Biomedical subjects

P M Schneider

Publications and source records attributed to P M Schneider.

At least 19 recordsLinked to original sources

PubMed2007

Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers.

BACKGROUND AND OBJECTIVES: We evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with various gastrointestinal cancers and if they decrease following complete surgical resection. METHODS: Blood samples from 40 gastrointestinal cancer patients were analyzed prior and following surgical resection by direct quantitative real-time reverse transcriptase-PCR (RT-PCR) assays. RESULTS: Survivin mRNA expression was pre-operatively detected in 35 of 40 cancer patients (88%). Post-operative survivin levels were significantly lower than pre-operative levels in 59% of resected patients and were non-detectable in 38% (Wilcoxon rank test: P < 0.04). CONCLUSIONS: This is the first report showing that direct quantitative real-time RT-PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection.

Adenocarcinoma↗

PubMed2007

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer.

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.

Aged↗

PubMed2006

DNA commission of the International Society of Forensic Genetics: Recommendations on the interpretation of mixtures.

The DNA commission of the International Society of Forensic Genetics (ISFG) was convened at the 21st congress of the International Society for Forensic Genetics held between 13 and 17 September in the Azores, Portugal. The purpose of the group was to agree on guidelines to encourage best practice that can be universally applied to assist with mixture interpretation. In addition the commission was tasked to provide guidance on low copy number (LCN) reporting. Our discussions have highlighted a significant need for continuing education and research into this area. We have attempted to present a consensus from experts but to be practical we do not claim to have conveyed a clear vision in every respect in this difficult subject. For this reason, we propose to allow a period of time for feedback and reflection by the scientific community. Then the DNA commission will meet again to consider further recommendations.

Alleles↗

PubMed2006

DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis.

The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. A previous recommendation published in 2001 has already addressed Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). Since then, the use of Y-STRs has become very popular, and a numerous new loci have been introduced. The current recommendations address important aspects to clarify problems regarding the nomenclature, the definition of loci and alleles, population genetics and reporting methods.

Alleles↗

PubMed2006

DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis.

The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. A previous recommendation published in 2001 has already addressed Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). Since then, the use of Y-STRs has become very popular, and numerous new loci have been introduced. The current recommendations address important aspects to clarify problems regarding the nomenclature, the definition of loci and alleles, population genetics and reporting methods

Alleles↗

PubMed2006

High rate of lymph-node metastasis in submucosal esophageal squamous-cell carcinomas and adenocarcinomas.

BACKGROUND AND STUDY AIMS: The application of endoscopic mucosectomy in early esophageal cancer is limited by the presence of lymph-node metastasis. The aim of this prospective study was to analyze the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor penetration, comparing squamous-cell carcinomas and adenocarcinomas. PATIENTS AND METHODS: A total of 60 patients with pT1 esophageal cancer--24 with squamous-cell carcinomas (SCCs) and 36 with adenocarcinomas--were treated with transthoracic en-bloc esophagectomy with two-field lymphadenectomy (n = 50) or transhiatal esophageal resection (n = 10). An average of 30 lymph nodes were examined, and the following characteristics were evaluated: histology, mucosal infiltration, depth of submucosal wall infiltration in three thirds (sm1, sm2, sm3), grading, resection category, ratio of metastatic to resected lymph nodes, and locations of metastatic nodes. RESULTS: The rates of lymph-node metastasis were 0% for the 16 mucosal carcinomas and 45% for the 44 submucosal carcinomas (P < 0.01). There were no significant differences in the extent of lymph-node involvement between submucosal adenocarcinomas (41%) and submucosal SCCs (50%). Sm1 carcinomas were associated with a lower rate of lymph-node metastasis (SCCs 33%, adenocarcinomas 22%) than sm3 carcinomas (SCCs 69%, adenocarcinomas 78%). Two patients (9%) with submucosal SCCs and five patients (23%) with submucosal adenocarcinomas were classified as having stage pM1 lymph. The average lymph-node ratio in patients with pN1 was 0.13 for adenocarcinomas and 0.1 for SCCs (difference not significant). In the multivariate analysis, the parameters mucosal vs. submucosal (P < 0.01) and G1/G2 vs. G3 (P < 0.05) showed a significant impact in relation to metastatic lymph nodes. CONCLUSIONS: The most important factor for predicting lymph-node metastasis in early esophageal cancer is the presence of submucosal infiltration. Early adenocarcinomas and SCCs do not differ with regard to their rate of lymphatic involvement. The rate of lymph-node metastasis increases with the depth of submucosal infiltration, but metastases can already occur in sm1 lesions. Submucosal infiltration is a contraindication for endoscopic mucosectomy. Limited surgical procedures without adequate lymphadenectomy do not appear to be appropriate in the treatment of patients with submucosal esophageal carcinomas.

Adenocarcinoma↗

PubMed2006

[Combined laparoscopic/endoscopic treatment of gastric stroma tumors].

INTRODUCTION: Surgical therapy of Gastrointestinal stroma tumor (GIST) is the treatment of choice. Local resection will be carried out if technically possible. We describe the technique of laparoscopic wedge resection combined with intraoperative gastroscopy in order to achieve complete tumor resection. METHOD: We report on 4 cases with gastrointestinal stroma tumors which were located in the gastric corpus (n = 2) and the cardia (n = 2). RESULTS: In all patients the tumor could be removed completely without any perioperative complications using laparoscopic wedge resection controlled by intraoperative endoscopy. The duration of hospitalisation after operation was 7 days (5-10). On the basis of the mean tumor size (mean 3.8 cm) and the low mitotic activity (mean 2.75/high power fields) the tumors belong to the group with low malignant potential. There is no evidence of recurrence after a mean follow up period of 23 (6-30) months. CONCLUSION: Combined laparoscopic/endoscopic wedge resection is a safe method for total resection of GIST of the stomach and should be preferred as alternative to open surgery.

Follow-Up Studies↗

PubMed2006

Lewis(y) antigen (CD174) and apoptosis in gastric and colorectal carcinomas: correlations with clinical and prognostic parameters.

Lewis(y) (Le(y)), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Le(y) expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Le(y) and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Le(y) reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Le(y) expression compared to other tumor types. In colorectal cancers, Le(y) was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Le(y) antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.

Adenocarcinoma↗

PubMed2005

[Preoperative evaluation of prognostic factors in esophageal squamous cell cancer].

Despite substantial improvements in the surgical therapy of esophageal squamous cell cancer, the prognosis still remains poor. This is mainly due to locally advanced tumors (T3-4, N+) or systemic metastases (M1) in the majority of patients at initial presentation. It is of the utmost importance to reliably detect relevant pretherapeutic prognostic indicators for optimal individual therapeutic strategies. Pretherapeutic prognostic indicators should therefore discriminate precisely between incurable and potentially curative disease. Preoperative or definitive multimodal treatment is increasingly being offered to patients with locally advanced tumors and opens a broad field for innovative techniques such as pretherapeutic molecular response prediction or early response detection by PET scan to further individualize and optimize treatment strategies.

Carcinoma, Squamous Cell↗

PubMed2005

Hepatitis B surface antigen presentation and HLA-DRB1*- lessons from twins and peptide binding studies.

The aim of this study was to investigate the underlying mechanisms of the genetic association between certain HLA-DRB1* alleles and the immune response to HBsAg vaccination. Therefore, HBsAg peptide binding to HLA-DR molecules was measured in vitro by peptide binding ELISAs. Additionally, HBsAg-specific T cell reaction and cytokine profile of immune response were analysed ex vivo in ELISPOT assays and DR-restriction of T-cell proliferative responses was investigated with HBsAg specific T cell clones. In addition, we compared HBsAg specific T cell responses of 24 monozygotic and 3 dizygotic twin pairs after HBsAg vaccination. Our results showed that the peptide binding assays did not reflect antigen presentation in vivo. DR alleles associated with vaccination failure like DRB1*0301 and 0701 efficiently presented HBsAg peptides. In 11 of 24 investigated monozygotic twin pairs we observed pronounced differences in the recognition of HBsAg peptides. This study indicates that HLA-DR associations with HBsAg vaccination response are not caused by differences in peptide binding or by a shift in the Th1/Th2 profile. Our findings strongly argue for differences in the T cell recognition of peptide/MHC complexes as the critical event in T cell responsiveness to HBsAg.

Adolescent↗

PubMed2005

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0.

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0.50; P < 0.001), Grave's disease (0.30; P = 0.002) and insulin-dependent diabetes mellitus (0.23; P = 0.04) and in British patients with dermatitis herpetiformis (0.42; P = 0.002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0.51, P = 0.0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P < 0.01) and a negative association of PIP with anti-C1q antibodies was also reflected in an increased prevalence (P = 0.006) and levels (P = 0.006) of anti-C1q antibodies in patients with subnormal PIP, as well as a negative correlation between PIP and anti-C1q antibodies (r = - 0.25, P = 0.02). These results show that the PIP defect cannot be explained by low levels of C4A alone and suggest that measurements of anti-C1q antibodies may be useful in future studies on the molecular cause of the PIP defect in autoimmune connective tissue disease.

Adolescent↗

PubMed2004

Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer.

We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase-polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for beta-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA >1 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (P<0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, non effective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment.

Adult↗

PubMed2004

Results of a collaborative study of the EDNAP group regarding mitochondrial DNA heteroplasmy and segregation in hair shafts.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in order to evaluate the distribution of mitochondrial DNA (mtDNA) heteroplasmy amongst the hairs of an individual who displays point heteroplasmy in blood and buccal cells. A second aim of the exercise was to study reproducibility of mtDNA sequencing of hairs between laboratories using differing chemistries, further to the first mtDNA reproducibility study carried out by the EDNAP group. Laboratories were asked to type 2 sections from each of 10 hairs, such that each hair was typed by at least two laboratories. Ten laboratories participated in the study, and a total of 55 hairs were typed. The results showed that the C/T point heteroplasmy observed in blood and buccal cells at position 16234 segregated differentially between hairs, such that some hairs showed only C, others only T and the remainder, C/T heteroplasmy at varying ratios. Additionally, differential segregation of heteroplasmic variants was confirmed in independent extracts at positions 16093 and the poly(C) tract at 302-309, whilst a complete A-G transition was confirmed at position 16129 in one hair. Heteroplasmy was observed at position 16195 on both strands of a single extract from one hair segment, but was not observed in the extracts from any other segment of the same hair. Similarly, heteroplasmy at position 16304 was observed on both strands of a single extract from one hair. Additional variants at positions 73, 249 and the HVII poly(C) region were reported by one laboratory; as these were not confirmed in independent extracts, the possibility of contamination cannot be excluded. Additionally, the electrophoresis and detection equipment used by this laboratory was different to those of the other laboratories, and the discrepancies at position 249 and the HVII poly(C) region appear to be due to reading errors that may be associated with this technology. The results, and their implications for forensic mtDNA typing, are discussed in the light of the biology of hair formation.

DNA, Mitochondrial↗

PubMed2004

[Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation].

Following surgical resection locally advanced oesophageal carcinomas exhibit a bad prognosis and therefore neoadjuvant therapeutic strategies were developed. Because success of therapy is associated with the extent of tumor regression in this context, the introduction of objective histopathological criteria seems to be very important. This study included 67 patients with oesophageal carcinomas (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil-containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24 cases adenocarcinomas were diagnosed. After completion of therapy, a surgical resection and a histopathological examination of the tissue specimens were performed. The extent of tumor regression was histologically evaluated and therapy-induced alterations were graded semiquantitatively. Thereby, a significantly favorable prognosis was observed in the group of patients that showed a regression of carcinomas of 90% or more. Additionally, the extent of a resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates correlated with the grade of regression. These results underline the importance of an exact examination and histomorphological evaluation of the response for the assessment of survival probability after neoadjuvant radiochemotherapy of oesophageal carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Molecular biology of esophageal cancer.

Squamous cell carcinoma (ESCC) is the most frequent histological subtype in esophageal cancer, although the incidence of esophageal adenocarcinoma (EAC) is increasing faster than any other malignancy in the western world. New developments in the understanding of molecular mechanisms in esophageal cancer comprise analysis of the genetic tumor profiles by CGH (comparative genomic hybridization), the detection of tumor suppressor gene inactivation, and the analysis of proto-oncogenes. Especially the inactivation of the p53 gene proved to be of particular importance for the development of esophageal cancer. Also p15 and p16 have been identified to be involved in the pathogenesis of esophageal cancer by influencing the cyclin kinase inhibitor cascade and DNA mismatch repair processes. Amplification of cyclin D1 results in growth advantage for tumor cells and enhances tumorigenesis; gene amplification and overexpression of cyclin D1 were frequently demonstrated especially in ESCC. Regarding the dysplasia-metaplasia-carcinoma sequence of Barrett's esophagus, inhibition of apoptosis by overexpression of bcl-2 proteins occurs as an early event.

Adenocarcinoma↗

PubMed2003

Differential SPARC mRNA expression in Barrett's oesophagus.

Barrett's oesophagus (BE) is the precursor lesion to adenocarcinoma of the oesophagus. Understanding of the molecular alterations in this multistage process may contribute to improved diagnosis and treatment. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that modulates cell adhesion and growth. Alterations in SPARC expression have been observed in a variety of solid tumours. The aim of this study was to assess the prevalence and timing of SPARC mRNA expression in Barrett's multistage disease and to investigate the impact of SPARC alterations on the development and progression of this disease. SPARC mRNA expression was measured using a quantitative real-time RT-PCR method in 108 specimens from 19 patients with BE without carcinoma, 20 patients with Barrett's-associated adenocarcinoma (EA), and a control group (CG) of 10 patients without evidence of gastro-oesophageal reflux disease. The median SPARC mRNA expression was significantly upregulated in BE tissues compared to paired normal oesophagus (NE) tissues for the BE group (P=0.004) and for the EA group (P<0.001). The SPARC mRNA expression was significantly higher in adenocarcinoma of the oesophagus compared to matching NE tissue and compared to Barrett's tissues in the EA group (P<0.001). Furthermore, SPARC expression values were significantly different between metaplastic and dysplastic Barrett's tissues (P=0.014). In histologically normal squamous oesophagus tissues obtained from carcinoma patients (EA group), the SPARC mRNA expression was significantly higher compared to NE mucosa from the BE group and the CG group (P=0.03). These findings suggest that the upregulation of SPARC mRNA expression is an early event in the development and progression of BE and EA, and that high SPARC expression may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread 'field effect' is present in the NE of patients with oesophageal adenocarcinoma.

Adenocarcinoma↗

PubMed2003

[Prognostic relevance of biological and molecular markers in oncology. Criteria for planning and interpreting studies].

Experts on different specialties (surgery, pathology, molecular biology and medical statistics) discussed the evaluation of prognostic factors during a workshop. The most important results presented are: (1) the prognostic relevance of new biological or molecular markers must be evaluated in a phase-III prognostic study. To establish such a marker in the UICC-TNM-classification in at least two different centers, two multivariate analyses according to defined criteria are necessary; (2) the standards of laboratory methods have to be defined, e.g.,which method to apply for RNA-analysis,which materials to used, etc; (3) intensive data analysis should be done before using methods of multivariate analysis. The criteria for the presentation of survival curves are given in detail; (4) in multivariate analysis, the Cox proportional hazard regression for survival outcomes is discussed with explanations and examples of the terms relative risk, odds-ratio, hazard and relative hazard. The arrangement and interpretation of a good prognostic study should be performed as an interdisciplinary approach.

Biomarkers, Tumor↗

PubMed2003

[How safe is high intrathoracic esophagogastrostomy?].

The surgical results of transthoracic en bloc esophagectomy and high intrathoracic esophagogastrostomy performed on 109 consecutive patients are presented. Adenocarcinoma was present in 59 patients, squamous cell carcinoma in 45 patients, and other neoplastic lesions of the esophagus in 5 patients: 29.5% of the patients received neoadjuvant radiochemotherapy or chemotherapy alone. In 35% of the patients, the preoperative risk was classified as normal, whereas in 42% and 23% of the patients the preoperative status was compromised or severely impaired, respectively. On average 33 lymph nodes were dissected from each specimen. The postoperative course was uneventful in 60% of the patients and prolonged or severe in 40% of the patients. The hospital mortality was 5.5% (six patients). Nine patients (8.2%) developed anastomotic leakage. Six of these nine patients were discharged after rethoracotomy and reanastomosis ( n=3) or endoscopic treatment with fibrin glue ( n=3). Three patients died despite rethoracotomy and reanastomosis. Only 2 of 103 discharged patients (1.9%) underwent postoperative endoscopic bougienage two or three times because of an anastomotic stenosis. High intrathoracic esophagogastrostomy is a safe anastomosis, which nevertheless requires diligent postoperative management.

Adenocarcinoma↗