Publications (20)80.07 Total impact
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Dataset: LUNG3985
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Article: Low miR-145 and high miR-367 are associated with unfavorable prognosis in resected NSCLC.
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ABSTRACT: The transcription factors SOX2 and OCT4 regulate the expression of the miR-302-367 cluster. miR-145 regulates SOX2 and OCT4 translation and p53 regulates miR-145 expression. We analysed the expression of the miR-302-367 cluster and miR-145 and the mutational status of p53 in resected NSCLC patients and correlated results with time to relapse (TTR).Tumour and paired normal tissue samples were obtained from 70 NSCLC patients. MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced.miR-145 was downregulated (P<0.0001) and miR-367 was upregulated (P<0.0001) in tumour compared to normal tissue. Mean TTR was 18.4 months for patients with low miR-145 levels and 28.2 months for those with high levels (P=0.015). Mean TTR was 29.1 months for patients with low miR-367 levels and 23.4 months for those with high levels (P=0.048). TTR was shorter for patients with both unfavorable variables (P=0.009). Low miR-145 expression (P=0.049), the combination of unfavorable miRNA levels (P=0.02), and the combination of low miR-145 with p53 mutations (P=0.011) were independent markers of shorter TTR.In conclusion, miR-145 and miR-367 expression could be novel markers for relapse in surgically treated NSCLC. p53 may play a role in modulating miR-145 expression in NSCLC.European Respiratory Journal 07/2012; · 5.89 Impact Factor -
Article: Low miR-145 and high miR-367 are associated with unfavorable prognosis in resected NSCLC
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ABSTRACT: The transcription factors SOX2 and OCT4 regulate the expression of the miR-302-367European Respiratory Journal 07/2012; · 5.89 Impact Factor -
Article: Low miR-145 and high miR-367 are associated with unfavorable prognosis inresected NSCLC
European Respiratory Journal 07/2012; · 5.89 Impact Factor -
Article: Trabectedin in patients with advanced non-small-cell lung cancer (NSCLC) with XPG and/or ERCC1 overexpression and BRCA1 underexpression and pretreated with platinum.
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ABSTRACT: Previous studies in sarcoma found that a composite gene signature, including high expression of nucleotide excision repair (NER) genes (XPG and/or ERCC1) and low expression of homologous recombination repair (HR) genes (BRCA1), identifies a highly sensitive population of patients with significantly improved outcome to trabectedin. This exploratory phase II trial evaluated a customized trabectedin treatment according to this gene signature in patients with non-small cell lung cancer (NSCLC) after the failure of standard platinum-based treatment. Patients were selected according to their mRNA expression (elevated XPG and/or ERCC1, with low BRCA1) using the following values as cutoff: XPG=0.99, ERCC1=3.47 and BRCA1=12.00. Trabectedin was administered as a 1.3mg/m(2) 3-hour intravenous infusion every 3 weeks (q3wk). The primary efficacy endpoint was the progression-free survival rate at 3 months. Objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) was a secondary efficacy endpoint. Two of 18 evaluable patients (11.1%; 95% CI, 1.38-34.7%) achieved progression-free survival rate at 3 months. The primary efficacy objective (at least 3 of 18 patients being progression-free at 3 months) was not met, and therefore the trial was early finalized. No objective responses per RECIST were achieved. Four patients had stable disease. Median PFS was 1.3 months, and median overall survival was 5.9 months. Trabectedin was usually well tolerated, with a safety profile similar to that described in patients with other tumor types. Customized treatment with trabectedin 1.3mg/m(2) 3-h q3wk according to composite gene signature (XPG and/or ERCC1 overexpression, and BRCA1 underexpression) was well tolerated, but had modest activity in NSCLC patients pretreated with platinum. Therefore, further clinical trials with trabectedin as single agent in this indication are not warranted.Lung cancer (Amsterdam, Netherlands) 12/2011; 76(3):354-61. · 3.14 Impact Factor -
Article: Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer.
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ABSTRACT: MicroRNAs are novel regulators of gene expression that are linked to the main oncogene networks, including the p53 pathway. p53 regulates the maturation process of miR-16 and miR-143. We analyzed the role as prognostic markers of miR-16 and miR-143 in 70 non-small-cell lung cancer (NSCLC) patients. MicroRNAs were analyzed by TaqMan MicroRNA assays. Disease-free survival (DFS) and overall survival (OS) were examined using Kaplan-Meier curves with log-rank tests and the Cox proportional hazard model. When patients were classified in three groups according to their miR-16 expression levels, those with normal levels had the best outcome while those with high levels had the worst. DFS was 22.4 months for patients with high levels, 71.8 months for those with normal levels, and 55.8 months for those with low levels (P = 0.05). OS was 23.9 months for patients with high levels, 97.6 months for those with normal levels, and 63.5 months for those with low levels (P < 0.001). In the multivariate analyses, high miR-16 levels emerged as an independent prognostic factor for poor DFS (P = 0.001) and OS (<0.001). Our results provide the first hints that miR-16 levels in tumor samples may be a prognostic marker in NSCLC.Journal of Surgical Oncology 04/2011; 103(5):411-5. · 2.10 Impact Factor -
Article: [Implication of radiological pattern in the prognosis of oligodendroglial tumors: correlation with genetic profile].
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ABSTRACT: 1p19q loss of heterozygosity (LOH1p19q) in oligodendroglial tumors has shown to be prognostic of prolonged survival and predictive of therapeutic responsiveness. During the last years, research is actively being directed to the discovery of radiological characteristics related to LOH1p19q. AIMS. To confirm the existence of molecular heterogeneity in oligodendroglial tumors in relation to their anatomic distribution, and to evaluate the correlation between molecular profile and other radiological and clinical characteristics and their prognostic impact. Fifty-four patients with oligodendroglial tumors managed according to a previously established protocol were included. Preoperative SE T1, T1 post-gadolinium and T2 magnetic resonance images were reviewed by two independent neuroradiologists, blinded to clinical and molecular information. LOH analysis was assessed from paired tumor-blood DNA acid samples. LOH1p was highly associated with LOH19q (p < 0.0001), LOH1p (odds ratio, OR = 6.19; 95% confidence interval, 95% CI = 1.66-22.68; p = 0.004), LOH19q (OR = 7.59; 95% CI = 1.84-31.34; p = 0.006) and LOH1p19q (OR = 5.38; 95% CI = 1.51-19.13; p = 0.007) were found to be more frequent in tumors located in the frontal lobe. Frontal location (hazard ratio, HR = 4.499; 95% CI = 1.027-193.708; p = 0.046), ring enhancement (HR = 0.213; 95% CI = 0.065-0.700; p = 0.011) and extent of resection (HR = 9.231; 95% CI = 1.737-49.050; p = 0.009) resulted independent prognostic factors for overall survival in the multivariate analysis. Glioma classification aims to better define patients prognosis. Besides histological and immunohistochemical analyses, molecular information has become of great importance. Our results indicate that the evaluation of some MR features may also be useful. Efforts must be directed toward the use of every available resource at each institution.Revista de neurologia 04/2011; 52(8):465-71. · 0.65 Impact Factor -
Article: Single nucleotide polymorphisms in tobacco metabolism and DNA repair genes and prognosis in resected non-small-cell lung cancer.
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ABSTRACT: If tobacco-related carcinogens are not inactivated or extruded from the cell, they can damage the DNA. Single nucleotide polymorphisms (SNPs) in genes involved in tobacco metabolism, DNA repair, and multidrug resistance have been related to lung cancer susceptibility. We examined 13 SNPs in 10 of these genes and correlated the results with time to progression (TTP) and overall survival (OS) in 71 smoker or former smoker patients with resected non-small-cell lung cancer (NSCLC). DNA was obtained from paraffin-embedded tumor. SNP analysis of the candidate genes was performed by allelic discrimination assay. Log-rank test, Kaplan-Meier plots, and Cox multivariate analysis were used to evaluate the association of TTP and survival with the SNPs evaluated. Patients with wild-type (wt) XPC rs2228001, wt CYP2C8 rs10509681, or non-wt NAT2 rs1799930 had a longer TTP. Patients with wt ERCC1 showed a nonsignificant trend towards longer TTP. No other relation between SNPs and TTP were observed. Patients harboring at least two unfavorable genotypes in these four genes had a shorter TTP and OS than patients with either one or no unfavorable genotypes. In the multivariate analysis, non-wt XPC rs2228001 and the presence of at least two unfavorable genotypes emerged as independent markers for shorter TTP. SNPs in tobacco metabolism and DNA repair genes may influence the clinical outcome of resected NSCLC.Journal of Surgical Research 02/2011; 167(1):e5-12. · 2.25 Impact Factor -
Article: A dual role for KRT81: a miR-SNP associated with recurrence in non-small-cell lung cancer and a novel marker of squamous cell lung carcinoma.
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ABSTRACT: MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma.PLoS ONE 01/2011; 6(7):e22509. · 4.09 Impact Factor -
Article: miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer.
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ABSTRACT: MicroRNAs (miRNAs) have been identified as promising prognostic markers in non-small-cell lung cancer (NSCLC) since they play an important role in oncogenesis. The miR-34 family is composed of three miRNAs (miR-34a, miR-34b and miR-34c) that are part of the p53 network and whose expression is directly induced by p53 in response to DNA damage or oncogenic stress. We have analyzed the impact of miR-34 expression on relapse and overall survival in surgically resected NSCLC patients. For this purpose, we used stem-loop reverse transcription-polymerase chain reaction to analyze the expression of the miR-34 family in paired tumor and normal tissue from 70 surgically resected NSCLC patients who received no postsurgical treatment until relapse. In addition, in patients with sufficient tumor tissue, we assessed p53 mutations and the methylation status of the MIRN34A gene promoter region and correlated these findings with miR-34a expression. Molecular findings were correlated with relapse and overall survival. The miR-34 family was downregulated in tumor compared with normal tissue, and low levels of miR-34a expression were correlated with a high probability of relapse (P = 0.04). A relation was also found between MIRN34A methylation and miR-34a expression (P = 0.008). Patients with both p53 mutations and low miR-34a levels had the highest probability of relapse (P = 0.001). In the multivariate analysis, miR-34a expression emerged as an independent prognostic marker for relapse. In summary, we have identified miR-34a as a novel prognostic marker in NSCLC patients, providing a potential mechanism for estimating a patient's risk of disease recurrence and a useful tool to help guide treatment decisions.Carcinogenesis 10/2009; 30(11):1903-9. · 5.70 Impact Factor -
Article: Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer: correlation with histology.
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ABSTRACT: Tumor markers have been extensively studied in lung cancer, reporting some relationship to the histology, but their clinical utility is not clear. ProGRP, CEA, SCC, CA 125, CYFRA 21-1 and NSE were studied prospectively in 155 patients with unconfirmed suspicion of lung cancer and in 647 patients with lung cancer: 182 squamous, 205 adenocarcinomas, 19 large-cell lung cancer (LCLC), 175 small-cell lung cancer (SCLC) and 66 unspecific non-small-cell lung cancer (NSCLC). Abnormal tumor marker serum levels were found in less than 5.3% of the patients with benign diseases, excluding CA 125 (21.3%). Tumor markers were related to histological type and tumor extension with significantly higher CEA (p <0.01) and CA 125 (p <0.007) serum levels in adenocarcinomas, SCC (p <0.0001) and CYFRA 21-1 (p <0.008) in squamous tumors and ProGRP (p <0.0001) and NSE (p <0.0001) in SCLC. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Patients with SCC serum levels >2 ng/ml were always NSCLC, while those with SCC <2 ng/ml and ProGRP >100 pg/ml and NSE >35 ng/ml were all SCLC patients. The sensitivity was 76.7 and 79.5%, specificity was 97.2 and 99.6%, with a positive predictive value of 98.6 and 98.6% and a negative predictive value of 60.7 and 92.9% in the differentiation of NSCLC and SCLC, respectively. Tumor marker determination in patients with suspicious signs of lung cancer suggests, in a few hours, the histological diagnosis in the majority of lung cancer patients.Tumor Biology 06/2009; 30(3):121-9. · 1.94 Impact Factor -
Article: Lung cancer and treatment in elderly patients: the Achilles Study.
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ABSTRACT: The number of elderly patients with cancer continues to increase. Approximately two-thirds of patients diagnosed with non-small cell lung cancer are 65 years, and nearly 50% are 70 years or older. The aim of our study was to discern whether clinical characteristics, toxicity, response rate, treatment and survival are different in patients enrolees 70 years of age and older with those in younger patients. We reviewed the database of six clinical trials with different doublet combinations in the Spanish Lung Cancer Group from 1998 to 2005. Patient's characteristics, stage, histology, response and survival were obtained. All 1653 patients were studied; 280 patients (17%) were over 70. No significant differences were found between the two groups with respect to gender, stages, response rate or histological type. However, a greater squamous histological tendency was found in the older group. No differences were found in the median number of cycles administered. The only significant differences were in the greater percentage of grade III/IV neutropenia among patients older than 70. Febrile neutropenia was similar in both groups. In our study, the oldest age group represented a small percentage of all patients included in clinical and pharmacogenetic trials. Although this might indicate bias when interpreting the results, age is not a contraindication to the treatment of the "fit" elderly. Patients with good performance status can be treated with standard doublets. We believe that special attention should be paid to cases with high risk of neutropenia. Research in this population should now be aimed at finding more selective treatments, based on the genetic differences that older patients have.Lung cancer (Amsterdam, Netherlands) 03/2009; 66(1):103-6. · 3.14 Impact Factor -
Article: MicroRNAs expressed during lung cancer development are expressed in human pseudoglandular lung embryogenesis.
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ABSTRACT: MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17-92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics. RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR. Members of the let-7 family were downregulated and members of the miR-17-92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008). Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.Oncology 03/2009; 76(3):162-9. · 2.27 Impact Factor -
Article: Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE.
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ABSTRACT: Tumor marker serum levels were prospectively studied in 289 patients with suspected, but unconfirmed, lung cancer and in 513 patients with lung cancer [417 non-small cell lung cancer (NSCLC) patients and 96 small cell lung cancer (SCLC) patients]. In patients with benign disease, abnormal serum levels were found for the following tumor markers: CEA (in 6.6% of patients); CA 19.9 (6.2%); CA 125 (28.7%); NSE (0.7%); CYFRA (8.7%); TAG-72.3 (4.2%); SCC (3.5%), and CA 15.3 (3.5%). Excluding patients with renal failure or liver diseases, tumor marker specificity improved with abnormal levels in 0.5% for NSE, 0.9% for SCC, 2.8% for CEA, CA 15.3 and TAG-72.3, 3.8% for CA 19.9, 4.2% for CYFRA and 21.4% for CA 125. Excluding CA 125, one of the markers was abnormal in 15% of patients without malignancy. Tumor marker sensitivity was related to cancer histology and tumor extension. NSE had the highest sensitivity in SCLC and CYFRA and CEA in NSCLC. Significantly higher concentrations of CEA, SCC, CA 125, CA 15.3 and TAG-72.3 were found in NSCLC than in SCLC. Likewise, significantly higher CEA (p < 0.0001), TAG-72.3 (p < 0.001), CA 15.3 (p < 0.0001) and CA 125 (p < 0.01) were found in adenocarcinomas than in squamous tumors. Using a combination of 3 tumor markers (CEA, CYFRA 21-1 in all histologies, SCC in squamous tumors and CA 15.3 in adenocarcinomas), a high sensitivity may be achieved in all histological types. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Using specific criteria for the differentiation of SCLC and NSCLC, the sensitivity was 84.2 and 68.8%, the specificity was 93.8 and 99.7%, the positive predictive value was 98.3 and 98.5% and the negative predictive value was 57.7 and 93.3%, respectively.Tumor Biology 01/2009; 29(6):371-80. · 1.94 Impact Factor -
Article: Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer.
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ABSTRACT: Although current treatment options for metastatic non-small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate. Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02). Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.Journal of Clinical Oncology 08/2007; 25(19):2747-54. · 18.37 Impact Factor -
Article: Excision repair cross complementing 6 (ERCC6) single nucleotide polymorphism (SNP) and outcome to gemcitabine(gem)/cisplatin(cis) or docetaxel(doc)/cis in stage IV non-small-cell lung cancer (NSCLC) patients (p): D2-02
Journal of Thoracic Oncology 07/2007; 2(8):S393. · 3.66 Impact Factor -
Article: Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas.
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ABSTRACT: Anaplastic gliomas constitute a heterogeneous group of tumors with different therapeutic responses to adjuvant chemotherapy with alkylating agents. O6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, is one of the implicated factors in glioma chemoresistance. The prognostic value of MGMT remains controversial due in part to the fact that previous published studies included heterogeneous groups of patients with different tumor grades. The aim of this study was to evaluate the prognostic significance of MGMT in patients with anaplastic glioma. Ninety-three patients with anaplastic glioma were analyzed for MGMT protein expression by immunohistochemistry. In addition, for those patients from whom a good yield of DNA was obtained (n = 40), MGMT promoter methylation profile was analyzed by methylation-specific PCR. MGMT prognostic significance was evaluated together with other well-known prognostic factors. Fifty-one tumors (54.8%) showed nuclear staining of MGMT. There was a trend towards longer overall survival for those patients with negative MGMT immunostaining (hazard ratio, 1.66; P = 0.066). In a secondary analysis including those patients who actually received chemotherapy (n = 72), the absence of MGMT expression was independently associated with better survival (hazard ratio, 2.12; P = 0.027). MGMT promoter methylation was observed in 50% of the analyzed tumors. No statistical correlation between MGMT expression and MGMT promoter hypermethylation was observed. Unlike previous studies, we did not find a correlation between MGMT promoter methylation and survival. However, we observed a correlation between MGMT protein expression and survival in those patients who received chemotherapy thus suggesting that the absence of MGMT expression is a positive predictive marker in patients with anaplastic glioma.Clinical Cancer Research 08/2005; 11(14):5167-74. · 7.74 Impact Factor -
Article: Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer.
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ABSTRACT: We studied the specificity and sensitivity of progastrin releasing peptide (ProGRP) in 37 healthy subjects and 195 patients with benign and 149 with malignant diseases other than lung cancer. Likewise, we compared the ProGRP with other tumor markers used in lung cancer (CEA, SCC, CYFRA and NSE) in 187 patients with NSCLC and in 66 SCLC patients. We considered 50 pg/ml, 5 ng/ml, 2 ng/ml, 3.3 ng/ml and 20 ng/ml as the upper limits of normality for ProGRP, CEA, SCC, CYFRA 21-1 and NSE, respectively. Abnormal ProGRP serum levels were found in 10% of patients with benign diseases and in 13% of patients with malignancies other than lung. Renal failure was the main source of false-positive results (51.6%). Slightly raised ProGRP serum levels, excluding renal failure, were found in 4.1% of patients with benign diseases (<80 pg/ml) and in 5% of patients with malignancies other than lung cancer or neuroendocrine tumors (<120 pg/ml). Abnormal levels of ProGRP, NSE, CEA, CYFRA and SCC were found in 30%, 22.5%, 55.6%, 65.2% and 26.7% of NSCLC and in 73%, 64%, 53%, 46% and 4.5% of SCLC, respectively. Tumor marker serum levels were related to histological type and tumor extension, with ProGRP being the most sensitive marker in SCLC, CEA in adenocarcinomas and CYFRA 21-1 in squamous tumors. The most sensitive combinations of tumor markers were ProGRP and NSE in SCLC (88%), and CEA plus CYFRA in NSCLC (82%). In summary, ProGRP is the tumor marker of choice in SCLC and NSE is a complementary tumor marker in this histological type.Anticancer research 25(3A):1773-8. · 1.73 Impact Factor -
Article: Pro-gastrin-releasing peptide in patients with benign and malignant diseases.
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ABSTRACT: The specificity and sensitivity of pro-gastrin-releasing peptide (ProGRP) was evaluated in 37 healthy subjects, 197 patients with benign diseases and 310 patients with malignant diseases of different origins. Abnormal ProGRP serum levels (>50 pg/ml) were found in 10% of the patients with benign diseases and in 26.1% of the patients with active cancer. None of the healthy subjects had abnormal ProGRP levels. The benign disease with the highest ProGRP concentration was renal failure, with abnormal values in 51.6% of the patients studied. Excluding patients with renal failure or patients with creatinine levels greater than 1.5 mg/dl, raised ProGRP values (<80 ng/ml) were found in 2.5% (4/160) of patients with benign diseases and in 4.9% of patients with active malignancies other than lung cancer or neuroendocrine tumors (<110 ng/ml). Abnormal ProGRP serum levels were found in 26.2% of patients with non-small cell lung cancer (NSCLC) (mean 40.5 +/- 35.4 pg/ml) and in 76.8% of patients with small cell lung cancer (SCLC) (mean 694 +/- 1,776 pg/ml) (p < 0.001). ProGRP serum levels >300 pg/ml were only found in SCLC patients (41.4%). ProGRP results were related to tumor extension in SCLC (sensitivity in limited disease 58.3%, in extensive disease 95.5%) but not in NSCLC. In summary, renal failure is the most frequent source of false-positive results with ProGRP, and this marker is useful in the histological differential diagnosis of lung cancer.Tumor Biology 25(1-2):56-61. · 1.94 Impact Factor -
Article: Detection of occult breast cancer cells by amplification of CK19 mRNA by reverse transcriptase-polymerase chain reaction: role of surgical manipulation.
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ABSTRACT: To assess if surgical manipulation increases peripheral blood cancer cells dissemination in early stage (I and II) breast cancer patients. We analyzed 64 patients using RT-PCR for cytokeratin-19 as a marker for peripheral blood breast cancer cell dissemination. Peripheral blood was obtained at 4 different time-points (24 hours before and after surgery, one week and one month later). RT-PCR was positive in 14 (24%) out of 59 evaluable patients. Circulating cells were detected in 4 out of 14 patients before surgery (7%) while in the remaining 10, the positivity was observed after surgery (17%). The percentage of patients with occult breast cancer cells increased significantly after surgery (p = 0.01). 1) 7% of early breast cancer patients had circulating tumor cells before surgery. 2) After surgery tumor cells were detected in 17% of patients. 3) Surgery significantly increased the presence of occult breast cancer cells. 4) The clinical significance of occult breast cancer cells should be tested within a larger clinical trial trying to assess their role as an independent prognostic factor.Anticancer research 22(5):2877-84. · 1.73 Impact Factor
Top co-authors
Top Journals
Institutions
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2011–2012
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Hospital Clínic de Barcelona
Barcelona, Catalonia, Spain -
Institut d’Investigacions Biomèdiques August Pi i Sunyer
Barcelona, Catalonia, Spain
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2009–2011
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University of Barcelona
- Departament de Medicina
Barcelona, Catalonia, Spain -
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, Spain
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2007
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Hospital Regional Universitario Carlos Haya Malaga
Málaga, Andalusia, Spain
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