Gemcitabine as single agent therapy in advanced non small cell lung cancer and quality of life in the elderly.

BACKGROUND: The aim of this study is to test the efficacy of gemcitabine as single agent therapy in advanced non-small cell lung cancer in the elderly by the evaluation of the clinical response, the survival increase and the quality of life. METHODS: Nineteen patients (age >65 years) with a PS >2, bearing an advanced non-small cell lung cancer (IIIb-IV) not treated with chemotherapy before, were charged between December 1996 and December 1998. Sixteen patients were treated with gemcitabine at the dose of 1000 mg/mq 1-8-15 every 28 days. CT scan, X-rays and skeletal scintigraphy were used in the evaluation of the therapeutic response. The toxicity was estimated by following WHO indexes. The quality of life and the modification of the specific symptoms were estimated by particular tests (Spitzer Index, IADL, EORTC-LC13). RESULTS: One complete response (6%), 4 partial responses (25%), 7 cases of illness stabilization (43%), 4 cases of illness progression, were shown. One year of survival was found in 43% of cases with a 14 week of therapeutic response and a global survival ratio of 12.4 weeks. Only 2 cases (12.5) of medium grade G3-leucopenia were found. All patients improved their quality of life (IADL and Spitzer indexes) with reduction of symptoms, (EORTC-LC13) and increase of self-agin and relationships. CONCLUSIONS: The effectiveness of gemcitabine as single agent therapy as not yet been tested due to the scanty number of patients, nevertheless it must be considered in relation to the improvement of the patient s quality of life.

Adjuvant treatment for breast cancer in the elderly.

Eighty one patients with breast cancer stages I, II and III (T3a) were given adjuvant treatment with tamoxifen (Nolvadex), chemotherapy, or both. Most patients had estrogen and progesterone receptors measurement. Twenty one (63.6%) patients of the tamoxifen group were node positive, all 25 (100%) of the chemotherapy plus tamoxifen group and 13 (56.5%) of the chemotherapy alone group. Tamoxifen was administered for at least 3 years. Disease free survival and overall survival were substantially similar after treatment with tamoxifen or chemotherapy plus tamoxifen. Side effects were more numerous and severe in patients given chemotherapy. In receptor positive elderly breast cancer patients tamoxifen represents an excellent adjuvant therapy independently of disease stage. Chemotherapy should be reserved for subjects at high risk of recurrence in controlled clinical trials.

Age-related variations in plasma and liver lipids of Yoshida rats: a comparison with Wistar rats.

Lipoprotein and liver lipids of spontaneously hyperlipidemic Yoshida rats were compared with those of normolipidemic Wistar animals for studying their age- and strain-related differences. Both strains showed an age-related increase in the total plasma cholesterol concentration. However, the Yoshida strain had a higher content of cholesteryl esters and triglycerides than the Wistar strain in both young and adult animals (2- and 8-month-old animals, respectively). The free cholesterol content was also higher, but only in the 8-month-old animals. Both strains showed an age-related increase in the proportion of HDL1 and a symmetrical decrease in both the HDL2 and HDL3 subfractions, but the variations were more evident in the Yoshida strain. The study of strain-related differences suggested that the spontaneous hypertriglyceridemia of the Yoshida strain was not only related to the higher amount and proportion of the VLDL fraction, but also to the higher content of triglycerides in the LDL fraction. The livers of Yoshida rats accumulated more triglycerides (with an age-related progression) than those of Wistar rats. The major lipid classes in the liver of Yoshida rats contained a significantly higher proportion of monounsaturated fatty acyls. Furthermore, this proportion showed an age-related increase in all the lipid classes, but in cholesteryl esters. This suggested that liver desaturases had a relevant role in the development of hyperlipidemia, and of its age-related variations, in the Yoshida strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of age on hepatic uptake of HDL1-cholesterol in male Wistar rats with bile duct cannulation.

We have shown previously that the age-dependent increase in plasma cholesterol levels observed in male Wistar rats is associated with relevant changes in the lipoprotein pattern (in particular, with a much higher proportion of the HDL1 class) that are evident in animals from the age of 9 months. In this study, the possibility that a decreased catabolism of HDL1 cholesterol may cause this is evaluated by infusing this lipoprotein fraction labeled with [14C]cholesterol into both young (3.5 +/- 0.5 months) and adult (13.0 +/- 1.0 months) male Wistar rats with a permanent biliary drainage. The clearance of radioactivity from the blood compartment was slower in the older animals than in the younger ones. Conversely, the incorporation of radioactivity into plasma cholesteryl esters and the secretion of radioactivity into bile was higher in the younger animals. These results support the hypothesis that the age-related increase in HDL1 proportion is due, at least in part, to a slower liver catabolism of HDL1-cholesterol.

Expression of epidermal and nerve growth factor receptors in human thymus and thymomas.

The expression of epidermal growth factor (EGF) and nerve growth factor (NGF) receptors has been investigated by immunohistochemical analysis in eight normal human thymuses and in 15 thymomas. Thymomas were classified into five different histological types--medullary, mixed, predominantly cortical, cortical thymoma and well-differentiated thymic carcinoma. In fetal and paediatric normal thymus, EGF-receptor was expressed by subcapsular, cortical and medullary epithelial cells, whereas immunoreactivity for NGF-receptor was detected on only subcapsular and medullary epithelial cells. In thymomas, independent of their histological type, EGF-receptor was expressed by a large majority of epithelial cells. In contrast, the pattern of expression of NGF-receptor in thymomas was different for the various histological types. These findings indicate that the expression of both EGF and NGF receptors in human thymomas substantially reflects their expression in normal thymus, and suggest that EGF and NGF may play a role in the ontogenesis of the human thymus as well as in the histogenesis of thymomas.

Age-related changes in blood and liver lipids of male Wistar rats.

The results of this study indicate that the age-dependent plasma cholesterol increase observed in male Wistar rats is correlated with changes in both the distribution of high-density lipoprotein fractions and the storage of hepatic cholesterol. Specifically, the lipoprotein distribution showed a significant increase in the proportion of HDL(1) and a symmetrical decrease in both the HDL(2) and HDL(3) fractions during the 3 month to 18 month age period. There were no significant changes in the very-low density and low-density lipoprotein fractions. The chemical composition of lipoproteins showed many age-related variations, especially in the proportion of cholesteryl ester and in the distribution of HDL subfractions. A study of fatty acyl composition of the major lipid classes showed that, within cholesteryl ester found in liver, there was an increase in the proportion of saturated fatty acids. Polyunsaturated fatty acids increased in the cholesteryl esters found in high-density lipoproteins of older rats. These observations suggest that the age-dependent accumulation of body cholesterol occurs by a reduced catabolism of HDL(1) fraction, and modifications in plasma and liver lipids.

Influence of age on the lipoprotein profile of male Wistar rats.

This study shows that the age-dependent increase in plasma cholesterol levels of the rat is correlated with changes in the distribution of the high-density lipoprotein (HDL) fractions. In particular, it has been shown that when the that of older animals (up to 18 months of age) the level of HDL1 fraction displays a relevant increase which derives from a proportional decrease in the levels of both HDL2 and HDL3 fractions. No relevant change is observed in the distribution of very-low density and low-density lipoprotein fractions. The distribution of the major components present in each lipoprotein fraction isolated evidences that cholesteryl ester proportion has an age-related increase in all the fractions except the HDL2. Furthermore, also the total plasma concentration of lipoproteins shows an age-related increase. The results obtained in this study with male Wistar rats suggest that animals older than 10 months can be used as an experimental model for dietary and pharmacological studies on age-related cholesterol alterations.