Mauro Piantelli

• Professor of Pathology
• University of Chieti-Pescara

Nutritional interventions facilitating the consumption of natural, affordable, and environment-compatible health-promoting functional foods are a promising strategy for controlling non-communicable diseases. Given that the complex of tomato micronutrients produces healthier outcomes than lycopene, its major antioxidant component, new strategies to...

It is well-established that the beneficial properties of single phytonutrients can be better attained when they are taken with the complex of the molecules present in their natural milieu. Tomato, the fruit providing the most comprehensive complex of prostate-health-preserving micronutrients, has been shown to be superior to its single-nutrient cou...

Background Platelet dysfunctions are shared by cardiovascular diseases and a wide range of inflammatory diseases. Aims To determine the ability of a new whole tomato-based food supplement (WTBFS) containing carotenoid and olive polyphenols to inhibit platelet aggregation. Methods Aggregation was evaluated in platelet-rich plasma using microtiter...

Trop-2 is a transmembrane signal transducer that is overexpressed in most human cancers, and drives malignant progression. To gain knowledge on the higher-order molecular mechanisms that drive Trop-2 signaling, we applied next-generation sequencing, proteomics, and high-resolution microscopy to models and primary cases of human colorectal cancer (C...

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2–driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in...

Background Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. The diagnosis of BPH is usually driven by lower urinary tract symptoms (LUTS) that can significantly affect patients’ quality of life. This phase II prospective, randomized double-blinded, placebo-controlled study aimed to determine the efficacy and...

Background: Benign prostatic hyperplasia is the most common urologic disease among elderly men. The diagnosis of BPH is usually in response to the appearance of lower urinary tract obstructive, and post-micturition symptoms (LUTS) that can significantly affect the quality of life. In Aim of this study was to evaluate in a phase II prospective, rand...

Background: Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. The diagnosis of BPH is usually driven by lower urinary tract symptoms (LUTS) that can significantly affect patients’ quality of life. This phase II prospective, randomized double-blinded, placebo-controlled study aimed to determine the efficacy an...

Background: Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. The diagnosis of BPH is usually driven by lower urinary tract symptoms (LUTS) that can significantly affect patients’ quality of life. This phase II prospective, randomized double-blinded, placebo-controlled study aimed to determine the efficacy an...

Background: Phospholipase Cγ1 (PLCγ1) is highly expressed in human tumours. Our previous studies reported that both stable and inducible PLCγ1 down-regulation can inhibit formation of breast-cancer-derived experimental lung metastasis. Further, high expression of PLCγ1 and its constitutively activated forms (i.e., PLCγ1-pY1253, PLCγ1-pY783) is ass...

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and is not a clinically homogeneous disease, but subsets of patients with distinct prognosis and response to therapy can be identified by genome-wide analyses. Mutations in major PDAC driver genes were associated with poor survival. By bioinformatics analysis,...

Objective: To evaluate the efficacy and safety of a novel tomato-based food supplement on the lower urinary tract symptoms (LUTS) of patients with benign prostatic hyperplasia (BPH). Methods: Twenty patients with BPH were enrolled in this observational study. They were assigned to consume daily a sachet of Lycoprozen® (5 grams) dissolved in water f...

The life expectancy for pancreatic cancer patients has seen no substantial changes in the last 40 years as very few and mostly just palliative treatments are available. As the five years survival rate remains around 5%, the identification of novel pharmacological targets and development of new therapeutic strategies are urgently needed. Here we dem...

Galectin-3-binding protein (Gal-3BP) has been identified as a cancer and metastasis-associated, secreted protein that is expressed by the large majority of cancers. The present study describes a special type of non-internalizing antibody-drug-conjugates that specifically target Gal-3BP. Here, we show that the humanized 1959 antibody, which specific...

Purpose: Non-muscle invasive bladder cancer (NMIBC) is a malignant disease characterized by high heterogeneity, which corresponds to dysregulated gene expression and alternative splicing (AS) profiles. Bioinformatics analyses of splicing factors potentially linked to bladder cancer progression identified the heterogeneous nuclear ribonucleoprotein...

Fig. S1. Effects of Vav1 on Akt mediated apoptosis of MDA‐MB‐231 cells.

Targeting different members of the Akt pathways is a promising therapeutic chance in solid tumors including breast cancer. The variable expression levels of Akt isoforms with opposite effects on tumor growth and metastasis, however, makes it difficult to select the inhibitors to be used for specific breast tumor subtypes. By using in vitro and in v...

Breast cancer, the most common malignancy among women, is usually detected at an early stage and has a low risk of relapse. Nevertheless, a significant number of patients cannot be cured solely by local treatment. Distinguishing between patients who are of low risk of relapse from those who are of high risk may have important implications to improv...

Trop-2 is overexpressed in most human cancers, suggesting selective pressure for a key, conserved function. Here we show that Trop-2 stimulates cancer cell growth through the activation of a constitutively expressed, yet otherwise dormant, growth-control module. We discovered that crosslinking of membrane Trop-2 with specific Abs leads to a cytopla...

Figure S5 3‐D cultures of transformed and non‐transformed mammary cells. A) Photographs of organoids formed by the different MDA‐MB‐231 cell lines expressing (scrambled) or non‐expressing (Sh1 and Sh2) FZD6 after 3 wk in culture. It is possible to note the more symmetrical shape of FZD6 depleted organoids compared to the control ones. Nuclei were s...

Table S1 Patients and tumour characteristics (n = 352)

Table S5 Multivariate analysis of FZD6 expression in triple negative tumours.

Figure S4 Expression of exogenous and endogenous FZD6 and RNAi efficiency in breast cancer cell lines. A) The bar plot shows RT‐qPCR analysis of FZD6 mRNA expression in MDA‐MB‐231 cells infected with lentiviruses containing the indicated shRNAs. Error bars display the calculated maximum (RQMax) and minimum (RQMin) expression levels and were compute...

Figure S6 A) Immunohistochemical analysis of tumours excised from mice injected with MDA‐MB‐231 cells The top panel shows a human breast cancer section (that served as a positive control) and the medium and bottom panels are sections from lymph nodes of mice injected with MDA‐MB‐231 cells infected with control or FZD6 (Sh1) targeting retroviruses....

Supplementary materials and methods

Supplementary figure legends

Figure S2 Analysis of copy number alterations (CNA) and RNA expression of FZD6. Absolute copy number levels for both METABRIC and KCL cohorts were established using ASCAT (REF: (http://www.pnas.org/content/107/39/16910.long)) A) METABRIC boxplot depicting distribution of FZD6 RNA expression among various copy number subtypes (i) for all Invasive Du...

Figure S3 Expression of FZD6 in breast cancer cell lines. (A) RT‐qPCR analysis of FZD6 mRNA expression in a panel of breast cancer cell lines. Error bars display the calculated maximum (RQMax) and minimum (RQMin) expression levels and were computed using RQ Manager (Applied Biosystems). (B) Western blot analysis showing expression of FZD6 protein i...

Table S2 Copy Number Variation (CNV) and overexpression of Frizzled (FZD) receptor 1 to 10 in primary breast cancer samples mined using the COSMIC repository (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/about).

Table S3 Assessment of metastatic growth in mice injected with MB‐MDA‐231 cells. A) The numbers of mice with breast cancer metastases in different organs are indicated as a percentage of the total. B) Metastatic score in the liver was calculated as described in the materials and methods.

Figure S1 The diagram depicts the studies from which samples of the KCL cohort used in this study were derived.

Table S4 FZD6 status according to clinicopathological features of patients

Table S6 Multivariate analysis of FZD6 expression in breast tumours

Frizzled receptors mediate Wnt ligands’ signalling, which is crucially involved in regulating tissue development, differentiation and is often deregulated in cancer. In this study we found that the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple negative breast cancer (TNBC) subtype...

Background Traditional prognostic indicators of breast cancer, i.e. lymph node diffusion, tumor size, grading and estrogen receptor expression, are inadequate predictors of metastatic relapse. Thus, additional prognostic parameters appear urgently needed. Individual oncogenic determinants have largely failed in this endeavour. Only a few individual...

In ApcMin mice (an animal model of colorectal carcinogenesis) fed a high-fat diet, low doses of resveratrol suppress intestinal adenoma development more potently than high doses do; however, these findings appear affected by multiple confounding factors, as resveratrol alone added to a standard diet has opposite outcomes.

The present study aimed to investigate the expression of human epidermal growth factor receptors (HERs) (HER1/HER2/HER3/HER4) and their phosphorylated forms (p-HER1/p-HER2/p-HER3/p-HER4) in pulmonary carcinoids (PCs). HER and p-HER protein expression was assessed by immunohistochemistry on tissue microarrays in 37 specimens of sporadic PCs, 29 typi...

Purpose: Inhibition of AKT is a key target area for personalized cancer medicine. However, predictive markers of response to AKT inhibitors are lacking. Correspondingly, the AKT-dependent chain of command for tumor growth, which will mediate AKT-dependent therapeutic responses, remains unclear. Experimental Design: Proteomic profiling was utilized...

It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focuse...

The ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent th...

A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin. The role of LGALS3BP in CRC prognosis was investigated. The role of LGALS3BP on CRC progression and clinical prognos...

Vav1, normally restricted to hematopoietic cells, results ectopically expressed in solid tumors, including breast cancer (Sebban et al., 2013) in which, contrarily to other neoplasias, seems to be higher in tumors from patients who remained diseasefree than in patients who developed recurrence (Lane et al., 2008). The significance of Vav1 expressio...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Breast cancer is the leading worldwide cause of death among women due to the high metastatic spread of this disease. As by definition, Cancer Initiating Cells (CICs) are a fraction of primary tumor cells harboring tumorigenic potential and successful outgrowth at met...

Resveratrol is a polyphenol found in grapes and berries that has antioxidant, antiproliferative and anti-inflammatory properties. For these reasons, it is available as a dietary supplement, and it is under investigation in several clinical trials. Few data are available regarding the effects of resveratrol on thyroid function. A previous study show...

Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we h...

ErbB-3 and its ligand NRG-1β are key players in driving oncogenic signaling and resistance to therapy through the activation of the PI3K/Akt pathway. We have recently reported that EV20, a humanized anti-ErbB3 antibody, possesses a marked antitumor activity in a variety of human tumor models, including pancreatic cancer (PC). Here, we report that d...

Gliomas are the most frequent brain tumors. Among them, glioblastomas are malignant and largely resistant to available treatments. Histopathology is the gold standard for classification and grading of brain tumors. However, brain tumor heterogeneity is remarkable and histopathology procedures for glioma classification remain unsatisfactory for pred...

Background and Aims GDM is associated with increased oxidative stress and overexpression of inflammatory cytokines, both of which might lead to endothelial dysfunction and vascular disease. As such, GDM could be viewed as a sort of “short lived” metabolic syndrome. Since umbilical cord vessels represent a suitable model for the study of vascular al...

Vav1 is one of the signalling proteins normally restricted to hematopoietic cells that results ectopically expressed in solid tumors, including breast cancer. By immunohistochemical analysis on TMAs containing invasive breast tumor from patients without lymph node involvement, we have found that Vav1 is expressed in almost all investigated cancers...

Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus Trop-2 maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and one in the cytoplasm. Of note, membrane-localized/functional Trop-2 was found to be differentially associated with...

Accumulating evidence indicates that serum and tissue levels of lectin, galactoside-binding soluble 3 binding protein (LGALS3BP), a secreted glycoprotein, are elevated in human cancers. Recently, we have identified LGALS3BP as a factor capable of stimulating angiogenesis of microvascular endothelial cells in vitro as well as in vivo. However, the p...

Congenital tufting enteropathy (CTE) is a life-threatening hereditary disease that is characterized by enteric mucosa tufting degeneration and early onset, severe diarrhea. Loss-of-function mutations of the human TROP1 gene (TACSTD1, EPCAM) have been indicated as the cause of CTE. However, loss of mTrop1 in mice appeared to lead to death in utero,...

Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an i...

Phospholipase Cγ1 (PLCγ1) is highly expressed in several tumors. We have previously reported that both stable and inducible PLCγ1 down-regulation resulted in an almost complete inhibition of breast cancer-derived experimental lung metastasis formation. The aim of our study is to evaluate the association between the expression of PLCγ1 and of PLCγ1...

Congenital tufting enteropathy (CTE) is a life-threatening hereditary disease that is characterized by enteric mucosa tufting degeneration and early onset, severe diarrhea. Loss-of-function mutations of the human EPCAM gene (TROP1, TACSTD1) have been indicated as the cause of CTE. However, loss of mTrop1/Epcam in mice appeared to lead to death in u...

Supporting Materials and Methods ; Supporting Results; Supporting References. (DOC)

Primer sequences. (DOC)

Genotype frequencies in litters from heterozygous mTrop1 +/−× mTrop1 +/− crossings. (DOC)

mTrop1 inactivation by targeted gene replacement. (TIF)

mTrop1 gene-trapped mice. (TIF)

Whole-embryo assessment of mTrop-1 expression. (TIF)

Embryonic mTrop-1 expression. (TIF)

Intestinal tract abnormalities in mTrop1 -null mice. (TIF)

mTrop1 expression in the developing embryo. (TIF)

Histology of tissues from WT and KO mice. (TIF)

mTrop1 -targeted ES clone. (TIF)

Originally identified as Trop1, epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that received great attention because of its putative involvement in metastatic spread of several solid tumors including breast cancer. Experimental evidence indicated that EpCAM is a key transcriptional target of p53 tumor suppressor, due to t...

Objective: Trop-1/Ep-CAM modulates growth and survival of transformed cells, and it is highly expressed in most carcinomas including breast cancer. Only membranous staining is typically considered in evaluating Trop-1/epithelial cell adhesion molecule (Ep-CAM) expression in tumor cells. However, there is evidence of retention of Trop-1/Ep-CAM, as...