Search PubMed⌕ Search

PubMed · 8412191

Oncogene mutations as intermediate markers.

Abstract

Tumors arise through a series of genetic changes which include activation of protoocogenes and inactivation of tumor suppressor genes. It is now possible to identify rare cells containing genetic mutations in an excess background of normal cells. Theoretically, the identification of a clonal population of cells sharing an early genetic marker for malignant transformation would lead to valuable intermediate endpoints and could diagnose premalignant lesions amenable to chemoprevention. Ideally, these genetic changes would be specific point mutations that occur early in the tumor cascade, prior to the development of a clinically significant tumor. To identify these markers, precise histopathologic and genetic tumor models must be described. Early candidate markers include p53 point mutations in squamous cell carcinoma of the aerodigestive tract.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D Sidransky, J Boyle, W Koch, P van der Riet. 1993. Oncogene mutations as intermediate markers.. https://doi.org/10.1002/jcb.240531026

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Synthesis and cancer chemopreventive activity of zapotin, a natural product from Casimiroa edulis.

An efficient method has been developed to synthesize zapotin (5,6,2',6'-tetramethoxyflavone), a component of the edible fruit Casimiroa edulis, on a multigram scale. The synthesis utilizes a regioselective C-acylation of a dilithium dianion derived from a substituted o-hydroxyactophenone to afford a beta-diketone intermediate that can be cyclized to zapotin in good overall yield, thus avoiding the inefficient Baker-Venkataraman rearrangement pathway. Zapotin was found to induce both cell differentiation and apoptosis with cultured human promyelocytic leukemia cells (HL-60 cells). In addition, the compound inhibits 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with human bladder carcinoma cells (T24 cells), and TPA-induced nuclear factor-kappa B (NF-kappaB) activity with human hepatocellular liver carcinoma cells (HepG2 cells). These data suggest that zapotin merits further investigation as a potential cancer chemopreventive agent.

Anticarcinogenic Agents↗

Structure-activity relationships of tea compounds against human cancer cells.

The content of the biologically active amino acid theanine in 15 commercial black, green, specialty, and herbal tea leaves was determined as the 2,4-dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To define relative anticarcinogenic potencies of tea compounds and teas, nine green tea catechins, three black tea theaflavins, and theanine as well as aqueous and 80% ethanol/water extracts of the same tea leaves were evaluated for their ability to induce cell death in human cancer and normal cells using a tetrazolium microculture (MTT) assay. Compared to untreated controls, most catechins, theaflavins, theanine, and all tea extracts reduced the numbers of the following human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2), and prostate (PC-3) as well as normal human liver cells (Chang). The growth of normal human lung (HEL299) cells was not inhibited. The destruction of cancer cells was also observed visually by reverse phase microscopy. Statistical analysis of the data showed that (a) the anticarcinogenic effects of tea compounds and of tea leaf extracts varied widely and were concentration dependent over the ranges from 50 to 400 microg/mL of tea compound and from 50 to 400 microg/g of tea solids; (b) the different cancer cells varied in their susceptibilities to destruction; (c) 80% ethanol/water extracts with higher levels of flavonoids determined by HPLC were in most cases more active than the corresponding water extracts; and (d) flavonoid levels of the teas did not directly correlate with anticarcinogenic activities. The findings extend related observations on the anticarcinogenic potential of tea ingredients and suggest that consumers may benefit more by drinking both green and black teas.

Anticarcinogenic Agents↗

Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells.

Diet high in vegetables and fruits has been associated with reduced cancer risk. However, the involved mechanisms are unknown. Previously, we reported that the dietary flavonoid apigenin could inhibit the proteasome activity and induce apoptosis in tumor cells. To further investigate the structure-proteasome-inhibitory activity relationships, we chose and tested five dietary flavonoids, including luteolin, apigenin, chrysin, naringenin and eriodictyol. We found that the order of inhibitory potencies and apoptosis-inducing potencies of these five compounds in 20S purified proteasome and tumor cells was: (1) luteolin > apigenin > chrysin, and (2) apigenin >> naringenin, and luteolin >> eriodictyol. Therefore, flavonoids with hydroxylized B ring and/or unsaturated C ring are natural potent proteasome inhibitors and tumor cell apoptosis inducers. Furthermore, neither apigenin nor luteolin could inhibit the proteasome and induce apoptosis in non-transformed human natural killer cells. This finding may provide a molecular basis for the clinically observed cancer-preventive effects of fruits and vegetables.

Anticarcinogenic Agents↗