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Article ; Online: Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma.

Pace, Angelica / Scirocchi, Fabio / Napoletano, Chiara / Zizzari, Ilaria Grazia / D'Angelo, Luca / Santoro, Antonio / Nuti, Marianna / Rahimi, Hassan / Rughetti, Aurelia

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological ... ...

Abstract	Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological processes through the recognition of specific sugar motifs. Lectins and their ligands are found on immune cells, endothelial cells and, also, tumor cells, pointing out a strong correlation among immunity, tumor microenvironment and vascularization. In GB, altered glycans and lectins contribute to tumor progression and immune evasion, shaping the tumor-immune landscape promoting immunosuppressive cell subsets, such as myeloid-derived suppressor cells (MDSCs) and M2-macrophages, and affecting immunoeffector populations, such as CD8
MeSH term(s)	CD8-Positive T-Lymphocytes ; Endothelial Cells/metabolism ; Galectins/metabolism ; Glioblastoma ; Humans ; Immunosuppression Therapy ; Lectins, C-Type ; Polysaccharides/metabolism ; Tumor Microenvironment
Chemical Substances	Galectins ; Lectins, C-Type ; Polysaccharides
Language	English
Publishing date	2022-06-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116312
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Article ; Online: Proteomic characterization of extracellular vesicles released by third stage larvae of the zoonotic parasite

Palomba, Marialetizia / Rughetti, Aurelia / Mignogna, Giuseppina / Castrignanò, Tiziana / Rahimi, Hassan / Masuelli, Laura / Napoletano, Chiara / Pinna, Valentina / Giorgi, Alessandra / Santoro, Mario / Schininà, Maria Eugenia / Maras, Bruno / Mattiucci, Simonetta

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1079991

Abstract: Introduction: Anisakis pegreffii: Methods: Genetically identified L3 of : Results and discussion: EVs showed spherical shaped structure (size 65-295 nm). Proteomic results were blasted against ... ...

Abstract	Introduction: Anisakis pegreffii Methods: Genetically identified L3 of Results and discussion: EVs showed spherical shaped structure (size 65-295 nm). Proteomic results were blasted against the
MeSH term(s)	Animals ; Humans ; Anisakis/genetics ; Larva ; Parasites ; Proteomics ; Anisakiasis/etiology ; Anisakiasis/parasitology ; Fish Diseases/parasitology
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1079991
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Article ; Online: Circulating CD137

Cirillo, Alessio / Zizzari, Ilaria Grazia / Botticelli, Andrea / Strigari, Lidia / Rahimi, Hassan / Scagnoli, Simone / Scirocchi, Fabio / Pernazza, Angelina / Pace, Angelica / Cerbelli, Bruna / d'Amati, Giulia / Marchetti, Paolo / Nuti, Marianna / Rughetti, Aurelia / Napoletano, Chiara

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to ...

Abstract	Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; T-Lymphocytes ; Head and Neck Neoplasms/drug therapy ; Biomarkers
Chemical Substances	pembrolizumab (DPT0O3T46P) ; Biomarkers
Language	English
Publishing date	2023-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24087114
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Article ; Online: Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs.

Pace, Angelica / Scirocchi, Fabio / Napoletano, Chiara / Zizzari, Ilaria Grazia / Po, Agnese / Megiorni, Francesca / Asquino, Angela / Pontecorvi, Paola / Rahimi, Hassan / Marchese, Cinzia / Ferretti, Elisabetta / Nuti, Marianna / Rughetti, Aurelia

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 626

Abstract: Background: Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the ... ...

Abstract	Background: Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy. In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations. Methods: NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student's t test to compare the analysis of two groups. Results: Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR). Conclusions: These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies.
MeSH term(s)	Humans ; MicroRNAs/genetics ; Up-Regulation/genetics ; Reactive Oxygen Species ; Cell Cycle Checkpoints ; G1 Phase
Chemical Substances	MicroRNAs ; pemigatinib (Y6BX7BL23K) ; Reactive Oxygen Species ; MIRN139 microRNA, human ; MIRN186 microRNA, human
Language	English
Publishing date	2023-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04450-7
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Article ; Online: Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis.

Scirocchi, Fabio / Strigari, Lidia / Di Filippo, Alessandra / Napoletano, Chiara / Pace, Angelica / Rahimi, Hassan / Botticelli, Andrea / Rughetti, Aurelia / Nuti, Marianna / Zizzari, Ilaria Grazia

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of ...

Abstract	Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated. A systematic literature search of original articles in PubMed, MEDLINE and Scopus was conducted. Studies reporting hazard ratios (HRs) with a 95% confidence interval (CI) or Kaplan−Meier curves or individual patient data for overall survival (OS) or progression-free survival (PFS) associated with baseline levels of sPD-L1 in cancer patients undergoing immunotherapy treatment were considered eligible. Twelve studies involving 1076 patients and different tumor types treated with immunotherapy were included in the analysis. High blood levels of sPD-L1 correlated with poorer OS and PFS in cancer patients treated with immunotherapy (HR = 1.49, 95%CI: 1.15, 1.93, p < 0.01, I2 = 77% for OS; HR = 1.59, 95%CI: 1.20, 2.12, p < 0.01, I2 = 82% for PFS). A subgroup analysis highlighted that high levels of sPD-L1 were associated with worse survival in patients affected by NSCLC (HR = 1.81 95%CI: 1.09−3.00, p = 0.02, I2 = 83% for OS; HR = 2.18, 95%CI: 1.27−3.76, p < 0.01, I2 = 88% for PFS). An HR > 1 indicated that patients with low levels of sPD-L1 have the highest rates of OS/PFS. In this meta-analysis, we clarified the role of sPD-L1 in different solid cancers treated exclusively with Immune checkpoint inhibitors (ICIs). sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.
MeSH term(s)	Humans ; B7-H1 Antigen ; Prognosis ; Immunotherapy ; Immunologic Factors ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms
Chemical Substances	B7-H1 Antigen ; Immunologic Factors
Language	English
Publishing date	2022-11-21
Publishing country	Switzerland
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232214496
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Article: Surgical management of acetabular fractures: a case series.

Rahimi, Hassan / Gharahdaghi, Mohammad / Parsa, Ali / Assadian, Maryam

Trauma monthly

2013 Volume 18, Issue 1, Page(s) 28–31

Abstract: Introduction: For decades, acetabular fractures were treated conservatively. Judet et al. in 1960s established the operative treatment of these fractures by continuous improvement of pre-operative evaluation and classification of fractures. Several ... ...

Abstract	Introduction: For decades, acetabular fractures were treated conservatively. Judet et al. in 1960s established the operative treatment of these fractures by continuous improvement of pre-operative evaluation and classification of fractures. Several studies demonstrated that accurate fracture reduction decreases the incidence of post-traumatic arthritis and improves functional outcome. Case series: We report 67 consecutive patients who underwent surgical treatment for acetabular fracture; 44 patients were available for follow-up. In 35 (79.5%) cases, congruent reductions were achieved. The final mean Harris hip score was 81.8 (53-95). Functional outcomes according to Harris score were excellent and good in 31 patients (70.5%). Conclusions: The results of internal fixation of displaced acetabular fractures in our series were satisfactory.
Language	English
Publishing date	2013-05-26
Publishing country	Iran
Document type	Case Reports
ZDB-ID	2713451-9
ISSN	2251-7472 ; 2251-7464
ISSN (online)	2251-7472
ISSN	2251-7464
DOI	10.5812/traumamon.7164
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Article: Failure of concrete canal lining on fine sandy soils: a case study for the Saveh Project

Rahimi, Hassan / Abbasi, Nader

Irrigation and drainage. 2008 Feb., v. 57, no. 1

2008

Abstract: This paper presents the results of an investigation conducted on the causes of failure of concrete linings in the Saveh Irrigation Project. Firstly, a detailed field survey was performed and all previous technical reports on this subject were studied. ... ...

Abstract	This paper presents the results of an investigation conducted on the causes of failure of concrete linings in the Saveh Irrigation Project. Firstly, a detailed field survey was performed and all previous technical reports on this subject were studied. Then, several test pits were dug at 500 m intervals along the canal embankment as well as its centre line and soil samples were taken from different depths at 50 cm intervals. All samples were tested for their chemical, physical and mechanical properties. The results of the tests showed that most samples were sandy and classified as chemically non-dispersive. However, the results of pinhole tests showed that some samples are physically medium to highly dispersive. Based on the overall results of the field and laboratory investigations, the main causes of the damage to the lining were related to three groups, i.e. design parameters, construction quality, and geotechnical properties of the foundation soil. Among these, the latter was mainly responsible for the damage. Based on the nature of damage, few remedial measures have been suggested. The canal was monitored for the last four years and no further indication of damage has been observed since then. Copyright © 2007 John Wiley & Sons, Ltd.
Keywords	irrigation canals ; concrete ; mechanical damage ; irrigation water ; sandy soils ; Iran
Language	English
Dates of publication	2008-02
Size	p. 83-92.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
ZDB-ID	2047418-0
ISSN	1531-0353
ISSN	1531-0353
DOI	10.1002/ird.350
Database	NAL-Catalogue (AGRICOLA)

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Article: APPLICATION OF GEOMEMBRANE TO CONTROL PIPING OF SANDY SOIL UNDER CONCRETE CANAL LINING (CASE STUDY: MOGHAN IRRIGATION PROJECT, IRAN)

Rahimi, Hassan / Abbasi, Nader / Shantia, Hassan

Irrigation and drainage. 2011 July, v. 60, no. 3

2011

Abstract: Fine sandy soils have always been known as one of those problematic soils which will erode rapidly and cause piping due to water flow. This phenomenon has caused the destruction of many concrete canal linings around the world. In the present study, the ... ...

Abstract	Fine sandy soils have always been known as one of those problematic soils which will erode rapidly and cause piping due to water flow. This phenomenon has caused the destruction of many concrete canal linings around the world. In the present study, the history of the design, construction and operation of a canal in the Moghan Irrigation and Drainage Network, in north-west Iran, is reviewed and the main causes of destruction of the concrete lining of the canal are discussed. Based on the results of geotechnical studies, it was found that the canal was constructed on wind-blown deposits consisting of very fine to fine sand and loess. During operation of the canal, the fine, clean sandy subgrade soil was highly eroded due to water seeping under the canal lining, causing severe piping and consequently destruction of the lining. Following field and laboratory investigations, the main cause of the problem was diagnosed as “physical dispersivity” of the subgrade soil, and application of a geomembrane under the concrete lining was chosen as the most economical and practical measure to remedy the problem. Copyright © 2010 John Wiley & Sons, Ltd.
Keywords	case studies ; concrete ; history ; irrigation canals ; irrigation systems ; laboratories ; loess ; pipes ; sand ; sandy soils ; soil ; water erosion ; water flow ; Iran
Language	English
Dates of publication	2011-07
Size	p. 330-337.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
ZDB-ID	2047418-0
ISSN	1531-0353
ISSN	1531-0353
DOI	10.1002/ird.574
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: IgM-Rheumatoid factor confers primary resistance to anti-PD-1 immunotherapies in NSCLC patients by reducing CD137

Ugolini, Alessio / Zizzari, Ilaria Grazia / Ceccarelli, Fulvia / Botticelli, Andrea / Colasanti, Tania / Strigari, Lidia / Rughetti, Aurelia / Rahimi, Hassan / Conti, Fabrizio / Valesini, Guido / Marchetti, Paolo / Nuti, Marianna

EBioMedicine

2020 Volume 62, Page(s) 103098

Abstract: Background: ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a ... ...

Abstract	Background: ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137 Methods: Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated. Findings: IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naïve and central memory T-cells and a significant reduction of CD137 Interpretation: In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naïve and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137 Fundings: AIRC, MIUR and Sapienza University of Rome.
MeSH term(s)	Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/immunology ; Carcinoma, Non-Small-Cell Lung/metabolism ; Disease Progression ; Drug Resistance, Neoplasm ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunoglobulin M/blood ; Immunoglobulin M/immunology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology ; Lung Neoplasms/metabolism ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Molecular Targeted Therapy ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Retrospective Studies ; Rheumatoid Factor/blood ; Rheumatoid Factor/immunology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism
Chemical Substances	Immune Checkpoint Inhibitors ; Immunoglobulin M ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; TNFRSF9 protein, human ; Tumor Necrosis Factor Receptor Superfamily, Member 9 ; Rheumatoid Factor (9009-79-4)
Language	English
Publishing date	2020-11-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2020.103098
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Article: Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences

2022 Volume 27, Page(s) 71

Abstract: Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors ( ... ...

Abstract	Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.
Language	English
Publishing date	2022-09-27
Publishing country	India
Document type	Journal Article
ZDB-ID	2513029-8
ISSN	1735-7136 ; 1735-1995
ISSN (online)	1735-7136
ISSN	1735-1995
DOI	10.4103/jrms.jrms_889_21
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