Tumor innervation and clinical outcome in pancreatic cancer

AbstractPancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the clinicopathological significance of tumor innervation is unclear. In this study, the presence of nerves and their cross-sectional size were quantified by immunohistochemistry for the neuronal markers S-100, PGP9.5 and GAP-43 in a series of 99 pancreatic cancer cases versus 71 normal adjacent pancreatic tissues. A trend was observed between the presence of nerves in the tumor microenvironment of pancreatic cancer and worse overall patient survival (HR = 1.8, 95% CI 0.77–4.28, p = 0.08). The size of nerves, as measured by cross-sectional area, were significantly higher in pancreatic cancer than in the normal adjacent tissue (p = 0.002) and larger nerves were directly associated with worse patient survival (HR = 0.41, 95% CI 0.19–0.87, p = 0.04). In conclusion, this study suggests that the presence and size of nerves within the pancreatic cancer microenvironment are associated with tumor aggressiveness.

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Serum levels of IL-6, IL-8, and IL-10 are indicators of prognosis in pancreatic cancer

Journal of International Medical Research ◽

10.1177/0300060518800588 ◽

2018 ◽

Vol 46 (12) ◽

pp. 5228-5236 ◽

Cited By ~ 13

Author(s):

Lanyun Feng ◽

Qi Qi ◽

Peng Wang ◽

Hao Chen ◽

Zhen Chen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Early Detection ◽

Broad Spectrum ◽

Patient Survival ◽

Serum Levels ◽

Poor Survival ◽

Improve Patient Survival ◽

Positive Correlations ◽

Prediction Of Prognosis ◽

Improve Patient

Objective Early detection and prognosis prediction are critical to improve patient survival in pancreatic cancer. This study aimed to investigate whether interleukins could serve as indicators of prognosis in pancreatic cancer. Methods Sixty-eight patients with pancreatic cancer were enrolled in the study during the period between 2012 and 2014. The serum levels of a broad spectrum of interleukins in these patients were determined, including IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-15, and IL-23. Results IL-6, IL-8, and IL-10 showed significant positive correlations with each other. Moreover, high levels of serum IL-6, IL-8, and IL-10 were independently strongly associated with poor survival of patients with pancreatic cancer. Conclusions Our results suggest that serum levels of IL-6, IL-8, and IL-10 could be useful markers for prediction of prognosis in patients with pancreatic cancer.

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Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma

Cancers ◽

10.3390/cancers13112689 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2689

Author(s):

Felix Popp ◽

Ingracia Capino ◽

Joana Bartels ◽

Alexander Damanakis ◽

Jiahui Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Checkpoint ◽

Patient Survival ◽

Checkpoint Inhibitors ◽

Tumor Infiltrating Lymphocytes ◽

Ductal Adenocarcinoma ◽

Lymph Node Status ◽

Clinicopathologic Parameters ◽

Survival Differences ◽

Infiltrating Lymphocytes

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.

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Infrared Diagnostics of Free Charge Carriers in Silicon Nanowires

International Journal of Nanoscience ◽

10.1142/s0219581x19400301 ◽

2019 ◽

Vol 18 (03n04) ◽

pp. 1940030 ◽

Cited By ~ 1

Author(s):

A. I. Efimova ◽

E. A. Lipkova ◽

K. A. Gonchar ◽

A. A. Eliseev ◽

V. Yu. Timoshenko

Keyword(s):

Silicon Nanowires ◽

Crystalline Silicon ◽

Free Charge Carrier ◽

Charge Carrier Concentration ◽

Attenuated Total Reflection ◽

Free Charge ◽

Cross Sectional ◽

Text Type ◽

Cross Sectional Size ◽

Potential Applications

Free charge carrier concentration in arrays of silicon nanowires (SiNWs) with cross-sectional size of the order of 100[Formula: see text]nm was quantitatively studied by means of the infrared spectroscopy in an attenuated total reflection mode. SiNWs were formed on lightly-doped [Formula: see text]-type crystalline silicon substrates by metal-assisted chemical etching followed by additional doping through thermoactivated diffusion of boron at 900–1000∘C. The latter process was found to increase the concentration of free holes in SiNWs up to [Formula: see text][Formula: see text]cm[Formula: see text]. Potential applications of highly doped SiNWs in thermoelectric energy converters and infrared plasmonic devices are discussed.

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Structure identification and IO space partitioning in a nonlinear fuzzy system for prediction of patient survival after surgery

International Journal of Intelligent Computing and Cybernetics ◽

10.1108/ijicc-06-2016-0021 ◽

2017 ◽

Vol 10 (2) ◽

pp. 166-182 ◽

Cited By ~ 2

Author(s):

Shabia Shabir Khan ◽

S.M.K. Quadri

Keyword(s):

Pancreatic Cancer ◽

Fuzzy Inference System ◽

Fuzzy System ◽

Fuzzy Inference ◽

Patient Survival ◽

Data Partitioning ◽

Structure Identification ◽

Inference System ◽

Content Type ◽

Neuro Fuzzy

Purpose As far as the treatment of most complex issues in the design is concerned, approaches based on classical artificial intelligence are inferior compared to the ones based on computational intelligence, particularly this involves dealing with vagueness, multi-objectivity and good amount of possible solutions. In practical applications, computational techniques have given best results and the research in this field is continuously growing. The purpose of this paper is to search for a general and effective intelligent tool for prediction of patient survival after surgery. The present study involves the construction of such intelligent computational models using different configurations, including data partitioning techniques that have been experimentally evaluated by applying them over realistic medical data set for the prediction of survival in pancreatic cancer patients. Design/methodology/approach On the basis of the experiments and research performed over the data belonging to various fields using different intelligent tools, the authors infer that combining or integrating the qualification aspects of fuzzy inference system and quantification aspects of artificial neural network can prove an efficient and better model for prediction. The authors have constructed three soft computing-based adaptive neuro-fuzzy inference system (ANFIS) models with different configurations and data partitioning techniques with an aim to search capable predictive tools that could deal with nonlinear and complex data. After evaluating the models over three shuffles of data (training set, test set and full set), the performances were compared in order to find the best design for prediction of patient survival after surgery. The construction and implementation of models have been performed using MATLAB simulator. Findings On applying the hybrid intelligent neuro-fuzzy models with different configurations, the authors were able to find its advantage in predicting the survival of patients with pancreatic cancer. Experimental results and comparison between the constructed models conclude that ANFIS with Fuzzy C-means (FCM) partitioning model provides better accuracy in predicting the class with lowest mean square error (MSE) value. Apart from MSE value, other evaluation measure values for FCM partitioning prove to be better than the rest of the models. Therefore, the results demonstrate that the model can be applied to other biomedicine and engineering fields dealing with different complex issues related to imprecision and uncertainty. Originality/value The originality of paper includes framework showing two-way flow for fuzzy system construction which is further used by the authors in designing the three simulation models with different configurations, including the partitioning methods for prediction of patient survival after surgery. Several experiments were carried out using different shuffles of data to validate the parameters of the model. The performances of the models were compared using various evaluation measures such as MSE.

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Positive neck margin at frozen section analysis is a significant preditor of tumour recurrence and poor survival after pancreatoduodenectomy for pancreatic cancer

Pancreatology ◽

10.1016/j.pan.2020.07.306 ◽

2020 ◽

Vol 20 ◽

pp. S160-S161

Author(s):

G. Guarneri ◽

S. Crippa ◽

G. Belfiori ◽

S. Partelli ◽

M. Pagnanelli ◽

...

Keyword(s):

Pancreatic Cancer ◽

Frozen Section ◽

Tumour Recurrence ◽

Poor Survival ◽

Frozen Section Analysis ◽

Section Analysis

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ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer

Journal of Cellular and Molecular Medicine ◽

10.1111/j.1582-4934.2007.00082.x ◽

2007 ◽

Vol 11 (5) ◽

pp. 1162-1174 ◽

Cited By ~ 50

Author(s):

N. Valkovskaya ◽

H. Kayed ◽

K. Felix ◽

D. Hartmann ◽

N. A. Giese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Patient Survival

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Structural Design of a Multifunctional Morphing Fowler Flap for a Twin-Prop Regional Aircraft

Volume 1: Development and Characterization of Multifunctional Materials; Modeling, Simulation, and Control of Adaptive Systems; Integrated System Design and Implementation ◽

10.1115/smasis2018-7937 ◽

2018 ◽

Author(s):

Francesco Rea ◽

Francesco Amoroso ◽

Rosario Pecora ◽

Maria Chiara Noviello ◽

Maurizio Arena

Keyword(s):

Finite Element ◽

Analysis Tool ◽

Load Path ◽

Element Analysis ◽

Cross Sectional ◽

Aerodynamic Performances ◽

Cross Sectional Size ◽

Elementary Methods ◽

Minimum Number ◽

Mode 3

In the framework of Clean Sky 2 Airgreen 2 (REG-IADP) European research project, a novel multifunctional morphing flap technology was investigated to improve the aerodynamic performances of the next Turboprop regional aircraft (90 passengers) along its flight mission. The proposed true-scale device (5 meters span with a mean chord of 0.6 meters) is conceived to replace and enhance conventional Fowler flap with new functionalities. Three different functions were enabled: overall airfoil camber morphing up to +30° (mode 1), +10°/−10° (upwards/downwards) deflections of the flap tip segment (mode 2), flap tip “segmented” twist of ±5° along the outer flap span (mode 3). Morphing mode 1 is supposed to be activated during take-off and landing only to enhance aircraft high-lift performances and steeper initial climb and descent. Thanks to this function, more airfoil shapes are available at each flap setting and therefore a dramatic simplification of the flap deployment system may be implemented. Morphing modes 2 and 3 are enabled in cruise and off-design flight conditions to improve wing aerodynamic efficiency. The novel structural concept of the three-modal morphing Fowler flap (3MMF) was designed according to the challenges posed by real wing installation issues. The proposed concept consists of a multi-box arrangement activated by segmented ribs with embedded inner mechanisms to realize the transition from the baseline configuration to different target aero-shapes while withstanding the aerodynamic loads. Lightweight and compact actuating leverages driven by electromechanical motors were properly synthesized to comply with stringent requirements for real aircraft implementation: minimum actuating torque, minimum number of motors, reduced weight, and available design space. The methodology for the kinematic design of the inner mechanisms is based on a building block approach where the instant center analysis tool is used to preliminary select the locations of the hinges’ leverages. The final geometry of the inner mechanisms is optimized to maximize the mechanical advantage as well as to provide the kinematic performances required by the three different morphing modes. The load-path was evaluated, and the cross-sectional size of leverages was subsequently optimized. Finally, actuating torques predicted by instant center analysis were compared to the calculated values from finite element analysis. The structural sizing process of the multi-box arrangement was carried out considering elementary methods, and results were compared with finite element simulations.

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