Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo.

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of beta1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking beta1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC.     

Clear cell dysplasia of the bladder. Report of a case with flow cytometric analysis.

Clear cell dysplasia of the bladder is a well-described morphologic entity that has been found in association with transitional cell carcinoma of the bladder. Its biologic role in bladder tumorigenesis is unknown, and no instances of its polidy analysis have been reported. The authors describe a case of clear cell dysplasia of the bladder found in association with a primary adenocarcinoma of the bladder. Flow cytometric analysis of bladder tissue involved by clear cell dysplasia, adenocarcinoma and cystitis cystica (all from the same bladder) demonstrated no DNA aneuploid populations. Cells from the area of clear cell dysplasia had an S + G2 + M fraction of 7%, indicating that it was a proliferative lesion. Cells from the adenocarcinoma had an S + G2 + M phase of 18%, and cells from an area of cystitis cystica had an S + G2 + M phase of 4%.     

Dark Matter of the Biosphere: the Amazing World of Bacteriophage Diversity

Bacteriophages are the most abundant biological entities in the biosphere, and this dynamic and old population is, not surprisingly, highly diverse genetically. Relative to bacterial genomics, phage genomics has advanced slowly, and a higher-resolution picture of the phagosphere is only just emerging. This view reveals substantial diversity even among phages known to infect a common host strain, but the relationships are complex, with mosaic genomic architectures generated by illegitimate recombination over a long period of evolutionary history.     

Cholesterylene, a newly recognized tissue lipid, found at high levels in the cornea.

In the course of measuring the concentration of cholesterol in an opacified dog cornea by gas-chromatography, relatively large amounts of an unidentified non-saponifiable lipid were recognized. When the unknown lipid was subjected to gas chromatographic-mass spectral analysis it displayed a major ion at m/z 368 M+. and was identified as cholesta-3,5-diene, cholesterylene, by computer match with mass spectral-registry data. Cholesterylene was then shown to be present in the corneas of normal dogs, cows and humans, accounting for 20-25% of the total steroid-sterol in dog corneas and 5-10% in cow and human. Cholesterylene, which can be considered as an extremely nonpolar dehydration product of cholesterol, has not previously been recognized in animal tissues. Although the source of corneal cholesterylene is unknown, preliminary results suggest non-enzymatic formation from cholesterol.     

GTP gamma S inhibits early c-myc protein accumulation but not DNA synthesis in Swiss 3T3 fibroblasts

Quiescent Swiss 3T3 fibroblasts stimulated with epidermal growth factor and insulin showed large transient increases in c-myc mRNA and c-myc protein accumulation which were maximal at about 2 h after addition of the co-mitogens. When the cells were loaded with 0.1 mM of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) by transient permeabilisation immediately before mitogenic stimulation, the increase in c-myc mRNA was similar to that observed in unloaded cells but the corresponding c-myc protein peak was reduced by at least 95%. The GTP gamma S completely blocked incorporation of [35S]methionine into cell proteins for 3-4 h after addition of the mitogens, but not thereafter, and caused a delay in the subsequent onset of DNA synthesis by the same period. The data show that less than 5% of the early increase in c-myc protein normally observed after mitogenic stimulation is required for its obligatory role in the progression of cells to S phase implied by other evidence.