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The effect of H1 receptor antagonists on peripheral blood mononuclear cells, adenoid cells and primary cell lines.

This study describes the in vitro effect of three H1 receptor antagonists (dexchlorpheniramine, terfenadine and loratadine) on human peripheral blood mononuclear cells (PBMC, n = 30) from allergic patients and healthy individuals. The three H1 receptor antagonists significantly inhibited antigen/mitogen-induced PBMC proliferation in a concentration-dependent manner. Allergen-specific T-cell responses in allergic individuals were similarly inhibited. The effect of the three drugs was also tested in cultures of mononuclear cells derived from adenoid tissue. The growth kinetics were investigated using spontaneously proliferating cell lines to examine whether the inhibition was caused by general toxicity. Three cell lines, HCT 8 (an ileocaecal adenocarcinoma) RPMI 8866 (B-cell line) and 166 A2 (T hybridoma) were tested. Loratadine (< 0.03 microM) and dexchlorpheniramine (< 0.62 microM) altered the kinetics of HCT 8 and RPMI 8866, respectively. When testing RPMI 8866 and 166 A2, the growth-inhibitory effect of terfenadine and loratadine could be neutralized by addition of cell culture filtrate from RPMI 8866 or 166 A2. These culture filtrates are rich in soluble low-affinity IgE receptor (sCD23) and IgE-binding factor (IgEBF), respectively. Our findings show that the antihistamines investigated display some non-convential in vitro anti-allergic properties possibly not related to their interaction with the H1 receptor. In addition, our results suggest: a) The H1 receptor antagonists used differ in their pattern of cell inhibition; b) The inhibitory effect is completely reversible at low drug concentrations.

Adenoids↗

Observer variability in histological malignancy grading of adenoid cystic carcinomas.

The value of malignancy grading of adenoid cystic carcinomas (ACC) is controversial. Some studies have shown that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component, in which recurrences develop even many years after initial treatment. Other studies have failed to correlate growth patterns with clinical course. No universally accepted grading system exists and no reproducibility studies of the existing grading systems have been performed. The aim of this study was to examine the reproducibility of grading based on semi-quantitative assessment of the solid growth pattern in ACC. Two different grading systems were assessed by 3 observers on a material of 59 ACC. Interobserver agreement was evaluated using the kappa statistic. The reproducibility of grading was poor, except for the category "solid component constituting 50% or more of the tumour" (kappa = 0.52). It is concluded that quantitative methods are necessary if grading is to be used in prognostic evaluation of ACC. The rarity of the tumours, however, combined with difficulties in diagnosis will impede such investigations unless multicentre studies are undertaken.

Carcinoma, Adenoid Cystic↗

Basaloid type adenoid cystic carcinoma of the breast.

We report a case of adenoid cystic carcinoma (ACC) of the breast with a prominent basaloid feature. The patient was a 62-year-old Japanese woman with a right breast mass, measuring 1.5 cm in diameter. Histologically, the tumor was composed of basal cell-like tumor cells, and it was originally diagnosed as invasive ductal carcinoma. The presence of PAS-positive basement membrane material around the tumor cell nests may be a diagnostic clue to ACC. The prognosis of ACC of the breast is considered to be favorable. However, basaloid type ACC may represent a poor prognosis, since our case revealed an aggressive behavior in spite of its small size.

Breast Neoplasms↗

Oesophageal adenoid cystic carcinoma and its management options.

Adenoid cystic carcinoma (ACC) commonly originates in the major salivary glands and respiratory tract, but extremely rarely in the oesophagus. We report the surgical and pathologic findings of a primary ACC of the oesophagus in a 59-year-old woman, and review the management options of this tumour.

Actins↗

Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid.

Human immunodeficiency virus-type 1 (HIV-1) replicates actively in infected individuals, yet cells with intracellular depots of viral protein are observed only infrequently. Many cells expressing the HIV-1 Gag protein were detected at the surface of the nasopharyngeal tonsil or adenoid. This infected mucosal surface contained T cells and dendritic cells, two cell types that together support HIV-1 replication in culture. The infected cells were multinucleated syncytia and expressed the S100 and p55 dendritic cell markers. Eleven of the 13 specimens analyzed were from donors who did not have symptoms of acquired immunodeficiency syndrome (AIDS). The interaction of dendritic cells and T cells in mucosa may support HIV-1 replication, even in subclinical stages of infection.

Adenoids↗

Growth of influenza A virus in primary, differentiated epithelial cells derived from adenoids.

Epithelial cells of adenoid origin were grown in tissue culture to examine viral replication in cells that are the primary target of many human pathogens. These cells remained highly differentiated, with subpopulations of cells which retained active ciliary motility and others which demonstrated specialized secretory functions. The epithelial cells were permissive for growth of influenza A virus. Primary respiratory epithelial cells provide a model system for examining virulence, cell tropism, and receptors which replicate in the nasopharynx.

Adenoids↗

Morphology and the natural history of cribriform adenocarcinoma (adenoid cystic carcinoma).

Forty-three examples of cribriform adenocarcinoma (adenoid cystic carcinoma) of mixed glandular origin are reported. Structural studies emphasise the classical cribriform pattern which indicates the capacity of this neoplasm to behave as both an epithelial and a connective tissue type tumour. In terms of survival, it does not appear to be an malignant as other forms of carcinoma arising in similar anatomical locations. The five-year crude survival rate (56%) compares favourably with that of other carcinomas of the palate and paranasal sinuses. A recurrence rate of the order of 20% may persist up to 10 years after primary treatment, and while this is not inimical to longer survival there is clearly a high morbidity.

Adult↗

Adenoid cystic carcinoma of the breast. A case report and review.

Adenoid cystic carcinoma of the breast is a malignant tumour of significant incidence with a better prognosis than histologically identical tumours occurring in other sites and as compared to other malignant tumours of the breast. The recognition of the tumour is important especially in the management of the individual patient but also in furthering understanding of growth, spread and biological behaviour of tumours.

Adult↗

Adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma is a rare malignant tumour of the breast. It usually presents as a painful, apparently benign lump near the nipple. The tumour has an interesting histology, natural history and mammographic appearance. Mastectomy is usually curative.

Breast Neoplasms↗

Surgical treatment of adenoid cystic carcinoma of the left main bronchus and trachea by left pneumonectomy, resection of 7.5 cm of trachea, and direct reanastomosis of right lung.

A 23-year-old woman, who had suffered recurrent acute bronchitis, dyspnoea, and stridor, was found to have a tracheal stenosis and complete left main bronchus obstruction. Biopsy of the tumour showed an adenoid cystic carcinoma. After pneumonectomy the trachea was closed through tumour tissue. Two weeks later a right thoracotomy showed that a tumour had invaded the trachea from the carina up to 6 cm and the right stem bronchus for 1 cm. Under extracorporeal circulation 7.5 cm of the trachea and right bronchus were resected. A direct tracheal anastomosis was easy to perform. Spontaneous respiration with efficient coughing returned after five days. Unfortunately, one month later, high fever caused by a lung abscess developed, which provoked a massive haemoptysis with fatal outcome.

Adult↗

Adenoid cystic carcinoma of the left main bronchus mimicking MacLeod's syndrome.

A 15 year old girl who was labelled as having MacLeod's syndrome on the basis of a chest radiograph was subsequently, at the age of 23 years, found to have an adenoid cystic carcinoma obstructing the left main bronchus. This case emphasises the need to exclude a central lesion in cases of unilateral hyperlucent lung.

Adult↗

Primary adenoid cystic carcinoma (cylindroma) of the trachea.

Two cases of adenoid cystic carcinoma of the trachea, and a review of the literature, are presented. This unusual and often undiagnosed tumor closely mimics asthma and chronic bronchitis. Although many patients die within 2 to 3 years of the onset of symptoms without appropriate treatment, adequate therapy should lead to survival of 10 years or more. The radiologist should make the initial diagnosis by noting the tumor, which is frequently located posterolaterally and in the middle third of the trachea.

Carcinoma, Adenoid Cystic↗

Endotracheal irradiation of adenoid cystic carcinoma of the trachea.

Management of advanced or recurrent primary tracheal neoplasms has been restricted to palliative external beam irradiation. A patient with recurrent adenoid cystic carcinoma of the trachea was recently treated again by combined external irradiation and endotracheal brachytherapy with iridium 192 sources; the results were dramatic without significant normal tissue toxicity. This endotracheal brachytherapy technique might be applied to tracheal tumors of different histology or more limited extent.

Adult↗

Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery.

The records of 71 patients with adenoid cystic carcinoma of the salivary glands were reviewed to determine the dose response relationships for this aggressive tumor. Local control after treatment was determined for all patients and analyzed with respect to extent of surgery and dose of radiation. Of 70 patients who were available for evaluation of local control, 28 (40%) had a local recurrence and 42 (60%) did not. The highest control rates were found in patients who underwent both radiation therapy and surgery. Patients who received a dose equal to or greater than 6,000 rad (60 Gy) in addition to surgery had significantly higher local control rates than those who received less than 6,000 rad (60 Gy). Distant metastases developed in 50% of patients regardless of local control, with the following distribution: 39% lung, 19% bone, and 10% disseminated soft-tissue metastases. Lymph node involvement was rare. Implications for combined modality treatment are discussed.

Adult↗

Adenoid cystic carcinoma of the head and neck: evaluation with MR imaging and clinical-pathologic correlation in 27 patients.

Twenty-seven adenoid cystic carcinomas (ACCs) of the head and neck in 27 patients were evaluated in a retrospective study based on findings at magnetic resonance (MR) imaging and pathologic and clinical examination. Clinical follow-up was obtained over a mean period of 6.3 years (range of follow-up, 3 months to 17 years); all patients underwent one to seven MR examinations. On T2-weighted images, lesions with low signal intensity corresponded to highly cellular tumors (solid subtype) with a poor prognosis; lesions with high signal intensity corresponded to less cellular tumors (cribriform or tubular subtype) with a better prognosis. MR images were not specific in differentiation of ACCs from other types of tumors; this result underscores the need for biopsy to ensure correct diagnosis. Local, intracranial, osseous, and perineural invasion was depicted, but because of its lack of specificity, MR imaging caused overdiagnosis of tumor extension, particularly perineural spread and bone abnormalities.

Adolescent↗

Expressions of nuclear factor kappaB, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: correlations with the angiogenesis and clinical outcome.

OBJECTIVE: To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands. METHODS: Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. RESULTS: The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival. CONCLUSION: The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.

Antigens, CD34↗

Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model.

We hypothesized that epidermal growth factor (EGF) receptor (EGFR) activation and vascular endothelial growth factor (VEGF)-induced angiogenic signals are important for the progression and metastasis of human salivary adenoid cystic carcinoma (ACC). To test this hypothesis, we evaluated the therapeutic effect of AEE788, a dual inhibitor of EGF and VEGF receptor (VEGFR) tyrosine kinases, on human salivary ACC. In clinical specimens of salivary ACC, EGF and VEGF signaling proteins were expressed at markedly higher levels than in adjacent normal glandular tissues. We examined the effects of AEE788 on salivary ACC cell growth and apoptosis and on the phosphorylation of EGFR and VEGFR-2 in salivary ACC cells. Treatment of salivary ACC cells with AEE788, alone or in combination with chemotherapy, led to growth inhibition, induction of apoptosis, and dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation. To determine the in vivo antitumor effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 alone, paclitaxel alone, cisplatin alone, a combination of AEE788 plus paclitaxel, a combination of AEE788 plus cisplatin, or a placebo. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. To study the mechanism of interaction between AEE788 and chemotherapy, AEE788 was found to potentiate growth inhibition and apoptosis of ACC tumor cells mediated by chemotherapy. Tumors of mice treated with AEE788 and AEE788 plus chemotherapy exhibited down-regulation of activated EGFR and VEGFR-2, increased tumor and endothelial cell apoptosis, and decreased microvessel density, which correlated with a decrease in the level of matrix metalloproteinase-9 and matrix metalloproteinase-2 expression and a decrease in the incidence of vascular metastasis. These data show that EGFR and VEGFR can be molecular targets for therapy of salivary ACC.

Animals↗