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Antonino Cavallaro

Publications and source records attributed to Antonino Cavallaro.

At least 19 recordsLinked to original sources

TIMP-2 modulates neointimal formation in experimental ePTFE arterial grafts.

BACKGROUND: In vascular reconstructive surgery, myointimal hyperplasia contributes to the adverse outcome of synthetic grafts. This phenomenon is because of unregulated extracellular matrix degradation and remodeling, and excessive smooth muscle cell proliferation and migration. Matrix metallopreoteinase 2 (MMP-2) is known as an important contributor to these events. The aims of our study was to investigate the effects of selective MMP-2 inhibitor (TIMP-2) in endothelialization rate, SMC proliferation, and myointimal hyperplasia in experimental ePTFE arterial grafts. METHODS: In 20 male Lewis rats, a 1-cm long ePTFE graft has been inserted at the level of the abdominal aorta. Animals were randomized in two groups (10 animals each): group A received six subcutaneous inoculations of TIMP-2 (2.5 microg) after surgery, group B received only the vehicle of TIMP-2. RESULTS: Neointimal thickness, as well as SMC density, were augmented in group B, whereas endothelial cells density was augmented in group A, and these findings were statistically significant. In group A SMC were better organized, just like SMC of thoracic aorta. In group B SMC were no organized. Furthermore, anti-TIMP-2 and anti-MMP-2 coloration revealed higher levels of TIMP-2 and lower levels of MMP-2 in group A versus group-B. CONCLUSIONS: Use of TIMP-2 affects the neointimal formation of experimental e-PTFE arterial grafts, leading to a better-organized neointima, with improved endothelialization.

Animals↗

High density lipoproteins downregulate basic fibroblast growth factor production and release in minimally oxidated-LDL treated smooth muscle cells.

Increase in plasma low density lipoprotein (LDL) levels and/or decrease in high density lipoprotein (HDL) levels are major risk factors for the development of atherosclerosis. An oxidative modification of LDL represents a key process in atherogenesis. It is well known that the LDL/HDL ratio is more important than the individual LDL and HDL levels to predict atherosclerosis. The purpose of our study was to investigate the effects of mildly oxidized LDL (minimally modified LDL: MM-LDL) and HDL, administrated alone or in combination, on the production and release of basic fibroblast growth factor (bFGF) by bovine aortic smooth muscle cells (SMCs) in culture. MM-LDL and HDL have opposite effects on aortic SMCs: MM-LDL increases both bFGF production and release and SMC proliferation, while HDL decreases both bFGF production and release and SMC proliferation. The effects of either MM-LDL or HDL on SMCs are mediated through a Gi-protein-coupled receptor. The simultaneous treatment of SMCs with MM-LDL and HDL (MM-LDL/HDL ratio=4.0) produced the inhibition of MM-LDL effects. Our data suggest that the protective role of HDL could also be exerted through the inhibition of the pro-atherosclerotic effects of MM-LDL on SMCs.

Animals↗

Surgical treatment of pancreatic head carcinoma in elderly patients.

HYPOTHESIS: The treatment of cancer in elderly patients has become a global clinical issue, considering the increasingly longer life expectancy. Three quarters of patients with pancreatic adenocarcinoma are older than 60 years. Surgical resection is the only chance of cure, and early outcome of pancreaticoduodenectomy in elderly patients is comparable with that obtained in a younger population. DESIGN: During an 11-year period, 166 patients underwent curative pancreaticoduodenectomy for pancreatic adenocarcinoma. Clinical and demographic factors were evaluated by univariate and multivariate analyses to test their effect on early outcome. SETTING: State university medical school tertiary care center. PATIENTS: One hundred sixty-six patients underwent curative pancreaticoduodenectomy for pancreatic adenocarcinoma. They were divided into 2 groups according to age (group A for patients older than 70 years, group B for patients younger than 70 years). INTERVENTION: Pancreaticoduodenectomy was performed using a Whipple procedure. An end-to-end pancreaticojejunostomy was constructed. Lymphadenectomy was carried out along the hepatoduodenal ligament, common hepatic artery, vena cava, superior mesenteric vein, and along the right side of the superior mesenteric artery. Four abdominal drainage sites were routinely used. MAIN OUTCOME MEASURES: The postoperative hospital stay was calculated and morbidity and mortality were assessed. RESULTS: Significantly higher operative morbidity and mortality were observed in group A (group A, 49.1% vs group B, 45.8% and 10.5% vs 3.7%, respectively). Underlying comorbid conditions in group B patients influenced postoperative morbidity but not mortality. Rate and nature of surgical complications were indicated as causes of significant higher mortality in group B patients. CONCLUSIONS: An aggressive surgical approach is justified for elderly patients with pancreatic adenocarcinoma. However, surgical complications that lead to reoperation are responsible for a high mortality in elderly patients. In addition to general causes, such as concomitant disorders, reduced functional reserve, poor tolerance to stress, and the texture of the pancreatic remnant, there are specific prognostic factors affecting pancreaticojejunostomy leakage and related mortality.

Adenocarcinoma↗

Endoscopic retrograde cholangiography for intrabiliary rupture of hydatid cyst.

BACKGROUND: Hydatid disease affects most commonly the liver, and rupture into the bile ducts is a frequent complication, occurring in 5% to 25% of cases. These complications can cause major clinical problems either preoperatively or postoperatively with post-resectional abscess or prolonged biliary fistula. We reviewed our experience with preoperative endoscopic retrograde cholangiography (ERC) and the diagnosis of major cyst-biliary fistula. METHODS: During a 7-year period, 78 patients underwent surgery for hepatic hydatid disease. Ten patients, in whom a major intrabiliary rupture of the cyst was suspected on the basis of clinical and radiological criteria, underwent preoperative ERC, with clearing of the biliary tree. Endoscopic sphincterotomy was performed in 7 cases when the fluid contained daughter cysts or pus. Three patients, in whom the biliary content was fluid only, did not undergo sphincterotomy. One patient in whom a preoperative ERC was not feasible underwent operative transduodenal sphincterotomy. In all 11 patients the cyst was resected. Two patients underwent preoperative ERC, but no fistula was detected . They were compared with the remaining group of 67 patients who underwent resectional surgery during the same period, for apparently uncomplicated echinococcal cysts, and with an historical group of 569 patients operated on from January 1966 to January 1995. RESULTS: According to the clinical and radiological preoperative criteria, there were 2 false positives. Preoperative ERC allowed visualization of the fistula, clearing of the biliary tree, and sphincterotomy in selected cases. The incidence of postoperative fistula was significantly decreased after the introduction of selective preoperative ERC, on the basis of preoperative clinical and radiological criteria. CONCLUSIONS: Preoperative ERC is very helpful in patients with cyst-biliary fistula, allowing visualization of the fistula and drainage of the biliary tree, and reducing the incidence of postoperative complications from 11.1% to 7.6%. In selected cases it can solve the problem, without further surgical therapy.

Biliary Fistula↗

Role of platelet-derived growth factor and transforming growth factor beta1 the in the regulation of metalloproteinase expressions.

BACKGROUND: We investigated the role and influence of platelet derived growth factor (PDGF) and transforming growth factor beta1 (TGF) in the pathologic mechanism at the basis of plaque instability regulating the expression of matrix metalloproteinases (MMPs). METHODS: Plaques obtained from 70 patients who underwent carotid endarterectomy were classified histologically as stable or unstable. Serum levels of PDGF and TGF were measured pre- and postoperatively. The serum activities of MMP-2 and MMP-9 were also analyzed. Human umbilical artery smooth muscle cells (HUASMCs) were stimulated in vitro with PDGF at various concentrations (20 and 50 ng/mL) and TGF (2 and 5 ng/mL) in a serum-free medium. The release of MMPs in the conditioned medium was assessed by enzyme-linked immunosorbent assay. Release of the MMPs was confirmed by Western blot analysis; their activity and expression were determined by zymography and reverse transcription-polymerase chain reaction. Specific inhibition tests were performed on HUASMCs to evaluate the role of these growth factors. RESULTS: Forty-two (60%) patients had an unstable carotid plaque and 28 (40%) a stable plaque. Preoperatively, patients affected with unstable carotid plaques had higher PDGF and lower TGF plasma levels than patients with stable carotid plaques (P < .001); the levels returned to normal at 1 and 30 days postoperatively, compared with 20 non-operated healthy volunteers. Release, activity, protein level, and expression of MMPs in PDGF-stimulated HUASMCs were greater than in the controls (P < .001), whereas these values in the TGF-stimulated HUASMCs were lower (P < .001). The addition of monoclonal anti-PDGF antibodies decreased the release, activity, protein level, and expression of MMPs, whereas the addition of monoclonal anti-TGF antibodies increased the release, activity, protein level and expression of MMPs (P < .001). CONCLUSIONS: TGF seems to be an important stabilizing factor and prevents plaque rupture through the decrease of MMPs.

Aged↗

Metalloproteinases and their inhibitors are markers of plaque instability.

BACKGROUND: Our aim was to investigate the release, activity, and expression of matrix metalloproteinases (MMPs)-1, -2, -3 and -9, and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 in patients undergoing carotid endarterectomy and to determine whether altered plasma levels of MMPs and TIMPs may be correlated with carotid instability. METHODS: The carotid plaques of 53 consecutive patients who underwent carotid endarterectomy were classified histologically as stable or unstable. The release of MMPs and TIMPs was analyzed in the serum of patients with stable and unstable carotid plaques, and in 15 age-matched healthy volunteers. The production, activity, and expression of MMPs and TIMPs were determined by Western blotting, zymography, and reverse transcriptase polymerase chain reaction in the carotid specimens. RESULTS: Twenty-nine (55%) patients had an unstable carotid plaque and 24 (45%) a stable plaque. Plasma levels of MMPs were higher in patients with unstable plaques compared to patients with stable plaques and healthy volunteers ( P < .001), whereas plasma levels of TIMPs were lower in patients with unstable plaques compared to patients with stable plaques and healthy volunteers ( P < .001). In the carotid specimens, we found increased activity, production, and expression of MMPs, and decreased activity, production and expression of TIMPs in unstable plaques compared to stable plaques ( P < .001). After endarterectomy, plasma levels of MMPs and TIMPs in patients with unstable and stable plaques returned to the values found in healthy volunteers. CONCLUSIONS: Our study demonstrated that an imbalance exists between MMPs and TIMPs in unstable carotid plaques, which is reflected in the plasma levels of these markers. These data may help in selecting patients at high risk for cerebral events.

Aged↗

Vascular endothelial growth factor increases the migration and proliferation of smooth muscle cells through the mediation of growth factors released by endothelial cells.

BACKGROUND: Vascular endothelial growth factor (VEGF), a highly specific chemotactic and mitogenic factor for vascular endothelial cells (EC), appears to be involved in the development of atherosclerosis. The purpose of our study was to assess if VEGF might indirectly stimulate SMC migration and proliferation in a EC-SMC coculture system, through the mediation of growth factors released by EC. METHODS: Bovine aortic SMC were cocultured with bovine aortic EC treated with hrVEGF, to assess SMC proliferation and migration. The release and mRNA expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta(1) (TGFbeta(1)) were assessed by ELISA and PCR analysis. RESULTS: hrVEGF (10 ng/ml), added to EC cocultured with SMC, induced a significant increase in tritiated thymidine uptake by SMC as compared to controls (P < 0.01) and a significant increase in SMC migration in respect to control (27%; P < 0.01). EC stimulated with hrVEGF increased the release and the expression of bFGF and decreased the release and the expression of TGFbeta(1) with a statistically significant difference in respect to controls (P < 0.001). CONCLUSIONS: VEGF indirectly stimulates SMC proliferation and migration through the modulation of bFGF and TGFbeta(1) released by EC.

Animals↗

Melatonin and vitamin D3 increase TGF-beta1 release and induce growth inhibition in breast cancer cell cultures.

BACKGROUND: Evidence has accumulated that 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is involved in the regulation of the proliferation of breast tumor cells. For complete tumor suppression high hypercalcemic doses of 1,25-(OH)(2)D(3) are needed. The aim of this study was to assess the effect of combined treatment of 1,25-(OH)(2)D(3) at low doses and melatonin (MEL) on the proliferation of estrogen-responsive rat breast cancer cell line RM4. MATERIALS AND METHODS: RM4 cell proliferation was assessed by [3H]thymidine uptake. The presence of TGF-beta(1) in serum-free conditioned medium was determined by inhibition antibody binding assay. RESULTS: In 17-betaE cultured RM4 cells both MEL and 1,25-(OH)(2)D(3) alone and in combination significantly reduced [3H]thymidine incorporation in a dose-related fashion. MEL by itself was ineffective in inhibiting the FCS-cultured RM4 cells, while 1,25-(OH)(2)D(3) strongly inhibited [3H]thymidine incorporation. Meanwhile, MEL increased the sensitivity of the FCS-cultured RM4 cells to 1,25-(OH)(2)D(3) in the combined regimen, from 20- to 100-fold. MEL significantly enhanced the TGF-beta(1) secretion from RM4 cells and vitamin D(3) increased the TGF-beta(1) secretion in a dose-dependent manner, from 2- to 7-fold. Moreover, a further enhancement of the TGF-beta(1) release was obtained with the combined treatment, but only for low 1,25-(OH)(2)D(3) concentrations. The addition of monoclonal anti-TGF-beta(1) antibody to the medium of RM4 cells exposed to vitamin D(3) alone or in combination with MEL increased the [3H]thymidine uptake compared to the correspondent cells cultured without antibody. CONCLUSIONS: Our data point to a potential benefit of combination therapy with 1,25-(OH)(2)D(3) and MEL in the treatment of breast cancer and suggest that the growth inhibition could be related, at least in part, to the enhanced TGF-beta(1) secretion.

Adjuvants, Immunologic↗

The expression of native and oxidized LDL receptors in brain microvessels is specifically enhanced by astrocytes-derived soluble factor(s).

Ex vivo rat brain microvessels express receptors for native as well as for oxidized low-density lipoproteins. In brain microvessels-derived endothelial cells, the expression levels of both receptors were enhanced by co-cultivation with rat astrocytes, even in the absence of actual contact between the two cell types, suggesting a soluble factor(s)-based mechanism of induction. No modulation effect could be evidenced in a heterologous cellular system. Since both receptors were found to be expressed also in astrocytes, these cells are likely to contribute substantially to the lipoprotein management at the blood-brain barrier and in the brain compartment.

Animals↗

Autocrine production of basic fibroblast growth factor translated from novel synthesized mRNA mediates thrombin-induced mitogenesis in smooth muscle cells.

Thrombin is known to stimulate smooth muscle cell (SMC) growth in culture but the mechanisms underlying growth stimulation remain unclear. Previous works have observed a significant increase in platelet-derived growth factor AA and basic fibroblast growth factor (bFGF) release by bovine aortic SMC after addition of thrombin. The aim of this study was to clarify the link between thrombin, bFGF and SMC proliferation by examining the kinetics of autocrine production of bFGF by thrombin-stimulated SMC and its contribution to thrombin-induced mitogenesis. Experiments were performed to assess the dynamics of thrombin-induced bFGF mRNA transcription and to distinguish, following thrombin stimulus, between the activation of 'old' bFGF protein and/or bFGF mRNA, or novel mRNA synthesis and subsequent translation. Bovine aortic SMCs were stimulated with thrombin in serum-free culture. bFGF mRNA expression was determined by RT-PCR. Mitogenic activity of thrombin was determined by 3H-thymidine uptake. Our results demonstrate that the peak of bFGF mRNA expression occurred 24 h after thrombin stimulation. Experiments performed with cycloheximide, a translation inhibitor, revealed a translation peak later than 24 h after thrombin stimulation. Thrombin-induced mitogenic activity in SMCs was partially inhibited by the addition of anti-bFGF antibody (p<0.001) and of hirudin (p<0.001). When hirudin was added 24 h after stimulation, thrombin-induced mitogenic activity was not inhibited. In conclusion, thrombin-induced mitogenesis was partially mediated by the autocrine production of bFGF, mainly due to protein synthesis by novel mRNA with a transcription peak at 24 h and a later translation peak.

Animals↗

Cancer surveillance in patients receiving long-term hemodialysis.

BACKGROUND: Cancer incidence in patients submitted to chronic hemodialysis still remains a subject of debate: there is evidence for increased risk, but the results are still controversial. Adoption of a specific surveillance protocol would appear useful. MATERIALS AND METHODS: In our Department we prospectively followed patients subject to long-term hemodialysis for a 10-year period, having adopted strict inclusion criteria. The protocol of surveillance included available, low cost and low-invasive examinations. RESULTS: The cancer incidence among our study group was significantly higher than expected (1.58%), similar to that reported in the literature, with prevalence of cancer of the kidney (2 patients), prostate, corpus uteri and colon (1 patient each). CONCLUSION: Through following the surveillance protocol, all patients were able to undergo radical oncological surgery, with prevalence of early stage disease at histopathological examination. Our data support the adoption of such protocols for cancer surveillance in hemodialysis units.

Adolescent↗

Papillary solid and cystic pancreatic tumor. Genetic prediction factors for malignancy: report of three cases.

BACKGROUND: Papillary solid and cystic pancreatic tumor (PSCPT) is a rare neoplasm of unknown pathogenesis, with an excellent overall prognosis after complete resection. The malignant potential of this tumor remains unclear and was the object of our investigation. PATIENTS AND METHODS: We report three cases of PSCPT submitted to radical resection in which histological and immunohistochemical studies, as well as genetic analysis of Kirsten-ras (K-ras) oncogene mutations, p53 and Fragile Histidine Triad (FHIT) gene expression, were evaluated. RESULTS: Low expression of Ki 67 was consistent with a low karyokinetic index of these tumors. Mutations of the K-ras gene were not present. Low-grade variations of p53, K-ras and FHIT genes were detected by immunohistochemistry. CONCLUSION: PSCPT is a rare neoplasm with low malignancy. Further genetic analysis is required to predict the potential malignancy of this tumor; nevertheless combined multimodality approaches may play a suitable role in identifying more aggressive forms.

Adolescent↗

Hürthle cell tumors of the thyroid gland. Personal experience and review of literature.

BACKGROUND: Oncocytic cell neoplasm of the thyroid is currently recognized as a histological entity, but doubts still exist about its clinical and evolutionary categorization. Controversies concern occurrence and frequency of malignant forms, natural history and therapeutic strategies. MATERIALS AND METHODS: The authors report six cases of Hürthle cell tumor. Five cases were adenoma, one was carcinoma. Morpho-functional pre-operative evaluation and inter-operative histopathological test were performed in all patients. One patient underwent lobectomy (absence of unusual characteristics of the adenoma Hürthle cell) and five underwent total thyroidectomies (1 carcinoma). All patients were treated with suppressive hormonal therapy. RESULTS: No mortality and morbidity was recorded. All patients are undergoing follow-up (adenomas: average 64.2 months; carcinoma: 132 months) and none of them show recurrent symptoms. DISCUSSION: Hürthle cell tumors can be diversified in adenoma and carcinoma. Almost all reports classify oncocytic nodules as malignant when capsular and/or vascular invasion is present or when there is peri-thyroid tissue infiltration or lymphatic or hematic metastases. A clear differentiation between adenoma and carcinoma is determined by a histological test. Also an intra-operative histopathological analysis is sometimes unable to show minimal signs of invasion. Conflicting observations about the biological behaviour of Hürthle cell neoplasm lead to different therapeutic strategies. The authors believe lobectomy is the treatment of choice when a clear histological diagnosis of adenoma has been made. When carcinoma is diagnosed or when doubts exist after intraoperative histological test, the authors recommend total thyroidectomy followed by scintigraphic test and preventive radio-active therapy. All patients should be treated with suppressive hormonal therapy and undergo periodic check-ups.

Adenoma, Oxyphilic↗

Hepatocyte ultrastructural aspects after preoperative biliary drainage in pancreatic cancer patients with cholestatic jaundice.

BACKGROUND: The usefulness of preoperative biliary drainage in long-standing obstructive jaundice remains controversial. This study was designed to assess microscopic and ultrastructural changes in the morphology of hepatocytes from patients with obstructive jaundice treated with biliary drainage for 14 days. PATIENTS AND METHODS: In 8 patients with jaundice due to pancreatic neoplasms we obtained two fine-needle liver biopsies: the first during a transhepatic cholangiographic examination before placing preoperative drainage and the second at surgery, on day 14 of drainage. Biopsy samples were examined by light and electron microscopy and correlated to serum liver functional tests recorded before and after biliary drainage. RESULTS: Pre-drainage biopsy presented diffuse morphological signs of congestion and cholestasis, lipid and bilirubin cytoplasm inclusions, loss of bile canaliculi microvilli and diffuse bile canaliculi dilatation. After-drainage biopsies presented reduction of bile canaliculi dilatation, partial restoring of bile canaliculi microvilli and persistence of diffuse hepatocyte structural and ultrastructural changes. Patients' laboratory values (bilirubin, alkaline phosphatase, SGGT, SGOT and SGPT), that were significantly impaired before drainage, returned almost to normal within two weeks after drainage. CONCLUSION: Preoperative biliary drainage in patients with long-standing obstructive jaundice has received wide yet controversial support due to a well established pathophysiological background. The present findings of scarce recovery of hepatocyte changes after 14 days' drainage seemingly question its appropriateness.

Aged↗

Comparative analysis of clinical features and prognostic factors in resected bronchioloalveolar carcinoma and adenocarcinoma of the lung.

BACKGROUND: Over the past few years, clinical, radiological and pathological classification of lung adenocarcinoma and its subtypes, particularly bronchioloalveolar carcinoma (BAC), has radically changed. PATIENTS AND METHODS: Out of a series of 384 non-small cell lung cancer (NSCLC) patients, submitted to surgical resection and followed-up in our Department from 1981 to 1999, the data of 151 adenocarcinomas (35 BAC and 116 non-BAC) were reviewed and analyzed for prognosis. RESULTS: BAC and non-BAC series were similar in clinical and radiographic findings, type of resection and stage. Stage I was a dominant favorable prognostic factor (10-year survival: 58% of BAC, 41.2% of non-BAC), albeit associated with a significant risk of second primary metachronous lung tumor (10-year risk: 25% of BAC, 32% of non-BAC). Other independent prognostic factors were: absence of lymph node involvement for BAC and stage III-IV for non-BAC. In term of prognosis, advantages of BAC over non-BAC were fewer cases with lymph node involvement, increased presence of "well-differentiated" cells (p = 0.016) and lower incidence of a second primary metachronous tumor. Moreover BAC patients with a single nodule or mass also had a higher survival expectancy (mean survival: 77 months versus 56 for non-BAC). An unfavorable feature was the higher incidence of diffuse or multicentric radiological forms (p = 0.012). For both groups the presence of multiple or satellite nodules remain a diagnostic and surgical challenge: in BAC cases the evaluation of clonality is recommended.

Adenocarcinoma↗

Palliative management of malignant rectosigmoidal obstruction. Colostomy vs. endoscopic stenting. A randomized prospective trial.

BACKGROUND: Colostomy was the palliative treatment of choice in patients with malignant unresectable rectosigmoid obstruction. Palliative endoscopic treatment of malignant rectosigmoid obstruction by endoluminal self-expanding metallic stents is nowadays a well-established procedure. PATIENTS AND METHODS: Twenty-two patients, referred for treatment with diagnosis of malignant obstruction of the rectosigmoid region presenting an advanced unresectable stage, were enrolled. Patients were randomly assigned into two treatment groups (endoscopic stenting vs colostomy) according to random-number tables. The length of procedure, morbidity and mortality rate, canalization of the gastrointestinal tract, restoration of oral intake and hospital stay were assessed. RESULTS: Endoscopic group: The median length of procedure was 36 minutes. No death was observed. None of the patients reported complications. All patients resumed bowel function within 24 hours. The restoration of oral intake was achieved one day after stent placement. The median hospital stay was 2.6 days. Colostomy group: The median length of the operation was 75.4 minutes. No mortality was reported. In 1 patient (9.1%) stoma prolapse was observed 3 days after the operation. Canalization of the gastrointestinal tract was restored when colostomy was opened (on postoperative day 3). All patients were able to resume oral feedings on postoperative day 3. The median hospital stay was 8.1 days. CONCLUSION: There were no statistically significant differences between the 2 groups concerning morbidity and mortality. Endoscopic stenting was significantly more effective concerning operative time, restoration of bowel function and oral intake and median hospitalization. Our results would suggest that endoscopically placed metal stents offer an effective alternative to surgical palliation in patients suffering from unresectable malignant rectosigmoid obstruction.

Aged↗

Nuclear methylation levels in normal and cancerous thyroid cells.

BACKGROUND: Most cancers show abnormal DNA methylation and a positive correlation between hypomethylation and tumour progression. PATIENTS AND METHODS: In our laboratory the extent of DNA methylation in individual nuclei in normal, cancer and non-cancer thyroid tissue samples was quantified according to a previously described method of computer-assisted semi-quantitative analysis. Cancer and non-cancer samples were obtained from nine patients with different thyroid pathologies (one multinodular goitre and eight carcinomas). Quantitative analysis was performed in two sets of samples, i.e. individual nuclei from touch preparations and from tissue sections. RESULTS: In all cancer specimens a statistically significant decrease of heterochromatin methylation was consistently observed. In both sets of samples a direct correlation was consistently observed between the extent of chromatin demethylation and the degree of malignancy. CONCLUSION: Our preliminary results suggest that our method of cell-by-cell detection of intranuclear methylation abnormalities may be a useful tool in early identification of thyroid cancer lesions.

Adult↗