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O Gallo

Publications and source records attributed to O Gallo.

At least 19 recordsLinked to original sources
PubMed2006

Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?

BACKGROUND: Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. AIMS: To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. METHODS: The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. RESULTS: In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A-->G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C-->T transition occurring at a dipyrimidine site and a CC-->TT tandem double-base transition. CONCLUSION: Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis.

Base Sequence↗
PubMed2004

A novel Notch3 gene mutation not involving a cysteine residue in an Italian family with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to accumulating neurologic deficits and dementia. CADASIL has been linked to nucleotide substitutions and deletions in the Notch3 gene. All the mutations described until now lead to unpaired cysteine residue in the epidermal growth factor-like repeats. The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue.

Adult↗
PubMed2001

Downregulation of transforming growth factor beta type II receptor in laryngeal carcinogenesis.

AIMS: To investigate whether anomalies of transforming growth factor beta type II receptor (TGF-beta RII) expression occur in the early stages of laryngeal carcinogenesis and to assess their importance in the development of laryngeal squamous cell carcinoma. TGF-beta RII status was examined in laryngeal premalignant lesions coupled with malignant evolution and compared with a control group of similar lesions without progression to cancer. METHODS: Immunohistochemical staining for TGF-beta RII was performed on 15 paraffin wax embedded biopsies from patients with precancerous laryngeal lesions who subsequently developed invasive squamous cell carcinoma of the larynx, and on 30 control biopsies from patients who did not develop cancer in a comparable follow up period. In addition, DNA extracted from 18 preneoplastic lesions and eight squamous cell carcinomas was amplified by the polymerase chain reaction at the poly A and the poly GT regions of the TGF-beta RII gene. RESULTS: In the group of lesions with progression to carcinoma, 11 of 15 cases showed loss (< 20% of epithelial cells) of TGF-beta RII immunoreactivity, whereas among non-evolved lesions only five of 30 had similar altered expression of the receptor (p < 0.001, two tailed Fisher's exact test). All squamous cell carcinomas showed a degree of receptor expression comparable with that of the corresponding preneoplastic lesion, with the exception of one case, in which loss of the receptor was evident only in invasive cancer. Mutation of the poly A sequence of the TGF-beta RII gene was identified in only one precancerous lesion and in the subsequent squamous cell carcinoma. CONCLUSIONS: These findings indicate that the downregulation of TGF-beta RII is an early event in laryngeal carcinogenesis, which may result in the loss of TGF-beta mediated growth inhibition, thereby facilitating the progression of laryngeal precancerous lesions to squamous cell carcinoma.

Adult↗
PubMed2000

Treatment of the contralateral negative neck in supraglottic cancer patients with unilateral node metastases (N1-3).

BACKGROUND: Elective treatment of the contralateral N0 neck in supraglottic cancer patients with unilateral metastases is controversial. METHODS: We reviewed 127 N1-3 cases with contralateral negative necks to compare elective contralateral dissection (ED: 24 cases) with a contralateral wait-and-see policy (WS: 103 cases) and subsequent delayed therapy (SDT: 40 cases) when contralateral disease became evident. Prognostic factors were studied to identify the risk of contralateral disease. RESULTS: Nine of 24 (37.5%) ED patients had occult contralateral metastases, and 40 of 103 (38.8%) WS patients had a delayed contralateral failure. Supraglottic cancers involving or extending up to the midline had a higher risk of contralateral metastases compared with well-lateralized tumors (p =.049). The risk of contralateral neck disease was more influenced by tumor site and stage than by histopathologic characteristics of ipsilateral metastases. WS patients with contralateral neck relapse showed a higher risk of distant metastases and of level I and V neck involvement than ED cases with no difference in terms of survival. CONCLUSIONS: The risk of contralateral occult neck involvement in supraglottic laryngeal cancers with unilateral metastases is high (about 40%), particularly for more advanced lesions extending to or involving the midline larynx; thus, a bilateral neck treatment in such cases is recommended.

Adult↗
PubMed2000

Prediction of recurrence by microsatellite analysis in head and neck cancer.

We examined the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in histopathologically negative surgical margins and cervical lymph nodes from head and neck cancer (HNC) patients. We used polymerase chain reaction (PCR)-based microsatellite analysis DNA to analyze primary tumors, paired surgical margins, and cervical lymph nodes from 41 HNC patients. Samples were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) at each of 10 markers. We identified 25 (61%) patients with primary HNC who appeared to have had a complete resection on the basis of the histopathological assessment and who were informative regarding microsatellite alterations in tumor tissue. In 11 of these 25 (44%) cases, PCR analysis of surgical margins showed the same microsatellite alterations as in the primary tumors. In 7 of these 11 patients, the carcinoma recurred locally, as compared with 1 out of 14 patients with negative margins (log rank test, P = 0.0049). Conversely, we were unable to detect clonal neoplastic cells in histopathologically negative lymph nodes examined by molecular analysis. Cox regression analysis showed that molecular positive margins were an independent prognostic factor (P = 0.04) for recurrence. This study demonstrates that microsatellite analysis may be a valuable tool for evaluating the risk of local recurrence.

Aged↗
PubMed1999

Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy.

We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the head and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous-cell carcinomas for analysis were obtained from 85 consecutive head-and-neck-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells bearing p53 mutations. A strong association was observed between tobacco exposure and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we found that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simultaneous detection of bcl-2 expression and a p53-gene mutation in a tumour biopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0. 045 and 0.033) within 5 years in HNSCC patients treated by RT. The present study shows a cumulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT, and provides further evidence for cross-talk between p53 and bcl-2, suggesting that these genes are important determinants of radiation-induced apoptosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 84:573-579, 1999.

Adult↗
PubMed1999

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Adult↗
PubMed1999

Clinical relevance of the histological classification of sinonasal intestinal-type adenocarcinomas.

To verify the prognostic value of the histological typing of intestinal-type adenocarcinoma (ITAC) of the sinonasal tract, 41 such lesions were separately classified by 2 pathologists both according to the World Health Organization (WHO) criteria for the histological typing of large intestine adenocarcinomas (well, moderately, poorly differentiated adenocarcinomas, and mucinous adenocarcinomas) and to the criteria of Kleinsasser and Schroeder (papillary-tubular cylinder cell type, alveolar-goblet cell type, signet-ring cell type, and transitional type). Using the WHO classification, 7 adenocarcinomas (17.1%) were well differentiated, 15 (36.6%) were moderately differentiated, and 6 (14.6%) were poorly differentiated; 13 cases (31.7%) were classified as mucinous adenocarcinoma. Following the Kleinsasser and Schroeder classification, 28 adenocarcinomas were of the papillary-tubular cylinder cell type (PTCC), 6 tumors (14.6%) were of the alveolar-goblet cell type (AGC), 1 (2.4%) was of the signet-ring cell (SRC) type, and 6 (14.6%) were of the transitional (TR) type. The interrater agreement in subtyping for both histological classifications was 92.6% (kappa, 0.89; P < .001). Kaplan-Meier analysis of cases stratified according to WHO classification showed that patients with mucinous and poorly differentiated adenocarcinomas had a significantly shorter disease-free interval and survival rate than patients with well and moderately differentiated adenocarcinomas (P = .02 and P < .001, respectively; log-rank test). Separate evaluation of survival for patients with AGC and TR adenocarcinomas did not show any statistically significant difference (P = .5). Clinical stage was advanced in most cases (92.6% of patients had T3 or T4 carcinomas) and had no prognostic relevance in the current series, as did treatment and occupational exposure. We conclude that the histological typing of ITACs is highly reproducible and appears to be related to the clinical outcome of the tumors. Adenocarcinomas with a prominent (>50%) mucinous component tend to have a similar clinical behavior, irrespective of their cyto-architectural features and the presence of an associated tubulopapillary component. Therefore, the separation into alveolar-goblet, signet-ring, and transitional forms has no prognostic impact.

Adenocarcinoma↗
PubMed1999

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity.

Reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. We used immunohistochemistry to study the expression of E-cad in 50 adenoid cystic carcinomas (ACCs) in salivary glands to evaluate correlations with clinicopathologic parameters and patient survival. Absent or low E-cad expression was observed more frequently in solid than in cribriform or tubular carcinomas. E-cad expression also was significantly correlated with histologic grade and the growth pattern. In addition, ACCs showing low or absent E-cad expression were more frequently larger than 4 cm in diameter, and distant metastases developed more frequently. Reduced expression correlated with shorter disease-free intervals and actuarial survival rates. Univariate and multivariate analysis identified tumor stage and E-cad expression as the only 2 parameters predictive of the disease-free interval. E-cad expression and tumor stage, grade, and type of growth were significant prognostic factors for survival in univariate analysis, while tumor stage, type of growth, and E-cad expression were the only significant covariates in multivariate analysis. These findings indicate that the loss of E-cad has an important role in the natural history of ACC, as it is associated with loss of differentiation and development of metastases. We also provide evidence that E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC, together with clinical stage and type of growth at the periphery of the tumor.

Adult↗
PubMed1998

Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer.

BACKGROUND: Angiogenesis (formation of new blood vessels) is associated with tumor growth and metastasis in patients with solid tumors, including those of the head and neck. Nitric oxide (NO) production may contribute to these processes. We assessed the role of the NO pathway in angiogenesis and tumor progression in patients with head and neck cancer. METHODS: Biochemical assays were used to measure NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) levels in specimens of tumor and normal mucosa obtained from 27 patients. Microvessels in tumor specimens were identified by CD-31-specific immunohistochemical staining. Associations between microvessel densities, levels of NOS, and cGMP were examined by use of two-sided statistical tests. Tumor specimens and human squamous carcinoma A-431 cells were grown as explants on the corneas of rabbits, and the effect of the NOS inhibitor N(omega)-nitro-L-arginine-methyl ester (L-NAME) was tested. RESULTS: Levels of total NOS, inducible NOS, and cGMP were higher in tumor specimens than in specimens of normal mucosa (all P<.0001). Tumor specimens from patients with lymph node metastases presented a higher total NOS activity (P = .005) and were markedly more vascularized than tumor specimens from patients with no lymph node involvement (P = .0002). Microvessel density at the tumor edge was an independent predictor of metastasis for this series of patients (odds ratio = 1.19; 95% confidence interval = 1.07-2.89; P = .04). A-431 cells and tumor specimens exhibiting high levels of NOS activity induced angiogenesis in the rabbit cornea assay; when NO production was blocked, tumor angiogenesis and growth were repressed. CONCLUSIONS: The NO pathway appears to play a key role in tumor angiogenesis and spread in patients with head and neck cancer.

Adult↗
PubMed1998

Prognostic significance of c-erbB-2 oncoprotein expression in intestinal-type adenocarcinoma of the sinonasal tract.

BACKGROUND: The c-erbB-2 gene codes for a putative transmembrane protein, similar in structure to the epidermal growth factor receptor. Amplification and/or overexpression of the gene has been recently described with a prognostic significance in a variety of human adenocarcinomas. METHODS: A monoclonal antibody against the c-erbB-2 oncoprotein has been used immunocytochemically in a retrospective study of formalin-fixed, paraffin-embedded samples from 28 consecutive intestinal-type adenocarcinomas (ITACs) of the nose and paranasal sinuses. RESULTS: Nine out of 28 primary adenocarcinomas (32%) showed positive staining. Clinical follow-up data, available for all patients, suggested in a univariate analysis a correlation between c-erbB-2 expression and poor prognosis, as measured by 5-year disease-free (p = .02) and overall survival curves (p = .07) as well as by recurrence of disease and the appearance of regional and distant metastases (p = .08). In multivariate analysis, c-erbB-2 expression was statistically significant in terms of disease-free survival (p = .046) but not of overall survival (p = .091) in our series. CONCLUSIONS: These data indicate that c-erbB-2 oncogene activation could be involved in sinonasal tract oncogenesis, with possible prognostic implications.

Adenocarcinoma↗
PubMed1998

Cox-2, iNOS and p53 as play-makers of tumor angiogenesis (review).

Cyclooxygenases (COXs) are key enzymes in the conversion of arachidonic acid to prostaglandins (PGs) and other eicosanoids. Nitric oxide synthase (NOS) is the enzyme that catalyzes the formation of nitric oxide (NO), a regulator of vascular permeability, from the guanidino nitrogen atom of L-arginine. Two isoforms of both enzymes occur: a constitutive one, Cox-1 and the inducible counterpart Cox-2; also NOS has a constitutive counterparts (cNOS) and an inducible form, called iNOS. The inducible isoforms of both enzymes are of maximum interest. It has been recently shown that cyclooxygenase-2 (Cox-2) is inducible by a variety of stimuli and that eicosanoids, mainly of the PGE2 species, are inducers of basic regulator of angiogenesis, including VEGF/VPF, bFGF, TGF-beta, PDGF, and endothelin-1. In addition, iNOS is inducible by Cox-2. p53 down-regulates the angiogenic process at various levels: it induces thrombospondin-1, a powerful antiangiogenic factor, down-regulates VEGF and NOS and, in addition, down-regulates hypoxia-induced angiogenesis, either inducing apoptosis or enhancing antiangiogenetic factors. It is noteworthy how important the p53 oncosuppressor is in the angiogenesis of solid tumor growth. Cox-2, iNOS and p53 are thus fundamental play-makers of the angiogenic process: they are discussed in detail and a tentative hierarchical cascade is proposed.

Animals↗
PubMed1997

Risk factors for distant metastases from carcinoma of the parotid gland.

BACKGROUND: Distant metastases (DM) have become an increasingly common cause of death in cancer patients because of the increasing therapeutic control of locoregional disease. However, little data exist regarding the role of clinical factors in predicting the likelihood of DM in patients with carcinoma of the parotid gland. METHODS: To analyze the incidence of DM and the factors involved in developing DM, the authors retrospectively studied clinical and survival data from 124 consecutive patients with parotid gland carcinoma who were surgically treated at the Institute of Otolaryngology of the University of Florence. RESULTS: DM occurred in 33 of 124 patients (26.6%). Patients with high grade carcinoma had a higher occurrence of DM than those with low grade disease (30.6% vs. 17.9%; P = 0.033). The presence or absence of tumor positive cervical lymph nodes in dissection specimens significantly influenced the occurrence of DM (68.2% vs. 23.7%) (P = 0.007), as well as the number of histologically positive cervical lymph nodes (P = 0.014). Clinical signs of local tumor extension, particularly facial nerve impairment, were found to be associated with a higher rate of DM (P = 0.008). Moreover, tumor size (P = 0.0216) and clinical stage (P = 0.010) were prognostically significant in predicting the incidence of DM. Interestingly, locoregional tumor failure (P = 0.096) did not affect the risk of DM. Multivariate Cox proportional hazards analysis showed that clinical stage and facial nerve infiltration were the most important factors in predicting the risk of DMs (P = 0.010; hazard ratio [HR]: 3.75; 95% confidence interval [CI]: 1.14-13.05 and P = 0.041; HR: 2.75; 95% CI: 1.04-7.30, respectively). CONCLUSIONS: Tumor stage and local aggressiveness were found to be the major prognostic factors in predicting the risk of distant failure in patients with carcinoma of the parotid gland.

Adolescent↗