Comparative localization of cathepsin B protein and activity in colorectal cancer.

Cathepsin B is a lysosomal cysteine proteinase that may participate in cancer progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protein expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expression was moderate in stroma and variable in epithelium, whereas activity was mainly present in distinct areas of stroma directly underneath the surface of the colon and in epithelium at the surface of the colon. Stroma in adenomas and carcinomas contained moderate to high protein levels but little activity except for areas of angiogenesis, inflammation, and necrosis, in which activity was high. In adenomas and the majority of well-differentiated carcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the basement membrane. Protein and activity levels were low and diffusely distributed in cancer cells in the remainder of the well-differentiated and moderately differentiated carcinomas and in all poorly differentiated carcinomas. Invasive fronts in most cancers contained moderate protein levels but high activity. We conclude that (a) activity localization is essential to understand the role of cathepsin B in cancer progression, and (b) cathepsin B activity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necrotic.     

Changes in population sizes and distribution of fur seals at Marion Island

 Population censuses of the Antarctic fur seal (Arctocephalus gazella) and the sub-Antarctic fur seal (A. tropicalis) were conducted during the 1994/1995 breeding season at Marion Island. Pup numbers, determined from direct counts and a mark-recapture experiment, were used to estimate population sizes. Pup numbers of A. tropicalis showed a mean annual change of 2.0% over the previous 6 years, culminating in an estimated total population of 49, 523 for 1994/1995. The population appears to be entering the maturity phase of population growth and may therefore have recovered from the effects of uncontrolled sealing that ended in the early twentieth century. Numbers at the major colonies on Marion Island showed little change since 1989 and these sites may have reached carrying capacity. The extension of breeding to other parts of the island continues. Over the same period, A. gazella pup numbers showed a mean annual change of 17% and the total population numbered 1,205 in 1994/1995. This species has possibly entered the rapid recolonisation phase of population growth. A few hybrid seals were found. Received: 25 October 1995/Accepted: 14 April 1996     

Loss of heterozygosity on 17p in human breast carcinomas: defining the smallest common region of deletion

The marker D17S5, mapping to the short arm of chromosome 17, was recently reported by us and others to undergo frequent heterozygous deletion in human primary breast carcinomas, implicating the presence of a tumor suppressor gene in this region. To narrow down the location of this gene more precisely, we have performed a deletion-mapping study in an extended series of 78 breast carcinomas, using nine polymorphic markers for the short arm and two polymorphic markers for the long arm of chromosome 17. Partial allele losses on 17p were observed in nine cases, which, taken together, suggest that the target gene for the deletions maps to the region extending between the markers D17S5 (17p13.3) and D17S67 (17p12).