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S Spaventi

Publications and source records attributed to S Spaventi.

At least 19 recordsLinked to original sources
PubMed2004

nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma.

BACKGROUND: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene. AIMS: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression. MATERIALS/METHODS: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real time" RT-PCR. RESULTS: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours. CONCLUSIONS: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis.

Adenocarcinoma↗
PubMed2001

Effect of the nonsteroidal anti-inflammatory drug indomethacin on proliferation and apoptosis of colon carcinoma cells.

PURPOSE: Nonsteroidal anti-inflammatory drugs lower the incidence of and mortality from colon cancer. In this paper, we present the effect of indomethacin on growth inhibition and alterations in the expression of several genes involved in cell cycle and apoptosis in CaCo-2 colon adenocarcinoma cells. METHODS: We used the MTT test to evaluate the effect of indomethacin on the proliferation rate of colon cancer and normal fibroblast cells in vitro. The expression of c-myc oncoprotein and p53 and p27 suppressor proteins was examined using the immunocytochemical method. RESULTS: We have shown that indomethacin reduces the proliferation rate of CaCo-2 colon cancer cells (up to 60% at the concentration of 4 x 10(-4) M), alters their morphology, and induces cell death by apoptosis. The most pronounced inhibitory effect was observed at the concentration of 6 x 10(-4) M where the growth was completely suppressed. However, the growth of normal fibroblasts (Hef 522) was much less inhibited (about 30% of inhibition at the concentration of 6 x 10(-4) M). Indomethacin reduces the proliferation rate and induces apoptosis in CaCo-2 colon cancer cells through enhanced expression of c-myc, p53, and p27 proteins. CONCLUSIONS: This is the first report about p27-increased expression in colon carcinoma cells induced by indomethacin treatment. Increased expression of p27 represents a new mechanism of apoptosis in cells treated with NSAIDs (indomethacin). This effect probably contributes to the anti-proliferative effect on colon cancer cells in vitro.

Adenocarcinoma↗
PubMed2000

Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival.

BACKGROUND/AIMS: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%-88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/ HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. METHODS: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. RESULTS: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P<0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. CONCLUSION: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.

Adenocarcinoma↗
PubMed1999

Loss of heterozygosity of APC and DCC tumor suppressor genes in human sporadic colon cancer.

We examined 36 cases of human sporadic colon carcinoma and corresponding normal tissue samples to evaluate loss of heterozygosity at the APC and DCC tumor suppressor genes loci using restriction fragment length polymorphism polymerase chain reaction and variable nucleotide tandem repeat analysis. Observed informativity was 83% for APC and 75% for DCC. DNA from 6 (20%) of 30 informative tumors exhibited loss of heterozygosity at the APC locus. Loss of heterozygosity at the DCC locus was observed in 7 (26%) of 27 informative tumor DNAs. Our results support the view that malignant progression is a consequence of more than one genetic change and suggest that inactivation of APC and DCC genes plays a role in a multistep process of colon tumor progression.

Adenocarcinoma↗
PubMed1999

The expression and role of insulin-like growth factor II in malignant hemangiopericytomas.

Hemangiopericytoma is a rare soft tissue tumor originating from contractile pericapillary pericytes. To address the issue of molecular genetic events that participate in genesis and progression of hemangiopericytoma we analyzed insulin-like growth factor (IGF) II and IGF I receptor in 29 tumors collected from a human tumor bank network. Seven of these tumors were associated with severe hypoglycemia; six were retroperitoneal and one was located in the leg. Of 22 tumors tested 12 (54.5%) exhibited IGF II mRNA, while almost 90% (17 of 19) of hemangiopericytomas exhibited IGF I receptor mRNA. Sera from some patients whose tumors expressed IGF II mRNA contained elevated levels of IGF II. Removal of the tumor eliminated most of the IGF II immunoreactivity from the sera. The potential role of IGF II as a growth-promoting factor was examined on three malignant primary hemangiopericytoma cell cultures. Extracellular addition of IGF II significantly enhanced cell proliferation in a dose-dependent manner. Antisense oligodeoxynucleotides that specifically inhibit IGF II mRNA, at a concentration of 40 or 80 micrograms/ml, inhibited the growth of hemangiopericytoma cells significantly, by 40%. Simultaneous administration of antisense deoxyoligonucleotides to both IGF II and IGF I receptor inhibited tumor cell proliferation by even 80%. Our data suggest that tumor cells produce IGF II, and that this in turn stimulates their proliferation by autocrine mechanisms.

Adolescent↗
PubMed1998

Molecular pathology of hemangiopericytomas accompanied by severe hypoglycemia: oncogenes, tumor-suppressor genes and the insulin-like growth factor family.

Relatively little is known about molecular genetic events that participate in the genesis and progression of hemangiopericytoma. In this study, we describe two cases of hemangiopericytoma accompanied by severe hypoglycemia. Tumor cells from patient 1 exhibited insulin-growth factor I (IGF I) and insulin-like growth factor I receptor (IGF IR) mRNA transcripts. Tumor cells from patient 2 exhibited IGF II, IGF IR and IGF binding proteins 1-3 mRNA. Serum from patient 2 contained IGF II, mostly in a large molecular form ("big" IGF II); the IGF II level did not change after the tumor removal. The presence of IGF IR in tumor cells was confirmed by immunoprecipitation with antibodies that recognize human IGF IR subunit (visualized as a 460-kDa band). The hemangiopericytoma cells derived from patient 1 expressed 210000 IGF I receptors/cell. Specific binding of IGF I to the tumor cell membrane fraction was higher in tissue from patient 1, while the tissue of patient 2 showed relatively low IGF I binding. In contrast, IGF II binding was much higher in tissue from patient 2. Both tumor tissues showed positive immunostaining for c-Jun; one tumor showed strong immunostaining for c-Myc, H-Ras and p53, while the other exhibited strong reaction with H-Ras antibodies only. No loss of the heterozygosity at the genes APC, NFI and nm23-H1 loci in tumor tissue obtained from patient 1 was found. In effect, our results suggest multiple molecular genetic changes in hemangiopericytoma -- activation of some oncogenes and the IGF growth factor family. IGF ligands together with IGF IR could be responsible for hypoglycemia and perhaps the transformed phenotype.

Abdominal Neoplasms↗
PubMed1997

The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer.

BACKGROUND & AIMS: HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor that is amplified and/or overexpressed predominantly in adenocarcinomas. This phenomenon has been most intensively studied in breast carcinoma where its amplification and overexpression correlate with the overall course of disease and poor prognosis. This study was designed to investigate HER-2/neu gene expression in benign and malignant colorectal lesions and to evaluate its prognostic importance in colorectal cancer. METHODS: Two hundred twenty-one samples of normal colon, benign lesions, and colorectal adenocarcinomas were studied for expression of HER-2/neu oncoprotein. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections of primary tumor and lymph nodes was performed. Immunoprecipitation followed by Western blotting of freshly frozen samples of the same tumors were also performed. RESULTS: Normal colon mucosa, benign lesions, and adenocarcinomas clearly differed in the expression levels and histological distribution of p185(HER-2/neu). Normal mucosa was mostly negative, but significant number of benign lesions and adenocarcinomas overexpressed HER-2/neu protein. Adenocarcinomas were significantly more positive than benign lesions. The results show significant correlation with the epithelial abnormality degree and clinical parameters including Dukes' classification and relapse-free and postoperative survival period. CONCLUSIONS: The p185(HER-2/neu) rate expression could serve as an independent prognostic factor in patients with p185(HER-2/neu)-positive colorectal malignancies.

Adenocarcinoma↗
PubMed1995

Interferon reduces recurrences of basal cell and squamous cell cancers.

BACKGROUND: Interferon is considered to be an important curative agent for dermatologic diseases. We report the follow-up experience of patients with basal cell or squamous cell carcinomas treated with human natural leukocyte interferon (HNLI). RESULTS: Among 52 patients with basal cell carcinoma (BCC) treated with HNLI more than 10 years ago, and among 58 treated more than 5 years ago, only 2 recurrences were observed. There were no recurrences in 75 patients who had a complete response to HNLI treatment, nor were there any in 20 patients with either a partial or complete response to r.IFM alpha 2c treatment. Of 52 patients with squamous cell carcinoma (SCC), 31 had been treated more than 10 years earlier, two recurrences of the disease at the site of the original lesion were observed. CONCLUSION: Interferon treatment makes it possible to achieve a persistent cure in patients with BCC and SCC in a high proportion of cases. The potential advantage of nonsurgical treatment are an enhancement of cosmetic results through the prevention of destruction of important anatomic structures.

Adult↗
PubMed1995

Local interferon therapy for melanoma patients.

BACKGROUND: Melanoma, once considered a rare form of cancer, is increasing in incidence throughout the world. The prognosis of malignant melanoma is inversely related to the depth of tumor invasion. METHODS: Twenty-seven patients were treated with r.IFN alpha 2c. Four patients were treated with human natural leukocyte interferon (HNLI). Interferon was applied locally. Historical control groups were used for comparison in the statistical analysis. The data were evaluated taking into account the single risk factor Clark levels III and IV. In the control group there were 10 patients with Clark levels III and IV; in the group of r.IFN apha 2c-treated patients there were 20 patients. The data were analyzed by using the Kaplan-Meier and Cox methods. RESULTS: The percentage of survivals was higher in the interferon-treated groups with Clark levels III and IV, than in the control group, that is 60% compared to 25%, and 40% compared to 33%, respectively. The results of the statistical analysis after 60 months of follow-up are significantly better in the interferon group (P = 0.0175). CONCLUSIONS: The control group was not selected at random. Therefore, on the basis of our results, one can say that the treatment of the melanoma patients, Clark levels III and IV, with the r.IFN alpha 2c is promising and that further investigation is justified.

Adult↗
PubMed1994

High c-erbB-2 protein level in colorectal adenocarcinomas correlates with clinical parameters.

Sections of normal colon, adenomas, and adenocarcinomas were examined by immunohistochemistry for the expression of c-erbB-2 proto-oncogene product in order to assess its potential diagnostic value in predicting the malignant potential of these lesions. We compared the degree of epithelial abnormality and clinical parameters, including Dukes' classification and survival time with the extent of immunoperoxidase staining. Sections of normal colon and tubular adenomas examined demonstrated a weak immunostaining localized to the luminal surface cells. However, higher level of c-erbB-2 expression was observed in dysplastic areas of one tubular and one villous adenoma. Out of 40 adenocarcinomas, only 2 samples showed weak immunoreaction, while 38 samples were moderately or strongly positive for c-erbB-2 protein. The intensity of staining correlated positively with the stage of disease and postoperative survival time.

Adenocarcinoma↗
PubMed1991

Collagenase derived from human fibrosarcoma is responsible for degradation of basement membranes.

A collagenase-like enzyme with the ability to degrade the proteins of artificial basement membranes (BM) was isolated from human fibrosarcoma. Secretion of the same peptide was observed from the primary fibrosarcoma cell cultures. This peptide degrades the artificial basement membranes derived from bovine corneal endothelial cells. Using electrophoretic methods it was found that the isolated and partially purified enzyme consists of eight bands of different molecular mass corresponding to the collagenase standard from Cl. histolyticum. Only two bands with molecular masses of 22,000 (pI 5.5) and 63,000 (pI 5.9) degrade BM.

Animals↗
PubMed1990

Artificial reversion of acute myeloid leukemia cells into normal phenotype.

1. Induction of tumor cell differentiation could reverse transformed cells into normal, mature cells. Important question is whether these malignant-to-normal reversed cells are really normal ones. 2. We have developed an experimental model based on the examination of three different levels of human acute myeloid leukemia cell properties before and after induction of differentiation: morphological (percentage of undifferentiated blast cells), functional (DNA ploidy, Fc receptors, phagocytic activity, clonogenic assay in soft agar, oxidative metabolism which accompanies phagocytosis in mature granulocytes) and genetical (expression of oncogene p53). 3. Several inducers have been employed: dimethylsulfoxide (DMSO) granulocyte-macrophage colony stimulating factor (GM-CSF); tunicamycin, interferon gamma, tumor necrosis factor and lipopolysaccharide. 4. Our results indicate that the reversion of leukemic cells into mature normal ones with some inducers (DMSO, GM-CSF) could be a complete process.

Cell Differentiation↗
PubMed1990

Comparison of technetium-99m and iodine-123 imaging of thyroid nodules: correlation with pathologic findings.

Three hundred and sixteen patients with solitary or dominant thyroid nodules were imaged both with technetium-99m- (99mTc) pertechnetate and iodine-123 (123I). The images were preferred, but differences were small and in 27%-58% of the cases there was no difference in quality between the two radionuclides. Discrepancies between 99mTc and 123I images were found in 5%-8% of cases, twice as often in multinodular goiters as in single nodules. Cytologic/histologic examination was performed on all nodules but no correlation was found between the pathology and the type of discrepancy. Twelve carcinomas were found (4%) but none in nodules showing a discrepancy. There was great variation among the observers about the preference for radionuclides and about the existence or type of discrepancies. The slightly better overall quality of 123I scans is probably not of diagnostic significance and does not justify the routine use of 123I instead of 99mTc. Routine reimaging of 99mTc hot nodules with radioiodine for cancer detection does not appear to be necessary.

Adult↗
PubMed1989

Growth factors in human tumors.

Various human tumor tissues contain different growth factors. In some cases progression of tumors is paralleled by elevated levels of these substances in blood or in tumor tissue. There is evidence that these growth promoting peptides might stimulate tumor growth. The growth of most tumors was associated with insulin-like substances (MW 45,000). We isolated and purified a substance immunologically cross-reactive with insulin (SICRI) from human melanoma. We found the molecular weight of affinity purified SICRI to be approximately 120,000. Our in vitro experiments with human renal carcinoma cells and growth factors suggest an important role of these molecules in tumor progression.

Cell Division↗
PubMed1989

Antimetabolic activity of L-ascorbic acid in human and animal tumors.

1. The effect of high concentrations of L-ascorbic acid on the growth of some human and animal transformed and non-transformed cell lines has been investigated. Directly implemented into culture of transformed cell lines it decreased [3H]thymidine, [3H]uridine and [3H]leucine incorporation into cells. Vitamin C inhibited DNA synthesis by transformed cells 3-4 times more efficiently than by normal cells. 2. In vivo treatment of athymic nude mice bearing human mammary carcinoma with 500 mg/kg L-ascorbic acid for the first 15 days markedly inhibited the growth of tumor cells. 3. As determined by alkaline elution, both DNA strand breaks and DNA cross links were observed in mammary carcinoma cells treated with vitamin C. DNA-DNA and DNA-protein cross links in cells treated with L-ascorbic acid were revealed by the proteinase K assay. Removal of vitamin C caused an immediate onset of spontaneous repair of single or double stranded DNA breaks. If, however, vitamin was reintroduced into cell culture, this spontaneous repair was reversed. 4. Our results indicate an antimetabolic activity of L-ascorbic acid in human and animal transformed cells, probably due to lethal damages in DNA.

Animals↗
PubMed1988

Trisomy and tetrasomy of the long arm of chromosome 1 in a direct preparation of human endometrial adenocarcinoma.

Chromosome banding analysis was performed on an endometrial adenocarcinoma. A minimal variety in the chromosome number and morphology was found. All analyzed pseudodiploid and aneuploid carcinoma cells had two chromosomes 1 of normal morphology and the presence of a marker or markers derived from chromosome 1. Tetrasomy of the long arm of chromosome 1 was found in 12 of 19 cells analyzed, accompanied by trisomy of the long arm of chromosome 1 in the rest of the cells. No other common chromosome marker was observed. Previously published data and our results suggest that trisomy and tetrasomy of the long arm of chromosome 1 may represent a specific karyotypic change in subtypes of endometrial adenocarcinoma.

Adenocarcinoma↗