Three Lewis lung carcinoma lines (3LL) with different metastatic behavior have been investigated with regard to their response to Razoxane (ICRF-159). The effects of different schedules were tested both on primary and secondary tumors. Results show that the lines are heterogeneous in their response to this antimetastatic agent and that, in particular, BM21548 the least metastatic line is also less sensitive to ICRF-159. A better response can be achieved with this line by a proper fractionation regimen which takes into account the delayed metastasis release from primary tumor. As far as M1087, the most metastatic line is concerned, secondaries are greatly affected by ICRF-159 treatment if performed at a moderately advanced stage of growth. On the contrary, metastases from early tumor stages can be better controlled by radical surgery of the primary implant than by treatment with ICRF-159.

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PubMedDate not supplied

Study on protein content of rabbit reticulocyte ribosomal subunits: correlation with functional activity.

The correlation between chemical composition (protein content) of native and derived ribosomal subunits and their activity in a cell-free system, programmed with haemoglobin messenger RNA, has been investigated. On the basis of isodensity sedimentation of formaldehyde fixed particles in CsC1 and of two-dimensional gel electrophoresis of ribosomal proteins, it appears that the native ribosomal subparticles contain a large protein complement than the derived subparticles and, correspondingly, they are less dependent on an external supply of initiation factors for haemoglobin synthesis in vitro.

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PubMedDate not supplied

[p53: prospects for gene therapy of cancer].

PURPOSE: To evaluate the prospects for cancer gene therapy through restoration of wild-type p53 (wt-p53) protein expression and/or function. DESIGN: To review the most significant data reported in the literature with particular attention in dissecting the biological questions that are still open and need to be clarified to improve TP53-based gene therapy. RESULTS: Considerable experimental evidence obtained in vitro and in vivo indicates that wt-p53 protein can suppress the transformed phenotype of several types of cancer in humans as well as other species. Wt-p53 protein suppress transformation by inducing different biological effects including maintenance of genomic stability, inhibition of cell proliferation, induction of apoptosis, differentiation or senescence. All these findings have rendered p53 a potential helpful target for therapy of many types of human cancers. CONCLUSIONS: Different experimental strategies based on i) TP53 gene-replacement, ii) restoration of wt-p53 activity, iii) replication of defective lytic viruses specifically in altered p53-expressing tumors, have given promising results in vitro and, in some cases also in vivo. At present, a few phase one clinical trials have been started for some of the gene-replacement strategies.

Apoptosis↗