Abstract Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimized codons show high expression levels at the first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time, allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimization of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.

Oncolytic adenovirus

Replication

10.1093/narcan/zcab015

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Citations (5)

Supplementary Data from Activation of the Osteopontin/Matrix Metalloproteinase-9 Pathway Correlates with Prostate Cancer Progression

Giancarlo Castellano Grazia Malaponte María Clorinda Mazzarino Mariangela Figini Francesco Marchese

Supplementary Data from Activation of the Osteopontin/Matrix Metalloproteinase-9 Pathway Correlates with Prostate Cancer Progression

Osteopontin

Matrix metalloproteinase 9

Tumor progression

10.1158/1078-0432.22439844

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Integrating Genomic Alterations in Diffuse Large B-Cell Lymphoma Identifies New Relevant Pathways and Potential Therapeutic Targets

Blood (2016)

Iván Dlouhy Kennosuke Karube Anna Enjuanes David Martin‐García Ferran Nadeu

CDKN2B

Epigenome

10.1182/blood.v128.22.152.152

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Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets

Leukemia (2017)

Kennosuke Karube Anna Enjuanes Iván Dlouhy Pedro Jares David Martin‐García

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.

10.1038/leu.2017.251

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Citations (158)

Progesterone Signaling to Chromatin in Breast Cancer Cells. Two Initial Cycles of Remodeling

Springer eBooks (2011)

Guillermo P. Vicent Roser Zaurín Cecilia Ballaré A. Silvina Nacht Roni H. G. Wright

Sex chromatin

10.1007/978-1-4614-1764-4_2

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Citations (1)

Pseudomelanosis of the Duodenum

Journal of Clinical Gastroenterology (1988)

Giancarlo Castellano F Canga José I. López Francisco Colina J. M. Gutierrez

We present the endoscopic, microscopic, and histochemical studies of a patient with pseudomelanosis of the duodenum. The pigment was located mainly in the lysosomes of macrophages in the lamina propria and was heterogeneous, showing features of melanin, pseudomelanin, and hemosiderin. The origin of this pigment remains unknown, but antihypertensive medication may have played a role.

Hemosiderin

Lamina propria

10.1097/00004836-198804000-00009

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Citations (19)

Aberrant phosphatidylcholine metabolism in human ovarian cancer

Chemistry and Physics of Lipids (2010)

Egidio Iorio Alessandro Ricci Maria Elena Pisanu Giancarlo Castellano Marina Bagnoli

Phosphatidylethanolamine

Phosphocholine

Lysophosphatidylethanolamine

Choline

Betaine

Lysophosphatidylcholine

10.1016/j.chemphyslip.2010.05.188

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Two in one: the genesis of central pain

Pain (1996)

Sergio Canavero Vincenzo Bonicalzi Giancarlo Castellano

Neurosurgical Pain Relief Unit and Service of Nuclear Medicine University of Turin 10126 Turin, Italy

10.1016/0304-3959(95)00197-2

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Citations (12)

P81 Occupational hypersensitivity to platinum group elements

Contact Dermatitis (2004)

Antonio Cristaudo Vincenzo Severino Giancarlo Castellano A Papale Sergio Caroli

Objective: the increasing industrial use of platinum–group elements (PGEs), namely Ir, Pd, Pt and Rh and related hypersensitivity such as respiratory symptoms, urticaria and contact dermatitis, have led to a growing need to monitor selected populations of exposed workers. Our aim is to determine the prevalence and the clinical characteristics of hypersensitivity to the platinum‐group elements; the levels of PGE measured in indoor airborne particulate matter and in biological samples (serum, urine and hair) taken from of employees in a platinum refining and catalyst manufacture; to correlate environmental exposure role and platinum salts concentrations in biological samples in the onset of allergy. Material and methods: 132 subjects variable exposed were informed about the purpose of this study and gave their consent. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test to platinum salts and to other common allergens and patch test to platinum salts. Airborne PGEs was collected by personal and area samples. Biological samples (serum, urine and hair) were collected. Analitical procedure based on sector field inductively coupled plasma mass spectometry (SP‐ICP‐MS) for the analysis of airborne filter, serum, urine and hair was used. Results: positive prick test to platinum salts were found in 18 workers, 4 out 14 gave simultaneous positive reactions to Pt, Rh and Ir. 2 out 14 gave a positive reaction to Pt and Pd. Positive patch test reactions to Pt were found in 2 subjects, 1 out 2 gave positive reaction also to Pd Conclusion: the preliminary results of the investigation indicate that Pt‐salts are important allergens in catalyst industry and that the clinical manifestation involves both the respiratory system and the skin

Patch test

Platinum group

10.1111/j.0105-1873.2004.00309hk.x

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