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G Cruciani

Publications and source records attributed to G Cruciani.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparative molecular field analysis using GRID force-field and GOLPE variable selection methods in a study of inhibitors of glycogen phosphorylase b.

A primary goal in any drug design strategy is to predict the activity of new compounds. Comparative molecular field analysis (CoMFA) has been used in drug design and three-dimensional quantitative structure/activity relationship (3D-QSAR) methods. The CoMFA approach permits analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in biological activity with changes in chemical structure. One of the characteristics of the 3D-QSAR method is the large number of variables which are generated in order to describe the nonbonded interaction energies between one or more probes and each drug molecule. Since it is difficult to know a priori which variables affect the biological activity of the compounds, much effort has been devoted to developing methods that optimize the selection of only those variables of importance. This work focuses on some of the aspects involved in the selection of such variables, applied to a series of glucose analogue inhibitors of glycogen phosphorylase b, using the program GRID to describe the molecular structures and using a method of generating optimal partial least squares estimations (program GOLPE) as the chemometric tool. This data set, consisting of over 30 compounds in which the three-dimensional ligand-enzyme bound structures are known, is well suited to study the effect of different data pretreatment procedures on the final model used for the prediction of new drug molecules. By relying on our knowledge of the real physical problem (i.e., using the combined crystallographic and kinetic results), it has been shown that suitable data pretreatment and variable selection have been found that does not result in a significant loss of relevant information. Moreover, by using an appropriate scaling procedure, GOLPE variable selection minimizes the risk of overfitting and overpredicting.

Binding Sites↗
PubMed1994

High-dose intra-arterial plus intraperitoneal chemotherapy combined with hemofiltration in liver metastases from colorectal cancer.

AIMS: Twenty-three patients with liver metastases from colorectal cancer were entered into a prospective, phase II pilot study to evaluate the efficacy and feasibility of intra-arterial high-dose chemotherapy (IAHC) + intraperitoneal chemotherapy (IPC) combined with hemofiltration. METHODS: All patients had abdominal laparotomy to position a hepatic artery infusion port and in 15 cases an implantable system for IPC. A double-lumen filtration catheter was placed in the vena cava via the saphenous or femoral vein and connected to a modified hemofiltration unit. The treatment schedule consisted of mitomycin (30-50 mg/m2) and epirubicin (60-90) mg/m2) as IAHC combined with cisplatin (60 mg/m2) given in a 2000 ml saline solution by IPC. The high-dose IAHC-IPC was followed by 4 cycles of intra-arterial standard dose chemotherapy through the arterial port-a-cath (6 mg/m2 mitomycin and 20 mg/m2 epirubicin) and if possible by another cycle of high dose IAHC-IPC. RESULTS: We delivered a total of 31 cycles of IAHC, 21 of which were combined with IPC. Ten cycles of IAHC were administered without concurrent IPC because of painful adhesions, clinical contraindications or patient refusal. Seven of 23 patients (30%) were pretreated and with progressive disease after systemic chemotherapy. Among 22 evaluable patients, we obtained 2 complete remissions (9%) and 11 partial remissions (50%); moreover, 4 of 7 pretreated patients obtained a response to treatment. As a result, an objective tumor response was observed in 59% of patients (13/22). Therefore, a dose-response behavior was demonstrated also in tumors with a low chemosensitivity. The median duration of response and survival was 10 and 14 months, respectively. Toxicity was usually mild, but we reported one toxic death due to treatment complications. CONCLUSIONS: Further prospective randomized studies are needed to confirm the results of our study.

Adult↗
PubMed1994

A search for specificity in DNA-drug interactions.

The GRID force field and a principal component analysis have been used in order to predict the interactions of small chemical groups with all 64 different triplet sequences of B-DNA. Factors that favor binding to guanine-cytosine base pairs have been identified, and a dictionary of ligand groups and their locations is presented as a guide to the design of specific DNA ligands.

Codon↗
PubMed1994

Chloroquine reduces whole body proteolysis in humans.

The antimalaric drug chloroquine is a well known inhibitor of lysosomal proteolysis in vitro. The present study tests the hypothesis that therapeutic doses of the drug decrease proteolysis also in vivo in humans. Leucine kinetics were determined in 20 healthy volunteers given 12 and 1.5 h before the studies 250 and 500 mg, respectively, of chloroquine phosphate (n = 10) or similar tablets of placebo (n = 10). Chloroquine reduced the rates of leucine appearance, a measure of whole body proteolysis, from 2.45 +/- 0.08 to 2.19 +/- 0.08 mumol.kg-1.min-1 (P = 0.038) and those of nonoxidative leucine disposal, an estimate of whole body protein synthesis, from 2.16 +/- 0.08 to 1.95 +/- 0.06 mumol.kg-1.min-1 (P = 0.050). The drug resulted also in a marginally significant (P = 0.051) decrement in the plasma concentrations of glucose. The effects of chloroquine on protein turnover might be potentially useful in counteracting protein wasting complicating several catabolic diseases, whereas those on glucose metabolism can explain the sporadic occurrence of severe hypoglycemic episodes in malaria patients chronically treated with this drug.

Adult↗
PubMed1993

Conservative treatment for T2-T4 bladder cancer with primary chemotherapy and radiotherapy: a pilot study.

AIMS AND BACKGROUND: After radical cystectomy, with or without pelvic radiotherapy, more than 50% of patients affected by infiltrating bladder cancer died of distant metastases. Polychemotherapy yields 25% complete remissions (CR) in patients with invasive transitional cell bladder carcinoma; although many concerns exist about the duration of such CR. This study was undertaken with the aim of evaluating the efficacy and safety of an integrated chemo-radiotherapeutic treatment, in order to broaden indications to a conservative surgical therapy. METHODS: Thirty-three consecutive patients with bladder urothelial cancer T2-T4, N0, M0, have been treated. Patients received neoadjuvant chemotherapy (rescue-M-VEC) consisted of methotrexate 30 mg/sqm plus folinic acid 15 mg after 24 h on days 1, 15, 22; vinblastine 3 mg/sqm on days 1, 15 and 22; epidoxorubicin 30 mg/sqm on day 1; cisplatin 70 mg/sqm on day 1. This cycle was repeated on day 29. After 2 cycles of rescue-M-VEC, patients underwent pelvic cobalt teletherapy 40 Gy combined with low dose cisplatin 25 mg/sqm/week. After restaging, responding patients underwent further radiation therapy (24 Gy) as booster consolidation. RESULTS: After 2 cycles of chemotherapy and pelvic radiotherapy 14/31 evaluable patients (45.2%) achieved CR and 11/31 (35.4%) partial remission, with an overall response rate of 80.6% (25/31). With a median follow up of 21 months the actuarial survival rate at 24 months was equal to 79.8%. Eleven radical cystectomies were performed, 6 of which at restaging in non responding patients and 5 during the follow up due to relapse. Of the 25 patients selected for bladder conservation, 12 (48%) have not yet shown relapses. Three out of 31 (9.7%) patients died of distant metastases. No severe toxicity has been observed: moreover no patient developed stomatitis after chemotherapy. CONCLUSIONS: Our results seem encouraging but longer follow-up and further phase III studies need to be carried out to demonstrate the feasibility of conservative treatment in muscle infiltrating bladder cancer.

Aged↗
PubMed1993

Physiological increments in plasma insulin concentrations have selective and different effects on synthesis of hepatic proteins in normal humans.

These studies tested the hypothesis that physiological increments in plasma insulin concentrations have selective effects on the synthesis of hepatic proteins in humans. Leucine kinetics and fractional synthetic rates of albumin, fibrinogen, antithrombin III, and apoB-100 were determined in 6 normal subjects, on two different occasions during either the infusion of saline (control study) or a euglycemic-hyperinsulinemic (0.4 mU.kg-1 x min-1 for 240 min) clamp, by a primed-constant infusion of [1-14C]Leu. The insulin infusion significantly decreased the rates of nonoxidative Leu disposal (1.70 +/- 0.10 vs. control 2.06 +/- 0.09 mol.kg-1 x min-1), increased the albumin (7.2 +/- 0.4 vs. 6.2 +/- 0.6%/day), decreased the fibrinogen (18 +/- 1 vs. 23 +/- 2%/day), and antithrombin III (28 +/- 3 vs. 40 +/- 4%/day) fractional synthetic rate, whereas it did not affect the total apoB-100 (49 +/- 5 vs. 52 +/- 6%/day) fractional synthetic rate. Thus, the insulin-induced decrement in the estimates of whole-body protein synthesis (nonoxidative Leu disposal) represents the mean result of opposite effects of hyperinsulinemia on the synthesis of proteins with different functions. The positive effect of insulin on albumin synthesis may play an important anabolic role during nutrient absorption by promoting the capture of a relevant amount of dietary essential amino acids into the protein, whereas the negative effect of insulin on fibrinogen synthesis might, at least partially, account for the increased plasma fibrinogen concentrations previously reported in poorly controlled diabetic patients.

Adult↗
PubMed1992

An Italian experience of high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in germ cell tumours. Suggestions for future direction.

In this paper an Italian cooperative trial investigates the role of a high-dose regimen with carboplatin, etoposide and ifosfamide in germ cell tumours. Twenty-eight patients underwent one or two transplants. Seventeen with progressive disease. Nine in sensitive relapse and two with stable disease after salvage therapy. Toxicity was generally moderate: two deaths occurred at day 15 from ABMT (one from VOD and one from tumour growth). Five patients are alive and disease free at least 10 months follow-up. In highly pre-treated patients this high-dose combination seems to give an option of cure for relapsed patients. Early transplantation is suggested.

Adolescent↗
PubMed1990

Mitoxantrone (M) and vinblastine (V) in the treatment of advanced breast cancer.

Twenty-four patients with metastatic breast cancer, all but 1 pretreated with one or more chemotherapeutic regimens, were entered in a pilot study to assess toxicity and efficacy of the combination mitoxantrone and vinblastine. Dominant sites of metastases were viscera in 9 patients, bone in 10 and soft tissues in 5. All patients received mitoxantrone 10 mg/m2 i.v. on day 1 and vinblastine 1.7 mg/m2 by 4 hour infusion on days 3, 4 and 5, every 3-4 weeks. Objective responses (1 CR, 7 PR) were observed in 8 (38%) of the 21 evaluable patients. Median duration of response was 10.5 months. Of 12 patients pretreated with an anthracycline containing regimen, 4 responded (1 CR and 3 PR). Major toxicity was myelosuppression, grade 4 in 2 cases and grade 3 in 2 others. No evident alopecia was observed and only 1 case of grade 1 cardiac toxicity. In conclusion, mitoxantrone followed by vinblastine is an effective regimen in metastatic breast cancer also in pretreated patients, and previous anthracycline administration does not seem to reduce the percentage of response. Moreover, toxicity is generally mild.

Adult↗
PubMed1990

A comparative chemometric study of QSAR descriptors.

Traditional descriptors for Qsar models are compared with two alternative blocks obtained by computer chemistry tools: electronic densities and principal properties. All three sets show similar prediction abilities by PLS modelling.

Models, Chemical↗
PubMed1990

Chemometric approach in a QSAR study: the antibacterial and antimicotic activities of benzofused heteroaromatic derivatives.

In order to establish quantitative relationships between the antibacterial activities of a number of thienyl- and furyl-benzimidazoles and benzoxazoles, the biological data were measured homogeneously for a selected set of 16 representative compounds of the available set of 103. The data were analyzed by the PLS method. The results of linear PLS modelling and PLS response surface modelling permitted a straightforward interpretation of the structural features relevant to the activities and the prediction of a possible optimal structure.

Anti-Bacterial Agents↗
PubMed1989

High-dose etoposide and autologous bone marrow transplantation as intensification treatment in small cell lung cancer: a pilot study.

A pilot study was conducted in which 15 patients with small cell lung cancer (SCLC) with limited or extended disease were treated with high dose etoposide (600 mg/m2 daily for 3 consecutive days) followed by autologous bone marrow transplantation (ABMT). Twelve patients underwent a double graft. All had achieved complete or partial remission with conventional induction chemotherapy (adriamycin and etoposide, plus cisplatin in five cases). After ABMT six of the 15 patients did not receive radiotherapy to the chest; all but four patients received prophylactic brain irradiation. No toxic deaths were recorded during the period of aplasia. Eleven patients relapsed and died after ABMT. The median time to death was 18 months. One other patient died at 13 months of unknown cause. At the present time three patients are alive and free of disease at 54, 51 and 47 months respectively. This pilot study shows that high dose etoposide and ABMT is well tolerated as late intensification for responsive SCLC. Definite conclusions about its precise role in therapy cannot yet be drawn.

Adult↗
PubMed1989

QSARs and pesticides design.

A multivariate analysis of phytotoxicity and measured ecotoxicity data of a set of 30 herbicidal triazines was carried out. Results indicate that it is feasible to design triazines that combine limited ecotoxicity with high herbicidal potency.

Animals↗
PubMed1987

Applicability of local hyperthermia as adjuvant to systemic chemotherapy.

With the aim of verifying the in vivo applicability of local hyperthermia combined with chemotherapy, 13 patients with superficial metastases from different histologic types of carcinoma, mostly from head and neck cancer, were entered in a pilot study. The chemotherapeutic regimen was cis-platinum, 20 mg/m2/d X 5 days, bleomycin, 10 mg/m2 on days 8 and 12, methotrexate, 100 mg/m2 on day 15, followed after 24 by folinic acid. Hyperthermia, using a microwave apparatus, and chemotherapy were delivered simultaneously. Objective remissions were achieved in 54% of patients, within the hyperthermia field (1 CR and 6 PR). No serious toxicity was noted. Methotrexate distribution after local hyperthermia was evaluated in 8 patients. Response duration was not gratifying, except for patients successively treated with radiation. In conclusion, the combination of chemotherapy plus local hyperthermia deserves subsequent evaluation as part of adjunctive programs.

Aged↗
PubMed1987

Cyclophosphamide, methotrexate,5-fluorouracil, alternating with adriamycin and mitomycin C in metastatic breast cancer: a pilot study.

To explore the clinical applicability of the Goldie and Coldman hypothesis, we treated 28 patients with metastatic breast cancer with alternating non-cross-resistant chemotherapy. The patients received cyclophosphamide, 600 mg/m2, 5-fluorouracil, 600 mg/m2, methotrexate, 40 mg/m2, alternated every three weeks with adriamycin, 60 mg/m2, and mitomycin C, 10 mg/m2. Only one patient had previously received palliative chemotherapy. Six patients had received adjuvant CMF, and 17 patients had been pretreated with endocrine therapy (13 for advanced disease, 4 as adjuvant). Fourteen patients had bone involvement, and 10 had visceral metastases. A mean of 12 cycles was given to 24 evaluable patients. The objective response rate was 67%: 11 patients (46%) achieved complete and 5 (21%) partial remission. Response rate in soft tissues was 83.3%, in bone 50%, in liver 100%, and in lung 80%. The median duration of response was 14 months, with 7 patients still in remission. No life-threatening toxicity was observed. Our preliminary results support the validity of this approach and the efficacy of this combination chemotherapy. A large-scale randomized study is warranted.

Adult↗
PubMed1986

Modulated chemo-hormonotherapy in advanced breast cancer. A pilot study.

Twenty-two patients with advanced breast cancer have been treated with sequential chemo-hormonotherapy consisting of tamoxifen 20 mg/day orally for 14 consecutive days, followed by no therapy for ten days, then estrogen 0.625 mg/day orally for three days; the next day methotrexate 200 mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v.; after 24 hours folinic acid 200 mg/m2 i.v. and 5-fluorouracil 600 mg/m2 i.v. Fifteen patients were evaluable for response, 22 were evaluable for toxicity. All but one were heavily pretreated with chemo and/or hormonotherapy. Nine of 15 had previously received palliative CMF (cyclophosphamide, methotrexate, 5-fluorouracil) (mean 9 cycles), and one patient 12 cycles adjuvant CMF. Thirteen of 15 previously received tamoxifen (median treatment of 18 months). Six patients had multiple metastatic disease, while five had visceral involvement. They were all postmenopausal, with median age 57 years, and median disease-free interval 31 months. ER status was not known and the median ECOG performance status was 1. Overall response rate was 20%. Only one patient attained complete remission; 46.6% were stable disease and 33.3% progressive disease. Accepting that the response rate is very low in pretreated patients, this 20% can be significant. Ninety cycles were administered to 22 patients and the treatment was very well tolerated: both hematologic and nonhematologic toxicities were mild.

Aged↗
PubMed1984

The mid-term effects of radiotherapy on T and B lymphocytes: an evaluation of cellular immunity with standard methods and monoclonal antibodies.

The mid-term effects of radiotherapy on T and B peripheral lymphocytes of 15 patients treated for various malignancies were evaluated. All patients had a significant impairment of lymphocyte functions, as measured by blastogenesis after stimulation with phytohemagglutinin and pokeweed mitogen. Such impairment lasted for 1 year after the completion of radiotherapy, when numerical variability of T and B subpopulations, observed during and after radiation treatment, was restored to initial values.

B-Lymphocytes↗
PubMed1983

Clinical relevance of bone marrow biopsy in staging and follow-up of breast cancer.

Bone marrow biopsies by Jamshidi needle were performed in 106 breast cancer female patients. Sixty-four of them were in follow-up after mastectomy, and neoplastic involvement of marrow was found in 21 patients (32.8%). Among the 42 women undergoing staging before mastectomy, the incidence of marrow involvement was 11.9% (5 women, all with radiographic positivity). Of the 37 women, either in follow-up or in the staging phase, with bone metastases detected by roentgenographic and isotopic examination, the bone biopsy was positive in 23 (62.1%), and 7 histologically had micrometastases. Three women, without any radiographic or isotopic sign of metastases, had positive biopsies. A good correlation was found between the hydroxyproline:creatinine ratio and neoplastic involvement of bone marrow.

Biopsy↗