Borja Guerra

Borja Guerra
Universidad de Las Palmas de Gran Canaria | ULPGC · Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS) - Research Institute of Biomedical and Health Sciences (IUIBS)

Molecular Biology. PhD (Physiology-Pharmacology)
Associate Professor of Pharmacology. Experimental Pharmacology. Drug Discovery. New antitumor drugs and SERMs/SERDs.

About

72
Publications
22,950
Reads
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1,771
Citations
Citations since 2017
16 Research Items
777 Citations
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2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
Introduction
Borja Guerra is Associate Professor of Pharmacology at the University of Las Palmas de Gran Canaria (ULPGC), Spain. He is also secretary of the Institute for Biomedical and Healthcare Research - ULPGC. Guerra’s research focuses on discovery and preclinical development of new inhibitors of JAK/STAT and BCR-ABL/STAT5 signaling and new SERMs/SERDs. He is author of 45 articles in journals included in the JCR (most of them in Q1) and 5 book chapters. Sum of times cited: 1366; h-index: 22.
Additional affiliations
December 2016 - present
Universidad de Las Palmas de Gran Canaria
Position
  • Professor (Associate)
September 2014 - December 2016
Universidad de Las Palmas de Gran Canaria
Position
  • Professor (Assistant)
March 2013 - September 2014
Centro Atlántico del Medicamento (CEAMED SA)
Position
  • Preclinical Development of antiCancer drugs (JAK/STAT inhibitors)
Education
January 2000 - October 2004
Universidad de La Laguna
Field of study
  • Physiology-Pharmacology
October 1993 - June 1999
Universidad de La Laguna
Field of study
  • Biology

Publications

Publications (72)
Article
Full-text available
Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, but the precise intracellular mechanisms underlying the progression of this inflammation associated cancer are not well established. SOCS2 protein plays an important role in the carcinogenesis of different tumors by regulating cytokine signalling through the J...
Chapter
Full-text available
Sarcomas are rare tumors that are difficult to treat. Many of them are chemo-resistant and with a high tendency to recur. Hence, finding new treatments is imperative in these tumors. Metabolic changes in tumor biology have become an essential characteristic in carcinogenesis processes, highlighting among them the role of lipids in these events, mai...
Article
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Tamoxifen improves the overall survival rate in hormone receptor-positive breast cancer patients. However, despite the fact that it exerts antagonistic effects on the ERα, it can act as a partial agonist, resulting in tumor growth in estrogen-sensitive tissues. In this study, highly functionalized 5-hydroxy-2H-pyrrol-2-ones were synthesized and eva...
Article
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Based on molecular docking studies on the ERα, a series of lignan derivatives (3–16) were designed and semisynthesized from the natural dibenzylbutyrolactones bursehernin (1) and matairesinol dimethyl ether (2). To examine their estrogenic and antiestrogenic potencies, the effects of these compounds on estrogen receptor element (ERE)-driven reporte...
Article
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Chronic myelogenous leukemia (CML) is a hematological malignancy that highly depends on the BCR-ABL1/ STAT5 signaling pathway for cell survival. First-line treatments for CML consist of tyrosine kinase inhibitors that efficiently target BCR-ABL1 activity. However, drug resistance and intolerance are still therapeutic limitations in Ph+ cells. There...
Article
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A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myel...
Article
Full-text available
A hallmark of cancer cells includes a metabolic reprograming that provides energy, the essential building blocks, and signaling required to maintain survival, rapid growth, metastasis, and drug resistance of many cancers. The influence of tumor microenviroment on cancer cells also results an essential driving force for cancer progression and drug r...
Chapter
Full-text available
Sex steroids have important physiological actions, which are not limited to reproductive organs, in both females and males. They exert important physiological roles, including the regulation of somatotropic-liver axis, intermediate metabolism, or gender dimorphism. This is in part because the liver is a sex steroid-responsive organ where sex steroi...
Article
Mixed ligand complexes [Cu(phen)(Lap)2] (1) and [Co(dppeO)(Lap)2] (2) were synthesized from the reaction of lapachol (Lap) with [Cu(phen)Cl2] or [Co(dppe)Cl2] in the presence of Et3N. Complexes (1) and (2) were fully characterized by X-ray crystallography, elemental analyses, and infrared spectroscopy. Antiproliferative activities of complexes (1)...
Chapter
Full-text available
Janus kinases (JAKs) play an essential role in the regulation of cytokine signal-ing. They control cell survival, proliferation, differentiation, immune response, and hematopoiesis. Deregulation of JAK signaling has been associated to the pathogen-esis of numerous immune-inflammatory diseases, hematological malignancies, and solid tumors. Thus, JAK...
Article
The signal transducer and activator of transcription (STAT) are transcription factors that work via JAK/STAT pathway regulating the expression of genes involved in cell survival, proliferation, differentiation, development, immune response, and, among other essential biological functions, hematopoiesis. JAK/STAT signaling is strictly regulated unde...
Article
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BCR-ABL1-STAT5 is an oncogenic signaling pathway in human chronic myelogenous leukemia (CML) and it represents a valid target for anti-CML drug design. Resistance to direct BCR-ABL1 inhibitors is a common clinical issue, so STAT5 inhibition has become an interesting alternative target. In this study, the effects of NPQC6, a novel naphtoquinone-coum...
Article
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Compared to normoxia, during sprint exercise in severe acute hypoxia the glycolytic rate is increased leading to greater lactate accumulation, acidification, and oxidative stress. To determine the role played by pyruvate dehydrogenase (PDH) activation and reactive nitrogen and oxygen species (RNOS) in muscle lactate accumulation, nine volunteers pe...
Article
The aim of this study was to determine reactive oxygen species (ROS) could play a role in blunting Thr(172)-AMPKα phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30s sprint (Wingate test) in two occasions w...
Article
Full-text available
Human Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder which is associated with activation of Bcr-Abl-Stat5 oncogenic pathway. Direct Bcr-Abl inhibitors are initially successful for the treatment of CML but over time many patients develop drug resistance. In the present study, the effects of CM363, a novel naphthoquinone (NP...
Article
Full-text available
Human Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder which is associated with activation of Bcr-Abl-Stat5 oncogenic pathway. Direct Bcr-Abl inhibitors are initially successful for the treatment of CML but over time many patients develop drug resistance. In the present study, the effects of CM363, a novel naphthoquinone (NP...
Article
GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of...
Article
GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of...
Article
The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age,...
Article
The effects of basketball on basal concentrations of testosterone and cortisol and its associations to body composition and physical performance remain to be determined. Aim: the main aim of this study was to determine the effects of playing position on physical fitness, percentage of body fat and hormonal profile in professional basketball players...
Article
In recognition of the policies of Diabetes , specifically that “[a]t the time of submission, authors should disclose details of related papers they have authored […], similar papers in press, and any …
Article
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17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor,...
Article
Age associated fat mass accumulation could be due to dysregulation of leptin signaling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signaling through Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), insuli...
Article
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This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system. Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (...
Article
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Recent studies have demonstrated that statins reduce cell viability and induce apoptosis in various types of cancer cells. The molecular mechanisms underlying these effects are poorly understood. The JAK/STAT pathway plays an important role in the regulation of proliferation and apoptosis in many tissues, and its deregulation is believed to be invo...
Article
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The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated fun...
Article
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The extremely high energy demand elicited by sprint exercise is satisfied by an increase in oxygen consumption combined with a high glycolytic rate, leading to a marked lactate accumulation, increased AMP/ATP ratio, reduced NAD(+)/NADH.H(+) and muscle pH, which are accompanied by marked Thr(172)-AMPKα phosphorylation during the recovery period. To...
Article
Full-text available
GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-i...
Article
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To determine if the muscle signalling response to a 30 s all-out sprint exercise is modulated by the exercise mode and the endocrine response, 27 healthy volunteers were divided in 2 groups that performed isokinetic (10 men and 5 women) and isoinertial (7 men and 5 women) Wingate tests. Blood samples and vastus lateralis muscle biopsies were taken...
Article
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AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)-AMPKα phosphorylation, 10 volunt...
Article
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To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglyc...
Article
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To determine if there is a sex dimorphism in the skeletal muscle signaling response to sprint exercise, 17 men and ten women performed a 30-s Wingate test. Muscle biopsies were taken before, immediately after the exercise and at 30 and 120 min during the recovery period. Thr(172)-AMPKα, Ser(221)-ACCβ, Thy(705)-STAT3, Thr(202)/Thy(204)-ERK1/2 and Th...
Article
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This study was designed to determine whether sprint exercise activates signaling cascades linked to leptin actions in human skeletal muscle and how this pattern of activation may be interfered by glucose ingestion. Muscle biopsies were obtained in 15 young healthy men in response to a 30-s sprint exercise (Wingate test) randomly distributed into tw...
Article
Endurance exercise induces SUPPRESSOR of CYTOKINE SIGNALING 3 (SOCS3) mRNA expression in rodent skeletal muscle and endurance training overimposed on strength training blunts the hypertrophic response to strength training by an unknown mechanism. The aim of this study was to determine the effects of a concurrent strength and endurance training on f...
Article
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To determine if muscle biopsies can be repeated using a single small (5-6 mm) skin incision without inducing immediate MAPK activation or inflammation in the noninjured areas, the phosphorylation of ERK1/2, p38-MAPK, c-Jun NH(2)-terminal kinases (JNKs), IκBα, IKKα, and signal transducer and activator of transcription 3 (STAT3) was examined concurre...
Article
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The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserve...
Article
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Leptin is an adipocytokine which plays a role in the regulation of appetite, metabolic rate and fat deposition. This hormone is primarily secreted by white adipose in proportion to the size of the fat stores and acts on brain and peripheral receptors. Intracellular signalling by leptin may be produced via activation of the JAK/STAT, MAPK, AMPK and...
Article
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In rodents, endurance training increases leptin sensitivity in skeletal muscle; however, little is known about the effects of exercise on the leptin signalling system in human skeletal muscle. Thus, to determine whether chronic muscle loading increases leptin receptor (OB-R170) protein expression, body composition dual-energy X-ray absorptiometry w...
Article
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This study was designed to examine potential in vivo mechanisms of AMP-activated protein kinase (AMPK) phosphorylation inhibition and its downstream signaling consequences during the recovery period after a single bout of sprint exercise. Sprint exercise induces Thr(172)-AMPK phosphorylation and increased PGC-1alpha mRNA, by an unknown mechanism. M...
Article
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The exon-1 of the androgen receptor (AR) gene contains two repeat length polymorphisms which modify either the amount of AR protein inside the cell (GGN(n), polyglycine) or its transcriptional activity (CAG(n), polyglutamine). Shorter CAG and/or GGN repeats provide stronger androgen signalling and vice versa. To test the hypothesis that CAG and GGN...
Article
To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin signalling and signal transducer and activator of transcri...
Article
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There is a substantial body of evidence indicating that exercise prior to the pubertal growth spurt stimulates bone growth and skeletal muscle hypertrophy to a greater degree than observed during growth in non-physically active children. Bone mass can be increased by some exercise programmes in adults and the elderly, and attenuate the losses in bo...
Article
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To determine if there is a gender dimorphism in the expression of leptin receptors (OB-R170, OB-R128 and OB-R98) and the protein suppressor of cytokine signaling 3 (SOCS3) in human skeletal muscle, the protein expression of OB-R, perilipin A, SOCS3 and alpha-tubulin was assessed by Western blot in muscle biopsies obtained from the m. vastus lateral...
Article
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Human skeletal muscle expresses leptin receptor mRNA; however, it remains unknown whether leptin receptors (OB-R) are also expressed at the protein level. Fourteen healthy men (age = 33.1 +/- 2.0 yr, height = 175.9 +/- 1.7 cm, body mass = 81.2 +/- 3.8 kg, body fat = 22.5 +/- 1.9%; means +/- SE) participated in this investigation. The expression of...
Article
Since the discovery of the satellite cells in 1961 a number of studies have examined the role that these cells play on muscle hypertrophy and regeneration, and on the hypertrophy response to strength training in humans. The interest for these cells has raised in the last years due to the fact that they could be used as a vehicle in techniques of ce...
Article
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Evidence for a protective role of estradiol in neurodegenerative diseases has steadily increased over the past decade, though the mechanisms of action and the participation of true estrogen receptors (ERs) have proven a complex score. The protective effects of estrogens take place partly through pathways involving canonical ER activation, which is...
Article
Rapid oestrogen neuroprotection against beta-amyloid peptide (Abeta)-induced toxicity, a main feature of Alzheimer's disease, may be partially initiated at the plasma membrane. However, the mechanism by which this oestrogen effect occurs is unknown. In a septal murine cell line (SN56), we observed that short exposures to either 17beta-oestradiol (E...
Article
Although estrogen (E2)-related neuroprotection has been repeatedly demonstrated in different models, the involvement of non-classical estrogen receptors (ERs) in this activity remains unclear. Using SN56 murine cholinergic cell line from the basal forebrain, we present evidence indicating that an ER associated with the plasma membrane participates...