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result(s) for
"Dominguez, Gemma"
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Cancer‐associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients
by
García, Vanesa
,
Soldevilla, Beatriz
,
Provencio, Mariano
in
Biomarkers, Tumor - metabolism
,
Colorectal Neoplasms - metabolism
,
Colorectal Neoplasms - mortality
2013
Tumor epithelial cells within a tumor coexist with a complex microenvironment in which a variety of interactions between its various components determine the behavior of the primary tumors. Cancer‐associated fibroblasts (CAF) and M2 macrophages, characterized by high expression of different markers, including α‐SMA, FSP1 and FAP, or CD163 and DCSIGN, respectively, are involved in the malignancy of different tumors. In the present study, expression of the above markers in CAF and M2 macrophages was analyzed using RT‐PCR and immunohistochemistry in the normal mucosa and tumor tissue from a cohort of 289 colorectal cancer patients. Expression of CAF and M2 markers is associated with the clinical outcome of colorectal cancer patients. Moreover, the combination of CAF and M2 markers identifies three groups of patients with clear differences in the progression of the disease. This combined variable could be a decisive factor in the survival of advanced‐stage patients. Taken together, these analyses demonstrate the prognostic involvement of interrelationships between DCSIGN, CD163, α‐SMA, FSP1 and FAP markers in the survival of colon cancer patients.
Journal Article
Automatic Facial Palsy Diagnosis as a Classification Problem Using Regional Information Extracted from a Photograph
by
Garcia-Capulin, Carlos H.
,
Parra-Dominguez, Gemma S.
,
Sanchez-Yanez, Raul E.
in
Artificial intelligence
,
Asymmetry
,
clinical decision support systems
2022
The incapability to move the facial muscles is known as facial palsy, and it affects various abilities of the patient, for example, performing facial expressions. Recently, automatic approaches aiming to diagnose facial palsy using images and machine learning algorithms have emerged, focusing on providing an objective evaluation of the paralysis severity. This research proposes an approach to analyze and assess the lesion severity as a classification problem with three levels: healthy, slight, and strong palsy. The method explores the use of regional information, meaning that only certain areas of the face are of interest. Experiments carrying on multi-class classification tasks are performed using four different classifiers to validate a set of proposed hand-crafted features. After a set of experiments using this methodology on available image databases, great results are revealed (up to 95.61% of correct detection of palsy patients and 95.58% of correct assessment of the severity level). This perspective leads us to believe that the analysis of facial paralysis is possible with partial occlusions if face detection is accomplished and facial features are obtained adequately. The results also show that our methodology is suited to operate with other databases while attaining high performance, even though the image conditions are different and the participants do not perform equivalent facial expressions.
Journal Article
XPA, XPC, and XPD Modulate Sensitivity in Gastric Cisplatin Resistance Cancer Cells
by
Dominguez, Gemma
,
Perona, Rosario
,
Pajuelo-Lozano, Natalia
in
Antibodies
,
Apoptosis
,
Bcl-2 family
2018
Cisplatin is an election drug widely used in clinic for the treatment of advanced gastric cancer. However, the heterogeneity of the gastric tumors and its resistance to the drugs, make in some cases the response very low and the prognosis unpredictable. In this manuscript we aim to find the molecular processes involved in cisplatin-induced apoptosis in two gastric cancer cell lines with different sensitivity to the treatment: AGS and MKN45. The apoptosis induction is higher in MKN45 than in AGS cells in response to CDDP. The intrinsic apoptotic pathway study revealed that MKN45 cells undergo degradation of Mcl-1 together with an increase of Bid and Bad levels, which results in sensitivity to CDDP. In addition, DNA repair NER pathway is impair in MKN45 cells due to low levels of XPC and the absence of translocation of XPA and XPD to the nucleus after stimuli. Altogether, these results suggest that NER and Bcl-2 protein family proteins are potential targets to improve the response to cisplatin treatment.
Journal Article
Towards Facial Gesture Recognition in Photographs of Patients with Facial Palsy
by
Garcia-Capulin, Carlos H.
,
Parra-Dominguez, Gemma S.
,
Sanchez-Yanez, Raul E.
in
Algorithms
,
Automation
,
Design
2022
Humans express their emotions verbally and through actions, and hence emotions play a fundamental role in facial expressions and body gestures. Facial expression recognition is a popular topic in security, healthcare, entertainment, advertisement, education, and robotics. Detecting facial expressions via gesture recognition is a complex and challenging problem, especially in persons who suffer face impairments, such as patients with facial paralysis. Facial palsy or paralysis refers to the incapacity to move the facial muscles on one or both sides of the face. This work proposes a methodology based on neural networks and handcrafted features to recognize six gestures in patients with facial palsy. The proposed facial palsy gesture recognition system is designed and evaluated on a publicly available database with good results as a first attempt to perform this task in the medical field. We conclude that, to recognize facial gestures in patients with facial paralysis, the severity of the damage has to be considered because paralyzed organs exhibit different behavior than do healthy ones, and any recognition system must be capable of discerning these behaviors.
Journal Article
TWIST1 Is Expressed in Colorectal Carcinomas and Predicts Patient Survival
by
Garcia, Jose M.
,
Garcia de Herreros, Antonio
,
Peña, Cristina
in
Adjuvant chemotherapy
,
Aged
,
Angiogenesis
2011
TWIST1 is a transcription factor that belongs to the family of basic helix-loop-helix proteins involved in epithelial-to-mesenchymal transition and invasion processes. The TWIST1 protein possesses oncogenic, drug-resistant, angiogenic and invasive properties, and has been related with several human tumors and other pathologies. Colorectal cancer is one of the tumors in which TWIST1 is over-expressed, but its involvement in the clinical outcome of the disease is still unclear. We tested, by RT-PCR, the expression levels of TWIST1 in normal and tumor paired-sample tissues from a series of 151 colorectal cancer patients, in order to investigate its prognostic value as a tumor marker. TWIST1 expression was restricted to tumor tissues (86.1%) and correlated with lymph node metastasis (LNM). Adjusted analysis showed that the expression levels of TWIST1 correlated with overall survival (OS) and disease-free survival (DFS). Importantly, TWIST1 expression levels predicted OS specifically at stages I and II. Moreover, patients with stage II tumors and high TWIST1 levels showed even shorter survival than patients with stage III tumors. These results suggest that TWIST1 expression levels could be a tumor indicator in stage II patients and help select patients at greater risk of poor prognosis who might benefit from adjuvant chemotherapy.
Journal Article
Modulation of DNA-Induced Damage and Repair Capacity in Humans after Dietary Intervention with Lutein-Enriched Fermented Milk
by
Pérez-Sacristán, Belén
,
Soldevilla, Beatriz
,
Blanco-Navarro, Inmaculada
in
Adolescent
,
Adult
,
Allergies
2013
Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.
Journal Article
Facial Paralysis Detection on Images Using Key Point Analysis
by
Garcia-Capulin, Carlos H.
,
Parra-Dominguez, Gemma S.
,
Sanchez-Yanez, Raul E.
in
Asymmetry
,
Automation
,
Classification
2021
The inability to move the muscles of the face on one or both sides is known as facial paralysis, which may affect the ability of the patient to speak, blink, swallow saliva, eat, or communicate through natural facial expressions. The well-being of the patient could also be negatively affected. Computer-based systems as a means to detect facial paralysis are important in the development of standardized tools for medical assessment, treatment, and monitoring; additionally, they are expected to provide user-friendly tools for patient monitoring at home. In this work, a methodology to detect facial paralysis in a face photograph is proposed. A system consisting of three modules—facial landmark extraction, facial measure computation, and facial paralysis classification—was designed. Our facial measures aim to identify asymmetry levels within the face elements using facial landmarks, and a binary classifier based on a multi-layer perceptron approach provides an output label. The Weka suite was selected to design the classifier and implement the learning algorithm. Tests on publicly available databases reveal outstanding classification results on images, showing that our methodology that was used to design a binary classifier can be expanded to other databases with great results, even if the participants do not execute similar facial expressions.
Journal Article
ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
2021
The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer.
Journal Article
Extracellular Tumor-Related mRNA in Plasma of Lymphoma Patients and Survival Implications
2009
We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma.
mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA.
Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.
Journal Article
In‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer
by
Barderas, Rodrigo
,
Rodríguez‐Cobos, Javier
,
Fernández‐Aceñero, María Jesús
in
Amino acids
,
Antibodies
,
Antibody microarrays
2022
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer‐related death worldwide. Alterations in proteins of the p53‐family are a common event in CRC. ΔNp73, a p53‐family member, shows oncogenic properties and its effectors are largely unknown. We performed an in‐depth proteomics characterization of transcriptional control by ∆Np73 of the secretome of human colon cancer cells and validated its clinical potential. The secretome was analyzed using high‐density antibody microarrays and stable isotopic metabolic labeling. Validation was performed by semiquantitative PCR, ELISA, dot‐blot and western blot analysis. Evaluation of selected effectors was carried out using 60 plasma samples from CRC patients, individuals carrying premalignant colorectal lesions and colonoscopy‐negative controls. In total, 51 dysregulated proteins were observed showing at least 1.5‐foldchange in expression. We found an important association between the overexpression of ∆Np73 and effectors related to lymphangiogenesis, vasculogenesis and metastasis, such as brain‐derived neurotrophic factor (BDNF) and the putative aminoacyl tRNA synthase complex‐interacting multifunctional protein 1 (EMAP‐II)–vascular endothelial growth factor C–vascular endothelial growth factor receptor 3 axis. We further demonstrated the usefulness of BDNF as a potential CRC biomarker able to discriminate between CRC patients and premalignant individuals from controls with high sensitivity and specificity. High‐density antibody microarrays and stable isotopic metabolic labeling allowed the identification of secreted dysregulated effectors by the ectopic ∆Np73 expression in HCT116 colorectal cancer (CRC) cells. After validating the dysregulation of the effectors by orthogonal techniques, an important association with lymphangiogenesis, vasculogenesis and CRC metastasis was found. Brain‐derived neurotrophic factor was validated by ELISA as potential biomarker of CRC.
Journal Article