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Biomedical subjects

E Baldini

Publications and source records attributed to E Baldini.

At least 19 recordsLinked to original sources
PubMed2006

Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas.

We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.

Blotting, Western↗
PubMed2006

Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study.

The aim of this study was to evaluate feasibility and toxicity of escalating doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the activity of the triplet in extensive disease small-cell lung cancer. Thirteen patients entered the phase I study: the maximum tolerated doses were epirubicin (EpiDX) 90 mg m-2 and paclitaxel (P) 175 mg m-2 with febrile neutropenia as dose-limiting toxicity. The recommended schedule for this regimen for the phase II study was EpiDX 75 mg m-2, P 175 mg m-2, etoposide (E) 100 mg m-2 intravenous (fixed dose) days 1-3 with courses repeated every 21 days. The prophylactic use of colony-stimulating factors (CSFs) was not allowed. Twenty patients entered the phase II trial: median age was 61 years (range 50-70), median Eastern Cooperative Oncology Group performance status 0 (0-2); nine patients had visceral disease and 17 had more than two metastatic sites. A total of 100 courses were administered with a median of 5 (range 1-6) per patients. Main toxicity (NCI-CTC) was myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses, respectively. Seven episodes of febrile neutropenia were documented and one patient required hospital admission. Nonhaematological toxicity was moderate. Seven out of 19 evaluable patients achieved a complete response (37%), nine patients (47.3%) a partial response with an overall response rate of 84.2% (95% confidence interval=60.4-96.6). In this poor prognostic population of patients the triplet epirubicin/paclitaxel/etoposide showed high antitumour activity with mild nonhaematological side effects. The use of CSFs should be able to improve the haematological profile.

Aged↗
PubMed2004

Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety.

The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mg m(-2) plus Paclitaxel 200 mg m(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mg m(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mg m(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel.

Adult↗
PubMed2004

Expression of matrix metalloproteinases and their specific inhibitors in normal and different human thyroid tumor cell lines.

In the present study we investigated, by means of zymography and reverse transcription-polymerase chain reaction (RT-PCR), the expression of different matrix metalloproteinases (MMPs) and of the specific tissue inhibitor of metalloproteinases [TIMPs] in human cell lines derived from normal thyrocytes (HTU5), follicular adenoma (HTU42), and follicular (FTC-133), papillary (B-CPAP), and anaplastic (CAL-62, 8305C) thyroid carcinomas. We demonstrated that normal thyrocytes constitutively express MMP-1, MMP-2, MMP-10, MMP-14, and TIMP-1, TIMP-2, TIMP-3, and TIMP-4, and this pattern of expression is profoundly modified in all thyroid tumor-derived cell lines. Analysis of the gelatinolytic activity in the different cell supernatants showed that the expressions of MMP-2 and MMP-9 are, respectively, increased or induced in all the neoplastic cell lines, except in CAL-62. Caseinolytic activity was found only in the supernatants of the 8305C and B-CPAP cells. Using RTPCR analysis we detected an increased expression of MMP-1 in cell lines derived from papillary and from one (8305C) of the two anaplastic carcinomas. MMP-13 mRNA was expressed only in the 8305C, FTC-133, and BCPAP cells. Among stromelysins, MMP-3 mRNA could not be detected in any cell line, while MMP-10 mRNA was expressed in all of them, although at variable levels. MMP-11 mRNA was absent in normal and follicular adenoma derived thyrocytes and induced in all carcinoma cell types. The expression of MMP-14 (MT1-MMP) mRNA was found significantly increased in all thyroid tumor cell lines with respect to HTU5 and HTU42 cells. The expression of TIMP-1 and TIMP-2 mRNAs was maintained in all cell lines tested, while that of TIMP-3 was lost in both anaplastic carcinoma cell lines and that of TIMP-4 was absent in the CAL-62. In conclusion, our data demonstrated a differential expression of MMPs and TIMPs in different thyroid tumor cell types with respect to normal thyrocytes. In particular, the induction of MMP-11 in all thyroid-derived carcinoma cell lines studied and of MMP-13 in all but one may represent, if confirmed in other thyroid tumor-derived cell lines and in thyroid tumor tissues, a new marker of thyrocyte transformation.

Cell Line↗
PubMed2003

Iodine supplementation restores fertility of sheep exposed to iodine deficiency.

The aims of the study were to monitor sheep iodine intake in different sheep breeding farms in Abruzzo and to evaluate the effects of iodine supplementation on ovine fertility. The urinary iodine concentrations (UIC) in animals of 8 out of the 11 breeding farms analyzed were borderline (UIC 100-150 microg/l) or very low (UIC < or = 50 microg/l). Only animals bred in 3 farms showed an adequate iodine intake with a mean UIC > or = 300 microg/l. Animals with very low iodine intake had lower T4 and T3 (p < 0.01) serum levels, compared to those with adequate iodine intake. To investigate the effects of iodine supplementation on ovine fertility, 32 ewes and 20 rams, characterized by low UIC, were randomly divided into 2 groups. One group (16 ewes and 10 rams) received a sc injection of 1 ml of Lipiodol, containing 480 mg of iodine, while the remaining animals were employed as control. This treatment was able to maintain UIC above 300 microg/l for 3 months and to increase T4 and T3 serum levels (p < 0.01). After 9 months, the fertility of control and treated animals was assessed by monitoring the rate of successful matings by ultrasonography. The results showed that 100% of treated ewes mated with treated rams were pregnant vs 37% of the control ewes mated with control rams (p = 0.007). The iodine content was 4-fold higher in milk from treated ewes (2393 +/- 453 microg/l), compared to controls (675 +/- 154 microg/l). The results demonstrated that iodine supplementation restores fertility of sheep living in iodine deficient areas and may represent a means to achieve a silent iodine prophylaxis of local populations.

Animals↗
PubMed2003

Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate (pCR) in patients with locally advanced breast cancer (LABC) treated with combined modality therapy. PATIENTS AND METHODS: Stage IIIA/IIIB patients received three courses of induction chemotherapy (ICT) with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by local therapy (total mastectomy or segmental mastectomy with axillary nodes dissection) and adjuvant chemotherapy (ACT) with three courses of CEF alternated with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Patients were randomized to receive ICT and ACT every 3 weeks (arm A, 'standard treatment') or every 2 weeks with granulocyte-macrophage colony-stimulating factor (GM-CSF) support (arm B, 'dose-dense treatment'). In both arms radiotherapy was administered after the end of chemotherapy (in selected cases) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years. RESULTS: A total of 150 patients were randomized (77 arm A and 73 arm B) and demographics were well balanced between the two arms. Compliance to treatment was excellent: 95% and 93% of patients in arms A and B, respectively, completed the treatment program with no modification or delay. Median duration of treatment (ICT+local+ACT) was 183 days (range 0-265) in arm A and 139 days (0-226) in arm B. The average relative dose intensity (ARDI) of chemotherapy was 1.3 with a 30% increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [62%; 95% confidence interval (CI) 49% to 73.2%] and pathological response rates to ICT was observed between the two arms. Median follow-up was 5 years (range 1-96 months); median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in standard therapy: this figure has not yet been reached in the dose-dense treatment. CONCLUSIONS: In LABC a dose-dense regimen, while allowing a 30% increase in the dose intensity of chemotherapy, did not provide significant improvement in pathological response rates. However, accelerated chemotherapy reduced the duration of the combined-modality program (6.1 versus 4.6 months) with no additional toxicities.

Adult↗
PubMed2001

Gemcitabine, Ifosfamide and Navelbine (GIN): activity and safety of a non-platinum-based triplet in advanced non-small-cell lung cancer (NSCLC).

To evaluate activity and toxicity of a non platinum-based triplet including Gemcitabine, Ifosfamide and Navelbine (GIN) in advanced NSCLC. Stage IIIB/IV NSCLC patients with WHO PS < 2 and bidimensionally measurable disease entered the study. Gemcitabine 1000 mg/sqm day 1 and 1000-800 mg/sqm day 4, Ifosfamide 3 g/sqm day 1 (with Mesna), Navelbine 25 mg/sqm day 1 and 25-20 mg/sqm day 4 were administered intravenously every 3 weeks. Objective responses (ORs) were evaluated every 2 courses: a maximum of 6 courses were administered in responding patients. According to Simon's optimal two-stage design more than 18 ORs out of 54 patients were required to establish the activity of this regimen. Fifty patients entered the study. Main characteristics of the 48 evaluated patients were: median age 63 years, ECOG performance status 0 = 65%, stage IV disease 79% and non-squamous histology 71%. The total number of courses administered was 200, median per patient 4 (range 1-6). Toxicities were evaluated according to WHO criteria: neutropenia grade 3-4 occurred in 47% of the courses; thrombocytopenia grade 3-4 in 6.6%; anaemia grade 3 in 3.5%. Twelve episodes of febrile neutropenia were reported and three patients required hospital admission. No toxic death was reported. Non-haematological toxicity, including skin rash, alopecia and fatigue, were generally. Twenty-five ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI: 37.4-66.5%). One-year survival was 46.5%. This non-platinum-based outpatient triplet showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose-limiting. The GIN regimen may represent a valuable alternative to standard platinum-based doublets and triplets in the treatment of advanced NSCLC and further studies with this platinum-free combination are warranted.

Adult↗
PubMed2001

Frequency and biochemical expression of C282Y/H63D hemochromatosis (HFE) gene mutations in the healthy adult population in Italy.

BACKGROUND/AIMS: The actual prevalence of the main hemochromatosis (HFE) mutations in the Italian adult population and their phenotypic expression have not yet been established. This information is key to advocate a mass-screening program. METHODS: Two thousand one hundred adults were tested for the C282Y/H63D HFE gene mutations by an automated genotyping assay as well as transferrin saturation (TS) and serum ferritin levels. RESULTS: No homozygotes for the C282Y mutation were found. Heterozygosity for the C282Y mutation was 3.1%, while heterozygosity and homozygosity for the H63D mutation were 21.5% and 2.5%, respectively. TS was significantly higher in C282Y heterozygotes and H63D homozygotes as compared to wild-type individuals (P < 0.01). Interestingly, of the HFE wild-type subjects 5.9% had a TS value above the 45% threshold. CONCLUSIONS: This study shows that (i) the predicted prevalence for C282Y homozygosity in Italy is 1:3900; (ii) the C282Y/H63D wild-type population has an increased baseline of iron parameters possibly due to genetic factors not linked to the C282Y/H63D mutations; (iii) since in the latter population the actual tissue iron burden cannot be assessed, phenotypic (TS) screening in Italy is not recommended until the true prevalence of all mutations in the HFE gene and in other hemochromatosis genes will be established.

Adult↗
PubMed2001

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study.

PURPOSE: To investigate the activity of the combination of gemcitabine (G) plus epirubicin (E) and taxol (T), (GET), in metastatic breast cancer, to evaluate the feasibility of this regimen as induction before high dose chemotherapy and to study the pharmacokinetic interactions of these three drugs. PATIENTS AND METHODS: Metastatic breast cancer patients, with bidimensionally measurable disease were eligible. Treatment consisted of G 1000 mg/sqm days 1 and 4 plus E 90 mg/sqm day 1 plus T 175 mg/sqm/3 h day 1, every 21 days. After six courses of GET, patients aged less than 60 years, in complete or partial remission or stable disease entered a programme of high dose chemotherapy (HDCT), as consolidation treatment. RESULTS: Thirtysix patients were included in this study. Grade 4 neutropenia was observed in 64% of the patients, with four episodes of febrile neutropenia; 39% of the patients experienced mild to moderate peripheral neuropathy; grade 2 and 3 mucositis occurred respectively in 9 (25%) and 6 (17%) patients. The overall response rate to GET was 92% (95% CI, 77.53%-98.25%); CR 31% and PR 61%. After six courses of GET, 25 patients received HDCT, leading to an overall response rate of 96% with 58% CR. At a median follow up of 25 months (range 8-39), 13 out of 36 patients are progression free and 26 alive. Median progression free survival is 21 months, while median overall survival has not yet been reached. The pharmacokinetic data show that G does not influence the interactions between E and T, while gemcitabine kinetics remains unchanged. CONCLUSIONS: The results of the present study indicate that the addition of G to E plus T as front line treatment for advanced breast cancer is well tolerated with an ORR of 92%. On the basis of the high activity and interesting progression free and overall survival rates, the GET combination deserves further evaluation in randomized trials.

Adult↗
PubMed2001

Epirubicin/taxane combinations in breast cancer: experience from several Italian trials.

Doxorubicin/paclitaxel (Taxol) combinations are very active in advanced breast cancer, with objective response rates up to 90%, but have shown a high incidence of cardiotoxicity. A phase I/II trial replacing doxorubicin with epirubicin (Ellence), a less cardiotoxic analog, produced an objective response rate of 84%, but with a low rate of cardiotoxicity. A careful cardiac monitoring in more than 100 patients treated with this combination has demonstrated that the risk of congestive heart failure is below 10% up to a cumulative epirubicin dose of 990 mg/m2. To examine the possibility that the pharmacokinetic and pharmacodynamic interactions that occur when anthracycline and paclitaxel are administered together might result in subadditive antitumor activity, a phase III study is comparing concomitant vs sequential administration of epirubicin and paclitaxel in patients with advanced breast cancer. A phase I/II study of epirubicin plus docetaxel as first-line chemotherapy for advanced breast cancer patients evaluated the maximum tolerated doses and for subsequent studies recommended epirubicin at 75 mg/m2 plus docetaxel at 80 mg/m2. In the adjuvant setting, an ongoing phase III trial is comparing epirubicin plus paclitaxel vs FEC (fluorouracil, epirubicin, and cyclophosphamide [Cytoxan, Neosar]) in node-positive patients. Preliminary data confirm the cardiac safety of these treatments.

Breast Neoplasms↗
PubMed2000

Agenesis of the horizontal segment of the left portal vein demonstrated by magnetic resonance imaging including phase-contrast magnetic resonance venography.

Two cases of agenesis of the horizontal segment of the left portal vein are reported. This very rare vascular anomaly probably corresponds to an embryological variation rather than to an obstruction of the left portal vein. In almost all cases liver ultrasonography is sufficient for identifying such vascular abnormalities. It shows a large aberrant vessel emerging from a right anterior segmental portal branch and running transversely in the quadrate lobe towards the teres ligamentum from which the portal supply to the left lobe arises. It is important to be able to recognize the magnetic resonance imaging features of this vascular variation, as magnetic resonance imaging may be the initial imaging study, and ultrasound may be technically challenging. To our knowledge, we present the first description of these features, including an enhanced gradient-echo T1-weighted sequence, a turbo spin-echo T2-weighted sequence with fat saturation, and a three-dimensional phase-contrast magnetic resonance portography.

Adult↗
PubMed2000

Sequential chemoradiation therapy with vinorelbine, ifosfamide, and cisplatin in stage IIIB non-small cell lung cancer: a phase II study.

Meta-analysis has demonstrated survival benefit for patients with stage IIIB non-small cell lung cancer treated with sequential chemoradiotherapy versus radiotherapy alone. The introduction of chemotherapy as part of a multimodality approach has improved the outcome in this poor prognostic subset of cancer patients. In the present phase II study we evaluated the safety and activity of a new cisplatin-based three-drug regimen consisting of vinorelbine/ifosfamide/cisplatin (VIP) followed by curative thoracic irradiation in 28 patients with stage IIIB non-small cell lung cancer. Patients received vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 g/m2 on day 1 (with mesna), and cisplatin 80 mg/m2 on day 1 every 3 weeks. After three courses of induction chemotherapy, patients with objective response or stable disease were eligible for thoracic radiotherapy. Twenty-six of the 28 patients received at least three courses of chemotherapy and were evaluable for response. The response rate to induction VIP was 58% (15 of 26 patients; one complete response and 14 partial responses). Seven patients had disease stabilization and four progressed during chemotherapy. Radiation treatment started from 4 to 6 weeks after the end of chemotherapy with standard fractionation (200 cGy/day, 5 fractions/wk/6 wk). Eighteen of 22 patients started thoracic irradiation; 14 completed the treatment plan, reaching the total dose of 60 Gy. The most relevant acute and late toxicities of radiotherapy were grade 3 dysphagia and pneumonitis in two patients and grade 3 lung fibrosis in six patients. By comparing the tumor volumes before and after radiation treatment we observed six clinical remissions, three stable diseases, and five local progressions. The first site of recurrence was local in 10 of 18 patients (56%), distant in seven patients (38.8%), and both local and distant in one patient. Median progression-free survival and overall survival for the patients treated with radiotherapy (18 patients) were 14 months (range, 4 to 36 months) and 26 months (range, 7 to 54+ months), respectively; the 1- and 2-year survival rates were 61% and 52%. Curative thoracic radiotherapy was well tolerated after VIP induction chemotherapy; it reduced residual tumor volume in six patients.

Adult↗
PubMed2000

[Epidemiological information obtained from anti-hepatitis C virus screening in blood donors and candidates for autologous transfusion from 1992 to 1996 in the Alpes-Maritimes region].

OBJECTIVES: To determine the evolution of the frequency of anti-hepatitis C virus antibodies from 1992 to 1996 in blood donors and in candidates for autologous transfusion in the Alpes-Maritimes region and to assess risk factors. METHODS: Anti-hepatitis C virus antibodies were assessed by second generation ELISA in 1992 and in the first quarter of 1993, and then by third generation ELISA; in all cases, anti-hepatitis C virus antibodies were confirmed by RIBA test. RESULTS: Since 1992 (when the second generation ELISA test became available), the prevalence of anti-hepatitis C virus antibodies in blood donors in the Alpes-Maritimes region (0.54% in 1992 to 0.20% in 1996) has decreased. Positive ELISA anti-hepatitis C virus was confirmed by RIBA in 53 to 68% of anti-hepatitis C virus blood donations. The percentage of anti-hepatitis C virus donors with ALT above the upper limit (donation exclusion threshold) was between 28 and 56%.The most frequent age interval for new anti-hepatitis C virus positive donors was between 30 and 40 years. Since 1992, a third of the anti-hepatitis C virus blood donors agreed to participate in a medical history questionnaire. One or several risk factors were found in almost all donors. The most frequent source of infection was nosocomial (50%). During the 5 years of the study, the number of candidates for autologous transfusion increased: 717 in 1992 to 1 528 in 1996. The prevalence of anti-hepatitis C virus in this older population (mean age: 64 years) decreased progressively (2.9% in 1992 to 1.1% in 1996, P<0, 01) since the prevalence of anti-HBc remained stable, near 12%. Among the 96 subjects found to be anti-hepatitis C virus positive before an autologous transfusion, 49 were transfused before 1990 and 40 had a history of surgery. CONCLUSION: The prevalence of anti-hepatitis C virus has decreased since 1992 in blood donors and in candidates for autologous transfusion which may suggest that there is better screening in the general population and presenting the spread of hepatitis C virus infection.

Adult↗
PubMed1999

Cyclin-D1 expression in node-positive (N+) and node-negative (N-) infiltrating human mammary carcinomas.

Cyclin-D1 (CD1) expression was analyzed in human mammary carcinomas by immunohistochemical (IHC) and flow-cytometry (FCM) methods: 52.5% and 50% of cases were strong expressors of CD1 by IHC and FCM analysis respectively. The percentage of CD1-positive cells was especially high in node-negative (N-) estrogen-receptor-positive (ER+) tumors, probably as a consequence of CD1 induction by estrogens in steroid-responsive tissues. However, CD1 expression was not related to ER positivity in node-positive tumors (N+). An interesting relationship between CD1 expression and H3-thymidine labelling index (H3Td-LI) was also found: CD1 and H3Td-LI were unrelated in N- tumors, while high CD1 expression was observed in N+ tumors with high DNA synthesis, as assessed by H3Td-LI. The combined measurement of DNA and CD1 showed that 27 specimens were aneuploid, 19 of them (19/27; 70%) strongly expressing CD1. Further studies are needed to clarify the role of CD1 in DNA abnormality of breast tumors. However, we cannot exclude that the CD1 may be differently de-regulated in the last phase of tumor progression, and that CD1 over-expression may contribute to the aneuploidy of mammary carcinomas.

Breast Neoplasms↗
PubMed1999

[Inflammatory pseudotumor of the intrahepatic biliary tract].

Hepatic inflammatory pseudotumors are rare, presenting with a severe clinical pattern mimicking neoplasm. The diagnosis is almost always based on pathological examination showing inflammatory lesions with a polymorphous infiltrate and variable amounts of fibrous tissue. Development in the biliary tract is rare. We report the case of a 53-year-old patient who was referred for poor general condition and jaundice; the initial diagnosis was cholangiocarcinoma. Pathological examination of the surgical specimen showed a right intrahepatic biliary duct inflammatory pseudotumor. The patient developed recurrent jaundice three months after surgery due to a lesion of the left biliary ducts. Treatment with cortisone resulted in rapid improvement of jaundice.

Bile Ducts, Intrahepatic↗