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G Botti

Publications and source records attributed to G Botti.

At least 19 recordsLinked to original sources
PubMed1996

Development of mammary and cutaneous gland tumors in transgenic mice carrying the RET/PTC1 oncogene.

RET/PTC1 is a chimeric oncogene created by the fusion of the tyrosine kinase domain of RET to the 5'-terminal region of another gene named H4. So far, this oncogene has been found activated only in human papillary thyroid carcinomas. In order to investigate its transforming properties in vivo, we have produced transgenic mice carrying RET/PTC1 under the control of the H4 promoter. The transgene was expressed in several tissues, consistently with the ubiquitous expression of the wild type H4 gene. Mammary adenocarcinomas and, less frequently, hyperplasia of sebaceous glands and rare benign skin tumors, named pilomatrixomas, developed in these mice. The tumors were shown to express the transgene both at the RNA and protein level. These results demonstrate that the transforming ability of the RET/PTC1 oncogene is not restricted to the thyroid epithelium in vivo. Despite its ubiquitous expression, however, RET/PTC1 was able to induce only a limited number of tumor types; specifically mammary epithelium was affected by transgene expression, thus suggesting that RET/PTC1 is able to couple with transforming pathways specific for these glandular cells.

Age Factors↗
PubMed1996

Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the placenta-derived growth factor.

Neoangiogenesis is a prerequisite for tumor growth and metastasis. In germ cell cancer patients with the disease limited to the testicle (stage A), tumor-associated neovascularization is predictive of metastatic disease (stage B). To investigate the molecular mechanisms underlying neovascularization in human germ cell tumors (GCTs), we analysed the expression of two angiogenic growth factors, vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF), and of their receptors (FLT-1) and Flk-1/KDR) in a panel of testicular tumors. In this study we show a marked increase in VEGF expression in 36/44 (81.8%) primary testicular-derived GCTs, as compared to normal testis, that significantly correlates with a high density of intratumor microvessels (r = 0.72461, P < 0.001; n = 24). As determined by RT - PCR and/or Western blot, the predominant VEGF isoforms expressed in GCTs are the VEGF121 and VEGF165, which are more efficiently secreted by the cells, and thus more active in eliciting angiogenesis. Conversely, in the case of PIGF, only a weak correlation with the vascular density of tumors is observed (r = 0.26599, P < 0.05; n = 24). Northern blot analysis also revealed significant up-regulation of VEGF/ PIGF receptors in highly vascularized germ cell tumors, compared to normal testes. These findings suggest that VEGF may act in a paracrine manner to induce neovascularization, oedema extravasation and cyst formation in human germ cell tumors. The correlation between VEGF expression and the vascular density of tumors, suggest that the evaluation of VEGF expression may be of help in predicting patients at risk for metastatic diseases. Finally, we demonstrate that VEGF up-regulation may occur at the RNA level since no gene amplification is observed; conversely, in in vitro models such as the embryonal stem cell line NTERA-2 and the choricarcinoma JEG-3 cell line, VEGF (but not PIGF) mRNA expression is regulated by hypoxic stress.

Base Sequence↗
PubMed1996

Radiation dose to the lenses in CT of the paranasal sinuses.

The radiation dose to the lens during CT of the paranasal sinuses was measured in 20 patients. In 10 patients, a "standard" technique with axial and coronal sections was used. In the remaining 10 patients, overlapping axial sections for bidimensional reconstruction were obtained. Radiation dose was measured using thermoluminescent dosimeters. The mean dose was 22 mGy in patients who underwent "standard" CT and 42 mGy in those who underwent CT with overlapping sections. Dose was dependent on the total number of slices and of transorbital axial sections. Coronal sections did not statistically increase the radiation dose to the lenses. Although these doses were significantly below the critical dose for cataracts, CT with overlapping sections gives a considerably higher radiation dose. We recommend the bidimensional reconstruction technique only for selected cases (e.g. preoperative assessment of the roof of the ethmoid sinuses or in patients who can or should not maintain the hyperextended position required for coronal views.

Ethmoid Sinusitis↗
PubMed1996

Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography.

UNLABELLED: Folate binding protein (FBP) GP38 is a membrane-associated glycoprotein that mediates the intracellular transport of folates. The enhanced expression of FBP in ovarian carcinomas provided a rational basis for clinical studies with specific monoclonal antibodies and some newly synthesized antifolate drugs. Because the outcome of these clinical studies ultimately depends on the degree of FBP expression, we measured the local concentration of FBP using 125I-MOv18 monoclonal antibody and quantitative autoradiography. METHODS: Tissue sections from 37 specimens of ovarian carcinoma and 13 nonmalignant ovaries were incubated with increasing concentrations of 125I-MOv18 with and without an excess of unlabeled antibody. Tissue-bound radioactivity was measured by quantitative autoradiography. RESULTS: Folate binding protein was found to be overexpressed in 91% of nonmucinous ovarian carcinomas, with local concentrations ranging between 1.14 and 82.84 pmole/g. Adjacent tumor sections simultaneously studied with 125I-MOv18 and a 125I-labeled folic acid derivative showed matching and superimposable regional distributions of bound radioactivity of the two radioligands, indicating that the antigen, specifically recognized by 125I-MOv18 in nonmucinous ovarian carcinomas, is capable of binding folates. Nonmalignant ovaries did not contain measurable amounts of antigen when assayed with 125MOv18 but showed a limited and specific binding of the 125I-folic acid derivative to tissue sections. The autoradiographic findings were confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells, by immunoperoxidase staining with MOv18 on tumor sections and by biochemical identification of FBP in membrane fractions from tissue samples. CONCLUSION: Folate binding protein is overexpressed up to 80-90-fold in nonmucinous ovarian carcinomas compared with nonmalignant ovaries. Quantitation of FBP may provide a useful tool in the design of clinical studies with specific monoclonal antibodies and certain antifolate drugs that enter the cell through FBP.

Adenocarcinoma, Mucinous↗
PubMed1996

[Prognostic value of extensive lymph node excision in curative resections of stomach cancers. Apropos of a series of 100 patients].

UNLABELLED: The aim of this work was to determine the frequency and localization of lymph node involvement and the prognostic value of extensive node dissection on survival in patients with cancer of the stomach. TYPE OF STUDY: Prospective study from 1981 to 1991 evaluating node dissection in adenocarcinoma of the stomach. PATIENTS: There were 179 gastrectomies during the 10-years study period including 100 performed as a curative treatment. The tumour was located in the lower part of the stomach in 48 cases, in the upper part in 25 cases in the middle part in 22 cases and involved the entire organs in 5 cases. METHODS: Distal subtotal gastrectomy (DSG) was performed in 45 cases, total gastrectomy (TG) in 16 and total gastrectomy extended beyond the stomach (TGE) in 33 cases. Polar gastrectomy (PG) was used in 6 cases. Type R2 node dissection was done for 90 patients and R1 dissection for 10. RESULTS: The tumour extended to the mucosa-submucosa (T1) in 17 cases, the musculosa (T2) in 22 cases, the serous membrane (T3) in 45 cases and to adjacent organs (T4) in 16 cases. A mean 18 nodes was examined per surgical specimen and node involvement was found in 59. The localizations showed that the coronary and hepatic chains (n. 7 and 8) were invaded at a rate comparable with the perigastric nodes (n. 3 and 6). The splenic chain was invaded in 1 patient out of 5 with localizations in the mid and upper portions. Corrected overall survival was 49% at 5 years. Survival depended on the node extension (p < 0.0002): survival reached 73% when no metastasis was found and fell to 48% with perigastric node involvement and 30% when the pedicular nodes were invaded. Survival was also a function of tumour stage (p < 0.0002): for T1 tumours it was 89%, for T2 86% and for T3 32%. Multivariance analysis (Cox) showed that parietal extension and node involvement were risk factors with a relative risk of 3.53 and 1.44 respectively. CONCLUSION: Extensive node dissection of the pedicular chains should improve survival without increasing morbidity or mortality in the treatment of cancer of the stomach.

Female↗
PubMed1995

Sociodemographic factors associated with the diagnostic staging of breast cancer in southern Italy.

BACKGROUND: There are marked regional differences in breast cancer mortality rates in Italy, probably linked to factors such as diagnostic delay, therapeutic strategies, and biologic and sociodemographic differences. To investigate a possible link between sociodemographic factors (e.g. age, education, and residence) and delay in the diagnosis of breast cancer, data were evaluated from all such patients from our Institute living in the Campania Region of Southern Italy for 1991-1993. METHODS: Patients were grouped into Tis-T1/N0-N+ versus T2-4/N0-N+ and the variables examined were age (< 40, 41-50, 51-60, > 60 years), education (< or = 5 vs. > 5 school years) and residence (urban vs. rural). An analysis was made using the Pearson's Chi-square test and the multiple logistic regression. RESULTS: Statistically significant differences were found for both residence (P = 0.04) and education level (P = 0.03) in the older than 60 years age group, but only for residence (P = 0.03) in the 51-60 years age group. The risks according to Mantel-Haenszel were 1.28 for education (P = 0.08) and 1.32 for residence in rural municipalities (P = 0.05). The odds ratio for residence in rural municipalities, adjusted by education and by the education-residence interaction, was 2.26 (95% confidence interval [CI], 1.12-4.54) in the 51-60 years age group and 1.74 (95% CI, 1.01-3.00) in the older than 60 years age group. CONCLUSIONS: These data clearly indicate that residents of rural municipalities, as well as poorly educated subjects, are more likely than their respective counter-parts to have a delayed diagnosis of breast cancer.

Adult↗
PubMed1995

Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.

Blotting, Western↗
PubMed1995

Dipyridamole echocardiography for diagnosis of coexistent coronary artery disease in hypertrophic cardiomyopathy. Echo-Persantine International Cooperative (EPIC) Study Group--Subproject Hypertrophic Cardiomyopathy.

The recognition of coexistent coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon electrocardiographic changes or perfusion defects. Dipyridamole-stress echocardiography has proved a sensitive and highly specific test for noninvasive diagnosis of CAD in various patient subsets. To establish the feasibility, safety, and diagnostic accuracy of dipyridamole-stress echocardiography in patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60 patients was referred for coronary angiography independently of test results; CAD was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel. Dipyridamole echocardiography/electrocardiography testing was completed in all patients, with no limiting side effects or adverse reactions. In the subgroup of 60 patients with coronary angiography (14 with and 46 without CAD), chest pain occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS); and transient dyssynergy in 10 patients (10 with and none without CAD, p < 0.0001). Assuming the transient regional dyssynergy to be the only criterion of positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100% specificity, 100% positive predictive value, and 93% diagnostic accuracy for diagnosis of angiographically assessed CAD. We conclude that high-dose dipyridamole echocardiography testing may be considered a feasible and accurate tool for the noninvasive diagnosis of CAD in patients with hypertrophic cardiomyopathy.

Adult↗
PubMed1995

Knowledge acquisition from the UMLS sources: application to the description of surgical procedures.

The re-usability of lexicons and knowledge in medicine is a crucial challenge. The Unified Medical Language System (UMLS) project has attempted to provide a repository of concepts, semantically categorized for biomedical domain. This paper describes some results about the relevance of UMLS structures for specific purposes. We have focused on the description of surgical procedures. Discussion concerns synonymy of terms, granularity of concepts, and ontology. A preliminary work on the exploitation of interconcept links by a computerized application reveals a heterogeneous implementation of those relationships. However, the UMLS provides a powerful knowledge base for developers.

General Surgery↗
PubMed1994

Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies.

Current evidence regarding the regulation of urokinase-dependent extracellular proteolysis indicates that plasminogen activation is a surface-associated process. We have compared the histological localization of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in breast cancer sections using a panel of monoclonal antibodies. First, the ability of six different anti-uPA monoclonal antibodies to recognize pro-uPA, uPA, and in vitro-formed complexes of uPA with either soluble uPAR or with plasminogen activator inhibitor type 1 was compared. Then the reactivity of the anti-uPAR antibodies was tested, and the occurrence of an uPA receptor of about M(r) 55,000 in samples from breast carcinoma was assessed by immunoprecipitating the uPA receptor from an in vitro 125I-labeled tumor extract. Immunocytochemical data from adjacent sections of 10 tumor specimens showed that antibodies recognizing free and bound uPA mostly stain the cytoplasm and the membrane of epithelial tumor cells in confined areas of the tumor and some fibroblast-like stromal cells. Acid pretreatment of tumor sections, which removes receptor-bound uPA, causes a strong reduction of the immunocytochemical reactivity of epithelial tumor cells, whereas staining of fibroblast-like cells is not considerably affected. Consistent with these results, epithelial tumor cells were mostly unreactive to anti-uPAR antibodies unless pretreated with acidic buffer, whereas fibroblast-like stromal cells showed a faint but acid-resistant staining with all anti-uPARs. In conclusion, these results show that occupied uPA receptors are definitely present on the membrane of epithelial tumor cells and suggest the occurrence of uPA-uPAR-dependent proteolytic activity on the surface of breast cancer cells.

Adult↗
PubMed1994

[Anesthetists and continuing education].

Although the importance of continuing medical education (CME) is a recognized fact, its modalities are still a controversial matter. In order to obtain informations on the demands and the difficulties to which French anaesthetist (AN) are faced with, the Committee for Education of the French Society of Anaesthesia (SFAR) carried out an inquiry with a questionnaire circulated to 7000 AN. The rate of answers was about 10%. With regard to age, gender, mode of activity and length of service in the specialty, the group of responders was representative of the French population of AN. The inquiry seems to demonstrate a strong motivation for CME, as well as demands for training courses, courses extending over two days or more, and a self-assessment. The funding of the expenses as well as the difficulties to obtain a locum tenens were the two main obstacles which limited the access to CME.

Anesthesiology↗
PubMed1994

[A study of 82 cerebral infarctions in the area of posterior cerebral arteries].

Of 598 consecutive non-selected cases of cerebral infarction included in a stroke registry, 82 cases (54 men and 28 women, mean age 66 +/- 14 years) of spontaneous and isolated posterior cerebral artery (PCA) territory infarction (right PCA in 36, left PCA in 35 and both in 11) were identified on the basis of CT combined with MRI in 51 cases. Infarction was superficial in 25 (group A), combined deep-superficial in 23 (group B) and deep in 34 (group C). Of 48 superficial lesions, 29 were massive while 19 were restricted to the territory of one branch. Of 57 deep lesions, 21 were located in the inferolateral thalamic territory, 10 in the paramedian thalamic territory, 12 in other midbrain or thalamic territories, and 14 in a combination of various midbrain and/or thalamic territories. Of 41 patients with unilateral superficial involvement, 39 had homonymous visual field defect. Unawareness of the visual defect and visual release hallucinations were observed with the same frequency in right and left lesions. Of 7 patients with bilateral superficial involvement, only 5 had bilateral visual field defect including incomplete cortical blindness in 3. The frequency of confusional state (n = 24) did not differ significantly in left versus right sided lesions while it was significantly higher in superficial or combined versus deep lesions (p = 0.05). Of 18 clinically evaluable patients with left PCA territory infarct, 14 had speech disorders including pure alexia in only one case. Of 15 patients with right territory infarction, 10 had spatial judgement disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Designing a sub-set of the UMLS knowledge base applied to a clinical domain: methods and evaluation.

The UMLS is a complex collection of interconnected biomedical concepts derived from standard nomenclatures. Designing a specific subset of the UMLS knowledge base relevant to a medical domain is a prerequisite for the development of specialized applications based on UMLS. We have developed a method based on the selection of the appropriate terms in original nomenclatures and the capture of a set of UMLS terms that are linked to them in the network to a certain degree. We have experimented it as the foundation for a concept base applied to urology. Results depend on the exhaustiveness of the relationships between the Metal concepts. A preliminary analysis of the sub-base reveals that some adaptations of vocabulary and ontology are required for clinical applications.

Algorithms↗
PubMed1993

Human urokinase receptor concentration in malignant and benign breast tumors by in vitro quantitative autoradiography: comparison with urokinase levels.

We measured the tissue concentration of human urokinase receptor (uPAR) in 22 breast carcinomas and 9 benign breast lesions using in vitro quantitative autoradiography. Tissue sections were incubated with increasing concentrations of 125I-pro-urokinase in the presence or absence of unlabeled competitor. Breast carcinomas were found to contain 5 times more uPAR than benign breast lesions with respect to their protein content [523 +/- 72 versus 108 +/- 20 (SE) fmol/mg (P < 0.001)]. Simultaneous quantitation of urokinase (uPA) by immunoenzymatic assay on tissue extracts from the same specimens showed that breast carcinomas also contain 19 times more uPA than benign tumors (611 +/- 134 versus 32 +/- 8 fmol/mg) (P < 0.01). The reliability of quantitative autoradiography measurements was confirmed by uPAR cross-linking assay on membrane fraction from either U937 histiocytic lymphoma cells or breast carcinomas and immunoperoxidase staining with an anti-uPAR antibody on tumor sections. Also, immunoperoxidase staining with an anti-uPA monoclonal antibody showed that uPA is indeed localized on the plasma membrane of epithelial tumor cells in confined areas of breast carcinomas whereas cells from benign breast lesions were devoid of uPA under the same experimental conditions. In conclusion, our findings support the hypothesis that uPAR plays a central role in the acquisition of an invasive phenotye and favor its potential use as a prognostic factor in patients with breast carcinoma.

Adult↗
PubMed1993

PCNA/cyclin and P-glycoprotein as prognostic factors in locally advanced breast cancer. An immunohistochemical, retrospective study.

AIMS AND BACKGROUND: The aim of the present study was to determine, retrospectively, whether the immunohistochemical expression of two biologic markers of aggressively, P-glycoprotein (P-gp) and PCNA/cyclin (PCNA), could be related to response to chemotherapy and prognosis in locally advanced breast cancer. METHODS: PC 10 Mab was used to determine the proliferation index (PCNA) and C-219 Mab to determine P-gp in 25 locally advanced breast carcinomas subjected to preoperative chemotherapy with MDR-related drugs. RESULTS: P-gp and PCNA were expressed in 76% and 100% of the tumors, respectively. No case of high P-gp expression was associated with good chemosensitivity, and all P-gp-negative cases showed the best chemotherapeutic response. P-gp and PCNA were both highly expressed in patients who developed local-regional or distant metastases. No recurrence was associated with a negative or low P-gp score. CONCLUSIONS: Statistical analysis showed that high P-gp expression was related to a poor response to chemotherapy and a short disease-free survival. A high PCNA score was not found to be significant for predicting chemosensitivity or survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Tumour uptake of 57-cobalt-bleomycin in patients with breast cancer.

17 patients with breast carcinoma were studied with 57-cobalt-bleomycin scintigraphy. Scans showed increased tumour uptake in all patients. Results expressed as percentage of the injected dose (ID) normalised by the size of the tumour region (% ID/pixel) showed higher tumour uptake in patients with T3-T4 breast carcinomas (n = 5) than in patients with T1-T2 breast cancer (n = 12) (8.4 +/- 0.55 x 10(-3) vs. 5.25 +/- 1.71 x 10(-3)% ID/pixel, respectively, P < 0.05). An inverse correlation between tumour uptake of 57-cobalt-bleomycin and progesterone receptor concentration was also found in all tumours tested (r = -0.60, P < 0.05, n = 10) and was confirmed in the group of patients with T2 breast carcinomas (r = -0.89, P < 0.05, n = 6). We conclude that a quantitative analysis of 57-cobalt-bleomycin uptake can give additional information suitable for the presurgical characterisation of a tumour.

Adult↗