One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of selective molecular targets for antineoplastic therapy. A substantial subset of human ovarian, endometrial, breast, colorectal, and prostatic cancers exhibit increased endogenous fatty acid biosynthesis and overexpress certain enzymes in the pathway. Cell lines derived from these tumors use endogenously synthesized fatty acids for cellular functions, whereas normal cells and tissues appear to utilize dietary lipids preferentially. We have previously shown that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in vitro. Here, we report observations in vivo using the i.p. model of the multiply drug-resistant OVCAR-3 human ovarian carcinoma in nude mice which demonstrate that: (a) fatty acid synthase overexpression in OVCAR-3 is comparable to levels in primary human tumors assessed by immunohistochemistry; (b) fatty acid synthetic activity of OVCAR-3 is comparably elevated in vitro and in vivo and is 4 to >20-fold higher than normal murine tissues; (c) treatment with the specific fatty acid synthase inhibitor, cerulenin, markedly reduces tumor cell fatty acid biosynthesis in vivo; (d) fatty acid synthase inhibition produces regression of established ascites tumor; and (e) treatment with cerulenin causes reduction in ascites incidence, delay in onset of ascites, and significantly increased survival (P<0.04).

Abstract. Nuclear pleomorphism is an important diagnostic factor in tumour pathology. Traditionally, nuclear pleomorphism is evaluated qualitatively or semiquantitatively, often as a component of tumour grade; the molecular basis of nuclear pleomorphism, however, remains unclear. In this study, we investigated the quantitative effects on nuclear morphology of overexpressing pp32, a recently described nuclear phosphoprotein highly expressed in self‐renewing and neoplastic cell populations. Assessment of Feulgen‐stained transfected and control lines of AT3.1, a rat prostatic carcinoma cell line, using a computerized Cellular Image Analysis System (BD CAS‐200) showed that stable overexpression of human pp32 in AT3.1 cells is accompanied by marked increases in the coefficient of variation of nuclear shape, nuclear size and chromatin textures but not in DNA content. In contrast, stable transfection with control vector, with ras, or with bcl‐2 failed to affect nuclear morphology. Cell cycle analysis further showed that pp32‐related increases in variation of nuclear structure manifested principally in G1. These studies suggest that pp32 plays a role either directly or indirectly in the control of nuclear shape of G1 cells.

Human interferon-alpha 2 (IFN) was analyzed by homology search computer program with the use of protein primary structures data bases. Results indicate that four domains with heightened ability to form homology pairs with different proteins exist in the IFN molecule. These domains occupy regions 35-56, 72-85, 97-110 and 124-136, mainly between the alpha-helical cylinders on the tertiary structure models. Additionally, results show in IFN structure the presence of amino-acid motifs that create the opportunity for this cytokine to influence directly the processes of DNA functioning in cell nuclei.