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Biomedical subjects

F Pensa

Publications and source records attributed to F Pensa.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between human mammaglobin mRNA expression in breast cancer tissue and clinico-pathologic features of the tumors.

Human mammaglobin (hMAM) has recently been recognized as a breast associated glycoprotein. Although the biological role of hMAM is unknown, it has been previously reported that hMAM gene expression is a marker of low biological and clinical aggressiveness of breast cancer (BC). In this study, 148 cases of BC tissues were investigated for hMAM mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). In order to evaluate its prognostic value, hMAM was correlated with age of patients, type and size of tumor, nodal stage, histologic grade, c-erbB-2 over expression, Ki67 labelling index, estrogen receptor (ER) status and progesterone receptor (PGR) status. Fisher's exact test was used to examine the association between different parameters and hMAM. hMAM was expressed in 138/148 (93%) of BC tissues examined. Among the 10 hMAM negative cases, 8 were invasive ductal carcinomas (microscopically higher G3 grade) and 2 infiltrating lobular carcinomas. We found a significant association (p = 0.020) between absence of hMAM mRNA and G3 histologic grade but not with any other prognostic parameters studied. The present study indicates that lack of hMAM expression is restricted to the BC with G3 grading. Further studies are needed to clarify the biological basis and the clinical significance of our results.

Adult↗
PubMed2002

A dose finding study of carboplatin and gemcitabine in advanced non-small cell lung cancer.

The excellent activity of the cisplatin-gemcitabine combination and favorable toxicological profile of carboplatin are the basis of carboplatin-gemcitabine combination therapy for non-small cell lung cancer. We carried out a dose-finding study with the aim of establishing the maximum tolerated dose (MTD) of carboplatin on day 1 in combination with gemcitabine at the dose of 1000 mg/m2 on days 1 and 8 in a 21-day cycle. The starting dose level for carboplatin was the area under the concentration time curve (AUC) 4 mg/ml/min. 18 patients were treated and a dose limiting toxicity was observed in 2 cases at the level of AUC 6 mg/ml/min. AUC 5 mg/ml/min was considered as the MTD for carboplatin in our regimen. Notably, 7 objective responses were observed.

Aged↗
PubMed2001

A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.

We have carried out a pilot study on 25 non-small cell lung cancer patients, administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1 and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg daily. An objective response was observed in 11 cases (44%). The regimen was active, but toxicity was remarkable with some cases of severe myelosuppression and mucositis.

Aged↗
PubMed1999

Effect of fenretinide on bone mineral density and metabolism in women with early breast cancer.

Prolonged administration of natural or synthetic retinoids has been associated with significant skeletal abnormalities, including osteoporosis. We studied the effects of the synthetic retinoid fenretinide (N-4-hydroxyphenylretinamide, or 4-HPR) administered for a mean of 40 months on bone mineral density and metabolism in 66 consecutive women with early breast cancer belonging to a secondary prevention trial. The mean (+/-SD) bone mineral density at the distal and ultradistal forearm were, respectively, 0.61+/-0.08 and 0.30+/-0.05 g/cm2 in 33 treated women and 0.62+/-0.07 and 0.29+/-0.07 g/cm2 in 33 control women (p = ns for both). Also, no significant difference was observed in markers of bone formation such as bone alkaline phosphatase and osteocalcin, nor in urinary bone resorption markers such as calcium, hydroxyproline, and type I bone collagen cross-linked N-telopeptide (NTx). However, a border-line higher excretion of urinary calcium and NTx was found in the 4-HPR group after adjustment for menopausal status. We conclude that prolonged administration of 4-HPR is not associated with significant alterations of bone mineral density of the forearm. However, a trend towards an increase in bone resorption markers suggests the need for further assessment at different skeletal sites.

Aged↗
PubMed1999

A phase II study of a three-drug combination (cisplatin, ifosfamide and vinorelbine) plus granulocyte-colony stimulating factor in advanced non small cell lung cancer.

Twenty-nine patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of cisplatin 20 mg/m2 days 1-3, ifosfamide 1500 mg/m2 days 1-2 (plus mesna as uroprotector) and vinorelbine 25 mg/m2 days 1 and 5; filgrastim was given at the dose of 300 microg subcutaneously from day 8 to day 15. A response rate of 28% was observed. The activity of this combination in an outpatient setting, with acceptable toxicity, has been demonstrated.

Adult↗
PubMed1998

Effect of fenretinide on plasma IGF-I and IGFBP-3 in early breast cancer patients.

Growing evidence substantiates the role of the insulin-like growth factor I (IGF-1) system in breast tumorigenesis. Retinoids have been shown to affect the IGF system several experimental models. We extended our previous data on plasma IGF-1 modulation by the synthetic retinoid fenretinide (4-HPR) and investigated the effect of the retinoid on plasma IGF binding protein (BP)-3, the major protein binding IGFs. IGF-1 and IGFBP-3 were measured on plasma samples obtained at randomization and after an interval of approximately 1 year, from 39 and 33 stage 1 breast cancer patients assigned to receive 4-HPR, and from 39 and 34 untreated controls, respectively. There was a significant decrease in plasma IGF-1 after 4-HPR administration, whereas no significant change was observed in controls. The effect of 4-HPR on IGF-1 levels was modified by menopausal status, inasmuch as the decrease in IGF-1 was particularly pronounced in pre-menopausal women, whereas the reverse was observed in untreated controls. By contrast, treatment induced an increase of IGFBP-3 with respect to controls. As a result of this dual effect, the bioavailability of IGF-1 for interaction with receptors at target levels further decreased in pre-menopausal 4-HPR treated patients compared with controls, suggesting that retinoid administration may result in lower concentrations of biologically active IGF-1. Our findings may have important implications for the clinical preventive activity of this retinoid.

Adult↗
PubMed1998

High-dose-intensity combination chemotherapy for advanced sarcomas: a pilot study.

A new polychemotherapy schedule involving high dose intensity and shortened intervals has been developed for patients with advanced sarcomas. Mesna at 2500 mg/m2 for 3 days, epidoxorubicin at 60 mg/m2 on day 1, ifosfamide at 2500 mg/m2 for 3 days, and dacarbazine at 450 mg/m2 for 2 days were given every 2 weeks to a consecutive series of 20 patients. All patients received granulocyte colony-stimulating factor (G-CSF; Filgrastim) subcutaneously at 300 microg from day 5 to day 12 of each cycle. The treatment was feasible and toxicity was acceptable, with grade IV myelotoxicity being observed only in one case. In all, 6 of 14 evaluable patients had an objective response; the median survival was 12 months. Toxicity was milder than that observed for the classic combination MAID, and the planned dose intensity was maintained in the majority of cases.

Adult↗
PubMed1998

Correlation between plasma transforming growth factor-beta 1 and second primary breast cancer in a chemoprevention trial.

The relationship between plasma transforming growth factor-beta 1 (TGF-beta 1) and second primary breast cancer was explored in a prevention trial of the synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide; 4-HPR). Plasma concentrations of TGF-beta 1 were measured by radioimmunoassay in plasma obtained at randomisation and after approximately 1 year of intervention in 28 women treated with 4-HPR and 27 untreated controls with stage I breast cancer. Baseline and 1 year growth factor concentrations were not significantly different between treated and control groups. After a median follow-up of 65 months, an increase in TGF-beta 1 over 1 year was the only significant, independent predictor of a shorter survival free from secondary primary breast cancer. Moreover, the change in TGF-beta 1 levels had a tendency to influence the treatment effect on second breast cancer incidence. Our data suggest that the role of plasma TGF-beta 1 as a surrogate endpoint of breast carcinogenesis should be assessed further.

Adult↗
PubMed1998

High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study.

Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of granulocyte colony-stimulating factor (G-CSF; specifically, filgrastim) administered at a dose of 300 microg subcutaneously from day 6 to day 11. The ratio between actually delivered dose intensity and planned dose intensity was 1.0 in 18 out the 20 patients. Toxicity was acceptable; response rate and survival are in the expected range. The present study demonstrated the feasibility of acceleration of chemotherapy cycles to obtain dose intensification in non-Hodgkin's lymphoma.

Adult↗
PubMed1998

A phase II trial of carboplatin, methotrexate and fluorouracil in fluorouracil-pretreated colorectal cancer.

5-Fluorouracil and leucovorin combination is the most commonly applied chemotherapy treatment for colorectal cancer patients, both in the adjuvant setting and for advanced disease. Patients resistant or refractory to the 5-fluorouracil-leucovorin combination have been treated in this phase II trial with carboplatin plus methotrexate and fluorouracil in sequence. Twenty patients with measurable lesions from advanced colorectal cancer were entered in the trial. The treatment plan was carboplatin 300 mg/m2 day 1, methotrexate 40 mg/m2 day 1, fluorouracil 600 mg/m2 day 2, every 21 days. Two patients with liver metastasis had a partial response. Median survival was 12 months (range 4-24). Toxicity was acceptable and no patient had to be hospitalized because of the treatment. In this set of patients activity of the new combination is marginal.

Aged↗
PubMed1998

A dose finding study for the combination of epidoxorubicin and vinorelbine, delivered every two weeks with G-CSF support, in advanced breast cancer.

The aim of this study was to find the maximum tolerated dose of epidoxorubicin as part of a regimen with vinorelbine at the dose of 25 mg/m2 on days 1 and 5, every 2 weeks in patients with advanced breast cancer. The optimal dose intensity of the two drugs was supported by administration of granulocyte colony stimulating factor (G-CSF) on days 7-12. Patients were treated with epidoxorubicin at three different dose levels (50-65-80 mg/m2 on day 1 of each cycle). No dose limiting toxicity was observed in the first three patients (treated at the dose of 50 mg/m2). We observed one case of dose limiting toxicity out of the 6 patients treated with 65 mg/m2 and 3/3 cases among patients treated with 80 mg/m2. We conclude that 65 mg/m2 is the maximum tolerated dose of epidoxorubicin in this regimen, which is also able to maintain adequate dose intensities.

Adult↗
PubMed1997

Second line chemotherapy with ifosfamide as outpatient treatment for advanced bladder cancer.

We have carried out a phase II study in advanced or metastatic transitional cell carcinoma of the bladder. Eligible patients had unresectable bladder cancer, previously treated with one line of systemic chemotherapy. Treatment consisted of ifosfamide 1000 mg/sm in a 2-hour infusion for 5 consecutive days from d.1 to d.5. Mesna was administered intravenously at a 20% of the ifosfamide dosage before ifosfamide and orally at 40% after 4 and 8 hours from the ifosfamide infusion. Twenty patients entered the study and received a total of 62 cycles: the treatment resulted feasible on an outpatient basis, with mild toxicity. Only one partial response was observed. With this dose and schedule, ifosfamide appeared less effective than in a previous report at higher doses. Toxicity was acceptable.

Administration, Oral↗
PubMed1995

Epidermal growth factor content of breast cyst fluids from women with breast cancer or proliferative disease of the breast.

The intracystic electrolyte content is generally used to identify different breast cyst subpopulations: cysts containing high K+ levels have been associated with an increased risk of subsequent breast cancer. In order to define whether other biochemical features of breast cyst fluid (BCF) might further explain such an increased risk, we determined the content of epidermal growth factor (EGF), a known mitogenic factor for normal and transformed breast epithelium, in cysts of women with breast cancer or proliferative lesions of the breast (atypical ductal or lobular hyperplasia and proliferative disease without atypia). Median intracystic EGF levels were significantly higher in patients with breast cancer or atypical hyperplasia than in cysts of women without any clinical or instrumental evidence of proliferative disease chosen as controls (p < 0.05 and p < 0.01, respectively). In patients affected by proliferative disease without atypia, intracystic EGF levels were not different either from controls or from the other study groups. No significant difference among groups was observed in the prevalence of Na+/K+ < 3 cysts, this being the most frequently observed type of cysts in all groups except in that with proliferative disease without atypia. No significant difference in EGF levels between cysts ipsilateral or contralateral to the biopsy was observed within each histological group. Our results indicate that EGF levels are higher in cysts aspirated from breasts with an associated proliferative pathology, either benign or neoplastic. The determination of intracystic EGF, combined with that of electrolyte content, might help to identify a subset of patients with gross cystic disease of the breast at potentially higher risk of developing breast cancer.

Adult↗
PubMed1995

Insulin-like growth factor-I (IGF-I) and IGF-binding proteins blood serum levels in women with early- and late-stage breast cancer: mutual relationship and possible correlations with patients' hormonal status.

The pathogenesis and progression of breast cancer involve complex interactions between hormones and polypeptide growth factors such as insulin-like growth factor-I (IGF-I). IGF-I has been found in stromal fibroblasts derived from malignant and benign breast tissue and it is a mitogen for several breast cancer cell lines. It circulates bound to specific high-affinity binding proteins, which could act as either positive or negative modulators of tumorigenesis. This study has been addressed to characterize IGF-I and its binding proteins in the serum of 85 unselected patients with early breast cancer. The IGF-I concentration was assessed by radioimmunoassay of 69 out of 85 samples before and after dissociation of the IGF-I and IGF-binding protein (IGF-BP) complex whereas IGF-BP of all 85 sera were analyzed by Western ligand blotting; estradiol and progesterone were measured by radioimmunoassay in native serum samples. In our study no differences in IGF-I serum levels between pre- and post-menopausal patients were observed. Patients with higher estradiol and progesterone serum levels did not present different IGF-I concentrations compared to patients with lower serum levels. Furthermore, IGF-I median values were not found to depend on estrogen receptor (ER) status. A heterogeneous quali-quantitative molecular pattern of binding proteins was detected: IGF-BP3 and IGF-BP1 were the most and the least expressed respectively. No correlations between ER status, or parameters related to the hormonal status, and IGF-I or binding proteins expression were observed. No significant differences in IGF-I concentration and IGF-BP expression were observed between cancer patients and a control group matched for age and menopausal status. Finally, preliminary collection of 20 sera derived from patients with late breast cancer was analyzed for IGF-I and its binding proteins content.

Adult↗
PubMed1994

Presence of immunoassayable transforming growth factor-beta 1 (TGF-beta 1) in breast cyst fluid (BCF): relationship with the intracystic electrolyte and epidermal-growth-factor (EGF) content.

We evaluated the presence and distribution of transforming growth factor-beta 1 (TGF-beta 1) in breast cyst fluid (BCF), and its relationship with intracystic epidermal growth factor (EGF). EGF and TGF-beta 1 were determined by radioimmunoassay on 47 BCFs (27 of the Na+/K+ < 3 type and 20 of the Na+/K+ > 3 type). As expected, EGF levels were inversely correlated with the Na+/K+ ratio, and were consequently higher in Na+/K+ < 3 cysts as compared with Na+/K+ > 3 cysts, (p < 0.005). By contrast, TGF-beta 1 levels were directly correlated with the Na+/K+ ratio (p < 0.01), being higher in Na+/K+ > 3 cysts, though not significantly (p = 0.057). A significant negative relationship was found between EGF and TGF-beta 1 concentration. When the analysis was performed separately in the 2 cyst sub-populations, EGF and TGF-beta 1 were found to be negatively and significantly correlated in Na+/K+ < 3 cysts only (p < 0.01). Our results demonstrate that Na+/K+ < 3 cysts contain high levels of EGF, a growth-stimulating factor, and very low levels of TGF-beta 1, a growth-inhibiting factor. This may provide an explanation for the higher risk of breast cancer observed in women with Na+/K+ < 3 cysts. Our results also suggest that EGF accumulation in this type of cysts might be regulated by TGF-beta 1.

Epidermal Growth Factor↗
PubMed1994

Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion.

The nonsteroidal androgen-receptor antagonist nilutamide has previously been shown to inhibit adrenal androgen steroidogenesis in patients with prostatic carcinoma treated in combination with an LHRH agonist. In order to understand better the mechanisms subserving this observation, we have studied the effects of nilutamide alone on the serum concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), and DHEA-sulphate (DHEA-S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D-Trp-6-LHRH. In addition, the adrenocorticotropic hormone (ACTH)-stimulated adrenal response and the thyrotropin releasing hormone (TRH)-stimulated prolactin (PRL) response observed in the patients treated with nilutamide were compared with a control group of healthy age-matched controls. No significant variation in the basal concentrations of adrenal androgens occurred either within or between both treatment groups. In response to ACTH, a decreased 17-alpha hydroxyprogesterone (17-OHP) accumulation and an augmented A/17-OHP ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the partial removal of the 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PRL levels were not affected by the antiandrogen, but the response to TRH was increased. We conclude that no significant inhibition of adrenal androgen secretion occurs after nilutamide or LHRH agonist treatment. Rather, administration of the antiandrogen alone may partially remove the physiological decrease in adrenal androgen secretion observed in the elderly.

Adrenal Glands↗