42 research outputs found
Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives
Tumours are complex systems with dynamic interactions between tumour cells, nontumour
cells, and extracellular components that comprise the tumour microenvironment (TME). The
majority of TME’s cells are cancer-associated fibroblasts (CAFs), which are crucial in extracellular
matrix (ECM) construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour
cell motility. CAF subtypes have been identified based on the expression of protein markers. CAFs
may act as promoters or suppressors in tumour cells depending on a variety of factors, including
cancer stage. Indeed, CAFs have been shown to promote tumour growth, survival and spread, and
secretome changes, but they can also slow tumourigenesis at an early stage through mechanisms that
are still poorly understood. Stromal–cancer interactions are governed by a variety of soluble factors
that determine the outcome of the tumourigenic process. Cancer cells release factors that enhance the
ability of fibroblasts to secrete multiple tumour-promoting chemokines, acting on malignant cells
to promote proliferation, migration, and invasion. This crosstalk between CAFs and tumour cells
has given new prominence to the stromal cells, from being considered as mere physical support to
becoming key players in the tumour process. Here, we focus on the concept of cancer as a non-healing
wound and the relevance of chronic inflammation to tumour initiation. In addition, we review CAFs
heterogeneous origins and markers together with the potential therapeutic implications of CAFs
“re-education” and/or targeting tumour progression inhibition.ConsejerĂa de EconomĂa, Conocimiento, Empresas y Universidad
de la Junta de AndalucĂa and European Regional Development Fund (ERDF), ref. P18-FR-2470,Ministry of Science, Innovation and Universities (ref. RTI2018-101309-B-C22)Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963
Clinical implications of inflammation in atheroma formation and novel therapies in cardiovascular diseases
PH-C is supported by an FPU grant from the Ministry of
Education, Culture and Sport. This work has been partially funded
by the University of Jaen, AcciĂłn I apoyo a la investigaciĂłn (BIO-349)
and by Modeling Nature (MNat), Project number QUAL21-11.Cardiovascular diseases (CVD) are the leading causes of death and disability in the
world. Among all CVD, the most common is coronary artery disease (CAD). CAD
results from the complications promoted by atherosclerosis, which is
characterized by the accumulation of atherosclerotic plaques that limit and
block the blood flow of the arteries involved in heart oxygenation.
Atherosclerotic disease is usually treated by stents implantation and
angioplasty, but these surgical interventions also favour thrombosis and
restenosis which often lead to device failure. Hence, efficient and long-lasting
therapeutic options that are easily accessible to patients are in high demand.
Advanced technologies including nanotechnology or vascular tissue engineering
may provide promising solutions for CVD. Moreover, advances in the
understanding of the biological processes underlying atherosclerosis can lead
to a significant improvement in the management of CVD and even to the
development of novel efficient drugs. To note, over the last years, the
observation that inflammation leads to atherosclerosis has gained interest
providing a link between atheroma formation and oncogenesis. Here, we have
focused on the description of the available therapy for atherosclerosis, including
surgical treatment and experimental treatment, the mechanisms of atheroma
formation, and possible novel therapeutic candidates such as the use of anti-
inflammatory treatments to reduce CVD.FPU grant from the Ministry of Education, Culture and SportUniversity of Jaen, Accion I apoyo a la investigacion
BIO-349Modeling Nature (MNat)
QUAL21-1
Cell surface immobilization of GABAARs in cerebellar granule cells depends on the M3/M4 cytoplasmatic loop of the alpha 1 subunit
Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain. The localization of GABA receptors type A (GABAARs) at strategically located domains of the neuronal membrane is of vital importance for fast inhibitory synapse transmission efficacy. We have shown before that the lateral mobility of GABAARs depends on subunit composition of the complex. To study the lateral mobility of GABAARs in living, cultured neurons, we transfected cerebellar granule cells with either the complete 1 GABAAR subunit or with a truncation of the 1 subunit that lacks the major intracellular loop (M3/M4). We examined the location and lateral mobility of receptors containing both versions of the 1 subunit in living neurons. From fluorescence recovery after photobleaching experiments we present novel evidences that the intracellular M3/M4 loop of the 1 subunit restricts the lateral mobility of GABAARs when expressed in neurons. In addition, our immunocytochemical studies suggested that receptors containing the truncated subunit seem to be unable to reach synaptic localizations. Here we show for the first time that the 1 intracellular loop (M3/M4) domain has a relevant role in controlling the lateral mobility of GABAARs in neurons, and we believe that this is a novel and important contribution in neurobiology of GABAA receptors
Editorial: Cellular reprogramming in development, disease, and design of cell-replacement therapies
Unifying Different Cancer Theories in a Unique TumourModel: Chronic Inflammation and Deaminases as Meeting Points
The increase in cancer incidences shows that there is a need to better understand tumour
heterogeneity to achieve efficient treatments. Interestingly, there are several common features among
almost all types of cancers, with chronic inflammation induction and deaminase dysfunctions singled
out. Deaminases are a family of enzymes with nucleotide-editing capacity, which are classified
into two main groups: DNA-based and RNA-based. Remarkably, a close relationship between
inflammation and the dysregulation of these molecules has been widely documented, which may
explain the characteristic intratumor heterogeneity, both at DNA and transcriptional levels. Indeed,
heterogeneity in cancer makes it difficult to establish a unique tumour progression model. Currently,
there are three main cancer models—stochastic, hierarchic, and dynamic—although there is no
consensus on which one better resembles cancer biology because they are usually overly simplified.
Here, to accurately explain tumour progression, we propose interactions among chronic inflammation,
deaminases dysregulation, intratumor genetic heterogeneity, cancer phenotypic plasticity, and even
the previously proposed appearance of cancer stem-like cell populations in the edges of advanced
solid tumour masses (instead of being the cells of origin of primary malignancies). The new tumour
development model proposed in this study does not contradict previously accepted models and it
may open up a window to interesting therapeutic approaches.FPU grant from the Ministry of Education, Culture and SportUniversity of Jaen, Accion I apoyo a la investigacion BIO-349Excellence Research Unit "Modeling Nature" (MNat)Junta de Andalucia
European Commission SOMM17/6109/UGRConsejeria de Salud y Familias de la Junta de Andalucia (FEDER funds) PEMP-0205-2020Ministry of Economy and Competitiveness (FEDER funds) PIE16/00045Ministry of Science, Innovation and Universities RTI2018-101309-B-C22Chair "Doctors Galera-Requena in cancer stem cell research" CMC-CTS96
Treatment resistance in pancreatic and biliary tract cancer: molecular and clinical pharmacology perspectives
Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract
cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted
therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular
mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and
changes in the tumor microenvironment. Identifying and overcoming these mechanisms is a major
focus of research: strategies being explored include combination therapies, modulation of the tumor
microenvironment, and personalized approaches.
Areas covered: We provide a current overview and discussion of the most relevant mechanisms of
resistance to chemotherapy, target therapy, and immunotherapy in both BTC and PC. Furthermore, we
compare the different strategies that are being implemented to overcome these obstacles.
Expert opinion: So far there is no unified theory on drug resistance and progress is limited. To
overcome this issue, individualized patient approaches, possibly through liquid biopsies or single-cell
transcriptome studies, are suggested, along with the potential use of artificial intelligence, to guide
effective treatment strategies. Furthermore, we provide insights into what we consider the most
promising areas of research, and we speculate on the future of managing treatment resistance to
improve patient outcomes.Award of EMBO Scientific Exchange Grant ref.: 10383, 2023ConsejerĂa de EconomĂa, Conocimiento, Empresas y Universidad de la Junta de AndalucĂa and European Regional Development Fund (ERDF), ref. P18-FR-2470, from the Ministry of Science, Innovation and Universities [ref. RTI 2018-101309-B-C22], and from the Chair “Doctors Galera-Requena in cancer stem cell
research” [CMC-CTS963].KWF Dutch
Cancer Society, Associazione Italiana per la Ricerca sul Cancro AIRCBennink Foundatio
Functionalized Nanostructures with Application in Regenerative Medicine
In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application
Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives
Intra-Articular Injections of Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National Health Care System
Intra-articular injection of platelet-rich plasma (PRP) has been established as a suitable treatment for knee osteoarthritis. Here, we present a double-blind randomized controlled clinical trial, conducted in a public Hospital of the Spanish National Health Care System, to evaluate the efficacy of injecting autologous PRP versus hyaluronic acid (HA) in knee osteoarthritis. PRP was manufactured in Malaga’s Regional Blood Center (Spain). Patients that met the eligibility criteria were randomized into a PRP group or a HA group. Pain and functional improvements were assessed pre- and post-treatment (three and six months follow-up) using the Visual Analogue Scale (VAS); the Knee and Osteoarthritis Outcome System (KOOS) scale and the European Quality of Life scale (EUROQOL). Both groups presented pain reduction at six months. The VAS scores for the PRP group improved by at least 50% from their initial value, particularly at three months following the final infiltration, with results resembling those of the HA group at six months. PRP was more effective in patients with lower osteoarthritis grades. Both treatments improved pain in knee osteoarthritis patients without statistically significant differences between them. However, PRP injection was proved to improve pain three months after the final infiltration and to be more effective in lower osteoarthritis grades
Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid
Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren–Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane®) and Group II with HA (Go-ON®). Patient’s evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA