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Biomedical subjects

A Ranieri

Publications and source records attributed to A Ranieri.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Retroperitoneal lymphadenectomy and disorders of ejaculation].

Retrograde ejaculation is a frequent and permanent complication after bilateral retroperitoneal lymphadenectomy (RPLND). Seminal emission and ejaculation are primarily under sympathetic control. Several studies after RPLND in patients with nonseminomatous testis cancer proved the role of preservation of the efferent fibers originating from the lumbar sympathetic ganglia. Based on the results of anatomical studies, a modified unilateral operative technique and nerve-sparing approach permit to preserve normal anterograde ejaculation without reduction of long-term survival.

Ejaculation↗
PubMed1998

Cyclin D1 and Cyclin E expression in malignant thyroid cells and in human thyroid carcinomas.

Evidence of the involvement of cyclin gene alterations in human cancer is growing. In this study, we sought to determine the pattern of expression of cyclin D1 and cyclin E in normal and malignant thyroid cells. Quiescent rat thyroid cells in culture, induced to synthesize DNA by thyrotropin (TSH), expressed cyclin D1 gene after 6 hr and cyclin E gene with a peak at 18 hr from the stimulus; K-ras-transformed rat thyroid cells, which grew without addition of hormones necessary for normal cell proliferation, expressed elevated levels of cyclin D1 and cyclin E, compared with normal differentiated thyroid cells. Human benign and malignant thyroid tumors and their relative normal tissues were then analyzed. Neither major genetic alterations nor amplifications for cyclin D1 and cyclin E genes were found by Southern blot analysis in genomic DNAs extracted from all types of thyroid tumors. Moreover, statistical analyses of densitometric values from Northern blots did not show increased levels of cyclin D1 and E mRNAs in the tumor samples, compared with normal thyroid. Immunohistochemical analyses of formalin-fixed paraffin-embedded sections of tissues with specific antibodies revealed a prevalent cytoplasmic cyclin E staining in the thyroid tissues analyzed. Cyclin D1, instead, was present in the cytoplasm of normal thyroids and adenomas, but in 31% of thyroid papillary carcinomas analysed, it was overexpressed, with a localization in the nucleus. Our in vivo observations suggest that unlike cyclin E, elevated nuclear cyclin D1 expression defines a subset of thyroid papillary carcinomas, and might be a contributory factor to thyroid tumorigenesis.

Animals↗
PubMed1998

Intravesical instillation of mitomycin-C in 242 patients with superficial bladder cancer at high risk of recurrence: long-term results.

OBJECTIVE: The present study evaluated the long-term results of intravesical mitomycin C (MMC) instillation after transurethral resection (TUR) in 242 consecutive patients with superficial bladder cancer at high risk of recurrence (stage Ta, grade 1-3, or stage T1, grade 1 and 2, primary multiple or recurrent tumor). MATERIALS AND METHODS: 242 patients were treated with weekly instillations of 40 mg MMC for 8 weeks after TUR. Tumor-free patients then followed a maintenance course with monthly instillations for 3 months. RESULTS: Median follow-up of disease-free patients is 43.5 (range 23-112) months. The incidence of first recurrence is 59.5% (144/242 patients) with a median time to first recurrence of 29 months. 95 patients (39.3%) remained disease-free. Three had disease progression as the first event. The risk of recurrence was significantly higher for multifocal tumors (p = 0.0023, hazard ratio 1.79, 95% CI 1.23-2.59). Overall, patients have been followed for a median time of 57 (range 10-114) months. During this period the recurrence rate was 4.9. Eleven more patients had disease progression. The progression rate is 5.8% (14/242), with a mean time to progression of 34 months. At present 209 patients are alive, 6 have died of bladder cancer, 16 of causes unrelated to the disease and 11 (4.5%) have been lost to follow-up. Thus the crude survival rate is 86.4%, disease-specific mortality 2.5%, and non-disease-specific mortality 6.6%. CONCLUSIONS: Patients with multiple tumors seem to benefit the least from MMC instillation. Probably recurrent disease could be better prevented with intravesical bacillus Calmette-Guérin.

Administration, Intravesical↗
PubMed1997

Human malignant thyroid tumors displayed reduced levels of transforming growth factor beta receptor type II messenger RNA and protein.

Transforming growth factor beta (TGF-beta) is a physiological regulator of thyroid epithelial cell growth and differentiation. This factor signals through a heteromeric complex composed of type I (TGF-beta receptor type I) and type II [TGF-beta receptor type II (TbetaRII)] receptors. Loss of TbetaRII expression has been related to resistance to TGF-beta inhibition of cell proliferation. In the present work, we analyzed the TbetaRII expression in a series of human thyroid tumors, from benign lesions (adenomas) to neoplastic lesions of increasing aggressiveness (papillary and follicular carcinomas) up to the extremely aggressive anaplastic tumors. Results obtained indicated a clear reduced expression of TbetaRII mRNA only in the group of thyroid carcinomas when compared with their relative normal tissues. Immunohistochemical analyses with specific anti-TbetaRII antibodies confirm these observations. These data indicate that loss of expression of TbetaRII can contribute to thyroid cancer progression, inducing cancer cells to escape the growth-inhibitory effect of TGF-beta.

Adenocarcinoma, Follicular↗
PubMed1997

Restored expression of transforming growth factor beta type II receptor in k-ras-transformed thyroid cells, TGF beta-resistant, reverts their malignant phenotype.

Transforming growth factor beta 1 (TGF beta 1) inhibits the growth of normal rat epithelial thyroid cells (FRTL-5 strain) by counteracting thyrotropin (TSH)-stimulated DNA synthesis and by slowing the cells in the G1 phase of the cell cycle. Here, we have studied two clones of FRTL-5 thyroid cell line transformed by the wild type (wt) v-k-ras oncogene (K.M.A1, K.M.A2) and one clone (A6) transformed by a temperature-sensitive (ts) v-k-ras mutant. Anchorage-dependent as well as anchorage-independent growth of these k-ras-transformed cells was not inhibited by TGF beta 1. TGF beta 1 resistance appeared to be dependent by a functional p21 k-ras, because A6 cell growth was partially inhibited at the nonpermissive temperature (39 degrees C). To determine the basis for TGF beta 1 resistance in k-ras-transformed thyroid cells, we looked for possible defects in the expression of type I (T beta R-I/ALK5) and type II TGF beta receptors (T beta R-II). Lower levels of type II receptors were present in all of the k-ras-transformed clones, as revealed by both Northern blot and cross-linking experiments. A partial reversion of the malignant phenotype of the wt k-ras-transformed clone was obtained in two clones isolated after transfection of the malignant thyroid cells (K.M.A1) with a T beta R-II expression vector. These two clones also showed restored levels of exogenous T beta R-II mRNA and protein, and both clones showed a partially reacquired sensitivity to TGF beta 1. Similarly, the reversion of the malignant phenotype of the A6 clone grown at the nonpermissive temperature was accompanied by a restored expression of the T beta R-II receptors. These data indicate that active k-ras oncogene can induce TGF beta 1 resistance in rat thyroid cells and suggest that one of the possible mechanisms of escape from TGF beta 1 growth control in k-ras-induced thyroid carcinogenesis involves a reduced expression of T beta R-II receptors.

Animals↗
PubMed1997

[Conservative therapy of renal parenchymal neoplasia].

We review our overall experience in 1375 patients, who underwent surgery for renal cell carcinoma in the Departments of Urology of Brescia and Bergamo from 1983 to 1996. 185 (13.4%) patients had nephron-sparing surgery: imperative procedure was performed in 74 cases, while an elective surgery was done in 111 patients. Three years minimal follow up was considered in order to evaluate the outcome of surgical treatment in 48 patients who underwent imperative nephron-sparing surgery and in 73 with an elective procedure. Disease specific survival was 80.8% in the first group and it was 97% in the latter.

Adult↗
PubMed1997

Oncogenes and antioncogenes involved in human thyroid carcinogenesis.

The development of cancer is due to the accumulation of multiple somatic mutations, in some cases following germline mutations, which occur in hereditary malignancies such as retinoblastomas or multiple endocrine neoplasia (MEN 2A and B). Genetic alterations or changes in the expression of growth regulatory genes can lead to the initiation of malignant transformation and to eventual tumor progression. Cells that have undergone these cumulative alterations in either the structure or expression of these regulatory genes generally possess a selective growth and/or metastatic advantage over other normal non-transformed cells. Thus, activation of dominantly transforming oncogenes by point mutations, gene amplification, chromosomal translocation or insertional mutagenesis can lead to uncontrolled cellular growth or to a disruption in normal differentiation or apoptosis. Equally contributory to the process of malignant progression is the inactivation of recessive tumor suppressor genes due to point mutations and/or loss of heterozygosity in one allele, which can ultimately lead to a reduction of homozygosity in both alleles. Thyroid tumors in humans represent a particularly suitable multistage model of epithelial tumorigenesis. In fact, even though most thyroid neoplasms originate from a single cell type, i.e. the thyroid follicular cell, they include a broad spectrum of tumors with different phenotypic characteristics and variable biological and clinical behaviour. Multiple degrees of malignancies have been defined: from the benign colloid adenomas through the slowly progressive differentiated papillary and follicular carcinomas to the invariably fatal anaplastic carcinomas, although these histological changes are not necessarily sequential. In this review an effort has been made to summarize and integrate new data published on genetic lesions and altered expression of genes involved in the tumorigenesis of the follicular type of thyroid cancer. We have focused our interest only on gene alterations inducing gain or loss of function, that have been studied in vivo in human thyroid tumor specimens by the use of different techniques, such as PCR mediated DNA analyses, sequencing, mRNA level evaluation and protein expression by immunohistochemical staining.

Genes, Tumor Suppressor↗
PubMed1996

[T1G3 transitional cell carcinoma of the bladder: our experience with 44 patients treated with intravesical BCG after TUR].

Forty-four patients affected by poorly differentiated (G3) superficial TCC invading lamina propria (stage T1) were treated with intravesical BCG. They underwent weekly instillations of 75 mg BCG for six week after trans-urethral resection (TUR) of bladder cancer. An additional induction course was given to patients who relapsed. A maintenance course with monthly instillations for twelve months followed in complete responder patients. After the first induction course, 34/44 patients (77.2%) showed complete response. In 10 patients a second induction course was necessary, with complete response in four. After one or two induction course, 38/44 patients (86.5%) showed complete response. The maintenance course was administered to 38 patients with 35/38 complete responses. After a median follow-up of 30 months, there were 29/44 (65.9%) disease free patients, 11/44 (25%) tumor recurrences and 4/44 (9%) tumor progressions. The drug has been well tolerated with few side effects. Our data suggest that intravescical BCG after TUR is effective in the treatment of high-risk superficial bladder cancer and we believe that it can be used a first approach in treating patients affected by T1G3 bladder cancer.

Administration, Intravesical↗
PubMed1996

[Precancerous lesions of the penis].

Premalignant penile lesions have been associated to squamous cancer, although the true incidence of progression of these entities to squamous cell carcinoma is unknown. These lesions may coexist with or may antecede the occurrence of carcinoma. For this reason close follow-up of the patient is necessary to detect early evidence of malignant degeneration.

Humans↗
PubMed1996

Low dose Pasteur bacillus Calmette-Guerin regimen in stage T1, grade 3 bladder cancer therapy.

PURPOSE: We assessed the effectiveness of intravesical bacillus Calmette-Guerin (BCG) for high risk transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A total of 51 patients with stage T1, grade 3 disease was treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after transurethral resection for bladder cancer. An additional induction course was given to patients with relapse. Tumor-free patients followed a maintenance course with monthly instillations for 12 months. RESULTS: After the initial induction course 37 of 51 patients (72.5%) remained tumor-free. A second induction course was necessary in 13 patients. After 1 or 2 induction courses 44 of 51 patients (86.3%) were tumor-free. The maintenance course was administered to 44 patients, with 41 remaining tumor-free. After a median followup of 33 months (range 3 to 63) 28 patients (54.9%) were disease-free, 12 (23.5%) had recurrent tumors and 7 (13.7%) had progression. The risk of treatment failure was significantly greater for solid than papillary tumors (p = 0.0006), recurrent than primary tumors (p = 0.0052) and coexisting carcinoma in situ (p = 0.124) in multivariate analysis, and for early recurrence (p = 0.0001) in univariate analysis only. The drug was well tolerated with few side effects. CONCLUSIONS: Our data suggest that this low dose Pasteur BCG regimen is effective in the treatment of high risk superficial bladder cancer. Some tumor characteristics, such as solid appearance, coexisting carcinoma in situ, history of superficial transitional cell carcinoma and early relapse after the initial induction course, seem to be negative prognostic factors.

Adjuvants, Immunologic↗
PubMed1995

Two-dimensional electrophoresis of thylakoid protein patterns in two wheat cultivars with different sensitivity to sulfur dioxide.

Plants of two wheat cultivars (Triticum aestivum L., cultivars Mec and Chiarano), differing in sensitivity towards sulfur dioxide, were fumigated with 96 nL L-1 of SO2 for four months. Thylakoid membranes were subjected to two-dimensional electrophoresis in order to detect possible changes in the protein patterns. We found the greatest alterations following treatment in the polypeptide profiles of the most sensitive cultivar, Mec, even if some significant changes were also detected in the plants of the cultivar Chiarano.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1995

Multiplex PCR analysis and genotype-phenotype correlations of frequent APC mutations.

Germline mutations of the adenomatous polyposis coli (APC) gene tend to cluster in discrete regions. Some of these mutations occur frequently in familial adenomatous polyposis coli (FAP) patients, and strategies for genetic diagnosis of the disease should include simple methods for their detection. We studied a total of 48 FAP-affected or "at-risk" members from 31 unrelated FAP pedigrees. Unrelated patients were analyzed using heteroduplex analysis on agarose minigels (HAAM) and multiplex allele-specific PCR. This novel strategy readily and reliably detected the three frequently occurring APC deletions at codons 1061, 1068, and 1309, allowing identification of mutant alleles in nine unrelated patients. A targeted mutational analysis, based on HAAM and amplification refractory mutation system (ARMS), allowed the rapid identification of 11 additional subjects with germline deletions, among relatives of the patients in whom mutations had been detected by multiplex PCR and HAAM. The use of two independent PCR-based tests, employing distinct sets of primers, reduces the possibility that artifacts occurring during DNA amplification may interfere with the diagnostic evaluation. The analysis of genotype-phenotype correlations provided evidence for heterogeneity with regard to the extent of colonic and extracolonic manifestations of the disease in subjects bearing identical mutations. However, the consistent association of the deletion at codon 1309 with more severe colonic disease than that observed in patients with mutations at codons 1061 and 1068, supports a correlation between mutation site and penetrance of FAP.

Adenomatous Polyposis Coli↗
PubMed1995

[Surgical treatment of benign prostatic hypertrophy: what and when TURP vs adenomectomy].

Surgical treatment is the gold standard for Benign Prostatic Hyperplasia (BPH) therapy. At the present diagnostic approach allows better patient selection and treatment assignment. In this work we have studied retrospectively the outcome of 120 BHP patients who underwent trans urethral resection (TURP) and of 145 BPH patients underwent "open" prostatectomy. In all the patients surgical time, prostate weight, indwelling catheter standing, rest in bed, early and late complications were evaluated. Irritative symptoms occurred after TURP in 10% of the cases. The two therapeutical options are not comparable for they technically different. The choice between the two depends on the accurate patient characterization and selection.

Bed Rest↗
PubMed1995

[Epidermoid carcinoma of the oral cavity. Considerations of the role of the papillomavirus].

Human papilloma virus (HPV) may have an important role in oral carcinoma etiology. Our work compares the presence of HPV in the epithelium of oral mucosa of patients with oral carcinoma with other factors of risk (smoking, alcohol, chronic mucosal trauma). We studied 33 patients operated for oral cancer at St. Salvatore Hospital in l'Aquila, in January-December 1990. The presence of HPV was proved by a direct valuation of morphological signs (coilocytosis, nuclear inclusions, etc.) and by immunohistochemical technique with primary antibodies against structural virus antigens. Among the 33 patients 19 (57.6%) were positive for HPV and 14 (42.4%) were negative. Among the HPV positive subjects 13 were smokers, 11 usually assumed alcohol and 6 had chronic mucosal trauma. Among the HPV negative subjects 9 were smokers, 7 assumed alcohol and 3 had chronic mucosal trauma. The statistical evaluation of data showed the lack of significance of viral infection compared to other factors of risk. In spite of a few cases examined, we suppose that HPV doesn't play a primary role in oral cancerogenesis, but is a concomitant cause with other factors of risk.

Adult↗
PubMed1995

Epithelial rat thyroid cell clones, escaping from transforming growth factor beta negative growth control, are still inhibited by this factor in the ability to trap iodide.

Transforming growth factor beta (TGF beta) acts on epithelial thyroid cells, negatively controlling their proliferation and functions. The effects of TGF beta on epithelial rat thyroid cells (FRTL-5) and on two TGF beta-resistant rat thyroid cell clones (FRTL-5H2 and FRTL-R) were investigated. FRTL-5H2 represents a rat thyroid cell clone overexpressing active erbB-2 oncogene, recently obtained after FRTL-5 cell infection with a retrovirus vector carrying the erbB-2 human oncogene (G. Mincione et al., Cancer Res., 53: 5548-5553, 1993). FRTL-R is a FRTL-5 subclone spontaneously isolated after long term in culture. FRTL-5H2 and FRTL-R cell clones were stimulated by TGF beta at the same concentration of 5 ng/ml that induced 70% inhibition of [3H]thymidine incorporation in control FRTL-5 thyroid cells. Nuclear events regulated by TGF beta, such as cyclin and cyclin-dependent kinase gene expression, were then analyzed. In FRTL-5 cells, TGF beta was found to reduce the expression of cdk2 and cyclin A genes; the same treatment did not modify nuclear gene expression in the resistant cell clones. TGF beta is known to reduce iodide uptake in thyroid cells; in both FRTL-5H2 and FRTL-R cells, TGF beta was found to inhibit the thyrotropin-induced iodide uptake. Thus, thyroid cell clones, resistant to the growth-inhibitory activity of TGF beta, were sensitive to TGF beta inhibition of iodide incorporation, suggesting that TGF beta activates divergent signaling pathways in these cells, separately controlling cell proliferation and differentiation parameters. Studies on TGF beta receptors showed similar amounts of TGF beta-binding species on FRTL-5 cells and TGF beta-resistant clones, while 125I-labeled TGF beta cross-linking experiments revealed differences; thus, the TGF beta-resistant cells showed a 40% decrease in the amount of labeled type II TGF beta receptor on the cell surface. However, this different pattern of TGF beta receptors cannot totally account for the shown TGF beta resistance to growth inhibition that might also be due to perturbation in signaling pathways.

Animals↗