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Article ; Online: Transcriptomic data of bevacizumab-adapted colorectal adenocarcinoma cells HCT-116

Sala Cesare / Lottini Tiziano / Lastraioli Elena / Ruffinatti Federico Alessandro / Visentin Luca / Arcangeli Annarosa

Data in Brief, Vol 48, Iss , Pp 109069- (2023)

2023

Abstract: A bioinformatic approach was applied to evaluate the effect of treatment with Bevacizumab on the gene expression profile of colorectal adenocarcinoma cells. The transcriptomic profile of Bevacizumab-adapted HCT-116 (Bev/A) colorectal adenocarcinoma cells ...

Abstract	A bioinformatic approach was applied to evaluate the effect of treatment with Bevacizumab on the gene expression profile of colorectal adenocarcinoma cells. The transcriptomic profile of Bevacizumab-adapted HCT-116 (Bev/A) colorectal adenocarcinoma cells was determined and compared with that of the corresponding control cell line by Agilent microarray analysis. Raw data were preprocessed, normalized, filtered, and subjected to a differential expression analysis using standard R/Bioconductor packages (i.e., limma, RankProd). As consequence of Bevacizumab adaptation, 166 differentially expressed genes (DEGs) emerged, most of them (123) resulted downregulated and 43 overexpressed. The list of statistically significant dysregulated genes was used as an input for functional overrepresentation analysis using ToppFun web tool. Such analysis pointed at cell adhesion, cell migration, extracellular matrix organization and angiogenesis as the main dysregulated biological process involved in Bevacizumab-adaptation of HCT116 cells. In addition, gene set enrichment analysis was performed using GSEA, searching for enriched terms within the Hallmarks (H), Canonical Pathways (CP), and Gene Ontology (GO) gene sets. GO terms that showed significant enrichment included: transportome, vascularization, cell adhesion and cytoskeleton, extra cellular matrix (ECM), differentiation and epithelial–mesenchymal transition (EMT), inflammation and immune response. Raw and normalized microarray data were deposited in the Gene Expression Omnibus (GEO) public repository with accession number GSE221948.
Keywords	Gene expression ; HCT116 ; Bevacizumab ; Bioinformatic analysis ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
Subject code	570 ; 612
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Generation of an Orthotopic Xenograft of Pancreatic Cancer Cells by Ultrasound-Guided Injection.

Lottini, Tiziano / Buonamici, Matteo / Duranti, Claudia / Arcangeli, Annarosa

Journal of visualized experiments : JoVE

2021 , Issue 177

Abstract: Pancreatic cancer (PCa) represents one of the deadliest cancer types worldwide. The reasons for PCa malignancy mainly rely on its intrinsic malignant behavior and high resistance to therapeutic treatments. Indeed, despite many efforts, both standard ... ...

Abstract	Pancreatic cancer (PCa) represents one of the deadliest cancer types worldwide. The reasons for PCa malignancy mainly rely on its intrinsic malignant behavior and high resistance to therapeutic treatments. Indeed, despite many efforts, both standard chemotherapy and innovative target therapies have substantially failed when moved from preclinical evaluation to the clinical setting. In this scenario, the development of preclinical mouse models better mimicking in vivo characteristics of PCa is urgently needed to test newly developed drugs. The present protocol describes a method to generate a mouse model of PCa, represented by an orthotopic xenograft obtained by ultrasound-guided injection of human pancreatic tumor cells. Using such a reliable and minimally invasive protocol, we also provide evidence of in vivo engraftment and development of tumor masses, which can be monitored by ultrasound (US) imaging. A noteworthy aspect of the PCa model described here is the slow development of the tumor masses over time, which allows precise identification of the starting point for pharmacological treatments and better monitoring of the effects of therapeutic interventions. Moreover, the technique described here is an example of implementation of the 3Rs principles since it minimizes pain and suffering and directly improves the welfare of animals in research.
MeSH term(s)	Animals ; Cell Line, Tumor ; Disease Models, Animal ; Heterografts ; Humans ; Mice ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Transplantation, Heterologous ; Ultrasonography/methods ; Ultrasonography, Interventional ; Xenograft Model Antitumor Assays
Language	English
Publishing date	2021-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/63123
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Corrigendum to "Transcriptomic data of Bevacizumab-adapted colorectal adenocarcinoma cells HCT-116" [Data In Brief, Volume 48, (Available online 17 March 2023) 1-9/Article 109069].

Sala, Cesare / Lottini, Tiziano / Lastraioli, Elena / Ruffinatti, Federico Alessandro / Visentin, Luca / Arcangeli, Annarosa

Data in brief

2023 Volume 49, Page(s) 109343

Abstract: This corrects the article DOI: 10.1016/j.dib.2023.109069.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.dib.2023.109069.].
Language	English
Publishing date	2023-06-24
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2023.109343
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Article ; Online: Expression of the ether-a-gò-gò-related gene 1 channel during B and T lymphocyte development: role in BCR and TCR signaling.

Sala, Cesare / Staderini, Martina / Lottini, Tiziano / Duranti, Claudia / Angelini, Gabriele / Constantin, Gabriela / Arcangeli, Annarosa

Frontiers in immunology

2023 Volume 14, Page(s) 1111471

Abstract: The functional relevance of ... ...

Abstract	The functional relevance of K
MeSH term(s)	Animals ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes ; Lymphocyte Activation ; Encephalomyelitis, Autoimmune, Experimental ; Ethers ; Receptors, Antigen, T-Cell
Chemical Substances	Ethers ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-09-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1111471
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Article: Combination Therapy with a Bispecific Antibody Targeting the hERG1/β1 Integrin Complex and Gemcitabine in Pancreatic Ductal Adenocarcinoma.

Lottini, Tiziano / Duranti, Claudia / Iorio, Jessica / Martinelli, Michele / Colasurdo, Rossella / D'Alessandro, Franco Nicolás / Buonamici, Matteo / Coppola, Stefano / Devescovi, Valentina / La Vaccara, Vincenzo / Coppola, Alessandro / Coppola, Roberto / Lastraioli, Elena / Arcangeli, Annarosa

Cancers

2023 Volume 15, Issue 7

Abstract: Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex. First, using the scDb (scDb-hERG1-β1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/β1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-β1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-β1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-β1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-β1 targeting the hERG1/β1 integrin complex as neoantigen.
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15072013
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Article: K

Iorio, Jessica / Duranti, Claudia / Lottini, Tiziano / Lastraioli, Elena / Bagni, Giacomo / Becchetti, Andrea / Arcangeli, Annarosa

Frontiers in pharmacology

2020 Volume 11, Page(s) 848

Abstract: Increasing evidence indicates that ion channels and transporters cooperate in regulating different aspects of tumor pathophysiology. In cancer cells, ... ...

Abstract	Increasing evidence indicates that ion channels and transporters cooperate in regulating different aspects of tumor pathophysiology. In cancer cells, H
Language	English
Publishing date	2020-06-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.00848
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Article ; Online: Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma.

Anichini, Giulia / Raggi, Chiara / Pastore, Mirella / Carrassa, Laura / Maresca, Luisa / Crivaro, Enrica / Lottini, Tiziano / Duwe, Lea / Andersen, Jesper B / Tofani, Lorenzo / Di Tommaso, Luca / Banales, Jesus M / Arcangeli, Annarosa / Marra, Fabio / Stecca, Barbara

Molecular cancer therapeutics

2023 Volume 22, Issue 3, Page(s) 343–356

Abstract: Cholangiocarcinoma (CCA) is characterized by resistance to chemotherapy and a poor prognosis. Therefore, treatments that can effectively suppress tumor growth are urgently needed. Aberrant activation of hedgehog (HH) signaling has been implicated in ... ...

Abstract	Cholangiocarcinoma (CCA) is characterized by resistance to chemotherapy and a poor prognosis. Therefore, treatments that can effectively suppress tumor growth are urgently needed. Aberrant activation of hedgehog (HH) signaling has been implicated in several cancers, including those of the hepatobiliary tract. However, the role of HH signaling in intrahepatic CCA (iCCA) has not been completely elucidated. In this study, we addressed the function of the main transducer Smoothened (SMO) and the transcription factors (TFs) GLI1 and GLI2 in iCCA. In addition, we evaluated the potential benefits of the combined inhibition of SMO and the DNA damage kinase WEE1. Transcriptomic analysis of 152 human iCCA samples showed increased expression of GLI1, GLI2, and Patched 1 (PTCH1) in tumor tissues compared with nontumor tissues. Genetic silencing of SMO, GLI1, and GLI2 inhibited the growth, survival, invasiveness, and self-renewal of iCCA cells. Pharmacologic inhibition of SMO reduced iCCA growth and viability in vitro, by inducing double-strand break DNA damage, leading to mitotic arrest and apoptotic cell death. Importantly, SMO inhibition resulted in the activation of the G2-M checkpoint and DNA damage kinase WEE1, increasing the vulnerability to WEE1 inhibition. Hence, the combination of MRT-92 with the WEE1 inhibitor AZD-1775 showed increased antitumor activity in vitro and in iCCA xenografts compared with single treatments. These data indicate that combined inhibition of SMO and WEE1 reduces tumor burden and may represent a strategy for the clinical development of novel therapeutic approaches in iCCA.
MeSH term(s)	Humans ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cholangiocarcinoma ; DNA Damage ; Hedgehog Proteins ; Protein-Tyrosine Kinases/genetics ; Receptors, G-Protein-Coupled/genetics ; Signal Transduction ; Smoothened Receptor/genetics ; Smoothened Receptor/metabolism ; Zinc Finger Protein GLI1/metabolism
Chemical Substances	Cell Cycle Proteins ; Hedgehog Proteins ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptors, G-Protein-Coupled ; Smoothened Receptor ; WEE1 protein, human (EC 2.7.10.2) ; Zinc Finger Protein GLI1
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0379
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Article ; Online: Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses.

Lottini, Tiziano / Iorio, Jessica / Lastraioli, Elena / Carraresi, Laura / Duranti, Claudia / Sala, Cesare / Armenio, Miriam / Noci, Ivo / Pillozzi, Serena / Arcangeli, Annarosa

Scientific reports

2021 Volume 11, Issue 1, Page(s) 8847

Abstract: The receptor for the luteinizing hormone (LH-R) is aberrantly over expressed in cancers of the reproductive system. To uncover whether LH-R over expression has a causative role in cancer, we generated a transgenic (TG) mouse which overexpresses the human ...

Abstract	The receptor for the luteinizing hormone (LH-R) is aberrantly over expressed in cancers of the reproductive system. To uncover whether LH-R over expression has a causative role in cancer, we generated a transgenic (TG) mouse which overexpresses the human LH-R (hLH-R) in the female reproductive tract, under the control of the oviduct-specific glycoprotein (OGP) mouse promoter (mogp-1). The transgene was highly expressed in the uterus, ovary and liver, but only in the uterus morphological and molecular alterations (increased proliferation and trans-differentiation in the endometrial layer) were detected. A transcriptomic analysis on the uteri of young TG mice showed an up regulation of genes involved in cell cycle control and a down regulation of genes related to the immune system and the metabolism of xenobiotics. Aged TG females developed tumor masses in the uteri, which resembled an Endometrial Cancer (EC). Microarray and immunohistochemistry data indicated the deregulation of signaling pathways which are known to be altered in human ECs. The analysis of a cohort of 126 human ECs showed that LH-R overexpression is associated with early-stage tumors. Overall, our data led support to conclude that LH-R overexpression may directly contribute to trigger the neoplastic transformation of the endometrium.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Cohort Studies ; Down-Regulation ; Endometrial Neoplasms/pathology ; Female ; Genitalia, Female/metabolism ; Humans ; Mice ; Mice, Transgenic ; Receptors, LH/genetics ; Receptors, LH/metabolism ; Transcriptome ; Up-Regulation
Chemical Substances	Receptors, LH
Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-87492-5
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Article ; Online: Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K.

Petroni, Giulia / Bagni, Giacomo / Iorio, Jessica / Duranti, Claudia / Lottini, Tiziano / Stefanini, Matteo / Kragol, Goran / Becchetti, Andrea / Arcangeli, Annarosa

Cell death & disease

2020 Volume 11, Issue 3, Page(s) 161

Abstract: We have studied how the macrolide antibiotic Clarithromycin (Cla) regulates autophagy, which sustains cell survival and resistance to chemotherapy in cancer. We found Cla to inhibit the growth of human colorectal cancer (CRC) cells, by modulating the ... ...

Abstract	We have studied how the macrolide antibiotic Clarithromycin (Cla) regulates autophagy, which sustains cell survival and resistance to chemotherapy in cancer. We found Cla to inhibit the growth of human colorectal cancer (CRC) cells, by modulating the autophagic flux and triggering apoptosis. The accumulation of cytosolic autophagosomes accompanied by the modulation of autophagic markers LC3-II and p62/SQSTM1, points to autophagy exhaustion. Because Cla is known to bind human Ether-à-go-go Related Gene 1 (hERG1) K
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Autophagosomes/drug effects ; Autophagosomes/metabolism ; Autophagy/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Clarithromycin/pharmacology ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/metabolism ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Ether-A-Go-Go Potassium Channels/drug effects ; Ether-A-Go-Go Potassium Channels/metabolism ; Humans ; Phosphatidylinositol 3-Kinases/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; Ether-A-Go-Go Potassium Channels ; KCNH1 protein, human ; Clarithromycin (H1250JIK0A)
Language	English
Publishing date	2020-03-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-020-2349-8
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Article ; Online: Correction: Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K.

Petroni, Giulia / Bagni, Giacomo / Iorio, Jessica / Duranti, Claudia / Lottini, Tiziano / Stefanini, Matteo / Kragol, Goran / Becchetti, Andrea / Arcangeli, Annarosa

Cell death & disease

2020 Volume 11, Issue 3, Page(s) 209

Abstract: The financial support for this Article was not fully acknowledged. The acknowledgements should have included the following: We thank M. Lulli (University of Florence, Italy) for acquiring images of immunofluorescence-labeled cells. This work was ... ...

Abstract	The financial support for this Article was not fully acknowledged. The acknowledgements should have included the following: We thank M. Lulli (University of Florence, Italy) for acquiring images of immunofluorescence-labeled cells. This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (#15627, #21510 and #19766 to A.A.); PAR FAS-Linea di Azione 1.1-Azione 1.1.2-Bando FAS Salute. 2014 (DD 4042/ 2014) Project OMITERC to A.A.; FAR 2018 to A.B.
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Published Erratum
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-020-2407-2
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