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Biomedical subjects

A Franchi

Publications and source records attributed to A Franchi.

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

Methotrexate-associated appearance and rapid progression of rheumatoid nodules in systemic-onset juvenile rheumatoid arthritis.

Rheumatoid nodules are a rare extraarticular manifestation of juvenile rheumatoid arthritis (JRA), usually detected in patients with polyarticular-onset disease and positive rheumatoid factor (RF). To date, there has not been a published report of rheumatoid nodules in systemic-onset JRA. Low-dose methotrexate (MTX) is generally considered to be the most useful second-line drug in the treatment of polyarticular JRA. In adult RA, MTX has been shown to be associated with appearance and progression of rheumatoid nodules. This report describes a 3-year-old girl with RF-negative, antinuclear antibody-negative systemic JRA who developed multiple rheumatoid nodules on the scalp and trunk during MTX therapy. The first nodule developed on the scalp 6 months after MTX treatment was initiated. Previous treatment with azathioprine was not associated with nodulosis. This represents an atypical case of MTX-associated accelerated nodulosis in systemic JRA, and raises the problem of treatment plan modification in the presence of this side effect.

Antirheumatic Agents↗
PubMed1997

Two-step development of a pituitary adenoma: from hyperprolactinemic syndrome to Cushing's disease.

In this report we describe the case of a young female patient with amenorrhea-galactorrhea syndrome apparently due to pituitary PRL-secreting adenoma who, after three years of dopaminergic therapy without any shrinkage of the tumor, developed true Cushing's disease. Progression from hyperprolactinemia to hypersecretion of ACTH has been rarely described and it may be due to different possibilities. However, histopathological and immunohistochemical studies of the adenoma showed a pattern of PRL negative and ACTH positive cells, excluding mixed pituitary tumor. In order to explain the progression from hyperprolactinemia with amenorrhea-galactorrhea to an ACTH hypersecretion syndrome, it must be hypothesized either pituitary stalk compression or the influence of paracrine regulation factor(s) (such as Galanine) due to an "initially silent" corticotropinoma. This case confirms that the presence of hyperprolactinemia in a patient with pituitary tumor and amenorrhea-galactorrhea syndrome is insufficient to confidently conclude for prolactinoma. Furthermore, it underlines the importance both of clinically monitoring the patient with prolactin pituitary adenoma if dopaminergic therapy does not reduce tumor volume, and of accurately and repeatedly measuring the other pituitary hormonal secretions.

Adult↗
PubMed1997

Comparison of integrin alpha chain expression in benign and malignant salivary gland tumors.

OBJECTIVE: This study investigates the distribution of the alpha chain of the integrin family of extracellular matrix receptors in a series of adenomas and carcinomas of salivary gland origin to determine if the malignant phenotype is associated with modification of the expression of these receptors. STUDY DESIGN: Cryostat sections of 36 tumor specimens were stained by a standard streptavidin-biotin-peroxidase technique using primary monoclonal antibodies against alpha 1-6 and alpha v integrin chains. The immunohistochemical reaction was scored using a three-point scale and the results were analyzed using Fisher's exact test. RESULTS: In salivary adenomas, alpha 2, alpha 3, alpha 4, alpha 6, and alpha v chains were widely expressed in most of the cases studied. The alpha 1 subunit was prominently expressed by the epithelial cells of Warthin's tumor, whereas a minority of pleomorphic adenomas showed immunoreactivity for this antigen. We observed alpha 5 subunit expression only in the mesenchymal-like component of pleomorphic adenomas. In salivary carcinomas, integrin alpha chain expression was heterogeneous, varying greatly between different histotypes and within the same histotype. The distribution of the antigens was similar to that of adenomas, except for the alpha 6 chain, which localized not only at the interface between cell and matrix, but also at sites of cell-cell contact. When the immunohistochemical levels of integrin alpha chain expression were compared in adenomas and carcinomas, expression significantly decreased for the alpha 6 and alpha v chains (p = 0.0007; p = 0.002, respectively). CONCLUSIONS: Loss of alpha 6 and alpha v integrin subunits occurring in salivary gland carcinomas could modify the adhesive properties of malignant cells, contributing to the invasive potential of these tumors.

Adenocarcinoma↗
PubMed1997

Desmoplastic trichilemmoma: a case report with immunohistochemical characterization of the extracellular matrix components.

The case of unusual desmoplastic variant of trichilemmoma arising in the neck of a 56-year-old man is reported. The tumour was characterized by the presence of a densely sclerotic stroma, surrounded by lobules of epithelial cells with features of outer root sheath differentiation, including glycogen-rich, clear cytoplasm and peripheral palisading. In the central part of the tumour, irregular cords of epithelial cells entrapped in the desmoplastic stroma were found. Differential diagnosis of this rare tumour includes invasive squamous cell carcinoma, morphealike type basal cell carcinoma, desmoplastic trichoepithelioma and desmoplastic trichoblastoma. By immunohistochemistry, the tumour epithelium stained with anti-cytokeratin antibodies while the stromal cells were positive with vimentin. The centro-tumoral extracellular matrix showed a diffuse and intense positivity for type I collagen and tenascin, whereas stains for laminin and type IV collagen were uniformly negative. We suggest that tenascin could be secreted by the epithelial neoplastic cells and play a role in the mesenchymal response, which results in desmoplasia.

Diagnosis, Differential↗
PubMed1997

Potential biomarkers in predicting progression of epithelial hyperplastic lesions of the larynx.

Factors contributing to malignant transformation of laryngeal pre-neoplastic lesions remain largely unknown. Potential etiologic factors may be related to a genetically controlled sensitivity to environmental carcinogens. In this study, we investigated bleomycin-induced chromosome fragility in 15 patients with laryngeal keratoses who experienced a malignant transformation of pre-neoplastic lesions during follow-up, as compared with chromosome fragility in 15 historical controls with no progression of laryngeal keratoses during a 10-year follow-up, in a match-paired analysis. Chromosomal analysis demonstrated a higher sensitivity to clastogens in patients with malignant progression of laryngeal pre-neoplastic lesions than that of control patients with no evolution of their original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify possible prognostic markers we studied proliferative activity (MIB-1 expression) and p53 gene aberration in biopsy samples from non-invasive and invasive laryngeal lesions in both groups. p53 immunostaining was observed in 10/15 (66.7%) of pre-neoplastic lesions and in 11/15 (73.3%) of metachronous laryngeal cancers. No differences in terms of p53 expression were noted between transformed and not-transformed lesions. Mutations at p53 gene were observed in 3/15 (20%) of pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancers analyzed. Our data suggest that p53 alteration is an early event in the genesis of a subset of laryngeal carcinomas and that there is no conclusive data about the possible clonal development of metachronous laryngeal carcinoma from a p53 mutated pre-invasive disease in the same patient. MIB-1 expression was found to progressively increase with degree of epithelial hyperplasia and dysplasia in both transformed (p = 0.007) and not-transformed (p < 0.1) lesions. Surprisingly, pre-invasive lesions with tumor evolution showed a lower proliferative activity when compared with laryngeal lesions without malignant transformation (p = 0.013). These data suggests that subjects with pre-neoplastic laryngeal lesion showing an increased susceptibility to carcinogens and with less proliferative disease could be at a higher risk for development of laryngeal carcinoma.

Antigens, Nuclear↗
PubMed1996

Prognostic implications of Sialosyl-Tn antigen expression in sinonasal intestinal-type adenocarcinoma.

The expression of the mucin antigen sialosyl-Tn (S-Tn) was evaluated immunohistochemically in a series of 30 intestinal type adenocarcinomas of the nasal cavities and paranasal sinuses to assess the relationship between the histological features of the lesions and their clinical behaviour. In grades 1 and 2 adenocarcinomas, the staining localised at the apical pole or within the cytoplasm of neoplastic cells, and in the content of glandular structures. Grade 3 adenocarcinomas had a very scanty expression of the antigen. Mucinous adenocarcinomas showed an intense immunoreaction within the cell cytoplasm and in the extracellular mucous pools. Conversely, non-neoplastic sinonasal mucosa had a very focal distribution of the antigen. Immunostaining was scored according to the percentage of low power microscopic fields showing positivity. Twenty-one adenocarcinomas (70%) were considered positive. No significant relationship was found between S-Tn positivity and the histological degree of differentiation of the lesion. The 5-year survival rate and disease-free interval of patients with S-Tn positive adenocarcinomas were significantly lower than those with negative adenocarcinomas (17.8% versus 72%, P = 0.0001; 16.6% versus 40%, P = 0.0001, respectively). These results indicate that S-Tn immunostaining appears to be a significant prognostic factor in patients with sinonasal intestinal type adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Tenascin expression in cutaneous fibrohistiocytic tumors. Immunohistochemical investigation of 24 cases.

We studied the immunolocalization of the extracellular matrix glycoprotein tenascin in a series of 24 cutaneous fibrohistiocytic tumors, including seven benign lesions (benign fibrous histiocytoma/dermatofibroma), six intermediate malignancy lesions (dermatofibrosarcoma protuberans), and 11 malignant lesions (three atypical fibroxantomas and eight malignant fibrous histiocytomas). The results of the immunohistochemical staining were evaluated semiquantitatively. All lesions expressed tenascin in the extracellular matrix, with some differences in the distribution of the immunoreactivity. In benign fibrous histiocytoma and in dermatofibrosarcoma protuberans, there was a homogeneous, intense, and diffuse staining of the extracellular matrix (++); the only exception was the homogenized, sclerotic collagen present in late, regressing benign fibrous histiocytoma, which showed a weak and patchy reactivity (+). In atypical fibroxantomas and in malignant fibrous histiocytomas, there was an irregular distribution of the positivity within the tumor matrix (+). Prominent staining of the cytoplasm of several neoplastic cells was observed in atypical fibroxantoma and malignant fibrous histiocytoma (++), focal cytoplasmic staining of scattered cells was found in dermatofibrosarcoma protuberans (+), and cytoplasmic staining was absent from benign fibrous histiocytoma (-). These findings indicate a relationship between cytoplasmic and extracellular matrix expression of tenascin in these lesions, with an increase in cytoplasmic staining and a decrease in extracellular matrix staining in the malignant forms. Based on these different staining patterns, tenascin immunolocalization could furnish some help in the differential diagnosis among benign, intermediate malignancy, and malignant cutaneous fibrohistiocytic tumors. Moreover, the intense tenascin staining at the edge of the lesion could be helpful in defining its extent and therefore provide an additional criterion to evaluate the radicality of the surgical procedure.

Dermatofibrosarcoma↗
PubMed1996

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination.

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.

Antigens, Nuclear↗
PubMed1995

p53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome.

BACKGROUND: Recent studies of the molecular biology of cancer have demonstrated that p53 tumor suppressor gene aberration is associated with the development and progression of several different cancer types. METHODS: To analyze the expression of the p53 oncoprotein in parotid gland neoplasms, 72 parotid gland tumors (including 46 malignant and 26 benign cases) were studied immunocytochemically using the murine monoclonal DO-7 anti-p53 antibody. In parotid gland cancers, no and low expression (-/+) or moderate and high expression (++/+++) of the p53 oncoprotein were examined for correlation with patient survival and other clinicopathologic features, including clinical stage, tumor size, regional lymph node status, facial nerve paralysis, local infiltration, and distant failures. RESULTS: Positive staining was observed focally in 3 of 26 (11%) benign tumors and in 31 (67%) of 46 malignant tumors. Cancers showing moderate and high expression of p53 tended to be more advanced and larger than those with no expression or low expression, and presented at diagnosis more frequently, with signs of local aggressiveness. Tumors with moderate and high expression of p53 were associated more frequently with regional and distant metastases (P = 0.07 and P = 0.004, respectively). Multiple logistic regression analysis showed that regional and distant metastases were associated independently with p53 expression (P = 0.068 and P = 0.047, respectively). Moreover, patients whose cancers had moderate or high p53 expression had lower disease free and overall actuarial survival rates than those with no or low p53 expression (P = 0.021 and P = 0.033, respectively). Univariate and multivariate analysis confirmed the independent predictive prognostic value of p53 expression in patients with parotid gland cancer (P = 0.044 and P = 0.039, respectively). Furthermore, p53 expression did not correlate positively with patients' smoking habits in this series. CONCLUSION: The p53 tumor suppressor gene may be involved in salivary gland carcinogenesis, and its oncoprotein expression is an independent indicator of clinical aggressiveness in patients with carcinoma of the parotid gland.

Gene Expression↗
PubMed1995

Ethanol inhibits luteinizing hormone-releasing hormone (LHRH) secretion by blocking the response of LHRH neuronal terminals to nitric oxide.

It has previously been shown that alcohol can suppress reproduction in humans, monkeys, and small rodents by inhibiting release of luteinizing hormone (LH). The principal action is via suppression of the release of LH-releasing hormone (LHRH) both in vivo and in vitro. The present experiments were designed to determine the mechanism by which alcohol inhibits LHRH release. Previous research has indicated that the release of LHRH is controlled by nitric oxide (NO). The proposed pathway is via norepinephrine-induced release of NO from NOergic neurons, which then activates LHRH release. In the present experiments, we further evaluated the details of this mechanism in male rats by incubating medial basal hypothalamic (MBH) explants in vitro and examining the release of NO, prostaglandin E2 (PGE2), conversion of arachidonic acid to prostanoids, and production of cGMP. The results have provided further support for our theory of LHRH control. Norepinephrine increased the release of NO as measured by conversion of [14C]arginine to [14C]citrulline, and this increase was blocked by the alpha 1 receptor blocker prazosin. Furthermore, the release of LHRH induced by nitroprusside (NP), a donor of NO, is related to the activation of soluble guanylate cyclase by NO since NP increased cGMP release from MBHs and cGMP also released LHRH. Ethanol had no effect on the production of NO by MBH explants or the increased release of NO induced by norepinephrine. Therefore, it does not act at that step in the pathway. Ethanol also failed to affect the increase in cGMP induced by NP. On the other hand, as might be expected from previous experiments indicating that LHRH release was brought about by PGE2, NP increased the conversion of [14C]arachidonic acid to its metabolites, particularly PGE2. Ethanol completely blocked the release of LHRH induced by NP and the increase in PGE2 induced by NP. Therefore, the results support the theory that norepinephrine acts to stimulate NO release from NOergic neurons. This NO diffuses to the LHRH terminals where it activates guanylate cyclase, leading to an increase in cGMP. At the same time, it also activates cyclooxygenase. The increase in cGMP increases intracellular free calcium, activating phospholipase A2 to provide arachidonic acid, the substrate for conversion by the activated cyclooxygenase to PGE2, which then activates the release of LHRH. Since alcohol inhibits the conversion of labeled arachidonic acid to PGE2, it must act either directly to inhibit cyclooxygenase or perhaps it may act by blocking the increase in intracellular free calcium induced by cGMP, which is crucial for activation of of both phospholipase A2 and cyclooxygenase.

Animals↗
PubMed1995

Prognostic significance of clinically false positive cervical lymph nodes in patients with laryngeal carcinoma.

BACKGROUND: A significant proportion of clinically positive palpable cervical lymph nodes in patients with head and neck cancer are histologically benign. The biologic and prognostic significance of this reactive lymph node enlargement has not been fully clarified. METHODS: In this study, the incidence of clinically positive microscopically negative cervical lymph nodes in a series of 902 patients who had neck procedures as a part of their primary treatment for N0-2 laryngeal cancer was analyzed and survival rates of 342 patients with true negative lymph nodes (N0- necks) were compared with those of 106 patients with clinically false positive lymph nodes (N1-2b- necks). In 86 patients with false positive lymph nodes, a histopathologic analysis was performed to determine the histomorphologic pattern of the enlarged lymph nodes and to evaluate which parameters, if any, correlated with 5-year patient survival. RESULTS: Overall actuarial survival did not differ significantly in the two groups. However, the actuarial survival curves in the false positive group were clearly better compared with those of the true negative group with more advanced laryngeal cancers, particularly T4 lesions (P < 0.05). Interestingly, the analysis of pattern of recurrence showed a higher incidence of distant metastases in false positive patients with advanced stage laryngeal cancer than in true negative subjects. In addition, the histologic examination of 375 enlarged hyperplastic cervical lymph nodes from 86 neck specimens showed the prevalence of sinus histiocytosis in the false positive group and its favorable prognostic significance. No statistically significant differences with regard to the number and size of enlarged lymph nodes were found. On the contrary, lymph node location seems to have a prognostic impact on survival and the reactive benign enlargement of a digastric lymph node is a possible poor prognostic factor. CONCLUSIONS: Survival of patients with clinically false positive, histologically benign hyperplastic cervical lymph nodes who have more advanced laryngeal carcinoma is higher than clinically negative patients, suggesting that the presence of palpable benign nodes may be a sign of the host's immune activation, with favorable prognostic significance.

Actuarial Analysis↗
PubMed1995

Functional and structural interactions between osteoblastic and preosteoclastic cells in vitro.

Osteoblasts are involved in the bone resorption process by regulating osteoclast maturation and activity. In order to elucidate the mechanisms underlying osteoblast/preosteoclast cell interactions, we developed an in vitro model of co-cultured human clonal cell lines of osteoclast precursors (FLG 29.1) and osteoblastic cells (Saos-2), and evaluated the migratory, adhesive, cytochemical, morphological, and biochemical properties of the co-cultured cells. In Boyden chemotactic chambers, FLG 29.1 cells exhibited a marked migratory response toward the Saos-2 cells. Moreover, they preferentially adhered to the osteoblastic monolayer. Direct co-culture of the two cell types induced: (1) positive staining for tartrate-resistant acid phosphatase in FLG 29.1 cells; (2) a decrease of the alkaline phosphatase activity expressed by Saos-2 cells; (3) the appearance of typical ultrastructural features of mature osteoclasts in FLG 29.1 cells; (4) the release into the culture medium of granulocyte-macrophage colony stimulating factor. The addition of parathyroid hormone to the co-culture further potentiated the differentiation of the preosteoclasts, the cells tending to fuse into large multinucleated elements. These in vitro interactions between osteoblasts and osteoclast precursors offer a new model for studying the mechanisms that control osteoclastogenesis in bone tissue.

Adult↗
PubMed1995

Recalcitrant organochlorine compounds in captive bottlenose dolphins (Tursiops truncatus): biomagnification or bioaccumulation?

Organochlorine residues were measured in the diet, blood, faeces and exhaled air of captive bottlenose dolphins (Tursiops truncatus) to evaluate the absorption efficiency from food and the eliminatory potential via faeces and exhaled air. Differences between air-breathing and water-breathing animals feeding on similar prey are briefly discussed. It is concluded that high concentrations of recalcitrant organochlorines currently found in marine mammals feeding on fish are essentially due to the lack of branchial elimination and not to their predator status.

Animals↗
PubMed1995

Neural system of the human posterior cruciate ligament in osteoarthritis.

The purpose of this study was to quantify the neural elements in a group of posterior cruciate ligaments from osteoarthritic patients in comparison with normal subjects. Nine ligaments obtained from total knee arthroplasty procedures and five control ligaments from amputated limbs or fresh cadavers were stained with gold chloride. The percentage area occupied by the receptors and the neural network was determined by means of a computer-assisted image analyzer. A significant reduction of the neural elements was observed in the group of ligaments from osteoarthritic patients (0.44 +/- 0.132 SEM vs 0.958 +/- 0.13 SEM, P = .001). The loss of mechanoceptors and the consequent reduction of neural afferences may reduce the functional stability of the joint, participating in the osteoarthritic degenerative process.

Aged↗
PubMed1995

Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: studies with blasts of leukaemic patients.

BACKGROUND: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients with acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from responsive patients showed low levels of O6-alkylguanine-DNA alkyltransferase (OGAT). DESIGN: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spontaneously decomposes into the active metabolite of dacarbazine) in a relatively large number of LB samples. RESULTS: OGAT levels varied widely among the LB of different patients, with a mean value higher in acute lymphoblastic leukaemias than in AML. About 25% of LB obtained from patients with AML showed low OGAT activity, in the range corresponding to that observed in leukaemic patients responsive to dacarbazine in vivo. A reasonable inverse correlation was found between OGAT levels and LB sensitivity to temozolomide. CONCLUSIONS: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determination could provide rapid and reliable information about a patient's susceptibility to these antitumor agents.

Adolescent↗