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A Ciarrocchi

Publications and source records attributed to A Ciarrocchi.

9 recordsLinked to original sources
PubMed2005

Induction of complete regressions of oncogene-induced breast tumors in mice.

Over the past decade, mouse models of cancer have come to resemble human disease much more closely than simple subcutaneous or orthotopic systems. Intervention strategies that work on these new model systems are more likely to have an impact clinically. We have shown recently that antiangiogenic stress imposed by loss of Id protein in endothelial progenitor cells results in dramatic central necrosis in breast tumors initiated in mice by overexpression of the her2/neu oncogene. Tumor cells remain viable at the periphery, perhaps via the hypoxic response pathway which allows the lesions to expand. Inhibition of this pathway by the inactivation of the Hif-1alpha chaperone Hsp90 in combination with antiangiogenic stress leads to the first reported complete regression of these aggressive breast tumors.

Angiogenesis Inhibitors↗
PubMed1992

Extracellular RGD-binding proteins modulate cell adhesion.

Cell/fibronectin adhesion in extracellular matrices is partly mediated by integrin receptor recognition of RGD domains in fibronectin. Since blood contains significant levels of soluble fibronectin we have now investigated the occurrence of extracellular RGD-binding proteins. Attachment assays indicate that extracellular RGD-binding proteins prevent cell adhesion, suggesting their potential as novel secreted modulators of blood-borne cell adhesive interactions. These extracellular RGD-binding proteins also showed electrophoretic changes with reducing agents, suggestive of intrachain disulphide bonds, like those found in RGD-binding integrins. However, they differed from the latter in their electrophoretic profile, which was greatly dependent on the presence of protease inhibitors. Plasma from tumor-bearing mice showed a greater proportion of fast-migrating RGD-binding species under reducing condition compared to similarly treated normal plasma, suggesting that tumor development is associated with a partial degradation of extracellular RGD-binding proteins.

Animals↗
PubMed1992

Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients without coronary artery disease.

Familial Hypercholesterolemia (FH) is a condition characterized by markedly elevated blood cholesterol, low-density lipoproteins (LDL), and apolipoprotein B-100 (apo B). The molecular basis of this monogenic disease is the defective functioning of the cellular receptor for LDL that recognizes apo B. Lipoprotein(a) [Lp(a)] is a circulating lipoprotein that is structurally related to LDL, as it also contains apo B. To assess the impact of the LDL receptor deficiency on the plasma Lp(a) concentration, we measured Lp(a) in 28 FH patients and in 31 unaffected relatives. Because elevation of Lp(a) concentration in plasma of patients with coronary artery disease (CAD) appears to occur independently from plasma cholesterol levels, to avoid potentially confounding problems, members of the families chosen had no history for the disease. Whereas apo B clearly showed a bimodality of distribution by being significantly higher in the FH patients (166 +/- 38 mg/dL) than in the unaffected relatives (92 +/- 18 mg/dL), Lp(a) concentration did not differ in the two groups of patients (30 +/- 24 mg/dL in the FH patients v 31 +/- 23 in the normolipidemic relatives). Similar results were obtained when only siblings were further considered. We conclude that although Lp(a) is closely related to LDL structurally, its level in plasma is not significantly affected by the LDL receptor activity.

Adolescent↗
PubMed1991

Duplication of exons 13, 14 and 15 of the LDL-receptor gene in a patient with heterozygous familial hypercholesterolemia.

During a survey of Italian patients with familial hypercholesterolemia (FH), we identified an FH heterozygous patient with a gross rearrangement of the low density lipoprotein (LDL) receptor gene. Southern blot analysis of the proband's DNA digested with restriction enzymes PvuII, BamHI, BglII and XbaI and hybridization with cDNA probes complementary to the 3' end of the gene revealed the presence of abnormal fragments that were approximately 7 kb larger than their normal counterparts. DNA digestion with other enzymes (EcoRV, NcoI, KpnI and StuI) and hybridization with probes complementary to exons 13-17 generated normal fragments and an abnormal fragment of 6.3-6.8 kb. These results are consistent with the presence of an insertion of approximately 7 kb caused by a duplication of exons 13, 14 and 15. This is a novel mutation that is most probably the result of an unequal crossing-over between repetitive sequences located in intron 12 and intron 15. This novel mutation has been designated FHBologna 2.

Aged↗
PubMed1991

Pravastatin in heterozygous familial hypercholesterolemia: low-density lipoprotein (LDL) cholesterol-lowering effect and LDL receptor activity on skin fibroblastS.

The cholesterol-lowering effect of provastatin, a new competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, was studied in 10 patients with heterozygous familial hypercholesterolemia (FH). Residual low-density lipoprotein receptor (LDL-R) activity was also evaluated in cultured skin fibroblasts prior to treatment, and showed a wide range of reduction from 30% to 70% of the normal value. Treatment with pravastatin 40 mg once daily reduced total and LDL cholesterol (LDL-C) after 6 months by 19.7% and 25.4%, respectively (P less than .001). Serum apolipoprotein (apo) B levels decreased significantly by 29.1% (P less than .001). No significant changes were observed in mean serum total triglycerides or high-density lipoprotein cholesterol (HDL-C) levels. A positive correlation between residual LDL-R activity and maximum percent reduction of LDL-C levels was observed (r = .676, P less than .05). No clinically important side effects were recorded and the treatment was well tolerated. Thus, pravastatin effectively reduces LDL in heterozygous FH, and this effect appears to be related to LDL-R status.

Cholesterol, LDL↗
PubMed1991

Dietary treatment for familial hypercholesterolemia--differential effects of dietary soy protein according to the apolipoprotein E phenotypes.

Familial hypercholesterolemia, one form of type IIa hyperlipidemia, usually responds poorly to standard low-lipid diets. To define the responsiveness to a soy-protein diet in this disease, one homozygous and twenty heterozygous type IIa patients were submitted to a 4-wk traditional hypocholesterolemic diet followed by 4 wk in which animal protein was substituted with texturized soy protein. Soy was then withdrawn for a further 4 wk. No significant changes in plasma lipids were observed during low-lipid diets. The soy diet, however, caused a marked decrease in total (-20.8%) and low-density-lipoprotein (-25.8%) cholesterol and in apolipoprotein B (-14.1%). The plasma cholesterol reduction was higher in patients with apolipoprotein E3/E3 or E3/E4 vs an almost negligible effect on E3/E2. These results confirm that soy-protein diets can lower cholesterol in type IIa patients with familial disease. Data on the sensitivity of patients with different apo-E isoforms agree with recent hypotheses suggesting that soy proteins may activate B,E receptors.

Adult↗
PubMed1989

Role of Ca2+ in H+ transport by rabbit gastric glands studied with A23187 and BAPTA, an incorporated Ca2+ chelator.

The role of Ca2+ in stimulation of H+ gastric secretion by cAMP-dependent and -independent secretagogues was studied in isolated rabbit glands using Ca2+ ionophore, A23187, and an intracellular Ca2+ chelator (BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) incorporated as its acetoxymethyl ester (BAPTA-AM). Acetylcholine (ACh), tetragastrin (TG), histamine and forskolin induced a transitory increase of intracellular Ca2+ concentration, [Ca2+]i, measured in gastric glands loaded with Ca2+-sensitive dye fura-2, and provoked an acid secretory response evaluated with aminopyrine accumulation ratio (AP ratio). The Ca2+-ionophore A23187 also induced an increase in [Ca2+]i and in AP ratio. cAMP-dependent secretagogues were more potent stimulants of acid secretion than cAMP-independent secretagogues. cAMP analogue, 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BR-cAMP) induced an increase in AP ratio without modifying [Ca2+]i. BAPTA-AM (5-25 microM) induced a transient decrease of resting [Ca2+]i which returned to basal level due to extracellular Ca2+ entry. Increases in [Ca2+]i produced by ACh and TG were abolished by BAPTA and those produced by Ca2+ ionophore A23187 were partially buffered. BAPTA inhibited in a dose-dependent manner H+ secretion induced by cholinergic and gastrinergic stimulants in the presence of cimetidine. A23187 increased the AP ratio to values similar to those obtained with ACh or TG and was not inhibited by BAPTA. BAPTA partially inhibited (40%) the increase in AP ratio induced by forskolin and histamine inspite of the complete inhibition of the Ca2+ response. BAPTA did not inhibit the response to 8-BR-cAMP. BAPTA inhibition of forskolin stimulation was reversed by A23187 and the response was potentiated. These results indicate that ACh and TG response are completely dependent on an increase of [Ca2+]i. The response to cAMP-dependent agonists histamine and forskolin depend both on Ca2+ and cAMP. For forskolin stimulation the response may be the result of a potentiation between Ca2+ and cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Characterization of three mutations of the low density lipoprotein receptor gene in Italian patients with familial hypercholesterolemia.

Three gross rearrangements of the low density lipoprotein receptor (LDL-R) gene were recognized during a survey of 23 unrelated Italian subjects with familial hypercholesterolemia (FH). Restriction endonuclease data were obtained by Southern blotting and hybridization with exon-specific probes. Proband FH-29 is heterozygous for a 4-kb deletion, which eliminates exons 13 and 14. This mutation is similar to that previously reported by other investigators in one Italian homozygous and two British and Canadian heterozygous patients. Proband FH-30 is homozygous for a 5.5-kb insertion caused by a duplication of exons 16 and 17 of the LDL-R gene. LDL-R mRNA isolated from skin fibroblasts of FH-30 was found to be larger than normal mRNA (5.6 versus 5.3 kb), in concordance with the insertion of the 236 nucleotides corresponding to exons 16 and 17. Proband FH-44 was found to have greater than 25-kb deletion, which eliminates the first six exons and the promoter region of the gene. This is the first example of a deletion that eliminates the promoter as well as the ligand-binding domain of the LDL-R gene. In the skin fibroblasts of this patient, the level of LDL-R mRNA was approximately half that found in control fibroblasts. We designate the new mutations found in FH-30 and FH-44 as FHviterbo and FHBologna-1, respectively, after the names of the Italian cities where the two patients were born.

Adult↗