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BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Gastrectomia , Quimioterapia AdjuvanteRESUMO
BACKGROUND: Gastric outlet obstruction (GOO) is a late complication of advanced gastric cancer, and it is controversial how to select the therapeutic strategies: gastrojejunostomy and palliative gastrectomy? Therefore, this study was to compare the surgical and survival outcomes of gastrojejunostomy and palliative gastrectomy. METHODS: In total, 199 gastric cancer patients with outlet obstruction treated by surgery between January 2000 and December 2015 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Patients were divided into gastrojejunostomy group and palliative gastrectomy group. Propensity score matching (PSM) was performed to balance the selection bias. RESULTS: After 1:1 PSM, a total of 104 patients were included for final analysis. The median overall survival (OS) times in the gastrojejunostomy group and palliative gastrectomy group were 8.50 and 11.87 months, respectively (P = 0.243). The postoperative complication rates in the gastrojejunostomy group and palliative gastrectomy group were 19.23% (10/52) and 17.31% (9/52), respectively (P = 0.800), and no treatment-related death was observed. Multivariate analysis showed that periton0eal seeding (P = 0.014) and chemotherapy (P < 0.001) were independent prognostic factors. Among them, peritoneal seeding was a risk factor and postoperative chemotherapy was a protective factor. CONCLUSIONS: Our results indicated that although the surgical complications of palliative gastrectomy were manageable, it showed no survival benefit. Therefore, relieving obstruction symptom, improving patients' quality of life and creating better conditions for chemotherapy appear to be the main therapeutic strategies for advanced gastric cancer with GOO.
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Gastrectomia/métodos , Derivação Gástrica/métodos , Obstrução da Saída Gástrica/cirurgia , Cuidados Paliativos , Pontuação de Propensão , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidadeRESUMO
The scattered light distribution of surfaces in the long-wave infrared (λâ¼8-12µm) is measured using a small set of thermal camera images. This method can extract scatter patterns considerably faster than standard laboratory bidirectional reflectance distribution function measurements and is appropriate for passive homogeneous surfaces. Specifically, six images are used in this study, each taken with respect to a thermal light source at an angle ranging from 10° to 60° to the normal of the surface. This data is deconvolved with the shape of the light source to estimate the scattering pattern. Both highly specular (black Masonite) and diffuse (painted drywall) surfaces are tested. Errors between the estimated scattering distribution and a directly measured one using a goniometer stage and quantum-cascade laser (QCL) are less than or equal to 3% except for extremely specular surfaces where viable QCL measurements cannot be made due to the increased relative contribution of speckle noise.
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BACKGROUND: The present study aims to report the surgical outcome and long-term survival of conversion surgery and clarify its role in advanced gastric cancer. PATIENTS AND METHODS: A total of 95 primary advanced gastric adenocarcinoma patients who underwent systemic chemotherapy and conversion surgery were reviewed retrospectively. The survival of conversion surgery was analyzed by Cox regression and the Kaplan-Meier method. Surgical outcomes were analyzed according to the Clavien-Dindo classification. RESULTS: The median survival time (MST) of the 95 patients was 26.8 months, and the postoperative MST was 19.3 months. The MSTs of the patients in categories 1, 2, 3, and 4 were 28.8, 25.5, 43.6, and 11.3 months, respectively. The MSTs of the patients who underwent R0 resection (47 cases) and R1/2 resection (48 cases) were 49.3 months and 21.9 months, respectively. The MST of patients treated with total gastrectomy was shorter (21.9 months) than that of patients who underwent proximal (55.0 months) or distal (46.3 months) gastrectomy. Patients who received more than 6 cycles of induction chemotherapy had a longer MST than patients who received 3-5 cycles or 1-2 cycles (MST: 55.0 months versus 21.1 months versus 21.7 months). The incident postoperative complications and postoperative mortality rates were 10.5% and 1.1%, respectively. CONCLUSIONS: Advanced gastric cancer patients may obtain a survival benefit from conversion surgery, except category 4. Performing a sufficient number of cycles of induction chemotherapy (usually ≥ 6 cycles) is recommended. Surgical oncologists should perform R0 resection and avoid total gastrectomy.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Terapia Combinada , Gastrectomia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer. METHODS: We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings. RESULTS: After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS. CONCLUSIONS: Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.
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Biomarcadores Tumorais/genética , Biomarcadores/análise , Quimioterapia Adjuvante/mortalidade , Neoplasias Pancreáticas/mortalidade , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaRESUMO
BACKGROUND: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes. METHODS: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM. RESULTS: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC. CONCLUSIONS: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
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Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de SobrevidaRESUMO
Heavy metals are a growing threat to human health due to the resulting damage to the ecology; the removal of heavy metals by lactic acid bacteria (LAB) has been a focus of many studies. In this study, 10 LAB strains were evaluated for their ability to absorb and tolerate lead. Lactobacillus plantarum YW11 was found to possess the strongest ability of lead absorbing and tolerance, with the rate of absorption as high as 99.9% and the minimum inhibitory concentration of lead on YW11 higher than 1000 mg/L. Based on the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics analysis of YW11, a total of 2009 proteins were identified both in the lead-treated strain and the control without the lead treatment. Among these proteins, 44 different proteins were identified. The abundance of 25 proteins increased significantly, and 19 proteins decreased significantly in the treatment group. These significantly differential abundant proteins are involved in the biological processes of amino acid and lipid metabolism, energy metabolism, cell wall biosynthesis, and substance transport. This study contributed further understanding of the molecular mechanism of L. plantarum in the binding and removal of lead to explore its potential application in counteracting heavy metal pollution of environment, food, and other fields.
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Lactobacillales/metabolismo , Chumbo/metabolismo , Proteômica/métodos , Adsorção , Proteínas de Bactérias/metabolismo , Ontologia Genética , Genes Bacterianos , Lactobacillales/efeitos dos fármacos , Lactobacillales/crescimento & desenvolvimento , Lactobacillales/ultraestrutura , Chumbo/toxicidade , Anotação de Sequência Molecular , Espectrometria por Raios X , Água/químicaAssuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Quimioterapia Adjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologiaRESUMO
Age-related macular degeneration (AMD) is a complex and progressive degenerative eye disease resulting in severe loss of central vision. Recent evidence indicates that immune system dysregulation could contribute to the development of AMD. We hypothesize that defective lysosome-mediated clearance causes accumulation of waste products in the retinal pigmented epithelium (RPE), activating the immune system and leading to retinal tissue injury and AMD. We have generated unique genetically engineered mice in which lysosome-mediated clearance (both by phagocytosis and autophagy) in RPE cells is compromised, causing the development of features of early AMD. Our recent data indicate a link between lipocalin-2 (LCN-2) and the inflammatory responses induced in this mouse model. We show that nuclear factor-κB (NF-κB) and STAT-1 may function as a complex in our animal model system, together controlling the upregulation of LCN-2 expression in the retina and stimulating an inflammatory response. This study revealed increased infiltration of LCN-2-positive neutrophils in the choroid and retina of early AMD patients as compared with age-matched controls. Our results demonstrate that, both in our animal model and in human AMD, the AKT2-NF-κB-LCN-2 signalling axis is involved in activating the inflammatory response, making this pathway a potential target for AMD treatment. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Lipocalina-2/genética , Lisossomos/imunologia , Degeneração Macular/genética , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Fatores Etários , Animais , Autofagia , Corioide/imunologia , Corioide/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação , Lipocalina-2/metabolismo , Lisossomos/metabolismo , Degeneração Macular/imunologia , Degeneração Macular/patologia , Camundongos , NF-kappa B/metabolismo , Neutrófilos/imunologia , Fagocitose , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retina/imunologia , Retina/lesões , Retina/metabolismo , Epitélio Pigmentado da Retina/imunologia , Epitélio Pigmentado da Retina/metabolismo , Regulação para CimaRESUMO
Tissue plasminogen activator (tPA) is administered after ischemic stroke to dissolve intravascular clots, but its use can lead to hemorrhagic transformation (HT). Therapeutic strategies to reduce hemorrhagic complications of tPA might be of benefit for stroke patients. Adenosine A2b receptor (A2bR) plays pivotal roles in regulating vascular protection in peripheral organs. This study explored whether A2bR agonist BAY 60-6583 reduces hemorrhage risk after tPA usage. Using a rat transient middle cerebral artery occlusion model, we showed that mRNA and protein expression of A2bR increased to a greater extent after ischemia-reperfusion than did expression of the other three adenosine receptors (A1, A2a, and A3). tPA administration reduced A2bR expression in ischemic brain microvessels. Post-treatment with BAY 60-6583 (1mg/kg) at the start of reperfusion reduced lesion volume in the absence or presence of tPA (10mg/kg) and attenuated brain swelling, blood-brain barrier disruption, and tPA-exacerbated HT at 24h. Additionally, BAY 60-6583 mitigated sensorimotor deficits in the presence of tPA. BAY 60-6583 inhibited tPA-enhanced matrix metalloprotease-9 activation, probably through elevation of tissue inhibitor of matrix metalloproteinases-1 expression, and thereby reduced degradation of tight junction proteins. These effects would likely protect cerebrovascular integrity. A2bR agonists as an adjuvant to tPA could be a promising strategy for decreasing the risk of HT during treatment for ischemic stroke.
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Agonistas do Receptor A2 de Adenosina/farmacologia , Isquemia Encefálica/tratamento farmacológico , Hemorragia Cerebral/prevenção & controle , Fibrinolíticos/toxicidade , Fármacos Neuroprotetores/farmacologia , Ativador de Plasminogênio Tecidual/toxicidade , Aminopiridinas/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Receptor A2B de Adenosina/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Soft tissue sarcomas (STS) are highly malignant tumors with limited treatment options owing to their heterogeneity and resistance to conventional therapies. Photodynamic therapy (PDT) and poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown potential for STS treatment, with PDT being effective for sarcomas located on the extremities and body surface and PARPi targeting defects in homologous recombination repair. To address the limitations of PDT and harness the potential of PARPi, herein, a novel therapeutic approach for STS treatment combining nanocapsules bearing integrated metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), i.e., MOF@COF, with PDT and PARPi is proposed. Nanocapsules are designed, referred to as ZTN@COF@poloxamer, which contain a Zr-based MOF and tetrakis (4-carbethoxyphenyl) porphyrin as a photosensitizer, are coated with a COF to improve the sensitizing properties, and are loaded with niraparib to inhibit DNA repair. Experiments demonstrate that this new nanocapsules treatment significantly inhibits STS growth, promotes tumor cell apoptosis, exhibits high antitumor activity with minimal side effects, activates the immune response of the tumor, and inhibits lung metastasis in vivo. Therefore, MOF@COF nanocapsules combined with PARPi offer a promising approach for STS treatment, with the potential to enhance the efficacy of PDT and prevent tumor recurrence.
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Estruturas Metalorgânicas , Nanocápsulas , Fotoquimioterapia , Inibidores de Poli(ADP-Ribose) Polimerases , Sarcoma , Fotoquimioterapia/métodos , Animais , Nanocápsulas/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Linhagem Celular Tumoral , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Humanos , Apoptose/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , FemininoRESUMO
Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.
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Quimiocinas CXC , Integrinas , Neoplasias Pulmonares , Osteossarcoma , Microambiente Tumoral , Humanos , Linhagem Celular Tumoral , Quimiocinas CXC/metabolismo , Fibroblastos/metabolismo , Integrinas/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Receptores de Colágeno , Fator de Crescimento Transformador beta/metabolismoRESUMO
Background: This study aims to build a focal adhesion-related genes-based prognostic signature (FAS) to accurately predict gastric cancer (GC) prognosis and identify key prognostic genes related to gastric cancer. Results: Gene expression and clinical data of gastric cancer patients were sourced from Gene Expression Omnibus and The Cancer Genome Atlas. Subsequently, the GEO dataset was randomly distributed into training and test cohorts. The TCGA dataset was used to validate the external cohort. Lasso Cox regression was used to detect OS-related genes in the GEO cohort. A risk score model was established according to the screened genes. A nomogram, based on the clinical characteristics and risk score, was generated to predict the prognosis of gastric cancer patients. Using time-dependent receiver operating characteristic (ROC) and calibration performances, we evaluated the models' validity. The patients were grouped into a high- or low-risk group depending on the risk score. Low-risk patients exhibited higher OS than high-risk patients (entire cohort: p < 0.001; training cohort: p < 0.001, test cohort: p < 0.001). Furthermore, we found a correlation between high-risk gastric cancer and extracellular matrix (ECM) receptor interaction, high infiltration of macrophages, CD44, and HLA-DOA. Conclusion: The generated model based on the genetic characteristics of the focal adhesion prognostic gene can aid in the prognosis of gastric cancer patients in the future.
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Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism-related genes in GC patients. Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors. Results: A risk predictive score model was established based on the expression of 19 lipid metabolism-related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high-risk and low-risk score groups. A nomogram containing patients' age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years. Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism-related genes, which could be a potential prognostic indicator and therapeutic target of GC.
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In this study, we developed a long noncoding RNA (lncRNA)-based prognostic signature for stratification of patients with head a nd neck squamous cell carcinoma (HNSCC). In total, 493 HNSCC samples obtained from the Cancer Genome Atlas database were divided into training and testing cohorts (3:2 ratio). We identified 3913 immune-related lncRNAs in the HNSCC training cohort by Pearson correlation analysis; only seven were independently associated with overall survival and were used to develop an immune-related lncRNA prognostic signature (IRLPS) grouping of HNSCC patients into high- and low-IRLPS subgroups. Univariate and multivariate Cox analyses revealed that low-IRLPS patients had a better prognosis in all the cohorts, which was retained after stratification by sex, grade, and HPV status. Although the TNM stage was also an independent prognostic factor, the IRLPS had a better discriminability with higher AUC at the 3- and 5-year follow-ups in all cohorts. Low-IRLPS samples had more immune cell infiltration and were enriched in immune-related pathways, while high- IRLPS samples were enriched in metabolic pathways. A nomogram constructed including age, TNM stage, and IRLPS showed good calibration. Thus, IRLPS improves the prognostic prediction and also distinguishes different tumor microenvironment (TME) in HNSCC patients.
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Neoplasias de Cabeça e Pescoço/genética , Nomogramas , RNA Longo não Codificante/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores Etários , Idoso , Bases de Dados Genéticas , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , TranscriptomaRESUMO
Exopolysaccharide (EPS)-producing lactic acid bacteria have been widely used in fermented milk, but interaction between the EPS and milk proteins has not been well studied. In this study, interaction between the EPS from Lactobacillus plantarum YW11 (EPS-YW11) and whey proteins (WP), and functional properties of the EPS-YW11/WP were investigated. The results showed that EPS-YW11 tended to encase WP by ζ-potential analysis with a decrease in the surface charge of the protein fraction (from -26.00 mV to 15.30 mV), and an increase in the melting temperature of the protein fraction (from 76.31 °C to 84.48 °C) as shown by differential scanning calorimetry. Circular dichroism spectrometry showed that the EPS could induce structural change of WP, that is, increment in the content of α-helixes and random coils, There was stronger interaction between EPS-YW11 and WP at higher temperatures (60 °C, 90 °C) due to formation of intermolecular H-bonds and OH stretching vibration as indicated by infrared spectral analysis. A significant improvement in the texture (hardness, springiness, gumminess, resilience, cohesiveness, and chewiness) of the EPS-YW11/WP complex was also observed when compared to that of the EPS or WP alone. This was confirmed by microstructural observation of the EPS-YW11/WP complex that formed branched and porous structures, and it became more complex and stable with increased temperature treatment. Due to the strong interaction the EPS-YW11/WP exhibited improved functionality. This study identifies the potential of the EPS-YW11 to serve as a functional agent in the processing of fermented dairy products with enhanced textural stability and bioactivities such as cholesterol-lowering, antioxidant, and antibiofilm.
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Biopolímeros/química , Produtos Fermentados do Leite/análise , Lactobacillus plantarum/química , Polissacarídeos Bacterianos/química , Proteínas do Soro do Leite/química , Animais , Antioxidantes/análise , Reatores Biológicos , Fermentação , TemperaturaRESUMO
Gastric cancer is a malignant tumor with high morbidity and mortality worldwide. However, increasing evidences have revealed the correlation between the glycolysis process and tumorigenesis. This study is aim to develop a list of glycolysis-related genes for risk stratification in gastric cancer patients. We included 500 patients' sample data from GSE62254 and GSE26942 datasets, and classified patients into training (n = 350) and testing sets (n = 150) at a ratio of 7: 3. Univariate and multivariate Cox regression analysis were performed to screen genes having prognostic value. Based on HALLMARK gene sets, we identified 9 glycolysis-related genes (BPNT1, DCN, FUT8, GMPPA, GPC3, LDHC, ME2, PLOD2, and UGP2). On the basis of risk score developed by the 9 genes, patients were classified into high- and low-risk groups. The survival analysis showed that the high-risk patients had a worse prognosis (p < 0.001). Similar finding was observed in the testing cohort and 2 independent cohorts (GSE13861 and TCGA-STAD, all p < 0.001). The multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for overall survival (p < 0.001). Furthermore, we constructed a nomogram that integrated the risk score and tumor stage, age, and adjuvant chemotherapy. Through comparing the results of the receiver operating characteristic curves and decision curve analysis, we found that the nomogram had a superior predictive accuracy than conventional TNM staging system, suggesting that the risk score combined with other clinical factors (age, tumor stage, and adjuvant chemotherapy) can develop a robust prediction for survival and improve the individualized clinical decision making of the patient.In conclusion, we identified 9 glycolysis-related genes from hallmark glycolysis pathway. Based on the 9 genes, gastric cancer patients were separated into different risk groups related to survival.
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Biomarcadores Tumorais/genética , Glicólise/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , TranscriptomaRESUMO
To understand the molecular mechanism involved in the survivability of cold-tolerant lactic acid bacteria was of great significance in food processing, since these bacteria play a key role in a variety of low-temperature fermented foods. In this study, the cold-stress response of probiotic Lactobacillus plantarum K25 isolated from Tibetan kefir grains was analyzed by iTRAQ proteomic method. By comparing differentially expressed (DE) protein profiles of the strain incubated at 10°C and 37°C, 506 DE proteins were identified. The DE proteins involved in carbohydrate, amino acid and fatty acid biosynthesis and metabolism were significantly down-regulated, leading to a specific energy conservation survival mode. The DE proteins related to DNA repair, transcription and translation were up-regulated, implicating change of gene expression and more protein biosynthesis needed in response to cold stress. In addition, two-component system, quorum sensing and ABC (ATP-binding cassette) transporters also participated in cell cold-adaptation process. These findings provide novel insight into the cold-resistance mechanism in L. plantarum with potential application in low temperature fermented or preserved foods.
Assuntos
Resposta ao Choque Frio , Lactobacillus plantarum/fisiologia , Probióticos , Proteoma , Proteômica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cromatografia Líquida , Temperatura Baixa , Biologia Computacional/métodos , Análise de Dados , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Anotação de Sequência Molecular , Proteômica/métodos , Espectrometria de Massas em TandemRESUMO
Gastric cancer is one of the most common malignant tumours in the world. As one of the crucial hallmarks of cancer reprogramming of metabolism and the relevant researches have a promising application in the diagnosis treatment and prognostic prediction of malignant tumours. This study aims to identify a group of metabolism-related genes to construct a prediction model for the prognosis of gastric cancer. A large cohort of gastric cancer cases (1121 cases) from public database was included in our analysis and classified patients into training and testing cohorts at a ratio of 7: 3. After identifying a list of metabolism-related genes having prognostic value, we constructed a risk score based on metabolism-related genes using LASSO-COX method. According to the risk score, patients were divided into high- and low-risk groups. Our results revealed that high-risk patients had a significantly worse prognosis than low-risk patients in both the training (high-risk vs low-risk patients; five years overall survival: 37.2% vs 72.2%; p < 0.001) and testing cohorts (high-risk vs low-risk patients; five years overall survival: 42.9% vs 62.9%; p < 0.001). This observation was validated in the external validation cohort (high-risk vs. low-risk patients; five years overall survival: 30.2% vs 40.4%; p = 0.007). To reinforce the predictive ability of the model, we integrated risk score, age, adjuvant chemotherapy, and TNM stage into a nomogram. According to the result of receiver operating characteristic curves and decision curves analysis, we found that the nomogram score had a superior predictive ability than conventional factors, indicating that the risk score combined with clinicopathological features can develop a robust prediction for survival and improve the individualized clinical decision making of the patient. In conclusion, we identified a list of metabolic genes related to survival and developed a metabolism-based predictive model for gastric cancer. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was confirmed.