Cancer cells (Cold Spring Harbor, N.Y. : 1989)最新文献

Most lung cancers are simultaneously stimulated by several autocrine and paracrine growth factors. Diseases resulting in excessive production of these factors and/or changes in the receptors, second messengers, or genes comprising their signal transduction pathways can thus result in the stimulation of continuous cell proliferation characteristic of cancer. Some carcinogenic N-nitrosamines mimic the stimulatory effect of cell-type-specific growth factors by binding to their receptors, and in this way mediate their selective carcinogenic effects. In this review I discuss the significance of receptor-mediated mitogenic signal transduction pathways for the initiation and progression of lung cancer, and describe novel lung cancer therapeutics that target components of these pathways.

Photodynamic therapy (PDT) is a promising new cancer treatment modality in which tumor cells are killed as a result of photoactivation of a tumor-localizing photosensitizing agent. Since activating light can be targeted specifically to tumors, and tumor-selective photosensitizing agents are being developed, this treatment has the potential to induce highly selective destruction of malignant cells. To date, PDT has been applied to a large variety of human carcinomas, resulting in successful eradication of single tumor nodules and several types of superficial tumors. Current research is aimed at improving the efficacy and tumor-selectivity and tumor destruction. The most immediate benefits of PDT are likely to be seen in patients treated with a combination of this and other forms of therapy.

Both in humans and in animals, papillomaviruses are the causative agents of a variety of benign epidermal tumors including common warts, flat warts, condylomas, and papillomas. These lesions most often regress, occasionally persist, and, in the presence of additional critical factors, can progress to cancer. Vaccines that protect against papillomavirus infection or induce tumor regression would be beneficial in the treatment of recalcitrant warts and in preventing malignant progression. Recently, successful prophylaxis and rejection of epidermal and alimentary canal tumors have been achieved in cattle with both conventional and genetically engineered vaccines. Successful vaccination in animals has important implications for the management of papillomavirus-associated tumors in humans, particularly laryngeal papillomas and cervical carcinomas.

DNA repair processes are critically important in the prevention of carcinogenesis, and currently much research is directed toward elucidation of the biochemical mechanisms by which DNA repair occurs. Techniques have been developed for examining individual genes to quantitate the lesions induced by various chemotherapeutic agents and to measure the rate of gene-specific DNA repair. In mammalian cells, the DNA repair response exhibits intragenomic heterogeneity-active genes are preferentially repaired and the transcribed strand of DNA is repaired more rapidly than the nontranscribed strand. These studies have provided new insight into the molecular biology of DNA repair and a new perspective on the role of repair processes in cellular resistance to DNA damage and malignancy. Elucidation of the mechanisms by which gene-specific lesions are formed and repaired will be important if we are to understand the fundamental processes of malignancy.

Structural abnormalities affecting band q13 of chromosome 11 have been reported in a variety of human tumors, particularly multiple endocrine neoplasia type 1 (MEN1), certain low-grade B-cell neoplasms, and a significant subset of breast and squamous cell carcinomas. The perturbations of the region are also varied, ranging from allele loss and deletions to specific translocations and DNA amplification. Given their clinical relevance in classifying tumors and identifying patients at increased risk, it is important to locate and characterize the genes on which these aberrations impinge. Here we assess the candidate genes identified thus far and the evidence that implicates them in tumorigenesis.

The effects of the raf and myc oncogenes on murine hemopoietic cells are quite distinct. The raf-1 gene, which encodes a serine/threonine kinase that is involved in signal transduction, preferentially transforms erythroid cells, whereas myc, which encodes a DNA-binding protein, induces lymphoid and myeloid neoplasms. Together, raf and myc form a potent leukemogenic combination and they act synergistically to transform cells from all hemopoietic lineages. Strikingly, the expression of exogenous raf and myc in lymphoid and erythroid cells enables these cells to change lineages and become myeloid cells, an observation that raises interesting questions concerning commitment to specific lineages.