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Fernanda Martini,
Elisa Mazzoni,
Alfredo Corallini,
Angelo Taronna,
Patrizia Querzoli, Eros Magri,
Roberto Marci,
Riccardo Dolcetti,
Giovanni Rezza,
Giuseppe Barbanti-Brodano,
Mauro Tognon
Epidemiology (Cambridge, Mass.) 05/2013; 24(3):464-465. · 5.51 Impact Factor
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Manuela Ferracin,
Massimo Pedriali,
Angelo Veronese,
Barbara Zagatti,
Roberta Gafà, Eros Magri,
Maria Lunardi,
Gardenia Munerato,
Giulia Querzoli,
Iva Maestri,
Linda Ulazzi,
Italo Nenci,
Carlo M Croce,
Giovanni Lanza,
Patrizia Querzoli,
Massimo Negrini
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ABSTRACT: Cancer of unknown primary (CUP) represents a common and important clinical problem. There is evidence that most CUPs are metastases of carcinomas whose primary site cannot be recognized. Driven by the hypothesis that the knowledge of primary cancer could improve patient's prognosis, we investigated microRNA expression profiling as a tool for identifying the tissue of origin of metastases. We assessed microRNA expression from 101 formalin-fixed, paraffin-embedded (FFPE) samples from primary cancers and metastasis samples by using a microarray platform. Forty samples representing ten different cancer types were used for defining a cancer-type-specific microRNA signature, which was used for predicting primary sites of metastatic cancers. A 47-miRNA signature was identified and used to estimate tissue-of-origin probabilities for each sample. Overall, accuracy reached 100% for primary cancers and 78% for metastases in our cohort of samples. When the signature was applied to an independent published dataset of 170 samples, accuracy remained high: correct prediction was found within the first two options in 86% of the metastasis cases (first prediction was correct in 68% of cases). This signature was also applied to predict 16 CUPs. In this group, first predictions exhibited probabilities higher than 90% in most of the cases. These results establish that FFPE samples can be used to reveal the tissue of origin of metastatic cancers by using microRNA expression profiling and suggest that the approach, if applied, could provide strong indications for CUPs, whose correct diagnosis is presently undefined.
The Journal of Pathology 04/2011; 225(1):43-53. · 6.32 Impact Factor
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ABSTRACT: The larynx is a secondary sex organ, and the hormone dependence of laryngeal carcinomas is considered an interesting matter of speculation. However, while tumors of other secondary sex organs, including the prostate, breast, and endometrium, have been recognized as hormone-dependent cancers, the laryngeal carcinomas are still subject to controversy. In this study, samples from 15 laryngeal carcinomas obtained at the time of surgery were assayed for specific estrogen alpha, progesterone, and androgen receptor expression, both at mRNA and protein levels. Detectable levels of specific estrogen and progesterone receptors, 53.3 and 73.3%, respectively, were found in the tumors. This positive detection by immunohistochemical analysis was higher in tumors than in normal mucosa adjacent to the tumor areas and was correlated with the absence of metastatic lymph nodes. No androgen receptor protein was detected in any sample analyzed, even if quantitative RT-PCR revealed high mRNA levels specific for this receptor. A strict correspondence between protein and mRNA hormone receptor levels was not found. This is in agreement with the transcriptional and protein synthesis mechanisms, and it is also compatible with the complex larynx tumorigenesis.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 03/2008; 265(9):1089-94. · 1.29 Impact Factor
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ABSTRACT: We review the effects of two transcription factor decoy oligonucleotides on apoptosis of human osteoclasts (OCs). The first decoy molecule was designed to inhibit nuclear factor kappa-B (NF-kappaB) binding to target sequence, the second to increase estrogen receptor (ER) alpha expression. We found that both decoy molecules are potent inducers of apoptosis of human OCs, associated with increase of caspase 3 activity and decrease of interleukin 6 expression. In addition, we provide evidence indicating that these oligonucleotides are active in vivo in inducing OCs apoptosis. Because OCs are essential for skeletal development and remodeling throughout the life of animal and man, the approach described is of potential clinical importance.
Annals of the New York Academy of Sciences 01/2007; 1091:509-16. · 3.15 Impact Factor
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ABSTRACT: In this study, we report the in vivo effects of a decoy oligonucleotide targeting the nuclear factor kappaB (NF-kappaB) on osteoclasts during forced orthodontic tooth movement in rats. Wistar rats were subjected to orthodontic forces, in the absence or presence of treatment with a decoy molecule mimicking a nonsymmetric NF-kappaB binding site (5'-CGC TGG GGA CTT TCC ACG G-3'). TUNEL staining of fragmented DNA revealed that treatment with NF-kappaB decoy but not with scramble double-stranded oligodeoxynucleotides (ODN) induced a high level of osteoclast apoptosis in vivo. Immunohystochemical analysis for death receptor Fas revealed strong positivity only in samples treated with NF-kappaB decoys, demonstrating that osteoclasts are sensitive to death induction via Fas signaling. Induction of apoptosis in osteoclasts could be a strategy for treatment of excessive osteoclast activity in pathologic conditions such as osteoporosis, peri-articular osteolysis, inflammatory arthritis, Paget's syndrome and tumour-associated osteolytic metastases.
International Journal of Molecular Medicine 12/2006; 18(5):807-11. · 1.98 Impact Factor
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APOPTOSIS 10/2006; 11(9):1653-6. · 4.79 Impact Factor
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ABSTRACT: Despite the identification of many putative biomarkers in breast cancer, a specific pattern of proteins to be used as a prognosticator is not well defined. A growing body of evidence supports the role of phospholipase C (PLC) in the invasion and metastasis of different tumors, including breast cancer. To assess whether the expression of specific PLC isoforms correlates with malignancy-related features of human breast tumors and, hence, could have prognostic significance, an immunohistochemical analysis of PLC-beta2 was performed on tissue microarrays and the relationship between PLC-beta2 expression and biological and clinico-pathological factors was assessed. The analysis of 77 samples of breast tumors with different histotypes revealed that PLC-beta2 is highly expressed in a large majority of the analyzed cancer tissue, particularly ductal and lobular carcinomas, in comparison with normal breast. The expression of PLC-beta2 in primary tumors correlated with size, proliferation index and final grade, while no significant relationship was observed with nodal status or estrogen receptor levels, or with the expression of tumor suppressor p53. Remarkably, high PLC-beta2 levels in primary tumors predict an unfavourable prognosis, suggesting the contribution of this protein to the progression of human mammary carcinomas. Our data indicate that PLC-beta2 expression correlates highly with breast cancer malignancy and suggest that it can be included, as an independent marker, among the prognostic indicators in current use.
International Journal of Oncology 05/2006; 28(4):863-72. · 2.40 Impact Factor
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Marilena V Iorio,
Manuela Ferracin,
Chang-Gong Liu,
Angelo Veronese,
Riccardo Spizzo,
Silvia Sabbioni, Eros Magri,
Massimo Pedriali,
Muller Fabbri,
Manuela Campiglio,
Sylvie Ménard,
Juan P Palazzo,
Anne Rosenberg,
Piero Musiani,
Stefano Volinia,
Italo Nenci,
George A Calin,
Patrizia Querzoli,
Massimo Negrini,
Carlo M Croce
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ABSTRACT: MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.
Cancer Research 09/2005; 65(16):7065-70. · 7.86 Impact Factor
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ABSTRACT: Simian virus 40 (SV40) sequences of the early region coding for the large T antigen (Tag) oncoprotein were investigated in DNA samples from human pleomorphic adenoma (PA) of parotid glands. Specific SV40 sequences were detected, by PCR and filter hybridization with an internal oligoprobe, in 28 of 45 (62%) human PA specimens. None of the DNA samples from 11 normal salivary gland tissues was SV40-positive. DNA sequence analysis, carried out in all PCR amplified products from SV40-positive PA specimens, confirmed the SV40 specificity and indicated that PCR products had a sequence not distinguishable from SV40 DNA wild-type strain 776. SV40 Tag expression was revealed by immunohistochemistry with the specific monoclonal antibody Pab 101 in PA thin sections with a highly sensitive technical approach which retrieved the nuclear viral oncoprotein in 26 out of 28 (93%) samples previously found SV40-positive by PCR. Detection of SV40 sequences and Tag expression in human PA suggests that this oncogenic virus may play a role as a cofactor in the onset and/or progression of this benign neoplasm, or that SV40 DNA could replicate and express the Tag in PA cells.
American Journal Of Pathology 11/2002; 161(4):1127-33. · 4.89 Impact Factor
