Overexpression of the calcium sensor visinin-like protein-1 leads to a cAMP-mediated decrease of in vivo and in vitro growth and invasiveness of squamous cell carcinoma cells

Visinin-like protein-1 (VILIP-1) is a member of the neuronal EF-hand Ca(2+)-sensor protein family. VILIP-1 is expressed in the central nervous system where it plays a crucial role in regulating cAMP levels, cell signaling, and differentiation. Screening of mouse skin tumor cell lines for differentially expressed genes showed high-level VILIP-1 expression in less aggressive squamous cell carcinoma (SCC) and papilloma cell lines. Conversely, expression was markedly decreased or lost in invasive SCC and spindle cell carcinoma cell lines. In addition, immunohistochemistry of normal skin and primary tumors showed that VILIP-1 is expressed in basal cells of the normal intrafollicular epidermis as well as in basal cells of papillomas. The expression was decreased in low-grade SCCs and disappeared in most high-grade SCCs. When two high-grade carcinoma cell lines were transfected with VILIP1-cDNA, the VILIP-1 transfectants had significantly higher cAMP levels than the respective vector alone-transfected lines. VILIP-1-transfected cells were less invasive (both in vivo and in vitro) than the control transfectants. Reduced invasiveness and elevation of cAMP levels were accompanied by decreased MMP-9, as well as decreased RhoA activity. These results indicate that VILIP-1 plays an important role in regulating tumor cell invasiveness and that its loss could aid in enhancing the advanced malignant phenotype.     

Human papillomavirus type 16 and 18 L1 protein peptide binding to VERO and HeLa cells inhibits their VLPs binding

Human papillomaviruses (HPVs) are the cause of epithelial lesions, HPV type 16 and type 18 being associated with the development of anogenital cancer. The L1 Major Capsid Protein (L1) represents about 90% of total HPV protein and is involved in virus-host cell interaction, but little is known about this binding process. L1 sequences from HPV types 16 and 18 were synthesized in 56 20-mer peptides, covering the entire protein, HPLC-purified, (125)I-radiolabeled and tested in VERO and HeLa cell-binding assays to identify those peptides with high specific binding activity. Peptides 18283 (residues 54-77) and 18294 (274-308) from HPV16 L1, as well as 18312 (59-78) and 18322 (259-278) from HPV18 L1, presented high specific target cell binding activity. Peptide 18283 and 18294 affinity constants were 300 and 600 nM, respectively. Enzyme cell treatment before binding assay indicated that VERO and HeLa cell peptide receptor is a surface-exposed protein. There was a 60% reduction in peptide 18283 binding to heparin lyase-treated cells. Cross-linking assays showed that these proteins molecular weights were around 69 and 54 kDa. Peptides 18283 and 18294 specifically inhibited HPV-16 VLP binding to HeLa cells. According to the L1- and VLP-reported structure, both peptides are close on the VLP-surface, belonging to the outer surface broad pockets suggested as being potential receptor sites. Furthermore, it has been reported that a conserved motif from peptide 18294 is the target for neutralizing antibodies. These results suggest that such binding sequences are used by the virus as cell-binding regions.     

Fine-needle aspiration biopsy cytology of malignant neoplasms of the sinonasal tract

BACKGROUND: Primary and metastatic malignancies that originate in the sinonasal tract are rare and histologically diverse. The role of fine-needle aspiration biopsy (FNAB) and the cytomorphologic features of these tumors have not been specifically addressed. METHODS: The authors reviewed 22 cytology cases (20 FNABs, 1 sputum sample, and 1 pleural fluid sample) from 18 patients with malignancies originating in the sinonasal tract (17 carcinomas, 3 melanomas, and 2 sarcomas) and assessed the cytomorphology, cytohistologic correlation, and ability of cytology to render a specific diagnosis. RESULTS: Primary and metastastic sites sampled by FNAB included masses in or around the nose (n = 2), orbit (2), maxillary sinus (2), frontal sinus (1), intraoral area (1), preauricular area (1), soft tissue neck masses, parotid and lymph nodes (10), and cervical spine (1). Exfoliative cytology was positive in two samples of sputum and pleural fluid, representing the initial cancer diagnosis before the sinonasal primary tumor was detected. Seventeen of 22 (77.3%) cases were classified as carcinoma not otherwise specified, carcinoma with specific differentiation, sarcoma, or melanoma. Cytology failed to correctly classify the specific subtype of three carcinomas. The cytologic features that were evaluated included cellularity, cellular arrangement, nuclear features, nuclear-to-cytoplasmic ratio, and the background appearance. CONCLUSIONS: Sinonasal tract malignancies demonstrate a wide range of cytologic findings but specific features allowing for an accurate and definitive diagnosis are often present in many tumors. Fine-needle aspiration cytology is an important diagnostic tool in the management of sinonasal malignancies and can be complemented by the use of ancillary studies for the diagnosis of poorly differentiated or nonepithelial tumors.     

Parathyroid carcinoma: is there a role for adjuvant radiation therapy?

BACKGROUND: The authors proposed to determine risk factors associated with postoperative progression of parathyroid carcinoma within the neck (locoregional) and to assess the efficacy of postoperative adjuvant radiation therapy in preventing disease progression within the neck. METHODS: A retrospective review of patients with pathologically confirmed parathyroid carcinoma who underwent surgical resection was performed. Risk factors identified on univariate analysis were applied in a proportional hazards analysis to identify significant independent predictors of locoregional disease progression and cause-specific survival after surgical resection. Fifty-seven patients were treated with surgery alone (no adjuvant radiation therapy [RT]) and were determined to have sufficient follow-up and pathologically confirmed features to be included in the current analysis. Four patients were treated with surgery and adjuvant RT. Four patients received RT to the neck and mediastinum for unresectable locoregional disease progression. Patients were followed for a median of 75.6 months (range, 8.4-358 months). RESULTS: Twenty-five patients (44%) developed locoregional disease progression at a median of 27.1 months after surgery (range, 6.2-138.3 months). The univariate analysis revealed that surgical margin status and the institution at which the initial surgery was performed were predictive of locoregional progression-free survival. The institution at which the initial surgery was performed was found to be an independent predictor of cause-specific survival. Of the four patients treated with surgery and adjuvant RT, all were alive and without disease at the time of last follow-up. All four patients who received RT for locoregional disease progression after initial surgery achieved locoregional disease control. CONCLUSIONS: Patients with parathyroid carcinoma are reported to have a significant risk of locoregional disease progression after surgery alone. The results of the current study demonstrated that the risk of postoperative disease progression can be predicted by surgical margin status and the institution at which the initial surgery is performed. Patients treated with surgery and postoperative RT may have a lower risk of locoregional disease progression and improved cause-specific survival. RT can be used to provide locoregional control of recurrent disease.     

Current situation in Spain of aerosol insect sprays registered for household use by the environmental health authorities

BACKGROUND: The recent transposition of the Biocides Directive by means of Royal Decree 1054/2002 involves a substantial change in different Environmental Health-related aspects. To assess the impact of these changes, an analysis of the current situation is provided, based on which the consequences of the implementation of this Directive in Spain may be assessed, in addition to setting out the main aspects which must be analyzed with a view to a Biocides Registry being put into place in accordance with the aforementioned Royal Decree. METHODS: The analysis was made based on the data included in the Spanish Ministry of Health and Consumer Affairs related to aerosol insect sprays registered for Household Use. Aerosols were chosen as a result of their being the type most numerous on the market for household use. RESULTS: The formulation of these aerosols includes 25 insecticides, 1 disinfectant and 2 synergizers. A majority of the 298 aerosol insect sprays include some pyretroid in their composition, by itself or combined with some other insecticide, disinfectant and/or synergizing compound. Most of these biocides are a mixture of active substances. CONCLUSIONS: Based on the analysis made, the need of setting out new procedures for assessing the effectiveness of the formulas prepared for the use in question (design of standardized testing protocols, assessment of effectiveness on the different pest species, the effect of the mixture of active ingredients, safety timeframes, ...), in addition to the aspects related to toxicology; ecotoxicology or physicochemical characteristics.     

Effects of acute and long-term diazepam administrations on neutrophil activity: a flow cytometric study

This study analyzed the effects of acute and long-term diazepam treatments on rat peripheral blood neutrophil activity and cortisol serum levels. Rats were acutely and long-term (21 days, once daily) treated with diazepam (10 mg/kg) or its vehicle (1.0 ml/kg). Blood was collected 1 h after treatments for flow cytometric analysis of neutrophil oxidative burst and phagocytosis. Corticosterone and diazepam concentrations were also determined. Results showed that: (1) both diazepam treatments increased lipopolysaccharide (LPS) and phorbol myristate acetate (PMA)-induced neutrophil oxidative burst; (2) the increase in oxidative burst after Staphylococcus aureus induction in acutely treated animals was higher than that observed after long-term treatment; (3) phagocytosis is increased by acute diazepam treatment and decreased by a long-term regimen; (4) acute, but not long-term, diazepam treatment increased corticosterone levels; (5) diazepam plasmatic levels after acute and long-term treatments were not different. These results indicate the development of tolerance to diazepam effects on corticosterone serum levels but not on neutrophil activity.     

Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis

BACKGROUND/AIMS: To conduct a systematic review and meta-analysis on the prevalence of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT). METHODS: Studies evaluating prevalence of HCV infection in patients with PCT were considered. Bibliographical searches were conducted in several electronic databases. Studies comparing HCV prevalence in PCT (cases) and in a reference group (controls) were included in the meta-analysis, combining the Odds Ratios (OR) of the individual studies. RESULTS: Fifty studies including 2,167 patients were identified. Mean HCV prevalence by serology was 47%, and 50% with polymerase chain reaction (PCR). HCV prevalence markedly varied depending on the country and the type of PCT (57% in the sporadic and 26% in the familial form). Eight case-control studies were identified. Seven studies compared HCV prevalence in PCT vs. healthy controls: 40% vs. 0.24%, respectively (OR=275; 95% confidence interval=104-725). Heterogeneity disappeared when only studies evaluating HCV infection by PCR were included. CONCLUSIONS: HCV prevalence in patients with PCT is approximately 50%, much higher than that reported in general population, suggesting a possible etiopathogenic role of HCV in PCT. The striking geographical variation in this association suggests that genetic and/or environmental factors may also be involved in the pathogenesis of this disorder.