Biomedical subjects

Marc A Reymond

Publications and source records attributed to Marc A Reymond.

8 recordsLinked to original sources

PubMed2004

Expression and functional proteomics studies in colorectal cancer.

Cell dysfunction results from multiple rather than from single gene interactions in the majority of colorectal cancers (CRC). Proteins, not mRNA, are the functional molecules in the cell, and the relationship between gene expression measured at the mRNA level and the corresponding protein level is not linear. Current proteomics tools allow for the determination of post-translational modifications, and hence the presence of protein isoforms--some of them being disease-relevant. Thus, proteomics approaches are a welcome complement to traditional genetic approaches. In CRC, expression proteomics studies were carried out with colorectal cell lines, whole tissue biopsies, and purified epithelial cells. For CRC, two-dimensional electrophoresis reference maps, protein, and membrane protein databases are available on the internet. Functional proteomics studies have been performed to better understand signaling pathways, to characterize the molecular targets of novel drugs, and to identify tumor-associated antigens in CRC. The increasing use of proteomics technologies, when addressing clinical problems, will accelerate the evolution towards personalized medicine in CRC.

Adenocarcinoma↗

PubMed2004

Using human samples in proteomics-based drug development: bioethical aspects.

Human samples and related medical data are expected to play an elevated role in application-based biomedical proteomics research. Against this framework, some facts should be kept in mind by academic and industrial researchers: international framework conditions on the use of human samples for research purposes are heterogeneous. For example, the value added by the use of human samples for product development is significant and the patient's personal and property rights may be affected. The body of national laws is growing and these laws are binding; guidelines published by international organizations should be respected. The most important aspect regards the informed consent of the patient, which is addressed in detail.

Animals↗

PubMed2003

Ethical and regulatory issues arising from proteomic research and technology.

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.

Ethics, Research↗

PubMed2003

Proteome analysis for the identification of tumor-associated biomarkers in gastrointestinal cancer.

Gastrointestinal cancers are usually diagnosed at advanced stages, making a curative treatment difficult. Biomarkers can help to overcome this problem by allowing earlier diagnosis, and thus better therapy. Proteomics tools are novel technologies to identify such biomarkers. This review summarizes advances in biomarker detection using two-dimensional gel electrophoresis (2D-PAGE), chromatography and mass spectrometry technologies. 2D-PAGE combined with mass spectrometry has led to the identification of several differentially expressed proteins in cancer tissue. However, for serum analysis, 2D-PAGE has severe limitations. For serum-based cancer diagnosis, surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry is a promising new technology. The potential of proteins identified with this technology as novel cancer biomarkers still needs to be confirmed in clinical trials.

Biomarkers, Tumor↗

PubMed2003

Informed consent for molecular-based diagnostic and prognostic studies in the cancer patient.

The consent of the subject who is donating cells, tissues, organs or body fluid for research purposes is a precondition for biomedical research on human samples. Before such consent can be obtained, comprehensive information should be provided to the subject by the investigators. This information includes the scope of research, the intended use of subject's body parts and associated data, the risks and benefits associated with the research project, and the right to withdraw their consent at any time without prejudice. Consent is free and must not be obtained under any kind of pressure. The traditional practice of obtaining consent for unspecified future use of biological samples and data generated from clinical trials is no longer adequate for genetic research. However, the investigator has still interest to keep the definition of the field of research as broad as possible. Privacy is an issue of importance for the patient, who is the primary supplier of human samples, and for his relatives. Benefit sharing is another field of contradictory discussion. Normal volunteers are a special case among gene expression studies. An example of informed consent form is provided.

Confidentiality↗

PubMed2002

Prediction of distant metastases after curative surgery for rectal cancer.

BACKGROUND: This study was performed to define selection criteria for adjuvant therapy in rectal cancer. MATERIALS AND METHODS: An immunohistochemical analysis using nine monoclonal antibodies against CEA, CD15s, CD44v6, DCC, E-cadherin, EGF-R, NM23, PAI-1, and P53 was performed on paraffin sections of two matched (age, gender, UICC stage [I-III], year of operation [1982-1991]) groups of patients (n = 2 x 64) with rectal carcinoma curatively treated by surgery alone. The two groups differed only with regard to metachronous distant metastatic spread. In order to exclude the influence of surgery, all patients had to meet the selection criterion "free of locoregional disease." Follow-up was prospective (median 80 months). Conventional staining procedures and immunohistochemical evaluation were used. Tumor grading and lymphatic and extramural venous invasion were also investigated. Analysis was performed with Fisher's exact test and Kaplan-Meier estimates of disease-free survival (log rank). The Cox model was used for multivariate analysis. RESULTS: In univariate analysis only grading (P < 0.001) and extramural venous invasion (P < 0.001) correlated significantly with metachronous metastases. In multivariate analysis, beside grading (P = 0.010) and extramural venous invasion (P = 0.011), CD15s (P = 0.042) was also of significance. All other immunohistochemical markers failed. CONCLUSIONS: The histopathological parameters grading and extramural venous invasion appear to be acceptable predictors of metachronous distant spread in curatively resected rectal cancer. In contrast to the immunohistochemical markers, grading seems to better reflect the individual tumor phenotype and its behavior.

Adult↗

PubMed2002

Tumor cell dissemination during laparoscopy: prevention and therapeutic opportunities.

Port-site recurrences (PSRs) are abdominal wall recurrences that occur in the subcutaneous tissue within a trocar site after cancer laparoscopy and are not associated with peritoneal carcinomatosis. In order to develop PSRs, viable tumor cells must be liberated from the primary tumor, be transported to a wound, and find there a favorable environment for growth. The short clinical delay in the occurrence of PSRs and their size suggest massive cell seeding into the abdominal wall. Traumatic handling of the tumor, slipping of trocars, liquid projection, as well as poor extraction techniques can all cause implantation of malignant cells into the subcutaneous tissue. Such contact can also occur postoperatively if the trocar channels remain open. Some histologies (e.g. gallbladder adenocarcinoma), the presence of ascites and advanced tumor stage are risk factors for PSRs. Further conditions--including the use of gas--might also play a limited role. The first preventive measure is the correct indication for a laparoscopic approach. Several techniques have been demonstrated to prevent PSRs in the animal model: (a) fixation of trocars to the abdominal wall; (b) prevention of leakage; (c) careful specimen handling; (d) reducing trauma to the abdominal wall; (e) specimen isolation before extraction from the abdominal cavity; (f) trocar-site irrigation with a cytotoxic solution, and (g) closure of peritoneum. Further innovative therapies are currently under investigation. In the clinical setting, correct indication, surgical expertise and application of prophylactic measures seem to be the best way to prevent the occurrence of PSRs.

Abdominal Wall↗

PubMedDate not supplied

Identification of gastric cancer patients by serum protein profiling.

Using surface-enhanced laser desorption ionization mass spectrometry (SELDI/TOF-MS) and ProteinChip technology, coupled with a pattern-matching algorithm and serum samples, we screened for protein patterns to differentiate gastric cancer patients from noncancer patients. A classifier ensemble, consisting of 50 decision trees, correctly classified all gastric cancers and all controls of a training set (100% sensitivity and 100% specificity). Eight of 9 stage I gastric cancers (88.9% sensitivity for stage I) were correctly classified. In addition, 28 sera from gastric cancer patients taken in different hospitals were correctly classified (100% sensitivity). Furthermore, all 11 control sera obtained from patients without gastric cancer (100% specificity) were classified correctly and 29 of 30 healthy blood-donors were classified as noncancerous. ProteinChip technology in conjunction with bioinformatics allows the highly sensitive and specific recognition of gastric cancer patients.

Algorithms↗