Epidermal growth factor-related peptides and their receptors in human malignancies

Publisher Summary It is known for some time that malignant transformation of human cells may be associated with the appearance of tumor associated antigens (TAA). Decades of research have been aimed at the identification of TAA that can serve as targets for the immunotherapy of malignant diseases. The dramatic progress in the understanding of molecular basis of target cell recognition by cytotoxic T lymphocytes (CTL) has provided the background to design effective strategies to identify TAA recognized by CTL on tumor cells. The extensive application of these strategies by a number of investigators has resulted in the identification of various families of TAA on various types of solid tumors. Mouse tumor models have played an important role in elucidating the mechanisms by which the immune system interacts with tumor cells and eradicates cancer. The second line of evidence is represented by the phenomenon of a “mixed response.” A mixed response occurs rather frequently in patients with metastases, although its actual frequency is not documented. Mixed responses are characterized by the different behavior of synchronous metastases in response to T cell-based immunotherapy. This important finding suggests that TAA-specific CTL may be present in some cancer patients but are unable to attack tumor cells due to the presence of inhibitory receptors.

Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance.

Autocrine and paracrine regulation by cytokines and growth factors in melanoma

We correlated the steady state transcription and protein secretion of interleukin 8 (IL-8) in 13 different human melanoma cell lines with their ability to grow and produce metastasis in nude mice. Highly metastatic cells expressed higher steady state levels of IL-8 mRNA transcripts than did low metastatic cells. In situ mRNA hybridization analyses confirmed the pattern of mRNA expression on a cellular level. Increased mRNA expression directly correlated with secretion of IL-8 protein as determined by enzyme-linked immunosorbent assay. Recombinant IL-8 stimulated the proliferation of low metastatic A375P cells in a dose-dependent manner, a stimulation that was abrogated by the use of a polyclonal antibody against IL-8. The data suggest that IL-8 can be an autocrine growth factor for human melanoma cells and that IL-8 is involved in melanoma metastasis.

https://cancerres.aacrjournals.org/content/canres/54/12/3242.full.pdf

Expression of Interleukin 8 Correlates with the Metastatic Potential of Human Melanoma Cells in Nude Mice

To gain molecular understanding of carcinogenesis, progression, and diversity of gastric cancer, 22 primary human advanced gastric cancer tissues and 8 noncancerous gastric tissues were analyzed by high-density oligonucleotide microarray in this study. Based on expression analysis of approximately 6800 genes, a two-way clustering algorithm successfully distinguished cancer tissues from noncancerous tissues. Subsequently, genes that were differentially expressed in cancer and noncancerous tissues were identified; 162 and 129 genes were highly expressed (P 2.5-fold in cancer tissues and noncancerous tissues, respectively. In cancer tissues, genes related to cell cycle, growth factor, cell motility, cell adhesion, and matrix remodeling were highly expressed. In noncancerous tissues, genes related to gastrointestinal-specific function and immune response were highly expressed. Furthermore, we identified several genes associated with lymph node metastasis including Oct-2 or histological types including Liver-Intestine Cadherin. These results provide not only a new molecular basis for understanding biological properties of gastric cancer, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric cancer.

https://cancerres.aacrjournals.org/content/canres/62/1/233.full.pdf

Global Gene Expression Analysis of Gastric Cancer by Oligonucleotide Microarrays

Constitutive Expression of Multiple Growth Factor Genes by Melanoma Cells but Not Normal Melanocytes

Normal human melanocytes, which require the phorbol ester 12- O -tetradecanoylphorbol-13-acetate (TPA) for growth in culture, were transfected with a SV40 T-antigen-containing plasmid by using the technique of electroporation, and were scored for colonies of morphologically altered cells. The frequency of transformed colonies was higher when selection was done in the absence rather than the presence of TPA in the medium. Three cell lines derived from transformed colonies were characterized. All show an enhanced growth rate compared to parental cells, anchorage independence, loss of dependence on medium supplements for growth, chromosomal abnormalities, an extended life span, and growth inhibition by TPA. They express nerve growth factor receptor and M r 97,000 protein, melanotransferrin, two antigens usually associated with melanocytic cells, but the transformed cells are not pigmented. The three cell lines underwent crisis at about passage 10 posttransfection; one cell line recovered and appears to have unlimited growth potential. None of the cell lines is tumorigenic. They should be interesting models for studying multistage carcinogenesis in human cells and transcriptional activation by TPA.

https://cancerres.aacrjournals.org/content/canres/49/13/3650.full.pdf

SV40-transfected human melanocyte sensitivity to growth inhibition by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

The invention concerns a method of carrying out blood tests. The invention is based on the knowledge that clinico-chemical blood parameters can be determined using not only blood serum but also blood plasma. Therefore, freshly taken blood samples, which are mixed with at least one thrombin inhibitor, can be used for determining both clinico-chemical parameters and haematological parameters. The clinico-chemical parameters can thus be determined using blood plasma, separation of coagulable components no longer being necessary.

Method of carrying out blood tests

Die vorliegende Erfindung betrifft ein Verfahren zum Durchfuhren von Bluttests. Der Erfindung liegt die Erkenntnis zugrunde, das klinisch-chemische Blutparameter nicht nur unter Verwendung von Blutserum, sondern auch unter Verwendung von Blutplasma bestimmt werden konnen. Daher konnen frisch entnommene Blutproben, die mit mindestens einem Thrombin-Inhibitor versetzt sind, sowohl fur die Bestimmung klinisch-chemischer Parameter als auch fur die Bestimmung hamatologischer Parameter eingesetzt werden. Die klinisch-chemischen Parameter konnen somit unter Verwendung von Blutplasma bestimmt werden; eine Abtrennung gerinnbarer Bestandteile ist nicht mehr notwendig.

Karl Melber

Papers

Constitutive Expression of Multiple Growth Factor Genes by Melanoma Cells but Not Normal Melanocytes

SV40-transfected human melanocyte sensitivity to growth inhibition by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

Method of carrying out blood tests

Verfahren zum durchführen von bluttests