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Epidemiological studies provided the first evidence that COX may be involved in the pathogenesis of cancer. In the process of carcinogenesis and in the route of intracellular signalling during carcinogenesis, COX-2 expression may be a universal phenomenon. In general, COX-2 is up-regulated throughout the tumorigenic process, from early hyperplasia to metastatic disease. COX-2 has been reported to be constitutively overexpressed in a variety of malignancies and is frequently constitutively elevated in prostate carcinoma. COX-2 was consistently overexpressed in premalignant lesions such as prostatic intraepithelial neoplasia, and carcinoma. Cases are described with evolution of proliferative inflammatory atrophy of the prostate and prostate carcinoma. The increase of evidence implicating COX-2 in cancer has stimulated clinical trials to investigate the efficacy of selective COX-2 inhibitors in individuals at risk for human cancer. Regarding prostate carcinoma there is much direct or indirect evidence to support the use of COX-2 inhibitors in this disease. Trials using these drugs in familial adenomatous polyposis (FAP) and other patients with a high risk of colorectal carcinoma are ongoing. [ABSTRACT FROM AUTHOR]

The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring. [ABSTRACT FROM AUTHOR]

Stem cells, as classically defined, are cells with a capacity to self-renew and to generate daughter cells that can differentiate down several cell lineages to form all of the cell types that are found in the mature tissue. Stem cells and tumour cells have many similar features, including infinite lifespan, self-renewal, multidrug resistance, telomerase expression and, in the instance of the prostate, androgen independence. Evidence supports a role for stem cells in the etiology of many types of cancer. The evolution of androgen-independent prostate carcinoma may reflect the emergence of stemlike prostate tumour cells. Because cancer may be a disease of stem cell lineages and Shh-Gli signalling controls the behaviour of precursors and of cells with stem cell properties in the mammalian tissues, prostate cancer might derive from inappropriate expansion of prostatic epithelial stem cell lineages caused by abnormal Shh-Gli function. This review attempts to integrate these recent results. [ABSTRACT FROM AUTHOR]

A new polymerase chain reaction (PCR)-based method is described for the isolation of clones of interest from a library when only part of a sequence is available. In actuality, this occurs with many genomes that have been partially sequenced using a random strategy. The method presented here, discriminating clusters by PCR (DCbyPCR), is a nonradioactive and improved alternative to colony hybridization. [ABSTRACT FROM AUTHOR]

A recombinant strain of Saccharomyces cerevisiae, secreting β-galactosidase from Kluyveromyces lactis, grew efficiently with more than 60 g lactose l-1. The growth rate (0.23 h-1) in a cheese-whey medium was close to the highest reported hitherto for other recombinant S. cerevisiae strains that express intracellular β-galactosidase and lactose-permease genes. The conditions for growth and β-galactosidase secretion in this medium were optimized in a series of factorial experiments. Best results were obtained at 23 °C for 72 h. Since the recombinant strain produced less than 3% ethanol from the lactose, it was also assayed for the production of fructose 1,6-bisphosphate from cheese whey, and 0.06 g l-1 h-1 were obtained. [ABSTRACT FROM AUTHOR]

Several Saccharomyces cerevisiae strains with a super-secreting phenotype have been transformed using a secretion plasmid containing the LAC4 gene and have proven to be effective in the secretion of Kluyveromyceslactis β-galactosidase. The strain CGY1585 (ssc1-1) showed the highest secretion (1.7 EU ml-1) in the culture medium. As far as we know, Kluyveromyceslactis β-galactosidase is the largest sized protein and the only intracellular one among those secreted by these mutants hitherto. The recombinant strains all grew in lactose media. [ABSTRACT FROM AUTHOR]