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Biomedical subjects

S Gandini

Publications and source records attributed to S Gandini.

At least 19 recordsLinked to original sources
PubMed2006

Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology.

AIM: To present our experience with sentinel lymph node biopsy (SLNB) performed in patients with multicentric breast cancer. METHODS: Between May 2001 and May 2004, 42 patients with multicentric breast cancer and a clinically negative axilla underwent lymphatic mapping either by a single subareolar (n = 25) or a double peritumoral/subdermal injection (n = 17) of 99Tc-HSA nanocolloids. The sentinel lymph node (SLN) was evaluated by intraoperative frozen section and axillary dissection was performed only in case of positive SLN. RESULTS: Mean age was 49 years (range 25-78). Mean number of SLNs identified by lymphoscintigraphy was 1.36 (range 1-5) and mean number of SLNs removed at surgery was 1.55 (range 1-5), with an identification rate of 100%. The mean number of hot spots identified by lymphoscintigraphy was similar in patients who underwent single or double injections (1.36 and 1.35, respectively). In 21 of 42 patients the SLN was positive, and in seven of these 21 patients the SLN was the only positive node. After a median follow-up of 24 months no overt axillary metastases occurred in patients with negative SLN. CONCLUSIONS: The number of SLNs is not dependent on the number and site of injections. SLNB is our standard procedure for nodal staging in patients with multicentric breast cancer and a clinically negative axilla.

Adult↗
PubMed2005

Systemic effects of surgery: quantitative analysis of circulating basic fibroblast growth factor (bFGF), Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) in patients with breast cancer who underwent limited or extended surgery.

BACKGROUND: To assess if feature, extent and duration of surgery could influence levels of systemic proangiogenic cytokines vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta). PATIENTS AND METHODS: We collected blood samples from 82 consecutive breast cancer patients who underwent various types of surgery, classified according to the magnitude of tissue injury in: minimal (quadrantectomy), moderate (mastectomy without reconstruction), and heavy [mastectomy followed by reconstruction with transversus recto-abdominal muscle cutaneous flap (TRAM)]. Samples were collected one day before surgery (D(-1)), at the end of surgical tumor removal (D0), and on 1st (D(+1)), 2nd (D(+2)) and 5th (D(+5)) day after surgery. Serum VEGF, bFGF and TGF-beta levels were measured by the enzyme immunoassay method. RESULTS: On average a continuous decrease was observed for all growth factors from the day before operation to the 5th day after operation. On day (D(+5)) an increase was observed for patients who underwent extended respect to moderate surgery. These differences were found statistically significant for bFGF and VEGF (p = 0.05 and p = 0.025 respectively). A statistically different trend for type of operation was observed also for TGF-beta at 24-48 h: a minor reduction, compared to time of operation, was observed for minimal surgery, an intermediate reduction for moderate surgery and a higher decrease for extended surgery. CONCLUSIONS: Angiogenic cytokines perioperative levels could be increased on 5th day (D(+5)) by extent of surgery and should induce perioperative stimulation of residual cancer cells. A better understanding of the time interval during which the sequelae of events in wound healing occur may be the basis for defining new therapeutic strategies that can interfere with tumor outgrowth sparing wound healing processes.

Aged↗
PubMed2005

Correlation between nutritional biomarkers and breast cancer: a case-control study.

A case-control study to explore associations between retinoids, tocopherols, total and beta-carotenes and breast cancer was conducted by analysing concentrations of these biomarkers in adipose tissue, cheek cells and plasma. A total of 414 French-Canadians in Montreal with new diagnoses of breast cancer were age-matched to 429 population-based controls. Subjects were interviewed using a questionnaire, and biological samples from 287 cases and 112 controls were collected within 3 months of the diagnosis. Mean beta carotene concentrations in cheek cells were significantly lower among controls. Odds ratios (ORs) from logistic regression analysis were used to compare higher and lower tercile concentrations. Significant positive associations were observed in adipose tissue for retinoid [OR=2.11; 95% CI (1.09-4.08)] and beta carotene [OR=3.18; 95% CI (1.70-5.93)]; in cheek cells for beta carotene [OR=2.22; 95% CI (1.21-4.50)] and for total carotenes [OR=2.94; 95% CI (1.59-5.42)] and in plasma for beta carotene [OR=1.53; 95% CI (0.80-2.93)] and total carotenes [OR=1.04; 95% CI (0.53-2.05)]. Among the control groups, significant Pearson correlations were observed between cheek cells and adipose tissue for total carotenes (r=0.27; p=0.01) and cheek cells and plasma (r=0.22; p=0.04). In contrast to previous works, this study shows that high concentrations of retinoids and carotenes in adipose tissue and cheek cells are associated with increased risk of breast cancer. However, all these studies are limited by small sample size. Although our study tested a limited number of controls, important associations were observed. These results suggest that the effect of disease on biomarkers is fundamental to the interpretation of epidemiological data. We suggest either that the high levels of these biomarkers found in cancer patients in this study may be due to the disease process that affects the pharmacokinetics of the biomarker or that the disease causes a change in dietary habits. In addition, in studies involving the application of biomarkers to cancer epidemiology it is imperative that a typical biomarker concentration is not associated with breast cancer risk before further examination of the methodological limitations of epidemiological studies investigating this relationship. Therefore, sample size, selection bias, information bias, and confounding should be considered in the design of studies investigating the aetiological relationship between biomarkers and breast cancer.

Adipose Tissue↗
PubMed2003

Effect of tamoxifen at low doses on ultrasensitive C-reactive protein in healthy women.

The use of tamoxifen as a breast cancer preventive agent may be contraindicated by an increased risk of endometrial cancer and venous thromboembolic events, particularly in postmenopausal women. Since these estrogenic effects may be dose-related, a dose reduction may reduce toxicity. We have recently shown a comparable activity of lower doses of tamoxifen on putative surrogate biomarkers of cardiovascular disease and breast cancer. To provide further insight into the effect of tamoxifen at low doses on the cardiovascular system, we compared the effect of three different doses on circulating levels of C-reactive protein (CRP), an independent risk marker for cardiovascular disease (CVD), which was lowered by tamoxifen at the standard dose of 20 mg day-1 in previous studies. We compared the changes in CRP after 2 months of either placebo (n = 24), or tamoxifen 10 mg alternate daily (n = 26), or 10 mg day-1 (n = 22), or 20 mg day-1 (n = 19) in healthy women aged 35-70 years. The median percent change was -2.2% (95% CI, -23.3 to 42.8) with placebo, -39.1 (95% CI, -59.9 to -28.7) with 10 mg alternate daily, -56.9% (95% CI, -68.6 to -38.4) with 10 mg day-1 and -42.9% (95% CI, -62.6 to 1.6) with 20 mg day-1 (P = 0.291 for the linear dose-response trend). Similar results were obtained when the data were classified according to blood tamoxifen concentrations, with a median reduction of 47% (95% CI, 65.5-36.3) for women with low tamoxifen concentrations (< 30 ng mL-1). We conclude that tamoxifen at low doses is able to lower ultrasensitive CRP and that this might be associated with a beneficial effect on CVD.

Adult↗
PubMed2001

Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions.

Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A1*4 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures.

Arylamine N-Acetyltransferase↗
PubMed2001

Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.

The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.

Anticarcinogenic Agents↗
PubMed2000

Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients.

A meta-analysis was carried out, in order to summarise published data on the relationship between breast cancer, fruit and vegetable consumption and/or the intake of beta-carotene and vitamin C. Relative risks were extracted from 26 published studies from 1982 to 1997. Random and fixed effects models were used. Between studies, heterogeneity was found for vegetables, fruit, vitamin C but not for beta-carotene. Summary relative risk (RR) estimates based upon a random effects model, except for beta-carotene, for 'high consumption' compared with 'low consumption', derived from the studies satisfying the inclusion criteria were as follows: vegetable consumption: RR=0.75 (95% CI (confidence interval) 0.66-0.85) from 17 studies; fruit consumption: RR=0.94 (95% CI 0.79-1.11) from 12 studies; vitamin C: RR=0.80 (95% CI 0.68-0.95) from 9 studies; beta-carotene: RR=0.82 (95% CI 0.76-0.91) from 11 studies. This analysis confirms the association between intake of vegetables and, to a lesser extent, fruits and breast cancer risk from published sources. Increasing vegetable consumption might reduce the risk of breast cancer.

Ascorbic Acid↗
PubMed1999

Age-period-cohort models: a comparative study of available methodologies.

This article compares the estimates produced by a number of solutions to the identifiability problem in age-period-cohort models using a series of disease rates with known structure. The results suggest that only those methods that are based on the estimable functions such as curvatures can be recommended for use in all circumstances. The other common approaches that give parameter estimates that are easier to interpret all have induced bias in the estimates. In particular methods based on the minimization of a penalty function to achieve identifiability are only of use if there is no change in the rates with time. Any drift in the rates tends to be expressed as a cohort-based trend. The methods based on individual records introduce a bias if there is a strong age effect in the direction of a decreasing cohort trend and a compensating increase based on period effects. The nonparametric testing method has little power to detect trends in the rates in small tables but ascribes a strong drift in the rates to both period and cohort trends. With careful interpretation, all methods estimate nonlinear components correctly.

Age Factors↗
PubMed1999

Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women.

PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. PATIENTS AND METHODS: We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. RESULTS: The means (+/- SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 +/- 15.1 and 43.7 +/- 22.5 with 10 mg every other day, 51.2 +/- 24.1 and 90.7 +/- 48.0 with 10 mg/d, and 136.0 +/- 52.7 and 230.6 +/- 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. CONCLUSION: An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent.

Antineoplastic Agents, Hormonal↗
PubMed1998

Biologic activity of tamoxifen at low doses in healthy women.

BACKGROUND: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use. METHODS: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/ alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. RESULTS: After adjustment for the baseline values, there were reductions in circulating levels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which showed a decrease, was the only parameter exhibiting change. CONCLUSIONS: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.

Adult↗
PubMed1978

Effect of dopamine infusion on gastric and pancreatic secretion and on gastrin release in man.

The effect of dopamine infusion on basal and pentagastrin-stimulated gastric secretion, on basal and secretin-CCK-PZ-stimulated pancreatic secretion, and on basal and meal-induced gastrin release has been evaluated in healthy volunteers. Both basal and stimulated gastric acid secretion were significantly inhibited during dopamine infusion with a significant rebound to pre-infusion values after discontinuing dopamine. These effects were prevented by pretreatment with the antidopaminergic drug, metoclopramide. A slight but now significant decrease in amylase and bicarbonate outputs was also observed during dopamine infusion, while gastrin release did not change. These data suggest the existence of dopaminergic mechanisms in the regulation of gastric acid secretion in man.

Adult↗
PubMed1977

[Cutaneous iontophoresis of hyaluronidase in the treatment of hemorrhages in hemophilic patients].

After a surgery of the theoretical background of iontophoretic technic and the physico-chemical properties of hyaluronidases, a clinical application is presented, based on over 500 hemophilic patients treated percutaneously, in cases both of hemarthrosis and hematomas. The results are presented and discussed. The conclusion is that hyaluronidase iontophoresis is useful and should be performed together with the other measures for the prevention and the treatment of the damages produced by hemorrhages in hemophilic patients.

Hemophilia A↗