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Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.
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Agaricus is a species-rich genus with more than 600 species around the world. In this work, three new species, Agaricus cacainus, A. baiyunensis, and A. praeclarefibrillosus are described from the specimens collected at Baiyun Mountain, Guangzhou, China, a subtropical area with a monsoon maritime climate, based on phylogenetic analyses and morphological examinations of internal transcribed spacer (ITS1-5.8S-ITS2 = ITS), D1/D2 domains of the large subunit of ribosomal DNA (28S), and a part of translation elongation factor 1-alpha (TEF1). Agaricus cacainus in A. sect. Amoeni is characterized by a parabolic to applanate, slightly depressed pileus covered with chocolate brown, appressed, triangular squamules against white background, a white, furfuraceous stipe, an unchanging context when cut, a fragile and evanescent annulus, usually 4- or 2-spored basidia, and mostly pyriform cheilocystidia. Agaricus baiyunensis in A. sect. Minores has a pileus with a slightly truncate top covered with light brown, downy-wooly fibrillose scales and a light yellowish stipe with membranous annulus. Agaricus praeclarefibrillosus in A. sect. Brunneopicti is characterized by a pileus surface with brownish, triangular, recurved scales and longitudinally splitting lines toward margin, a cottony stipe with white, tiny, recurved fibrils, a single annulus, and variously shaped cheilocystidia, with sparsely ornamented basidiospores. The detailed comparison of their morphological characteristics with closely related species is provided.
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Agaricus , DNA Fúngico , DNA Espaçador Ribossômico , Filogenia , China , Agaricus/classificação , Agaricus/genética , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Análise de Sequência de DNA , Esporos Fúngicos/citologia , Esporos Fúngicos/classificação , RNA Ribossômico 28S/genética , Fator 1 de Elongação de Peptídeos/genética , Dados de Sequência MolecularRESUMO
Previous studies have implicated SNHG3, a long non-coding RNA, in various human cancers, suggesting its oncogenic role. However, its specific involvement in thyroid cancer and the underlying molecular mechanisms remain unclear. Therefore, this study aims to elucidate the role of SNHG3 in human thyroid cancer and its interaction with the miR-339-5p/GPR62 axis. Understanding these mechanisms could provide insights into potential therapeutic targets for managing thyroid cancer. Results revealed significant upregulation of SNHG3 in human thyroid cancer tissues and cell lines. Knockdown of SNHG3 significantly suppressed proliferation, migration and invasion of CUTC5 and IHH-4 thyroid cancer cells. Knockdown of SNHG3 induces apoptosis in CUTC5 and IHH-4 cells and also inhibits the growth of xenografted tumors in vivo. Different in vitro assays revealed the interaction of SNHG3 with microRNA-339-5p (miR-339-5p) in thyroid cancer cells. Expression of miR-339-5p was significantly downregulated in thyroid cancer tissues and cell lines. However, the knockdown of SNHG3 caused significant upregulation of miR-339-5p. Interestingly, overexpression of miR-339-5p exerted tumor-suppressive effects in CUTC5 and IHH-4 cells via post-transcriptional suppression of GPR62. Knockdown of GPR62 significantly inhibited the proliferation, migration and invasion of CUTC5 and IHH-4 cells. Nonetheless, inhibition of miR-339-5p or overexpression of GPR62 avoids the growth inhibitory effects of SNHG3 knockdown in CUTC5 and IHH-4 cells. Results indicated that SNHG3 exerts oncogenic molecular function in thyroid cancer via miR-339-5p/GPR62 axis and may act as a therapeutic target for its management.
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BACKGROUND: Swallowing disorder is a common clinical symptom that can lead to a series of complications, including aspiration, aspiration pneumonia, and malnutrition. This study aimed to investigate risk factors of post-extubation dysphagia (PED) in intensive care unit (ICU) patients with endotracheal intubation, and to develop a risk-predictive model for PED, which could serve as an assessment tool for the prevention and control of PED. METHODS: Patients retrospectively selected from June to December 2021 in a tertiary hospital served as the derivation cohort. Patients recruited from the same hospital from March to June 2022 served as the external validation cohort for the predictive model. We used a combination of variable screening and least absolute shrinkage and selection operator (LASSO) regression to select the most useful candidate predictors and checked the multicollinearity of independent variables using the variance inflation factor method. Multivariate logistic regression analysis was performed to calculate the odds ratio (OR; 95% confidence interval [95% CI]) and P-value for each variable to predict diagnosis. The screened risk factors were introduced into R software to build a nomogram model. The performance of the model, including discrimination ability, calibration, and clinical benefit, was evaluated by plotting the receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 305 patients were included in this study. Among them, 235 patients (53 PED vs. 182 non-PED) were enrolled in the derivation cohort, while 70 patients (17 PED vs. 53 non-PED) were enrolled in the validation cohort. The independent predictors included age, pause of sedatives, level of consciousness, activities of daily living (ADL) score, nasogastric tube, sore throat, and voice disorder. These predictors were used to establish the predictive nomogram model. The model demonstrated good discriminative ability, and the area under the ROC curve (AUC) was 0.945 (95% CI 0.904-0.970). Applying the predictive model to the validation cohort demonstrated good discrimination with an AUC of 0.907 (95% CI 0.831-0.983) and good calibration. The decision-curve analysis of this nomogram showed a net benefit of the model. CONCLUSION: A predictive model that incorporates age, pause of sedatives, level of consciousness, ADL score, nasogastric tube, sore throat, and voice disorder may have the potential to predict PED in ICU patients.
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OBJECTIVES: To study the effect of sex on the clinical outcome of extremely preterm infants (EPIs)/extremely low birth weight infants (ELBWIs) by propensity score matching. METHODS: A retrospective analysis was performed for the medical data of 731 EPIs or ELBWIs who were admitted from January 1, 2011 to December 31, 2020. These infants were divided into two groups: male and female. A propensity score matching analysis was performed at a ratio of 1:1. The matching variables included gestational age, birth weight, percentage of withdrawal from active treatment, percentage of small-for-gestational-age infant, percentage of use of pulmonary surfactant, percentage of 1-minute Apgar score ≤3, percentage of mechanical ventilation, duration of mechanical ventilation, percentage of antenatal use of inadequate glucocorticoids, and percentage of hypertensive disorders in pregnancy. The two groups were compared in the incidence rate of main complications during hospitalization and the rate of survival at discharge. RESULTS: Before matching, compared with the female group, the male group had significantly higher incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and patent ductus arteriosus (P<0.05), while after matching, the male group only had a significantly higher incidence rate of BPD than the female group (P<0.05). There was no significant difference in the rate of survival at discharge between the two groups before and after matching (P>0.05). CONCLUSIONS: Male EPIs/ELBWIs have a higher risk of BPD than female EPIs/ELBWIs, but male and female EPIs/ELBWIs tend to have similar outcomes.
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Displasia Broncopulmonar , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Gravidez , Pontuação de Propensão , Estudos Retrospectivos , Caracteres SexuaisRESUMO
We examined the growth and physiological characteristics of Chlorophytum comosum and Chlorophytum comosum var. variegatum by hydroponics at different Cd2+ concentrations (0, 20, 80, 200 µmol·L-1). The results showed that 20 µmol·L-1 Cd2+ did not affect those two varieties, with no changes of single leaf area, total leaf area, chlorophyll (Chl) a content, Chl (a+b) content, carotenoid content, Chla/Chlb value, intercellular carbon dioxide concentration (Ci) and transpiration rate (Tr) compared with the control (CK). Under the 80 µmol·L-1 Cd2+ stress, the initial fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) were the highest for both varieties. As for Cd2+ at 200 µmol·L-1, the biomass, chlorophyll content, maximum net photosynthetic rate (Pn), stomatal conductance (gs), maximum photochemical quantum yield (Fv/Fm), actual photochemical quantum yield Y(II), the transfer factor (TF) of both varieties and all parts biomass decreased to the lowest, while peroxidase (POD), ascorbic acid peroxidase (APX) and catalase (CAT) activities of two varieties and MDA content of C. comosum var. variegatum increased in different degrees. With the increases of Cd2+ stress, the Cd content in organs of two varieties showed an increasing trend, with higher Cd accumulation in roots. C. comosum had higher Cd content and bioconcentration factor (BCF) in all organs than C. comosum var. variegatum. It suggested that two varieties had the ability to resist Cd stress. The tolerance of C. comosum was stronger, and thus could be considered as a green plant to remediate Cd contaminated water or soil.
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Cádmio , Clorofila , Ascorbato Peroxidases/metabolismo , Cádmio/toxicidade , Fotossíntese , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismoRESUMO
BACKGROUND: The effect of blood eosinophils (EOSs) on mortality in acute respiratory distress syndrome (ARDS) patients and whether corticosteroids affect this effect are unclear. METHODS: The Medical Information Mart for Intensive Care III database (version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching (PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2% (18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality (hazard ratio [HR] 0.731; 95% confidence interval [95% CI] 0.581-0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality (HR 0.697, 95% CI 0.535-0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model (P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group (18.60% [85/457] vs. 26.70% [122/457], P=0.003). CONCLUSIONS: Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.
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In this study, the effects of exogenous abscisic acid (ABA) on the growth and physiolo-gical characteristics of Machilus yunnanensis seedlings were examined under well water supply conditions (70%-75% field capacity, FC) and different drought stress conditions, i.e., light drought stress (50%-55% FC) and severe drought stress (30%-35% FC), respectively. The results showed that drought stress reduced leaf relative water content, plant height, and total biomass of seedlings significantly decreased, as well as net photosynthetic rate and maximal photochemistry efficiency (Fv/Fm), but enhanced root/shoot and malondialdehyde contents (MDA). Exogenous ABA improved the adaptability of seedlings under drought stress, especially under severe drought stress, with leaf relative water content being improved 21.0%. Plant height and biomass allocation were improved by exogenous ABA under drought, while root/shoot was improved by 1.1 times compared with the well watered plants. The accumulation of MDA was decreased, the activities of CAT and SOD were significantly increased, and the proline content was increased 6.7 times by exogenous ABA under drought. Exogenous ABA application alleviated the negative effect of drought on photosynthetic organs, reduced the decrease of net photosynthetic rate and stomatal conductance under drought, and enhanced Fv/Fm value. The results suggested that exogenous ABA treatment could enhance the resistance of M. yunnanensis to drought stress.
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Ácido Abscísico , Secas , Fotossíntese , Folhas de Planta , Plântula , Estresse Fisiológico , ÁguaRESUMO
Aphyocypris normalis (Teleostei: Cyprinidae) is an endemic species in South China, but little is known about its genetic structure. This study examined the population structure of A. normalis using sequences of the mitochondrial DNA control region and cytochrome b gene (2,086 bp). In total, 107 specimens were collected from nine populations. All 105 mtDNA haplotypes were identified as belonging to two allopatric phylogroups. The results of a statistical dispersal-vicariance analysis (S-DIVA) suggested that the ancestral populations of A. normalis were distributed widely on Hainan Island and east of the Leizhou Peninsula. A comparison of the fixation indices NST (0.532) and GST (0.004) revealed that the phylogeny and geography had a significant relationship. Our study found that (1) the Wuzhishan and Yinggeling Mountain Range was an important barrier limiting gene exchange between populations on both sides; (2) cyclic climate changes may have shaped migrations and population differentiations; and (3) different colonization times caused different population diversities between codistributed species. In addition, the inter- and intraspecific diversities of the genus Aphyocypris were estimated.
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Japanese encephalitis (JE) is a serious public health issue. This study was undertaken to better understand the relationship between JE distribution and environmental factors in China. JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System. ArcGIS, remote sensing techniques, and R software was used to exhibit and explore the relationship between JE distribution and environmental factors. Our results indicated that JE cases were mostly concentrated in warm-temperate, semitropical and tropical zones with annual precipitation > 400 mm; Broad-leaved evergreen forest, shrubs, paddy field, irrigated land, dryland, evergreen coniferous forest, and shrubland were risk factors for JE occurrence, and the former five were risk factors for counties with high JE incidence. These findings will inform the effective allocation of limited health resources such as intensive vaccination, surveillance and training in areas with high environmental risk factors.
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Encefalite Japonesa/epidemiologia , Meio Ambiente , Monitoramento Epidemiológico , China/epidemiologia , Encefalite Japonesa/virologia , Humanos , Incidência , Fatores de RiscoRESUMO
BACKGROUND: To determine the seroprevalence, latent infection rate and risk factors for severe fever with thrombocytopenia syndrome virus (SFTSV) infection, a cross-sectional study was conducted in the general population of the Western region of Anhui Province of China from 1 September to 31 December 2014. METHODS: Twelve villages with the highest rates of endemic SFTS infection were selected from six towns in two counties in the western region of Anhui Province. Blood samples were collected and tested for the presence of SFTSV-IgG antibodies by ELISA. Each participant was interviewed using a structured questionnaire before blood collection. Participants with seropositive specimens were further investigated using another structured questionnaire. RESULTS: Of 2126 blood specimens collected, 99 (4.66%) were seropositive for SFTSV. None of the participants had been diagnosed with SFTS before the blood collection or were accompanied by fever, thrombocytopenia and leukocytopenia after blood collection. Multivariate logistic regression model analysis revealed living in areas of uncontrolled vegetation growth, long-term residents of the locality and tick bites as high risk factors for SFTSV infection. CONCLUSIONS: The overall seroprevalence of SFTSV is higher in the western region of Anhui, possibly due to latent infection, with the main risk factors being living in areas of uncontrolled vegetation growth, long-term residents of the locality and tick bites. Further investigations are warranted to clarify the modes of SFTS virus transmission, while vector management, education on tick bite prevention and personal hygiene management should be implemented for high risk groups in endemic areas.
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Febre por Flebótomos/epidemiologia , Febre por Flebótomos/imunologia , Phlebovirus/imunologia , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Febre por Flebótomos/virologia , Fatores de Risco , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.
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Carcinoma/metabolismo , Carcinoma/mortalidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Área Sob a Curva , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Biomarcadores , Carcinoma/terapia , Terapia Combinada , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/terapia , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker. METHODS: We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay. RESULTS: Using the 3rd quartile values (0.8 µg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1-84.9)) vs. (69%, 95%CI (59.2-78.8)), DMFS (87%, 95%CI (83.1-90.9)) vs. (77%, 95%CI (69.2-84.8)), and overall survival (82%, 95%CI (76.1-87.9)) vs. (76%, 95%CI (66.2-85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml. CONCLUSIONS: High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.
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Quimiorradioterapia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Carcinoma , DNA Viral/sangue , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/mortalidade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
Paclitaxel is a main ingredient in the combination chemotherapy treatment of advanced human cervical squamous cell carcinomas. We investigated the roles and underlying molecular mechanisms of PinX1 in cervical squamous cell carcinomas (CSCC) cells response to paclitaxel and its clinical significances. The expression dynamics of PinX1 was first examined by immunohistochemistry in 122 advanced CSCC patients treated with cisplatin/paclitaxel chemotherapy. The expression of PinX1 was significantly associated with the effects of cisplatin/paclitaxel chemotherapy in advanced CSCCs (P<0.05). High expression of PinX1 correlated with CSCC's response to cisplatin/paclitaxel chemotherapy, and was an independent predictor of shortened survival (P<0.05). A series of in vivo and in vitro assays were performed to elucidate the function of PinX1 on CSCC cells chemosensitivity to paclitaxel and underlying mechanisms. In CSCC cells, the levels of PinX1 were only associated with the cytotoxicity and sensitivity of paclitaxel, in which knockdown of PinX1 dramatically enhanced paclitaxel cytotoxicity, whereas the reestablishment of PinX1 levels substantially reduced the paclitaxel-induced killing effect. In addition, we identified that the ability of PinX1 to stabilize the tension between sister kinetochores and maintain the spindle assembly checkpoint was the main reason CSCC cells undergo apoptosis when treated with paclitaxel, and further studies demonstrated that shortened distance between sisters kinetochores by nocodazole confers upon PinX1-replenished cells a sensitivity to the death inducing paclitaxel effects. Furthermore, our study of CSCC cells xenografts in nude mice confirmed the role of PinX1 in paclitaxel sensitivity in vivo. Our data reveal that PinX1 could be used as a novel predictor for CSCC patient response to paclitaxel, and the role of PinX1-mediated paclitaxel sensitivity might represent a new direction for the development of a new generation of microtubule drugs.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Telômero/efeitos dos fármacos , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Células HeLa , Humanos , Cinetocoros/efeitos dos fármacos , Cinetocoros/metabolismo , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Interferência de RNA , Fuso Acromático/metabolismo , Análise de Sobrevida , Telomerase/metabolismo , Telômero/metabolismo , Fatores de Tempo , Transfecção , Resultado do Tratamento , Moduladores de Tubulina/administração & dosagem , Proteínas Supressoras de Tumor/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This study was aimed to investigate the potential role of microRNA-29c (miR-29c) in regulating the sensitivities of nasopharyngeal carcinoma (NPC) to ionizing radiation (IR) and cisplatin. Low expression of miR-29c was positively associated with therapeutic resistance in 159 NPC cases. Our further in vitro and in vivo studies illustrated ectopic restoration of miR-29c substantially enhanced the sensitivity of NPC cells to IR and cisplatin treatment by promoting apoptosis. Furthermore, we detected miR-29c repressed expression of anti-apoptotic factors, Mcl-1 and Bcl-2 in NPC tissues and cell lines. These data indicate miR-29c might serve as a potential therapeutic sensitizer in NPC treatment.
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Antineoplásicos/farmacologia , Cisplatino/farmacologia , MicroRNAs/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Carcinoma , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Radiação Ionizante , Resultado do TratamentoRESUMO
BACKGROUND: The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients. METHODS: The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression. RESULTS: We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers. CONCLUSION: Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.
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Neoplasias da Mama/metabolismo , Metástase Linfática , Proteínas rab de Ligação ao GTP/metabolismo , Sequência de Bases , Western Blotting , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Estudos de Coortes , Primers do DNA , Transição Epitelial-Mesenquimal , Feminino , Humanos , Imuno-Histoquímica , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Taxa de SobrevidaRESUMO
OBJECTIVE: To quantitatively evaluate the contamination area and risk of a live pathogen during tissue homogenization by either ultrasonic processor or tissue disperser. METHODS: A recombinant Herpes Simplex Virus (rHSV) containing GFP gene was used as the index virus, and fresh liver tissue from healthy mice was used as simulated specimen. After 10% liver homogenate was mixed with rHSV (100 TCID50/0.1 mL) in a 5 mL tube, the stability of rHSV in liver homogenate and influences of an ultrasonic processor and a tissue disperser on viral infectivity were determined by GFP expressions in cell cultures. The contaminating areas of live viruses during homogenization were evaluated by a cell culture-based sedimentary. The contamination radii were counted by measurement of the distance between the operator and the farthest GFP positive well. RESULTS: The infectivity of rHSV in 10% liver homogenate maintained almost unchanged after it was incubated at room temperature for 30 min. Treatment with an ultrasonic processor clearly dropped down the virus infectivity, while a disperser not. Obvious spills and slashes of live viruses were observed in processes of homogenization with those two apparatuses. The contamination radii are positively related with sample volume, output energy of operator and handling time. CONCLUSION: Homogenizing infectious samples with an ultrasonic processor and a tissue disperser at commonly used conditions caused obvious spills and splashes of live viruses, which possesses high risk to induce Laboratory acquired infections (LAIs).
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Simplexvirus/fisiologia , Ultrassom , Simplexvirus/patogenicidade , VirulênciaRESUMO
Acute pancreatitis is an inï¬ammatory disease characterized by local tissue injury which can trigger a systemic inï¬ammatory response. So vascular complications of pancreatitis are a major cause of morbidity and mortality. Pulmonary embolism in acute pancreatitis has been reported to be very rare. We reported a case of pulmonary embolism with acute pancreatitis. A 38-year-old woman broke out upper abdomen pain without definite inducement. She had no nausea and vomiting, fever, dyspnea, cough and expectoration, chest pain. The patient had been diagnosed with acute pancreatitis in local hospital. The patient was treated with antibiotics and proton pump inhibitors, and the abdomen pain was alleviated slightly. But the patient came forth cough and expectoration with a little blood, progressive dyspnea. A computed tomographic scan of the abdomen revealed pancreatitis. Subsequent computer tomography angiography of chest revealed pulmonary embolism (both down pulmonary arteries, left pulmonary artery and branch of right pulmonary artery). Dyspnea of the patient got well with thrombolytic treatment and anticoagulation therapy. Pulmonary embolism is a rare but potentially lethal complication of pancreatitis. Familiarity with this complication will aid in its early diagnosis, therapy and prevent pulmonary embolism, a rare but catastrophic phenomenon.