Artigos de revistas sobre o tema "Analyse des infiltrations"
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D, Krause, Guiu B, Lerais J-M, Vadanici L, Vignon N, Cercueil J.-P, Loffroy R e Demondion X. "Infiltrations rachidiennes foraminales lombaires : analyse des risques potentiels". Journal de Radiologie 91, n.º 9 (setembro de 2010): 1086–92. http://dx.doi.org/10.1016/s0221-0363(10)70153-0.
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Krausé, D., R. Loffroy, B. Guiu, N. Méjean, M. G. Mourot De Rougemont, L. Vadanici e J. P. Cercueil. "Infiltrations foraminales cervicales : analyse des risques potentiels (experience de 10 ans)". Journal de Radiologie 90, n.º 10 (outubro de 2009): 1265. http://dx.doi.org/10.1016/s0221-0363(09)75054-1.
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Silveira, Heloísa Emília Dias da, e João Jorge Diniz Barbachan. "Estudo comparativo entre limites radiográfico e histológico em ameloblastomas". Revista da Faculdade de Odontologia de Porto Alegre 40, n.º 2 (28 de outubro de 2021): 49–54. http://dx.doi.org/10.22456/2177-0018.119603.
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The aim of this study was to analyse the presence of histological infiltrations of neoplastic cells within the bone, and compare the distance of these infiltrations with the radiografic limits of the ameloblastoma. For this purpose, six integral surgical samples, with identifiable radiographic limits of the tumor, sent to the Pathology Service of Dental School of the Federal University of Rio Grande do SuÌ, were processed. From the resuÌts obtained, can be concluded úat, alúough ameloblastoma presents well-defined radiographic limits, it is infiltrative from the histological view point. Infiltrations occurs at few and distinctive sites. varying in this study from 0.10 cm to 1.40 cm, related to the radiographic borders of the neoplasm.
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Silveira, Heloísa Emília Dias da, e João Jorge Diniz Barbachan. "Estudo comparativo entre limites radiográfico e histológico em ameloblastomas". Revista da Faculdade de Odontologia de Porto Alegre 41, n.º 1 (31 de julho de 2021): 49–54. http://dx.doi.org/10.22456/2177-0018.110315.
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The aim of this study was to analyse the presence of histological infiltrations of neoplastic cells within the bone, and compare the distance of these infiltrations with the radiografic limits of the ameloblastoma. For this purpose, six integral surgical samples, with identifiable radiographic limits of the tumor, sent to the Pathology Service of Dental School of the Federal University of Rio Grande do Sul, were processed. From the results obtained, can be concluded that, although ameloblastoma presents well-defined radiographic limits, it is infiltrative from the histological view point. Infiltrations occurs at few and distinctive sites, varying in this study from 0.10 cm to 1.40 cm, related to the radiographic borders of the neoplasm.
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Trellu, Sabine, Sabrina Dadoun, Francis Berenbaum, Bruno Fautrel e Laure Gossec. "Infiltrations intra-articulaires dans la rhizarthrose : revue systématique et méta-analyse d’essais comparatifs randomisés". Revue du Rhumatisme 83, n.º 3 (maio de 2016): 177–82. http://dx.doi.org/10.1016/j.rhum.2016.03.001.
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Krausé, D., R. Loffroy, B. Guiu, N. Méjean, M. G. Mourot De Rougemont, L. Vadanici e J. P. Cercueil. "OA-WS-34 Infiltrations foraminales cervicales : analyse des risques potentiels (experience de 10 ans)". Journal de Radiologie 90, n.º 10 (outubro de 2009): 1574–75. http://dx.doi.org/10.1016/s0221-0363(09)76180-3.
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Debionne, T., M. Auroux, S. Mainbourg e R. Chapurlat. "Efficacité des infiltrations intra-articulaires de plasma riche en plaquettes comparé au placebo dans la gonarthrose : revue systématique de la littérature et méta-analyse". Revue du Rhumatisme 90 (dezembro de 2023): A251. http://dx.doi.org/10.1016/j.rhum.2023.10.377.
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Labat, J. J., T. Riant, R. Robert, B. Rioult, A. Lassaux, M. Khalfallah, B. Rabischong e A. M. Leroi. "Analyse de l’effet thérapeutique à trois mois des infiltrations du nerf pudendal dans les névralgies pudendales par syndrome canalaire. Étude prospective, randomisée à trois bras, comparant l’efficacité des corticoïdes locaux à des infiltrations à grands volumes versus bras contrôle. Réalisée chez 201 patients". Douleurs : Evaluation - Diagnostic - Traitement 13 (novembro de 2012): A85—A86. http://dx.doi.org/10.1016/j.douler.2012.08.234.
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Xiong, Ying, Zewei Wang, Quan Zhou, Han Zeng, Hongyu Zhang, Zhaopei Liu, Qiuren Huang et al. "Identification and validation of dichotomous immune subtypes based on intratumoral immune cells infiltration in clear cell renal cell carcinoma patients". Journal for ImmunoTherapy of Cancer 8, n.º 1 (março de 2020): e000447. http://dx.doi.org/10.1136/jitc-2019-000447.
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BackgroundIncreasing evidence has elucidated the clinical significance of tumor infiltrating immune cells in predicting outcomes and therapeutic efficacy. In this study, we comprehensively analyze the tumor microenvironment (TME) immune cell infiltrations in clear cell renal cell carcinoma (ccRCC) and correlated the infiltration patterns with anti-tumor immunity and clinical outcomes.MethodsWe analyzed immune cell infiltrations in four independent cohorts, including the KIRC cohort of 533 patients, the Zhongshan ccRCC cohorts of 259 patients, the Zhongshan fresh tumor sample cohorts of 20 patients and the Zhongshan metastatic ccRCC cohorts of 87 patients. Intrinsic patterns of immune cell infiltrations were evaluated for associations with clinicopathological characteristics, underlying biological pathways, genetic changes, oncological outcomes and treatment responses.ResultsUnsupervised clustering of tumor infiltrating immune cells identified two microenvironment subtypes, TMEcluster-A and TMEcluster-B. Gene markers and biological pathways referring to immune evasion were upregulated in TMEcluster-B. TMEcluster-B associated with poor overall survival (p<0.001; HR 2.629) and recurrence free survival (p=0.012; HR 1.870) in ccRCC validation cohort. TMEcluster-B cases had worse treatment response (p=0.009), overall survival (p<0.001; HR 2.223) and progression free survival (p=0.015; HR 2.7762) in metastatic ccRCC cohort. The predictive accuracy of International Metastatic Database Consortium risk score was improved after incorporation of TME clusters.ConclusionsTMEcluster-A featured increased mast cells infiltration, prolonged survival and better treatment response. TMEcluster-B was a heavily infiltrated but immunosuppressed phenotype enriched for macrophages, CD4+T cells, Tregs, CD8+T cells and B cells. TMEcluster-B predicted dismal survival and worse treatment response in clear cell renal cell carcinoma patients.
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Dipalma, Gianna, Assunta Patano, Irene Ferrara, Fabio Viapiano, Anna Netti, Sabino Ceci, Daniela Azzollini et al. "Acceleration Techniques for Teeth Movements in Extractive Orthodontic Therapy". Applied Sciences 13, n.º 17 (29 de agosto de 2023): 9759. http://dx.doi.org/10.3390/app13179759.
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For a world that is constantly trying to speed up every procedure while obtaining the maximum result, traditional orthodontics have the biological limitation of using light and constant forces that allow tooth movement in a time frame that is only sometimes short. The treatment time could be lengthened if surgical procedures are programmed in the plan. Methods to accelerate tooth movement and reduce the duration of treatment while minimising complications are investigated and reported in the dental literature (e.g., low-level laser therapy, corticotomy, and micro-osteoperforations). This systematic review aims to analyse and summarise the strategies for quickening orthodontic movement during extraction orthodontic treatment, including any potential drawbacks or adverse consequences. The review will evaluate each approach’s effectiveness, safety, and evidence quality, compare their benefits and disadvantages, and analyse the implications for clinical practice and future research. Pubmed, Science Direct, Scopus, and Web of Science were searched using the keywords “acceleration” AND “dental movement” AND “orthodontic” between 1 April 2003 and 1 April 2023. After carefully scanning the study findings, forty-four publications were chosen for the systematic review. Most therapies discussed and provided in the literature seem promising and successful in enhancing orthodontic treatments. The success of operations like corticotomies, piezo-incisions, micro-osteoperforations, osteogenic distraction, low-level laser therapy, the administration of pharmacological treatments, and infiltrations with PRF and PRP were statistically significant and appear to be promising and effective in optimising orthodontic treatments. These strategies expedite treatment and enhance the patient experience, potentially broadening orthodontic appeal and minimising issues like cavities and enamel demineralisation. Further studies, with larger samples and standardised treatment protocols, are needed to investigate the efficacy of these tooth movement acceleration modalities.
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Yao, Qi, Xinqi Ge, Zhichao Lu, Jinlong Shi, Jianhong Shen e Jian Chen. "HAUS Augmin-Like Complex Subunit 1 Influences Tumour Microenvironment and Prognostic Outcomes in Glioma". Journal of Oncology 2022 (12 de julho de 2022): 1–19. http://dx.doi.org/10.1155/2022/8027686.
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Background. The expression of HAUS Augmin-like complex subunit 1 (HAUS1), a protein-coding gene, is low in normal samples among various cancers with pan-cancer analysis. The depletion of HAUS1 in cells decreases the G2/M cell compartment and induces apoptosis. However, the detailed expression pattern of HAUS1 and its correlation with immune infiltration in glioma (LGG and GBM) (LGG: low-grade glioma; GBM: glioblastoma) remain unknown. Therefore, in this study, we examined the role and prognostic value of HAUS1 in glioma. Methods. Transcriptional expression data of HAUS1 were collected from the CGGA and TCGA databases. The Kaplan–Meier analysis, univariate and multivariate Cox analyses, and receiver operating characteristic (ROC) curves were used to analyse the clinical significance of HAUS1 in glioma. The STRING database was used to analyse protein-protein interactions (PPI), and the “ClusterProfiler” package was used for functional enrichment analysis to examine the possible biological roles of HAUS1. In addition, the HAUS1 promoter methylation modification was analysed using MEXPRESS, and the association between HAUS1 expression and tumour-infiltrating immune cells was investigated using CIBERSORT. Results. Based on the data retrieved from TCGA (703 samples) and CGGA (1018 samples), an elevated expression of HAUS1 was observed in glioma samples, which was associated with poorer survival of patients, unfavourable clinical characteristics, 1p/19q codeletion status, WHO grade, and IDH mutation status. Furthermore, multivariate and univariate Cox analyses revealed that HAUS1 was an independent predictor of glioma. HAUS1 expression level was associated with several tumour-infiltrating immune cells, such as Th2 cells, macrophages, and activated dendritic cells. The outcomes of ROC curve analysis showed that HAUS1 was good to prognosticate immune infiltrating levels in glioma with a higher area under the curve (AUC) value (AUC = 0.974). Conclusions. HAUS1 was upregulated and served as a biomarker for poor prognosis in patients with glioma. High HAUS1 expression was associated with several tumour-infiltrating immune cells such as Th2 cells, macrophages, and activated dendritic cells, which had high infiltration levels. Therefore, these findings suggest that HAUS1 is a potential biomarker for predicting the prognosis of patients with glioma and plays a pivotal role in immune infiltration in glioma.
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Seyboldt, Christoph, Mathias Liewald e Daniel Heydt. "Production of Aluminium Based Interpenetrating Phase Composites Using Semi-Solid Forming". Key Engineering Materials 716 (outubro de 2016): 502–9. http://dx.doi.org/10.4028/www.scientific.net/kem.716.502.
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The following paper deals with the production of Interpenetrating Phase Composites (IPC) using semi-solid forming technology. Therefore, adequate ceramic foams were selected and infiltrated by processing the aluminium alloy A356 in the semi-solid state. In the studies presented in this paper, the infiltrations of two ceramic materials (Al2O3 and SiC) with three different pore sizes (10, 20 and 30 ppi) were investigated. During the forming process the liquid phase fraction of the aluminium was varied to analyze infiltration effects in relation to the raw material´s liquid phase fraction. Afterwards, microsections of the produced specimens were analyzed in order to characterize their microstructure and the quality of infiltration. The results showed that completely filled composite components with good mechanical properties can be produced by infiltrating ceramic preforms with a semi-solid aluminium alloy.
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Labat, J. J., T. Riant, B. Rioult, A. Lassaux, M. Khalfallah, A. M. Leroi e J. Rigaud. "Analyse de l’effet thérapeutique à trois mois des infiltrations du nerf pudendal dans les névralgies pudendales. Étude prospective, randomisée à trois bras, de l’efficacité des corticoïdes locaux vs bras contrôle chez 201 patients". Progrès en Urologie 22, n.º 13 (novembro de 2012): 837. http://dx.doi.org/10.1016/j.purol.2012.08.221.
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Wang, Wenzhi, Xiaoying Liu e Lei Zheng. "Correlation Analysis of Immune Cell Infiltration in Recurrent Endometrial Carcinoma". Journal of Biomedical Nanotechnology 19, n.º 7 (1 de julho de 2023): 1239–46. http://dx.doi.org/10.1166/jbn.2023.3635.
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Numerous studies have established a close relationship between tumor progression, prognosis, and the infiltration of immune cells in the tumor microenvironment. This study aimed to investigate the differences in infiltrating immune cells between recurrent endometrial cancer and non-recurrent endometrial cancer. Firstly, gene expression data of endometrial cancer were obtained from the GEO database. Differential gene analysis using Geo2R identified significant gene expression differences, and KEGG and GO analyses were conducted on the qualified differential genes. Subsequently, CIBERSORT was employed to analyze the infiltration of 22 immune cell types in the tumor microenvironment, identifying differential immune cells. The results revealed significant differences in gene expression between recurrent and non-recurrent endometrial carcinoma. Interestingly, CIBERSORT analysis demonstrated a significant increase in monocyte infiltration in recurrent endometrial cancer compared to non-recurrent cases. Monocyte infiltration was found to play a crucial role in the progression of endometrial cancer recurrence. These findings provide valuable insights for clinicians to develop personalized treatment strategies for patients with recurrent endometrial cancer.
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Ouattara, Karim, Elisée Napari Yeo, Inza Kone e Blandine Schafner. "Identification des critères et risques de la création du corridor écologique transfrontalier entre le Liberia et la Côte d’Ivoire". International Journal of Biological and Chemical Sciences 16, n.º 4 (1 de novembro de 2022): 1631–45. http://dx.doi.org/10.4314/ijbcs.v16i4.22.
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Depuis plusieurs décennies la pression sur les aires protégées s’accroit à travers des infiltrations humaines pour la chasse, l’agriculture et l’orpaillage. De nos jours, les couloirs écologiques constituent une alternative durable face à la fragmentation et à l’isolement des aires protégées. Afin d’anticiper sur les éventuelles conséquences d’un isolement consommé du Parc national de Taï en Côte d’Ivoire et celui de Grebo Khran au Liberia, les gouvernements des deux pays ont décidé de mettre en place un corridor écologique entre ces parcs. Dans l’optique de réussir ce processus de conservation, une étude a été menée pour identifier les critères et les risques à prendre en compte dans la mise en place d’un tel couloir écologique. Pour cela, une analyse bibliographique basée sur l’écologie de plusieurs espèces animales a été réalisée en combinaison avec des consultations inclusives à travers des enquêtes et des rencontres ciblées avec les parties prenantes, dont les communautés locales, les décideurs et les scientifiques. Ainsi, cette étude a décrit les principaux critères et risques institutionnels, socio-économiques et écologiques ainsi que les principaux risques sanitaires. Il ressort de l’étude que le développement d’un tel couloir écologique repose sur des fondements écologiques et des enjeux institutionnels et socio-économiques.
For several decades the pressure on protected areas has been increasing through human infiltration for hunting, agriculture, and gold mining. Nowadays, ecological corridors are a sustainable alternative to the fragmentation and isolation of protected areas. In order to anticipate the possible consequences of a consummate isolation of the Taï National Park in Côte d'Ivoire and the Grebo Khran National Park in Liberia, the governments of both countries have decided to establish an ecological corridor between these parks. With a view to the success of this conservation process, a study was carried out to identify the criteria and risks to be considered in the establishment of such an ecological corridor. For this purpose, a literature review based on the ecology of several animal species was carried out in combination with inclusive consultations through surveys and targeted meetings with stakeholders, including local communities, decision makers and scientists. The study described the main institutional, socio-economic, and ecological criteria and risks, as well as the main health risks. This study shows that the development of such an ecological corridor is based on ecological foundations and institutional and socio-economic issues.
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Lu, Zheng-Min, Shi-Ling Pan, Wen-Li Yuan, Jia-Li Feng, Dan Tian e Xue-Qin Shang. "Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer". Medicine 102, n.º 50 (15 de dezembro de 2023): e36480. http://dx.doi.org/10.1097/md.0000000000036480.
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CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.
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Liu, Fuqiang, Tao Wei, Lin Liu, Fangxia Hou, Cuixiang Xu, Hua Guo, Wei Zhang et al. "Role of Necroptosis and Immune Infiltration in Human Stanford Type A Aortic Dissection: Novel Insights from Bioinformatics Analyses". Oxidative Medicine and Cellular Longevity 2022 (16 de abril de 2022): 1–18. http://dx.doi.org/10.1155/2022/6184802.
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Background. Stanford type A aortic dissection (TAAD) is one of the most life-threatening cardiovascular emergencies with high mortality and morbidity, and necroptosis is a newly identified type of programmed cell death and contributes to the pathogenesis of various cardiovascular diseases. However, the role of necroptosis in TAAD has not been elucidated. This study was aimed at determining the role of necroptosis in TAAD using bioinformatics analyses. Methods. The RNA sequencing dataset GSE153434 and the microarray dataset GSE52093 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes of necroptosis (NRDEGs) were identified based on differentially expressed genes (DEGs) and necroptosis gene set. Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks and identify the key functional modules of NRDEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of NRDEGs were also performed. Additionally, Spearman correlations were used to construct the necroptosis-related transcription factor-target genes regulatory network, immune infiltration patterns were analyzed using the ImmuCellAI algorithm, and the correlation between immune cell-type abundance and NRDEGs expression was investigated. The expression levels of NRDEGs and immune infiltration were additionally verified in the GSE52093 dataset. Results. We found that the necroptosis pathway was considerably enriched and activated in TAAD samples. Overall, 25 NRDEGs were identified including MLKL, RIPK1, and FADD, and among them, 18 were verified in the validation set. Moreover, GO and KEGG enrichment analyses found that NRDEGs were primarily involved in the tumor necrosis factor signaling pathway, nucleotide-binding oligomerization domain-like receptor signaling pathway, and interleukin-17 signaling pathway. The imbalance of Th17/Treg cells was identified in the TAAD samples. Furthermore, correlation analysis indicated that expression of NRDEGs was positively associated with proinflammatory immune-cell infiltrations and negatively associated with anti-inflammatory or regulatory immune-cell infiltrations. Conclusions. The present findings suggest that necroptosis phenomenon exists in TAAD and correlates with immune cell infiltration, which indicate necroptosis may promote the development of TAAD through activating immune infiltration and immune response. This study paves a new road to future investigation of the pathogenic mechanisms and therapeutic strategies for TAAD.
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Liao, Pan, Shuzhen Han e Honglan Qu. "Expression, Prognosis, and Immune Infiltrates Analyses of E2Fs in Human Brain and CNS Cancer". BioMed Research International 2020 (15 de dezembro de 2020): 1–17. http://dx.doi.org/10.1155/2020/6281635.
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Objective. We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. Methods. We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. Results. E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3–6 and E2F1–8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. Conclusion. E2F1–8 and E2F2–8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3–6 and E2F1–8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.
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Maeda, Shingo, Tomoki Motegi, Aki Iio, Kenjiro Kaji, Yuko Goto-Koshino, Shotaro Eto, Namiko Ikeda et al. "Anti-CCR4 treatment depletes regulatory T cells and leads to clinical activity in a canine model of advanced prostate cancer". Journal for ImmunoTherapy of Cancer 10, n.º 2 (janeiro de 2022): e003731. http://dx.doi.org/10.1136/jitc-2021-003731.
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BackgroundTargeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate cancer remains unclear. Here, we showed the therapeutic efficacy of anti-Treg treatment in a canine model of advanced prostate cancer.MethodsWe used dogs with naturally occurring prostate cancer to study the molecular mechanism underlying Treg infiltration and the effect of anti-Treg treatment. Tumor-infiltrating Tregs was evaluated by immunohistochemistry, and the association with prognosis was examined in dogs with spontaneous prostate cancer. The molecular mechanism of Treg infiltration was explored by RNA sequencing and protein analyses. A non-randomized canine clinical trial was conducted to define the therapeutic potential of anti-Treg treatment for advanced prostate cancer. Human prostate cancer datasets were analyzed to compare gene expression in dogs and humans.ResultsTumor-infiltrating Tregs were associated with poor prognosis in dogs bearing spontaneous prostate cancer. RNA sequencing and protein analyses showed a possible link between the CCL17–CCR4 pathway and the increase of tumor-infiltrating Tregs. Dogs with advanced prostate cancer responded to mogamulizumab, a monoclonal antibody targeting CCR4, with decreased circulating Tregs, improved survival, and low incidence of clinically relevant adverse events. Urinary CCL17 concentration and BRAFV595E mutation were independently predictive of the response to mogamulizumab. Analysis of a transcriptomic dataset of human prostate cancer showed that the CCL17–CCR4 axis correlated with Foxp3. In silico survival analyses revealed that high expression of CCL17 was associated with poor prognosis. Immunohistochemistry confirmed that tumor-infiltrating Tregs expressed CCR4 in human patients with prostate cancer.ConclusionsAnti-Treg treatment, through CCR4 blockade, may be a promising therapeutic approach for advanced prostate cancer in dogs and some population of human patients.
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Lawal, Bashir, Li-Ching Lin, Jih-Chin Lee, Jia-Hong Chen, Tanios S. Bekaii-Saab, Alexander T. H. Wu e Ching-Liang Ho. "Multi-Omics Data Analysis of Gene Expressions and Alterations, Cancer-Associated Fibroblast and Immune Infiltrations, Reveals the Onco-Immune Prognostic Relevance of STAT3/CDK2/4/6 in Human Malignancies". Cancers 13, n.º 5 (25 de fevereiro de 2021): 954. http://dx.doi.org/10.3390/cancers13050954.
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Signal transducer and activator of transcription 3 (STAT3)/Cyclin-dependent kinases are multifunctional proteins that play an important implicative role in cancer initiations, progression, drug resistance, and metastasis, and has been extensively explored in cancer therapy. However, the genetic alterations of STAT3/CDK2/4/6 and its role in predicting immune infiltration and immunotherapeutic response are yet to be well exploited. In this study, we use in silico methods to analyze differential expression, prognostic value, genetic and epigenetic alterations, association with tumor-infiltrating immune cells, and cancer-associated fibroblast (CAF) infiltrations of STAT3/CDK2/4/6 in multiple cancer types. Our results revealed that the expression of STAT3/CDK2/4/6 was altered in various cancers and is associated with poor overall and disease-free survival of the cohorts. Moreover, genetic alterations in STAT3/CDK2/4/6 co-occurred with a number of other genetic alterations and are associated with poorer prognoses of the cohorts. The protein-protein interaction (PPI) network analysis suggests CDK2/4/6/STAT3 may directly interact with factors that promote tumorigenesis and immune response. We found that STAT3/CDK2/4/6 expressions were associated with infiltrations of CAF and the various immune cells in multiple cancers and it’s associated with poor response to immunotherapy. Collectively, our study suggested that STAT3/CDK2/4/6 are important onco-immune signatures that play central roles in tumor immune invasion, poor prognoses and, immune therapy response. Findings from the present study may therefore be clinically useful in prognosis assessment and follow-up management of immunotherapy.
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Yan, Li, Chunyan Hu, Yangyang Ji, Lifen Zou, Yang Zhao, Yi Zhu e Xiaoshen Wang. "Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma". Journal of Immunology Research 2022 (23 de maio de 2022): 1–11. http://dx.doi.org/10.1155/2022/9089397.
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Background. This study is aimed at investigating the expressions and prognostic values of secreted or membrane-located proteins (SMPs) in laryngeal squamous cell carcinoma (LSCC). The correlations between the expressions of SMPs and immune cells’ infiltrations were also investigated. Methods. The expression data of normal laryngeal and LSCC samples were obtained from the TCGA and GEO datasets. The differentially expressed SMPs were identified, and their prognostic values were analyzed. The biological functions of differentially expressed and worse-survival-related SMPs were explored. LASSO regression, Cox multivariate analysis, and nomogram were used to construct a model to predict the survival. Then, the infiltrations of the 24 immune cell populations were calculated using the GSVA method, and the correlations between the expression of SMPs and the immune infiltration were investigated. Results. 122 samples (12 normal and 120 LSCC) of the TCGA database and 114 samples (57 normal and 57 LSCC) of GSE127165 were included. We identified that 138 SMPs were significantly upregulated in LSCC samples of both the TCGA and GEO datasets, among which 52 SMPs were significantly correlated with worse survival. GO and KEGG analyses revealed those 52 SMPs significantly participate in tumor microenvironment and immune cells’ communication. Nine of 52 SMPs (ABCC5, ATP1B3, CLEC11A, FLNA, FSTL3, MMP1, NME1, OAS3, and PHLDB2) were included in the nomogram to effectively and accurately predict the LSCC patients’ survival. The expressions of most SMPs, such as MMP1 and FSTL3, were significantly positively correlated with the immune infiltration of LSCC. Conclusions. In this study, the expression, prognostic values, and correlations with immune infiltration of SMPs were analyzed in LSCC samples. Our analyses identified several significant SMPs differentially expressed between normal laryngeal and LSCC samples, correlated with worse survival, and related to the immune infiltration.
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Chen, Huihui, Jingyi Zhao, Junhui Hu, Xu Xiao, Wenda Shi, Yinhui Yao e Ying Wang. "Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis". BioMed Research International 2022 (6 de abril de 2022): 1–15. http://dx.doi.org/10.1155/2022/1926661.
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Aims. This study is aimed at investigating the pathogenesis of rheumatoid arthritis (RA) by identifying key biomarkers, associated immune infiltration, and small-molecule compounds using bioinformatic analysis. Methods. Six datasets were obtained from the Gene Expression Omnibus database, and the batch effect was adjusted. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse differentially expressed genes (DEGs). Furthermore, candidate small-molecule drugs associated with RA were selected from the Connectivity Map (CMap) database. The least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and multivariate logistic regression analyses were performed on DEGs to screen for RA diagnostic markers. The receiver operating characteristic curve, concordance index, and GiViTi calibration band were the metrics used to assess the diagnostic markers of RA identified in this analysis. The single-sample gene set enrichment analysis was performed to calculate the scores of infiltrating immune cells and evaluate the activities of immune-related pathways. Finally, the correlation between screening markers and RA diagnosis was determined. Results. A total of 227 DEGs were identified. Functional enrichment analysis and KEGG revealed that DEGs were enriched by the immune response. CMap analysis identified 11 small-molecule compounds with therapeutic potential for RA. In gene expression, the activities of 13 immune cells and 12 immune-related pathways significantly differed between patients with RA and healthy controls. DPYSL3 and SPP1 had the potential to diagnose RA. SPP1 expression was positively correlated with DPYSL3 in 11 immune cells and 10 immune-related pathways. Conclusion. This study comprehensively analysed DEGs and immune infiltration and screened for potential diagnostic markers and small-molecule compounds of RA.
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Yang, Jianle, Yu Fan e Shuzhong Liu. "ATF3 as a potential diagnostic marker of early-stage osteoarthritis and its correlation with immune infiltration through bioinformatics analysis". Bone & Joint Research 11, n.º 9 (1 de setembro de 2022): 679–89. http://dx.doi.org/10.1302/2046-3758.119.bjr-2022-0075.r1.
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Aims This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689.
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Croteau, David, Lisa Scarpace, David Hearshen, Jorge Gutierrez, James L. Fisher, Jack P. Rock e Tom Mikkelsen. "Correlation between Magnetic Resonance Spectroscopy Imaging and Image-guided Biopsies: Semiquantitative and Qualitative Histopathological Analyses of Patients with Untreated Glioma". Neurosurgery 49, n.º 4 (1 de outubro de 2001): 823–29. http://dx.doi.org/10.1097/00006123-200110000-00008.
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Abstract OBJECTIVE Since intratumoral heterogeneity of gliomas is not adequately reflected in conventional magnetic resonance imaging (MRI), we sought to determine a correlation between different proton magnetic resonance spectroscopic imaging (1H MRSI) metabolic ratios and the degree of tumor infiltration in diffusely infiltrating gliomas. In this report, we describe the microscopic anatomy of gliomas on imaging. METHODS Image-guided biopsies with semiquantitative and qualitative histopathological analyses from a series of 31 untreated patients with low- and high-grade gliomas were correlated with multivoxel 1H MRSI referenced to the same spatial coordinates. RESULTS This series yielded 247 tissue samples and 307 observations. Choline-containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetylaspartate appear to correlate best with the degree of tumor infiltration. Similar correlations were present within each grade after stratification. Despite the interpatient overlap of metabolic ratios between normal tissue and mild tumor infiltration, preliminary analyses revealed that 1H MRSI appears more accurate than conventional MRI in defining the tumor boundary and quantifying the degree of tumor infiltration. CONCLUSION This is the first study showing histopathological validation of tumor boundaries using 1H MRSI. These results support the conclusion that 1H MRSI accurately reflects the extent of the disease in patients with gliomas. This has important diagnostic and therapeutic implications for more accurately assessing the burden of disease as well as for planning and assessing response to therapy.
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Kapfhammer, A., T. Winkens, T. Lesser, A. Reissig, M. Steinert e M. Freesmeyer. "Enhancing 18F-FDG-PET/CT analysis in lung cancer patients". Nuklearmedizin 54, n.º 06 (2015): 247–54. http://dx.doi.org/10.3413/nukmed-0763-15-08.
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SummaryAim: To retrospectively evaluate the feasibility and value of CT-CT image fusion to assess the shift of peripheral lung cancers with/-out chest wall infiltration, comparing computed tomography acquisitions in shallow-breathing (SB-CT) and deep-inspiration breath-hold (DIBH-CT) in patients undergoing FDG-PET/ CT for lung cancer staging. Methods: Image fusion of SB-CT and DIBH-CT was performed with a multimodal workstation used for nuclear medicine fusion imaging. The distance of intrathoracic landmarks and the positional shift of tumours were measured using semitransparent overlay of both CT series. Statistical analyses were adjusted for confounders of tumour infiltration. Cutoff levels were calculated for prediction of no-/infiltration. Results: Lateral pleural recessus and diaphragm showed the largest respiratory excursions. Infiltrating lung cancers showed more limited respiratory shifts than non-infiltrating tumours. A large respiratory tumour-motility accurately predicted non-infiltration. However, the tumour shifts were limited and variable, limiting the accuracy of prediction. Conclusion: This pilot fusion study proved feasible and allowed a simple analysis of the respiratory shifts of peripheral lung tumours using CT-CT image fusion in a PET/CT setting. The calculated cutoffs were useful in predicting the exclusion of chest wall infiltration but did not accurately predict tumour infiltration. This method can provide additional qualitative information in patients with lung cancers with contact to the chest wall but unclear CT evidence of infiltration undergoing PET/CT without the need of additional investigations. Considering the small sample size investigated, further studies are necessary to verify the obtained results.
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Zhang, Lan, Qing Zhang, Zebo Huang, Mingxia Zhu, Tongshan Wang, Wei Zhu, Xiaping Wang e Xin Zhou. "Integrated Analyses of m6A Regulator-Based Signature on Its Clinical Application and Immunogenomic Landscape in Stomach Adenocarcinoma". BioMed Research International 2022 (20 de setembro de 2022): 1–20. http://dx.doi.org/10.1155/2022/2053719.
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Background. The whole tumor microenvironment (TME) infiltration features monitored by integrated roles of different RNA N6-methyladenosine (m6A) regulators remain elusive. Our study is aimed at exploring the association between m6A modification patterns, TME cell-infiltrating levels, and patients’ prognosis in stomach adenocarcinoma (STAD) patients. Methods. Consensus clustering was performed based on the integrated analyses of 17 m6A regulators and 229 m6A-related hallmark genes in STAD (The Cancer Genome Atlas (TCGA) cohort, n = 443 ; Gene Expression Omnibus (GEO) GSE57303, n = 70 , GSE62254 n = 300 , and GSE84437 n = 433 ). A m6ASig scoring system was calculated by the principal component analysis (PCA), and its prognostic value was validated in an independent dataset GES15459. Results. Three m6A clusters were identified among 1246 STAD patients, which had significant overall survival (OS) differences and demonstrated different TME immune cell infiltration and biological behaviors. According to the m6ASig score, which was generated from the m6A-related hallmark genes, STAD patients were divided into the high-m6ASig group ( n = 585 ) and low-m6ASig group ( n = 586 ). Patients in the high-m6ASig group had a notably prolonged OS and higher immune cell infiltration. Moreover, patients with higher m6ASig score were associated with higher microsatellite instability (MSI); higher PD-L1, CTLA4, and ERBB2 expressions; and greater tumor mutation burden (TMB). Patients with higher m6ASig score demonstrated a better immune response and drug sensitivity. Conclusion. Our m6ASig scoring system could characterize TME immune cell infiltration, thus predict patient’s prognosis and immunotherapy and chemotherapy efficacy, offering a novel tool for the individualized therapeutic implications for STAD patients.
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Gerlach, Magdalena M., Darius Juskevicius, Visar Vela, Stefan Dirnhofer e Alexandar Tzankov. "Bone Marrow Infiltration of Angioimmunoblastic T-Cell Lymphoma: Identification and Prognostic Impact of Histologic Patterns and Diagnostic Application of Ancillary Phenotypic and Molecular Analyses". Archives of Pathology & Laboratory Medicine 144, n.º 5 (26 de setembro de 2019): 602–11. http://dx.doi.org/10.5858/arpa.2019-0007-oa.
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Context.— Angioimmunoblastic T-cell lymphomas originate from T follicular helper cells and express respective markers (BCL6, CD10, CXCL13, ICOS, and PD-1). Although commonly present, bone marrow involvement by angioimmunoblastic T-cell lymphoma can be diagnostically challenging. Additionally, only little is known about the distribution of T follicular helper cells in healthy and reactively changed bone marrows or in samples affected by other lymphomas. Objective.— To establish a diagnostic approach to reliably identify bone marrow infiltration of angioimmunoblastic T-cell lymphoma. Design.— We analyzed the morphologic infiltration pattern and the expression of T follicular helper-cell markers in 42 matched paired lymph node and bone marrow samples and applied comparative clonality testing. Furthermore, we studied the expression of BCL6 and PD-1 in a control cohort of healthy, reactively changed, and otherwise affected bone marrows. Results.— We identified 3 different bone marrow infiltration patterns correlating with overall survival (interstitial/micronodular infiltration with or without eosinophilia and diffuse infiltration with eosinophilia). The matched pairs showed a consistent (co)expression of PD-1 and BCL6 with a generally weaker expression in the bone marrow than in the lymph nodes. Comparative clonality testing was helpful in only a minority of cases. Infiltrates of the most important differential diagnoses contained either PD-1– or BCL6-positive tumor-infiltrating cells, but no coexpressing cells. Conclusions.— Bone marrow infiltration by angioimmunoblastic T-cell lymphoma displays 3 different patterns that correlate with prognosis. BCL6 and PD-1 can be reliably used to identify lymphoma infiltrates and to help rule out several differential diagnoses. Comparative clonality testing rarely provides additional value and cannot replace morphologic and phenotypic analyses.
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Stout, Annabel, Natalya Facey, Anjali Bhatnagar, Kirstie Rice, Fedor Berditchevski, Daniel Kearns, Amy Metcalf, Alaa Elghobashy e Abeer M. Shaaban. "Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer—Relation to Tumour Characteristics and Impact on Prognosis". International Journal of Molecular Sciences 25, n.º 8 (20 de abril de 2024): 4524. http://dx.doi.org/10.3390/ijms25084524.
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Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided.
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Richardet, Eduardo, Luciana Paola Acosta, Martin Paradelo, Martin Pairola, Cecilia Di Tada, Matias Molina, Luciano Salvador Dicalbo, Rocio Paola Villavicencio e Martin Eduardo Richardet. "Tumor-infiltrating lymphocytes as a prognostic factor in patients with stage I to III breast cancer." Journal of Clinical Oncology 35, n.º 15_suppl (20 de maio de 2017): e12042-e12042. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e12042.
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e12042 Background: Current evidence makes reference to the potential role that tumor-infiltrating lymphocytes (TILs) as a prognostic factor in breast cancer and numerous types of tumors. Different studies have shown that the interaction with the immune response of the host is relevant to the response to chemotherapy. TILs are cell phenotype T CD3 +, which can, in turn, stratify in cytotoxic T lymphocytes (CD8), and regulatory T cells (CD4+ CD25+ FOXP3+).Our aim was to identify whether there was a relationship between TILs and SLE in patients with stage I to III breast cancer who have undergone chemotherapy adjuvant treatment. The secondary endpoint was to analyze the association between subtype infiltrating lymphocytes (CD4 and CD8) and SLE. Methods: Retrospective and analytical study in our institution IONC. Patients with stage I to III breast cancer was analized which had standard risk factors and required adjuvant treatment with chemotherapy. 87 patients completed with the selection criteria. The infiltration degree by H/E was evaluated and CD4 and CD8 by IHQ was marked. SLE was analyzed through the Kaplan-Meier method. Results: 87 samples were analyzed, in 46 patients (52,8 %) evidenced TILs and in 41 patients (47.12%) there were no TILs in their tumor samples. SLE was higher for those patients who had TILs with respect to those patients who did not have any TILs, 45.3 months as opposed to 30.85 months respectively (p: 0,038) and these differences were statistically different. In the TILi analysis, it could observed that 91% patients not revealed infiltrations in their tumor samples.When correlating CD4 and CD8 was carried out, 33% of the patients showed CD4 TILs in their tumor samples and 49.4% evidenced CD8 TILs. There were no SLE differences regarding the presence or the absence of CD4. The high number of CD8 was associated to a higher SLE; 39.06 months as opposed to 37.5 months, but these differences were not statistically different. Conclusions: We could conclude that patients who had showed TILs in their tumor samples had a higher SLE with respect to those who did not show any infiltration and this was statistically significant. There were no differences when samples were analyzed on the presence or absence of CD4 and CD8.
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Kiser, Jackson W., Thad Benefield, Ronald K. Lattanze, Kelley A. Ryan e James Crowley. "Assessing and Reducing Positron Emission Tomography/Computed Tomography Radiotracer Infiltrations: Lessons in Quality Improvement and Sustainability". JCO Oncology Practice 16, n.º 7 (julho de 2020): e636-e640. http://dx.doi.org/10.1200/jop.19.00302.
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PURPOSE: Accurate administration of radiotracer dose is essential to positron emission tomography (PET) image quality and quantification. Misadministration (infiltration) of the dose can affect PET/computed tomography results and lead to unnecessary or inappropriate treatments and procedures. Quality control efforts ensure accuracy of the administered dose; however, they fail to ensure complete delivery of the dose into the patient’s circulation. We used new technology to assess and improve infiltration rates and evaluate sustainability. METHODS: Injection quality was measured, improved, and sustained during our participation in a multicenter quality improvement project using Define, Measure, Analyze, Improve, Control methodology. Five technologists monitored injection quality in the Measure and Improve phases. After seven new technologists joined the team in the Control phase, infiltration rates were recalculated, controlling for technologist- and patient-level correlations, and comparisons were made between these two groups of technologists. RESULTS: In the Measure phase, five technologists monitored 263 injections (13.3% infiltration rate). Nonantecubital fossa injections had a higher probability of infiltration than antecubital fossa injections. After implementing a quality improvement plan (QIP), the same technologists monitored 278 injections in the Improve phase (2.9% infiltration rate). The 78% decrease in infiltration rate was significant ( P < .001) as was the decrease in nonantecubital fossa infiltrations ( P = .0025). In the Control phase, 12 technologists monitored 1,240 injections (3.1% infiltration rate). The seven new technologists had significantly higher rates of infiltration ( P = .017). CONCLUSION: A QIP can significantly improve and sustain injection quality; however, ongoing monitoring is needed as new technologists join the team.
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Zhuang, Zifan, e Chundi Gao. "Development of a Clinical Prognostic Model for Metabolism-Related Genes in Squamous Lung Cancer and Correlation Analysis of Immune Microenvironment". BioMed Research International 2022 (6 de setembro de 2022): 1–15. http://dx.doi.org/10.1155/2022/6962056.
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Background. The incidence of squamous lung cancer (LUSC) has substantially increased. Systematic studies of metabolic genomic patterns are fundamental for the treatment and prediction of LUSC. Because cancer metabolism and immune cell metabolism have been studied in depth, metabolism and the state and function of immune cells have become key factors in tumor development. This also indicates that metabolic genes and the tumor immune microenvironment (TME) are crucial in tumor treatment. This study is aimed at dissecting the connection between TME and LUSC digestion-related qualities. Methods. The information used in this study was obtained from The Cancer Genome Atlas dataset. Metabolism-related genes in patients with LUSC were screened, and relevant clinical data were collated. Next, genes associated with prognosis were screened using univariate COX regression and LASSO regression analyses. Finally, a timer database study was conducted to analyze the molecular mechanisms of immune cell infiltration of LUSC prognosis-related metabolic genes at the immune cell level. Results. Nine metabolism-related genes were identified: ADCY7, ALDH3B1, CHIA, CYP2C18, ENTPD6, GGCT, HPRT1, PLA2G1B, and PTGIS. A clinical prediction model for LUSC based on metabolism-related genes was constructed. In addition, 22 subpopulations of tumor-infiltrating immune cells (TIIC) in the TME were analyzed using the CIBERSORT algorithm. Finally, we used the TIMER database to analyze the immune infiltration of LUSC and the relationship between metabolism-related genes and immune cells. Conclusion. Our study identified metabolic genes associated with the prognosis of LUSC, which are important markers for its diagnosis, clinically relevant assessments, and prognosis. The relationship between metabolic genes with prognostic impact and immune infiltration was also analyzed, and a metabolic gene-based clinical prediction model was identified, providing a new perspective for LUSC treatment.
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Tian, Jianbo, Yimin Cai, Yue Li, Zequn Lu, Jinyu Huang, Yao Deng, Nan Yang et al. "CancerImmunityQTL: a database to systematically evaluate the impact of genetic variants on immune infiltration in human cancer". Nucleic Acids Research 49, n.º D1 (3 de outubro de 2020): D1065—D1073. http://dx.doi.org/10.1093/nar/gkaa805.
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Abstract Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http://www.cancerimmunityqtl-hust.com/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.
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Guo, Christina, Jan Rekowski, Mateus Crespo, Bora Gurel, Wei Yuan, Adam Sharp, Rafael Grochot et al. "Abstract 3415: The neutrophil-to-lymphocyte ratio (NLR) reflects intratumor myeloid derived suppressor cell (MDSC) infiltration in metastatic castration-resistant prostate cancers (mCRPC)". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 3415. http://dx.doi.org/10.1158/1538-7445.am2022-3415.
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Abstract Background: High neutrophil-to-lymphocyte ratio (NLR) associates with worse overall survival (OS) from prostate cancer (PC) and low response rates to abiraterone and taxane chemotherapy and may reflect systemic inflammatory changes. A direct link between high NLR and intratumoral myeloid infiltration has not been demonstrated to date. We evaluated the relationship between NLR and intratumor immune cell densities in mCRPC biopsies. Design: mCRPC biopsies from 71 patients treated at The Institute of Cancer Research/Royal Marsden Hospital (ICR/RMH, UK) were stained by immunofluorescence for CD11b, CD15, and DAPI and by immunohistochemistry for CD3 to algorithmically quantify PMN-MDSC and T cell densities in the tumor and stromal compartments. NLR (neutrophil count divided by lymphocyte count), ALP, LDH, and albumin were obtained from blood collected contemporaneous with mCRPC biopsies. Clinical data were retrospectively collected. Negative binomial regression determined the association between leucocyte densities and log-transformed NLR. Modified Poisson regression estimated the risk ratio (RR) for the presence of PMN-MDSCs in relation to higher NLR (>3). OS was analysed using Cox regression and Kaplan-Meier. RNAseq data from Stand Up 2 Cancer/Prostate Cancer Foundation (SU2C/PCF, n=159) and RMH cohorts (n=98) were analysed by Spearman’s correlation. Results: NLR positively associated with the density of PMN-MDSCs infiltrating the tumor (p=0.0004) and stromal (p=0.0007) compartments of mCRPC biopsies as determined by Halo࣪ computational modelling. Tumors with high NLR were more likely to be infiltrated by PMN-MDSCs (RR: 1.41; 95% confidence interval [CI]: 1.04-1.92; p=0.03). NLR independently associated with worse OS from the time of mCRPC biopsy after adjusting for LDH, ALP, metastasis at the time of diagnosis, and albumin (HR: 1.71; 95% CI: 1.20-2.46). Patients with low NLR and an absence of tumor-infiltrating PMN-MDSC had longer OS than those with a high NLR, tumor-infiltrating PMN-MDSCs or a combination of both (p=0.015). Whilst there was no association between NLR or PMN-MDSC density and CD3 T cell density, RNAseq analyses of two independent CRPC cohorts showed that MDSC signatures strongly and positively associated with signatures of T cell terminal exhaustion (SU2C/PCF: rs=0.74; p<1x10-6; RMH: rs=0.64; p<1x10-6) providing credence for the impact of MDSCs on T effector function. Conclusion: Peripheral blood NLR was positively correlated with prostate tumor-infiltrating PMN-MDSC density supporting the interaction between the circulating myeloid compartment and intratumoral myeloid infiltration in patients with advanced PC. Citation Format: Christina Guo, Jan Rekowski, Mateus Crespo, Bora Gurel, Wei Yuan, Adam Sharp, Rafael Grochot, Khobe Chandran, Semini Sumanasuriya, Ana Ferreira, Andrea Alimonti, Johann S. de Bono. The neutrophil-to-lymphocyte ratio (NLR) reflects intratumor myeloid derived suppressor cell (MDSC) infiltration in metastatic castration-resistant prostate cancers (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3415.
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Berntsson, Jonna, Maria Christina Svensson, Karin Leandersson, Bjorn Nodin, Agnieszka Krzyzanowska, Anders Bjartell, Jakob Eberhard e Karin Jirstrom. "The prognostic impact of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite." Journal of Clinical Oncology 35, n.º 7_suppl (1 de março de 2017): 47. http://dx.doi.org/10.1200/jco.2017.35.7_suppl.47.
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47 Background: Several studies report dense infiltration of tumour-infiltrating T cells and natural killer cells to be associated with an improved prognosis in colorectal cancer (CRC); but whether these associations differ by tumour location remain unknown. This study investigated the prognostic impact of immune cell infiltration in CRC, with particular reference to the anatomical subsite of the primary tumour. Methods: Immunohistochemical expression of CD3, CD8, FoxP3, and CD56 was analysed in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: In the entire cohort, dense infiltration of all the investigated immune cells correlated significantly with an improved 5-year OS in both univariable and multivariable analysis, adjusted for age, TNM stage, differentiation grade, and vascular invasion. Dense infiltration of CD3+ and CD8+ cells were independent favourable prognostic factors for tumours in the right colon (hazard ratio [HR] = 0.53, 95 % confidence interval [CI] 0.29-0.95 and HR = 0.35, 95% CI 0.19-0.65, respectively), but not in the left colon or rectum. When microsatellite instability status was included in the adjusted model, only CD8+ cells remained an independent favourable prognostic factor in right-sided tumours. Dense infiltration of FoxP3+ cells was an independent favourable prognostic factor for tumours in the rectum (HR = 0.54, 95% CI 0.30-0.99), but not in the right or left colon. Infiltration of CD56+ cells did not carry any independent prognostic impact after stratifying for primary tumour site. Conclusions: The results from this study demonstrate that the prognostic impact of certain T cell subsets in CRC differs by primary tumour site, being most evident in right-sided tumours. These findings indicate that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.
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A. S., Akinwumiju, e Olorunfemi M. O. "Morphometric Analyses of Osun Drainage Basin, Southwestern Nigeria". Journal of Geography and Geology 8, n.º 4 (29 de novembro de 2016): 9. http://dx.doi.org/10.5539/jgg.v8n4p9.
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This study evaluated some morphometric parameters with a view to assessing the infiltration potential of Osun Drainage Basin (ODB), Southwestern Nigeria. Input data were derived from SPOT DEM using ArcGIS 10.3 platform. ODB has an area extent of 2,208.18 km2, and is drained by 1,560 streams with total length of 2,487.7 km. The Relief Ratio (5.6) suggests that ODB is characterized by topographic high and topographic low. Thus, infiltration potential would be low as surface runoff would have less time to infiltrate before entering the drainage channels. The computed values of Drainage Texture (0.52), Stream Number (1,560), Total Stream Length (2,487.7 m) and Main Stream Length (119 m) indicate that larger percentage of annual rainwater would leave ODB as river discharge. Stream Frequency, Basin Perimeter, Length of Overland Flow and Drainage Density influence Infiltration Number across the basin. Infiltration Number increases with increasing Stream Frequency (r = 0.95) and Drainage Density (r = 0.78); and Length of Overland Flow increases with decreasing Drainage Density (r = -0.83), Stream Frequency (r = -0.51) and Infiltration Number (r = -0.45). The study concluded that basin’s infiltration potential is moderate as suggested by the mean Infiltration Number.
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Dušek, J., M. Dohnal e T. Vogel. "Numerical analysis of ponded infiltration experiment under different experimental conditions". Soil and Water Research 4, Special Issue 2 (19 de março de 2010): S22—S27. http://dx.doi.org/10.17221/1368-swr.
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One of the most important properties, affecting the flow regime in the soil profile, is the topsoil saturated hydraulic conductivity (<I>K<SUB>s</SUB></I>). The laboratory-determined <I>K<SUB>s</SUB> </I>often fails to characterise properly the respective field value; the <I>K<SUB>s</SUB> </I>lab estimation requires labour intensive sampling and fixing procedures, difficult to follow in highly structured and stony soils. Thus, simple single- or double-ring ponded infiltration experiments are frequently performed in situ to obtain the field scale information required. In the present study, several important factors, affecting the infiltration rate during the infiltration experiments, are analysed using three-dimensional axisymmetric finite-element model S2D. The examined factors include: (1) the diameter of the infiltration ring, (2) the depth of water in the ring, (3) the depth of the ring insertion under the soil surface, (4) the size and the shape of the finite-element mesh near the ring wall, and (5) the double- vs. single-ring setup. The analysis suggests that the depth of the ring insertion significantly influences the infiltration rate. The simulated infiltration rates also exhibit high sensitivity to the shape of the finite-element mesh near the ring wall. The steady-state infiltration rate, even when considering a double-ring experiment, is significantly higher than the topsoil saturated hydraulic conductivity. The change of the water depth in the outer ring has only a small impact on the infiltration rate in the inner ring.
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Jerebtsova, Marina, Asrar Ahmad, Namita Kumari, Ornela Rutagarama e Sergei Nekhai. "Oxygen Levels Affect Macrophage HIV-1 Gene Expression and Delay Resolution of Inflammation in HIV-Tg Mice". Viruses 12, n.º 3 (1 de março de 2020): 277. http://dx.doi.org/10.3390/v12030277.
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While antiretroviral therapy increases the longevity of people living with HIV (PLWH), about 30% of this population suffers from three or more concurrent comorbidities, whose mechanisms are not well understood. Chronic activation and dysfunction of the immune system could be one potential cause of these comorbidities. We recently demonstrated reduced macrophage infiltration and delayed resolution of inflammation in the lungs of HIV-transgenic mice. Additionally, trans-endothelial migration of HIV-positive macrophages was reduced in vitro. Here, we analyze macrophages’ response to LPS challenge in the kidney and peritoneum of HIV-Tg mice. In contrast to the lung infiltration, renal and peritoneal macrophage infiltrations were similar in WT and HIV-Tg mice. Higher levels of HIV-1 gene expression were detected in lung macrophages compared to peritoneal macrophages. In peritoneal macrophages, HIV-1 gene expression was increased when they were cultured at 21% O2 compared to 5% O2, inversely correlating with reduced trans-endothelial migration at higher oxygen levels in vitro. The resolution of macrophage infiltration was reduced in both the lung and the peritoneal cavity of HIV-Tg mice. Taken together, our study described the organ-specific alteration of macrophage dynamics in HIV-Tg mice. The delayed resolution of macrophage infiltration might constitute a risk factor for the development of multiple comorbidities in PLWH.
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Li, Lin, Leyang Wu, Xingpeng Yin, Chenyang Li e Zichun Hua. "Bulk and Single-Cell Transcriptome Analyses Revealed That the Pyroptosis of Glioma-Associated Macrophages Participates in Tumor Progression and Immunosuppression". Oxidative Medicine and Cellular Longevity 2022 (26 de setembro de 2022): 1–35. http://dx.doi.org/10.1155/2022/1803544.
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Glioma is the most common of all central nervous system (CNS) malignancies and is associated with a poor prognosis. Pyroptosis has been proven to be associated with the progression of multiple tumors and CNS diseases. However, the relationships between pyroptosis and clinical prognosis and immune cell infiltration are unclear in glioma. In this study, we conducted a comprehensive exploration of pyroptosis in glioma. First, prognosis-related genes were screened at each key regulatory locus in the pyroptosis pathway, and the prognostic ability and coexpression relationships of GSDMD and its upstream pathway genes NLRC4/CASP1/CASP4 were identified and well validated in multiple datasets. Tissue microarray-based immunohistochemistry results showed higher levels of NLRC4 and N-terminal GSDMD in high-grade gliomas, providing conclusive evidence of pyroptosis in gliomas. The robustness of the prognostic model based on these four genes was well validated in TCGA and CGGA cohorts. Bulk RNA-seq-based analysis showed that the group defined as the high-risk group according to the model showed activation of multiple inflammatory response pathways and impaired synaptic gene expression and had a higher infiltration of bone marrow-derived macrophages (BMDMs) and a hypersuppressed immune microenvironment. More importantly, three independent single-cell RNA-seq (scRNA-seq) datasets demonstrated that tumor-infiltrating macrophages, particularly BMDMs but not tissue-resident microglia, showed significant coexpression of the GSDMD and CASP genes, and BMDMs from high-grade gliomas accounted for a higher proportion of immune infiltrating cells and had higher expression of pyroptosis genes. Finally, we revealed the activation of pathways in response to LPS/bacteria and oxidative stress during BMDM development toward the pyroptosis cell fate by pseudotime trajectory analysis, suggesting potential BMDM pyroptosis initiators. The above results provide not only novel insights into the pathological mechanisms of glioma but also novel therapeutic targets for glioma, suggesting the potential application of pyroptosis inhibitors (e.g., disulfiram).
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Chan, Jenq-Shyong, Yang Wang, Virgilius Cornea, Prabir Roy-Chaudhury e Begoña Campos. "Early Adventitial Activation and Proliferation in a Mouse Model of Arteriovenous Stenosis: Opportunities for Intervention". International Journal of Molecular Sciences 22, n.º 22 (13 de novembro de 2021): 12285. http://dx.doi.org/10.3390/ijms222212285.
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Background: Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure, for which there are currently no effective therapies. We examined the pattern and phenotype of cellular proliferation at different timepoints in a mouse model characterized by a peri-anastomotic AVF stenosis. Methods: Standard immunohistochemical analyses for cellular proliferation and macrophage infiltration were performed at 2, 7 and 14 d on our validated mouse model of AVF stenosis to study the temporal profile, geographical location and cellular phenotype of proliferating and infiltrating cells in this model. Results: Adventitial proliferation and macrophage infiltration (into the adventitia) began at 2 d, peaked at 7 d and then declined over time. Surprisingly, there was minimal macrophage infiltration or proliferation in the neointimal region at either 7 or 14 d, although endothelial cell proliferation increased rapidly between 2 d and 7 d, and peaked at 14 d. Conclusions: Early and rapid macrophage infiltration and cellular proliferation within the adventitia could play an important role in the downstream pathways of both neointimal hyperplasia and inward or outward remodelling.
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Mironovs, Viktors, Vjaceslavs Zemcenkovs e Jekaterina Kuzmina. "Manufacturing of Complex-Shape PM Products Consisting of Several Powder Elements". Solid State Phenomena 331 (29 de abril de 2022): 73–78. http://dx.doi.org/10.4028/p-8les70.
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The article’s primary purpose is to give a technological assessment of manufacturing complex-shaped parts using powder metallurgy. The process is considered in the example of a complex-shaped product consisting of several elements manufactured separately from the Fe-C-Cu powder mixture and then combined into a single structure. The joining was carried out by impregnation of porous structural elements with the fusion of copper-containing material. It has been demonstrated that the infiltration process is affected by many factors: porosity of structural elements, wettability of their pore channels, fluid flowability of the infiltrating material, and other factors. The research was carried out on the mass products - centrifugal pump stages for oil production. The elements compaction was carried out on hydraulic press at a pressure of 500 MPa, which ensured the average density of the parts after sintering up to 7.8-8.4 g/cm3. During sintering and impregnation, various types of defects of the pieces were detected, which were caused by the excessive thickness of the infiltrating material, different densities of the walls, and insufficient wettability in the connection zones of the elements.The investigations have shown that manufacturing complex components by prefabricating single elements and their subsequent sintering combined with infiltration is feasible. It can be done in a chamber furnace as well as with belt sintering. However, it is necessary to carefully prepare the mold before sintering, choose the infiltrating agent, and analyse possible disadvantages.
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Faveeuw, C., M. C. Gagnerault e F. Lepault. "Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice." Journal of Immunology 152, n.º 12 (15 de junho de 1994): 5969–78. http://dx.doi.org/10.4049/jimmunol.152.12.5969.
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Abstract The nonobese diabetic mouse is a relevant model for insulin-dependent diabetes mellitus which results from the destruction of pancreatic beta cells by mononuclear cells infiltrating the islets of Langerhans. Other organs such as salivary glands display inflammatory infiltration. Using immunohistochemical and flow cytometry analyses, we have studied the expression of diverse homing and adhesion molecules in salivary glands and the pancreas in nonobese diabetic mice. In salivary glands, ICAM-1 was expressed by endothelial and dendritic cells within the lymphocytic infiltration. HEV-like structures expressing PNAd were observed in the areas of lymphocytic infiltration whereas MAdCAM-1 was absent. Lymphocytes infiltrating salivary glands expressed LFA-1 and Pgp-1 although Mel-14 Ag was absent. In infiltrated islets, ICAM-1 was expressed by endothelial cells, dendritic cells, and mononuclear cells. We confirm the presence of HEV-like structures expressing MAdCAM-1 and PNAd in inflamed islets. With regard to peripheral lymphocytes, the proportion of CD4 and CD8 cells expressing Mel-14 was decreased in the infiltrated islets, whereas the expression of LFA-1, Pgp-1, and LPAM-1/2 was increased. B lymphocytes exhibited up-regulation of LPAM-1/2. Moreover, the proportion of CD4, CD8, and B lymphocytes expressing CD69 was increased in the pancreas. These results indicate that first, infiltration of islets of Langerhans results at least partly from modifications of adhesion molecule expression in the pancreas, which allow extravasation of mononuclear cells into the islets via at least three different pathways; and second, that activated cells are concentrated in the infiltrates as compared with peripheral lymphoid organs.
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Sasiarini, Laksmi, Aktaruddin Arief Santoso e Djoko Wahono Soeatmadji. "The Impact of Subchronic Soybean Milk and Genistein Supplementation on Pancreatic Fatty Infiltrations of Sprague Dawley Male Mice". Clinical and Research Journal in Internal Medicine 1, n.º 2 (11 de novembro de 2020): 79–87. http://dx.doi.org/10.21776/ub.crjim.2020.001.02.4.
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Isoflavones (genistein, daidzein) on soybean milk have phytoestrogenic properties. In Asia, the blood phytoestrogen levels can reach 160 ng/ml (80 times higher than Western). This may potentially disrupt endocrine functions regarding its binding with estrogen receptors.. Since the function and distribution of adipose tissues are regulated by estrogen receptors, the reduction of estrogen receptor-α(ERα) results in ectopic fats distribution around visceral tissues, such as the pancreas. Aim: To investigate the impact of subchronic soybean milk and genistein supplementation on pancreatic fatty infiltrations in mice. Methods: The experiment used 35 Sprague dawley male mice under 7 treatment groups within 60 days: negative control with standard rationed food, 3 groups with a variable dose of soybean milk: 100 mg, 200 mg, and 400 mg, and 3 groups with a variable dose of genistein: 0.4 mg, 0.8 mg, and 1.6 mg. Histological measurements on the level of pancreatic fatty infiltrations were conducted after. Analyses used Kruskal-Wallis and post-hoc Mann-Whitney. Results: Medium to a high level of pancreatic fatty infiltrations were found at the control group while there is a decreasing trend on the level of pancreatic fatty infiltrations on groups with soybean milk and subchronic genistein compared with the control group, proportional to higher dosage supplementation. The reduction of pancreatic fatty infiltration levels on groups with soybean milk and subchronic genistein supplementation is not statistically significant compared to control. Conclusion: Supplementation of soybean milk and subchronic genistein do not significantly reduce the levels of pancreatic fatty infiltrations in Sprague dawley male mice.
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Thiel, Vera, Simon Renders, Jasper Panten, Julian Mochayedi, Rienk Offringa, Martin Sprick e Andreas Trumpp. "Abstract 3650: Trace'n'Seq: Assessing neuronal infiltration and its impact in pancreatic ductal carcinoma". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 3650. http://dx.doi.org/10.1158/1538-7445.am2022-3650.
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Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor entity with dismal prognosis. PDAC is characterized by an extensive desmoplastic stroma and the tumor microenvironment (TME) has been recognized to play crucial roles in tumor development, therapy resistance, progression and metastasis. Although different cell types of the TME have been molecularly analyzed, tumor-infiltrating neurons could not be considered so far, because their cell bodies are located in adjacent ganglia of the peripheral nervous system and thus they are not part of the tumor mass (Demir, Thiel et al, Nature Cancer 2020; Demir, Thiel et al. Cancer Cell 2020). One of the unique features of PDAC is the strong infiltration by nerve fibers which correlates directly with tumor malignancy. In recent years it has been shown that either neurotransmitters secreted by neurons, or modulators of neuronal infiltration secreted by cancer cells can influence tumor growth. Here we use 3D light sheet fluorescence microscopy imaging (LSFM) of full tissue cleared PDAC specimen of tumors growing in genetically engineered mouse models or patient-derived xenograft models. Our data showthat these PDACs are innervated by a complex array of sensory and sympathetic neurons. To molecularly analyse neurons innervating the tumor mass, we have developed a novel approach we termed Trace’n’seq. This combines retrograde axonal tracing and FACS analysis with single cell RNA sequencing with the aim to identify, isolate and analyse hundreds of traced neurons infiltrating tumors or their respective healthy organs. Thereby, we have identified previously undescribed neuronal cell types and provide a landscape of sympathetic and sensory nerves innervating the healthy pancreas as well as PDAC. Our single cell transcriptomic analysis revealed signs of reprogramming of neuronal behaviour orchestrated by the tumor cells. These datasets combined with single cell profiling of PDAC cells and its associated stroma provide a first complete, unbiased insight into neurons infiltrating both healthy pancreas and PDAC. Based on a comprehensive interactome analysis of the interplay between tumor cells, stroma and the neurons, we have identified various candidate genes involved in tumor-nerve signalling. We are currently performing gain-and loss- of function approaches to dissect the role of individual factors. In summary, with Trace'n'seq, we have developed a novel technology pipeline to isolate tissue innervating neurons to investigate the role of neuronal infiltration in the development and progression of PDAC. Citation Format: Vera Thiel, Simon Renders, Jasper Panten, Julian Mochayedi, Rienk Offringa, Martin Sprick, Andreas Trumpp. Trace'n'Seq: Assessing neuronal infiltration and its impact in pancreatic ductal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3650.
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Zhang, Jun, Bin Li, Boming Zhao, Yongjian Qi, Liaobin Chen, Jun Chen e Biao Chen. "Immune Cell Infiltration Characteristics of Pigmented Villous Nodular Synovitis and Prediction of Potential Diagnostic Markers Based on Bioinformatics". BioMed Research International 2022 (7 de junho de 2022): 1–17. http://dx.doi.org/10.1155/2022/8708692.
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Background. Pigmented villous nodular synovitis (PVNS) is a tumor-like proliferative disease characterized by impairment of daily activities, decreased quality of life, and a high recurrence rate. However, the specific pathological mechanisms are still ill-defined and controversial. The purpose of this study was to define potential diagnostic markers and evaluate immune cell infiltration in the pathogenesis of PVNS. Method. The expression profile of GSE3698 was reanalyzed in the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) were identified using the R package “limma” and analyzed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Next, the DEGs were imported into the STRING database and Cytoscape to construct a protein–protein interaction (PPI) network. Then, cytoHubba and ROC curve analyses were used to determine potential diagnostic biomarkers of PVNS. Finally, we used CIBERSORT to estimate the proportions of 22 immune cell subtypes in PVNS and analyzed the correlation between diagnostic markers and infiltrating immune cells. Result. We found 139 DEGs (including 93 upregulated genes and 46 downregulated genes). TYROBP, FCER1G, LAPTM5, and HLA-DPB1 were identified as potential diagnostic biomarkers of PVNS. Immune cell infiltration analysis indicated that neutrophils and M2 macrophages might be associated with the genesis and progression of PVNS. Furthermore, our correlation analysis of diagnostic markers and infiltrating immune cells found that TYROBP, FCER1G, LAPTM5, and HLA-DPB1 were positively correlated with M2 macrophage infiltration and that neutrophils, TYROBP, FCER1G, and LAPTM5 were negatively correlated with plasma cell infiltration. Conclusions. We identified TYROBP, FCER1G, LAPTM5, and HLA-DPB1 as potential diagnostic markers for PVNS and concluded that immune cell infiltration plays an important role in the genesis and progression of PVNS.
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Luo, Cancan, Han Nie e Li Yu. "Identification of Aging-Related Genes Associated with Prognostic Value and Immune Microenvironment Characteristics in Diffuse Large B-Cell Lymphoma". Oxidative Medicine and Cellular Longevity 2022 (13 de janeiro de 2022): 1–30. http://dx.doi.org/10.1155/2022/3334522.
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Diffuse large B-cell lymphoma (DLBCL) is a complex invasive tumour that occurs mainly among the elderly. Therefore, we analysed the relationship between ageing-related genes (AG) and DLBCL prognosis. Datasets related to DLBCL and human AGs were downloaded and screened from the Gene Expression Omnibus (GEO) database and HAGR website, respectively. LASSO and Cox regression were used to analyse AGs in the dataset and construct an AG predictive model related to DLBCL prognosis. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment were used to analyse the function of the AG predictive model. The immune microenvironment and immune cell infiltration in DLBCL and their relationship with the AG prediction model were also analysed. After the analysis, 118 AGs were identified as genes related to DLBCL prognosis. Using the LASSO and Cox regression analyses, 9 AGs (PLAU, IL7R, MYC, S100B, IGFBP3, NR3C1, PTK2, TBP, and CLOCK) were used to construct an AG prognostic model. In the training and verification sets, this model exhibited excellent predictive ability for the prognosis of patients with DLBCL who have different clinical characteristics. Further analysis revealed that the high- and low-risk groups of the AG prognostic model were significantly correlated with immune cell infiltration and tumour microenvironment in DLBCL. Functional enrichment analysis also showed that the genes in the AG model were associated with immune-related functions and pathways. In conclusion, we constructed an AG model with a strong predictive function in DLBCL, with the ability to predict the prognosis of patients with different clinical features. This model provides new ideas and potential therapeutic targets for the study of the pathogenesis of DLBCL.
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Fu, Liu, Zhe Wang, Fengxiang Jiang, Guohua Wei, Longe Sun, Chuanyong Guo, Jianye Wu e Jianhuan Zhu. "High Expression of EIF4G2 Mediated by the TUG1/Hsa-miR-26a-5p Axis Is Associated with Poor Prognosis and Immune Infiltration of Gastric Cancer". Journal of Oncology 2022 (16 de setembro de 2022): 1–25. http://dx.doi.org/10.1155/2022/9342283.
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Objective. Eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) is involved in the occurrence and development of various tumors. However, the effect of EIF4G2 in gastric cancer (GC) has not been fully explored. The purpose of this study was to explore the function and mechanism of EIF4G2 in GC. Methods. The Tumor Immune Estimation Resource 2.0 database was used to analyze EIF4G2 expression in various cancers and the relationship between EIF4G2 expression and tumor-infiltrating immune cells. Gene Expression Profiling Interactive Analysis was utilized to assess the EIF4G2 expression level and its effect on survival in GC. UALCAN was conducted to analyze EIF4G2 expression in various subgroups of GC. The Kaplan–Meier plotter was employed for survival analysis. Receiver operator characteristic (ROC) curve analysis was applied to evaluate the diagnostic role of EIF4G2 in GC. LinkedOmics was used to identify the co-expressed genes and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The Tumor-Immune System Interaction database was employed to analyze the correlation between EIF4G2 expression and tumor-infiltrating lymphocytes. The starBase web platform was used to predict the upstream microRNAs and long noncoding RNAs. Results. EIF4G2 expression was upregulated in GC tissues compared to normal controls. High expression of EIF4G2 indicated poor prognosis in GC. ROC analysis revealed that EIF4G2 had good diagnostic ability to distinguish GC from normal tissues. Immune infiltration analysis indicated that EIF4G2 expression may be involved in the modulation of tumor immune infiltration in GC. Finally, we determined that the Taurine Upregulated 1 (TUG1)/hsa-miR-26a-5p/EIF4G2 axis was the most likely regulatory pathway involved in GC development. Conclusions. EIF4G2 was upregulated in GC and elevated expression of EIF4G2 indicated unfavorable prognosis. Moreover, EIF4G2 expression may be involved in the regulation of tumor immune cell infiltration. The TUG1/hsa-miR-26a-5p axis is a likely upstream regulatory mechanism of EIF4G2 in GC. EIF4G2 may thus serve as a prognosis biomarker and present a new therapeutic target.
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Zhaoran, Su, Christina Susanne Linnebacher e Michael Linnebacher. "Increased SEC23A Expression Correlates with Poor Prognosis and Immune Infiltration in Stomach Adenocarcinoma". Cancers 15, n.º 7 (30 de março de 2023): 2065. http://dx.doi.org/10.3390/cancers15072065.
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Background: Previous studies have described that the SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance in stomach adenocarcinoma (STAD). The aim of this study was to bioinformatically analyze the role of SEC23A in STAD, followed by patient tissue sample analyses. Materials and methods: SEC23A expression levels in STAD and normal gastric tissues were analyzed in the Cancer Genome Atlas and Gene Expression Omnibus databases; results were verified in fresh clinical STAD specimens on both gene and protein expression levels. SEC23A expression correlated with survival parameters by Kaplan–Meier and multivariate Cox regression analyses. The top genes co-expressed with SEC23A were identified by gene set enrichment analysis (GSEA) using the clusterProfiler package in R. Furthermore, the R package (immunedeconv), integrating the CIBERSORT algorithm, was used to estimate immune cell infiltration levels in STAD. Results: SEC23A gene and sec23a protein expression were both significantly upregulated in STAD, and this correlated with the pT stage. Moreover, high SEC23A expression was associated with poor disease-free and overall survival of STAD patients. Cox analyses revealed that besides age and pathologic stage, SEC23A expression is an independent risk factor for STAD. GSEA indicated that SEC23A was positively associated with ECM-related pathways. In the CIBERSORT analysis, the level of SEC23A negatively correlated with various infiltrating immune cell subsets, including follicular helper T cells, Tregs, activated NK cells and myeloid dendritic cells. Finally, the expression levels of immune checkpoint-related genes, including HAVCR2 and PDCD1LG2, were significantly increased in the high SEC23A expression group. Conclusions: We observed the significantly upregulated expression of SEC23A in STAD, an association with disease progression, patients’ prognosis and infiltrating immune cell subsets. Thus, we propose SEC23A as an independent prognostic factor with a putative role in immune response regulation in STAD.
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Ghatalia, Pooja, Jennifer Gordetsky, Sejong Bae, Stacey M. Watkins, Sunil Sudarshan, Gurudatta Naik e Guru Sonpavde. "Association of a combined panel of tumor infiltrating lymphocytes, plasma cells, and macrophages with recurrence of localized clear cell (cc) renal cell carcinoma (RCC) undergoing surgery." Journal of Clinical Oncology 34, n.º 2_suppl (10 de janeiro de 2016): 502. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.502.
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502 Background: Tumor infiltrating Programmed-Death (PD)-1 and FoxP3-expressing lymphocytes and macrophages appear to be associated with higher risk of recurrence in patients (pts) with ccRCC undergoing surgery for localized disease. We aimed to combine the presence of morphologically identified lymphocytes, plasma cells and macrophages into a readily available composite immune cell panel and to evaluate its association with tumor recurrence. Methods: We identified pts with ccRCC who underwent nephrectomy at UAB for whom we had annotation for objective tumor recurrence and a minimum follow-up of 2 years. Central pathology review was conducted by a single urologic oncology certified pathologist to capture pathologic variables (stage, grade, necrosis, histologic components, cystic changes) and immune cell (lymphocyte/plasma cell/macrophage) infiltration. Logistic regression (univariate and multivariate) analyses were conducted to evaluate the association of these variables with tumor recurrence. Results: Of the 159 identified and evaluable pts, 33 (20.7%) recurred and 126 did not. On univariate analyses, sarcomatoid/rhabdoid histologic components, lymphocyte/plasma cell infiltration, necrosis, pathological T stage and histologic grade were all statistically significantly associated with a risk of recurrence (p < 0.05). On multivariate analysis, in addition to pathologic stage (p = 0.0018), only the combination of higher lymphocyte/plasma cell and macrophage infiltration (p = 0.0347) was independently associated with recurrence; patients were 8.7 times more likely to recur (95% CI: 1.66, 45.28). Conclusions: A readily available and widely applicable composite panel of morphologically identified lymphocytes, plasma cells and macrophages infiltrating the tumor predicts recurrence of pts with localized ccRCC undergoing surgery, after controlling for clinical and pathologic prognostic factors. Our hypothesis-generating data require validation and further interrogation of specific markers expressed on immune cells may refine an immune panel that confers prognostic impact.
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Heimes, Anne-Sophie, Natali Riedel, Katrin Almstedt, Slavomir Krajnak, Roxana Schwab, Kathrin Stewen, Antje Lebrecht et al. "Prognostic Impact of CD38- and IgκC-Positive Tumor-Infiltrating Plasma Cells in Triple-Negative Breast Cancer". International Journal of Molecular Sciences 24, n.º 20 (16 de outubro de 2023): 15219. http://dx.doi.org/10.3390/ijms242015219.
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Due to a higher mutational load, triple-negative breast cancer (TNBC) is characterized by a higher immunogenicity compared to other subtypes. In this context, we analyzed the prognostic significance of tumor-infiltrating plasma cells in a cohort of 107 triple-negative breast cancer patients. Tumor-infiltrating plasma cells were analyzed via immunohistochemistry using the plasma cell markers CD38 and IgκC. The prognostic impact of the CD38 and IgκC expression was evaluated using the Kaplan–Meier plots and Cox regression analyses. A Spearman-Rho correlation coefficient was used to evaluate a possible association between plasma cell infiltration and the BRCA mutation status. The study cohort consisted of 107 patients with early-stage TNBC, who were treated between 2009 and 2016 at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany. The median follow-up was five years. The Kaplan–Meier survival analysis showed that higher tumor infiltration with CD38-positive plasma cells was associated with significantly longer metastasis-free survival (MFS) (p = 0.039 Log Rank). In the multivariate Cox regression analysis for metastasis-free survival, in which additional clinicopathological factors (age, tumor size, nodal status, and grading) were considered, CD38 was identified as an independent prognostic factor within the analyzed cohort (HR 0.438, 95% CI 0.195–0.983; p = 0.045). In addition to the CD38 expression, the nodal status was also identified as an independent prognostic factor in multivariate Cox regression. Regarding the IgκC expression, a higher IgκC expression was shown to be associated with a better outcome, although this effect was not statistically significant. Furthermore, we were able to show a significant correlation between plasma cell infiltration and the BRCA mutation status. A favorable prognostic significance of tumor-infiltrating plasma cells could be demonstrated in triple-negative breast cancer immunohistochemically analyzed for the CD38 and IgκC expression. CD38 was identified as an independent prognostic factor via multivariate Cox regression.
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Zheng, Yufeng, Xue Liu, Na Li, Aimei Zhao, Zhiqiang Sun, Meihua Wang e Judong Luo. "Radiotherapy combined with immunotherapy could improve the immune infiltration of melanoma in mice and enhance the abscopal effect". Radiation Oncology Journal 41, n.º 2 (30 de junho de 2023): 129–39. http://dx.doi.org/10.3857/roj.2023.00185.
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Purpose: To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes. Materials and Methods: Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration. Results: We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis. Conclusion: Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.