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BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.
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Neoplasias da Vesícula Biliar , Pólipos , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores Etários , Idoso , Fatores de Risco , Colecistectomia , China/epidemiologia , Período Pré-Operatório , Adulto Jovem , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.
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Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Teorema de Bayes , Doenças da Vesícula Biliar/cirurgia , Colecistectomia , Ultrassonografia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Pólipos/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.
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Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Teorema de Bayes , Doenças da Vesícula Biliar/cirurgia , Ultrassonografia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Pólipos/patologia , Estudos RetrospectivosRESUMO
We demonstrate a scheme to measure the saturable nonlinearity of atomic vapor by mapping its nonlinear response function onto a light beam profile. Our analysis shows that a part of a nonlinear optical solution solved in a model governing the nonlinear beam dynamics in atomic vapor can be used to perform this measurement, even in the presence of large absorption. A desired beam profile is achieved by an evolution of a well-known structured beam, namely the Airy beam. Using this simple yet effective method, we retrieve the saturable nonlinear response function of rubidium (Rb) atomic vapor in experiment, and employ it in light propagation simulation that reproduces well observed nonlinear dynamics, which nevertheless cannot be fitted in a strong nonlinear regime with an ideal Kerr approximation. Our method is applicable to a broad spectrum of materials featured with saturable nonlinearities.
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We report a scheme to achieve efficient direct mapping of the nonlinear optical response into a spatial beam profile. Compared with previous methods where a standard two-dimensional Airy beam was used as a probe, a modulated beam configuration allows for an improved mapping efficiency, stemming from the induced nonlinearity caused by the applied modulation. We find that the mapping efficiency along different orientations is highly related to the beam patterns and the type of nonlinearity. The improvement of the mapping quality and new, to the best of our knowledge, features found in simulations are further verified in experiments by testing a photorefractive nonlinearity. Our results represent a further step towards an effective tool for the direct measurement of the nonlinear optical response with low power consumption.
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We demonstrate for the first time that the nonlinear response of a medium can be mapped directly onto a dynamical wave profile as governed by a generalized nonlinear Schrödinger equation. As analyzed in an accelerating coordinate, the intrinsic gravitylike potential helps "isolate" the effects related to a strong repulsive nonlinear interaction from the dispersion or diffraction in a steady state. Thus, under appropriate conditions, the associated nonlinear response curve can be read out directly in the profile of the nonlinear state. A simple scheme is proposed to approach adiabatically these modes through a shaped input wave profile. Our analysis is further verified experimentally by directly visualizing a Kerr (saturable) nonlinearity experienced by an optical pulse (beam) in a nonlinear fiber (photorefractive crystal), validating the versatility of this approach for different types of optical nonlinearities.
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We study free-space coupling of optical fields to the whispering-gallery-mode resonators by employing self-accelerating beams orbiting a semicircle. The best coupling condition is obtained through theoretical analysis, in accord with the numerical results. Comparing with the conventional Gaussian-like beams, much enhanced coupling efficiency is achieved with such self-accelerating beams, particularly when a large numerical aperture of an optical system is used or a higher-order azimuthal mode is considered. Conditions with slight deviation from the ideal radius of self-accelerating beams are further discussed, aiming to realize an optimized high coupling efficiency.
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PURPOSE: One of the current challenges facing cancer gene therapy is the tumour-specific targeting of therapeutic genes. Effective targeting in gene therapy requires accurate spatial and temporal control of gene expression. To develop a sufficient and accurate tumour-targeting method for cancer gene therapy, we have investigated the use of hyperthermia to control the expression of a transgene under the control of the human telomerase reverse transcriptase (hTERT) promoter and eight heat shock elements (8HSEs). MATERIALS AND METHODS: Luciferase reporters were constructed by inserting eight HSEs and the hTERT promoter (8HSEs-hTERTp) upstream of the pGL4.20 vector luciferase gene. The luciferase activity of the hTERT promoter and 8HSEs-hTERT promoter were then compared in the presence and absence of heat. The differences in luciferase activity were analysed using dual luciferase assays in SW480 (high hTERT expression), MKN28 and MRC-5 cells (low hTERT expression). The luciferase activity of the Hsp70B promoter was also compared to the 8HSEs-hTERT promoter in the above listed cell lines. Lentiviral vector and heat-induced expression of EGFP expression under the control of the 8HSEs-hTERT promoter in cultured cells and mouse tumour xenografts was measured by reverse transcription polymerase (RT-PCR), Western blot and immunofluorescence assays. RESULTS: hTERT promoter activity was higher in SW480 cells than in MKN28 or MRC-5 cells. At 43 °C, the luciferase activity of the 8HSEs-hTERT promoter was significantly increased in SW480 cells, but not in MKN28 or MRC-5 cells. Importantly, the differences in luciferase activity were much more obvious in both high (SW480) and low (MKN28 and MRC-5) hTERT expressing cells when the activity of the 8HSEs-hTERT promoter was compared to the Hsp70B promoter. Moreover, under the control of 8HSEs-hTERT promoter in vitro and in vivo, EGFP expression was obviously increased by heat treatment in SW480 cells but not in MKN28 or MRC-5 cells, nor was expression increased under normal temperature conditions. CONCLUSIONS: The hTERT promoter is a potentially powerful tumour-specific promoter and gene therapy tool for cancer treatment. Incorporating heat-inducible therapeutic elements (8HSEs) into the hTERT promoter may enhance the efficiency and specificity of cancer targeting gene therapy under hyperthermic clinical conditions.
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Terapia Genética , Proteínas de Choque Térmico HSP70/genética , Neoplasias/terapia , Telomerase/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Proteínas de Fluorescência Verde/genética , Resposta ao Choque Térmico , Temperatura Alta , Humanos , Luciferases/metabolismo , Camundongos Endogâmicos BALB C , Neoplasias/genética , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Surgical indications for the treatment of gallbladder polyps are controversial. Evaluation of gallbladder polyps with malignant tendency and indications for cholecystectomy in patients with long diameter polyps of 10 to 15 mm require further analysis and discussion. In this study, our objective was to re-evaluate indications for the surgical resection of gallbladder polyps and construct a nomogram model for the prediction of gallbladder polyps with malignant tendency. METHODS: Clinicopathologic data of 2,272 patients who had undergone cholecystectomy for gallbladder polyps were collected from 11 medical centers in China. Risk factor analyses and nomogram prediction model for gallbladder polyps with malignant tendency were conducted. RESULTS: Excluding 311 patients with cholelithiasis and 488 patients with long diameter polyps ≤5 and >15 mm, factors that differed significantly among patients with gallbladder polyps having a long diameter of 6 to 9 mm (885 cases) and 10 to 15 mm (588 cases) were polyp detection time, CEA and CA19-9 levels, number of polyps, fundus, echogenicity, gallbladder wall thickness and postoperative pathologic features (P < .05). Among 588 patients with gallbladder polyps with a long diameter of 10 of 15 mm, multivariate analysis indicated the following independent risk factors of gallbladder polyps with malignant tendency: single polyps (OR = 0.286/P < .001), polyps with broad base (OR = 2.644/P = .001), polyps with medium/low echogenicity (OR = 2.387/P = .003), and polyps with short diameter of 7 to 9 or 10 to 15 mm (OR = 3.820/P = .005; OR = 2.220/P = .048, respectively). The C-index of the nomogram model and internal validation were .778 and .768, respectively. In addition, a sample online calculator for the nomogram prediction model had been created (https://docliqi.shinyapps.io/dynnom/). CONCLUSION: Indications for cholecystectomy in patients with gallbladder polyps with a long diameter of 10 to 15 mm should be assessed by combining the information on short diameter, number of polyps, fundus, and echogenicity. The nomogram model can be used to predict the risk for the development of gallbladder polyps with malignant tendency.
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Colecistectomia Laparoscópica/métodos , Neoplasias da Vesícula Biliar/diagnóstico , Estadiamento de Neoplasias/normas , Nomogramas , Pólipos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pólipos/cirurgia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. RESULTS: In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/ß-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear ß-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. CONCLUSION: Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , Via de Sinalização Wnt , Regiões 3' não Traduzidas , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Interferência de RNA , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The intestine function recovery decoction (IFRD) is a traditional Chinese medicine that has been used for the treatment of adhesive intestinal obstruction. In this study, the preventative effects and probable mechanism of the IFRD were investigated in a rat model. We randomly assigned rats to five groups: normal, model, control, low dose IFRD, and high dose IFRD. In the animal model, the caecum wall and parietal peritoneum were abraded to induce intra-abdominal adhesion formation. Seven days after surgery, adhesion scores were assessed using a visual scoring system, and histopathological samples were examined. The levels of serum interleukin-6 (IL-6) and transforming growth factor beta-1 (TGF-ß1) were analysed by an enzyme-linked immunosorbent assay (ELISA). The results showed that a high dose of IFRD reduced the grade of intra-abdominal adhesion in rats. Furthermore, the grades of inflammation, fibrosis, and neovascularization in the high dose IFRD group were significantly lower than those in the control group. The results indicate that the IFRD can prevent intra-abdominal adhesion formation in a rat model. These data suggest that the IFRD may be an effective antiadhesion agent.
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BACKGROUND: Postoperative intra-abdominal adhesions are common complications after abdominal surgery. The exact molecular mechanisms that are responsible for these complications remain unclear, and there are no effective methods for preventing adhesion formation or reformation. The aim of the study reported here was to investigate the preventive effects and underlying potential molecular mechanisms of selective cyclooxygenase-2 (COX-2) inhibitors in a rodent model of postoperative intra-abdominal adhesions. MATERIALS AND METHODS: The expression of COX-2 in postoperative intra-abdominal adhesions and normal peritoneal tissue was examined by immunohistochemistry and Western blot analysis. Assays were performed to elucidate the effect of COX-2 inhibition on hypoxia-induced fibroblast activity in vitro and on intra-abdominal adhesion formation in vivo. RESULTS: Hypoxia-induced COX-2 expression in peritoneal fibroblasts was increased in postoperative intra-abdominal adhesions. Inhibition of COX-2 attenuated the activating effect of hypoxia on normal peritoneal fibroblasts in vitro. Data indicate that selective COX-2 inhibitor prevents in vivo intra-abdominal adhesion by inhibition of basic fibroblast growth factor and transforming growth factor-beta expression, but not through an antiangiogenic mechanism. Furthermore, using selective COX-2 inhibitors to prevent intra-abdominal adhesions did not adversely affect the weight, bowel motility, or healing of intestinal anastomoses in a rat model. CONCLUSION: These results show that hypoxia-induced COX-2 expression in peritoneal fibroblasts is involved in the formation of intra-abdominal adhesions. Inhibition of COX-2 prevents postoperative intra-abdominal adhesions through suppression of inflammatory cytokines.
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Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Fibroblastos/efeitos dos fármacos , Cavidade Peritoneal/citologia , Aderências Teciduais/prevenção & controle , Parede Abdominal/patologia , Anastomose Cirúrgica , Animais , Peso Corporal , Hipóxia Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Hipóxia/patologia , Complicações Pós-Operatórias/prevenção & controle , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/etiologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Cicatrização/efeitos dos fármacosRESUMO
Human telomerase reverse transcriptase (hTERT) is upregulated in most cancer cell types as well in immortalized cells. The underlying mechanism for such upregulation, however, remains largely unknown. We report here that bile acids under acidified media increase hTERT expression via c-myc activation in primary human gastric cancer cell lines. Human gastric cancer MKN28, MGC803 and SGC7901 cells were treated with 100 µM deoxycholic acid (DCA) or chenodeoxycholic acid (CDCA) with or without acidified media in the presence or absence of the c-myc inhibitor 10058-F4 for 24 h. hTERT and c-myc protein levels were determined by western blot analysis. hTERT and c-myc mRNA levels were determined by RT-PCR. The promoter activities of hTERT and c-myc transcription were determined using promoter reporter luciferase assays for both. Telomerase enzyme activity was analyzed by stretch PCR. hTERT mRNA and protein levels were significantly increased by bile acids in acidified media and were accompanied with enhanced telomerase activity. No changes were found at a pH of 7.0 or with acidified media alone. Similarly, the mRNA and protein levels of c-myc were also increased by bile acids in acidified media but not at a pH of 7.0 or with acidified media alone. Importantly, pharmacologic inhibition of c-myc using 10058-F4 prevented hTERT induction by DCA or CDCA in gastric cancer cells under acidic conditions. Bile acids (DCA and CDCA) under acidic conditions increased hTERT expression in human gastric cancer cells by activation of c-myc transcription. This suggests that acidified bile acids may promote tumorigenesis and affect cell ageing via telomerase activation.
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Ácidos e Sais Biliares/administração & dosagem , Proteínas Proto-Oncogênicas c-myc/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Telomerase/biossíntese , Ácidos e Sais Biliares/metabolismo , Linhagem Celular Tumoral , Ácido Quenodesoxicólico/administração & dosagem , Ácido Desoxicólico/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Neoplasias Gástricas/genética , Telomerase/antagonistas & inibidores , Telomerase/genética , Tiazóis/administração & dosagem , Ativação Transcricional/efeitos dos fármacosRESUMO
Caudalrelated homeobox transcription factor 2 (CDX2) is a transcription factor, which is specifically expressed in the adult intestine. It is essential for the development and homeostasis of the intestinal epithelium and its functions as a tumor suppressor have been demonstrated in the adult colon. The present study aimed to examine the inhibitory effects of the overexpression of CDX2 on subcutaneouslytransplanted tumors, derived from LoVo colon cancer cells, in nude mice, and to provide experimental evidence for the biotherapy of colon cancer. A pEGFPC1CDX2 eukaryotic expression vector was transfected into the LoVo cells via lipofection, and LoVo cells stablyexpressing CDX2 (pEGFPC1CDX2 cells) were obtained using G418 selection. A nude mouse subcutaneouslytransplanted tumor model was established by inoculating the nude mice with the pEGFPC1CDX2 cells, and the effects of overexpression of CDX2 on transplanted tumor growth in the LoVo cells were observed. Western blotting results demonstrated that the protein expression of CDX2 in the LoVo cells was higher in the pEGFPC1CDX2 cell group, compared with that in the pEGFPC1 cell group and the untreated cell group. At 20 days postinoculation with either pEGFPC1CDX2 or pEGFPC1, the transplanted tumor masses were significantly lower in the pEGFPC1CDX2 group, compared with those in the pEGFPC1 and untreated groups. Immunohistochemistry revealed that the expression levels of CDX2 and matrix metalloproteinase2 (MMP2) were detected in each group, and the protein expression of CDX2 was increased in the tumor tissues from the nude mice in the pEGFPC1CDX2 group. However the expression of MMP2 was downregulated in the tumor tissues of the nude mice in the pEGFPC1CDX2 group. Taken together, these data suggested that pEGFPC1CDX2 cells exhibited suppressed tumor growth in vivo. Overexpression of CDX2 was observed in transplanted tumors in the pEGFPC1CDX2 group, and the gene expression of MMP2 was reduced. These results indicate that CDX2 inhibited the growth of colorectal tumor cells, possibly by downregulating the gene expression.