María Del Mar Abad

• Doctor of Medicine
• University of Salamanca

Background/Objectives: Recent advances in the treatment of non-small cell lung cancer (NSCLC) have shifted from conventional chemotherapy to targeted therapies aimed at specific genetic mutations, particularly in the adenocarcinoma subtype. These therapies have improved overall survival and quality of life. However, some patients still face barrier...

281 Background: Mutations in RAS/BRAF ( RAS/BRAFm ) and PIK3CA ( PIK3CAm ) genes have been described as mechanisms of resistance to anti-EGFR agents in mCRC. However, the utility of liquid biopsy in their baseline detection remains unknown. We aim to analyse oncological outcomes according to RAS/BRAF and PIK3CA mutational status in tissue & plasma...

Despite the existence of effective therapy options for patients with localized colorectal cancer, advanced-stage patients have limited therapies. Genomic profiling is a promising tool for guiding treatment selection as well as patient monitoring. Here, we describe a novel gene rearrangement (CCDC6::CASP7) detected in a patient with advanced colorec...

Introduction Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early‐stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma...

Colorectal cancer (CRC) is the second most frequent cause of cancer-related deaths. Mortality is largely due to limited treatment options for patients who present with advanced disease. Genomic abnormalities that are potentially characteristic of such advanced stages of the disease are complex and are not yet fully understood. In fact, only 30% of...

Background: Activating mutations of PIK3CA gene are described in about 30-40% of BC. They confer overall worse prognosis and resistance to endocrine and chemotherapeutic therapy. Concordance between testing methods (tissue & plasma) are not widely studied. We aim to correlate tissue & plasma assays and to analyze the discordant cases and prognostic...

598 Background: Loss of MGMT expression has been suggested as a predictor of response to alkylating agents in pancreatic neuroendocrine tumors (pNET), however, its determination is controversial. We aim to analyze the prognostic value of MGMT status assessed by immunohistochemistry (IHC) or pyrosequencing (PSQ) in patients with pNET receiving CAPTE...

Background Advanced colorectal cancer (CRC) is difficult to treat. For that reason, the development of novel therapeutics is necessary. Here we describe a potentially actionable plasma membrane target, the amino acid transporter protein subunit CD98hc. Methods Western blot and immunohistochemical analyses of CD98hc protein expression were carried...

In recent years, non-small cell lung cancer treatment has been revolutionized. EGFR tyrosine kinase inhibitors and our improved understanding of its alterations have driven new diagnostic strategies. Liquid biopsies have emerged as a useful tool in these contexts, showing potential utility in early diagnosis combined with low-dose CT scans, as well...

Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the...

Context.—: The neurotrophic tropomyosin receptor kinase (NTRK) family gene rearrangements have been recently incorporated as predictive biomarkers in a "tumor-agnostic" manner. However, the identification of these patients is extremely challenging because the overall frequency of NTRK fusions is below 1%. Academic groups and professional organizat...

Sporadic colorectal cancer (sCRC) initially presents as metastatic tumors in 25–30% of patients. The 5-year overall survival (OS) in patients with metastatic sCRC is 50%, falling to 10% in patients presenting with synchronous metastatic disease (stage IV). In this study, we systematically analyzed the mutations of RAS, PIK3CA and BRAF genes in circ...

Background: The dismal prognosis of advanced ovarian cancer calls for the development of novel therapies to improve disease outcome. In this regard, we set out to discover new molecular entities and to assess the preclinical effectiveness of their targeting. Methods: Cell lines, mice and human ovarian cancer samples were used. Proteome profiling...

Despite advances in recent years in the study of the molecular profile of sporadic colorectal cancer (sCRC), the specific genetic events that lead to increased aggressiveness or the development of the metastatic process of tumours are not yet clear. In previous studies of the gene expression profile (GEP) using a high-density array (50,000 genes an...

BACKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome, whereas biomarkers are critical for the success of precision therapies. AIM To investigate whether iCEMIGE (integration of CEll-morphometrics, MIcrobiome, and GEne biomarker signatures) improves risk stratification of breast canc...

Background Despite the incorporation of novel therapeutics, advanced triple negative breast cancer (TNBC) still represents a relevant clinical problem. Considering this, as well as the clinical efficacy of antibody-drug conjugates (ADCs), we aimed at identifying novel ADC targets that could be used to treat TNBC. Methods Transcriptomic analyses we...

Administering preoperative radiochemotherapy (RCT) in stage II-III tumors to locally advanced rectal carcinoma patients has proved to be effective in a high percentage of cases. Despite this, 20–30% of patients show no response or even disease progression. At present, preoperative response is assessed by a combination of imaging and tumor regressio...

Simple Summary Immunome in Sporadic Colorectal Cancer as source for biomarkers. Hence, a self-assembled protein array has been designed and developed to perform a serum screening to determined specific immune response against tumor antigens proteins as potential diagnostics biomarker panel. Abstract Sporadic Colorectal Cancer (sCRC) is the third l...

Intraluminal shedding of tumor cells is a rare infrequent sporadic colorectal cancer (sCRC) mechanism of spreading. Less than 30 cases of sCRC metastasis into anal fistula have been reported. Here, we study a 72-year-old male with an adenocarcinoma arising in an anal fistula. Subsequent studies revealed another tumor in the rectum without distant m...

In recent years, important advances have been achieved in the understanding of the genetic abnormalities present in colorectal tumors and their association with their ontogeny and progression. Accordingly, while the presence of mutations in the APC and/or KRAS genes is associated with neoplastic transformation, mutations in SMAD and DCC, different...

Sporadic colorectal cancer (sCRC) is the third most frequent cancer worldwide and the second most common cause of cancer-related deaths (mainly due metastatic dissemination). We investigated the immunohistochemical expression of frequently altered proteins in primary tumors from 51 patients (25 liver metastatic and 26 non-metastatic cases) with a m...

Lung cancer represents the leading cause of cancer death worldwide [1]. Because of that, intense efforts are being devoted to the development of novel therapeutic strategies to fight the disease [2]. In this respect, identification of new oncogenic drivers offers therapeutic opportunities in tumours in which those molecules or other cooperating ele...

It is well known that activating mutations in the KRAS and NRAS genes are associated with poor response to anti-EGFR therapies in patients with metastatic colorectal cancer (mCRC). Approximately half of the patients with wild-type (WT) KRAS colorectal carcinoma do not respond to these therapies. This could be because the treatment decision is deter...

The prognostic impact of KRAS mutations and other KRAS-related and nonrelated genes such as BRAF, NRAS and TP53, on sporadic colorectal cancer (sCRC) remain controversial and/or have not been fully established. Here we investigated the frequency of such mutations in primary sCRC tumors and their impact on patient progression-free survival (PFS) and...

Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise genetic events leading to the development of distant metastasis remain poorly understood. Thus, accurate prediction of metastatic disease in newly-diagnosed sCRC patients remains a challenge. Here, we evaluated the speci...

Background: Metastatic dissemination is the most frequent cause of death sporadic colorectal cancer (sCRC) patients. The genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. Material and Methods: We evaluate the molecu...

Background and aim: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer; most patients die during the first 6 months after diagnosis. With a 5% 5-year survival rate, is the fourth leading cause of cancer death in developed countries. In this regard, several clinical, histopathologic and biological characteristics of t...

Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors b...

Resumen A pesar de que las infecciones por virus de la familia Herpesviridae son muy frecuentes, tan solo 8 subtipos afectan al hombre (virus herpes simplex tipos 1 y 2, virus varicela-zoster, virus Epstein-Barr, citomegalovirus y virus herpes humano tipos 6, 7 y 8). Entre las infecciones causadas por enterovirus destacan el Poliovirus, el Coxsacki...

An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels. Here, we present a model in which there are complex interactions at different cellular and...

Significant advances have been achieved in recent years in the identification of the genetic and the molecular alterations of pancreatic ductal adenocarcinoma (PDAC). Despite this, at present the understanding of the precise mechanisms involved in the development and malignant transformation of PDAC remain relatively limited. Here, we evaluated for...

Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoad...

Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 6 months of diagnosis. However, 20% to 25% patients undergoing total tumor resection remain alive and disease-free 5 years after diagnostic surgery. Few studies on tumor markers have predicted patient prognosis and/or survival. We evaluated the effect of tumor cytogenetic copy nu...

Metastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identificatio...

To carry out a psychometric evaluation of the Spanish-language version of the Dundee Ready Education Environment Measure (DREEM) applied to dental students. A total of 1,391 students from nine Spanish public schools of dentistry responded to the DREEM questionnaire. To analyse the reliability of the DREEM questionnaire, the internal consistency was...

To analyse the 'Educational Climate' (EC) of dental students in Spain. The study group consisted of 1391 students from nine Spanish Public Schools of Dentistry, who responded to the questionnaire based on 'Dundee Ready Education Environment Measure' (DREEM). This questionnaire has 50 items that are grouped into five domains: Learning, Teachers, Aca...

Recently, it has been suggested that C2ORF40 is a candidate tumor suppressor gene in breast cancer. However, the mechanism for reduced expression of C2ORF40 and its functional role in breast cancers remain unclear. Here we show that C2ORF40 is frequently silenced in human primary breast cancers and cell lines through promoter hypermethylation. C2OR...

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Despite response to chemotherapy, relapses are frequent and resistance to available treatments is often seen in the metastatic setting. Therefore, identification of new therapeutic targets is required. With this aim, we have profiled the activation status of 44 receptor ty...

FBXW7 acts as a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of FBXW7 expression, which could be partially attributed by the genomic deletion or mutation of FBXW7 locus, is frequently observed in various human cancers. However, the mechanisms regulating FBXW7 expression still remain poorly understood. Here...

Genomic structure of FBXW7α. 1αa, 1αc, 1αb and 1αe are additional exons identified in this study. (DOC)

The mRNA levels of Fbxw7α, Fbxw7β and Fbxw7γ in the different tissues were determined by RT-PCR analysis using corresponding primer pairs (Forward primers: Fα, Fβ, Fγ, and common reverse primer cdc4R) listed in Table S1. Normal tissues include: 1-esophagus, 2-adipose, 3-heart, 4-bladder, 5-kidney, 6-brain, 7-liver, 8-lung, 9-cervix, 10-colon, 11-sp...

The sequences of each FBXW7a 5′-UTR AS form. (DOC)

The primers used in this study. (DOC)

Differential change in mRNA expression level of FBXW7α AS forms in human prostate (A) and bladder (B) cancers. The mRNA expression profile of FBXW7α AS forms was determined by semi-quantitative RT-PCR. “M” for DNAs ladder Marker. (DOC)

Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. We pr...

Cancer is the subject of intense research around the world, but many questions about how the disease works remain unanswered. How exactly does cancer start and how do tumours grow? In fact, at present there are ten times more anticancer drugs being tested in clinical trials than there were 15 years ago. However, many of the new anticancer agents ar...

Most genetic studies in colorectal carcinomas have focused on those abnormalities that are acquired by primary tumors, particularly in the transition from adenoma to carcinoma, whereas few studies have compared the genetic abnormalities of primary versus paired metastatic samples. In this study, we used high-density 500K single-nucleotide polymorph...

Association between specific CN alterations found in PDAC tumors (n = 20) and both tumor size and histopathology. (DOC)

The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy numbe...

Otero-Motta AP, Ordóñez JL, González-Celador R, Rivas B, García-Macías MC, Bullón A, Abad MM. Prevalence of human papillomavirus genotypes in cytologic abnormalities from unvaccinated women living in north-western Spain. APMIS 2011; 119: 204–215. Cervical cancer and its precursors low-grade squamous intraepithelial lesions (LSIL) and high-grade squ...

This work was partially supported by grants from Gerencia Regional de Salud de Castilla y Leon (Valladolid, Spain; 86 ⁄ A ⁄ 06), Fundacion Memoria de Don Samuel Solorzano Barruso (Salamanca, Spain; FS ⁄ 15-2007-2008), Caja de Burgos (Obra Social, Burgos, Spain) and RTICC from the Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo, Madri...

Most frequently detected amplified regions (for >3 contiguous SNPs with average log2 copy number ratio >0.22) in primary colorectal tumours from metastatic CRC patients genotyped on the Affymetrix 500K SNP array platform (n = 23). Only recurrently amplified DNA copy-number regions found in at least half of the cases, are listed. (0.10 MB DOC)

Primary colorectal cancer with paired liver metastasis (n = 23): Identification of recurrent chromosomal breakpoint regions for the 1p12, 8p12, 17p11.2 and 20p12.1 chromosome regions as defined by the Affymetrix 500K SNP array genotyping platform. Breakpoints occurred in 9 cases (39%) at the 118097448-120939802 genome coordinate for chromosome 1 (p...

For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic ch...

Unlabelled: Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on...

Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique i...

Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets. Mitogen-activated protein kinases (MAPK) play...

Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell pro...

To determine the grade of neuroprotection of combined treatment with moderate hypothermia, tirilazad and magnesium sulfate. Cerebral ischemia is one of the problems of great interest at present, with limited therapeutic measures. Hypothermia, one of the more efficient measures, together with neuroprotector pharmaceuticals, could be a valid alternat...

Objective To determine the grade of neuroprotection of combined treatment with moderate hypothermia, tirilazad and magnesium sulfate. Cerebral ischemia is one of the problems of great interest at present, with limited therapeutic measures. Hypothermia, one of the more efficient measures, together with neuroprotector pharmaceuticals, could be a vali...

10069 Background: ErbB2 overexpression is the major determinant of response to trastuzumab (Herceptin, H). Recently, some authors have reported the potential role of the expression of NRG on ErbB2 activation in breast cancer cells, and its consequences in response to treatment with H. In the present study we analyze the relationship between respons...

Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. we have studied...

Objectives: Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. Mat...

Objectives: Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. Mat...

To the Editor: We read with great interest the article written by Raspollini et al. ([1][1]). The authors studied a series including 32 cases of uterine leiomyosarcomas, which showed a 50% rate of positive immunostaining for KIT. Based on these results,the authors suggested the possibility of

OBJECTIVES: We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these mark...

We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these markers happen i...

AimsTo know the proteic expression of the genetic alterations that take place in the precocious stages of the field cancerization of oral cavity in our means. To study the MIB-1, cyclin D1, p16 and p53 expression levels to value if the alterations in the expression levels of these markers happen in a sequential pathway through the different stages...

Gastrointestinal stromal tumors (GIST) are a distinctive group of mesenchymal neoplasms of the gastrointestinal tract. The oncogene KIT has a central role in the pathogenesis of GIST, with c-kit receptor tyrosine kinase (KIT) protein expression being the gold standard in its diagnosis. The identification of GIST patients has become crucial, because...