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Biomedical subjects

L Giacomelli

Publications and source records attributed to L Giacomelli.

At least 19 recordsLinked to original sources

CD105-assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma.

AIMS: Angiogenesis is essential for malignancies growth. CD105 is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. The aim of this study has been to determine the expression of CD105 in laryngeal squamous cell carcinoma (SCC) and to investigate the role of CD105-assessed mean vascular density (MVD) in predicting patients' prognosis. METHODS: The sections of 43 consecutive cases of laryngeal SCC were stained with mouse monoclonal antibody CD105. All the measures were performed by a computer-based image analysis system. The percentage of the fields occupied by CD105-assessed micro-vessels was determined. RESULTS: The mean CD105-assessed MVD were 11% and 6% in laryngeal SCC with and without malignancy recurrence, respectively. Multivariate logistic regression stated that CD105-assessed MVD was significantly related to disease recurrence (p=0.030). CONCLUSIONS: Our preliminary results suggest that CD105-assessed MVD may be a valuable parameter for predicting patients having an increased risk of developing laryngeal carcinoma loco-regional recurrence.

Adult↗

Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas.

We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.

Blotting, Western↗

Gene expression in the cell cycle of human T lymphocytes: I. Predicted gene and protein networks.

The key genes involved in the cell cycle of human T lymphocytes were identified by iterative searches of gene-related databases, as derived also from DNA microarray experimentation, revealing and predicting interactions between those genes, assigning scores to each of the genes according to numbers of interaction for each gene weighted by significance of each interaction, and finally applying several types of clustering algorithms to genes basing on the assigned scores. All clustering algorithms applied, both hierarchical and K-means, invariably selected the same six "leader" genes involved in controlling the cell cycle of human T lymphocytes. Relations of the six genes to experimental data describing switching between stages of cell cycle of human T lymphocytes are discussed.

Algorithms↗

Nuclear maspin detection in renal cell tumours: possible diagnostic role and correlation with p53 status.

AIMS: To investigate the presence of maspin in renal tumours in an attempt to improve our understanding of the underlying mechanism of renal carcinogenesis and for diagnostic purposes. METHODS AND RESULTS: We examined 122 renal neoplasms of varying histological types and immunohistochemically investigated maspin and p53 expression. All clear cell carcinomas (CC) were negative for maspin, whereas oncocytomas (OC), papillary renal cell carcinomas (PC), chromophobe carcinomas (CPC) and, at least focally, collecting duct carcinomas (CDC) stained positively. We found that p53 positivity had a statistically significant correlation with metastasis (P=0.009) in CC and maspin showed a significant inverse correlation with the presence of metastasis in PC and CDC (P=0.02). CONCLUSIONS: The detection of maspin may be useful for differential diagnostic purposes and suggests a different underlying mechanism in the development of the various histological types of renal carcinomas.

Adenoma, Oxyphilic↗

Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx.

AIMS: Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down-regulated in human breast, prostatic, and colonic cancers but apparently up-regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma. METHODS AND RESULTS: Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow-up period longer than 24 months. The expression of p53, p27 and MIB-1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease-free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB-1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB-1 or p27 expression. CONCLUSIONS: These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma.

Adult↗

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P < 0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

Adult↗

[The Bochdalek hernia in the adult: case report and review of the literature].

The Bochdalek hernia, the most common diaphragmatic hernia, except the hiatus hernia, is located on the posterolateral side of this muscle. This pathology is generally diagnosed in children; in fact only 105 such cases occurring in adults have been described in the literature. In these cases, surgical intervention is made necessary by the severity of potential complications. The Author's attention was drawn to a woman of 60 years of age, affected by pituitary nanism, who suffered from a left hand Bochdalek hernia. The symptomatology, characterised by abdominal pains and constipation had been presented for about one year. The computerised tomography confirmed the hernia of abdominal viscera in the thorax cavity. The intervention was conduced via the abdomen: the hernia were reduced, the hernial hole were closed with a double strata and the muscular plane reinforced with a synthetic prosthesis (dual mesh). The postoperative process was regular and the patient dismissed on 11th postoperative day.

Female↗

Cytokine, infiltrating macrophage and T cell-mediated response to development of primary and secondary human liver cancer.

BACKGROUND: Kupffer cells, monocytes and infiltrating T cells have been considered the major source of interleukin-1beta and tumour necrosis factor-alpha in the liver. AIMS; To explore the expression of interleukin-1beta and tumour necrosis factor-alpha and to evaluate the density and the distribution of T lymphocytes and monocytes/macrophages in the liver of patients with primary and secondary tumours. METHODS: Tumoural and peritumoural liver samples were examined from 21 patients with hepatocellular carcinoma, 10 with hepatic metastases, 5 with benign focal liver lesions and 4 healthy adult livers. Interleukin-1beta and tumour necrosis factor-alpha mRNAs were detected by a semiquantitative comparative reverse transcriptase polymerase chain reaction. T lymphocytes and monocytes/macrophages were detected by immunohistochemistry. RESULTS: Higher levels of interleukin-1beta, tumour necrosis factor-alpha, CD3+ and CD68+ cells were found in the tissue surrounding hepatocellular carcinoma and metastases than in the tumour itself. A strong expression of CD68+ and CD3+ cells was found mainly along the tumour-host interface but the highest expression of CD3+ cells was found at the metastasis interfaces. Interleukin-1beta expression, CD3+ and CD68+ cell densities were higher in peritumoural samples than in so-called "normal" liver tissue. CONCLUSIONS: An increased production of interleukin-1beta and, to a lesser extent, of tumour necrosis factor-alpha mRNA coincides with the presence of cancer be it primary or secondary, both in healthy and cirrhotic livers. The presence of cancer, irrespective of the presence of underlying liver damage, appears to play the most important role.

Adult↗

Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence.

AIMS: Fas ligand (FasL) expression by cancer cells may mediate tumour immune privilege. The purpose of the present study was to investigate the timing and significance of FasL expression during the colorectal adenoma-carcinoma sequence. METHODS: FasL expression was studied by immunohistochemistry in 170 formalin-fixed tissue sections representing the entire colorectal adenoma-carcinoma sequence. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to search for FasL mRNA. Analysis of survival was performed in patients with carcinomas. RESULTS: A significant positive linear correlation was found between FasL expression and tumour progression throughout the colorectal adenoma-carcinoma sequence (r(s)=0.677 P<0.001). A pattern of high FasL expression was detected in 19% of high grade adenomas, 40% of stage I-II, 67% of stage III and 70% of stage IV carcinomas. No significant differences were observed between FasL expression in the primary tumours and that in the corresponding liver metastases. The specificity of FasL expression was confirmed at RT-PCR. For stage I-II carcinomas, the 5 year survival was 90% in patients without, or with moderate, tumoural FasL expression compared with 60% in those with high tumoural FasL expression (P<0.05). CONCLUSIONS: Our findings suggest that FasL expression may be involved in the development of colorectal cancer and its progression.

Adenocarcinoma↗

P27kip1 expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer.

BACKGROUND: Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression. METHODS: Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response). RESULTS: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy. CONCLUSIONS: Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.

Adult↗

[Endoscopic surgery of chronic venous insufficiency (CVI)].

The endoscopic technique in chronic venous insufficiency is simple and almost complication free. Our preliminary results due to a good postoperative course and to a quick return to social activity induce the Authors to indicate this type of procedure as the best treatment in chronic venous insufficiency.

Chronic Disease↗

[Role of total thyroidectomy in benign multinodular benign goiter].

The Authors report a review of the Literature and their personal series to evaluate the role of total thyroidectomy in the surgical management of non-toxic multinodular goiter. On the basis of the data obtained, the Authors consider total thyroidectomy the therapy of choice for this pathology.

Adolescent↗

[A case of loco-regional recurrence of carcinoma of the male breast].

The case of a 47-year-old man surgically treated with Halsted mastectomy for breast cancer and submitted to Tamoxifen therapy for more than four years is reported. A loco-regional recurrence following withdrawal of oestrogen antagonist therapy was observed and surgically treated by local excision. Normal karyotype analysis of peripheral leucocytes, normal male phenotype of the patient, his height and the lack of family history for breast cancer, as well as a possible dysfunction of the endocrine system were considered in the aetiopathogenesis of the disease.

Antineoplastic Agents, Hormonal↗

Lamellar bodies coexist with vesicles and micelles in human gallbladder bile. Ursodeoxycholic acid prevents cholesterol crystal nucleation by increasing biliary lamellae.

The aggregative forms of lipids in human gallbladder bile and their relation to cholesterol crystallization are controversial. Using combined chemical, gel-chromatographic, optical/electron microscopic and quasielastic light-scattering methods, we investigated this issue in native gallbladder bile obtained from nine untreated cholesterol gallstone patients and eight cholesterol gallstone patients treated for 1 week with 600 mg/day of ursodeoxycholic acid. Bile obtained at cholecystectomy was ultracentrifuged for 2 h at 150,000 g to obtain isotropic samples. The conventional cholesterol crystal observation time was 3.1 +/- 4.1 (SD) days in controls and 19.0 +/- 1.9 days in the ursodeoxycholic acid-treated group (p < 0.001). Bile was analyzed by high-resolution gel-chromatography using 7 mM sodium taurocholate in the elution buffer. Biliary lipids eluted in four chromatographic zones: zone #I, corresponding to the column void volume, contained only minimal amounts of lipids; zone #II (apparent m.w. 100-220 kDa) comprised 29.1 +/- 12.4% of biliary cholesterol in the untreated group and 8.3 +/- 4.3% in the ursodeoxycholic acid-group (p < 0.001). At negative staining electron microscopy, this region was composed of roundish vesicles ranging from 7 to 20 nm in diameter. Zone #III (apparent m.w. 50-100 kDa) carried 59.1 +/- 2.1% of cholesterol in untreated patients and 81.2 +/- 9.5% in ursodeoxycholic acid-rich biles, respectively (p < 0.001). At negative staining electron microscopy, this region was composed of lamellar stacks of variable length, usually with 5 nm interspaces and up to 30 nm in width. In ursodeoxycholic acid-rich biles, lamellae often appeared in the form of concentric fingerprint-like images. Quasielastic light-scattering measurements in this region were compatible with the size estimates obtained at electron microscopy. Zone #IV (apparent m.w. 6-50 kDa) carried 11.8 +/- 9.4% and 11.6 +/- 9.0% of cholesterol, respectively (not significant). Since this region comprised a considerable fraction of endogenous bile salts and had no distinct morphological structures, it was interpreted as mixed micelles. The cholesterol crystal observation time showed a significant inverse correlation (r = -0.85, p < 0.001) with percent cholesterol carried by vesicles (zone #II) and a direct correlation (r = 0.86, p < 0.001) with percent cholesterol carried by lamellar bodies (zone #III). Vesicles and lamellae identical to those observed in isolated gel-chromatographic fractions were observed also on direct electron microscopic examination of unfractionated isotropic native biles. Similar findings were observed also in matched model biles.(ABSTRACT TRUNCATED AT 400 WORDS)

Bile↗

[Ambulatory phlebectomy: our experience].

The Authors report their experience of out-patient phlebectomy. Over a period of 5 years they have examined 186 patients (156 females, 30 males): 166 had micro- and extra-saphenic varicosities, while 20 had recurrent varices. Patients with ostium failure were excluded. Muller's out-patient phlebectomy implies an accurate mapping of varicosities, local anaesthesia, microincisions which are only exceptionally sutured. The Authors consider that an accurate elastic pressure bandage is indispensable and useful in order to improve the dynamics of the PVC and to avoid haemorrhages. Such a surgical technique bears aesthetic, economic and haemodynamic advantages.

Adolescent↗