Reflections on the European conference 'Molecular Screening of Individuals at High Risk for Developing Cancer: Medical, Ethical, Legal, and Social Issues'

The fascinating progress of molecular biology in the last decades has made possible the early identification of persons at risk of developing malignant neoplasms, such as thyroid, colon, and breast cancer. This has changed conventional medical practice and has raised a number of ethical questions. Despite the fact that there has been substantial development throughout the Western countries in legislation dealing with medical information, there is an acute need for further exploration and assessment of the moral and social dimensions of medical practices to achieve more precise and uniform regulations. These topics were discussed in a multidisciplinary European Conference entitled 'Molecular Screening of Individuals at High Risk of Developing Cancer: Medical, Ethical, Legal, and Social Issues,' which took place in March, 1999, in Athens, Greece

A misquoted mutation in exon16 of the BRCA2 gene

A pathogenic mutation in the BRCA2 gene, nt7602del16, has been misquoted as a mutation, possibly due to the incorrect inclusion of the last 16 nucleotides of exon15 of the BRCA2 gene as part of the intron15-exon16 BRCA2 gene sequence in publicly available databases. This was concluded following mutational screening by sequencing and enzymatic mapping of the BRCA2 gene exon15-exon16 region in DNA from peripheral blood samples from a total of 74 breast cancer and non-breast cancer patients as well as healthy individuals and the cell line MCF7. Careful interpretation of genetic variants and direct feedback to the corresponding sequence databases prevent systemic errors by integrating updated data into broadly referenced sources. © The Japan Society of Human Genetics and Springer-Verlag 2006

Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: Study of their in vitro immunological interactions

Background: Many studies have suggested that the immune response may play a crucial role in the progression of hepatocellular carcinoma (HCC). Therefore, our aim was to establish a (i) functional culture of primary human tumor hepatocytes and non-tumor from patients with hepatocellular carcinoma (HCC) and (ii) a co-culture system of HCC and non-HCC hepatocytes with autologous peripheral blood mononuclear cells (PBMCs) in order to study in vitro cell-to-cell interactions.Methods: Tumor (HCC) and non-tumor (non-HCC) hepatocytes were isolated from the liver resection specimens of 11 patients operated for HCC, while PBMCs were retrieved immediately prior to surgery. Four biopsies were obtained from patients with no liver disease who had surgery for non malignant tumor (normal hepatocytes). Hepatocytes were either cultured alone (monoculture) or co-cultured with PBMCs. Flow cytometry measurements for MHC class II expression, apoptosis, necrosis and viability (7AAD) were performed 24 h, 48 h and 72 h in co-culture and monocultures.Results: HCC and non-HCC hepatocytes exhibited increased MHC-II expression at 48h and 72h in co-culture with PBMCs as compared to monoculture, with MHC II-expressing HCC hepatocytes showing increased viability at 72 h. PBMCs showed increased MHC-II expression (activation) in co-culture with HCC as compared to non-HCC hepatocytes at all time points. Moreover, CD8+ T cells had significantly increased apoptosis and necrosis at 48h in co-culture with HCC hepatocytes as compared to monocultures. Interestingly, MHC-II expression on both HCC and non-HCC hepatocytes in co-culture was positively correlated with the respective activated CD8+ T cells.Conclusions: We have established an in vitro co-culture model to study interactions between autologous PBMCs and primary HCC and non-HCC hepatocytes. This direct interaction leads to increased antigen presenting ability of HCC hepatocytes, activation of PBMCs with a concomitant apoptosis of activated CD8+ T cells. Although, a partially effective immune response against HCC exists, still tumor hepatocytes manage to escape. © 2013 Doumba et al.; licensee BioMed Central Ltd

Autoantibody profile in cutaneous lupus erythematosus subsets: correlations between various autoantibodies of the same isotype

The objective of the present study was an extensive analysis of the autoantibody profile in the most common subsets of cutaneous lupus erythematosus (LE), acute and subacute cutaneous lupus erythematosus (ACLE, SCLE) as well as discoid lupus, localized or disseminatus (DLE loc, DLE dis). Antibodies (Abs) against glomerular extracts, actin. myosin and cardiolipin were examined in the various cutaneous lupus subgroups, in addition to ANA and Abs against DNA, ENA and IgG (rheumatoid factor). Abs against glomerular extracts were detected mainly in ACLE and SCLE, whereas Abs against actin, myosin and cardiolipin were found in all cutaneous lupus subsets. The detailed record of the autoantibody profile helped in the serological differential diagnosis of the various cutaneous lupus subsets, suggesting also that SCLE and DLE dis are distinct subsets in the spectrum of cutaneous LE. Finally, correlations between autoantibodies of the same isotype were carried out, providing implications for regulation of autoantibody production. Copyright © 1994, Wiley Blackwell. All rights reserve

The presence of anti-carcinoembryonic antigen (CEA) antibodies in the sera of patients with gastrointestinal malignancies

Using an enzyme-linked immunoassay we tested the sera of 71 patients with digestive system cancer, 35 patients with various nonmalignant disorders, and 28 normal individuals for anti-CEA activity. Antibodies were found in the sera of 51% of the patients. Most of the patients positive for the antibodies (70%) had no evidence of metastatic disease. Fewer than 10% of the sera from control groups had anti-CEA activity. The authors concluded that the patients suffering from cancer of the GI system are capable of producing tumor-specific antibodies. These antibodies could be used as a tumor marker and/or as a possible index for the function of the immune system. The presence of a large tumor mass could lead to the removal of these antibodies from the circulation. © 1994 Plenum Publishing Corporation

Long-term survival of a female patient with primary malignant melanoma of the urethra.

Primary malignant melanoma of the female urethra comprises 0.2% of all melanomas and has poor prognosis. In the period 1972-1992, 75 cases of primary urethra carcinomas were treated at the Roswell Park Cancer Institute. Among them, only an 80-year-old woman was diagnosed with primary malignant melanoma. Despite conservative treatment, she lived for 7 years. We believe that local surgical excision can be an option for treatment in selected patients as it retains quality of life

Does axillary dissection affect prognosis in T1 breast tumors?

The treatment of patients with breast cancer has undergone many revisions over recent decades. The current trend is toward limited resections and breast conservation. Some authors advocate the abandonment of axillary lymph node dissection (ALND) for small tumors. While it is accepted that ALND has no therapeutic effect in breast cancer patients, its prognostic significance for small tumors is debated. Eligibility criteria for surgical treatment without axillary dissection are evolving. Considering that problem, we retrospectively reviewed the charts of 100 patients with T1 invasive carcinoma of the breast treated at Hippokration Hospital of Athens between 1986 and 1987. Patients were divided into two groups: those that underwent ALND (n=76) and those that did not (n=24). The following data were recorded: age, tumor size, grade, hormone receptor status and postoperative treatment. The ten-year overall and disease-free survival were analysed. A multivariate analysis was used to identify prognostic variables. There was no statistically significant difference in the ten-year overall and disease-free survival between the two groups. The univariate analysis showed that tumor size predicts both recurrence and survival. In the multivariate analysis tumor size was found to be an independent prognostic factor for overall survival. ALND did not influence the ten-year survival or the recurrence rate. Tumor size was the only statistically significant and independent prognostic factor for T1 breast cancer patients

High BAX/BCL2 mRNA ratio predicts favorable prognosis in laryngeal squamous cell carcinoma, particularly in patients with negative lymph nodes at the time of diagnosis

Objectives: Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. Therefore, accurate prognostic stratification of LSCC patients based on molecular prognostic tumor biomarkers would definitely lead to a better clinical management of this malignancy. The aim of this study was the investigation of the potential combinatorial prognostic value of BCL2 and BAX mRNA expression in LSCC. Design and methods: Total RNA was isolated from 105 cancerous laryngeal tissue specimens obtained from patients having undergone surgical treatment for primary LSCC. After cDNA preparation, a low-cost, in-house developed, sensitive and accurate real-time quantitative PCR (qPCR) methodology was applied for the quantification of BCL2 and BAX mRNA levels. Then, we carried out a biostatistical analysis to assess the prognostic value of the BAX/BCL2 mRNA expression ratio. Results: High BAX/BCL2 mRNA expression constitutes a favorable prognosticator in LSCC, predicting significantly longer disease-free survival (P=0.011) and overall survival (P=0.014) of patients. More importantly, the significant prognostic value of the BAX/BCL2 mRNA expression appeared to be independent of the histological grade and size of the malignant laryngeal tumor as well as TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan–Meier survival analysis demonstrated also that the BAX/BCL2 ratio can stratify node-negative (N0) LSCC patients into two subgroups with significantly different DFS and OS (P=0.021 and P=0.009, respectively). Conclusions: The BAX/BCL2 mRNA ratio is a putative molecular tissue biomarker in CLL and hence deserves further validation in larger cohorts of LSCC patients. © 2016 The Canadian Society of Clinical Chemist

Deferoxamine administration in septic animals: Improved survival and altered apoptotic gene expression

Background: Oxidative damage is one of the major factors that lead to cell damage, organ dysfunction and death in sepsis. Thus, an attractive candidate for the pharmacologic treatment of the septic syndrome is desferoxamine (DFX), an antioxidant iron chelator used for the removal of iron and a potential free radical scavenger. Objective: The impact of DFX administration on the survival of septic animals. The effect on cell integrity and cycle of vital organs. Methods: Sepsis was induced in 40 rats using the cecal ligation and puncture method (CLP) and 20 rats randomly received twice subcutaneously DFX (total dose: 40 mg/kg). Rats were monitored for 36 h and all vital organs were harvested for pathology examination and immunohistochemical detection of Bax, Bcl-2, cytochrome c and caspase-8 apoptosis regulating proteins. Results: Mean survival in the DFX group was 34.2 h (median 36.0, S.D. 4.4) and 30.2 h (median 36.0, S.D. 9.1) in the control group (p=0.04), while 36 h after follow up 85% of the DFX-treated rats and 55% of placebo rats were alive (p=0.04). Expression of pro-apoptotic bax protein was significantly increased in the heart, liver and kidney of animals in the DFX group compared to the control group. Conclusions: Treatment with the polymeric iron chelator DFX significantly increases survival of septic subjects and alters the expression of bax, an apoptosis regulating protein in certain organs (heart, liver and kidney). © 2004 Published by Elsevier B.V