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Biomedical subjects

G Viale

Publications and source records attributed to G Viale.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas. Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL).

bcl-2 protein and Ki-67 (MIB-1) were studied in 32 acinic cell carcinomas (ACCs), all with a minimum of 5 years' clinical follow-up. Tumour apoptosis was evaluated by TdT dUTP nick end labelling (TUNEL) and by morphological criteria. Five patients died of their disease. Patients with stage I tumours had significantly better survival compared with other stages (P < 0.05). Patients with MIB-1-negative tumours had significantly better survival than patients with MIB-1-positive tumours (P = 0.05). This study confirms a previous report that MIB-1 is an independent prognostic factor for survival in patients with ACC. Stage I tumours had high expression of bcl-2 protein, but there was no difference when compared with other stages. TUNEL positivity was most prevalent in stage I tumours, compared with stages II, III, and IV (P < 0.05), probably indicating more apoptosis. This could imply a capacity of stage I tumours ('early tumours') for early selection of tumour cells for elimination by apoptosis. There was no significant difference between expression of bcl-2 and TUNEL, between these parameters and clinical outcome, or between any parameter and morphological subclassification. We conclude that MIB-1 has prognostic value in ACC. Clinical staging, bcl-2, and TUNEL are also potentially useful as prognostic markers.

Apoptosis↗
PubMed1997

bcl-2 expression in pleural and extrapleural solitary fibrous tumours.

This study evaluated the immunoreactivity for bcl-2, a molecule involved in the control of programmed cell death, in cases of pleural (14) and extrapleural (2) solitary fibrous tumour (SFT), malignant mesotheliomas of different histological types, and a variety of extrapleural CD34-positive and CD34-negative spindle-cell tumours. In all SFTs, strong and diffuse immunostaining was demonstrated with anti-bel-2 antibody, sharply contrasting with the complete lack of staining observed in all mesotheliomas. The specificity of immunodetection of bcl-2 in SFT was confirmed by immunoblot analysis, showing a band consistent with the bcl-2 protein. At extrapleural locations, strong bcl-2 immunoreactivity was observed in Schwannoma (2/3 cases), synovial sarcoma (4/4 cases), and all cases of CD34-positive gastrointestinal stromal tumour (GIST; 10/10 cases). Most sarcomas were bcl-2-negative. Lack of bcl-2 expression was demonstrated in tumours which can pose problems in the differential diagnosis of SFT and can exhibit haemangiopericytoma-like features, including haemangiopericytoma (3 cases), dermatofibrosarcoma protuberans (16 cases), and deep-seated fibrous histiocytoma (3 cases). The constitutive expression of bcl-2 in SFT widens the spectrum of available markers for these tumours, providing a useful adjunct to their differential diagnosis in difficult cases at pleural and extrapleural sites, and contributing to the understanding of their histogenesis and molecular pathogenesis.

Adult↗
PubMed1997

The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients.

BACKGROUND: The prognostic implications of p53 accumulation, bcl-2 immunoreactivity and tumour proliferative fraction in ovarian carcinomas are still debated. PATIENTS AND METHODS: One hundred twelve ovarian carcinomas were immunostained for p53 protein, for bcl-2 and for the cell cycle-associated Ki-67 antigen. The immunostaining results were correlated with conventional clinico-pathological variables, response to induction chemotherapy, and patient survival. RESULTS: p53 accumulation and bcl-2 immunoreactivity in more than 10% of neoplastic cells were detected in 61 (54.5%) and 42 (37.5%) cases, respectively. A positive correlation between p53 accumulation and high (more than 30% neoplastic cells) MIB1 labelling index (r = 0.235; P = 0.015) was ascertained, whereas no significant association was found between bcl-2 immunoreactivity and p53 accumulation or MIB1 labeling index. Both p53 accumulation and MIB1 immunoreactivity correlated significantly with a reduced overall survival, but the association was lost in multivariate analysis. However, patients with tumours simultaneously showing p53 accumulation and MIB1 labelling index higher than 30% had significantly reduced overall survivals, in both univariate and multivariate analyses. CONCLUSION: The simultaneous evaluation of p53 accumulation and MIB1 labelling index has independent prognostic implications in common epithelial malignancies of the ovary, irrespective of the disease stage.

Cell Division↗
PubMed1997

Impact of risperidone on the use of mental health care resources.

OBJECTIVE: The effects of risperidone treatment on health care utilization and treatment costs were examined among patients with treatment-refractory schizophrenia or schizoaffective disorder. METHODS: Data from the Santa Clara County Mental Health Department were used to measure inpatient and ambulatory services and outpatient medications related to the treatment of mental disorders. Data for 139 patients were analyzed for periods before and after initiation of risperidone treatment. A mean +/- SD of 14 +/- 2.1 months of data were available in both the before and after periods, for a mean total study period of 28 months. RESULTS: The patients' mean age was 40 years (range, 18 to 78 years), and 46 percent were women. After the start of risperidone treatment, days in acute care inpatient facilities were reduced by 26 percent, and days in residential treatment were reduced by 57 percent. These reductions were accompanied by an increase in the use of lower-cost services, such as community living, treatment planning, and partial hospital-day treatment. There was a 3.4 percent increase in total psychiatric health care costs after initiation of treatment with risperidone. CONCLUSIONS: Overall, risperidone treatment resulted in a shift or resource utilization from provider-delivered services to pharmaceutical care without a significant change in total health care cost.

Adolescent↗
PubMed1996

Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas.

Experimental studies suggest that angiogenesis plays an important role in the pathogenesis of ascites and progression of ovarian cancer. To evaluate the association of intratumoral microvessel density (IMD) with the conventional clinicopathologic features and to determine the capability of these factors in predicting responsiveness to platinum-based chemotherapy and overall survival (OS) we studied 112 ovarian carcinomas. IMD was determined using the anti-CD31 antibody and immunocytochemistry. In the entire series, we correlated IMD with the other features. In the subgroup of patients with FIGO stage III-IV (60 cases), we correlated the factors studied, determined prior of treatment, with response to therapy and prognosis. The median IMD value, in the "hot spot", in the entire series was of 48 microvessels/field. IMD values were significantly higher in mucinous carcinomas than in the other histologic types. In FIGO stage III-IV patients IMD, age and performance status (PS) were significantly associated with the probability of pathologic response to chemotherapy in univariate analysis. However, only IMD and PS retained significance in multivariate analysis. The overall capability of the 2 variables to predict response was high. In FIGO stage III-IV patients IMD, age, PS, the amount of post-operative residual disease (PORD), histologic type and response to chemotherapy were significant prognostic indicators of OS in univariate analysis. In multivariate analysis only histologic type, PORD and PS retained significance. The overall capability of these 3 variables to predict OS was satisfactory.

Adult↗
PubMed1996

Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12.

Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.

Humans↗
PubMed1996

In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting.

The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%).

Antibodies, Monoclonal↗
PubMed1996

Involvement of BCL-2 oncoprotein in the development of enterochromaffin-like cell gastric carcinoids.

To evaluate the involvement of the apoptosis-suppressing protein BCL-2 in the gastrin-dependent mechanism of induction of gastric enterochromaffin-like (ECL) cell carcinoids, the endocrine cell of the oxyntic mucosa were immunohistochemically investigated in (a) 10 normogastrinemic subjects with histologically normal gastric mucosa; (b) 22 patients with endocrine cell hyperplasia and affected by hypergastrinemic conditions with different risk of gastric carcinoid development, such as sporadic Zollinger-Ellison syndrome (sZES; n = 9), ZES associated with multiple endocrine neoplasia-1 (MEN-1; n = 4), and atrophic fundal gastritis (AFG; n = 9); (c) 14 patients with ECL gastric carcinoids accounting for a total of 31 tumors investigated. In the normal oxyntic mucosa, BCL-2 was consistently expressed by a subset of endocrine cells accounting for 50.0% (median; range, 24.6-74.0%) of the total number of endocrine cells immunostained for chromogranin A (CgA) in consecutive sections. BCL-2 immunoreactive cells were located mostly in the middle mucosal layer, suggesting a role for the protein during downward migration of maturing endocrine cells. No BCL-2 immunoreactivity was found in other specialized gastric epithelial cells. Expression of BCL-2 by hyperplastic oxyntic endocrine cells (mostly ECL cells) varied in parallel with the risk of carcinoid development. In fact, the ratio of BCL-2- to CgA-immunoreactive cells was reduced (median, 4.6%; p less than 0.0001; range, 0.9-42.0%) in sZES, a condition showing virtually no risk, unchanged (median, 55.6%; range 29.4-83.8 %) in cases of MEN-1/ZES with intermediate risk, and increased (median 87.6%; p less than 0.014; range, 48.8-199.4%) in cases of AFG, a condition at the highest risk of carcinoid. In ECL cell carcinoids, BCL-2 expression varied markedly from one tumor to another even in the same patient and was low or absent in most cases. In both hyperplastic and neoplastic ECL cells, an inverse relation between BCL-2 expression and CgA immunoreactivity, that is, the cell granule content, was found. These results suggest that BCL-2 expression by hyperplastic ECL cells is independent of the influence of serum gastrin and may contribute to the development of ECL cell carcinoid tumors by extending cell exposure to oncogenic factors. Once a carcinoid tumor is established, BCL-2 expression becomes inconsistent.

Adult↗
PubMed1996

Calretinin: a novel immunocytochemical marker for mesothelioma.

Immunohistochemistry is a powerful diagnostic adjunct in the differential diagnosis between malignant mesothelioma (especially of the epithelial type) and adenocarcinoma metastatic to the serous membranes. Most of the immunological probes commonly used, however, recognize antigens expressed by the epithelial malignancies and absent from mesothelial cells and mesotheliomas. Probes suitable for the positive identification of mesotheliomas are comparatively scarce and much less commonly used because of their reduced sensitivity and specificity, their unsuitability for staining routinely fixed and embedded tissues, or their lack of commercial availability. We now document that two different polyclonal antisera to calretinin consistently immunostain mesothelial cells and malignant mesotheliomas both in routinely fixed and embedded tissue sections and in cytological preparations of serous effusions. The diagnostic sensitivity of this novel immunocytochemical approach reached 100%, allowing immunostaining of all 44 mesotheliomas investigated, which included five biphasic and three sarcomatoid types. The specificity of calretinin immunoreactivity was checked against 294 adenocarcinomas of different origin (19 serosal metastases and 275 primary tumors potentially able to metastatize to serosal membranes) relevant for the discussion of the differential diagnosis with malignant mesothelioma: only 28 cases showed focal immunoreactivity for calretinin. We conclude that calretinin is a most useful marker for the positive identification of malignant mesotheliomas.

Adenocarcinoma↗
PubMed1996

Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy.

Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.

Adjuvants, Immunologic↗
PubMed1996

The microtubule-affecting drug paclitaxel has antiangiogenic activity.

Endothelial cell migration is a critical event during angiogenesis, and inhibitors of cell motility can affect the angiogenic process. Paclitaxel (Taxol(R)), a microtubule-stabilizing antineoplastic cytotoxic drug, inhibits motility and invasiveness of several cell types. The aim of this study was to investigate the effect of paclitaxel on endothelial cell functions and on angiogenesis. In vivo, paclitaxel (20-28 mg/kg i.v.) significantly inhibited the angiogenic response induced by tumor cell supernatant embedded in a pellet of reconstituted basement membrane (Matrigel) injected s.c. into C57BL/6N mice. In vitro, paclitaxel inhibited endothelial cell proliferation, motility, invasiveness, and cord formation on Matrigel in a dose-dependent manner. The antiangiogenic activity of paclitaxel was not linked to its cytotoxicity, since inhibition of endothelial cell chemotaxis and invasiveness occurred at drug concentrations which did not affect endothelial cell proliferation. Another cytotoxic drug, cisplatin, that inhibited endothelial cell proliferation in vitro, did not affect angiogenesis in vivo. These data indicate that paclitaxel has a strong antiangiogenic activity, a property that might contribute to its antineoplastic activity in vivo.

Animals↗
PubMed1995

Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations.

Angiogenesis is a crucial step in tumor growth and progression. Its quantitation by microvessel counting is of prognostic value in several types of malignancies. Scarce data are available on angiogenesis in gastrointestinal tumors. We studied 36 adenomas and 178 large bowel carcinomas to evaluate the onset of angiogenesis in colorectal tumorigenesis and to assess the prognostic significance of microvessel quantitation. Endothelial cells were immunostained with an anti-CD31 mAb; in each case three microscopic fields (x 200) with the highest number of microvessels were counted: the average value of the three fields was used to evaluate the significance of microvessel density (MVD). MVD of normal mucosa (41 cases) served as controls. MVD was 42 +/- 10 in the normal mucosa, 64 +/- 10 in adenomas, and 115 +/- 39 in carcinomas (normal versus adenomas, P < 0.001; adenomas versus carcinomas, P < 0.0001). The transitional mucosa adjacent to carcinomas displayed intermediate levels of MVD (89 +/- 23; P < 0.001 versus adenomas; P < 0.001 versus carcinomas). High MVDs were not associated with metastases, disease stage, and patient survival. The data indicate that angiogenesis is an early, critical step in colorectal tumorigenesis. MVD, however, does not provide significant prognostic information in colorectal cancer patients.

Adenocarcinoma↗
PubMed1995

IL-13 down-regulates CD14 expression and TNF-alpha secretion in normal human monocytes.

CD14, a glycosylphosphatidylinositol (GPI)-linked protein expressed on monocytes and neutrophils, regulates monocyte-lymphocyte interactions and serves as the LPS receptor. We showed previously that IL-4 down-regulates the expression of human CD14 by acting at the transcriptional level. We now investigate whether CD14 expression could also be regulated by IL-13, another member of the chromosome 5 cytokine gene family. IL-13 dose-dependently inhibited CD14 expression on human monocytes. By contrast, expression of CD23 and CD11b was enhanced strongly. Down-regulation of CD14 involved neither shedding nor activation of endogenous GPI anchor-cleaving enzymes. Indeed, soluble CD14 was not increased in the supernatants of IL-13-stimulated monocytes, and expression of CD55/DAF, another GPI-linked protein, was unaffected by IL-13. CD14 transcript levels were reduced sixfold in IL-13-treated monocytes. These results suggest that IL-13 down-regulates membrane CD14 by suppressing CD14 RNA expression. IL-13-dependent down-regulation of CD14 resulted in the inhibition of CD14-mediated events. Indeed, CD14-mediated release of TNF-alpha was inhibited markedly (approximately 75%) in monocytes stimulated with LPS (100 ng/ml) after a 72-h preincubation with IL-13. However, IL-13 also directly inhibited monokine secretion, because it blocked PMA-induced, CD14-independent TNF-alpha release. Down-regulation of CD14 and TNF-alpha secretion may play a major role in the anti-inflammatory effects of IL-13 on LPS-stimulated monocytes.

Antigens, CD↗
PubMed1995

The clinical significance of p53 aberrations in human tumours.

p53 aberrations are the most common genetic alteration found in human tumours and this review summarizes the current understanding of the clinical significance of p53 abnormalities. Immunohistochemical and molecular techniques can demonstrate alterations at the protein and gene level, respectively, but with a significant discordance between the findings of either technique. The tumours evaluated in this review include cancers of the breast, lung, gastrointestinal tract, genitourinary tract, and others. In most cases, only data on p53 protein are available and in each of these tumour types discrepant conclusions on the clinical value of p53 abnormalities as prognostic indicators have been reached. The role of p53 in the context of anticancer adjuvant therapy has also been analysed. Experimental data suggest that p53 affects the apoptotic response to anticancer agents, but this has not yet been proven in a clinical series where this demonstration and its effect on therapy could represent one of the most important endpoints in p53 clinical research. The use of standardized techniques to evaluate p53 gene mutation and protein accumulation within controlled clinical series of patients entering prospective trials is essential to answer the many remaining questions on the clinical significance of p53 aberrations.

Chromosome Aberrations↗
PubMed1995

Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma.

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.

Adolescent↗
PubMed1995

bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas.

The bcl-2 gene is an oncogene that inhibits programmed cell death (apoptosis). We investigated by immunocytochemistry bcl-2 expression in normal colonic mucosa, hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel. The purpose of the investigation was twofold; to assess the possible role of bcl-2 in colorectal tumorigenesis and to evaluate its clinical significance. The cases studied included 24 hyperplastic polyps, 49 adenomas, and 205 colorectal carcinomas. In both normal mucosa and hyperplastic polyps bcl-2 immunoreactivity was detected only in the proliferative cells of the colonic crypts. Conversely, bcl-2 immunoreactivity was noted in all adenomas irrespective of the degree of dysplastic change; it was diffuse in 84% of adenomas and focal in the remaining cases. In colorectal carcinomas bcl-2 expression was undetectable in 50% and focal (less than 50% immunostained neoplastic cells) in 38% of tumors. The remaining 12% of the carcinomas displayed diffuse (more than 50% immunostained neoplastic cells) bcl-2 immunoreactivity. In colorectal carcinomas bcl-2 expression was not correlated with relevant clinicopathologic parameters, including disease stage, tumor location and growth fraction, DNA ploidy, and p53 protein accumulation, and had no prognostic significance by univariate or multivariate analysis. These results suggest that bcl-2 oncoprotein may play a role in colorectal tumorigenesis, probably in the early phases of the adenoma-carcinoma sequence. bcl-2 expression in established tumors has no prognostic significance.

Adenocarcinoma↗