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Gallucci G.,Cardiology Unit | Tartarone A.,Oncology Unit | Tocchetti C.G.,Italian National Cancer Institute | Bochicchio A.M.,Oncology Unit | And 6 more authors.
Future Oncology | Year: 2013

Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support. © 2013 Future Medicine Ltd.

Natalicchio M.I.,Riuniti Hospital | Improta G.,Laboratory of Clinical Research and Molecular Diagnostics | Zupa A.,Laboratory of Clinical Research and Molecular Diagnostics | Cursio O.E.,Catholic University | And 12 more authors.
Future Oncology | Year: 2014

Aim: To evaluate whether pyrosequencing (PS) improves the KRAS mutational status predictive value. Patients & methods: A retrospective analysis of KRAS mutations by PS and direct sequencing (DS) in 192 metastatic colorectal carcinomas (mCRCs), subgrouped in 51 KRAS mutated at PS and 141 KRAS wild-type at DS. Results: DS failed to detect low-frequency KRAS mutations in four out of 51 mCRCs, whereas PS detected 12 additional low-frequency KRAS mutations in 141 mCRCs KRAS wild-type at DS. After reanalyzing by PS 97 KRAS wild-type tumors treated with anti-EGF receptor (EGFR) antibodies, nine additional mutations were revealed in nonresponders, whereas none of responders exhibited a KRAS-mutated genotype. Of note, KRAS-mutated tumors upon PS showed a worst progression-free survival after EGFR therapy. Finally, PS allowed the detection of additional NRAS, BRAF and exon 20 PIK3CA mutations mostly in KRAS wild-type mCRCs resistant to EGFR therapy. Conclusion: PS detection of low-frequency mutations may improve the KRAS predictive value for EGFR therapy selection. © 2014 Future Medicine Ltd.

Pepe P.,Cannizzaro Hospital | Improta G.,Laboratory of Clinical Research and Molecular Diagnostics | Fraggetta F.,Cannizzaro Hospital | Emmanuele C.,Cannizzaro Hospital | And 4 more authors.
Anticancer Research | Year: 2014

Aim: The prostate-specific antigen (PSA) nadir and long-term outcome in patients with pT3b prostate cancer were evaluated. Patients and Methods: From July 2000 to December 2012, in 100 patients (median age=62 years) with pT3b prostate cancer following radical retropubic prostatectomy (RRP) preoperative and pathological findings predictive of PSA nadir (≤0.2 vs. >0.2 ng/ml) were retrospectively evaluated; moreover, biochemical recurrence-free survival (bRFS), cancer specific survival (CSS) and overall survival (OS) in patients who underwent watchful waiting (16 cases), adjuvant (84 cases) and salvage (10 cases) therapy were recorded. Results: A PSA nadir >0.2 ng/ml was correlated with node involvement, Gleason score ≥9, cT2, PSA >20 ng/ml, positive surgical margins and total cancer percentage >20%. At a median follow-up of 90 months (range=10-155 months) bRFS, OS and CSS were 92%, 96% and 80%, respectively. Conclusion: Radical retropubic prostatectomy combined with adjuvant and salvage treatments demonstrated a satisfactory outcome for pT3b prostate cancer. © 2014, International Institute of Anticancer Research. All rights reserved.

Improta G.,Laboratory of Clinical Research and Molecular Diagnostics | Pelosi G.,Fondazione IRCCS Instituto Nazionale Tumori | Pelosi G.,University of Milan | Tamborini E.,Fondazione IRCCS Instituto Nazionale Tumori | And 5 more authors.
OncoImmunology | Year: 2013

Some experimental evidence indicates that uncommon BRAF mutations consisting in the substitution of 2 adjacent nucleotides within codon 600 are in a cis configuration and associate with BRAF gene amplification. These findings suggest that BRAFV600 mutations are unlikely to occur as homozygous alterations in clinical melanoma samples, with gene amplification perhaps contributing to mask the heterozygous state.

Improta G.,Laboratory of Clinical Research and Molecular Diagnostics | Zupa A.,Laboratory of Clinical Research and Molecular Diagnostics | Possidente L.,Laboratory of Clinical Research and Molecular Diagnostics | Tartarone A.,IRCCS CROB Hospital | And 5 more authors.
Oncology Letters | Year: 2013

Evaluation of the mutational status of KRAS is a crucial step for the correct therapeutic approach in treating advanced colorectal cancer as the identification of wild-type KRAS tumors leads to more specific and less toxic treatments for patients. Although several studies have highlighted the differences between primary and metastatic tumors, the possibility of two or more mutations in the same codon has seldom been reported. The present study reports an additional case of an advanced adenocarcinoma of the colon showing two somatic mutations (p.G12D and p.G12V) in the same codon (codon 12) of exon 2 of the KRAS gene, thus supporting the possibility of two differing clonal origins of the tumor. Although the clinical significance of multiple mutations remains unknown at present, based on the limited data available in the literature, this rare event appears to be associated with a more aggressive disease, as in the present case. This case report demonstrates the existence of intratumoral heterogeneity and the coexistence of distinct clones within a tumor that may have profound clinical implications for disease progression and therapeutic responses.

PubMed | Laboratory of Clinical Research and Molecular Diagnostics
Type: Journal Article | Journal: Oncoimmunology | Year: 2013

Some experimental evidence indicates that uncommon

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