Ugo Testa's research while affiliated with Istituto Superiore di Sanità and other places

Publications (14)

Article
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In the present study, we characterized the metabolic background of different Acute Myeloid Leukemias’ (AMLs) cells and described a heterogeneous and highly flexible energetic metabolism. Using the Seahorse XF Agilent, we compared the metabolism of normal hematopoietic progenitors with that of primary AML blasts and five different AML cell lines. We...
Chapter
MicroRNAs (miRs) are small noncoding RNA that exert their biological activity at the level of gene regulation. miRs play an important role in normal hematopoiesis in the control of hemopoietic cell proliferation and differentiation from stem cells to mature elements of the various cell lineages. miRNA expression is dysregulated in human leukemias,...
Article
Introduction Lung cancer is the leading cause of cancer mortality worldwide; lung adenocarcinoma (LUAD) corresponds to about 40% of lung cancers. LUAD is a genetically heterogeneous disease and the definition of this heterogeneity is of fundamental importance for prognosis and treatment. Areas covered Based on primary literature, this review provi...
Article
Minimal or measurable residual disease (MRD) is a term that refers to the submicroscopic tumor disease persisting after therapy. Sensitive immunophenotypic and molecular techniques are used to detect the small amount of residual tumor cells, conferring a detection capacity clearly more sensitive of common cytomorphologic techniques. MRD evaluation...
Article
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The development of molecular studies to define the somatic genetic alterations has revolutionized the diagnostic and therapeutic management of acute myeloid leukemia (AML). AML is a highly heterogenous disease that includes many molecular subtypes; each subtype is heterogeneous both for the presence of variable co-mutations and complex combinations...
Article
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Metabolism in acute myeloid leukemia (AML) cells is dependent primarily on oxidative phosphorylation. However, in order to sustain their high proliferation rate and metabolic demand, leukemic blasts use a number of metabolic strategies, including glycolytic metabolism. Understanding whether monocarboxylate transporters MCT1 and MCT4, which remove t...
Article
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Angiogenesis is a word that refers to new blood vessel formation, and this process is of fundamental importance for physiological development and tissue homeostasis, as well as the genesis of several diseases, including tumors. Thus, studies carried out in the last years have shown that angiogenesis is essential for the growth of many solid tumors....
Article
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Vitamin C (ascorbate) is an essential dietary requirement, with fundamental redox, anti-oxidant functions at physiologic concentrations. Vitamin C is a cofactor for Fe²⁺ and 2-oxoglutarate-dependent dioxygenases, englobing large families of enzymes, including also epigenetic regulators of DNA and histone methylation. Importantly, vitamin C is invol...
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Genome sequencing studies have characterized the genetic alterations of different tumor types, highlighting the diversity of the molecular processes driving tumor development. Comprehensive sequencing studies have defined molecular subtypes of colorectal cancers (CRCs) through the identification of genetic events associated with microsatellite stab...
Article
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Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors. In the last years, there has been a dramatic improvement in the understanding of the molecular alterations driving cellula...
Article
Full-text available
Renal cell cancer (RCC) involves three most recurrent sporadic types: clear-cell RCC (70–75%, CCRCC), papillary RCCC (10–15%, PRCC), and chromophobe RCC (5%, CHRCC). Hereditary cases account for about 5% of all cases of RCC and are caused by germline pathogenic variants. Herein, we review how a better understanding of the molecular biology of RCCs...
Article
In normal dividing tissues, cell homeostasis is maintained by rare cellular elements, the stem cells, that have the unique property of self-renewal and differentiation to generate a population of functionally mature tissue elements. Recent studies carried out in the last three decades support the existence of stem cells also in tumors, the so-calle...
Chapter
Tumor vascularization refers to the formation of new blood vessels within a tumor and is considered one of the hallmarks of cancer. Tumor vessels supply the tumor with oxygen and nutrients, required to sustain tumor growth and progression, and provide a gateway for tumor metastasis through the blood or lymphatic vasculature. Blood vessels display a...

Citations

... Although there are few studies about angiogenesis in hematological malignancy, BM angiogenesis in AML patients has been observed and may play a role in the pathogenesis (Hussong et al., 2000;Padro et al., 2000;Testa et al., 2020). BM microvessel density of AML patients is higher than that of healthy individuals at the time of diagnosis and decreases after remission (Padro et al., 2000;Song et al., 2015). ...
... AUC at five year is 0.75 in the Okayama cohort (He et al., 2020). A detailed and comprehensive study of the cooccurring genetic abnormalities characterizing different LUAD subsets was also conducted for a better understanding of the disease heterogeneity, and for the discovery of new therapeutic targets (Testa et al., 2022). ...
... Our present study suggests that the AML secretome alters the MSC capacity of extracellular protein release and thereby modulates the bidirectional MSCs communication with the leukemic cells (and possibly also communication with other stromal cells). Targeting of the crosstalk between AML cells and MSCs may represent a new therapeutic strategy, but this approach may be more effective for certain patients and should therefore be considered especially for individualized (personalized) therapy [53]. ...
... The aqueous fractions from cells and extracellular media were reconstituted in 700 µL D 2 O using TSP (0.1 mM) as NMR internal standards. In contrast, lipid fractions from cells were resuspended in a CD3OD/CDCl3 solution (2:1 v/v) with 0.05% of tetramethylsilane (TMS) as an internal reference [25]. ...
... Unlike most mammals, humans are unable to synthesize ascorbic acid from oxidated glucose, missing the gulonolactone (L-) oxidase (GULO), a key enzyme involved in the catalysis of the last enzymatic step in ascorbate synthesis, and are thereby dependent on vitamin C intake from the diet (Du et al., 2012). The dietary daily requirement of vitamin C is 75-90 mg/day, which is usually taken under the form of both ascorbate and DHA (Valdés, 2006;Testa et al., 2021). Indeed, even if DHA levels are extremely low under physiological conditions (Du et al., 2012), it is rapidly recycled back to ascorbate by DHA reductase, using glutathione (GSH) as a reducing agent (Mandl et al., 2009). ...
... Previous studies have addressed the mutational landscape in primary and metastatic CRCs and found that genomes of metastases are essentially not different from those of primary tumors. [8,9]. Only a few studies investigated gene expression profiles in primary tumors and metastases utilizing distinct comparative models to identify prognostic metastasis signatures and biomarkers [8][9][10][11]. ...
... Notably, several common mutations do not alone provide the clone with proliferative advantage, with HSCs that are defective in their growth and differentiation in vitro and that engraft poorly in immunodeficient recipient mice [16]. For example, Isocitrate Dehydrogenase (IDH) mutations are epigenetic modifiers and do not have a proliferative advantage per se [17,18]. Similarly, Serine and Arginine Rich Splicing Factor 2 (SRSF2) mutations influence the splicing machinery and require additional proliferative mutations [19]. ...
... Comprehensive molecular characterization of RCC confirmed the association of VHL gene mutations and the involvement of epigenetic reprogramming in the development of the disease [121,158]. PBRM1, or protein polybromo-1, which is a subunit of ATPdependent chromatin-remodeling complexes, and SET2D, a histone methyltransferase that specifically trimethylates lysine 36 of histone H3 (H3K36me3), were among the top mutated genes in RCC. Interestingly, both genes are located on the short arm of chromosome 3, similar to VHL, in the range of 3p-21 to 3p-25. ...
... EPCs have been known to promote cancer progression by releasing several cytokines that induce tumor neovascularization and enhance survivability and migratory capacity of cancer cells [29,30]. We showed that the conditioned medium derived from TAZ-KD EPCs increased apoptosis, inhibited migration, reduced the percentage of side population (SP) enriched for cancer stem cells in human lung adenocarcinoma cell lines, and increased their sensitivity to chemotherapeutic agents. ...