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Biomedical subjects

G Santelli

Publications and source records attributed to G Santelli.

At least 37 records · Page 2Linked to original sources
PubMed1996

Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter: KRAS expression in thyroids analyzed by in situ hybridization.

We have previously generated transgenic mice bearing a molecular construct obtained by fusing the rat thyroglobulin promoter with the human Kirsten ras oncogene (KRAS). These mice showed thyroid abnormalities, although at very low incidence and after a long latency period. A six-month thyrotropin (TSH) stimulation of thyroid glands, followed by a two-month suspension, induced a significant increase in the number of lesions in transgenic mice as compared with a nontransgenic control group. Our goal was to follow the progression and the reversion of the tumorigenesis process in relationship with the levels of expression of the KRAS in this experimental model. In situ hybridization was used to detect expression of KRAS mRNA in sections of thyroids of the various groups of mice. A positive hybridization was observed in follicular cells of TSH-stimulated transgenic mice, whereas no expression could be appreciated in control nontransgenic mice. A positive signal was also observed in thyroid glands excised from transgenic mice after the 2-month suspension of treatment; however, the number of expressing cells was decreased compared with transgenic mice killed immediately after 6 months of a goitrogen regimen. Finally, every cell in the single thyroid carcinoma observed after the two-month suspension was positive for the transgene mRNA. This study further strengthens the role of the expression of mutated KRAS in the early stages of thyroid follicular cell transformation and indicates that when the expression of the mutated KRAS becomes independent of exogenous TSH stimulation, this event coincides with a further progression towards tumorigenesis.

Adenoma↗
PubMed1995

Mutated human Kirsten ras, driven by a thyroglobulin promoter, induces a growth advantage and partially dedifferentiates rat thyroid epithelial cells in vitro.

We have earlier shown that expression of the human activated Ki-ras, directed by the rat thyroglobulin (TG) promoter in the thyroid gland of transgenic mice, is able to induce thyroid benign tumors, albeit at low incidence. A likely explantation of our results is that the low levels of exogenous Ki-ras transcripts are not sufficient to induce multifocal tumors in the thyroid gland. We have performed experiments to analyze the effects of a similar construct in vitro upon thyroid-cell proliferation and differentiation. Transfection of FRTL-5 rat thyroid cells with the human Ki-rasval12 fused to the rat TG promoter is rapidly followed by reduced expression of the differentiation markers thyroglobulin, thyroperoxydase and thyrotropin receptor, but not by fully malignant cell transformation. The data reported support the hypothesis that Ki-ras mRNA levels are critical to the process of complete neoplastic transformation of thyroid epithelial differentiated cells in vitro.

Amino Acid Sequence↗
PubMed1995

Dbl expression driven by the neuron specific enolase promoter induces tumor formation in transgenic mice with a p53(+/-) genetic background.

The dbl oncogene, generated by the truncation of the amino-terminal portion of the proto-oncogene sequence, encodes a guanine-nucleotide-releasing factor. The transforming activity of this oncogene has never been demonstrated in vivo or in vitro except in the NIH 3T3 mouse fibroblast cell line. The expression of the proto-dbl transcript is confined to tissues and tumors of neuroectodermal derivation. Therefore, to study the transforming activity of the dbl oncogene in vivo, we have generated transgenic mice that express this oncogene in neuroepithelial tissues. Mice carrying the dbl oncogene did not develop a tumor. Successively, to establish whether dbl interacts with the tumor suppressor gene p53 in tumorigenesis, we have used a p53 deficient mouse strain. The results reported here indicate that dbl is capable of causing tumor formation in vivo when its expression is driven in an appropriate cellular and genetic environment.

Animals↗
PubMed1995

Expression of the RET oncogene induces differentiation of SK-N-BE neuroblastoma cells.

Expression of the RET proto-oncogene, a cell surface receptor for an as yet unknown ligand, is associated with tumors, tissues, and cell lines of neural crest origin. Accumulating evidence suggests that RET activity is involved in the process of neuronal differentiation. Moreover, induction of phenotypic differentiation of neuroblastoma cell lines is associated with the rapid accumulation of RET transcripts. To verify the role of RET in neuronal differentiation, we introduced into the human neuroblastoma cell line SK-N-BE four versions of the RET oncogene, activated by different mechanisms: RET/PTC1 and RET/PTC3, which are activated by rearrangement with heterologous genes; and two activated RET mutants, which carry the single amino acid substitution found associated to the inheritance of the multiple endocrine neoplasia type 2A (retMEN2A allele) and type2B (retMEN2B allele), respectively. We demonstrate that, after transfection with the RET oncogenes, SK-N-BE cells display a reduced growth rate and acquire a neurite-bearing phenotype accompanied by enhanced expression of the axonal growth-associated protein, GAP-43, and the high molecular weight neurofilament, NF200. These results indicate that, when activated, RET is able to cause growth inhibition and to promote neuronal differentiation of neuroblastoma cells.

Blotting, Northern↗
PubMed1993

Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter.

Transgenic mice have been generated bearing three fusion genes consisting of: (a) a 900-base pair rat thyroglobulin promoter followed by a gene coding for a chloramphenicol acetyl transferase activity; (b) the same promoter followed by the complementary DNA of the human activated Ki-ras oncogene; (c) a 2000-base pair rat thyroglobulin promoter followed by the complementary DNA of the human activated Ki-ras. We have shown that the 900-base pair rat thyroglobulin promoter is able to direct the expression of the reporter gene specifically in the thyroid gland of transgenic mice. The mice bearing the two Ki-ras constructs, which express the transgene in thyroid glands, show thyroid abnormalities, although at very low incidence. These lesions appear after a long latency and with a benign aspect, thus suggest that, in agreement with literature data on naturally occurring human thyroid tumors, the action of an activated ras gene is not sufficient to attain a complete malignant conversion of thyroid glands in vivo. However, ras expression in thyroid follicular cells represents a favorable ground for tumor development, as shown by the fact that goitrogen stimulation experiments increase the occurrence of tumors.

Adenoma↗
PubMed1991

[Various echographic features in testicular torsion].

The Authors discuss the informations that can be obtained from sonography in testicular torsion on the basis of 21 patients. The different sonographic features of the twisted testis, which are time-related, are reported and stressed. Ultrasonography is a very sensitive diagnostic tool and can be a useful complement of clinical examination.

Adolescent↗
PubMed1991

[Rupture of the testicle: comparison of the echographic picture and operative findings].

9 patients suffering from testicular rupture, owing to blunt scrotal trauma, were examined with ultrasound and then underwent surgical exploration. Sonography correctly diagnosed testicular rupture in 8 patients, 1 false-negative occurred. Clinical examination often is difficult in evaluating testicular trauma, sonography provides a useful tool for improved diagnosis in testicular rupture.

Adolescent↗
PubMed1989

Prognostic relevance of urinary neopterin in non-Hodgkin's lymphomas.

Neopterin excretion levels were assessed in 66 consecutive patients affected by non-Hodgkin's lymphomas (NHL). The logarithm of the mean value of the whole series was 2.71 (log [mumol neopterin/mol creatinine]), significantly higher (P less than 0.001) than the control value (2.12). Fifty-six of 66 patients had a raised excretion of neopterin in amounts statistically related to the stage of disease. The mean value (2.51) of patients in Stages I-II was lower than the mean value (2.86) of patients in Stage III-IV (P less than 0.001). The 2-year probability of survival was 64% for patients in Stages I-II and 34% for patients in Stages III-IV. However, patients with lower neopterin excretion (less than 2.65) fared better than patients with higher neopterin excretion, regardless of the stage. Longitudinal analysis showed a trend toward a correlation between response to therapy and neopterin excretion. In NHL, the raised neopterin excretion appears to be a consequence of activation of the host immune system rather than a product of the malignant cells. But this excessive activation of the monocytes-macrophages, as reflected by urinary neopterin levels, is not accompanied by a better outcome. In conclusion, although neopterin cannot be considered a typical tumor marker, nevertheless it is an useful prognostic marker in NHL.

Biopterins↗
PubMed1989

Neopterin and alpha-interferon in patients affected by Kaposi's sarcoma from Africa.

The presence of circulating alpha-interferon and neopterin was investigated in sera of 47 patients affected by African Kaposi's sarcoma, both HIV-seropositive (13 patients) and HIV-seronegative (34 patients). For comparison, analyses were also performed in 20 HIV-seropositive symptomatic African subjects as well as in 20 African and 20 Italian healthy individuals. Alpha-interferon and neopterin levels appeared significantly higher in comparison with healthy control groups (P less than 0.001) but not with HIV-seropositve African individuals without Kaposi's sarcoma. Moreover, alpha-interferon and neopterin levels were significantly higher in progressive Kaposi's sarcoma (27 patients) than in regressive Kaposi's sarcoma (20 patients) (P less than 0.001). A significant correlation between alpha-interferon and neopterin was observed (r = 0.57; P less than 0.01). Furthermore, alpha-interferon levels of HIV-seropositive Kaposi's sarcoma patients resulted significantly higher in comparison with the seronegative ones (P less than 0.05). It is concluded that alpha-interferon and neopterin may be reliable prognostic markers in Kaposi's sarcoma patients.

Adult↗
PubMed1989

Recurrent essential mixed cryoglobulinemia in renal allografts. Report of two cases and review of the literature.

This report describes two patients in whom essential IgG-IgM mixed cryoglobulinemia (EMC) glomerulonephritis led to end-stage renal disease. Both patients underwent primary hemodialysis, and during the period of uremia clinical and biological manifestations of the disease fully resolved. Transplantation was performed, and in both cases cryoglobulinemia quickly recurred (30 days and 6 months after transplantation, respectively) with clinical renal and extrarenal flare, and reappearance of the biological markers of the disease (decrease in C3 and C4 components of serum complement, detection of rheumatoid activity and of cryoglobulinemia in the serum). The literature on EMC glomerulonephritis leading to end-stage renal disease is reviewed. Factors that may have contributed to extinguishing the disease and to further recurrence following transplantation-consequences of uremic state, alloimmunization and intercurrent infectious disease-are discussed.

Adult↗
PubMed1988

Urinary neopterin and immunological features in patients with Kaposi's sarcoma.

We studied neopterin excretion levels and immunological features of 20 patients affected by Kaposi's sarcoma (KS), compared to 30 normal controls. Eighteen patients had the classic form of Kaposi's sarcoma (CKS), while two patients were anti-human immunodeficiency virus (HIV) seropositive and affected by the epidemic form associated with the acquired immunodeficiency syndrome (AIDS). In CKS patients, a trend of an increase of neopterin levels with more advanced stages appeared from our data whereas a significant reduction in CD3+ and CD4+ lymphocytes subsets was observed already at early stages (P less than 0.01). CD8+ cells did not show significant variations. A significant increase in serum IgA immunoglobulins (P less than 0.05) was also observed. Comparative analysis of the two patients affected by AIDS/KS showed the profound deficit in T-cell immunity but also the prognostic value of neopterin monitoring. Furthermore these findings seem to confirm Kaposi's sarcoma as an 'opportunistic neoplasia' and indicate neopterin as a useful prognostic marker.

Aged↗
PubMed1988

Membranous nephropathy in a bone marrow transplant recipient.

A bone marrow transplant recipient is described who had development of nephrotic syndrome in association with chronic graft-versus-host disease (GVHD) and on cyclosporine (CsA) treatment withdrawal. Renal biopsy revealed a membranous glomerulonephritis (MG). The possible relationship between this autoimmune disorder, the immunological features of GVHD in experimental animals, and the influence of CsA is discussed.

Adult↗