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Biomedical subjects

G Cruciani

Publications and source records attributed to G Cruciani.

64 records · Page 4Linked to original sources
PubMed1980

[Hydroxyprolinuria and bone metastases of breast cancer].

The urinary excretion of Hydroxyproline (OH-P), evaluated as OH-P/creatinine ratio, has been examined in the follow up of 142 breast cancer patients. The mean value obtained in the women with bone lytic lesions, prior to treatment, was 5.3 +/- 1.9 (min. 3, max. 9), whereas in the women without bone metastases it was 1.7 +/- 0.5 (min. 0.6, max. 3), similar to the control group. The patients affected by osteoplastic lesions had a normal OH-P/creatinine ratio. The highest values of OH-P/creatinine ratio were found in women with bone marrow infiltration, ascertained by bone needle biopsy. In the group of patients with bone lytic metastases, a good correlation between changes of OH-P/creatinine ratio and response to hormonal or chemotherapeutic treatment has been observed. Therefore the OH-P/creatinine ratio could be effectively useful, with other clinical parameters, in the follow up of breast cancer patients.

Bone Neoplasms↗
PubMedDate not supplied

Progress in predicting human ADME parameters in silico.

Understanding the development of a scientific approach is a valuable exercise in gauging the potential directions the process could take in the future. The relatively short history of applying computational methods to absorption, distribution, metabolism and excretion (ADME) can be split into defined periods. The first began in the 1960s and continued through the 1970s with the work of Corwin Hansch et al. Their models utilized small sets of in vivo ADME data. The second era from the 1980s through 1990s witnessed the widespread incorporation of in vitro approaches as surrogates of in vivo ADME studies. These approaches fostered the initiation and increase in interpretable computational ADME models available in the literature. The third era is the present were there are many literature data sets derived from in vitro data for absorption, drug-drug interactions (DDI), drug transporters and efflux pumps [P-glycoprotein (P-gp), MRP], intrinsic clearance and brain penetration, which can theoretically be used to predict the situation in vivo in humans. Combinatorial synthesis, high throughput screening and computational approaches have emerged as a result of continual pressure on pharmaceutical companies to accelerate drug discovery while decreasing drug development costs. The goal has become to reduce the drop-out rate of drug candidates in the latter, most expensive stages of drug development. This is accomplished by increasing the failure rate of candidate compounds in the preclinical stages and increasing the speed of nomination of likely clinical candidates. The industry now understands the reasons for clinical failure other than efficacy are mainly related to pharmacokinetics and toxicity. The late 1990s saw significant company investment in ADME and drug safety departments to assess properties such as metabolic stability, cytochrome P-450 inhibition, absorption and genotoxicity earlier in the drug discovery paradigm. The next logical step in this process is the evaluation of higher throughput data to determine if computational (in silico) models can be constructed and validated from it. Such models would allow an exponential increase in the number of compounds screened virtually for ADME parameters. A number of researchers have started to utilize in silico, in vitro and in vivo approaches in parallel to address intestinal permeability and cytochrome P-450-mediated DDI. This review will assess how computational approaches for ADME parameters have evolved and how they are likely to progress.

Catalysis↗
PubMedDate not supplied

Hyperthermia and paclitaxel--epirubicin chemotherapy: enhanced cytotoxic effect in a murine mammary adenocarcinoma.

Multimodality therapy is considered of great interest in the treatment of locally advanced solid tumours. In previous experiments, paclitaxel (TX) and epirubicin (EP) were combined with different schedules, obtaining a superadditive effect on the growth of a murine mammary carcinoma. In the present study, the authors have analysed the possible use of hyperthermia (HT) to increase the efficacy of TX and EP combinations. Tumours were transplanted into the right hind foot of female hybrid (C3D2F1) mice. Both TX and EP were administered i.p in two different doses. Hyperthermia was applied using a water bath at 43.2 degrees C for 1 h. Results were analysed in terms of Tumour Growth Delay (TGD). The maximum tolerated doses in combined protocols were TX 45 mg/kg and EP 9 mg/kg, with an interval time of 24h between the two administrations. TGDs of some of the schedules performed are reported: EP + HT = 11 days, TX + HT = 16 days, TX + EP (with an interval time of 24 h) = 14 days, and TX + EP + HT = 22 days. In the experimental model, HT significantly increases the effects of both TX and EP. TX + EP + HT treatment is the most effective (significantly different from TX + EP), but not in a significant way when compared to TX + HT treatment. These results suggest the possible use of a TX + HT protocol for local tumour response, whereas EP could be added in order to achieve a better systemic control.

Adenocarcinoma↗
PubMedDate not supplied

Combined use of gemcitabine and radiation in mice.

The aim of this study was to explore, in a murine tumor, if the effectiveness of radiation, in doses and schedules commonly used in clinical practice is potentiated by the combined use of the recently developed drug gemcitabine. Gemcitabine (30-360 mg/kg b.w.) was administered i.p. in female C3D2F1 mice bearing a mammary adenocarcinoma alone or combined with X-rays. Firstly, gemcitabine (single administration) was administered alone or at 20 min, 4 h, and 24 h before X-ray treatments. The significant effect observed only at 24 h time interval, depended on the X-ray dose and not on the gemcitabine dose. Secondly, 4 gemcitabine administrations every 3 days were used in fractionated combined schedules (overall treatment time of 10 days). We studied the relationship among different doses of gemcitabine, alone or combined with 10 daily X-ray treatments (2 Gy/fraction). We observed an interactive effect of gemcitabine up to its threshold dose of 60 mg/kg/fraction. Furthermore, 10 X-ray daily treatments and 4 X-ray treatments every 3 days (total doses 20-40 Gy) were performed with gemcitabine 60 mg/kg/fraction to study the effect of different doses and schedules of X-rays. Tumor growth delays increase with higher X-ray doses, and this occurs more with 4 X-ray treatments than with 10 X-ray treatments. Our results re-affirm the uselessness of high gemcitabine doses, and indicate the effectiveness of combined gemcitabine-radiation fractionated protocols.

Animals↗
PubMedDate not supplied

4'-Epi-doxorubicin and hyperthermia in a murine mammary carcinoma: influence of the dose and fractionation.

Our aim was to analyse the dose-response rate of 4'-epi-doxorubicin (EP) alone and of EP combined with hyperthermia (HT) treatments in tumor-bearing mice. A spontaneous mammary carcinoma, transplanted into the right foot of female hybrid (C3H/RIxDBA/2J) mice, was used. EP (from 5 to 30 mg/kg) was administered i.p. and local HT (45-60 minutes at 42 or 43 degrees C) was carried out. Mice were treated with EP and/or HT in 1, 2 or 3 doses at 8 day intervals; in the case of 3 HT treatments EP was administered before the first or before each HT session (same EP total dose). When EP was given alone, in 1 or 2 fractions, results showed a clear dose-response relationship: tumor growth delay depended on the total dose only. Combining different EP single doses and 1 HT treatment (43 degrees C), an additive effect and perhaps a synergistic effect at the highest doses was observed. Among all tested combinations, the best results were observed combining 3 HT with only 1 EP treatment.

Animals↗
PubMedDate not supplied

[Four year follow-up of social adjustment of a cohort of schizophrenic patients].

Sixty-seven first episode schizophrenic patients (PSE-Catego criteria) have been included in this study in order to evaluate their prognosis and the factors predictive of their evolution. Potential predictive factors consisted of anamnestic and demographic data, scores on the Disability Assessment Schedule (DAS-WHO) and relatives' Expressed Emotion index (EE), measured by the Camberwell Family Interview (CFI). The outcome was assessed monthly by the Global Assessment Scale (GAS/DSM III-R). At four years, 39 patients (58%) were still being followed. 33% of the patients presented a good evolution (EGF > or = 51) and 67% of the patients a bad evolution (EGF < 51). Four factors predictive of the psychosocial adaptation were extracted using regression analysis: premorbid psychosocial evolution, EE, sex and psychiatric family history. These 4 factors predicted correctly 85% of cases. Moreover, the monthly follow-up of these patients pointed to three types of evolution: the patients presenting a good and stable evolution (22%), those presenting a bad and stable evolution (33%) and those presenting an oscillating evolution which fluctuated between good and bad periods (44%). However, no predictive factors of the psychosocial adaptation of these oscillating patients could be identified through the statistical analysis. These results take all their importance regarding the treatment of schizophrenic patients, for whom the therapeutic plans which have to be settled should take into account their prognosis in the most precise manner. Moreover, the predictive value of EE on psychosocial adaptation for a 4 years period is confirmed.

Adolescent↗