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5.
Oncogene ; 36(19): 2737-2749, 2017 05 11.
Article in English | MEDLINE | ID: mdl-27991928

ABSTRACT

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.


Subject(s)
Breast Neoplasms/genetics , DNA-Binding Proteins/genetics , Lung Neoplasms/genetics , Proto-Oncogenes/genetics , SOX9 Transcription Factor/genetics , TOR Serine-Threonine Kinases/genetics , Transcription Factors/genetics , Adaptor Proteins, Signal Transducing/genetics , Adult , Aged , Breast Neoplasms/pathology , Carrier Proteins/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Lung Neoplasms/secondary , MCF-7 Cells , MDS1 and EVI1 Complex Locus Protein , Microfilament Proteins/genetics , Middle Aged , Neoplasm Metastasis , Osteonectin/genetics , Regulatory-Associated Protein of mTOR , Signal Transduction/genetics , TOR Serine-Threonine Kinases/antagonists & inhibitors , Xenograft Model Antitumor Assays
6.
Rev. esp. anestesiol. reanim ; 61(7): 396-400, ago.-sept. 2014.
Article in Spanish | IBECS | ID: ibc-124933

ABSTRACT

La hipotermia terapéutica es un tratamiento efectivo para la protección neurológica tras parada cardíaca extrahospitalaria, y podría ser beneficiosa también en la parada cardíaca intrahospitalaria. Su utilización en pacientes posquirúrgicos es limitada debido al riesgo incrementado de complicaciones específicas, especialmente de hemorragia. Existen diferencias en los tiempos de hipotermia terapéutica empleados, tanto para alcanzar la temperatura objetivo, como en la duración de la terapia, por lo que la estrategia óptima todavía está por determinar. Presentamos un caso de utilización de hipotermia terapéutica durante 48 h tras una parada cardíaca, en el contexto de drenaje quirúrgico de un derrame pericárdico severo con compromiso hemodinámico (AU)


Therapeutic hypothermia is an effective treatment for neurological protection after out-of-hospital cardiac arrest, and may also be beneficial for in-hospital cardiac arrest. Its use is limited in post-surgical patients due to the risk of specific complications, particularly bleeding. There are significant differences among previous publications regarding the time to reach the target temperature and the duration of therapy, so the optimal strategy is not yet established. We present the case of a patient who suffered a perioperative cardiac arrest related to a pericardial tamponade, and who underwent therapeutic hypothermia for 48 h (AU)


Subject(s)
Humans , Male , Middle Aged , Hypothermia/drug therapy , Hypothermia/surgery , Pericardial Effusion/drug therapy , Pericardial Effusion/therapy , Heart Arrest/drug therapy , Cardiac Tamponade/drug therapy , /trends , Isoproterenol/therapeutic use , Neurophysiology/methods
7.
Rev. esp. anestesiol. reanim ; 61(7): 401-403, ago.-sept. 2014.
Article in English | IBECS | ID: ibc-124934

ABSTRACT

Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms (AU)


La necrosis esofágica aguda o esófago negro es una entidad clínica infrecuente que debe su nombre al aspecto necrótico de la mucosa esofágica observado durante una endoscopia digestiva alta. Se relaciona siempre con estados clínicos de gravedad y su etiología es habitualmente isquémica. Presentamos el primer caso de necrosis esofágica aguda tras anestesia subaracnoidea para la realización de una artroplastia parcial de cadera. Se discuten los mecanismos fisiopatológicos subyacentes (AU)


Subject(s)
Humans , Female , Aged, 80 and over , Anesthesia , Necrosis/chemically induced , Necrosis/complications , Hypotension/complications , Hypotension/diagnosis , Hypotension/drug therapy , Esophagus , Hemorrhage/complications , Hemorrhage/drug therapy , Risk Factors , Esophageal Perforation/complications , Esophageal Perforation/drug therapy
8.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 40(2): 89-96, mar. 2014. tab, ilus
Article in Spanish | IBECS | ID: ibc-121486

ABSTRACT

Dada la creciente implicación de diversos especialistas en la atención preoperatoria (debido por un lado a la realización de cirugías menores en el ámbito de la atención primaria y por otro lado a la necesaria coordinación de los médicos de atención primaria con los servicios quirúrgicos y de anestesiología hospitalarias para optimizar los resultados de nuestros pacientes), creemos que es necesaria una actualización sobre el manejo de las medicaciones crónicas en este periodo. A continuación intentaremos revisar la bibliografía actual sobre las recomendaciones en cuanto a la suspensión o continuación de los fármacos más frecuentes (AU)


As different specialists are becoming increasingly involved in the preoperative management of our patients (for two main reasons; Primary Care doctors have to perform minor surgical procedures, and as coordination between Primary Care and In-hospital Care is more and more necessary in order to improve their outcomes), we believe that an update is needed as regards the management of chronic medications in this period. We will try to review the current literature dealing with the recommendations about withdrawing or continuing these drugs (AU)


Subject(s)
Humans , Male , Female , Preoperative Care/methods , Preoperative Period , Anesthesiology/methods , Antibiotic Prophylaxis/methods , Antibiotic Prophylaxis , Platelet Aggregation Inhibitors/therapeutic use , Monoamine Oxidase Inhibitors/therapeutic use , Primary Health Care/methods , Hemostasis , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Cardiovascular Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Antidepressive Agents, Tricyclic/therapeutic use
9.
Rev Esp Anestesiol Reanim ; 61(7): 396-400, 2014.
Article in Spanish | MEDLINE | ID: mdl-24035536

ABSTRACT

Therapeutic hypothermia is an effective treatment for neurological protection after out-of-hospital cardiac arrest, and may also be beneficial for in-hospital cardiac arrest. Its use is limited in post-surgical patients due to the risk of specific complications, particularly bleeding. There are significant differences among previous publications regarding the time to reach the target temperature and the duration of therapy, so the optimal strategy is not yet established. We present the case of a patient who suffered a perioperative cardiac arrest related to a pericardial tamponade, and who underwent therapeutic hypothermia for 48h.


Subject(s)
Drainage , Hypothermia, Induced/methods , Pericardial Effusion/surgery , Postoperative Complications/therapy , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Carcinoma, Bronchogenic/complications , Carcinoma, Bronchogenic/diagnosis , Cardiac Tamponade/etiology , Cardiovascular Agents/therapeutic use , Drug Therapy, Combination , Electric Countershock , Emergencies , Heart Arrest/etiology , Heart Arrest/therapy , Heart Diseases/complications , Heart Diseases/drug therapy , Humans , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Male , Middle Aged , Neoplasms, Unknown Primary/complications , Neoplasms, Unknown Primary/diagnosis , Pericardial Effusion/complications , Pericardiectomy , Pneumonia, Pneumococcal/complications , Postoperative Complications/etiology , Reperfusion Injury/etiology , Respiration, Artificial , Time Factors , Water-Electrolyte Imbalance/complications
10.
Semergen ; 40(2): 89-96, 2014 Mar.
Article in Spanish | MEDLINE | ID: mdl-23969220

ABSTRACT

As different specialists are becoming increasingly involved in the preoperative management of our patients (for two main reasons; Primary Care doctors have to perform minor surgical procedures, and as coordination between Primary Care and In-hospital Care is more and more necessary in order to improve their outcomes), we believe that an update is needed as regards the management of chronic medications in this period. We will try to review the current literature dealing with the recommendations about withdrawing or continuing these drugs.


Subject(s)
Minor Surgical Procedures/methods , Pharmaceutical Preparations/administration & dosage , Preoperative Care/methods , Cooperative Behavior , Humans , Primary Health Care/methods
11.
Rev Esp Anestesiol Reanim ; 61(7): 401-3, 2014.
Article in English | MEDLINE | ID: mdl-24054057

ABSTRACT

Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.


Subject(s)
Anesthesia, Spinal/adverse effects , Esophagus/blood supply , Hypotension/etiology , Ischemia/etiology , Postoperative Complications/etiology , Acute Disease , Aged, 80 and over , Arthroplasty, Replacement, Hip , Blood Component Transfusion , Combined Modality Therapy , Esophagus/pathology , Fatal Outcome , Female , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Hip Fractures/surgery , Humans , Hypotension/therapy , Intraoperative Complications/etiology , Intraoperative Complications/therapy , Necrosis , Postoperative Complications/pathology , Shock/etiology , Supine Position
12.
Oncogene ; 31(15): 1988-94, 2012 Apr 12.
Article in English | MEDLINE | ID: mdl-21892211

ABSTRACT

The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5'-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion 'rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival.


Subject(s)
DNA-Binding Proteins/metabolism , Kruppel-Like Transcription Factors/metabolism , Neoplasms/metabolism , Transcription Factors/metabolism , Adenosine/analogs & derivatives , Adenosine/pharmacology , Animals , Breast Neoplasms/metabolism , Enhancer of Zeste Homolog 2 Protein , Female , Humans , Kruppel-Like Transcription Factors/genetics , Male , Mice , Mice, Nude , Neoplasm Transplantation , Neoplasms/genetics , Polycomb Repressive Complex 2 , Prostatic Neoplasms/metabolism , RNA Interference , Transfection
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