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Biomedical subjects

A Barbarisi

Publications and source records attributed to A Barbarisi.

At least 19 recordsLinked to original sources
PubMed2004

Synthesis and characterisation of poly(2-hydroxyethyl methacrylate) polyelectrolyte complexes.

Copolymerisation of charged and neutral monomers is a well-known methodology to introduce charged moieties in a polymeric chain to obtain polyelectrolytes. New polyelectrolyte complexes have been synthesised by radical copolymerisation of neutral methacrylic monomer 2-hydroxyethyl methacrylate (HEMA) with cationic 2-methacryloyloxyethyltrimethyl ammonium chloride and anionic 2-acrylamido-2-methylpropane-sulphonic acid monomers in 10:1:1 and 10:1:2 stechiometric ratio. Chemical structure of the synthesised terpolymers was confirmed by FT-IR spectroscopy, moreover, X-ray photoelectron spectroscopy showed the presence of a cationic charge excess on the 10:1:2 terpolymer surface with respect to 10:1:1 terpolymer. Swelling studies for 10:1:2 terpolymers showed a high water content in the swollen state and a "smart behaviour" upon changes in external stimuli such as pH, while, 10:1:1 terpolymer presented the behaviour of a neutral polymer. Mechanical and differential scanning calorimetry analysis confirmed that terpolymer networks were stabilised by ionic co-operative interactions. Infact, the inclusion of oppositely ionic charges in the polymeric network of p(HEMA) represent a way to achieve higher elastic modulus as they stabilise the terpolymer networks. Cytotoxicity and cytocompatibility studies demonstrated that all materials were not toxic, moreover, the presence of a cationic charge excess on 10:1:2 terpolymer surface was able to promote fibroblast adhesion.

Absorption↗
PubMed2003

[Cancer risk in breast lesions: diagnostic and therapeutic strategy].

BACKGROUND: The classification, diagnostic recognition and surgical treatment of breast lesions at risk of neoplastic transformation represent some of the most important objectives in breast research. Attention has been focused on lesions at risk of neoplastic transformation in breast pathology, such as: atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), multiple intraductal papilloma and sclerosing adenosis. METHODS: Our experience regards activity carried out from 1996 to 2001; the diagnostic approach included routine performance of echotomographic examination, mammography screening indicated in women >40 and, in selected cases, in women <40; FNAB was carried out in all lesions containing suspicious cells. In the case of non-palpable lesions we carried out a CT-guided FNAB using the stereotaxic technique. In cases of secreting breast, galactography proved useful. As regard clinically suspect nipple secretions, cytology was useful in the diagnosis of intraductal papillomatous lesions. Surgery was indicated for: mammographically negative nodular lesions with cytological finding of suspect lesions. Continuous, spontaneous mono-orificial, serous, sero-hematic or hematic secretion of the nipple also in the presence of negative and/or inconclusive galactographic and cytological findings. From a nosological viewpoint we have distinguished 3 groups: A) 49 women (average age 47.3 years) with suspect lesions subjected to biopsy. On the basis of the cytological response we carried out: 37 quadrantectomies with extemporary examination, 4 excisional biopsies, 5 radical ductectomies and 3 microductectomies. B) 26 patients (36.7 years) subjected to mammary biopsy for non-suspect lesions; in 24 cases excisional biopsy of the lesion and in 2 cases radical ductectomy. C) Control group consisting of 141 women (average age 44.5 years) suffering from benign pathology not suspected of lesions at risk and not subjected to surgery. RESULTS: The final histological examination evidenced: Group A: 7 cases of T1aN0M0 carcinoma (14.3%); 20 lesions at risk (40.8%); 22 lesions not at risk; Group B: 25 (96.1%) lesions not considered at risk, in 1 case (3.9%) area of sclerosing adenosis with ductal proliferation and slight atypias; Group C: in 4 cases (3.1%) the onset at follow-up of lesions at risk made it necessary to remove the lesion. Histology did not confirm the presence of cancer in any case. CONCLUSIONS: The diagnostic and therapeutic protocol proposed enables us to identify and radically treat high risk patients (Group A) and follow them up closely. On the contrary, Group B evidenced a very low incidence of lesions at risk which escaped preoperative diagnosis and in confirmation of this in Group C, during follow-up, the onset of only 4 lesions at risk was identified in which histological examination however excluded the presence of cancer.

Adult↗
PubMed2001

17-beta estradiol elicits an autocrine leiomyoma cell proliferation: evidence for a stimulation of protein kinase-dependent pathway.

The mechanism by which estradiol (E2) acts on cell proliferation is still unclear. In this paper, we report the results of a series of experiments in an attempt to elucidate the effector pathway(s) involved in coupling the E2 receptors binding to cellular growth response in leiomyoma cells (LSMC). Under conditions of E2-dependent growth, E2 treatment of LSMC triggers rapid and transient activation of the MAP-kinase pathway. Interestingly, we demonstrate that the early downstream signal transduction events determined by E2-stimulation in quiescent LSMC, including the rapid protein tyrosine phosphorylation of a subset of intracellular proteins, such GAP, PI-3-K, and PLCgamma, and the concomitant activation of ancillary protein kinases, are related to E2-induced PDGF secretion. Moreover, we identify the PDGF, alone or in association with other growth factors, as the main growth factor involved in the proliferation response of LSMC to E2 stimulation. The addition of neutralizing antibodies anti-PDGF was able to inhibit the mitogenic activity present in LSMC conditioned media samples. On the other hand, E2 did not affect the constitutive expression as well as the ligand affinity of PDGF receptors on LSMC plasmamembrane. Cell treatment with the antiestrogen ICI 182780 correlate both with a perturbation of E2-induced transductional circuit and with the disappearance of the mitogenic factor, PDGF, in LSMC conditioned media; the latter therefore, represents the main autocrine mediator of cell growth modulation, upregulated by E2 and down-regulated by antiestrogenic compound. Our experiments suggest that growth factor secretion is an initial and integral part of the signaling events mediated by the estradiol receptors, not related, at least in part, to E2 transcriptional modulation.

Cell Division↗
PubMed2001

Impact of surgical treatment on quality of life of patients with gastrointestinal tumors.

Quality-of-life assessment is becoming an important concern even of surgeons. The new trend applies specifically to surgical oncology, where particular attention is now being paid to the outcome of surgical treatment. Gastrointestinal cancers are heterogeneous in their presentation and in treatment, but they share common aspects related to the surgical approach. A functional outcome is fundamental in all the operations performed for gastrointestinal cancers and many improvements have been made thanks to the increased rate of conservative approaches and the amelioration of the technology applied to surgery. The measurement of the surgical outcome and the methods to be applied is still undergoing extensive evaluation but the flourishing interest in the issues concerning quality of life all over the surgical community will rapidly lead to a better definition of goals and results.

Colorectal Neoplasms↗
PubMed2001

Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis in the absence of biallelic inactivation of the adenomatous polyposis coli gene.

Papillary thyroid carcinoma (PTC) is a rare extracolonic manifestation of familial adenomatous polyposis, determined by germline mutations of the adenomatous polyposis coli (APC) gene. The aim of this study was to assess the presence of loss of heterozygosity of APC in the thyroid tumoral tissue. Specimens from six female patients, aged 20-36, were analyzed for germline and somatic mutations of the APC gene by restriction enzyme analysis and sequence analysis. Five of the six also had analysis for ret/PTC, a chimeric gene, the activation of which is restricted to papillary TC. Because a previous study showed that germline mutations in familial adenomatous polyposis-associated thyroid carcinoma were located between codons 140 and 1513, the search for somatic mutations of the APC gene was restricted to this genomic area. Three of the six patients, belonging to the same kindred, had a germline mutation at codon 1061. The remaining three, one per kindred, had germline mutations at codons 1061, 1061, and 1309, respectively. None of the six patients had loss of heterozygosity for APC or somatic mutation in the explored genomic area (codon 545 and codons 1061-1678). Four of five had activation of ret/PTC in the thyroid tumoral tissue, as ret/PTC1 isoform. Either APC has a tissue-specific dominant effect in the thyroid gland or the germline mutation confers a generic susceptibility to cancer development, but other factors (sex-related factors, environmental radiation, modifier genes) are also required for TC development. This usually involves ret/PTC activation, suggesting a possible cooperation between altered function of APC and gain of function of ret.

Adenomatous Polyposis Coli↗
PubMed2000

Carnitine: an osmolyte that plays a metabolic role.

Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic ones. It is the sole source of carbon and nitrogen in some bacteria; it serves as osmoprotectant in others. It is a carrier of acyl moieties, and exclusively of long-chain fatty acids for mitochondrial beta-oxidation in mammals. The conspicuously similar composition of the intracellular milieu among widely different species in relation to organic osmolyte systems involves the methylamine family to which carnitine belongs. This prompted us to examine the osmolytic properties of carnitine in an attempt to clarify the metabolic functions carnitine has acquired during evolution. An understanding of the metabolic functions of this organic compatible solute impinge on research involving this compound.

Animals↗
PubMed2000

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system.

An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.

Antineoplastic Agents↗
PubMed2000

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer.

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.

Adult↗
PubMed2000

Phase I dose escalation study of gemcitabine and paclitaxel plus colony-stimulating factors in previously treated patients with advanced breast and ovarian cancer.

Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced breast and ovarian cancer. In this Phase I study, we used fixed doses of gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in the first small patient group at a dose of 90 mg/m2, which was then escalated in subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all patients received granulocyte colony-stimulating factor 300 microg by subcutaneous injection on days 5 and 6, and granulocyte macrophage colony-stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at each dose level. Dose escalation was stopped if at least a third of the patients in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The maximum tolerated dose (MTD) was defined as the dose level immediately below that causing DLT in one-third of the patients or more. Evaluation of the tumour response was performed every three cycles. Forty-five patients (31 with breast cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only at the seventh PTX dose level was DLT observed after the first course of therapy: three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia. DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose escalation was stopped at that level and the dose immediately before it (PTX 240 mg/m2) was considered as the MTD and recommended for further studies. No toxic deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally mild. Among 30 evaluable patients with metastatic breast cancer, four complete responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an overall response rate of 53% (95% confidence interval (CI) 34-72). The median duration of response was 31 weeks. Among 13 evaluable patients with advanced ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall response rate of 46% (95% CI 19-78). The median duration of response was 32 weeks. Our study shows that gemcitabine and PTX can be administered in combination in patients with breast and ovarian cancer without unexpected toxicities and with encouraging therapeutic results.

Adult↗
PubMed1977

[Enzymatic changes in the lymph in the thoracic duct and right lymphatic duct during extracorporeal circulation in the dog (author's transl)].

The authors analysed the various enzymes in the lymph of the thoracic duct and the right lymphatic duct in a series of 15 dogs submitted to extracorporeal circulation, the experimentors noted a series of diffuse cellular lesions which involved transiently the main organs. This lesion seems only to occur at first; independent of the duration of the by-pass, probably due to hypoxia following the rapid and massive introduction of priming. Our conclusion from this research is that lymph analysis is more revealing for knowledge of enzyme behaviour than blood analysis. A differential study of lymph in the right lymphatic duct and in the thoracic duct is surprisingly much less important.

Animals↗