Biomedical subjects

Giovanni Sacchi

Publications and source records attributed to Giovanni Sacchi.

6 recordsLinked to original sources

PubMed2006

Role of PTHrp and PTHrp-engaged pathways in MCF-7 cells migration/invasion.

In this paper the effect of N-terminal parathyroid hormone-related protein (PTHrp) and PTHrp-engaged pathways on MCF-7 breast cancer cell migration/invasivity and matrix metalloproteinases (MMPs) production were investigated. We found that: a) migration is not affected by PTHrp and Forskolin (FK)-activated PKA, while Phorbol Myristate Acetate (PMA)-activated PKC strongly stimulates MCF-7 cells motility. b) MMPs production was unaffected by PTHrp, but FK reduced membrane-type (MT)-1 MMP expression. Conversely, PMA induced a marked increase of MT1-MMP and MMP-9. c) Chemical activation of PKC is not sufficient, by itself, to confer invasive ability to MCF-7 cells, unless they were provided with additional factors, supplied by fibroblasts. d) Matrix invasion likely occurs through an activation cascade, involving at least three components: pro-MMP-9 and MT-1 MMP (supplied by PMA-stimulated MCF-7 cells) and pro MMP-2 (supplied by fibroblasts). e) The selective chemical inhibition of the adenylylciclase (AC)/PKA and phospholipase C (PLC)/PKC pathways confirmed that MCF-7 cells invasivity is not affected by exogenous PTHrp, which can only modulate their growth. However, the PTHrp responsibility in breast cancer invasion cannot be completely excluded. Indeed, fibroblasts are known to respond to PTHrp (which is a normal product of MCF-7 as well as other breast cancer cells) with enhanced release of MMP-2. On the basis of the documented requirement of fibroblast-derived MMP-2 for MCF-7 cell invasivity, a novel humoral fibroblast-breast cancer cell interaction, mediated by PTHrp, can be recognised.

Breast Neoplasms↗

PubMed2005

Sclerosing peritonitis: a nosological entity.

The peritoneal histology of 224 peritoneal dialysis (PD) patients without sclerosing peritonitis (SP) and of 39 PD patients with SP was evaluated. Of the 224 patients, 180 showed simple sclerosis (SS). In these subjects, slight thickness of sclerosis (10 - 70 microm), slight parvicellular infiltration (5/180), slight arterial thickening with no vessel occlusion (19/180), and slight tissue calcification (1/180) were observed. In the 39 patients with SP, striking histological changes versus SS were detected: thickness of sclerosis 250 - 4000 microm, p < 0.01; inflammation 39/39, p < 0.01 (parvicellular infiltration 36/39, p < 0.01; microabscesses 15/39, p < 0.05; giant cells 38/39, p < 0.01; granulation tissue 38/39, p < 0.01); arterial alterations 39/39, p < 0.01 (thickening 39/39, p < 0.01; occlusion 39/39, p < 0.01; calcification 26/39, p < 0.01; ossification 9/39, p < 0.01); tissue calcification 12/39, p < 0.01 (with ossification 4/39, with bone marrow 2/39). The thickness of sclerosis in SS was higher in parietal (30 - 70 microm) than in visceral peritoneum (10 - 40 microm, p < 0.05); in SP it was higher in visceral (600 - 4000 microm) than in parietal peritoneum (250 - 2000 microm, p < 0.05). These striking differences suggest consideration of SS and SP as two separate nosological entities. Differences in frequency, animal models, etiology, and clinical impact seem to confirm this hypothesis, showing that SP is not just the evolution of SS.

Humans↗

PubMed2003

Lymphatic vessels in colorectal cancer and their relation with inflammatory infiltrate.

PURPOSE: The aim of this study was to determine why colorectal tumors confined to submucosa rarely metastasize. Under normal conditions, the submucosa contains many large lymphatic vessels with thin walls that would presumably favor the spread of cancer cells through the lymphatic system. METHODS: Specimens of colorectal cancer tissue, the border between tumor and normal tissue, and normal tissue were obtained from patients undergoing radical resection of colorectal cancer. The material was embedded in methacrylate resin for light microscopy and Epon for transmission electron microscopy examination. Light microscopy observations were routinely performed on serial sections. RESULTS: No lymphatic vessels were ever found in the tumor mass. The border area contained peritumoral inflammatory infiltrate of variable thickness. Where submucosal lymphatic vessels came into contact with peritumoral inflammatory infiltrate, they were profoundly altered: their endothelium was fragmented, and their walls were disrupted. These altered lymphatic vessels were almost always accompanied by mast cells, which were observed in the process of degranulating toward the lymphatic endothelium. No such alterations were detected in blood vessels. CONCLUSION: Our results suggest that mast cells, probably influenced by inflammatory infiltrate and/or colorectal cancer cells, destroy lymphatic vessels, which prevents cancer cells from spreading through the lymphatic system.

Aged↗

PubMed2002

Focal adhesion molecules expression and fibrillin deposition by lymphatic and blood vessel endothelial cells in culture.

The microfibrils of anchoring filaments, a typical ultrastructural feature of initial lymphatic vessels, consist mainly of fibrillin and are similar to the microfibrils of elastic fibers. As we previously demonstrated, they radiate from focal adhesions of lymphatic endothelium to the perivascular elastic network. Although present in large blood vessels, fibrillin microfibrils have never been detected in blood capillaries. Here we report immunohistochemical evidence that cultured bovine aortic and lymphatic endothelial cells express fibrillin microfibrils. These microfibrils form an irregular web in lymphatic endothelial cells, whereas in blood vessel endothelial cells they are arranged in a honeycomb pattern. Cultured lymphatic and blood vessel endothelial cells also produce focal adhesion molecules: focal adhesion kinase, vinculin, talin, and cytoskeletal beta-actin. Our data suggest that anchoring filaments of initial lymphatic vessels in vivo may be produced by endothelium. Through their connection with focal adhesions, they may form a mechanical anchorage for the thin wall of initial lymphatic vessels and a transduction device for mechanical signals from the extracellular matrix into biochemical signals in endothelial cells. The complex anchoring filaments-focal adhesions may control the permeability of lymphatic endothelium and finely adjust lymph formation to the physiological conditions of the extracellular matrix. The different deposition of fibrillin microfibrils in blood vessel endothelial cells may be related to the necessity of withstanding shear forces. Thus, in our opinion, differences in fibrillin deposition imply a different role of fibrillin in blood vessel and lymphatic endothelium.

Actins↗

PubMedDate not supplied

Ossification of the peritoneal membrane.

BACKGROUND: Peritoneal dialysis (PD) patients rarely develop sclerosing peritonitis (SP), a severe, life-threatening condition of unknown pathogenesis. Ossification of the peritoneum (PO) is a rare occurrence, which has, however, been reported in PD patients with SP. OBJECTIVE: To investigate etiopathogenetic correlations between PO and SP by histopathological examination. METHOD: We examined biopsy specimens, obtained by laparoscopy or during surgery from 36 patients with SP, from all parts of Italy in the past 8 years for evidence of peritoneal calcification or ossification. Other studies were performed on a sample of dense white material found under the parietal peritoneum of 1 patient during laparoscopy. RESULTS: Ossification of the peritoneum was found in 4/16 patients with calcifications. In addition to PO, we also found bone marrow in two specimens and arterial ossification in one case. In specimens with calcifications, and especially those with ossification, there was evidence of peritoneal inflammation with infiltration of lymphocytes, multinuclear giant cells, macrophages, and mast cells. The chemical composition of the whitish material was 85% calcium chloride and 15% hydroxyapatite. CONCLUSIONS: Calcifications alone were found in 33% (12/36) of cases of SP; 11% of SP cases were complicated by both peritoneal calcification and ossification (4/36), which indicates great availability of calcium under conditions of inflammation. Where does this calcium come from? In 1 patient with PO, the quantity of calcium was enormous and its unusual composition suggested a link with the calcium contained in dialysis solution.

Adult↗

PubMedDate not supplied

Omental milky spots and peritoneal dialysis--review and personal experience.

BACKGROUND: Little research has been dedicated to milky spots (MS), except for their role in oncology. In the field of peritoneal dialysis (PD), studying MS could help in understanding peritoneal defenses. METHODS: We reviewed the methods for detecting and counting omental MS and studied modifications induced by chemical and inflammatory stimuli. The reactions of MS to peritoneal catheters, PD solutions, and infection were studied in 32 rabbits. We also evaluated changes in MS in 39 serial omental biopsies from 16 patients with different histories of PD, and examined peritoneal biopsies from 38 patients with sclerosing peritonitis. RESULTS: The catheter provoked an immediate increase in the number and size of MS in rabbits. Intraperitoneal infusion of commercial PD solution containing 1.38% or 3.86% glucose for 30 days led to a slight but significant increase in the number and size of MS, without differences between the two glucose concentrations. Peritonitis caused a sharp increase in the number of MS in rabbits and humans, and a particular transformation. In patients with simple sclerosis, we observed normal MS having the same number and size as in patients without simple sclerosis. A few MS were found in only 2 patients with sclerosing peritonitis. CONCLUSIONS: Peritoneal dialysis activates omental MS. Peritoneal infection leads to a marked increase in the activity of MS, some of which undergo a singular transformation, casting doubt on previous theories about differentiation of MS from other lymphatic organs. Comparison with oncological studies indicates certain contact points. The presence of MS in PD patients with simple sclerosis is in contradiction to other morphological studies sustaining that MS act only when in contact with a fenestrated mesothelial basement membrane. Finally, the shortage of MS in patients with sclerosing peritonitis raises certain questions about etiopathogenesis.

Animals↗