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Biomedical subjects

L Santi

Publications and source records attributed to L Santi.

At least 19 recordsLinked to original sources
PubMed1998

TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis.

The matrix metalloproteinase (MMP) inhibitor TIMP-2 has a high specificity for gelatinase A/MMP-2. An imbalance between gelatinase A and TIMP-2 in favor of enzymatic activity is linked to the degradation of the extracellular matrix (ECM) associated with several physiologic and pathologic events, including angiogenesis, invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors. We transfected B16F10 murine melanoma cells, a highly invasive and metastatic cell line, with an expression vector harboring a cDNA encoding for human TIMP-2. The clones obtained were isolated and examined for TIMP-2 over-expression and changes in tumor cell phenotype. The amount of recombinant TIMP-2 produced correlated with a reduction in invasion. In an in vivo angiogenesis assay, TIMP-2-transfected clones showed reduced levels of blood vessel formation, and in vitro conditioned media from TIMP-2 transfectants showed diminished induction of endothelial cell migration and invasion. TIMP-2 over-expression limited tumor growth in vivo and neoangiogenesis when cells were injected subcutaneously in mice in the presence of Matrigel. However, TIMP-2 overexpressing clones were found to be more resistant to apoptosis than parental and control melanoma cells, while necrosis was increased. Our data confirm the role of TIMP-2 in the down-regulation of metastasis and angiogenesis but indicate a possible involvement in tumor cell survival.

Animals↗
PubMed1998

Molecular Probe Data Base (MPDB).

In this paper, the current status of the Molecular Probe Data Base (http://www.biotech.ist.unige.it/interlab/ mpdb.html ) is briefly presented together with a short analysis of its activity during 1997. This has been performed by statistically evaluating the 'logs' of the Internet servers that are used for its distribution with reference to the geographical origin of the requests, the words that were utilized to carry out of the searches and the oligonucleotides that were retrieved. Planned enhancements of this database are also described. They include a revision of its data structure and, even more relevant, of its data management procedures.

Computer Communication Networks↗
PubMed1997

Molecular Probe Data Base (MPDB).

Molecular Probe Data Base contains detailed information on synthetic oligonucleotides with a sequence of up to 100 nucleotides. This database prevalently contains information related to human oligonucleotides used in diagnostics. Molecular Probe Data Base has been made available on-line through the Internet by means of Network Information Retrieval (NIR) tools since 1993. Two years ago, a collaboration with EMBL Data Library was also set up, so that the Molecular Probe Data Base has been integrated with other molecular biology data banks in the sphere of the SRS WWW network browser. In this paper, the most recent enhancements and the current status of the Molecular Probe Data Base are briefly presented.

Base Sequence↗
PubMed1997

A retrospective comparison of detection and treatment of breast cancer in young and elderly patients.

The medical records of all women (297 cases) with breast cancer > or = 70 years of age, presenting at our Institute from January 1980 to December 1989, were reviewed. Data from 226 elderly women was compared to that from 100 stage-matched patients < 50 years of age, presenting during the same 10-year study interval. Conservative surgery was significantly more frequent in young patients (71.1%) compared to elderly women (26.1%) and radical mastectomy according to Halsted was undertaken in 34.3% of the elderly group compared to 8.9% of young patients (p < 0.001). Since 'incidental' diagnosis was significantly more frequent in the elderly group (59.9% versus 6.0%) (p < 0.001), primary care physicians may play an important role in the early diagnosis of breast cancer in the majority of elderly women.

Adult↗
PubMed1997

Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA.

BACKGROUND: Heparan sulfate proteoglycans are one of the major components of extracellular matrix and are secreted at different levels by several normal and tumoral cells. Perlecan, the basement membrane proteoglycan, has structural domains involved in cell/matrix interactions and growth factor storage. Metastatic melanoma cells show an increase in perlecan expression as compared to low metastatic ones. We examined whether reduction of perlecan expression could down-modulate the malignant phenotype in melanoma clones. MATERIALS AND METHODS: We transfected B16-F10 murine malignant melanoma cells with a perlecan antisense cDNA construct and tested the in vitro behavior of the selected clones. RESULTS: The expression of antisense mRNA corresponded to a reduction of perlecan synthesis. The clones with reduced perlecan synthesis showed a down-regulation of proliferation and invasion. CONCLUSIONS: These results further indicate the importance of perlecan as a regulator of growth factor activity affecting the biological properties of metastatic cells, and suggest the potential use of antisense perlecan DNA in anti-melanoma gene therapy approaches.

DNA, Antisense↗
PubMed1997

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study.

The associations between fasting plasma insulin concentration and risk factors for cardiovascular disease were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)-total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol, concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F = 7.1; P < 0.001). However, systolic blood pressure and uric acid were close to statistical significance (P = 0.06-0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e, three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F = 4.0; P < 0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.

Adolescent↗
PubMed1997

Assessing research productivity in an oncology research institute: the role of the documentation center.

An evaluation method used to assess the quality of research productivity and to provide priorities for budget allocation purposes is presented. This method, developed by a working group of the National Institute for Research on Cancer (IST), Genoa, Italy, is based on the partitioning of categories of the Science Citation Index and Journal Citation Reports (SCI-JCR) into deciles, which normalizes journal impact factors in order to gauge the quality of the productivity. A second parameter related to the number of staff of each institute department co-authoring a given paper has been introduced in order to guide departmental budget allocations. The information scientists of the IST Documentation Center who participated in the working group played a pivotal role in developing the computerized database of publications, providing and analyzing data, supplying and evaluating literature on the topic, and placing international bibliographic databases at the working group's disposal.

Documentation↗
PubMed1996

RB1 oncosuppressor gene over-expression inhibits tumor progression and induces melanogenesis in metastatic melanoma cells.

The retinoblastoma gene (RB1) is frequently deleted or mutated in many tumor types and in all cases of retinoblastoma. Apart from its role in regulation of the cell cycle, the RB1 gene product (p110RB1) appears to be involved in control of differentiation. Malignant metastatic cells show many properties of poorly differentiated cells, and are highly invasive in vitro and in vivo. We have transfected the human RB1 cDNA in an expression vector under the control of the beta-actin promoter into B16F10 murine melanoma cells. These cells highly overexpress RB1 mRNA and the p110RB1 product, show reduced growth rate and increased melanogenesis in vitro. Vector control transfectants showed no alteration of invasiveness. The p110RB1 over-expressing cells also had a reduced capacity to migrate and invade through an artificial basement membrane, key characteristics of metastatic cells. When injected into nude mice, the p110RB1 over-expressing cells showed reduced tumor growth and reduced metastatic potential. The few metastasis observed were predominantly melanotic. These data indicate that RB1 gene expression is involved in melanoma cell differentiation and plays a role in downregulation of migration, invasion and metastatic potential of these cells.

Animals↗
PubMed1996

Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck.

BACKGROUND: In 1992, we reported the first analysis of a randomized trial comparing alternating radiotherapy and chemotherapy with radiotherapy alone in the treatment of squamous cell carcinoma of the head and neck. The results of that 3-year analysis indicated that the combined treatment had superior efficacy. PURPOSE: After an additional 2 years of follow-up, we again compared the efficacy of the two treatment regimens, with attention paid to differences in overall survival, progression-free survival, and locoregional relapse-free survival. METHODS: One hundred fifty-seven patients with untreated, unresectable squamous cell carcinoma of the head and neck were randomly assigned to receive either chemotherapy (four courses of cisplatin [20 mg/m2] and fluorouracil [200 mg/m2], given daily for 5 consecutive days during weeks 1, 4, 7, and 10) plus radiotherapy (three courses of 20 Gy each, given in fractions of 2 Gy per day during weeks 2-3, 5-6, and 8-9) or radiotherapy alone (70 Gy total dose, given in fractions of 2 Gy per day, 5 days per week). Eighty patients received the combined therapy, and 77 were treated with radiotherapy alone. Responses, failures, and toxic effects associated with the two treatment regimens were compared. Overall survival, progression-free survival, and locoregional relapse-free survival were calculated according to the Kaplan-Meier method; the logrank test was used to compare survival parameters between the two patient groups. Reported P values are two-sided. RESULTS: As reported previously, toxic effects associated with the combined therapy included both chemotherapy- and radiotherapy-related effects; however, the incidence and severity of mucositis were nearly identical among patients in the two treatment arms. The combined treatment was associated with a statistically significant increase in the frequency of complete response (i.e., the disappearance of clinically detectable disease for at least 4 weeks) (43% for the combined-treatment group compared with 22% for the radiotherapy-only group; P = .037, chi-squared test). Five-year estimates of overall survival in the combined-treatment group compared with the radiotherapy-only group were 24% (95% confidence interval [CI] = 14%-40%) and 10% (95% CI = 4%-24%), respectively (P = .01, logrank test). The estimates of progression-free survival at 5 years in the combined-treatment group compared with the radiotherapy-only group were 21% (95% CI = 11%-37%) and 9% (95% CI = 3%-22%), respectively (P = .008, logrank test). Finally, the 5-year estimates of locoregional relapse-free survival were 64% (95% CI = 36%-84%) in the combined-treatment group and 32% (95% CI = 10%-65%) in the radiotherapy-only group (P = .038, logrank test). CONCLUSIONS AND IMPLICATIONS: The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.

Antimetabolites, Antineoplastic↗
PubMed1996

Molecular probe data base (MPDB).

The molecular probe data base (MPDB) contains detailed information on synthetic oligonucleotides, including their identification, target genes, applications and bibliographic references. It is available on-line through Internet and can be searched by using Network Information Retrieval tools. In this article the most recent enhancements of MPDB, both in terms of data contents and new ways of access, are described. These include a recently established collaboration with EMBL Data Library, in the sphere of SRSWWW network browser, in view of a better integration of MPDB with other molecular biology databases.

Computer Communication Networks↗
PubMed1996

Analysis of IL-2 receptor expression and of the biological effects of IL-2 gene transfection in small-cell lung cancer.

We have analysed the expression of interleukin-2 receptor (IL-2R) on a panel of small-cell lung cancer (SCLC) cell lines. None of the 11 SCLC cell lines studied expressed detectable surface IL-2R alpha or beta chains by indirect immunofluorescence. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses indicated that only one out of 11 cell lines expressed detectable IL-2R beta mRNA while two expressed a weak positivity for IL-2R gamma. Five SCLC cell lines were transfected with the plasmid vector RSV.5 neo containing IL-2 cDNA coding sequence. Stable transfectants secreted biologically active IL-2 (ranging from 25 to 100 U ml-1 in the culture supernatant). IL-2 transfection did not produce significant modifications in the expression of surface molecules such as IL-2R alpha and beta chains, intercellular adhesion molecule-1 (ICAM-1), CD44, HLA class I and II or in IL-2R beta or gamma mRNA. More importantly, IL-2-transfected N592 and NCI H69 cell lines completely lost their tumorigenic potential in nude mice after subcutaneous injection, whereas experimental controls transfected with RSV.5 neo vector only, displayed an in vivo growth pattern identical to that of untransfected cells. In addition, in the N592 model, IL-2-producing N592 inhibited the growth of wild-type N592 injected at the same site, while injection of parental cells on the opposite side did not significantly affect the growth of wild-type tumour cells. Histopathological analysis of the rejection process of IL-2-transfected cells demonstrated the presence of MAC-1+, MAC-3+ macrophages and of RB68C5+ granulocytes, whereas T cells were undetectable and NK cells were scarcely represented. In addition, a reduction of the tumour blood vessels was observed. The possible relevance of these data for the development of vaccination strategies using cytokine-engineered tumour cells in SCLC is discussed.

Animals↗
PubMed1996

Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study.

Stage IIIb non-small-cell lung cancer (NSCLC) has a poor prognosis. The median survival is approximately 6 months, and only 30% of patients are alive 1 year after diagnosis. The need for effective treatment is evident. The aim of this study was to evaluate whether the infusion of tumor-infiltrating lymphocytes (TILs), isolated from resected tumor, expanded in vitro and injected together with recombinant Interleukin-2, is feasible and may at least partially modify the poor prognosis in these patients. The infusion of TILs, derived from surgically resected NSCLC and expanded in vitro, together with subcutaneous (s.c.) injections of recombinant interleukin-2 (rIL-2) was attempted in a group of 11 patients. Treated patients were infused i.v. with in vitro expanded TILs (from 4 to 70 x 10(9) cells), and rIL-2 was injected s.c. at doses varying from 61 to 378 x 10(6) IU. Toxic side effects (fever and, in some cases, hypotension) were observed and limited the dose of rIL-2 infused. Follow-up was continued for 40 months. The mean survival time was 13.8 months. Three of five TIL-treated patients with residual disease have no evident disease after 1 year, and two of them are still alive and have no evidence of disease after 40 months. This pilot study suggests that the infusion of in vitro expanded TILs, derived from surgical samples, is feasible and seems to prolong overall survival and to control the residual disease in patients with advanced NSCLC.

Aged↗
PubMed1996

Attitude of women towards early cancer detection and estimation of the compliance to a screening program for cervix and breast cancer.

Before the start of a feasibility study for cervical and breast cancer screening in two towns (Genoa and Rome) in Italy, a random sample (N = 349) of the target population was interviewed with the aim of evaluating (i) the degree of knowledge as to the purpose of the screening tests; (ii) the attitude towards early detection of these cancers; and (iii) the potential compliance to the program. Pap test: 48.7% of women were correctly informed about the object of the test; information was associated with the degree of education (p < 0.0001). Periodic Pap test was reported by 77.9% of women: the proportion was higher among younger (p = 0.013) and married women (p = 0.001). A 1-year interval between two tests was more frequently reported by younger women (p < 0.001). Estimated participation in the cervical cancer screening program was 63.3%. Increasing age (OR = 0.78; CI = 0.6-1.0), the married status (OR = 0.39; CI = 0.18-0.83) and lack of knowledge of the object of the test (OR = 0.47; CI = 0.25-0.87) hindered participation in the program. Mammography: 53.3% of women reported that it is a method used for early detection of breast cancer. Well-educated women were more likely to be correctly informed (p < 0.0001). Previous mammography was reported by 49.3% of women aged 50 to 69 years who never experienced breast cancer symptoms; married women more frequently reported having had the test (p = 0.02). Estimated participation in the breast cancer screening program was 59%. Women aged 60 years and over were less prone to participate (OR = 0.44; CI = 0.22-0.89). Increasing age was the most relevant barrier to participation in screening programs, and strong efforts should be made to involve older women, due to their greater chance of getting cancer.

Adult↗
PubMed1996

Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study.

OBJECTIVE: To examine the relationships of serum uric acid concentration with several risk factors of cardiovascular diseases (CVD). SUBJECTS: 957 men 18 y old participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. MEASUREMENTS: Body mass index (BMI), waist/hip ratio (WHR), serum uric acid, serum lipids, blood pressure, fasting insulin and behavioural variables. RESULTS: Serum uric acid concentration showed positive associations with BMI (r = 0.24; P < 0.0001), WHR (r = 0.19; P < 0.0001) and serum triglyceride levels (r = 0.19; P < 0.0001); it was also significantly correlated to systolic (r = 0.08; P < 0.01) and diastolic (r = 0.11; P < 0.001) blood pressure, fasting insulin (r = 0.11; P < 0.001), total (r = 0.12; P < 0.001) and LDL cholesterol (r = 0.10; P < 0.01) plasma concentrations. Life-style characteristics, such as smoking and physical activity did not show any significant association, while daily alcohol intake was positively associated with uric acid concentration (r = 0.09; P < 0.01). While the adjustment for fasting insulin did not substantially change these results, the magnitude of the correlations between uric acid and CVD risk factors markedly decreased when allowance was made for BMI and WHR. Only triglycerides maintained an independent correlation with uric acid levels (r = 0.17; P < 0.0001). In multivariate regression analysis, serum triglycerides, BMI and WHR (at borderline significance) were independent positive predictors of uric acid (R2 of the model 0.122, P < 0.001), while fasting insulin concentration did not give any independent contribution to explain the variability uric acid levels. CONCLUSIONS: These data indicate that, already in young, essentially health subjects, hyperuricaemia associates with several components of the so-called insulin resistance syndrome, thus suggesting that increased levels of uric acid might be another member of this syndrome. In addition, these data suggest that obesity and central body fat distribution, rather than hyperinsulinaemia/insulin resistance, play a major role in linking hyperuricaemia with CVD risk factors clustering in the insulin resistance syndrome. Nevertheless, hypertrigliceridemia is related to hyperuricemia independently of obesity and central body fat distribution.

Adipose Tissue↗
PubMed1995

How uniform are post-graduate training programs in medical oncology in the European Union?

BACKGROUND: Medical oncology is a relatively new discipline whose rapid evolution is not paralleled by advances in the academic curricula. The present study was designed to provide a description of the status of post-graduate training programs in medical oncology in the European Union. RESULTS: Our survey shows that 'some form' of training in medical oncology is available in 10 countries of the European Union, but that there are officially recognized Schools of Specialization in this discipline in only four (Great Britain, Portugal, Republic of Ireland and Spain). Italy and France offer training programs in medical oncology as specific tracks of the School of Specialization in Oncology. A 'special competence' in medical oncology, within the specialty of internal medicine, is issued in 3 additional countries (Denmark, Belgium and the Netherlands). Finally, training in medical oncology is linked to that in haematology in Germany. A wide variation was found among the different European countries regarding the requirements for admission to these training programs. Similarly, the duration of the programs in the various schools ranges between 2 and 6 years and the total number of years from graduation to achievement of the title of specialist ranges from 4 to 9 years. CONCLUSIONS: Our survey discloses a broad heterogeneity of academic attitude regarding medical oncology in the European Union and points to the need for recognition of this discipline as a specific and essential specialization.

Education, Medical, Graduate↗
PubMed1994

A short term analysis of the behaviour of conditionally immortalized neuronal progenitors and primary neuroepithelial cells implanted into the fetal rat brain.

Conditionally immortalized (temperature-sensitive) striatal-derived neuronal progenitor cell lines and primary neuroepithelial cells were transplanted into the CNS of gestational day 15-16 rat fetuses using an 'in utero' surgical procedure. Each fetus received 2.5-3 x 10(4) donor cells previously labelled in vitro by incubation with 5-bromo-2'-deoxyuridine (BrdU). At 5 days following transplantation, 69% of the fetuses were still alive. Engrafted cells were detected by BrdU immunohistochemistry, and the appearance of the engrafted cells and the time course of Nestin and PCNA expression were measured at 6, 24, 64 h and 5 days after transplantation. The evolution of Large T-Antigen immunoreactivity in engrafted temperature-sensitive (ts) cells was also evaluated at the above time intervals. The results indicate that the majority of the implanted cells were aggregated into clusters 24 h after transplantation. These clusters were not visible at 6 h, when most of the cells were isolated. The clusters were located in both the ventricles and parenchyma. These findings were common to both ts cells and striatal primary neuroepithelial cells. At 64 h and 5 days, isolated cells associated with the germinal layer and scattered throughout the parenchyma were also found. In the clusters, Nestin expression decreased proportionally with time following transplantation. Furthermore, Large T-Antigen immunoreactivity disappeared from ts cells between 6 and 24 h after transplantation. Finally, measurements of the temporal evolution of PCNA expression within the clusters indicate a progressive reduction in the mitotic activity of the transplanted cells. The results demonstrate that striatal primary neuroepithelial cells and conditionally immortalized neuronal progenitors can survive, migrate and/or compartimentalize into clusters whilst changing their antigenic properties and ability to proliferate.

Animals↗
PubMed1994

Inhibition of AIDS-Kaposi's sarcoma cell induced endothelial cell invasion by TIMP-2 and a synthetic peptide from the metalloproteinase propeptide: implications for an anti-angiogenic therapy.

In the initial phases of angiogenesis, endothelial cells must degrade and cross the vessel basement membrane, as do tumor cells during invasion and metastasis formation. Various metalloproteinases have been implicated in tumor cell invasion, in particular MMP-2 (72 kDa collagenase IV, gelatinase A), which has been demonstrated to be associated with tumor metastasis formation. Supernatants from AIDS-Kaposi sarcoma (KS) cells induce normal endothelial cells to invade through a reconstituted basement membrane (Matrigel) in vitro, which correlates with the angiogenic potential of KS cells in vivo. Here we demonstrate that two specific inhibitors of MMP-2, TIMP-2 and a peptide from the MMP-2 propeptide region (peptide 74), inhibit endothelial cell invasion induced by AIDS-KS cell supernatants. Smooth muscle cells were much less sensitive to these inhibitors. These data suggest that MMP-2 activation is a key event in endothelial cell invasion, the initial phase of tumor-associated neoangiogenesis. Inhibition of this enzyme could be an effective treatment for KS and tumor-associated angiogenesis.

Acquired Immunodeficiency Syndrome↗