ABSTRACT
BACKGROUND: The pathogenesis of head and neck squamous carcinoma (HNSCC) is a complex and multistage process, which is characterized by the accumulation of genetic and epigenetic aberrations. Most of our knowledge concerning the regulation of gene expression by the epigenome is based on changes in DNA methylation and post-translational histone modifications that affect the phenotypic plasticity of cells under physiological and pathological conditions. STATE OF THE ART: Numerous experimental studies have unraveled the impact of epigenetic alterations during initiation and malignant progression of HNSCC and substantiate their contribution in the context of tumor stem cells and treatment resistance. Due to their stability epigenetic modifications serve as promising diagnostic and prognostic biomarkers, and the reversible nature makes key regulators attractive targets for innovative treatment options.
Subject(s)
Epigenesis, Genetic/genetics , Gene Targeting/methods , Genetic Therapy/methods , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/therapy , DNA Methylation/genetics , Genes, Neoplasm/genetics , Humans , Models, GeneticABSTRACT
From a total of 65 colorectal adenocarcinomas studied by cytogenetic methods, 33 were selected for the present study; in addition to other karyotypic anomalies, these 33 showed a loss of the short arm of chromosome 17. This loss was either the result of a deletion or rearrangement, or caused by the loss of a whole chromosome 17. The 17p- tumors were characterized by a high grade of karyotypic abnormality including a high incidence of cases with double minutes. A gain of chromosomes 2, 7, 19, and 20, and the loss of chromosome 18 and the Y-chromosome were the most frequent numerical anomalies associated with 17p-, as were structural changes of chromosomes 1 and 5. The most impressive difference in the pattern of proto-oncogene over-expression between the 17p- tumors and those without this anomaly was the significantly increased frequency of cases with c-erbB over-expression. Some significant, but also loose, associations were found between cytogenetic/oncogenetic and histopathologic or clinical features of these tumors. The patterns of genetic changes in cells of colorectal carcinomas may thus reflect the potential of the future development, rather than the present clinical features, of the respective tumor. Therefore, the character of the change seems to be more prognostic than diagnostic.
Subject(s)
Adenocarcinoma/genetics , Chromosome Aberrations , Chromosomes, Human, Pair 17 , Colorectal Neoplasms/genetics , Proto-Oncogenes/genetics , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proto-Oncogene MasABSTRACT
A complex analysis of oncogene over-expression in ovarian cystadenocarcinomas of 20 patients was performed. Radioactively labelled cDNAs were synthesized from total cellular RNA from tumor cells and hybridized to dot blot filters. On each filter more than 20 different plasmids containing cloned oncogene fragments were immobilized. In concordance with published data fms was found over-expressed in 40% of the tumors. Elevated expression levels of the EGF receptor was also frequently detected. 35% of the tumors showed elevated N-ras mRNA levels. All those tumors' showed a highly dedifferentiated phenotype and were classified as G3-tumors. More over, simultaneous over-expression of different oncogenes correlated surprisingly strongly with tumor grading.
ABSTRACT
More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.
Subject(s)
Breast Neoplasms/genetics , Oncogenes , Proto-Oncogenes , Animals , Breast Neoplasms/pathology , Cloning, Molecular , Female , Gene Expression , Gene Expression Regulation, Neoplastic , Humans , Immunoblotting , Proto-Oncogene Proteins/analysis , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purificationABSTRACT
KIE: Statistical evidence for the transmission of acquired immunodeficiency syndrome (AIDS) through blood and blood products is cited, and the potential legal ramifications for blood suppliers are discussed. An AIDS victim could bring a claim against a hospital or blood bank on the contention that the facility had supplied an unfit product for patient use. Remedies for recovery in such a case might be based on a breach of implied warranties, strict liability, or negligence. Precautions which blood suppliers and physicians can take to reduce the potential for liability are suggested.^ieng