María Sereno

Hospital Universitario Infanta Sofía, Madrid, Madrid, Spain

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Publications (32)87.65 Total impact

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    ABSTRACT: Purpose: Paclitaxel, a widely-used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of inter-individual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a whole-exome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy. Experimental Design: Blood samples from eight patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes. Results: WES revealed two patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20 allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4*20 carriers, and two missense variants exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P=0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P=5.9x10-5). Conclusion: This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization.
    Clinical Cancer Research 11/2014; 21(2). DOI:10.1158/1078-0432.CCR-14-1758 · 8.19 Impact Factor
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    ABSTRACT: Background Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. Patients and methods We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient. Results The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. Conclusions We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.
    Clinical and Translational Oncology 10/2014; 17(4). DOI:10.1007/s12094-014-1233-3 · 1.60 Impact Factor
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    ABSTRACT: Purpose Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. Patients and methods A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. Results Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. Conclusions The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.
    Clinical and Translational Oncology 07/2014; 17(2). DOI:10.1007/s12094-014-1202-x · 1.60 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.
    Clinical and Translational Oncology 03/2014; 16(8). DOI:10.1007/s12094-014-1171-0 · 1.60 Impact Factor
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    ABSTRACT: Lung cancer is currently one of the most common malignancies in the world and peritoneal involvement is rare in these types of tumors. Clinical manifestations of these metastases are also uncommon and include intestinal perforation and obstruction. The present study reviewed certain aspects of the complication of peritoneal involvement and illustrated it with four cases of patients that were diagnosed with primary lung carcinoma and secondary peritoneal carcinomatosis (PC). The outcome of these patients is poor and they rarely respond to chemotherapy. Surgery is successful in the majority of cases.
    Oncology letters 09/2013; 6(3):705-708. DOI:10.3892/ol.2013.1468 · 0.99 Impact Factor
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    ABSTRACT: Oxaliplatin is one of the main drugs used in digestive tumors treatment. Peripheral neuropathy is a well-recognized dose-limiting toxicity of OXL. Two types of neuropathy have been described with this agent: acute or transient and chronic or persistent, with different etiology, clinical manifestations and prognosis. This paper is an exhaustive review about the main aspects of oxaliplatin induced peripheral neuropathy, focus in clinical features, treatment, prevention strategies and future approach.
    Critical reviews in oncology/hematology 08/2013; 89(1). DOI:10.1016/j.critrevonc.2013.08.009 · 4.05 Impact Factor
  • Journal of Emergency Medicine 12/2012; 45(2). DOI:10.1016/j.jemermed.2012.09.027 · 1.18 Impact Factor
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    ABSTRACT: BACKGROUND: Squamous cell carcinoma (SCC) is the predominant histological type in men, and adenocarcinoma is the most common subtype in women in the world. The incidence of SCC is decreasing in men, while the incidence of adenocarcinoma (AC) is stable or slightly increasing in western countries. There is active research on the AC subtype but SCC remains poorly studied. CONCLUSIONS: In this review, we have studied different aspects of the SCC subtype, including epidemiology, clinical features, pathology, molecular biology markers, and new therapeutic targets, treatments and prognosis implications.
    Critical reviews in oncology/hematology 07/2012; 84(3). DOI:10.1016/j.critrevonc.2012.06.009 · 4.05 Impact Factor
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    ABSTRACT: PURPOSE: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. METHODS: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. RESULTS: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. CONCLUSION: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.
    International journal of radiation oncology, biology, physics 04/2012; 84(5). DOI:10.1016/j.ijrobp.2012.01.083 · 4.18 Impact Factor
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    ABSTRACT: Highlights ► We present a case report of a patient with an ovarian carcinosarcoma who achieve a complete response with PLD as a second-line therapy. ► There is little evidence regarding the effectiveness of second-line therapies in ovarian carcinosarcoma. ► Our case illustrates that the RECIST criteria is unreliable in predicting the histopathological treatment response in carcinosarcomas. ► FDG-PET was significantly more accurate than size-based criteria
    04/2012; 2(2):67–68. DOI:10.1016/j.gynor.2012.02.004
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    ABSTRACT: Small cell lung cancer is the most aggressive lung cancer subtype. The standard treatment approach is based on cisplatin regimens. Although response rates to treatment are approximately 60-80%, the median survival is still very poor. Excision repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced DNA adducts and has been related with prognosis and cisplatin response. Topotecan is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and immunohistochemistry. A significant association was found between the inmunohistochemistry expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In the survival analysis, a significant correlation between a better PFS with a low TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary, our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis to predict cisplatin response and prognosis in SCLC patients.
    International Journal of Oncology 02/2012; 40(6):2104-10. DOI:10.3892/ijo.2012.1378 · 3.03 Impact Factor
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    ABSTRACT: Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information.
    Annals of Oncology 11/2011; 23(6):1579-85. DOI:10.1093/annonc/mdr532 · 6.58 Impact Factor
  • European Journal of Cancer 09/2011; 47. DOI:10.1016/S0959-8049(11)71638-0 · 4.82 Impact Factor
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    ABSTRACT: Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.
    Clinical and Translational Oncology 09/2011; 13(9):599-610. DOI:10.1007/s12094-011-0705-y · 1.60 Impact Factor
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    ABSTRACT: We present the case of a 70-year-old woman with emphysematous cystitis. She was a diabetic patient and she was on chemotherapy treatment for a breast cancer. She complaint of severe asthenia and pain in her right lower extremity, but no fever or urinary symptoms. A computed tomography (CT) scan was suggestive of severe emphysematous cystitis. Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients. A conservative treatment approach using antibiotics and bladder catheterization is typically successful, with a complication rate less than 20%.
    McGill journal of medicine: MJM: an international forum for the advancement of medical sciences by students 06/2011; 13(1):13.
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    ABSTRACT: Preoperative chemoradiotherapy (CRT) is the treatment of choice for rectal cancer (RC), but half of the patients do not respond, suffer unnecessary toxicities, and surgery delays. We aimed to develop a model that could predict a clinically meaningful response to CRT by using formalin-fixed paraffin-embedded (FFPE) biopsies. We first carried out an exploratory screening of candidate genes by using SAGE technology to evaluate dynamic changes in the RC transcriptome in selected refractory patients before and after CRT. Next, 53 genes (24 from SAGE and 29 from the literature) were analyzed by qPCR arrays in FFPE initial biopsies from 94 stage II/III RC patients who were preoperatively treated with CRT. Tumor response was defined by using Dworak's tumor regression grade (2-3-4 vs. 0-1). Multivariate Cox methods and stepwise algorithms were applied to generate an optimized predictor of response and outcome. In the training cohort (57 patients), a 13-gene signature predicted tumor response with 86% accuracy, 87% sensitivity, and 82% specificity. In a testing cohort (37 patients), the model correctly classified 6 of 7 nonresponders, with an overall accuracy of 76%. A signature-based score identified patients with a higher risk of relapse in univariate (3-year disease-free survival 64% vs. 90%, P = 0.001) and multivariate analysis (HR = 4.35 95% CI: 1.2-15.75, P = 0.02), in which it remained the only statistically significant prognostic factor. A basal 13-gene signature efficiently predicted CRT response and outcome. Multicentric validation by the GEMCAD collaborative group is currently ongoing. If confirmed, the predictor could be used to improve patient selection in RC studies.
    Clinical Cancer Research 04/2011; 17(12):4145-54. DOI:10.1158/1078-0432.CCR-10-2257 · 8.19 Impact Factor
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    ABSTRACT: INTRODUCTION: TNM and histological subtype are the most important prognostic criteria in gastric cancer. In this study, we have tried to identify an immunohistochemical protein profile involved in gastric recurrence after a radical surgery. MATERIALS AND METHODS: In this paper, protein panels involved in gastric carcinogenesis and progression was analyzed by immunohistochemistry expression: p53, Ki-67, Bcl-2, COX-2, c-erb-B2, EPO-R, E-cadherin, and β-catenin in 44 gastrectomy samples coming from gastrectomy pieces of patients diagnosed and operated on adenocarcinoma of the stomach followed by adjuvant treatment based on MacDonald chemoradiation regimen. An immunostaining profile that could predict the relapse after the end of adjuvant treatment was tried to find. These results have shown that the expression of the adverse prognostic protein profile based on positive p53 immunohistochemical expression and non-conserved E-cadherin/B-catenin staining is associated with tumor recurrence and a poor disease-free survival in operated gastric cancer patients with curative intent followed by adjuvant chemoradiation according to MacDonald's regimen. A protein profile based on immunohistochemical expression of p53 and E-cadherin-B-catenin that has a significant correlation to disease-free survival was identified in gastric cancer samples.
    Journal of Gastrointestinal Cancer 03/2011; 43(2):181-9. DOI:10.1007/s12029-011-9267-z
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    ABSTRACT: A 40-year-old woman with liver metastasis resulting from colorectal adenocarcinoma suffered from a severe hypersensitivity reaction to cetuximab. She also experienced grade 3 skin toxicity. The administration of cetuximab was suspended, and she was offered panitumumab as an alternative treatment. Whereas she did not experience another infusion reaction, her skin rash worsened with the administration of panitumumab, a fully human anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb).
    Clinical and Translational Oncology 11/2010; 12(11):775-7. DOI:10.1007/s12094-010-0595-4 · 1.60 Impact Factor
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    ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies.
    Clinical and Translational Oncology 02/2010; 12(2):81-91. DOI:10.1007/S12094-010-0474-z · 1.60 Impact Factor
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    ABSTRACT: The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.
    Cancer Treatment Reviews 05/2009; 35(3):246-54. DOI:10.1016/j.ctrv.2008.11.004 · 6.47 Impact Factor

Publication Stats

281 Citations
87.65 Total Impact Points

Institutions

  • 2008–2014
    • Hospital Universitario Infanta Sofía
      Madrid, Madrid, Spain
  • 2011
    • Hospital Universitario Puerta de Hierro-Majadahonda
      Махадаонда, Madrid, Spain
  • 2007–2008
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2004–2008
    • Hospital Universitario La Paz
      • Servicio de Oncología
      Madrid, Madrid, Spain