0000000000940002
AUTHOR
Sandra Cascio
showing 61 related works from this author
Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?
2007
Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…
4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily).
2007
Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…
Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico…
2006
Background Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. Patients and methods A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. Results During these mutational screening procedures one case presented three mutations classified…
Insulin-dependent leptin expression in breast cancer cells.
2008
Abstract Pathologic conditions associated with hyperinsulinemia, such as obesity, metabolic syndrome, and diabetes, seem to increase the risk of breast cancer. Here, we studied molecular mechanisms by which insulin activates the expression of leptin, an obesity hormone that has been shown to promote breast cancer progression in an autocrine or paracrine way. Using MDA-MB-231 breast cancer cells, we found that (a) insulin stimulated leptin mRNA and protein expression, which was associated with increased activation of the leptin gene promoter; (b) insulin increased nuclear accumulation of transcription factors hypoxia inducible factor (HIF)-1α and Sp1 and their loading on the leptin promoter;…
Pharmacogenomics in colorectal carcinomas: Future perspectives in personalized therapy
2005
The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes …
A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer
2005
A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother's proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband's brother and her two sons. Direct automatic sequen…
Gastrointestinal stromal tumors (GISTs): Focus on histopathological diagnosis and biomolecular features
2007
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index,…
Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.
2009
Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide…
Nuclear insulin receptor substrate 1 interacts with estrogen receptor alpha at ERE promoters.
2004
Insulin receptor substrate 1 (IRS-1) is a major signaling molecule activated by the insulin and insulin-like growth factor I receptors. Recent data obtained in different cell models suggested that in addition to its conventional role as a cytoplasmic signal transducer, IRS-1 has a function in the nuclear compartment. However, the role of nuclear IRS-1 in breast cancer has never been addressed. Here we report that in estrogen receptor alpha (ERalpha)-positive MCF-7 cells, (1) a fraction of IRS-1 was translocated to the nucleus upon 17-beta-estradiol (E2) treatment; (2) E2-dependent nuclear translocation of IRS-1 was blocked with the antiestrogen ICI 182,780; (3) nuclear IRS-1 colocalized and…
Laser Pressure Catapulting (LPC): Optimization LPC-System and Genotyping of Colorectal Carcinomas
2005
Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by se…
Nm-23-H1 expression does not predict clinical survival in colorectal cancer patients
2003
The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by im…
Mechanism of leptin expression in breast cancer cells: role of hypoxia-inducible factor-1α
2007
We reported previously that the obesity hormone leptin is overexpressed in breast cancer biopsies. Here, we investigated molecular mechanisms involved in this process, focusing on conditions that are associated with obesity, that is, hyperinsulinemia and induction of hypoxia. By using quantitative real-time PCR, immunofluorescent detection of proteins and enzyme-linked immunosorbent assays, we found that treatment of MCF-7 breast cancer cells with high doses of insulin or the hypoxia-mimetic agent CoCl2, or culturing the cells under hypoxic conditions significantly increased the expression of leptin mRNA and protein. Notably, the greatest leptin mRNA and protein expression were observed und…
Insulin-like growth factor 1 differentially regulates estrogen receptor-dependent transcription at estrogen response element and AP-1 sites in breast…
2007
Cross-talk between insulin-like growth factor 1 (IGF-1) and estrogen receptor alpha (ER) regulates gene expression in breast cancer cells, but the underlying mechanisms remain unclear. Here, we studied how 17-beta-estradiol (E2) and IGF-1 affect ER transcriptional machinery in MCF-7 cells. E2 treatment stimulated ER loading on the estrogen response element (ERE) in the pS2 promoter and on the AP-1 motif in the cyclin D1 promoter. On ERE, similar amounts of liganded ER were found at 1-24-h time points, whereas on AP-1, ER binding fluctuated over time. At 1 h, liganded ER was recruited to ERE together with histone acetyltransferases SRC-1 and p300, ubiquitin ligase E6-AP, histone methyltransf…
TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.
2006
The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutatio…
TP 53, H-K-Ras, P16INK4A gene molecular analysis in salivary gland tumors.
2006
Founder mutations in BRCA1 and BRCA2 genes
2007
BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive f…
Expression of the obesity hormone leptin and its receptor correlates with hypoxia-inducible factor-1 alpha in human colorectal cancer.
2007
Background: The obesity hormone, leptin, has been found to play a role in development and proliferation of normal and malignant tissues. Leptin activity is mediated through the leptin receptor (ObR) that is often expressed in different human cancer cells. Previously, we found that the expression of leptin and ObR can be stimulated by hypoxia-mimetic agents. The aim of this study was to analyze the abundance of and relationships among leptin, ObR and hypoxia-inducible factor-1α (HIF-1α, transcriptional regulator) in human colorectal cancer. Materials and methods: We investigated the expression of leptin, ObR and HIF-1 a in colorectal cancer specimens from 135 patients who underwent curative …
miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells.
2010
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR-20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF-7 breast cancer cells under normoxic and hypoxia-mimicking conditions (CoCl(2) exposure). Using immunoblotting, ELISA, and quantitative real-time PCR, we demonstrated that miR-20b decreased VEGF protein levels at 4 and 24 h following CoCl(2) treatment, and VEGF mRNA at 4 h of treatment. In addition, miR-20b reduce…
Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli.
2006
Abstract Purpose: Recent in vitro studies suggested that the autocrine leptin loop might contribute to breast cancer development by enhancing cell growth and survival. To evaluate whether the leptin system could become a target in breast cancer therapy, we examined the expression of leptin and its receptor (ObR) in primary and metastatic breast cancer and noncancer mammary epithelium. We also studied whether the expression of leptin/ObR in breast cancer can be induced by obesity-related stimuli, such as elevated levels of insulin, insulin-like growth factor-I (IGF-I), estradiol, or hypoxic conditions. Experimental Design: The expression of leptin and ObR was examined by immunohistochemistry…
BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.
2007
PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total…
TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma
2005
ToprospectivelyevaluatetheprognosticsignificanceofTP53,H-,K-,andN-Rasmutations,DNA-ploidyandS-phasefraction(SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed byflow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triplemutations.Intotal,46TP53mutationswereobserved.Themajority(41%)oftheseoccurinexon5(19/46),…
Ductal lavage: a way of carefully tracing the breast-secreting duct
2006
Background: Breast cancer is the most commonly diagnosed neoplasia in women after nonmelanoma skin tumors. Unfortunately, present-day diagnostic methods are unable to identify the presence of a cancer until it has been developing for several years. Currently, ductal lavage seems to represent a new method of reaching an early diagnosis of breast cancer. Materials & methods: This study analyzed 30 patients with ages ranging from 40 to 55 years; and in 26 of these patients, we were able to obtain a sufficient quantity of material for cytological and biomolecular analysis. Results & conclusion: We propose an easy, reproducible method that makes it possible to obtain a detailed map of the nipple…
Use of saliva as a biological medium in non invasive screening for oral cancer
2008
DNA aneuploidy, high SPF and specific p53 mutations are independent prognostic factors in colorectale cancer (CRC)
2004
DNA-aneuploidy and high SPF and specific p53 mutations are independent prognostic factors in colorectal cancer (CRC).
2004
TP53 Mutation in exon 5 and S-Phase Fraction but not Mutations in Ras gene family and DNA-ploidy are Indipendent prognostic indicators in Laryngeal S…
2005
BRCA1/2 variants of uncertain clinical significance in patients with famlial and hereditary breast/ovarian cancer
2007
TRANSKETOLASE-LIKE 1 EXPRESSION IN PAPILLARY THYROID CARCINOMAS SMALLER THAN 1.5 CM
2008
Analysis of TP53, Ki-Ras and P16INK4A promoter methylation as potential prognostic factors in patients with colorectal cancer
2007
TP53 mutations are not prognostic indipendent indicators in bladder cancer
2005
The prognostic role of TP53 mutations in advanced laryngeal squamous cell carcinoma (LSCC).
2005
Analysis of Ki-ras mutations in stage I rectal carcinomas and respective regional lymphonodes
2005
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
2006
Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…
GENOTYPE ANALYSIS OF COLORECTAL CARCINOMAS THROUGH LASER PRESSURE CATAPULTING (LPC)
2007
BRCA 1/2 GENES MUTATIONAL SCREENING IN SICILIAN BREAST AND/OR OVARIAN CANCER FAMILIES
2007
A study of a new germline mutation in BRCA1 gene in two Sicilian families: a founder mutation?
2006
BRCA 1/2 VARIANTS OF UNCERTAIN CLINICAL SIGNIFICANCE IN PATIENTS WITH FAMILIAL AND HEREDITARY BREAST/OVARIAN CANCER
2007
A missense mutation associated to early onset breast cancer in a sicilian woman.
2006
Aplotype analysis in four sicilian families with 5083del19bp-BRCA1.
2007
TP53 in exon 5 and s-Phase fraction but not mutations in Ras gen family and DNA-ploidy are indipendent indicators in laryngeal squamous cell carcinoma
2005
Mutational analysis of BRCA1 gene in sicilian patient at risk for inherited breast and/or ovarian cancer: experience of reference center the biomolec…
2005
Detection and clinical relevance of free-circulating tumor DNA in blood of patients with colorectal cancer
2004
BRCA1 germline mutations in Sicilian breast and/or ovarian cancer families and their implications for genetic counselling.
2006
TP53 mutations are not prognostic independent indicators in bladder cancer.
2005
Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer
2007
Insulin-like growth factor 1 differentially regulates estrogen receptor-dependent transcription at estrogen response element and AP-1 sites in breast…
2006
TP53 mutation are not prognostic indipendent indicators in bladder cancer
2005
BRCA1/BRCA2 genes mutational screening in Sicilian breast and/or ovarian cancer families.
2007
Detection and clinical relevance of free circulating tumor DNA in blood of patients with gastrointestinal cancer
2004
Genotype analysis of colorectal carcinomas through laser pressare catapulting (LPC)
2007
Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by pa…
TP53, H-K-RAS, P16INK4A GENE MOLECULAR ANALYSIS IN SALIVARY GLAND TUMORS
2007
Analysis of Ki-Ras mutations in stage I rectal carcinomas and respective regional lymph nodes.
2007
In this work we show that the percentage of Ki-RAS mutations in codons 12 and 13 in rectal cancer are sensibly lower than in colon cancer, providing further evidence that these two kinds of tumors should be considered two different entities. Moreover, we show that the detection in regional lymph nodes of the same mutation of primary tumor might represent an indicator of lymph nodes metastasis in rectal carcinoma not detected in routine histologic examination.
HPV-INFECTION IN ORAL SQUAMOUS CELL CARCINOMA IN RELATION WITH S-PHASE KINASE-INTERACTING PROTEIN 2 AND P27KIP1 PROTEIN EXPRESSION
2008
Detection of free-circulating tumor DNA in plasma of patients with gastrointestinal cancer.
2005
DNA-Aneuploidy, High SPF and Specific P53 Mutations are Indipendent Prognostic Factors in Colorectal Cancer (CRC)
2004
A.Mutational analysis of BRCA1 in sicilian patients at risk for inherited of reference center for the biomolecular characterizaztion of neoplasm and …
2005
Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)
2007
BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same…