Immunohistochemical Detection of Carcinogen-DNA Adducts and DNA Repair in Mouse Skin

4-Hydroxyaminoquinoline 1-oxide (4HAQO) and (±)-trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroben-zo[a]pyrene (BP-DE)-DNA adducts were immunohisto-chcmically demonstrated in the nuclei of mouse skin using antibodies directed against carcinogen (4HAQO or BP) modified DNA. The specificity of the immunostaining was confirmed by several tests, including preincubation of the antibody with carcinogen modified DNA or related molecules, and digestion of the sections with DNase.Subcutaneous injection of 4HAQO dissolved in isotonic solution into an isolated portion of the mouse skin clamped off with ring-shaped forceps resulted in dose-dependent generation of DNA adducts in the nuclei of epithelial cells, fibroblasts, and panniculus carnosus cells. BP-DNA adducts could also be similarly detected dose-dependently in the nuclei of skin cells after local application of BP-DE. Nuclear staining was absent in animals injected with isotonic solution alone, and the intensity of staining correlated well with the level of unscheduled DNA synthesis (UDS) demonstrated autoradiographically after treatment with 4HAQO. Killing of mice at different time points after a single injection of 4HAQO revealed a gradual decrease in the intensity of the staining. Thus the postulated generation and repair of DNA adducts can be followed at the cellular level using the presently described method. J Invest Dermatol 92:275S–279S, 198

Molecular and Phenotypic Profiling for Precision Medicine in Pancreatic Cancer: Current Advances and Future Perspectives

Pancreatic cancer is the most common lethal malignancy, with little improvement in patient outcomes over the decades. The development of early detection methods and effective therapeutic strategies are needed to improve the prognosis of patients with this disease. Recent advances in cancer genomics have revealed the genetic landscape of pancreatic cancer, and clinical trials are currently being conducted to match the treatment to underlying mutations. Liquid biopsy-based diagnosis is a promising method to start personalized treatment. In addition to genome-based medicine, personalized models have been studied as a tool to test candidate drugs to select the most efficacious treatment. The innovative three-dimensional organoid culture platform, as well as patient-derived xenografts can be used to conduct genomic and functional studies to enable personalized treatment approaches. Combining genome-based medicine with drug screening based on personalized models may fulfill the promise of precision medicine for pancreatic cancer

Transient Effectiveness of an Oral 5-Fluorouracil Derivative, S-1, for Epirubicin, Cyclophosphamide and Paclitaxel Refractory Skin Metastases from Possible Occult Breast Cancer in a Male

Recent chemotherapies for skin metastases from breast cancer have shown to be effective for regression, disappearance, and favorable quality of life. We describe the case of a 76-year-old male showing transient effectiveness with an oral 5-fluorouracil derivative, S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate), for epirubicin, cyclophosphamide and paclitaxel refractory skin metastases from possible occult breast cancer. The male patient was initially diagnosed as having lymph node metastases in the left axilla as possible occult breast cancer. The skin metastases developed after chemotherapy with a combination of epirubicin and cyclophosphamide, subsequent chemotherapy with paclitaxel, and radiotherapy. Chemotherapy with paclitaxel was resumed for skin metastases, but it was not effective. Alternative chemotherapy with the oral agent S-1 was administered. The skin metastases completely disappeared after the second course, but recurred at the end of the third course. This case suggests that S-1 may be a candidate for chemotherapy for skin metastases from occult breast cancer in males

チリにおける経済法(二)

11 full imprès, b/n. Els fulls d’aquesta sèrie corresponen a la divisió 12 x 8 de la malla de distribució del Mapa topográfico nacional de España 1:50 000.80 x 60 cm1:5 000254 pp