Boronated porphyrins in NCT: Results with a new potent tumor localizer

Several chemical methods are available for the solubilization of boronated porphyrins. We have previously reported the tumor localization of nido carboranyl porphyrins in which the icosahedral carborane cages have been opened to give B/sub 9/C/sub 2/ anions. One of these species has shown tumor boron levels of nearly 50 ..mu..g B/g when delivered by week-long subcutaneous infusions. We report here recent in vivo experiments with a new, highly water-soluble porphyrin based on the hematoporphyrin-type of compound in which aqueous solubility is achieved using the two propionic acid side chains of the ''natural'' porphyrin frame. 7 refs

Keeping those telomeres short! an innovative intratumoral long-term drug delivery system

Telomerase activation and an alternative lengthening of telomeres (ALT) mechanism are two telomere-lengthening cancer cell survival mechanisms elicited by both chemo- and/or radiotherapy. Telomere lengthening interferes with cell lethality and results in the immortalization of cancer cells. To counteract these mechanisms, we developed a drug delivery system (DDS) consisting of a polymeric implant that is inserted directly into tumors. The DDS releases, continuously and gradually, a cationic porphyrin (PdTMPyP4) for >30 days after a single application, and inhibits telomerase activation. The PdTMPyP4 porphyrin is incorporated into a poly(co-glycolic lactic)acid (PLGA) polymer, solidified and cut into small rods. PdTMPyP4 release from the rods was measured spectrophotometrically over time. Uptake of Pd in the DNA of in L428 Hodgkins lymphoma cells was measured by ICP-MS, and telomerase activation by the TRAP assay. The rods were placed into the growth medium of cells whose growth rate was measured for 11 and 19 days. The cylinders were also inserted directly into KHJJ murine mammary tumors borne on the thighs of BALB/c mice and the tumor growth rate measured. In vitro, >10^9Pd atoms were measured in the DNA of each L428 cell and telomerase activity was reduced by ~15 % within 24 h. A one-time application of the rod in the cell medium induced a factor of >5 greater lethality compared to a blank rod or untreated controls. In vivo, a one-time insertion of the rod into tumors resulted in the retardation of the growth rate by factors of 3-5 compared to untreated controls. Systemic uptake after intratumoral insertion of the rod was negligible. The results suggest that the direct intratumoral insertion of a PdTMPyP4-containing polymeric rod would be of benefit as an adjuvant treatment for patients undergoing chemo- or radiotherapy. By preventing the lengthening of telomeres and therefore the unrestricted growth of cancer cells, our DDS will provide a significant therapeutic advantage to these treatments without affecting normal tissues

Characterization of biological types of cattle: indicator traits offertility in beef cows

Genetic diversity among breeds of cattle allows producers to select animals for specific environments or market conditions. Reproductive efficiency is a multi-component trait that is largely influenced by environmental influences such as health and nutritional status; however, there are clearly genetic components to reproductive efficiency, and breed differences in a number of indicator traits associated with fertility and cow productivity have been identified. Historical indicators of fertility include scrotal circumference, age at puberty, and postpartum interval. Both age at puberty and postpartum interval are laborious traits to collect in heifers and cows because they require many days of detection of behavioral estrus. In recent years, the addition of ultrasonography to management practices has allowed for the collection of female traits such as follicle diameter, antral follicle counts, and fetal age that are not as labor intensive. These additional diagnostic traits provide novel phenotypes for the identification of genetic markers of fertility and cow productivity, which would be the ultimate goal. Genetic markers of the number of follicles in the bovine ovary have the potential to identify heifers that will be highly productive cows. Furthermore, identifying and understanding the genes that control various reproductive traits and the response to stressors, such as temperature and nutrient availability, could improve production efficiency by improving management and breeding decisions in a wide range of production environments