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Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy

World Journal of Gastrointestinal Oncology 2020年第2期12卷 173-181页

作者： Panagiotis Sarantis Evangelos Koustas Adriana Papadimitropoulou Athanasios G Papavassiliou michalis v karamouzis Molecular Oncology Unit Department of Biological ChemistryMedical SchoolNational and Kapodistrian University of AthensAthens 11527Greece Center of Basic Research Biomedical Research Foundation of the Academy of AthensAthens 11527Greece First Department of Internal Medicine “Laiko”General HospitalMedical SchoolNational and Kapodistrian University of AthensAthens 11527Greece

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal diseases,with an average 5-year survival rate of less than 10%.Unfortunately,the majority of patients have unresectable,locally advanced,or metastatic disease at the time of ***,traditional treatments such as chemotherapy,surgery,and radiation have not been shown to significantly improve ***,there has been a swift increase in cancer treatments that incorporate immunotherapybased strategies to target all the stepwise events required for tumor initiation and *** results in melanoma,non-small-cell lung cancer and renal cell carcinoma are very ***,the application of checkpoint inhibitors,including anti-CTLA4,anti-PD-1,and anti-PD-L1 antibodies,in pancreatic cancer has been *** studies have revealed that the PDAC microenvironment supports tumor growth,promotes metastasis and consists of a physical barrier to drug *** therapies hold great promise for enhancing immune responses to achieve a better therapeutic *** this review,we provide an outline of why pancreatic cancer is so lethal and of the treatment hurdles that *** emphasis is given to the role of the tumor microenvironment,and some of the latest and most promising studies on immunotherapy in PDAC are also presented.

关键词： Pancreatic ductal adenocarcinoma Tumor microenvironment Immunotherapy Gemcitabine Treatment Cancer stem cells

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Role of autophagy in cholangiocarcinoma:An autophagy-based treatment strategy

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1229-1243页

作者： Evangelos Koustas Eleni-Myrto Trifylli Panagiotis Sarantis Athanasios G Papavassiliou michalis v karamouzis Department of Biological Chemistry Medical SchoolNational and Kapodistrian University of AthensAthens 11527Greece

Cholangiocarcinomas(CCAs)are diverse biliary epithelial tumours involving the intrahepatic,perihilar and distal parts of the biliary *** three entirely variable entities have distinct epidemiology,molecular characteristics,prognosis and strategy for clinical ***,many cholangiocarcinoma tu-mor-cells appear to be resistant to current chemotherapeutic *** role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in *** multistep nature of autophagy offers a plethora of re-gulation points,which are prone to be deregulated and cause different human diseases,including ***,it offers multiple targetable points for designing novel therapeutic *** cells have evolved to use auto-phagy as an adaptive mechanism for survival under stressful conditions such as energy imbalance and hypoxic region of tumors within the tumor microenvir-onment,but also to increase invasiveness and resistance to *** purpose of this review is to summarize the current knowledge regarding the interplay between autophagy and cholangiocarcinogenesis,together with some preclinical studies with agents that modulate autophagy in order to induce tumor cell ***,a combinatorial strategy,which comprises the current anti-cancer agents and autophagy modulators,would represent a positive CCA patient approach.

关键词： Autophagy Autophagy modulators Chemotherapy Cholangiocarcinoma

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Upgraded role of autophagy in colorectal carcinomas

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World Journal of Gastrointestinal Oncology 2018年第11期10卷 367-369页

作者： Evangelos Koustas Panagiotis Sarantis Athanassios G Papavassiliou michalis v karamouzis Division of Molecular Oncology Department of Biological Chemistry Medical SchoolNational and Kapodistrian University of Athens

Autophagy is a basic catabolic process closely asso-ciated with degradation of cellular components. The role of autophagy in colorectal cancer(CRC) remains controversial. The mechanism of autophagy has been identified as protecting mechanism against tumorige-nesis by isolation of damaged organelles or as cytopro-tective provides energy in hypoxic regions of CRC tumors. Mutations in proto-oncogenes, such as RAS and BRAF, have been associated with autophagy initiation through signaling pathways of BRAF/MEK/ERK and PI3 K/AKT/m TOR. A combination therapy of chemotherapeutic agents and autophagy inhibitors such as hydroxychloroquine or immunotherapy might represent a major step that could be evaluated as a putative novel therapeutic strategy in CRC patients.

关键词： Autophagy Tumorigenesis Clinical trials Autophagy inhibitors Colorectal cancer

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Roles of CREB-binding protein (CBP)/p300 in respiratory epithelium tumorigenesis

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Cell Research 2007年第4期17卷 324-332页

作者： michalis v karamouzis Panagiotis A Konstantinopoulos Athanasios G Papavassiliou Department of Biological Chemistry Medical SchoolUniversity of Athens75M Asias Street11527 AthensGreece

CREB-binding protein(CBP)and its homologue p300 are transcriptional co-activators of various sequence-specifictranscription factors that are involved in a wide array of cellular activities,such as DNA repair,cell growth,differentia-tion and *** studies have suggested that CBP and p300 might be considered as tumour suppressors,withtheir prominent role being the cross-coupling of distinct gene expression patterns in response to various *** their actions mainly via acetylation of histones and other regulatory proteins(e.g.p53).A major paradox in CBP/p300 function is that they seem capable of contributing to various opposed cellular *** epitheliumtumorigenesis represents a complex process of multi-step accumulations of a gamut of genetic and epigenetic *** modulation through the alternate formation of activating and repressive complexes is the ultimateconverging point of these derangements,and CBP/p300 represents key participants in this ***,illuminationof their molecular actions and interactions could reveal new potential targets for pharmacological interventions in re-spiratory epithelium carcinogenesis.

关键词： CBP p300 lung cancer acetylation transcription factor

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Implication of gut microbiome in immunotherapy for colorectal cancer

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1665-1674页

作者： Evangelos Koustas Eleni-Myrto Trifylli Panagiotis Sarantis Nikolaos Papadopoulos Georgios Aloizos Ariadne Tsagarakis Christos Damaskos Nikolaos Garmpis Anna Garmpi Athanasios G Papavassiliou michalis v karamouzis Department of Biological Chemistry Medical SchoolNational and Kapodistrian University of AthensAthens 11527Greece 1st Department of Internal Medicine 417 Army Share Fund Hospital of AthensAthens 11521AtticaGreece Beth Israel Deaconess Medical Center BostonMA 02215United States N.S.Christeas Laboratory of Experimental Surgery and Surgical Research Medical SchoolNational and Kapodistrian University of AthensAthens 11527Greece Second Department of Propedeutic Surgery Laiko General HospitalMedical SchoolNational and Kapodistrian University of AthensAthens 11527Greece First Department of Pathology Medical SchoolNational and Kapodistrian University of AthensAthens 11527Greece

Colorectal cancer(CRC) constitutes the third most frequently reported malignancy in the male population and the second most common in women in the last two decades. Colon carcinogenesis is a complex, multifactorial event, resulting from genetic and epigenetic aberrations, the impact of environmental factors, as well as the disturbance of the gut microbial ecosystem. The relationship between the intestinal microbiome and carcinogenesis was relatively undervalued in the last decade. However, its remarkable effect on metabolic and immune functions on the host has been in the spotlight as of recent years. There is a strong relationship between gut microbiome dysbiosis, bowel pathogenicity and responsiveness to anti-cancer treatment;including immunotherapy. Modifications of bacteriome consistency are closely associated with the immunologic response to immunotherapeutic agents. This condition that implies the necessity of gut microbiome manipulation. Thus, creatingan optimal response for CRC patients to immunotherapeutic agents. In this paper, we will review the current literature observing how gut microbiota influence the response of immunotherapy on CRC patients.

关键词： Colorectal cancer Gut microbiome Immunotherapy Checkpoint inhibitors Tumor micro-environment

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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

作者： Bridget Martinez Philip v.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular vesicles/exosomes blood serum brain tissue brain tissue extracellular vesicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

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Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

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Neural Regeneration Research 2025年第10期20卷 2776-2786页

We performed a PubMed search for microRNAs in autism spectrum disorder that could serve as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular vesicles,1 with blood cells,and 2 with peripheral blood mononuclear *** of the studies involved children and the study cohorts were largely *** of the studies had performed microRNA sequencing or quantitative polymerase chain reaction assays to measure microRNA *** five studies had used real-time polymerase chain reaction assay to validate microRNA expression in autism spectrum disorder subjects compared to *** microRNAs that were validated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of *** important limitations were identified in the studies reviewed,and need to be taken into account in future *** studies are warranted with children and adults having different levels of autism spectrum disorder severity and consideration should be given to using animal models of autism spectrum disorder to investigate the effects of suppressing or overexpressing specific microRNAs as a novel therapy.

关键词： autism spectrum disorder biomarker blood cells blood plasma blood serum diagnosis microRNA peripheral blood mononuclear cells serum neural cell adhesion molecule L1-captured extracellular vesicles whole blood

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MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

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Semantic Segmentation of Lumbar vertebrae Using Meijering U-Net(MU-Net)on Spine Magnetic Resonance Images

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 733-757页

作者： Lakshmi S v v Shiloah Elizabeth Darmanayagam Sunil Retmin Raj Cyril Department of Computer Science and Engineering College of Engineering GuindyAnna UniversityChennai600025India Department of Information Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower back pain is one of the most common medical problems in the world and it is experienced by a huge percentage of people *** to its ability to produce a detailed view of the soft tissues,including the spinal cord,nerves,intervertebral discs,and vertebrae,Magnetic Resonance Imaging is thought to be the most effective method for imaging the *** semantic segmentation of vertebrae plays a major role in the diagnostic process of lumbar *** is difficult to semantically partition the vertebrae in Magnetic Resonance Images from the surrounding variety of tissues,including muscles,ligaments,and intervertebral discs.U-Net is a powerful deep-learning architecture to handle the challenges of medical image analysis tasks and achieves high segmentation *** work proposes a modified U-Net architecture namely MU-Net,consisting of the Meijering convolutional layer that incorporates the Meijering filter to perform the semantic segmentation of lumbar vertebrae L1 to L5 and sacral vertebra ***-colour mask images were generated and used as ground truth for training the *** work has been carried out on 1312 images expanded from T1-weighted mid-sagittal MRI images of 515 patients in the Lumbar Spine MRI Dataset publicly available from Mendeley *** proposed MU-Net model for the semantic segmentation of the lumbar vertebrae gives better performance with 98.79%of pixel accuracy(PA),98.66%of dice similarity coefficient(DSC),97.36%of Jaccard coefficient,and 92.55%mean Intersection over Union(mean IoU)metrics using the mentioned dataset.

关键词： Computer aided diagnosis(CAD) magnetic resonance imaging(MRI) semantic segmentation lumbar vertebrae deep learning U-Net model

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An SPH Framework for Earthquake-Induced Liquefaction Hazard Assessment of Geotechnical Structures

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 251-277页

作者： Sourabh Mhaski G.v.Ramana Department of Civil Engineering Indian Institute of Technology DelhiNew Delhi110016India

Earthquake-induced soil liquefaction poses significant risks to the stability of geotechnical structures *** understanding of the liquefaction triggering,and the post-failure large deformation behaviour is essential for designing resilient *** present study develops a Smoothed Particle Hydrodynamics(SPH)framework for earthquake-induced liquefaction hazard assessment of geotechnical *** coupled flowdeformation behaviour of soils subjected to cyclic loading is described using the PM4Sand model implemented in a three-phase,single-layer SPH framework.A staggered discretisation scheme based on the stress particle SPH approach is adopted to minimise numerical inaccuracies caused by zero-energy modes and tensile ***,non-reflecting boundary conditions for seismic analysis of semi-infinite soil domains using the SPH method are *** numerical framework is employed for the analysis of cyclic direct simple shear test,seismic analysis of a level ground site,and liquefaction-induced failure of the Lower San Fernando *** agreement for liquefaction triggering and post-failure behaviour demonstrates that the SPH framework can be utilised to assess the effect of seismic loading on field-scale geotechnical *** present study also serves as the basis for future advancements of the SPH method for applications related to earthquake geotechnical engineering.

关键词： Earthquake seismic liquefaction stress particle PM4Sand smoothed particle hydrodynamics(SPH)

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