18 results on '"Biasco, Guido"'
Search Results
2. An online international comparison of thresholds for triggering a negative response to the “Surprise Question”: a study protocol
- Author
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White, Nicola, Oostendorp, Linda, Vickerstaff, Victoria, Gerlach, Christina, Engels, Yvonne, Maessen, Maud, Tomlinson, Christopher, Wens, Johan, Leysen, Bert, Biasco, Guido, Zambrano, Sofia, Eychmüller, Steffen, Avgerinou, Christina, Chattat, Rabih, Ottoboni, Giovanni, Veldhoven, Carel, and Stone, Patrick
- Published
- 2019
- Full Text
- View/download PDF
3. The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST).
- Author
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Nannini, Margherita, Urbini, Milena, Astolfi, Annalisa, Biasco, Guido, Pantaleo, Mara A., and Pantaleo, Maria A
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GASTROINTESTINAL stromal tumors ,GENETIC mutation ,RENIN-angiotensin system ,FRAGMENTATION reactions ,DNA fingerprinting - Abstract
Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations. Therefore, given this still growing and rapidly evolving scenario, the progressive molecular fragmentation may inevitably lead over the time to the disappearance of KIT/PDGFRA WT GIST, destined to be singularly defined by their molecular fingerprint. [ABSTRACT FROM AUTHOR]
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- 2017
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4. MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma--a step towards personalized therapy.
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Garajová, Ingrid, Funel, Niccola, Fiorentino, Michelangelo, Agostini, Valentina, Ferracin, Manuela, Negrini, Massimo, Frassineti, Giovanni Luca, Gavelli, Giampaolo, Frampton, Adam Enver, Biasco, Guido, and Giovannetti, Elisa
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- 2015
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5. Whole exome sequencing (WES) on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in gastrointestinal stromal tumors (GIST).
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Astolfi, Annalisa, Urbini, Milena, Indio, Valentina, Nannini, Margherita, Giusy Genovese, Chiara, Santini, Donatella, Saponara, Maristella, Mandrioli, Anna, Ercolani, Giorgio, Brandi, Giovanni, Biasco, Guido, and Pantaleo, Maria A.
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MUCINOUS adenocarcinoma ,FORMALDEHYDE ,GASTROINTESTINAL stromal tumors ,CYSTS (Pathology) ,NUCLEOTIDE sequencing ,GENETICS - Abstract
Background: Next generation sequencing (NGS) technology has been rapidly introduced into basic and translational research in oncology, but the reduced availability of fresh frozen (FF) tumor tissues and the poor quality of DNA extracted from formalin-fixed, paraffin-embedded (FFPE) has significantly impaired this process in the field of solid tumors. To evaluate if data generated from FFPE material can be reliably produced and potentially used in routine clinical settings, we performed whole exome sequencing (WES) from tumor samples of Gastrointestinal stromal tumors (GIST), either extracted FF or FFPE, and from matched normal DNA. Methods: We performed whole exome enrichment and sequencing at 100bp in paired end on four GIST samples, either from FFPE or fresh-frozen tissue, and from matched normal DNA. Results: The integrity of DNA extracted from FFPE was evaluated by a modified RAPD PCR method, thus identifying high quality (HQ) and low quality (LQ) FFPE. DNA library production and exome capture was feasible for both classes of FFPE, despite the smaller yield and insert size of LQ-FFPE. WES produced data of equal quality from FF and FFPE, while only HQ-FFPE yielded an amount of data comparable to FF samples. Bioinformatic analysis showed that the percentage of variants called both in FF and FFPE samples was very high in HQ-FFPE, reaching 94-96 % of the total number of called variants. Classification of somatic variants by nucleotide substitution type showed that HQ-FFPE and FF had similar mutational profiles, while LQ-FFPE samples carried a much higher number of mutations than the FF counterpart, with a significant enrichment of C > T/G > A substitutions. Focusing on potential disease-related variants allowed the discovery of additional somatic variants in GIST samples, apart from the known oncogenic driver mutation, both from sequencing of FF and FFPE material. False positive and false negative calls were present almost exclusively in the analysis of FFPE of low quality. On the whole this study showed that WES is feasible also on FFPE specimens and that it is possible to easily select FFPE samples of high quality that yield sequencing results comparable to the FF counterpart. Conclusions: WES on FFPE material may represent an important and innovative source for GIST research and for other solid tumors, amenable of possible application in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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6. SDHC methylation in gastrointestinal stromal tumors (GIST): a case report.
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Urbini, Milena, Astolfi, Annalisa, Indio, Valentina, Heinrich, Michael C., Corless, Christopher L., Nannini, Margherita, Ravegnini, Gloria, Biasco, Guido, and Pantaleo, Maria A.
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DNA methylation ,SUCCINATE dehydrogenase ,GASTROINTESTINAL stromal tumors ,GENETIC mutation ,GENE expression ,GENETICS - Abstract
Background: Gastrointestinal stromal tumors (GIST) recently have been recognized as a genetically and biologically heterogeneous disease. In addition to KIT or PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH) subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit genes, some are SDHx wild type. Epigenetic regulation by DNA methylation of CpG islands recently has been found to be an alternative mechanism underlying the lack of SDH complex in GIST. Case presentation: We report a particular case of dSDH GIST, previously analyzed with microarrays and next-generation sequencing, for which no molecular pathogenetic events have been identified. Gene expression analysis showed remarkable down-modulation of SDHC mRNA with respect to all other GIST samples, both SDHA-mutant and KIT/PDGFRA-mutant GIST. By a bisulfite methylation assay targeted to 2 SDHC CpG islands, we detected hypermethylation of the SDHC promoter. Conclusion: Herein we report an additional case of dSDH GIST without SDHx mutation but harboring hypermethylation in the SDHC promoter, thus confirming the complexity of the molecular background of this subtype of GIST. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Efficacy of weekly docetaxel in locally advanced cardiac angiosarcoma.
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Minichillo, Santino, Pantaleo, Maria Abbondanza, Nannini, Margherita, Coccolo, Fabio, Gatto, Lidia, Biasco, Guido, and Brandi, Giovanni
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DOCETAXEL ,DRUG efficacy ,ANGIOSARCOMA ,TUMOR treatment ,RADIOTHERAPY ,CARDIOTOXICITY ,THERAPEUTICS - Abstract
Background: Primary cardiac angiosarcoma is extremely aggressive; however, it is often misdiagnosed because of its rarity. For locally advanced tumors, doxorubicin-based chemotherapy regimens are the standard of treatment, even if the gain in term of progression-free survival is limited and is no longer than 5 months. Case presentation: We report the case of a Caucasian 23-year-old man with locally advanced cardiac angiosarcoma who underwent radical surgical resection after a prolonged response to weekly docetaxel and complementary radiotherapy. Conclusion: Combined treatment with weekly docetaxel and radiotherapy may be a valid alternative for the treatment of locally advanced cardiac angiosarcoma; the combination can lead to radical surgical resections, avoiding the cumulative cardiotoxicity of antracycline-based regimens. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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8. Integrated genomic study of quadruple-WT GIST (KIT/PDGFRA/SDH/RAS pathway wild-type GIST).
- Author
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Nannini, Margherita, Astolfi, Annalisa, Urbini, Milena, Indio, Valentina, Santini, Donatella, Heinrich, Michael C., Corless, Christopher L., Ceccarelli, Claudio, Saponara, Maristella, Mandrioli, Anna, Lolli, Cristian, Ercolani, Giorgio, Brandi, Giovanni, Biasco, Guido, and Pantaleo, Maria A.
- Subjects
GASTROINTESTINAL stromal tumors ,TUMORS in children ,PLATELET-derived growth factor receptors ,SUCCINATE dehydrogenase ,NEUROFIBROMATOSIS 1 - Abstract
Background: About 10-15% of adult gastrointestinal stromal tumors (GIST) and the vast majority of pediatric GIST do not harbour KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations (J Clin Oncol 22:3813-3825, 2004; Hematol Oncol Clin North Am 23:15-34, 2009). The molecular biology of these GIST, originally defined as KIT/PDGFRA wild-type (WT), is complex due to the existence of different subgroups with distinct molecular hallmarks, including defects in the succinate dehydrogenase (SDH) complex and mutations of neurofibromatosis type 1 (NF1), BRAF, or KRAS genes (RAS-pathway or RAS-P). In this extremely heterogeneous landscape, the clinical profile and molecular abnormalities of the small subgroup of WT GIST suitably referred to as quadruple wild-type GIST (quadruple
WT or KITWT /PDGFRAWT /SDHWT /RAS-PWT ) remains undefined. The aim of this study is to investigate the genomic profile of KITWT /PDGFRAWT /SDHWT /RAS-PWT GIST, by using a massively parallel sequencing and microarray approach, and compare it with the genomic profile of other GIST subtypes. Methods: We performed a whole genome analysis using a massively parallel sequencing approach on a total of 16 GIST cases (2 KITWT /PDGFRAWT /SDHWT and SDHBIHC+ /SDHAIHC+ , 2 KITWT /PDGFRAWT /SDHAmut and SDHBIHC- /SDHAIHC- and 12 cases of KITmut or PDGFRAmut GIST). To confirm and extend the results, whole-genome gene expression analysis by microarray was performed on 9 out 16 patients analyzed by RNAseq and an additional 20 GIST patients (1 KITWT /PDGFRAWT SDHAmut GIST and 19 KITmut or PDGFRAmut GIST). The most impressive data were validated by quantitave PCR and Western Blot analysis. Results: We found that both cases of quadrupleWT GIST had a genomic profile profoundly different from both either KIT/PDGFRA mutated or SDHA-mutated GIST. In particular, the quadrupleWT GIST tumors are characterized by the overexpression of molecular markers (CALCRL and COL22A1) and of specific oncogenes including tyrosine and cyclin- dependent kinases (NTRK2 and CDK6) and one member of the ETS-transcription factor family (ERG). Conclusion: We report for the first time an integrated genomic picture of KITWT /PDGFRAWT /SDHWT /RAS-PWT GIST, using massively parallel sequencing and gene expression analyses, and found that quadrupleWT GIST have an expression signature that is distinct from SDH-mutant GIST as well as GIST harbouring mutations in KIT or PDGFRA. Our findings suggest that quadrupleWT GIST represent another unique group within the family of gastrointestintal stromal tumors. [ABSTRACT FROM AUTHOR]- Published
- 2014
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9. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study.
- Author
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Berruti, Alfredo, Fazio, Nicola, Ferrero, Anna, Brizzi, Maria Pia, Volante, Marco, Nobili, Elisabetta, Tozzi, Lucia, Bodei, Lisa, Torta, Mirella, D'Avolio, Antonio, Priola, Adriano Massimiliano, Birocco, Nadia, Amoroso, Vito, Biasco, Guido, Papotti, Mauro, and Dogliotti, Luigi
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NEUROENDOCRINE tumors ,BEVACIZUMAB ,DRUG side effects ,VASCULAR endothelial growth factors ,GENETIC polymorphisms ,PROTEINURIA ,TUMOR treatment - Abstract
Background: We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. Methods: This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Results: Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. Conclusion: The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. [ABSTRACT FROM AUTHOR]
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- 2014
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10. The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting.
- Author
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Maleddu, Alessandra, Pantaleo, Maria A., Nannini, Margherita, and Biasco, Guido
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GASTROINTESTINAL stromal tumors ,GASTROINTESTINAL tumors ,GENETIC mutation ,PROTEIN-tyrosine kinases ,EXONS (Genetics) - Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Most GIST harbor a mutation affecting either the KIT or PDGFRA genes, whereas a small subgroup of tumors is wild type for mutations.Mutation of tyrosine kinase receptors is a mechanism of drug resistance that can occur either at the beginning of treatment (primary resistance) or during the course of therapy (secondary resistance). In addition, mutational status can predict the response to treatment with tyrosine kinase inhibitors, but the role of mutational status as a prognostic factor remains controversial.Evidence of a potential role of mutational status as a prognostic factor has emerged over the past decade. The presence of KIT exon 11 insertion/deletion involving either one or both Trp557-Lys558 amino acids correlates with a poorer clinical outcome if compared to patients with tumors wild type for KIT exon 11 mutations. A malignant clinical behavior has also been documented for KIT exon 13 and KIT exon 9 mutant GIST. Patients with GIST harboring a PDGFRA mutation seem to have a better prognosis than the others.The aim of this paper is to review the clinical significance of tyrosine kinase mutational status. [ABSTRACT FROM AUTHOR]
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- 2011
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11. The National Tumor Association Foundation (ANT): A 30 year old model of home palliative care.
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Casadio, Marina, Biasco, Guido, Abernethy, Amy, Bonazzi, Valeria, Pannuti, Raffaella, and Pannuti, Franco
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CANCER patients , *PALLIATIVE treatment , *CAREGIVERS , *HOSPICE care , *NURSING care facilities - Abstract
Background: Models of palliative care delivery develop within a social, cultural, and political context. This paper describes the 30-year history of the National Tumor Association (ANT), a palliative care organization founded in the Italian province of Bologna, focusing on this model of home care for palliative cancer patients and on its evaluation. Methods: Data were collected from the 1986-2008 ANT archives and documents from the Emilia-Romagna Region Health Department, Italy. Outcomes of interest were changed in: number of patients served, performance status at admission (Karnofsky Performance Status score [KPS]), length of participation in the program (days of care provided), place of death (home vs. hospital/hospice), and satisfaction with care. Statistical methods included linear and quadratic regressions. A linear and a quadratic regressions were generated; the independent variable was the year, while the dependent one was the number of patients from 1986 to 2008. Two linear regressions were generated for patients died at home and in the hospital, respectively. For each regression, the R square, the unstandardized and standardized coefficients and related P-values were estimated. Results: The number of patients served by ANT has increased continuously from 131 (1986) to a cumulative total of 69,336 patients (2008), at a steady rate of approximately 121 additional patients per year and with no significant gender difference. The annual number of home visits increased from 6,357 (1985) to 904,782 (2008). More ANT patients died at home than in hospice or hospital; this proportion increased from 60% (1987) to 80% (2007). The rate of growth in the number of patients dying in hospital/hospice was approximately 40 patients/year (p < 0.01), vs. approximately 177 patients/year for patients who died at home. The percentage of patients with KPS < 40 at admission decreased from 70% (2003) to 30% (2008); the percentage of patients with KPS > 40 increased. Mean days of care for patients with KPS > 40 exceeded mean days for patients with KPS < 40 (p < 0.001). Patients and caregivers reported high satisfaction with care in each year of assessment; in 2008, among 187 interviewed caregivers, 95% judged the quality of doctors' assistance, and 91% judged the quality of nurses' assistance, to be "optimal." Conclusions: The ANT home care model of palliative care delivery has been well-received, with progressively growing numbers of patients served. It has resulted in a greater proportion of home deaths and in patients' accessing palliative care at an earlier point in the disease trajectory. Changes in ANT chronicle palliative care trends in general. [ABSTRACT FROM AUTHOR]
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- 2010
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12. The emerging role of insulin-like growth factor 1 receptor (IGF1r) in gastrointestinal stromal tumors (GISTs).
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Pantaleo, Maria A., Astolfi, Annalisa, Nannini, Margherita, and Biasco, Guido
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GASTROINTESTINAL mucosa ,GROWTH factors ,ADULTS ,INSULIN ,ONCOLOGY ,CYTOKINES - Abstract
Recent years have seen a growing interest in insulin-like growth factor 1 receptor (IGF1R) in medical oncology. Interesting data have been reported also on IGF1r in gastrointestinal stromal tumors (GISTs) especially in children and in young adult patients whose disease does not harbour mutations on KIT and PDGFRA and are poorly responsive to conventional therapies. However, it is too early to reach conclusions on IGF1R as a novel therapeutic target in GIST because the receptor's biological role is still to be defined and the clinical significance in patients needs to be studied in larger studies. We update and comment the current literature on IGF1R in GISTs and discuss the future perspectives in this promising field. [ABSTRACT FROM AUTHOR]
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- 2010
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13. Preclinical evaluation of KIT/PDGFRA and mTOR inhibitors in gastrointestinal stromal tumors using small animal FDG PET.
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Pantaleo, Maria Abbondanza, Nicoletti, Giordano, Nanni, Cristina, Gnocchi, Chiara, Landuzzi, Lorena, Quarta, Carmelo, Boschi, Stefano, Nannini, Margherita, Di Battista, Monica, Castellucci, Paolo, Fanti, Stefano, Lollini, Pier Luigi, Bellan, Elena, Castelli, Mauro, Rubello, Domenico, and Biasco, Guido
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CANCER research ,CANCER patients ,TRANSPLANTATION of organs, tissues, etc. ,ONCOLOGY ,CYSTS (Pathology) ,BIOCHEMISTRY ,TUMOR growth ,DRUG resistance ,PROTEIN-tyrosine kinases ,MEDICAL radiography - Abstract
Background: Primary and secondary drug resistance to imatinib and sunitinib in patients with gastrointestinal stromal tumors (GISTs) has led to a pressing need for new therapeutic strategies such as drug combinations. Most GISTs are caused by mutations in the KIT receptor, leading to upregulated KIT tyrosine kinase activity. Imatinib and nilotinib directly inhibit the kinase activity of KIT, while RAD001 (everolimus) inhibits mTOR. We report a preclinical study on drug combinations in a xenograft model of GIST in which effects on tumor dimensions and metabolic activity were assessed by small animal PET imaging. Methods: Rag2-/-; γcommon -/- male mice were injected s.c. into the right leg with GIST 882. The animals were randomized into 6 groups of 6 animals each for different treatment regimens: No therapy (control), imatinib (150 mg/kg b.i.d.) by oral gavage for 6 days, then once/day for another 7 days, everolimus (10 mg/kg/d.) by oral gavage, everolimus (10 mg/kg/d.) + imatinib (150 mg/kg b.i.d.) by oral gavage for 6 days, then once/day for another 7 days, nilotinib (75 mg/kg/d.) by oral gavage, nilotinib (75 mg/kg/d.) + imatinib (150 mg/kg b.i.d) by oral gavage for 6 days, then once/day for another 7 days. Tumor growth control was evaluated by measuring tumor volume (cm
³ ). Small animal PET (GE Explore tomography) was used to evaluate tumor metabolism and performed in one animal per group at base-line then after 4 and 13 days of treatment. Results: After a median latency time of 31 days, tumors grew in all animals (volume 0,06-0,15 cm3) and the treatments began at day 38 after cell injection. Tumor volume control (cm³ ) after 13 days of treatment was > 0.5 for imatinib alone and nilotinib alone, and < 0.5 for the 2 combinations of drugs and for everolimus alone. The baseline FDG uptake was positive in all animals. FDG/SUV/TBR was strongly reduced over time by everolimus both as a single agent and in combination with imatinib respectively: 3.1 vs. 2.3 vs. 1.9 and 2.5 vs 2.3 vs 0. Conclusions: As single agents, all drugs showed an anti-tumor effect in GIST xenografts but everolimus was superior. The everolimus plus imatinib combination appeared to be the most active regimen both in terms of inhibiting tumor growth and tumor metabolism. The integration of everolimus in GIST treatment merits further investigation. [ABSTRACT FROM AUTHOR]- Published
- 2010
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14. Erratum to: The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST).
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Nannini, Margherita, Urbini, Milena, Astolf, Annalisa, Biasco, Guido, and Pantaleo, Maria A
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GASTROINTESTINAL cancer ,AUTOIMMUNE diseases - Published
- 2017
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15. An online international comparison of thresholds for triggering a negative response to the 'Surprise Question': a study protocol
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Yvonne Engels, Johan Wens, Linda J. M. Oostendorp, Maud Maessen, Patrick Stone, Christina Gerlach, Bert Leysen, Nicola White, Carel Veldhoven, Christina Avgerinou, Guido Biasco, Steffen Eychmüller, Rabih Chattat, Giovanni Ottoboni, Christopher Tomlinson, Sofia C. Zambrano, Victoria Vickerstaff, White, Nicola, Oostendorp, Linda, Vickerstaff, Victoria, Gerlach, Christina, Engels, Yvonne, Maessen, Maud, Tomlinson, Christopher, Wens, Johan, Leysen, Bert, Biasco, Guido, Zambrano, Sofia, Eychmüller, Steffen, Avgerinou, Christina, Chattat, Rabih, Ottoboni, Giovanni, Veldhoven, Carel, and Stone, Patrick
- Subjects
Palliative care ,Survival ,Study Protocol ,0302 clinical medicine ,Belgium ,Germany ,Surveys and Questionnaires ,610 Medicine & health ,Netherlands ,Multiple choice ,media_common ,lcsh:RC952-1245 ,General Medicine ,Prognosis ,Death ,Surprise ,Italy ,Negative response ,030220 oncology & carcinogenesis ,0305 other medical science ,Psychology ,Switzerland ,medicine.medical_specialty ,Attitude to Death ,Attitude of Health Personnel ,Prognosi ,media_common.quotation_subject ,education ,lcsh:Special situations and conditions ,1117 Public Health and Health Services ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,03 medical and health sciences ,Surprise question ,All institutes and research themes of the Radboud University Medical Center ,General Practitioners ,030502 gerontology ,medicine ,Humans ,National level ,Protocol (science) ,Internet ,Correction ,Certificate ,United Kingdom ,Vignette ,Family medicine ,Human medicine ,Gerontology - Abstract
Background The Surprise Question (SQ) “would I be surprised if this patient were to die in the next 12 months?” has been suggested to help clinicians, and especially General Practitioners (GPs), identify people who might benefit from palliative care. The prognostic accuracy of this approach is unclear and little is known about how GPs use this tool in practice. Are GPs consistent, individually and as a group? Are there international differences in the use of the tool? Does including the alternative Surprise Question (“Would I be surprised if the patient were still alive after 12 months?”) alter the response? What is the impact on the treatment plan in response to the SQ? This study aims to address these questions. Methods An online study will be completed by 600 (100 per country) registered GPs. They will be asked to review 20 hypothetical patient vignettes. For each vignette they will be asked to provide a response to the following four questions: (1) the SQ [Yes/No]; (2) the alternative SQ [Yes/No]; (3) the percentage probability of dying [0% no chance – 100% certain death]; and (4) the proposed treatment plan [multiple choice]. A “surprise threshold” for each participant will be calculated by comparing the responses to the SQ with the probability estimates of death. We will use linear regression to explore any differences in thresholds between countries and other clinician-related factors, such as years of experience. We will describe the actions taken by the clinicians and explore the differences between groups. We will also investigate the relationship between the alternative SQ and the other responses. Participants will receive a certificate of completion and the option to receive feedback on their performance. Discussion This study explores the extent to which the SQ is consistently used at an individual, group, and national level. The findings of this study will help to understand the clinical value of using the SQ in routine practice. Trial registration Clinicaltrials.gov NCT03697213 (05/10/2018). Prospectively registered. Electronic supplementary material The online version of this article (10.1186/s12904-019-0413-x) contains supplementary material, which is available to authorized users.
- Published
- 2019
16. Liquid biopsy in gastrointestinal stromal tumors: a novel approach.
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Nannini M, Astolfi A, Urbini M, Biasco G, and Pantaleo MA
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- DNA Mutational Analysis, Humans, Molecular Diagnostic Techniques, Prognosis, DNA, Neoplasm blood, Gastrointestinal Neoplasms blood, Gastrointestinal Neoplasms pathology, Gastrointestinal Stromal Tumors blood, Gastrointestinal Stromal Tumors pathology
- Abstract
The role of molecular analysis in the management of gastrointestinal stromal tumors (GIST) remains indisputable. To date, tumor tissue extracted from specimens obtained by surgical or biopsy procedures has been the only source of the tumor DNA required for the molecular and genomic assessment of cancer. However, tumor tissue sampling has several clinical limitations: for example, the invasiveness of these procedures precludes repeated sampling. Thus, it is possible to obtain only a static molecular picture of the disease, a picture that lacks the inter- and intra-metastatic molecular heterogeneity that characterizes most GIST. In contrast, circulating tumor DNA obtained from a patient's bloodstream, known as liquid biopsy, can theoretically overcome the limitations of tissue biopsies and provide the same molecular and genomic information. GIST are recognized as a paradigm of molecular biology among solid tumors. Although few but promising data on liquid biopsy in GIST have been accumulated to date, these tumors may provide the optimal field for application of this challenging approach.
- Published
- 2014
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17. Dystrophin deregulation is associated with tumor progression in KIT/PDGFRA mutant gastrointestinal stromal tumors.
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Pantaleo MA, Astolfi A, Urbini M, Fuligni F, Saponara M, Nannini M, Lolli C, Indio V, Santini D, Ercolani G, Brandi G, Pinna AD, and Biasco G
- Abstract
Background: Intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene have been recently described in gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS). We evaluated the copy numbers and gene expression levels of DMD in our series of GIST patients who were already studied with wide genome assays, to investigate more fully a correlation between dystrophin status and disease annotations., Findings: Our study highlighted a recurrent intragenic deletion on chromosome X, involving the DMD gene that codes for human dystrophin in GIST patients. Of 29 KIT/PDGFRA mutant GIST samples, 9 (31%) showed deletions of the DMD gene, which were focal and intragenic in 8 cases, and involved loss of an entire chromosome in one case (GIST_188). DMD loss was seen in only 5 patients with metastasis, whereas 18 out of 20 patients with localized disease had wild-type DMD (P = 0.0004, Fisher exact test). None of the 6 KIT/PDGFRA WT GIST showed DMD alterations., Conclusions: Our study confirms the presence of DMD deletions only in KIT/PDGFRA mutant GIST and this event is almost associated with metastatic disease. These findings are, of course, quite preliminary but support development of potential therapeutic strategies that target and restore DMD function in the treatment of metastatic GIST.
- Published
- 2014
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18. Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib.
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Pantaleo MA, Mandrioli A, Saponara M, Nannini M, Erente G, Lolli C, and Biasco G
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- Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Carcinoma, Renal Cell drug therapy, Coronary Angiography, Coronary Stenosis diagnostic imaging, Humans, Male, Middle Aged, Niacinamide analogs & derivatives, Phenylurea Compounds, Protein Kinase Inhibitors therapeutic use, Pyridines therapeutic use, Sorafenib, Antineoplastic Agents adverse effects, Benzenesulfonates adverse effects, Carcinoma, Renal Cell complications, Coronary Stenosis chemically induced, Protein Kinase Inhibitors adverse effects, Pyridines adverse effects
- Abstract
Background: Tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of metastatic renal cell carcinoma (mRCC). The cardiotoxic effects of sorafenib and sunitinib may cause hypertension, left ventricular ejection fraction (LVEF) dysfunction and/or congestive heart failure (CHF), and arterial thrombo-embolic events (ATE). Only three cases of coronary artery disease related to sorafenib therapy have been described in the literature, and all were due to arterial vasospasm without evidence of coronary artery stenosis on angiography. Cardiotoxicity is commonly associated with the presence of cardiovascular risk factors, such as a history of hypertension or coronary artery disease., Case Presentation: We describe a patient who experienced an unusual cardiac event after 2 years of sorafenib treatment. A 58-year-old man with mRCC developed acute coronary syndrome (ischemia/infarction) associated with critical sub-occlusion of the common trunk of the left coronary artery and some of its branches, which was documented on coronary angiography. The patient underwent triple coronary artery bypass surgery, and sorafenib treatment was discontinued. He did not have any cardiovascular risk factors, and his cardiac function and morphology were normal prior to sorafenib treatment., Conclusions: Further investigation of a larger patient population is needed to better understand cardiac damage due to TKI treatment. Understanding the usefulness of careful cardiovascular monitoring might be important for the prevention of fatal cardiovascular events, and to avoid discontinuation of therapy for the underlying cancer.
- Published
- 2012
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