9 results on '"de la Cruz-Ojeda P"'
Search Results
2. Quantification and Characterization of CTCs and Clusters in Pancreatic Cancer by Means of the Hough Transform Algorithm
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Francisco José Calero-Castro, Sheila Pereira, Imán Laga, Paula Villanueva, Gonzalo Suárez-Artacho, Carmen Cepeda-Franco, Patricia de la Cruz-Ojeda, Elena Navarro-Villarán, Sandra Dios-Barbeito, María José Serrano, Cristóbal Fresno, and Javier Padillo-Ruiz
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circulating tumor cell ,cluster ,pancreatic cancer ,Hough transform ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Circulating Tumor Cells (CTCs) are considered a prognostic marker in pancreatic cancer. In this study we present a new approach for counting CTCs and CTC clusters in patients with pancreatic cancer using the IsofluxTM System with the Hough transform algorithm (Hough-IsofluxTM). The Hough-IsofluxTM approach is based on the counting of an array of pixels with a nucleus and cytokeratin expression excluding the CD45 signal. Total CTCs including free and CTC clusters were evaluated in healthy donor samples mixed with pancreatic cancer cells (PCCs) and in samples from patients with pancreatic ductal adenocarcinoma (PDAC). The IsofluxTM System with manual counting was used in a blinded manner by three technicians who used Manual-IsofluxTM as a reference. The accuracy of the Hough-IsofluxTM approach for detecting PCC based on counted events was 91.00% [84.50, 93.50] with a PCC recovery rate of 80.75 ± 16.41%. A high correlation between the Hough-IsofluxTM and Manual-IsofluxTM was observed for both free CTCs and for clusters in experimental PCC (R2 = 0.993 and R2 = 0.902 respectively). However, the correlation rate was better for free CTCs than for clusters in PDAC patient samples (R2 = 0.974 and R2 = 0.790 respectively). In conclusion, the Hough-IsofluxTM approach showed high accuracy for the detection of circulating pancreatic cancer cells. A better correlation rate was observed between Hough-IsofluxTM approach and with the Manual-IsofluxTM for isolated CTCs than for clusters in PDAC patient samples.
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- 2023
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3. The Role of Non-Coding RNAs in Autophagy During Carcinogenesis
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Patricia de la Cruz-Ojeda, Rocío Flores-Campos, Elena Navarro-Villarán, and Jordi Muntané
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autophagy ,beclin-1 ,cancer ,miRNA ,lncRNA ,Biology (General) ,QH301-705.5 - Abstract
Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.
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- 2022
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4. MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages
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Rebecca Raue, Ann-Christin Frank, Dominik C. Fuhrmann, Patricia de la Cruz-Ojeda, Silvia Rösser, Rebekka Bauer, Giulia Cardamone, Andreas Weigert, Shahzad Nawaz Syed, Tobias Schmid, and Bernhard Brüne
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macrophage ,breast tumor ,miR ,tumor microenvironment ,Biology (General) ,QH301-705.5 - Abstract
Macrophages constitute a major part of the tumor-infiltrating immune cells. Within the tumor microenvironment, they acquire an alternatively activated, tumor-supporting phenotype. Factors released by tumor cells are crucial for the recruitment of tumor-associated macrophages. In the present project, we aimed to understand the role of hsa-miR-200c-3p (miR-200c) in the interplay between tumor cells and macrophages. To this end, we employed a coculture system of MCF7 breast tumor cells and primary human macrophages and observed the transfer of miR-200c from apoptotic tumor cells to macrophages, which required intact CD36 receptor in macrophages. We further comprehensively determined miR-200c targets in macrophages by mRNA-sequencing and identified numerous migration-associated mRNAs to be downregulated by miR-200c. Consequently, miR-200c attenuated macrophage infiltration into 3-dimensional tumor spheroids. miR-200c-mediated reduction in infiltration further correlated with a miR-200c migration signature comprised of the four miR-200c-repressed, predicted targets PPM1F, RAB11FIB2, RDX, and MSN.
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- 2022
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5. Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer
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María A. Rodríguez-Hernández, P de la Cruz-Ojeda, Mª José López-Grueso, Elena Navarro-Villarán, Raquel Requejo-Aguilar, Beatriz Castejón-Vega, María Negrete, Paloma Gallego, Álvaro Vega-Ochoa, Victor M. Victor, Mario D. Cordero, José A. Del Campo, J. Antonio Bárcena, C. Alicia Padilla, and Jordi Muntané
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Autophagy ,Cell death ,Endoplasmic reticulum stress ,mTOR ,Redox status ,PGC-1α ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages.There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.
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- 2020
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6. Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer
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Raúl González, María A. Rodríguez-Hernández, María Negrete, Kalina Ranguelova, Aurelie Rossin, Carmen Choya-Foces, Patricia de la Cruz-Ojeda, Antonio Miranda-Vizuete, Antonio Martínez-Ruiz, Sergio Rius-Pérez, Juan Sastre, José A. Bárcena, Anne-Odile Hueber, C. Alicia Padilla, and Jordi Muntané
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Apoptosis ,Cell proliferation ,CD95 ,GSNOR ,Hepatocarcinoma ,Nrf2 ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 receptor leading to an increase of caspase-8 activity and cell proliferation, as well as reduction of caspase-3 activity in liver cancer cells. In addition, Sorafenib transiently increased mRNA expression and activity of S-nitrosoglutathione reductase (GSNOR) in HepG2 cells. Different experimental models of hepatocarcinogenesis based on the subcutaneous implantation of HepG2 cells in nude mice, as well as the induction of HCC by diethylnitrosamine (DEN) confirmed the relevance of Trx1 downregulation during the proapoptotic and antiproliferative properties induced by Sorafenib. In conclusion, the induction of apoptosis and antiproliferative properties by Sorafenib were related to Trx1 downregulation that appeared to play a relevant role on SNO of NOS3 and CD95 in HepG2 cells. The transient increase of GSNOR might also participate in the deactivation of CD95-dependent proliferative signaling in liver cancer cells.
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- 2020
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7. Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs
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Patricia de la Cruz-Ojeda, Rocío Flores-Campos, Sandra Dios-Barbeito, Elena Navarro-Villarán, and Jordi Muntané
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hepatocarcinoma ,miRNA ,nitric oxide synthase ,lncRNA ,tumor-associated macrophages ,cancer associated fibroblasts ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Nitric oxide (NO) has been identified and described as a dual mediator in cancer according to dose-, time- and compartment-dependent NO generation. The present review addresses the different epigenetic mechanisms, such as histone modifications and non-coding RNAs (ncRNAs), miRNA and lncRNA, which regulate directly or indirectly nitric oxide synthase (NOS) expression and NO production, impacting all hallmarks of the oncogenic process. Among lncRNA, HEIH and UCA1 develop their oncogenic functions by inhibiting their target miRNAs and consequently reversing the inhibition of NOS and promoting tumor proliferation. The connection between miRNAs and NO is also involved in two important features in cancer, such as the tumor microenvironment that includes key cellular components such as tumor-associated macrophages (TAMs), cancer associated fibroblasts (CAFs) and cancer stem cells (CSCs).
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- 2021
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8. Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot
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Magali Humbert, María Morán, Patricia de la Cruz-Ojeda, Jordi Muntané, Tabea Wiedmer, Nadezda Apostolova, Sharon L. McKenna, Guillermo Velasco, Walter Balduini, Leopold Eckhart, Bassam Janji, Belém Sampaio-Marques, Paula Ludovico, Eva Žerovnik, Rupert Langer, Aurel Perren, Nikolai Engedal, and Mario P. Tschan
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autophagy ,biomarkers ,pathology ,disease ,Biology (General) ,QH301-705.5 - Abstract
Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples.
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- 2020
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9. Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis
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Suleva Povea-Cabello, Manuel Oropesa-Ávila, Patricia de la Cruz-Ojeda, Marina Villanueva-Paz, Mario de la Mata, Juan Miguel Suárez-Rivero, Mónica Álvarez-Córdoba, Irene Villalón-García, David Cotán, Patricia Ybot-González, and José A. Sánchez-Alcázar
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apoptosis ,apoptotic microtubule network ,microtubules ,actin filaments ,genotoxic drugs ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
During apoptosis, cells undergo characteristic morphological changes in which the cytoskeleton plays an active role. The cytoskeleton rearrangements have been mainly attributed to actinomyosin ring contraction, while microtubule and intermediate filaments are depolymerized at early stages of apoptosis. However, recent results have shown that microtubules are reorganized during the execution phase of apoptosis forming an apoptotic microtubule network (AMN). Evidence suggests that AMN is required to maintain plasma membrane integrity and cell morphology during the execution phase of apoptosis. The new “two coffins” hypothesis proposes that both AMN and apoptotic cells can adopt two morphological patterns, round or irregular, which result from different cytoskeleton kinetic reorganization during the execution phase of apoptosis induced by genotoxic agents. In addition, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses. These findings suggest that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response. From a pathological point of view, round-shaped apoptosis can be seen as a physiological and controlled type of apoptosis, while irregular-shaped apoptosis can be considered as a pathological type of cell death closer to necrosis.
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- 2017
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