Papers by Annamaria Ruzzo
Journal of Clinical Oncology
4021 Background: AR is an endogenous ligand of Epidermal Growth Factor Receptor (EGFR), whose bin... more 4021 Background: AR is an endogenous ligand of Epidermal Growth Factor Receptor (EGFR), whose binding is prevented in the presence of cetuximab. Methods: We retrospectively assessed KRAS mutational status and AR expression at immunohistochemistry (IHC) in 86 irinotecan-refractory EGFR-positive mCRC patients treated with cetuximab plus irinotecan. AR-IHC was performed on tissue sections from paraffin-embedded primary tumors. Specimens were defined AR-low or AR-high according to a score (range 0–300) obtained multiplying intensity (0 to 3+) by percentage of stained cells (0–100%). According to the results of a ROC analysis, we identified a cut-off value of 18. The association between AR-IHC and treatment outcome in terms of response rate (RR), PFS, and OS was investigated in the subgroup of KRAS wild-type patients. Results: Eighty-six consecutive patients were included. M/F = 44/42, median age = 67 (41–78), median number of previous lines of chemotherapy = 2 (1–5). Among 51 (59%) KRAS...
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Cancers
Loss of p53 promotes vascular endothelial growth factor (VEGF)-A up-regulation and the angiogenic... more Loss of p53 promotes vascular endothelial growth factor (VEGF)-A up-regulation and the angiogenic potential of cancer cells. We investigated TP53 somatic mutations in 110 primary gastric adenocarcinomas of two retrospective metastatic series including 48 patients treated with second-line Ramucirumab/Paclitaxel and 62 patients who received first-line chemotherapy with Cisplatin or Oxaliplatin plus 5-Fluorouracil. Missense mutations were classified by tumor protein p53 (TP53) mutant-specific residual transcriptional activity scores (TP53RTAS) and used to stratify patients into two groups: transcriptionally TP53Active and TP53Inactive. The primary endpoint was overall survival (OS). An additional analysis was addressed to measure VEGF/VEGF receptor 2 (VEGFR2) expression levels in relation to the TP53RTAS. In the Ramucirumab/Paclitaxel group, 29/48 (60.4%) patients had TP53 mutations. Ten patients with TP53Inactive mutations showed better OS than carriers of other TP53 mutations. This e...
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Gastric Cancer
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Journal of Clinical Oncology
3518 Background: Despite several attempts, no predictors of benefit from BV have been so far iden... more 3518 Background: Despite several attempts, no predictors of benefit from BV have been so far identified. We reported the association of VEGF rs833061 T/T to a worse outcome in mCRC pts treated with first-line FOLFIRI+BV, but not in a historical cohort treated with FOLFIRI. Recent post-hoc analyses on randomized trials suggested the potential prognostic and/or predictive role of other VEGF and VEGFR1/2 SNPs. Methods: Moving from our retrospective finding, we designed a prospective validation trial in mCRC pts treated with first-line FOLFIRI+ BV to detect a HR for PFS of 1.7 for VEGF rs833061 T/T compared to C- variants. With two-sided a=0.05 and b=0.20, 199 events were required. Accrual was faster than expected and in the meanwhile promising results about other SNPs were reported and we therefore included a confirmatory analysis of VEGF rs699946 A/G, VEGFR1 rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and rs2305948 C/T and EPAS rs4145836 A/G SNPs. Germ-line ...
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Scientific Reports
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Frontiers in oncology, 2018
Bladder cancer is a very common malignancy. Although new treatment strategies have been developed... more Bladder cancer is a very common malignancy. Although new treatment strategies have been developed, the identification of new therapeutic targets and reliable diagnostic/prognostic biomarkers for bladder cancer remains a priority. Generally, they are found among differentially expressed genes between patients and healthy subjects or among patients with different tumor stages. However, the classical approach includes processing these data taking into consideration only the expression of each single gene regardless of the expression of other genes. These complex gene interaction networks can be revealed by a recently developed systems biology approach called Weighted Gene Co-expression Network Analysis (WGCNA). It takes into account the expression of all genes assessed in an experiment in order to reveal the clusters of co-expressed genes (modules) that, very probably, are also co-regulated. If some genes are co-expressed in controls but not in pathological samples, it can be hypothesi...
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Nature medicine, Jan 9, 2018
In the Supplementary Information originally published with this article, a lane was missing in th... more In the Supplementary Information originally published with this article, a lane was missing in the β-actin blot in Supplementary Fig. 2. The lane has been added. The error has been corrected in the Supplementary Information associated with this article.
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Nature medicine, Jan 28, 2018
The role of KRAS, when activated through canonical mutations, has been well established in cancer... more The role of KRAS, when activated through canonical mutations, has been well established in cancer . Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ovarian adenocarcinomas. KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS-GTP levels. Here we demonstrate that inhibition of the guanine-exchange factors SOS1 and SOS2 or the protein tyrosine phosphatase SHP2 can attenuate this adaptive process and that targeting these factors, both genetically and pharmacologically, can enhance the sensitivity of KRAS-amplified models to MEK inhibition in both in vitro and in vivo settings. These data demonstrate the relevance of copy-number amplification as a mechanism of KRAS activation, and un...
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Cancer, May 7, 2016
MET gene amplification and Met protein overexpression may be associated with a poor prognosis. Th... more MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC). Samples from 447 GEC patients were analyzed for MET gene amplification (FISH) and Met protein expression (IHC and SRM). Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relations between Met, overall survival (OS), and clinical/pathological characteristics. Spearman's rank coefficient was used to assess the correlation between parameters. Patients with MET-amplified tumors had worse OS when: the MET/centromere enumeration probe for chromosome 7 FISH ratio was ≥ 2 (ha...
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Scientific reports, Jan 26, 2016
The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. ... more The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR-219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS o...
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Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology, Oct 31, 2011
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Tumor Biol, 2004
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Human Genetics, Oct 1, 1989
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Oncology Reports, 2008
The polymorphisms of interleukin-1ß (IL1ß) genes have been controversially correlated with gastri... more The polymorphisms of interleukin-1ß (IL1ß) genes have been controversially correlated with gastric cancer risk. We examined all the available published studies through a meta-analysis approach. Twenty-one studies assessing the correlation between ILIß gene ...
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British Journal of Cancer, Feb 1, 2010
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Curr Cancer Drug Targets, 2010
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Leukemia Research, 2015
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Gene geography : a computerized bulletin on human gene frequencies, 1987
We report the haplotype characterization of 20 cystic fibrosis (CF) families for the allelic syst... more We report the haplotype characterization of 20 cystic fibrosis (CF) families for the allelic systems MET-H, D7S16, D7S13 and D7S8. Linkage disequilibrium between MET-H and CF was found in the population investigated. Twelve of the examined families were fully informative, 6 partially informative and 2 completely uninformative.
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Papers by Annamaria Ruzzo