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Biomedical subjects

Giovanni Scambia

Publications and source records attributed to Giovanni Scambia.

At least 109 records · Page 6Linked to original sources
PubMed2002

Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin.

In this study we investigated whether the flavonoid silybin and its bioavailable derivative IdB 1016 (silipide) could enhance the antitumour activity of cisplatin (CDDP), the most commonly used drug in the treatment of gynaecological malignancies. Silybin alone up to 10 (M was unable to produce a relevant in vitro growth inhibition of A2780 cells, whereas CDDP was effective, giving an IC50 value of 0.5+/-0.14 microM. When silybin was combined with CDDP, a dose-dependent and statistically significant (p<0.05) increase of the CDDP activity was noticed, yielding IC50 values of 0.35+/-0.07 and 0.263+/-0.004 microM at silybin concentrations of 1 and 10 microM, respectively. The same trend was observed for in vivo experiments. IdB 1016 alone (1350 mg/kg) did not significantly affect tumour growth, whereas CDDP at the Maximum Tolerated Dose (12 mg/kg) produced a tumour weight inhibition (TWI%) of 80% and a log10 cell kill (LCK) of 0.7. Administration of both drugs resulted in a potentiation of the antitumour activity and TWI% and LCK increased to 90% and 1, respectively. Interestingly, mice receiving the combination recovered earlier in terms of body weight loss as compared to CDDP-treated mice. CDDP at 6 mg/kg yielded TWI of 44% and LCK of 0. The concomitant administration of IdB 1016 (1800 mg/kg) enhanced CDDP anti-tumour activity, with 68% TWI and 0.6 LCK. Finally, an antiangiogenic effect of IdB 1016 in an in vivo experimental model was demonstrated. Median haemoglobin value for the Matrigel from the vehicle-treated controls was 2.43 versus a value of 0.321 for the IdB 1016-treated animals.

Animals↗
PubMed2002

Neoadjuvant treatment of locally advanced carcinoma of the uterine cervix with epirubicin, paclitaxel and cisplatin.

PURPOSE: The present study was conducted to explore whether neoadjuvant chemotherapy with a combination of epirubicin, paclitaxel and cisplatin could improve the operability and pathological response rate in locally advanced cervical cancer patients. METHODS: Between April 1996 and July 2000, 42 patients with carcinoma of the uterine cervix, FIGO stage Ib(2)-IVa, were treated with two or three 21-day cycles of an epirubicin 100 mg/m(2), paclitaxel 175 mg/m(2), cisplatin 100 mg/m(2) regimen. RESULTS: All patients were eligible for evaluation of toxicity and response. A total of 92 courses of therapy were administered. Three patients had a 20% reduction from the starting dose due to haematological toxicity. Grade 3-4 leukopenia was observed in 15% of cycles, requiring G-CSF support in half of them. Major non-haematological toxicity consisted of grade 3 alopecia (100%), and grade 3 nausea and vomiting (40%). A total of 33 clinical responses (78.5%, 95% CI 63.8-93.2) were recorded, 8 complete responses (CR) and 25 partial responses (PR). Of the 42 patients, 32 (76.2%) underwent radical surgery. At pathological examination 8 complete or microscopic pathological responses, 17 PRs, and 9 patients with stable disease were observed. The median follow-up time was 17 months for the 42 patients enrolled (range 3-62 months). Among the patients submitted to radical surgery, five recurrences were observed, with a median disease-free survival of 47 months. Median overall survival had not been reached at the time of this report. These results appear to be in the range reported for other neoadjuvant cisplatin-based regimens not including paclitaxel. CONCLUSIONS: Neoadjuvant chemotherapy with the epirubicin, paclitaxel and cisplatin combination followed by radical surgery proved to be a safe and effective approach to advanced cervical cancer.

Adult↗
PubMed2002

Gynecological malignancies in elderly patients: is age 70 a limit to standard-dose chemotherapy? An Italian retrospective toxicity multicentric study.

OBJECTIVE: One hundred and forty-eight consecutive gynecological oncological patients aged >or=70 were administered chemotherapy during the years 1990-2000. METHODS: Median age was 73 years (range 70-84). Fifty-five (37.2%) women were over 75 years old. One or more comorbid conditions were present in 118 (79.7%) patients. Standard schedules were administered to 97.3% of cases, with a total number of 1046 cycles of therapy administered (median, 6; range, 1-35, per patient). RESULTS: Of a total of 233 chemotherapy regimens globally administered, G3-G4 hematological toxicity was documented in 38.2% of cases. Only 10 (6.8%) of the 148 patients discontinued treatment because of G3-G4 hematological toxicity. No severe nonhematological toxicity was observed. Two dose reductions and three treatment delays, but no discontinuation of treatment, were required during second-line regimens. Treatment delay >7 days was required in 16.9% of cases. CONCLUSIONS: Chronological age did not adversely influence the ability to receive aggressive treatment.

Age Factors↗
PubMed2002

Minilaparotomy in early stage endometrial cancer: an alternative to standard and laparoscopic treatment.

OBJECTIVE: Our objective was to determine whether minilaparotomy could be a safe and feasible approach for the surgical treatment of early endometrial cancer patients and whether it could be considered a valid alternative to the laparoscopic treatment. METHODS: A pilot study of 50 consecutive patients with FIGO stage I-IV endometrial cancer undergoing surgery at our Department was performed between May and December 2001. All patients were evaluated for a minimal transabdominal approach. Exclusion criteria were considered: special histotype, poorly differentiated tumors, clinical stage >/=Ic, Ca125 >35 U/ml, BMI >30, lymph nodal involvement assessed by MRI, and severe cardiopulmonary disease precluding steep Trendelenburg position. RESULTS: Twenty-six (52%) cases were considered eligible for minilaparotomy. The mean age was 55.4 years and the mean BMI was 24.1. All patients underwent TAH, BSO, pelvic lymphadenectomy +/- omental or peritoneal biopsy. A mean number of 28 pelvic lymph nodes were removed. The mean operative time was 113.0 min and the mean intraoperative blood loss was 220.0 ml. There was 1 severe operative hemorrhage and 1 patient needed postoperative blood transfusion. No immediate complications of wound infection or separation occurred. The mean hospital stay was 3.4 days. Intra- and postoperative parameters were compared to laparotomy controls and literature data on laparoscopy, showing substantially comparable results. CONCLUSION: Minilaparotomy is a feasible alternative to the standard treatment in endometrial cancer patients. It offers the patient a cost-effective procedure that avoids many of the potential complications of standard therapy, prevents long hospital recovery periods, and accomplishes all of the important goals of standard recommendations.

Adult↗
PubMed2002

BRCA1-related malignancies in a family presenting with von Recklinghausen's disease.

BACKGROUND: The association between neurofibromatosis and gynecologic malignancies is rarely reported in the literature. Both BRCA1 and NF1 genes are located on the long arm of chromosome 17. CASE: We have observed a pedigree showing several individuals affected by both type 1 neurofibromatosis (NF1) and breast or coelomatic cancers. The number of individuals affected, their degree of relationship, and the early age at onset were suggestive of an hereditary breast/ovarian cancer syndrome. Linkage analysis was performed in order to establish whether markers in the chromosome 17 region containing the BRCA1 and NF1 loci were shared by affected individuals. Screening for BRCA1 mutations was performed by PTT and SSCP. Analysis of chromosome 17 DNA markers in the five family members tested show that three individuals affected by both NF1 and carcinomas share a common haplotype including the NF1 and BRCA1 loci on chromosome 17. Mutation analysis showed the presence of a nonsense mutation within BRCA1 exon 12 in two individuals, mother and daughter, affected by breast and peritoneal cancer, respectively, as well as in the son, who had rectal cancer at the early age of 27 years. All three subjects also had NF1. CONCLUSION: The concurrence of NF1 and hereditary breast/ovarian cancer in this family is likely due to the presence of two linked mutations at the NF1 and BRCA1 loci.

Adult↗
PubMed2002

Effects of novel taxanes SB-T-1213 and IDN5109 on tubulin polymerization and mitosis.

SB-T-1213 and IDN5109 are semisynthetic, orally available taxanes that are up to 400-fold more active than paclitaxel against drug-resistant cells. IDN5109 is in clinical trials. We investigated the primary target for SB-T-1213 and IDN5109 and whether the compounds interact with microtubules differently than paclitaxel. Unlike paclitaxel, at 1-10 microM both novel taxanes initiate microtubule polymerization in vitro with no lag. They enhance polymerization equally or more potently than paclitaxel. SB-T-1213 induces unusual microtubules with attached extra protofilaments or open sheets, and IDN5109 induces large protofilamentous sheets. Both inhibit HeLa cell proliferation, block mitosis at the metaphase/anaphase transition, bundle microtubules at high drug concentrations, and induce abnormal metaphase spindles and apoptosis. They target microtubules but alter their polymerization and structure differently than paclitaxel. These differences may play a role in their enhanced cytotoxicity and efficacy.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Transforming growth factor-beta1 causes transcriptional activation of CD34 and preserves haematopoietic stem/progenitor cell activity.

Stem/progenitor cells endowed with in vitro and in vivo haematopoietic activity express the surface protein CD34. Transforming growth factor beta1 (TGF-beta1) is one of the soluble molecules that regulate cell cycle and differentiation of haematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has previously been shown that TGF-beta1 maintains human CD34+ haematopoietic progenitors in an undifferentiated state, independently of any cell cycle effect. Here, we have shown that TGF-beta1 upregulates the human CD34, an effect that was evident in primary stem/progenitor cells (CD34+lin-) both at the transcriptional and protein levels, and was not associated with any relevant effect on cell growth. The presence of TGF-beta1 influenced differentiation, maintaining primary CD34+/Lin- in an undifferentiated state. This effect was associated with Smad activation and with a dramatic decrease in p38 phosphorylation. Moreover, blocking p38 phosphorylation by the SB202190 inhibitor increased CD34 RNA levels but did not enhance CD34 protein expression in CD34+/Lin- cells, suggesting that modulation of multiple signalling pathways is necessary to reproduce TGF-beta1 effects. These data establish the role that TGF-beta1 has in the modulation of the CD34 stem/progenitor protein and stem/progenitor functions, providing important clues for understanding haematopoietic development and a potential tool for the modulation of human haematopoiesis.

Antigens, CD34↗
PubMed2002

Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro.

Erythropoietin (EPO), a renal cytokine regulating haematopoiesis, is also produced by different cell types within the central nervous system, where it acts via the activation of specific receptors. Current evidence shows that EPO exerts neurotrophic and neuroprotective activities in different in vivo and in vitro models of brain damage. In the present study we investigated the effects of EPO on primary cultures of rat cortical microglia and astrocytes. We found that: (i) EPO exerted a marked stimulatory effect on microglial cell viability, assessed through the MTS assay, whereas astrocytes were almost unaffected; (ii) the cytokine increased microglial cell population size in a concentration-dependent manner; however, as microglia cultures undergo spontaneous apoptosis after separation from astrocytes, the apparent effect on cell proliferation could be attributed to EPO antagonism of normal apoptosis; (iii) subsequent flow cytometry analysis on microglial cells demonstrated both the trophic role of factor(s) released by astrocytes in mixed cultures, and the putative anti-apoptotic action of EPO; (iv) the latter was further confirmed through the assessment of gene expression of anti- and pro-apoptotic factors, which showed that EPO is able to shift the Bcl : Bax ratio towards a net anti-apoptotic effect; (v) EPO did not affect the pro-inflammatory function of microglial cells.

Animals↗
PubMed2002

Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21.

Homeostasis of the hematopoietic system is maintained by proliferation and differentiation of a small number of long-term surviving, self-renewing stem cells, which give rise to the fully mature elements. The fine interplay between differentiation, proliferation and death by apoptosis determines the equilibrium of this system. Thus, genes involved in the control of these processes are very important in the regulation and development of hematopoietic cells especially in the initial stages. The interactions among cyclins, their specific cyclin-dependent kinases (CDKs) and, a number of cyclin-dependent kinase inhibitors (CDKIs) such as p27 and p21, exert a direct control on the cell cycle but can also produce other independent effects on hematopoietic differentiation. Proteins of the Bcl-2 family are also crucial in regulating the balance between entry into apoptosis and survival capacity and their roles change in the course of differentiation. In addition, a number of autocrine and paracrine soluble factors (such as TGF-beta1) modulate the behavior and differentiation potential of hematopoietic elements. Studies on a few in vitro systems of early hematopoietic differentiation have stressed the importance of Bcl-2 and of the CDKIs p27 and p21 at this stage, have confirmed cell-cycle independent effects and have demonstrated how the modulation and the effects in response to different stimuli is mostly dependent on the differentiation stage of the target cells.

Cell Cycle↗
PubMed2002

Cell cycle regulation in human hematopoietic stem cells: from isolation to activation.

Hematopoietic stem cells (HSCs) reside mostly in the bone marrow and are defined by their ability to self-renew and to give rise by proliferation and differentiation to all blood lineages. Despite this strict definition HSCs cannot be unequivocally identified in the hematopoietic cell pool. Despite innumerable studies over the years, which focused on the search of the ideal phenotypic marker to selectively isolate stem cells, most of the known markers still define heterogeneous populations in different stages of commitment. Functional features attributed to stem cells have also been investigated, and among these the use of fluorescent markers which allow tracking of the cell division record of each cell. A second issue, after the initial isolation process, is the expansion ex vivo in order to obtain production of large numbers of homogeneous cell populations for both biological studies and clinical applications. Expansion ex vivo is difficult to modulate and normally occurs only along with commitment and consequent loss of multipotentiality. Moreover expansion obtained ex vivo is significantly reduced to that achievable in vivo. One of the key features of HSCs is a very slow proliferation rate, but when the appropriate stimuli are delivered, the proliferation rate can drastically increase. In normal physiological conditions a strict balance is maintained between the number of cells that maintain the original pool and those that proliferate and differentiate. Numerous data in recent years are providing some clue to elucidate the key steps in this tightly controlled process, but the dynamics that regulate which and how many cells self-renew to maintain the pool, and which proliferate and become committed to give rise to the mature blood elements, are still unclear.

Cell Culture Techniques↗
PubMed2002

Demonstration of human herpesvirus 8 in a case of primary vaginal epithelioid angiosarcoma by in situ hybridization, electron microscopy, and polymerase chain reaction.

We demonstrate the presence of human herpesvirsus 8 (HHV-8) in a primary vaginal location of angiosarcoma (AS) by polymerase chain reaction (PCR), in situ hybridization, and ultrastructural direct visualization of viral particles. The latter two techniques for the first time confirm HHV-8 detection in an AS by PCR; these results contribute to the debate caused by the controversial data produced by the almost exclusive use of PCR for investigating the possible presence of HHV-8 in AS, and its possible implications. Moreover, the investigated AS is the seventh published primary vaginal one, and the fourth unrelated to radiotherapy. Interestingly, the affected patient had used a ring pessary for 10 years because of an uterovaginal prolapse.

Aged↗
PubMed2002

Phase I study of gemcitabine and liposomal doxorubicin in relapsed ovarian cancer.

Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients. A total of 82 courses are evaluable, with a median number of three cycles administered per patient (range 2-8). GEM was administered on days 1 and 8 by 30-min intravenous infusion immediately after CAE given by 60-min intravenous infusion on day 1; cycles were repeated every 21 days. The starting doses were CAE 20 mg/m(2) and GEM 600 mg/m(2). Following dose levels were 20/800; 20/1,000; 30/800; 30/1,000; 35/800, and 35/1,000 for CAE and GEM, respectively. The MTD was reached at dose level 5, with febrile neutropenia and thrombocytopenia as dose-limiting toxicities. After the MTD, granulocyte-colony stimulating factor was administered in 15% of cycles. Non-hematological toxicity was mild and manageable. All patients are so far evaluable for response. Among them, 5 partial responses (21.7%; 95% confidence interval, CI: 4.9-38.5), 5 disease stabilizations (21.7%, 95% CI: 4.9-38.5) and 13 progressions (56.6%, 95% CI: 36.4-76.8) have been registered. These results warrant further research in a phase II study.

Adult↗
PubMed2001

Semiquantitative RT-PCR analysis to assess the expression levels of multiple transcripts from the same sample.

We describe a semiquantitative RT-PCR protocol optimized in our laboratory to extract RNA from as little as 10,000 cells and to measure the expression levels of several target mRNAs from each sample. This procedure was optimized on the human erythroleukemia cell line TF-1 but was successfully used on primary cells and on different cell lines. We describe the detailed procedure for the analysis of Bcl-2 levels. Aldolase A was used as an internal control to normalize for sample to sample variations in total RNA amounts and for reaction efficiency. As for all quantitative techniques, great care must be taken in all optimization steps: the necessary controls to ensure a rough quantitative (semi-quantitative) analysis are described here, together with an example from a study on the effects of TGF-beta1 in TF-1 cells.

Journal Article↗
PubMedDate not supplied

A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas.

STUDY OBJECTIVE: Comparison between laparoscopy and minilaparotomy in the management of intramural and/or subserosal uterine myomas. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Two hundred-thirteen women with at least one subserosal and/or intramural uterine myoma. INTERVENTION: Laparoscopy and minilaparotomy myomectomy. MEASUREMENTS AND MAIN RESULTS: We performed 213 myomectomies, 120 by minilaparotomy and 93 by laparoscopy. Median number of myomas removed per patient was 1.4 (range 1-3) and 2.9 (range 1-5) in the laparoscopy and minilaparotomy groups, respectively (p<.05). The estimated blood loss was not significant in either of the two groups, and no intraoperative or early postoperative complications were registered. The median operating time was 62.3 minutes (range 45-80 min) and 61.6 minutes (range 40-90 min) in the laparoscopy and minilaparotomy groups, respectively (p=NS). Median duration of ileus was 1.4 days (range 1-2) in the laparoscopy group and 1.3 days (range 1-2 days) in the minilaparotomy group (p=NS). Median length of hospital stay was 2.3 days (range 2-3 days) and 2.8 days (range 2-3 days) in the laparoscopy and minilaparotomy groups, respectively (p=NS.). CONCLUSION: Myomectomy by minilaparotomy can be considered a minimally invasive alternative to laparoscopy in the surgical management of intramural and subserosal myomas.

Adult↗
PubMedDate not supplied

Laparoscopic diagnosis of asymptomatic megaureter.

The rare case of an asymptomatic megaureter in a young woman demonstrates that laparoscopy can be helpful in the differential diagnosis for unknown retroperitoneal masses. The accurate dissection of the retroperitoneal structures together with a thorough knowledge of the retroperitoneal anatomy should always be considered in these cases.

Adult↗
PubMedDate not supplied

Estradiol and phytoestrogens differently influence the rodent postmenopausal mammary gland.

OBJECTIVE: In the following study, we investigated treatment-related changes in mammary gland histomorphology and structure after the administration of soy to adult virgin ovariectomized (OVX) female rats. Additionally, mammary receptor regulation was extensively evaluated by immunohistochemical analysis, and tissue proliferative activity analyzed by cell nuclear proliferating antigen expression (Ki67). DESIGN: OVX rats were treated, for 6 weeks, with either the vehicle, the soy extract (SSE 100 mg/kg/d PO), or 17beta-estradiol (0.5 mg/kg/d PO); a sham control group (SHAM) was also included in the study. When killed, mammary glands were collected and subsequently processed for light microscopy or immunohistochemistry. Immunoreactivity was quantified by a scoring system that took into account both the percentage of positive cells and the intensity of the staining. RESULTS: The 17beta-estradiol--treated rats had stimulated mammary glands compared with OVX rats, with an average lobulo-alveolar development not different from the SHAM controls. Only a partial regression of the glandular atrophy was observed in OVX rats receiving 100 mg/kg/d SSE, with a histological appearance between that of the OVX and SHAM controls. No significant changes were observed among experimental groups in the median ERalpha scores of the epithelial compartment (score of 3 in all groups); in the stromal compartment, a tendency toward decreased expression was seen with 17beta-estradiol rats compared with OVX controls (scores of 2 and 5, respectively). A significant reduction in ERbeta immunostaining was observed in the mammary glands of SSE-treated rats, in both epithelium and stroma (scores of 4 and 3, respectively), compared with those of OVX controls (score of 8 in both compartments). The ERbeta receptor status was not significantly affected by 17beta-estradiol. Compared with OVX rats (score of 1), PR expression was up-regulated by 17beta-estradiol (score of 6), whereas an ovariectomy-like pattern was observed after the administration of SSE (score of 0). Ki67 immunoreactivity in the epithelium and stroma was increased by the administration of 17beta-estradiol (scores of 4 and 5, respectively) and was unchanged after SSE treatment (scores of 0 and 2, respectively), compared with OVX controls (scores of 1 and 2, respectively). CONCLUSIONS: The differences observed in the histological pattern, hormonal receptor status regulation, and Ki67 modulation suggest a different role for phytoestrogens and 17beta-estradiol in postmenopausal rodent mammary glands.

Animals↗