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Biomedical subjects

O Gallo

Publications and source records attributed to O Gallo.

At least 55 records · Page 3Linked to original sources

Detection of Epstein-Barr virus genome in sinonasal undifferentiated carcinoma by use of in situ hybridization.

Associations between Epstein-Barr virus and undifferentiated carcinomas of nasopharynx, parotid gland, and thymus have recently been reported. Epstein-Barr virus has also been associated with malignant lymphoma of the nose and paranasal sinuses. These findings raise the possibility that Epstein-Barr virus may additionally be linked to undifferentiated carcinoma of the nose and paranasal sinuses (SNUC), an uncommon but distinctive and highly aggressive neoplasm. Histologically, SNUC consists of small and medium cells, the precise characterization of which often requires immunocytochemical analysis. This study investigates the presence of DNA sequences of Epstein-Barr virus in biopsy specimens of 13 cases of SNUC that were defined immunocytochemically by use of previously reported criteria. In situ hybridization was used to detect Epstein-Barr virus genome in different cell types in routinely processed, paraffin-embedded tissues. Epstein-Barr virus-specific DNA sequences were detected in tumor cells of SNUC specimens from 5 of the 13 cases examined. No correlation was found between positive hybridization and primary tumor site, morphologic subtype, or disease course. Epstein-Barr virus DNA was detected in 38% (5 of 13) of the SNUC samples analyzed. This finding suggests that this virus may play a role in the pathogenesis of this rare neoplasm.

Adult↗

p53 oncoprotein overexpression correlates with mutagen-induced chromosome fragility in head and neck cancer patients with multiple malignancies.

In this study, we analysed immunocytochemically p53 expression in first primary and second primary cancers from 25 head and neck cancer patients (HNCPs) with multiple malignancies in comparison with oncoprotein expression in tumour tissues from 25 historical HNCP controls with single cancer in a match-paired analysis. Moreover, we investigated bleomycin-induced chromosome fragility in both groups of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25 (44%) from single cancer patients and 28 out of 50 (56%) tumours from HNCPs with multiple malignancies were p53 positive. In the group of multiple primary cancers, nine patients (36%) showed positive staining of both first and second primaries, whereas six (24%) had positive labelling of first primary cancer but not of the subsequent second primary, four (16%) patient showed p53 expression only in the second primary cancer and six (24%) patients showed no p53 immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher sensitivity to clastogens of HNCPs with multiple tumours than of HNCPs with a single cancer (P < 0.01), and a significant correlation between chromosome fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple malignancies more than in those with single head and neck cancer (P = 0.11). Moreover, we found that patients with p53-positive staining of both first and second primaries showed a statistically significant higher mutagen sensitivity than those with a single p53 immunoreactive tumour or those in whom both cancers were p53 negative (P < 0.01). Our data suggest that subjects with increased susceptibility to carcingogens after exposure to tobacco or alcohol are at higher risk for multiple cancers in which one of the most common genetic events is aberrant p53 expression.

Aged↗

[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol].

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Anemia, Sideroblastic↗

Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6.

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.

Actins↗

Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal and hypertrophic adenoids.

The adenoids have been studied by immunocytochemistry and electron microscopy in children with and without adenoidal enlargement. Compared with normal adenoids, the enlarged ones showed a marked increase in the number of intraepithelial gamma-delta TCR+ lymphocytes and a slight increase in the number of intraepithelial CD8+ lymphocytes. This was accompanied by large amounts of dendritic human lymphocyte antigen (D related) (HLA-DR+) S-100+ accessory cells in the lymphoid tissue underlying the epithelium. By electron microscopy, dead epithelial cells apposed to intraepithelial lymphocytes, and clefts of the epithelial lamina, could be seen frequently in the enlarged adenoids, whereas, in the normal ones, they could not. Based on these findings, the hypothesis is drawn that imbalance of the system of the intraepithelial cytotoxic lymphocytes may lead to increased killing of epithelial cells and uncontrolled penetration of exogenous agents, and hence be involved in the pathogenesis of adenoidal hypertrophy.

Adenoids↗

Lack of detection of human papillomavirus (HPV) in transformed laryngeal keratoses by in situ hybridization (ISH) technique.

Laryngeal keratosis (LK) is a precancerous mucosal change with a variable possibility of malignant transformation. Recent studies evidencing HPV-DNA genomes in a large series of non-malignant and malignant laryngeal lesions suggest a role of HPV in the transformation of laryngeal lesions possibly in synergistic interaction with other carcinogens. In this study, we analyzed 115 biopsy specimens from benign laryngeal lesions to evaluate the risk of malignant transformation and its relationship to degree of dysplasia and to histological features of virus cell infection. The rate of transformation of LK was 8% (9/115). Our results indicate that the risk of transformation in laryngeal keratoses without dysplasia (LKWOD) is lower than that in laryngeal keratoses with dysplasia (2.2% vs 25%, respectively) (p < 0.05). An increased risk of malignant evolution in laryngeal keratoses with dysplasia (LKWD) was also related to the degree of dysplasia (rate of transformation of 12.5, 22.2 and 36% in mild, moderate and severe dysplasia, respectively). Histological features suggesting HPV infection (koilocytic-like atypia and epithelial papillary hyperplasia) were found in 6 LK only, no case subsequently developing cancer. In both benign and transformed LK, analyzed by ISH, we failed to detect HPV genomes, suggesting a major role of others carcinogens, such as tobacco and/or alcohol, in the transformation of LK.

Adult↗

Epstein-Barr virus (EBV) infection and undifferentiated carcinoma of the parotid gland in Caucasian patients.

The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and some epithelial neoplasms such as nasopharyngeal lymphoepithelioma and occasional undifferentiated carcinomas in several organs including the salivary glands. However, clonal EBV genomes have been detected in undifferentiated carcinomas of the parotid gland exclusively in Alaskan natives and Eskimos, both groups being at the highest risk for nasopharyngeal carcinoma. The authors investigated the possibility that EBV may be present in undifferentiated parotid carcinomas in Caucasian subjects. To test this hypothesis, in situ hybridization (ISH) technique with biotinylated EBV-DNA probes was utilized on routinely processed, paraffin-embedded tissues from 7 cases of undifferentiated carcinomas of the parotid gland. EBV genomes were demonstrated in the cytoplasm of tumor cells from 3 out of 7 specimens tested. Surprisingly, EBV genomes were found in 3 out of 5 (60%) undifferentiated carcinomas that had developed in patients with a history of a long-persisting asymptomatic parotid mass, which had suddenly increased in size. Conversely, none of the undifferentiated carcinomas with continuous and rapid growth studied was found to be positive for EBV-DNA by ISH technique. Taken together, these data might suggest a possible role of EBV in the transformation of benign parotid gland lesions into malignant and aggressive undifferentiated carcinoma of the parotid gland, the so-called carcinoma expleomorphic adenoma.

Adult↗

Increased thromboxane A2 production at primary tumor site in metastasizing squamous cell carcinoma of the larynx.

In order to evaluate the possible role of prostaglandins (PG) in invasion and metastasis of malignant cells in larynx carcinoma, arachidonic acid (AA) metabolite production by tumor tissue, peritumor tissue and node metastasis was investigated in comparison to that by healthy mucosa and unaffected lymph nodes. The study was performed by evaluating PGE2, 6ketoPGF1 alpha and thromboxane B2 (TXB2) production by radioimmunoassay in specimens from eight patients who underwent surgical treatment. The highest rate of AA metabolism was observed in peritumor tissue. PGE2 was the main metabolite produced in all tissues and its levels were significantly higher than those of 6ketoPGF1 alpha and TXB2 (p < 0.05). 6ketoPGF1 alpha production was higher (p < 0.01) than that of TXB2 and did not significantly change among the different tissues. TXB2 production was significantly increased (p < 0.05) by peritumor tissue as compared to healthy mucosa. The ratio between TXB2 and 6ketoPGF1 alpha production was found to be almost twofold higher in tumor tissue, peritumor tissue, metastatic and non-metastatic lymph nodes as compared to control tissue. The lowest AA metabolism was found in affected lymph nodes. These findings demonstrate a different AA metabolism at primary tumor sites in comparison to healthy mucosa suggesting a prometastatic role of TXB2 and supporting the hypothesis of the occurrence of an imbalance between TXB2 and 6ketoPGF1 alpha production in favouring metastatic spread.

6-Ketoprostaglandin F1 alpha↗

Management of occult neck metastases in oral cavity squamous carcinoma.

A large experience with patients who had radical neck dissection for oral squamous carcinoma has been reviewed in order to compare elective lymphadenectomy results with those achieved when neck dissection was delayed until metastases appeared or was performed initially for limited N1 neck disease. No significant difference in survival rates was observed, but neck failure was a more significant problem when treatment was delayed. This was most obvious in patients treated for tongue cancer. Although the impact of elective neck treatment on "cure" rates will require prospective studies, it seems clear that elective lymphadenectomy can enhance regional control of cancer and improve the quality of the patients' survival.

Adult↗

Selective jugular node dissection in patients with squamous carcinoma of the larynx or pharynx.

We reviewed our experience with 66 patients who had 85 jugular node dissections (JND) between 1984 and 1991. When JND was used as a staging procedure in 56 patients with N0 squamous carcinoma of the larynx or hypopharynx, it identified 15 of 19 patients (79%) who had occult metastases. The pattern of neck failure in six patients after JND strongly suggests that the dissection must be carried posterior to the internal jugular vein in order to achieve adequate sampling. Neck failure was a relatively minor problem in this patient population, and the indications for elective JND may be less than compelling in most patients with N0 class laryngeal or pharyngeal squamous carcinomas. Our very limited experience with JND for resection of N1 disease supports a growing consensus that limited lymphadenectomy and aggressive radiotherapy may yield comparable results in carefully selected patients with palpable metastases. Obviously, these are issues that can only be resolved by prospective, randomized studies.

Adult↗

Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer.

In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.

Aged↗

Detection of Epstein-Barr viral genome in tumor cells of Warthin's tumor of parotid gland.

The presence of Epstein-Barr virus (EBV) DNA-sequences in specimens of Warthin's tumor in the parotid gland was studied. Using an in situ hybridization technique, EBV genome was detected in distinct cell types in routinely processed tissues. The authors' results indicated that EBV is frequently present in the cytoplasm (possibly because of a chronic, productive infection) of neoplastic cells of multiple/bilateral Warthin's tumor (MBWT) (86.7%), and only occasionally of solitary Warthin's tumor (SWT) (16.7%). In addition, EBV genome has often been documented in the cytoplasm of ductal cells (75% of MBWT and 33.3% of SWT), and occasionally of acinar cells (16.7% of both MBWT and SWT) of residual normal salivary gland tissue surrounding both MBWT and SWT. The almost constant presence of EBV DNA in tumor cells of MBWT, as opposed to the occasional finding in SWT, suggested a strong association between infection of cells with this virus and the development of multiple/bilateral lesions. The positivity of ductal epithelium supported speculations about the role of ductal cells as a histogenetic precursor of the tumor. This was the first report on the detection of EBV genome in Warthin's tumor.

Adenolymphoma↗

Undifferentiated carcinoma of the nose and paranasal sinuses. An immunohistochemical and clinical study.

Among twenty-six "undifferentiated" tumors of the nasal cavity and paranasal sinuses treated from 1970 to 1990 at the Institute of Otolaryngology of Florence University, 13 were ultimately diagnosed as true undifferentiated sinusonasal carcinoma (SNUC) by conventional light microscopy and use of monoclonal antibodies to epithelial membrane antigen and cytokeratins. SNUC patients, who ranged in age from 20 to 82 years, often had multiple sinonasal symptoms due to very large tumors (nine of 13 tumors were staged as T3-T4) with short average delay of 4 months between onset of symptoms and diagnosis. Both data suggest the high growth capacity and aggressiveness of such a tumor. In our series, follow-up evidenced an overall crude 5-year survival rate of 15.5%. Worse prognostic factors are neck metastases and orbital invasion, according to the behavior of more common carcinomas of the nose and paranasal sinuses. We also found a better prognosis for SNUC primarily arisen in the nasal cavity than in paranasal sinuses (crude 5-year survival rate of 66% vs. 10%, respectively). The histopathological and clinical analysis of our series shows that SNUC is a highly aggressive, uncommon tumor of the nose paranasal sinuses, which should be recognized in advance for a more aggressive treatment by combined multiple therapy.

Adult↗

Characterization of a novel cell line from pleomorphic adenoma of the parotid gland with myoepithelial phenotype and producing interleukin-6 as an autocrine growth factor.

A cell line was obtained from a primary culture of a pleomorphic adenoma of the parotid gland in a 24-year-old woman. The cells of the line (PA 16/23) grew spontaneously in minimal culture conditions and showed stable morphologic characteristics over 30 passages. PA 16/23 cells had immunophenotypic and ultrastructural features similar to those of transformed myoepithelial cells, which are regarded as the precursors of pleomorphic adenomas. Furthermore, these cells have been demonstrated immunocytochemically to contain interleukin-6 (IL-6) on light and electron microscopic examination. IL-6 also has been found by enzyme-linked immunosorbent assay in the culture supernatant and has been proven to be capable of stimulating growth of the PA 16/23 cells.

Adenoma, Pleomorphic↗