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1.
M. Fracchia G. Galatola I. Sarotto V. Guraldo M. Perona A. Pera M. Risio 《Digestive and liver disease》2005,37(7):509-514
BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid. 相似文献
2.
K W Burn L Casalini S Martini M Mazzini E Nava C Petrovich G Rosi M Sarotto R Tinti 《Applied radiation and isotopes》2004,61(5):987-991
An epithermal facility for treating patients with brain gliomas has been designed and is under construction at the fast reactor TAPIRO at ENEA Casaccia (Italy). The calculational design tools employed were the Monte Carlo codes MCNP/MCNPX together with the DSA in-house variance reduction patch. A realistic anthropomorphic phantom ("ADAM") was included to optimise dose profiles and in-phantom treatment-planning figures-of-merit. The adopted approach was to minimise the treatment time whilst maintaining a reasonable therapeutic ratio. It is shown that TAPIRO, in spite of its low power of 5 kW, is able to provide an epithermal beam that is of good quality and of sufficient intensity to allow a single beam patient irradiation, under conservative assumptions, of 50 min. 相似文献
3.
Risio M De Rosa G Sarotto I Casorzo L Capussotti L Torchio B Aglietta M Chiecchio L 《International journal of oncology》2003,23(5):1381-1387
Seventy-two archival specimens of advanced gastric adenocarcinoma were analyzed by fluorescence in situ hybridization and immunohistochemistry for HER2 gene status. Gene amplification and concomitant protein overexpression were detected in 15.2% of cases. Intratumor topographical variability of HER2 amplification was observed, indicative of the late involvement of HER gene in gastric tumorigenesis. No significant correlations were found between HER2 status and histopathologic type, grade of differentiation, and Goseki classification of carcinomas, suggesting that HER2 gene is variably linked with the morphogenesis of gastric adenocarcinoma. A significant decrease of the incidence of HER2 amplified carcinomas in function of the duration of the storage of paraffin blocks was observed: 42-33% for tumor specimens paraffin-embedded in 2002-2001; 8.3%, 15.7%, 11.1% for the years 2000, 1999, 1998, respectively; 0% for cases embedded during 1997. According to these results, the reliability of the FISH and immunohistochemical assays decreases after prolonged storage of paraffin-embedded specimens. 相似文献
4.
Ughetto Stefano Migliore Cristina Pietrantonio Filippo Apicella Maria Petrelli Annalisa DErrico Laura Durando Stefania Moya-Rull Daniel Bellomo Sara E. Rizzolio Sabrina Capela Tania Ribisi Salvatore Degiuli Maurizio Reddavid Rossella Rapa Ida Fumagalli Uberto De Pascale Stefano Ribero Dario Baronchelli Carla Sgroi Giovanni Rausa Emanuele Baiocchi Gian Luca Molfino Sarah Manenti Stefania Bencivenga Maria Sacco Michele Castelli Claudia Siena Salvatore Sartore-Bianchi Andrea Tosi Federica Morano Federica Raimondi Alessandra Prisciandaro Michele Gloghini Annunziata Marsoni Silvia Sottile Antonino Sarotto Ivana Sapino Anna Marchi Caterina Cassoni Paola Guarrera Simonetta Corso Simona Giordano Silvia 《Gastric cancer》2021,24(4):897-912
Gastric Cancer - Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them... 相似文献
5.
Valentina Rossi Ivana Sarotto Furio Maggiorotto Paola Berchialla Franziska Kubatzki Nicoletta Tomasi Stefania Redana Rossella Martinello Giorgio Valabrega Massimo Aglietta Riccardo Ponzone Filippo Montemurro 《The oncologist》2012,17(11):1418-1425
Background.
Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti–HER-2 treatment. However, commonly defined “HER-2−” tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm.Methods.
We studied 1,150 women (median age, 58 years; range, 22–94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis.Results.
Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2− by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2+/HER-2− by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2− status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649.Conclusion.
A HER-2 2+/HER-2− status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/HER-2− status are ideal candidates for studies testing this hypothesis. 相似文献6.
Filippo Montemurro MD Furio Maggiorotto MD Giorgio Valabrega MD Franziska Kubatzki MD Valentina Rossi MD Alessandra Magistris MD Francesco Marocco MD Marco Gatti MD Ivana Sarotto MD Massimo Aglietta MD Riccardo Ponzone MD 《Annals of surgical oncology》2012,19(12):3755-3761
Background
This study was designed to evaluate how the omission of axillary dissection would have altered the indication for adjuvant chemotherapy (ACT) in patients with early breast cancer submitted to conservative surgery with one or two positive sentinel lymph nodes (SLNs).Methods
We identified 321 women in our institutional database who fulfilled the characteristics. All underwent completion axillary lymph node dissection (AD). Each case was blindly reviewed by our breast team in two rounds, and the total number of positive lymph nodes was disclosed only in the second. At each round, the panel chose between: (1) recommend, (2) discuss, (3) do not recommend ACT. Changes between round 1 and 2 were studied by the marginal homogeneity test. Exploratory logistic regression analyses were performed to study predictors of non-SLN involvement and of changes in the indication for ACT.Results
AD revealed non-SLNs metastases in 96 patients (30?%). Fifty-two patients (16?%) had their initial indication changed at round 2 (p?<?0.001). Most of the changes were toward ACT (83?%), and all except two occurred in patients with immunohistochemically defined luminal A and luminal B/HER2-negative tumors. In these two subgroups, a Ki67 above the median value (21?%) was the only independent predictor of no change in the indication to ACT at round 2.Conclusions
Omission of AD in patients with one or two positive SLNs may change the indication to ACT in a significant proportion of patients with hormone receptor-positive/HER2-negative tumors. All implications should be taken into account before abandoning AD, including a possible biologically tailored surgical approach. 相似文献7.
Iolanda Borelli Guido C. Casalis Cavalchini Serena Del Peschio Monica Micheletti Tiziana Venesio Ivana Sarotto Anna Allavena Luisa Delsedime Marco A. Barberis Giorgia Mandrile Paola Berchialla Paola Ogliara Cecilia Bracco Barbara Pasini 《Familial cancer》2014,13(3):401-413
The MLH1 c.2252_2253delAA mutation was found in 11 unrelated families from a restricted area south-west of Turin among 140 families with mutations in the mismatch repair genes. The mutation is located in the highly conserved C-terminal region, responsible for dimerization with the PMS2 protein. Twenty-five tumour tissues from 61 individuals with the c.2252_2253delAA mutation were tested for microsatellite instability (MSI) and protein expression. We compared the clinical features of these families versus the rest of our cohort and screened for a founder effect. All but one tumours showed the MSI-high mutator phenotype. Normal, focal and lack of MLH1 staining were observed in 16, 36 and 48 % of tumours, respectively. PMS2 expression was always lost. The mutation co-segregated with Lynch syndrome-related cancers in all informative families. All families but one fulfilled Amsterdam criteria, a frequency higher than in other MLH1 mutants. This was even more evident for AC II (72.7 vs. 57.5 %). Moreover, all families had at least one colon cancer diagnosed before 50 years and one case with multiple Lynch syndrome-related tumours. Interestingly, a statistically significant (p = 0.0057) higher frequency of pancreatic tumours was observed compared to families with other MLH1 mutations: 8.2 % of affected individuals versus 1.6 %. Haplotype analysis demonstrated a common ancestral origin of the mutation, which originated about 1,550 years ago. The mutation is currently classified as having an uncertain clinical significance. Clinical features, tissue analysis and co-segregation with disease strongly support the hypothesis that the MLH1 c.2252_2253delAA mutation has a pathogenic effect. 相似文献
8.
Valabrega G Montemurro F Sarotto I Petrelli A Rubini P Tacchetti C Aglietta M Comoglio PM Giordano S 《Oncogene》2005,24(18):3002-3010
The HER2 gene encodes a tyrosine kinase receptor overexpressed in 25-30% of human breast cancers. Clinical trials have shown the efficacy of the anti-HER2 monoclonal antibody Trastuzumab in metastatic breast cancer patients. Nevertheless, 70% of patients are unresponsive from start of treatment and nearly all become unresponsive during treatment. Possible mechanisms for these failures could depend on impairment of the machinery responsible for receptor downregulation. To test this hypothesis, we analysed the genomic sequences encoding regions known to be critical for HER2 downregulation, of both HER2 and of the ubiquitin ligase Cbl. We investigated 63 breast cancers, and found no mutations in these regions. We thus considered alternative mechanisms -- such as TGFalpha production -- possibly interfering with HER2 downregulation. In selected cases, by comparing breast cancer neoplastic tissue before and after Trastuzumab treatment, we found induction of TGFalpha expression. Moreover, by in vitro expression of exogenous TGFalpha in breast cancer cells, we observed a dramatic reduction in Trastuzumab-induced HER2 endocytosis, downregulation and cell growth inhibition. Our results suggest that unresponsiveness to Trastuzumab may not be due to intrinsic defects in the machinery responsible for HER2 downregulation, but can be associated with a TGFalpha-related mechanism of escape to HER2 downregulation. 相似文献
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10.
Fernando D. Dip Mario Nahmod Francisco Suarez Anzorena Alejandro Moreira Luis Sarotto Carolina Ampudia Sudhir N. Kalaskar Pedro Ferraina Raul J. Rosenthal Steven D. Wexner 《Surgical endoscopy》2014,28(9):2730-2733