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Gastric cancer ( GC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. GC is a heterogeneous disease and the endpoint of a long multistep process largely influenced by Helicobacter pylori infection, genetic susceptibility, and environmental factors. In a subset of GC cases, infection with the Epstein-Barr virus ( EBV) may also be involved. The development of GC is the consequence of the accumulation of multiple epi/genetic changes during the patient's lifetime that will result in oncogenic activation and/or tumor suppressor pathways' inactivation. This review will focus on the most recent updates on the characterization of the molecular phenotypes of sporadic and hereditary GC. This article will also update the most recent findings on the relationship between H. pylori infection and stem cells at the origin of GC. The understanding of the molecular genetics underlying gastric carcinogenesis is of paramount importance to identify novel potential targets for the development of screening and prognostic markers that can be clinically valuable for the management of GC patients and for the design of clinical trials. [ABSTRACT FROM AUTHOR]

Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization. [ABSTRACT FROM AUTHOR]

Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear. Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand, bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. Apoptosis of AM was evaluated by Apoptag immunohistochemistry. IPF patients received either interferon-g and corticosteroids or azathioprine and corticosteroids for six months. Results. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment. Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway. [ABSTRACT FROM AUTHOR]

Aim: Topoisomerases represent a class of nucleic enzymes involved in the DNA replication, transcription and also chromosome topological formation. Topoisomerase IIa (Topo Iia – gene location 17q21) inhibition promotes cell death and for this reason, it is a target for specific chemotherapy (anthracyclines, podophyllotoxines). Our aim was to investigate the potential prognostic significance of its protein expression in squamous cell carcinomas of the tongue (TSCCs) based on a quantitative, digital image analysis method. Materials and methods: We analysed immunohistochemically eighty-seven ( n = 87) archival, primary TSCCs using a monoclonal anti-Topo IIa antibody. A computerised image analysis assay was applied for the evaluation of the results [nuclear labelling index (NLI)]. Survival analysis was also performed. Results: Topo IIa protein was overexpressed in 48/87 (55.1%) cases. High NLI values were detected in 17/48 (35.4%), whereas moderate levels of expression were detected in 31/48 (64.6%) cases. Statistical significance was not assessed correlating overall protein expression to grade or stage of the examined tumours ( P = 0.88, P = 0.73, respectively), but only to the anatomical region ( P = 0.04). Cox regression analysis showed that Topo IIa and also the size of the tumours were strongly associated to the survival of the patients ( P = 0.01, P = 0.02, respectively). Conclusions: Topo IIa protein overexpression is a frequent event in TSCCs. Topo IIa may be used as a prognostic factor and also as a basis for targeted chemotherapy strategies in TSCCs. Furthermore, digital image analysis improves the quantification of immunohistochemical stains in an accurate and fast way. [ABSTRACT FROM AUTHOR]

BACKGROUND: Peritoneal mesothelioma is a rare disease associated with poor prognosis. Acute abdomen as the first presentation is an extremely rare occurrence. We report an exceptional case of a patient who was found to have a jejunal perforation due to infiltration of peritoneal mesothelioma. METHODS: A 62-year-old man was admitted with clinical signs of peritonitis. Computerized tomographic scans showed a mass distal to the ligament of Treitz, thickening of the mesentery and a small amount of ascites. RESULTS: Emergency laparotomy revealed a perforated tumor 15 cm distal to the ligament of Treitz and diffuse peritoneal disease. Segmental small bowel resection and suboptimal cytoreduction were performed. Histopathology and immunohistochemistry showed infiltration of malignant mesothelioma. During the postoperative period pleural mesothelioma was also diagnosed. Despite adjuvant chemotherapy, the patient died of disseminated progressive disease 7 months after surgery. CONCLUSIONS: Peritoneal mesothelioma is a rare malignancy with grim prognosis. Small bowel involvement is a poor prognostic indicator. Our case of a small bowel perforation due to direct infiltration by peritoneal mesothelioma appears to be the first reported in the English literature. [ABSTRACT FROM AUTHOR]

The serum circulatory levels of apoptosis related molecules measured in patients with oral lichen planus (OLP) and healthy individuals in order to investigate possible alterations associated with the clinical forms of OLP. Serum levels of tumor necrosis factor (TNF)- α, soluble Fas (sFas) and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in 13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects. Significantly elevated levels of TNF- α and sFas detected in OLP patients as compared with controls. Serum concentrations of Bcl-2 although increased in 17/26 patients, they were not statistically significant. Reticular OLP exhibited slightly elevated TNF- α and significantly elevated Bcl-2 serum levels, compared with erosive OLP. These data suggest that a putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive OLP may be associated with promotion of the disease activity. [ABSTRACT FROM AUTHOR]

ABSTRACT Background. A high incidence of Helicobacter pylori among family members of children with H. pylori gastritis has previously been documented on biopsy material. The main objective of this study was the genetic clarification of H. pylori strains involved in intrafamilial dispersion. Materials and Methods. Formalin-fixed, paraffin-embedded material of antral mucosa from 32 members of 11 families was studied for the presence of genetic homogeneity. To achieve this goal, the entire genome of H. pylori was studied by the polymerase chain reaction (PCR)-based random amplified polymorphic DNA (RAPD) fingerprinting method. Furthermore, the Urease A gene was analyzed using a multiplex PCR-assay and an alternative mutation detection method based on the Hydrolink™ analysis. Results. RAPD fingerprinting confirmed that closely related H. pylori strains were involved in the intrafamilial dispersion. Mutations and small deletions in Urease A gene were found in 22 out of 32 individuals. Conclusions. The homology of the H. pylori genome in members of the same family strongly supports the hypothesis of transmission of H. pylori from person-to-person or from a common source. [ABSTRACT FROM AUTHOR]

Apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue in oral lichen planus (OLP). In the present study, OLP biopsies were immunohistochemically evaluated for TNF-alpha and apoptosis-regulating proteins in an attempt to compare their phenotypic expression. Deparaffinized tissue sections from 22 OLP and 10 control oral biopsy specimens were immunohistochemically stained with anti-Bcl-2, anti-Bcl-x, anti-Bax and anti-TNF-alpha antibodies. Keratinocytes did not show any immunoreactivity for Bcl-2, while a uniform intense staining for this protein was evident in the lymphocytic infiltrate of OLP specimens. Immunoreactivity for TNF-alpha was seen in 17/22 OLP cases. All control tissues were TNF-alpha negative, thus indicating a possible involvement of this cytokine in the pathogenesis of OLP The differences in the staining intensities of Bcl-x and Bax between OLP and normal epithelium were slight; therefore an obvious association of the phenotypic TNF-alpha expression with these apoptosis-regulating proteins was not apparent. [ABSTRACT FROM AUTHOR]

Apoptosis appears to be the mode of cell death by `Mich damaged cells are removed from the lesional tissue in oral lichen planus (OLP). In the present study. OLP biopsies were immunohistochernically evaluated for TNF-α and apoptosis-regulating proteins in an attempt to compare their phenotypic expression. Deparaffinized tissue sections from 22 OLP and 10 control oral biopsy specimens were immunohistochemically stained with anti-Bcl-2, anti-Bcl-x. anti-Bax and anti-TNF-α antibodies. Keratinocytes did not show any immunoreactivity for Bcl-2, while a uniform intense staining for this protein was evident in the lymphocytic infiltrate of OLP specimens. Immunoreactivity for TNF-α was seen in 17/22 OLP cases. All control tissues were TNF-α negative, thus indicating a possible involvement of this cytokine in the pathogenesis of OLR The differences in the staining intensities of Bcl-x and Bax between OLP and normal epithelium were slight; therefore an obvious association of the phenotypic TNF-α expression with these apoptosis-regulating proteins was not apparent. [ABSTRACT FROM AUTHOR]

Aims Reports concerning the expression of cytoplasmic components of the mitogen-activating protein kinase (MAPK) pathway in lung cancer are limited. One of the molecules participating in this pathway is the product of the c-mos proto-oncogene. In vitro investigations, in somatic cells, have shown that c-mos expression has opposing effects on cell cycle progression suggesting that it may represent an important determinant of aberrant cell function. In this study we analysed, by immunohistochemical means, its status in a series of lung carcinomas and correlated the findings with clinicopathological parameters and survival of the patients. Methods and results Sixty cases of lung carcinomas were included in the study. These comprised 52 non-small (NSCLCs) and eight small cell lung carcinomas (SCLCs). Sections from the carcinomas were immunostained with the polyclonal anti-c-mos antibody P-19. Specificity was tested by using the appropriate control peptide and control cell lines. Expression was observed in 63% of the cases, with NSCLCs showing higher reactivity (67%) than SCLCs (37.5%). Staining was observed mainly to the cytoplasm and membranes of the cancerous cells, but some nuclei reacted as well. An intratumour heterogeneous immunoreactivity was noticed. The most interesting and unexpected finding was that c-mos positive staining was associated with better recurrence-free survival in our series, regardless of histological type (P = 0.035). Furthermore, favourable disease-related and recurrence-free survival was observed in the SqC group with c-mos immunoreactivity (P < 0.001). Conclusions c-mos proto-oncogene is expressed in a significant proportion of lung carcinomas and may play a role in its development. The fact that its expression is associated with a relatively good prognosis may be indicative of a negative impact on tumour growth. [ABSTRACT FROM AUTHOR]

BackgroundTo date it is not known whether gastric juice vitamin C levels are influenced by Helicobacter pylori CagA(+) strains. The aim of the present study, therefore, was to study the impact of H. pylori CagA status on gastric juice vitamin C levels. Materials and methodsWe studied 30 H. pylori(+) patients, and the results were compared with 10 endoscopically and histologically normal H. pylori(-) subjects (control group) who were similar to the H. pylori(+) group in terms of age and sex. In all patients, gastric juice vitamin C levels were determined and the severity of gastritis was graded on a scale of 0 (absent) to 3 (severe). CagA was determined by immunoblotting the sera from patients against H. pylori antigens. ResultsAmong 30 H. pylori(+) patients, 20 were CagA(+) and 10 CagA(-). In the entire group of H. pylori(+) patients, the median gastric juice vitamin C levels (mg L-1) were 16.35 (range 3.5–33.6) and were significantly lower (P < 0.001) than in the control group of H. pylori(-) patients [35.5 (23.1–50.2)]. In addition, in the entire group of H. pylori(+) patients there was a highly significant (P < 0.0001) inverse correlation between the gastritis activity score and the gastric juice vitamin C levels. In the group of H. pylori CagA(+) patients, the median levels of gastric juice vitamin C were 13.8 (3.5–31.2) and were significantly lower than the corresponding levels in both the H. pylori CagA(-) group [24.8 (22–33.6), P < 0.01] and the H. pylori(-) control group [35.5 (23.1–50.2), P < 0.001], the last groups being similar. Furthermore, the gastritis activity median score in the H. pylori CagA(+) group [2 (1–3)] was significantly higher (P < 0.05) than in the H. pylori CagA(-) group [1 (1–2)]. ConclusionThese data indicate that infection with CagA(+) H. pylori strains significantly lowers the gastric juice vitamin C levels in comparison with CagA(-) H. pylori strains, which might have a... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the development of psoriasiform lesions in three patients after the administration of abatacept, a selective inhibitor of T-cell costimulation for rheumatoid arthritis treatment.

Background: The serum circulatory levels of apoptosis related molecules measured in patients with oral lichen planus (OLP) and healthy individuals in order to investigate possible alterations associated with the clinical forms of OLP., Methods: Serum levels of tumor necrosis factor (TNF)-alpha, soluble Fas (sFas) and Bcl-2 studied by enzyme-linked immunosorbent assay in whole blood samples in 13 OLP reticular, 13 OLP atrophic-erosive form patients and 26 healthy subjects., Results: Significantly elevated levels of TNF-alpha and sFas detected in OLP patients as compared with controls. Serum concentrations of Bcl-2 although increased in 17/26 patients, they were not statistically significant. Reticular OLP exhibited slightly elevated TNF-alpha and significantly elevated Bcl-2 serum levels, compared with erosive OLP., Conclusions: These data suggest that a putative dysfunction in the Fas/FasL mediated apoptosis might be involved in the OLP pathogenesis. A downregulation of Bcl-2 serum levels in the atrophic-erosive OLP may be associated with promotion of the disease activity.