohistochemically investigated the expression of phospho-PRAS40(Thr246) in 141 gastric cancer tumors, and evaluated its clinicopathological and prognostic significance. RESULTS: Sixty-four cases (45.4%) were defined as phospho-PRAS40(Thr246) positive. Phospho-PRAS40(Thr246) correlated positively with lymph node metastasis, lymphatic infiltration, vascular infiltration and shorter survival. Furthermore, phospho-PRAS40(Thr246) is an independent prognostic factor for gastric cancer. CONCLUSIONS: Our data suggest that phospho-PRAS40(Thr246) was frequently expressed in gastric cancers, and correlated with malignant progression and poor prognosis of patients. PI3K pathway-targeted therapies should be considered in the future treatment of gastric cancers.
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BACKGROUND: Although hepatectomy is often performed with the Pringle maneuver, the problem of hepatic ischemia-reperfusion injury (HIRI) can also be serious. Thus, the present study was designed to investigate the protective effect of S-adenosylmethionine (SAMe) on HIRI, especially for patients with hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection and cirrhosis. METHODS: Eighty-one HCC patients with chronic HBV infection, undergoing partial hepatectomy with inflow occlusion, were divided into three groups. In the pretreatment group (PR group, n = 26), patients were given SAMe two hours before surgery. In the post-treatment group (PO group, n = 25), patients were given SAMe six hours after surgery. And in the control group (control group, n = 30), patients received partial hepatectomy without any SAMe. All pre-, intra- and postoperative blood samples were collected to measure the plasma levels of transaminases, bilirubin and cytokines. The results were compared among the three groups. RESULTS: There were no statistically significant intergroup differences observed in age, gender, hepatic inflow occlusion time and the results of liver function tests. Preoperative administration of SAMe (PR group) significantly reduced the plasma levels of alanine transaminase (ALT), aspartate transferase (AST), total bilirubin (TBIL) and direct bilirubin (DBIL) as compared to the other two groups. In the PO group, TBIL and DBIL were significantly lower than in the control group. Significant differences were also seen in IL-6 and TNF-α between the PR group and the other groups. In all groups, postoperative liver reserve function in the PR group as revealed by ICGR15 (Post ICGR15) was at its best before abdominal closure. Compared to the control group, the risk of complications and the hospital stay after surgery were significantly meliorated in the PR group. Additionally, patients with cirrhosis had a more acute rate of change in ALT and AST than non-cirrhotic patients. CONCLUSIONS: Taken together, our preliminary findings suggest that preoperative administration of SAMe is useful and safe for reducing the HIRI in partial hepatectomy, especially for HCC patients whose disease is associated with chronic HBV infection and cirrhosis.
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Carcinoma Hepatocelular/cirugía , Hepatectomía/efectos adversos , Hepatitis B/cirugía , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/cirugía , Daño por Reperfusión/tratamiento farmacológico , S-Adenosilmetionina/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/virología , Femenino , Estudios de Seguimiento , Hepatitis B/complicaciones , Hepatitis B/virología , Virus de la Hepatitis B/patogenicidad , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/virología , Pruebas de Función Hepática , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismoRESUMEN
The study investigated the extraction process of active ingredients from akebia stem and an analysis of their anti-gastric cancer activity. Three different extraction methods were used to obtain extracts, namely the decoction method (group A), reflux extraction method (group B), and maceration method (group C), of which reflux extraction method and maceration method used ethanol as the extraction solvent, while decoction method used distilled water for extraction. The differences in anti-gastric cancer activity of the three extracts were compared. MTT assay was used to test and compare the inhibitory effects of extracts obtained in A, B, and C groups on gastric cancer cells. The results showed that the dry extract obtained by heat reflux extraction with "water-ethanol" ratio of 1:2, extractant volume of 70 ml, with ethanol as extraction solvent presented the best inhibitory activity on gastric cancer SGC-7901 cells in this study. Its inhibitory effect did not change over time, and was directly proportional to the concentration.
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Antineoplásicos Fitogénicos/uso terapéutico , Magnoliopsida/química , Fitoterapia , Extractos Vegetales/uso terapéutico , Tallos de la Planta/química , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Etanol , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , AguaRESUMEN
A molecularly imprinted polymers (MIPs) of Ractopamine (RCT) was prepared by thermal polymerization method, and the adsorptive characters of the MIPs was investigated with ultraviolet spectrophotometric method. The results showed that RCT had the maximum absorbance value at the wavelength of 272 nm, the regression equation of RCT was y = 7.354 1x + 0.001 0, R2 = 0.999 9, and the average adsorption rate of MIPs was 83.4%. According to the adsorption kinetics, the adsorption time should be controlled within 10 minutes. Infrared spectrum analysis indicated that the MIPs was formed by hydrogen bonds between RCT and functional monomer methacrylic acid, the MIPs of RCT recognized RCT and combined with it exclusively via hydrogen bonds. The investigation is very useful and important for establishing RCT detection methods based on molecularly imprinted technology.
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Impresión Molecular , Fenetilaminas/análisis , Polímeros , Adsorción , Enlace de Hidrógeno , Metacrilatos , Espectrofotometría UltravioletaRESUMEN
BACKGROUND: The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization. METHODS: We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution). RESULTS: TP53 was found to be a most reliable index (P <10(-7); area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53). CONCLUSIONS: The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.
Asunto(s)
Biomarcadores de Tumor/análisis , Proteína p53 Supresora de Tumor/análisis , Transformación Celular Neoplásica , Genes p53 , Humanos , Hibridación in SituRESUMEN
OBJECTIVE: To investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism. METHODS: Nocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay. The cells were treated with paclitaxel, docetaxel, vincristine, epirubicin, 5-Fu, VP16 and oxaliplatin, respectively. Those cells were labeled with annexin V-FITC/PI and analyzed by flow cytometry. Bcl-2 was knocked down in T-MDA-MB-231 cells using SiRNA and their growth inhibition was evaluated by MTT assay to evaluate the reversing effect of Bcl-2-silencing on drug resistance. RESULTS: The polyploid T-MDA-MB-231 cells grew in vitro continuously and maintained constant DNA content. They had a larger cell size, and grew more slowly than MDA-MB-231 cells. The IC(50(s)) of T-MDA-MB-231 cells were significantly higher than that of the MDA-MB-231 cells: paclitaxel: (6.37 ± 0.07) vs. (2.05 ± 0.83) µmol/L; docetaxel: (32.98 ± 1.48) vs. (11.95 ± 0.98) µmol/L; vincristine: (35.28 ± 1.66) vs. (14.58 ± 0.94) µmol/L; oxaliplatin: (19.07 ± 0.45) vs. (9.75 ± 1.05) µmol/L; 5-Fu: (85.49 ± 3.21) vs. (31.35 ± 1.51) µmol/L; and epirubicin: (0.53 ± 0.06) vs. (0.15 ± 0.01) µmol/L, (all P < 0.05). The IC(50(s)) of VP16 in T-MDA-MB-231 cells was (2.85 ± 0.50)µmol/L, significantly lower than the (12.20 ± 1.55) µmol/L in MDA-MB-231 cells (P < 0.05), and that of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (19.59 ± 0.48) µmol/L, significantly higher than the (12.20 ± 1.55) µmol/L in the MDA-MB-231 cells (P < 0.05). The IC(50(s)) of docetaxel of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (21.52 ± 0.68) µmol/L, significantly decreased and lower than that before Bcl-2 silencing (32.98 ± 1.48) µmol/L. CONCLUSIONS: Our results indicate that polyploid tumor cells induced by spindle poison Nocodazole are more resistant to most of chemotherapeutic drugs. Downregulation of Bcl-2 increases the sensitivity of polyploid cells to docetaxel. The high expression of Bcl-2 may be one of the drug resistance mechanisms of polyploid tumor cells. The polyploid tumor cells are relatively sensitive to VP16, suggesting that VP16 might be an effective candidate drug for treatment of chemoresistant polyploid tumors.