Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis

Objective

Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated.

Methods

A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed.

Results

A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.55–2.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.40–0.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.83–2.25), though not significantly and with a moderate heterogeneity.

Conclusions

The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53.     

Hunting for protein markers of hypoxia by combining plasma membrane enrichment with a new approach to membrane protein analysis

Nontransient hypoxia is strongly associated with malignant lesions, resulting in aggressive behavior and resistance to treatment. We present an analysis of mRNA and protein expression changes in neuroblastoma cell lines occurring upon the transition from normoxia to hypoxia. The correlation between mRNA and protein level changes was poor, although some known hypoxia-driven genes and proteins correlated well. We present previously undescribed membrane proteins expressed under hypoxic conditions that are candidates for evaluation as biomarkers.     

Oxidative damage in human gingival fibroblasts exposed to cigarette smoke

Cigarette smoke, a complex mixture of over 7000 chemicals, contains many components capable of eliciting oxidative stress, which may induce smoking-related disorders, including oral cavity diseases. In this study, we investigated the effects of whole (mainstream) cigarette smoke on human gingival fibroblasts (HGFs). Cells were exposed to various puffs (0.5-12) of whole cigarette smoke and oxidative stress was assessed by 2',7'-dichlorofluorescein fluorescence. The extent of protein carbonylation was determined by use of 2,4-dinitrophenylhydrazine with both immunocytochemical and Western immunoblotting assays. Cigarette smoke-induced protein carbonylation exhibited a puff-dependent increase. The main carbonylated proteins were identified by means of two-dimensional electrophoresis and MALDI-TOF mass spectrometry (redox proteomics). We demonstrated that exposure of HGFs to cigarette smoke decreased cellular protein thiols and rapidly depleted intracellular glutathione (GSH), with a minimal increase in the intracellular levels of glutathione disulfide and S-glutathionylated proteins, as well as total glutathione levels. Mass spectrometric analyses showed that total GSH consumption is due to the export by the cells of GSH-acrolein and GSH-crotonaldehyde adducts. GSH depletion could be a mechanism for cigarette smoke-induced cytotoxicity and could be correlated with the reduced reparative and regenerative activity of gingival and periodontal tissues previously reported in smokers.     

Implant prosthetic rehabilitation of the patients with mandibular resection following oral malignoma surgery

Patient underwent mandibular resection due to surgical therapy of oropharingeal malignoma. Facial asymmetry and cosmetic distortion are frequent consequences of such interventions, which may also include deviation and intrusion of the mandible, motor and sensory disorders, abnormal intermaxillary relations and malocclusion. Implant-supported prosthesis could be an optimal solution to prosthodontic treatment of such patients. However, there is a problem in determination of stable (interocclusal) intermaxillary relations. This article describes the choice of therapy and procedures undertaken in prosthetic rehabilitation of a patient who underwent mandibular resection and radiotherapy with supported prosthesis retained with four implants.     

Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA

The inhibition of male-specific lethal-2 (msl-2) mRNA translation in female flies is essential for X chromosome dosage compensation in Drosophila melanogaster. Translational repression of msl-2 requires sex-lethal (SXL) binding to uridine-rich sequences in both the 5' and 3' untranslated regions (UTRs) of the message. We delineate the msl-2 mRNA sequence elements that are important for regulation by SXL and identify functionally critical sequences adjacent to regulatory SXL binding sites. We demonstrate that SXL inhibits translation initiation and prevents the stable association of the 40S ribosomal subunit with the mRNA in a manner that does not require the presence of a cap structure at the 5' end of the mRNA. These results elucidate a critical regulatory step for dosage compensation in Drosophila melanogaster.     

Inverted sinonasal papilloma--a report of 31 cases and review of the literature

Inverted papilloma is an epithelial neoplasm of the lateral nasal wall and adjacent sinuses characterized by a marked propensity for recurrence and a significant association with carcinoma. In this retrospective study we present 31 cases treated by our departments between 1982 and 1999. The aim was to compare our results to those of other authors especially regarding surgical management. The male to female ratio of these patients was 2:1 and most patients were in the 6th and 7th decades of life. Conservative surgery was used in most cases as the initial treatment. The overall recurrence rate was low and there were 3 cases associated with carcinoma. We conclude that the results of conservative surgery in selected cases are comparable to those using radical methods. A review of the literature is presented and particular attention is dedicated to the literature concerning analysis of p53 expression, HPV and Epstein-Barr infection and apoptosis in inverted papilloma.     

Comparison the cytotoxicity of hydroxyapatite measured by direct cell counting and MTT test in murine fibroblast NIH-3T3 cells

The worldwide growing interest to biomaterials over the last years results from their irreplaceable role in medical clinic. Hydroxyapatite is used in bone reconstruction because of its similar chemical structure compared to the inorganic composition of human bone and it is basic building component of many newly prepared biomaterials. In this study, we evaluated cytotoxic/antiproliferative activity of hydroxyapatite extract using murine fibroblast cell line NIH-3T3 and two in vitro different cytotoxic assays: growth inhibition assay and MTT assay. Hydroxyapatite extract after 72 h of incubation manifested the significant in vitro cytotoxic/antiproliferative effect only at the highest concentration tested (100 %). The antiproliferative effect of hydroxyapatite extract at the other concentrations tested (75 %, 50 %, 25 %, 10 %, 5 % and 1 %) was directly proportional to the concentration and the time of influence. The inhibition of cell proliferation was 86.8 - 0 %. The sensitivity of cell growth inhibition assay (direct counting of viable cells) to the extract influence was higher than that of MTT test.     

Nutrition of Borneo's ‘exploding’ ants (Hymenoptera: Formicidae: Colobopsis): a preliminary assessment

Functional effects of ants in rainforest canopies depend on difficult to characterize ant diets. In Bornean dipterocarp forests, certain diurnal, arboreal, territorial, and ecologically dominant ‘COCY’ ant species (Colobopsis cylindrica clade) grazed epiphytic biofilms on adaxial leaf surfaces, as well as on tree trunks and branches. Microscopic examination of worker buccal pellets revealed numerous (mainly ascomycete) fungal spores, together with insect appendages and cuticle. Direct observations, video‐imaging, and δ¹⁵N isotope data rule out feeding by predation, but isotopes cannot separate fungi from plant and insect exudates as principal nitrogen sources. Lipid‐rich products, extracted from pellets in situ, are hypothesized sources of essential sterols. Also present in pellets were colorful mandibular gland (MG) compounds unique to this ant clade and deployed, as a derived character state, in suicidal defense of foraging territories. Mildly antimicrobial and highly adhesive MG products also occur basally in the clade and may have first evolved for roles in microbial sterilization and food‐gathering and processing. Proteomic studies of YG COCY ants detected 2% proteins in hypertrophied, product‐filled MG reservoirs, but SDS‐PAGE qualitative analysis revealed mostly low‐molecular mass proteins and peptides (8–15 kDa), too small for enzymes but consistent with membrane‐binding proteins and/or antimicrobial peptides. Breakdown of chitin and chitosan in pellets may occur with enzymes derived from molting fluids in insect cuticle (proteases and chitinases) and/or fungi and bacteria. To the extent that COCY workers collect and consume pathogenic and/or beneficial phyllosphere microbes, ant effects on plants may be mediated by these activities.