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S Miraglia

Publications and source records attributed to S Miraglia.

18 recordsLinked to original sources
PubMed2006

The role of haemoglobin level in predicting the response to first-line chemotherapy in advanced colorectal cancer patients.

The purpose of the study was to evaluate the influence of baseline haemoglobin level in predicting response to 5-fluorouracil (5FU)-based first-line chemotherapy in advanced colorectal cancer patients. Data from 631 patients were collected from three different institutions. Globally, overall response rate was 35.8% (226 out of 631). Factors influencing response rate were 5FU dose intensity (high: 43.1%, low: 34.0%, P = 0.03); oxaliplatin (yes: 45.8%, no: 22.9%, P < 0.0001), performance status (PS 0: 46.1%, 1: 28.8%, 2: 26.7%, P < 0.0001), and haemoglobin levels (> or = 12 g dl(-1): 40.4%, < 12 g dl(-1): 29.2%, P = 0.004). In subgroup analysis significant differences in response rate between anaemic and nonanaemic patients were recorded in those patients treated with infusional chemotherapies (45.7 vs 25.5%, P < 0.0001), with high 5FU dose intensity (50.3 vs 32.7%, P = 0.005), with PS = 0 (49.8 vs 37.9%, P = 0.03), and with liver metastases (44.8 vs 33.8%, P = 0.002), whereas no difference was evident in those subjects treated with bolus schedules or according to gender. Anaemia was a strong predictor for activity of first-line 5FU-based chemotherapy especially in those groups that showed the best responses, for example high performance status, infusionally treated, higher 5FU dose and those with liver secondaries. Patients with higher haemoglobin levels recorded a greater response rate and a longer time to progression and survival than anaemic subjects. Prospective evaluation of role of correcting anaemia on response to therapy is justified by these results.

Adult↗
PubMed2001

Two-gap state density in MgB(2): a true bulk property or a proximity effect?

We report on the temperature dependence of the quasiparticle density of states in the simple binary compound MgB(2) directly measured using scanning tunneling microscope (STM). To achieve high quality tunneling conditions, a small crystal of MgB(2) is used as a tip in the STM experiment. The "sample" is chosen to be a 2H- NbSe(2) single crystal presenting an atomically flat surface. At low temperature the tunneling conductance spectra show a gap at the Fermi energy followed by two well-pronounced conductance peaks on each side. They appear at voltages V(S) approximately +/-3.8 mV and V(L) approximately +/-7.8 mV. With rising temperature both peaks disappear at the T(C) of the bulk MgB(2), a behavior consistent with the model of two-gap superconductivity. The possibility of a particular proximity effect is also discussed.

Journal Article↗
PubMed2001

Evidence for two superconducting energy gaps in MgB(2) by point-contact spectroscopy.

Experimental support is found for the multiband model of the superconductivity in the recently discovered system MgB(2) with the transition temperature T(c) = 39 K. By means of Andreev reflection, evidence is obtained for two distinct superconducting energy gaps. The sizes of the two gaps ( Delta(S) = 2.8 meV and Delta(L) = 7 meV) are, respectively, smaller and larger than the expected weak coupling value. Because of the temperature smearing of the spectra the two gaps are hardly distinguishable at elevated temperatures, but when a magnetic field is applied the presence of two gaps can be demonstrated close to the bulk T(c) in the raw data.

Journal Article↗
PubMed2001

Combined regional and systemic chemotherapy by a mini-invasive approach for the treatment of colorectal liver metastases.

From February 1996 to December 1998, 95 patients affected with colorectal liver metastases underwent the positioning of an intraarterial hepatic catheter by a transcutaneous subclavian access, under local anesthesia. All patients were evaluated for catheter implantation complications. Moreover, 61 patients of 95 treated at our center were retrospectively evaluated for results of chemotherapy performed with two different schedules of hepatic artery infusion (HAI) combined with systemic chemotherapy (SC). Eleven patients (group A) were treated with combined SC (5-fluorouracil continuous infusion) and HAI (floxuridine). A subsequent 50 patients underwent HAI (floxuridine, 4 cycles) followed, if a response or stable disease were observed, by combined SC and HAI (group B). Three cases of aneurysm of subclavian artery occurred, which were treated by the positioning of a radiologic arterial stent and the reimplantation of the catheter by a femoral access. Thrombosis of the hepatic artery was registered in four cases. We observed 10.5% occurrence of dislocation of the catheter, which was always moved again in the hepatic artery. In group A, with 45% clinical objective response rate and 10% stable disease rate, median survival time and median time to extrahepatic progression were 9 and 6 months, respectively. In group B, we observed 44% clinical objective responses and 26% stable disease after HAI. Patients without disease progression and therefore submitted to sequential SC and HAI had a median survival time of 21 months and a median time to extrahepatic progression of 16 months. The development of the mini-invasive technique of implantation of an arterial port can avoid laparotomy for HAI. Percutaneous implantation of an arterial port has a low rate of technical complications. HAI followed by combined systemic and regional chemotherapy has good results in terms of survival and time to extrahepatic progression.

Adult↗
PubMed2000

The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions.

The human AC133 antigen and mouse prominin are structurally related plasma membrane proteins. However, their tissue distribution is distinct, with the AC133 antigen being found on hematopoietic stem and progenitor cells and prominin on various epithelial cells. To determine whether the human AC133 antigen and mouse prominin are orthologues or distinct members of a protein family, we examined the human epithelial cell line Caco-2 for the possible expression of the AC133 antigen. By both immunofluorescence and immunoprecipitation, the AC133 antigen was found to be expressed on the surface of Caco-2 cells. Interestingly, immunoreactivity for the AC133 antigen, but not its mRNA level, was down-regulated upon differentiation of Caco-2 cells. The AC133 antigen was specifically located at the apical rather than basolateral plasma membrane. An apical localization of the AC133 antigen was also observed in various human embryonic epithelia including the neural tube, gut, and kidney. Electron microscopy revealed that, within the apical plasma membrane of Caco-2 cells, the AC133 antigen was confined to microvilli and absent from the planar, intermicrovillar regions. This specific subcellular localization did not depend on an epithelial phenotype, because the AC133 antigen on hematopoietic stem cells, as well as that ectopically expressed in fibroblasts, was selectively found in plasma membrane protrusions. Hence, the human AC133 antigen shows the features characteristic of mouse prominin in epithelial and transfected non-epithelial cells, i.e. a selective association with apical microvilli and plasma membrane protrusions, respectively. Conversely, flow cytometry of murine CD34(+) bone marrow progenitors revealed the cell surface expression of prominin. Taken together, the data strongly suggest that the AC133 antigen is the human orthologue of prominin.

AC133 Antigen↗
PubMed1999

Sorbitol removal by the metastatic liver: a predictor of systemic toxicity of intra-arterial chemotherapy in patients with liver metastases.

BACKGROUND/AIM: Hepatic arteriovenous shunting in the metastatic liver reduces the advantages of intraarterial infusion of chemotherapeutic agents because of the passage of drugs into the systemic circulation. The aim of this study was to quantitatively assess spontaneous functional hepatic arteriovenous shunting in patients with liver metastases and to determine its implication in the increase in systemic toxic effects of intra-arterial infusion chemotherapy with floxuridine. METHODS: Twenty-five patients who underwent implantation of arterial ports for regional chemotherapy of liver metastases were studied. Functional hepatic arterio-venous shunting was evaluated through the bioavailability of intra-arterially administered D-sorbitol, a safe, natural compound whose kinetic features make its hepatic clearance flow dependent. In addition, D-sorbitol hepatic clearance (a parameter reflecting functional liver blood flow) and common liver function tests were evaluated for each studied patient. Patients were then grouped with respect to the percentage of medically-assessed liver occupation by metastases and with respect to systemic toxicity of the chemotherapeutic treatment. Both univariate and multivariate analyses by Student's t-test and stepwise logistic regression, respectively, were performed in both groups for each of the evaluated parameters (age, liver function tests, D-sorbitol hepatic clearance and arterial bioavailability). RESULTS: Arterial bioavailability of D-sorbitol ranged between 0.05 and 0.72 and was significantly greater in patients with more than 50% liver occupation (0.39+/-0.19) compared with those with minor liver involvement (0.17+/-0.13; p = 0.003); it was also significantly greater in patients experiencing high-grade systemic toxicity (0.40+/-0.19) compared with those with low-grade toxicity (0.16+/-0.11; p<0.001). Multivariate analysis showed that arterial bioavailability of D-sorbitol was the only parameter among those evaluated which was able to predict systemic toxicity of this kind of chemotherapy. CONCLUSIONS: Our results show that, in the metastatic liver, arterial bioavailability of D-sorbitol, an index of functional arteriovenous shunting, varies widely, is significantly greater in patients with massive liver occupation and it is a good predictor of systemic toxicity of intra-arterial regional chemotherapy with floxuridine.

Adult↗
PubMed1999

Homogeneous Cell- and Bead-Based Assays for High Throughput Screening Using Fluorometric Microvolume Assay Technology.

High throughput drug screening has become a critical component of the drug discovery process. The screening of libraries containing hundreds of thousands of compounds has resulted in a requirement for assays and instrumentation that are amenable to nonradioactive formats and that can be miniaturized. Homogeneous assays that minimize upstream automation of the individual assays are also preferable. Fluorometric microvolume assay technology (FMAT) is a fluorescence-based platform for the development of nonradioactive cell- and bead-based assays for HTS. This technology is plate format-independent, and while it was designed specifically for homogeneous ligand binding and immunological assays, it is amenable to any assay utilizing a fluorescent cell or bead. The instrument fits on a standard laboratory bench and consists of a laser scanner that generates a 1 mm(2) digitized image of a 100-µmm deep section of the bottom of a microwell plate. The instrument is directly compatible with a Zymark Twistertrade mark (Zymark Corp., Hopkinton, MA) for robotic loading of the scanner and unattended operation in HTS mode. Fluorescent cells or beads at the bottom of the well are detected as localized areas of concentrated fluorescence using data processing. Unbound flurophore comprising the background signal is ignored, allowing for the development of a wide variety of homogeneous assays. The use of FMAT for peptide ligand binding assays, immunofluorescence, apoptosis and cytotoxicity, and bead-based immunocapture assays is described here, along with a general overview of the instrument and software.

Journal Article↗
PubMed1997

AC133, a novel marker for human hematopoietic stem and progenitor cells.

AC133 is one of a new panel of murine hybridoma lines producing monoclonal IgG antibodies (mAbs) to a novel stem cell glycoprotein antigen with a molecular weight of 120 kD. AC133 antigen is selectively expressed on CD34(bright) hematopoietic stem and progenitor cells (progenitors) derived from human fetal liver and bone marrow, and blood. It is not detectable on other blood cells, cultured human umbilical vein endothelial cells (HUVECs), fibroblast cell lines, or the myeloid leukemia cell line KG1a by standard flow cytometric procedures. All of the noncommitted CD34(+) cell population, as well as the majority of CD34(+) cells committed to the granulocytic/monocytic pathway, are stained with AC133 antibody. In vitro clonogenicity assays have demonstrated that the CD34(+)AC133(+) double-positive population from adult bone marrow contains the majority of the CFU-GM, a proportion of the CFU-Mix, and a minor population of BFU-E. The CD34(dim) and AC133(-) population has been shown to contain the remaining progenitor cells. AC133-selected cells engraft successfully in a fetal sheep transplantation model, and human cells harvested from chimeric fetal sheep bone marrow have been shown to successfully engraft secondary recipients, providing evidence for the long-term repopulating potential of AC133(+) cells. A cDNA coding for AC133 antigen has been isolated, which codes for a polypeptide consisting of 865 amino acids (aa) with a predicted size of 97 kD. This antigen is modeled as a 5-transmembrane molecule, a structure that is novel among known cell surface structures. AC133 antibody provides an alternative to CD34 for the selection and characterization of cells necessary for both short- and long-term engraftment, in transplant situations, for studies of ex vivo expansion strategies, and for gene therapy.

Animals↗
PubMed1997

A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning.

Phenotypic analysis of hematopoietic stem and progenitor cells (HSCs) has been an invaluable tool in defining the biology of stem cell populations. We have recently described the production of AC133, a monoclonal antibody (MoAb) that binds to a novel cell surface antigen present on a CD34(bright) subset of human HSCs. This antigen is a glycosylated protein with a molecular weight of 120 kD. Here, we report the molecular cloning of a cDNA encoding this antigen and show that it does not share homology with any previously described hematopoietic or other cell surface antigen(s). The AC133 polypeptide has a predicted size of 97 kD and contains five-transmembrane (5-TM) domains with an extracellular N-terminus and a cytoplasmic C-terminus. Whereas the expression of tetraspan (4-TM) and 7-TM molecules is well documented on mature and immature hematopoietic cells and leukocytes, this 5-TM type of structure containing two large (255-amino acid [aa] and 290-aa) extracellular loops is unique and does not share sequence homology with any known multi-TM family members. Expression of this protein appears limited to bone marrow in normal tissue by immunohistochemical staining; however, Northern analysis suggests that the mRNA transcript is present in a variety of tissues such as the kidney, pancreas, placenta, and fetal liver. The AC133 antigen is also expressed on subsets of CD34+ leukemias, suggesting that it may be an important early marker for HSCs, as well as the first described member of a new class of TM receptors.

ADP-ribosyl Cyclase↗
PubMed1996

[Two cases of melanoma metastasis. Description and review of the literature].

The metastases of malignant melanoma can appear after many years to primitive diagnosis and can involve many organs. There are reported two cases of metastatic melanoma presenting in a parotid gland and in the small bowel. The rarity of the metastatic melanoma to parotid gland and the difficulty of diagnosing intestinal involvement are discussed together with a review of the literature. The surgical treatment was justified by therapeutic and diagnostic aim, without positive influence on survival.

Aged↗