Salvador Aliño - Academia.edu (original) (raw)

Papers by Salvador Aliño

Cells, 2021

Neuroblastoma (NB) is the most common extra-cranial malignancy in preschool children. To portray ... more Neuroblastoma (NB) is the most common extra-cranial malignancy in preschool children. To portray the genetic landscape of an overly aggressive NB leading to a rapid clinical progression of the disease, tumor DNA collected pre- and post-treatment has been analyzed. Array comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and pharmacogenetics approaches, respectively, have identified relevant copy number alterations (CNAs), single nucleotide variants (SNVs), and polymorphisms (SNPs) that were then combined into an integrated analysis. Spontaneously formed 3D tumoroids obtained from the recurrent mass have also been characterized. The results prove the power of combining CNAs, SNVs, and SNPs analyses to assess clonal evolution during the disease progression by evidencing multiple clones at disease onset and dynamic genomic alterations during therapy administration. The proposed molecular and cytogenetic integrated analysis empowers the disease follow-up and the pre...

International journal of molecular sciences, Jan 25, 2024

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Biology of the Cell, 1989

Prostaglandins are secreted by a variety of tumor cell lines. The prostaglandin synthesis inhibit... more Prostaglandins are secreted by a variety of tumor cell lines. The prostaglandin synthesis inhibitor indomethacin (IND) inhibits 3LL tumor growth after both intramuscular or intrasplenic transplantation (45 and 72%, respectively). Moreover, when tumor cells were cultured with IND, the sensitivity of 3LL cells to natural cytotoxic (NC) effector cells was increased (30%) and a higher cytotoxicity was reached when both target and effector cells were treated. This effect was reversed partially or totally when the assay was performed in the presence of laminin or an octapeptide from the laminin B1 chain. In addition, we correlate the increased cytotoxicity mediated by IND with an enhanced ability of 3LL tumor cells to bind labeled laminin (55%). In summary, our results show that the blockage or modulation of cell surface laminin binding components could be directly correlated with the sensitivity of tumor target cells to be eliminated by way of natural cytotoxicity.

Journal of Immunology, Apr 15, 1986

Drug transfer into lymphoblasts mediated by liposomes bound to distinct sites on H-2 encoded I-A,... more Drug transfer into lymphoblasts mediated by liposomes bound to distinct sites on H-2 encoded I-A, I-E, and K molecules.

Biochem Biophys Res Commun, 1993

Experientia, 1984

The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatos... more The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.

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Revista española de fisiología, 1983

The inhibitory action of dopamine on basal gastric secretion and that stimulated by pentagastrin ... more The inhibitory action of dopamine on basal gastric secretion and that stimulated by pentagastrin with previous administration of domperidone in 26 male patients, between 18 and 48 years of age, suffering duodenal ulcer has been studied. The administration of domperidone (0.25 mg/kg) produces a significant reduction of the inhibitory action of dopamine on basal gastric secretion and that stimulated by pentagastrin at dose 0.15 microgram/kg/h. Besides dopamine shows a minor, non significant, inhibitory action on acid gastric secretion stimulated by maximal doses of pentagastrin, while showing no differences against the group without administration of domperidone.

Transplantation Proceedings, 2011

Pharmacogenetics explains part of the interindividual variability in drug responses. Many publish... more Pharmacogenetics explains part of the interindividual variability in drug responses. Many published works about the effects of single nucleotide polymorphisms (SNPs) on immunosuppressive drug blood levels present contradictory results. We evaluated the SNPs in ABCB1 (glycoprotein P) and CYP3A5 (metabolic enzyme) genes, seeking correlate them with tacrolimus or cyclosporine levels during the first year after heart transplantation. One blood sample was obtained from each of 41 patients: 26 treated with cyclosporine and 15 with tacrolimus. We characterize the SNPs rs1045642,

Experimental Cell Research, 1988

This study compares the in uivo effect of exogenous administration of prostaglandin E2 (30 @kg) a... more This study compares the in uivo effect of exogenous administration of prostaglandin E2 (30 @kg) and its precursor, arachidonic acid (30 @kg), with the effect of indomethacin (5 mg/kg) on the 6-['Hlthymidine uptake of antral mucosa of mice by autoradiographical methods. Likewise, the effect of somatostatin (30 &kg) on 6-[jH]thymidine uptake is studied. Evaluation of the number of labeled cells, in the histological sections of the gastric mucosa, showed that arachidonic acid, prostaglandin E2, and somatostatin induced an increase in the number of labeled cells (107, 44, and 45%, respectively), while indomethatin induced a decrease of 32 % compared to the control group. These results suggest that prostaglandins may mediate stimlatory effects on thymidine uptake of gastric mucosa cells in the first step after drug administration. 0 1988 Academic press, IK.

Gene Ther Mol Biol, 2005

Summary Success has been achieved with nonviral gene delivery to mouse liver, resulting in long-t... more Summary Success has been achieved with nonviral gene delivery to mouse liver, resulting in long-term therapeutic plasma levels of human α-1 antitrypsin (hAAT) protein, employing the hydrodynamic procedure. Now we contribute to explore the mechanism involved in the successful procedure, with the aim of circumventing the existing serious limitations for application to clinical practice. The results from mouse hydrodynamic gene

Inflammatory Bowel Diseases, Aug 1, 2017

Background: The aim of this work is to evaluate the efficacy of hydrodynamic venous IL10 gene del... more Background: The aim of this work is to evaluate the efficacy of hydrodynamic venous IL10 gene delivery to "ex vivo" human colon segments and to determine its potential interest in Crohn's disease treatment. Methods: Twenty human colon segments were obtained from surgical resections. Hydrodynamic transfection through the main vein of the pedicle with 50 mL of hIL10 plasmid (20 mg/mL) solution was performed on 13 of them. Tissue sections were cultured and DNA, RNA, and protein copies were determined after 1, 2, and 4 days. Data obtained were compared with 6 nontransfected specimens. Finally, 1 specimen was injected with gold nanoparticles, and their distribution was examined under electron microscope. Results: IL10 DNA levels were higher in treated tissues than in controls (P , 0.001), decreasing along time. The amount of hIL10 RNA was significantly increased in treated tissues when compared with controls (P ¼ 0.001). The indexes of protein IL10 translation in treated groups were much higher (P , 0.001) than the basal production. The protein expression was higher in transfected tissue (10-50-fold, with respect to control tissue); this difference being established during the first hours and maintained during, at least, 4 days. With electron microscopy, we hardly observed large (15 nm) gold nanoparticles within the tissue, always in the submucosa. However, multiple small (4 nm) nanoparticles were observed within the cytoplasm of enterocytes in mucosa. Conclusions: Hydrodynamic procedure efficiently delivers the IL10 gene to the human colon, achieving levels of tissue protein expression high enough to mediate pharmacological effects with interest in controlling immune response in patients with Crohn's disease.

PubMed, Nov 1, 1996

B16 melanoma-bearing mice were treated with anti-interleukin 4 antibody, indomethacin or its comb... more B16 melanoma-bearing mice were treated with anti-interleukin 4 antibody, indomethacin or its combination to evaluate the ability of the primary tumor to induce lung metastasis and the antitumor host response. Flow cytometry of tumor cells incubated with sera from tumor-bearing mice showed B16 melanoma to induce a significant antitumor humoral response (39.0 +/- 1.1% positive cells versus 1.8 +/- 0.9% in the control). The treatment of tumor-bearing mice with antimouse anti-interleukin 4 monoclonal antibody plus indomethacin significantly increased (P < .01) the mean value of lung metastasis (from 6.1 +/- 3.0 in the controls to 50.8 +/- 21.8). Also, a significant increase in natural cytotoxicity against tumor cells was observed when both peripheral blood mononuclear cells and splenocytes were used as effector cells. In contrast, an antibody-dependent cellular cytotoxicity decrease was found with effector cells from both normal and tumor-bearing mice. In the former, the antibody-dependent cellular cytotoxicity decrease was 49.4% and 58.4% (P < .05) for peripheral blood mononuclear cells and splenocytes, whereas in the second case the decrease was 40.7% (P < .05) and 29.1% (P < .01), respectively. These results suggest that an efficient antibody-dependent cellular cytotoxicity response might be necessary to secure an effective host antitumor immune response.

Experimental Cell Research, Dec 1, 1988

Pharmacogenomics, Jul 1, 2019

Pharmacogenetics (PGx) in clinical practice is a tool that the clinician can use to guide, in a p... more Pharmacogenetics (PGx) in clinical practice is a tool that the clinician can use to guide, in a personalized way, the most suitable treatment that will be administered to the patient. The objective of this review is to summarize in a practical and accessible rational way, the advances that currently exist for the application of PGx in colorectal cancer chemotherapy management through the study of the patients' germline polymorphisms. To define the polymorphisms that can be applied, we rely on three fundamental cornerstones: the recommendations of drug regulatory agencies; the implementation guidelines prepared by expert consortia in PGx and information from clinical annotations (the drug/polymorphism relation) according to the scientific level of evidence assigned by PharmGKB experts.

Pharmacogenomics Journal, Dec 8, 2015

Introduction and hypothesis The aim of this review was to investigate the impact of native tissue... more Introduction and hypothesis The aim of this review was to investigate the impact of native tissue repair for pelvic organ prolapse (POP) on overall sexual function and dyspareunia. Methods Cochrane Incontinence Group Specialized Register of Controlled Trials, The Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were searched for trials of prolapse surgery assessing sexual function and dyspareunia before and after surgery. We assessed observational studies and randomized controlled trials investigating the impact of surgical correction of POP on sexual function. Surgical interventions assessed were anterior and/or posterior repair with or without a vaginal hysterectomy. Studies including patients undergoing concurrent incontinence surgery or vaginal mesh insertion were excluded from the analysis. Dyspareunia was analyzed separately. Results We identified 674 potential citations, of which 14 articles assessed sexual function and/or dyspareunia before and after traditional prolapse surgery. The results suggest evidence for significant improvement in sexual function postsurgery, with a standardized mean difference of −0.55, 95 % confidence interval (CI) −0.68 to −0.43 in favor of surgical correction. Dyspareunia rates were also significantly improved postoperatively, with overall odds ratio of at least 2.5 times as likely as the chances of deterioration. Discussion Sexual function is significantly improved and dyspareunia significantly reduced following native tissue prolapse surgery. There were several methodological problems with the quality of the primary research, particularly related to study heterogeneity, use of different outcome measures, and absence of well-designed randomized controlled trials.

European Surgical Research, 2013

Several studies report results that suggest the need of vascularization blocking for efficient ge... more Several studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 μg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital constants were monitored during the surgery to assess the safety of the procedure. Basal systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3 mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm, reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained above 98% during the intervention, and no relevant changes were observed in the ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively). These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s injection. Efficiency of gene transfer was studied with simultaneous (cava and portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver tissue samples were collected 24 h after injection and qPCR was carried out on each lobe sample. The results confirmed the efficiency of the procedure. Gene delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA) and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene transcription showed no significant differences between 20 ml/s (15,701.8-21,475.8 eGFP RNA copies/100 ng of total

Transplantation Proceedings, Oct 1, 2010

Pharmacogenetics is the study of the cause of various individual responses to the same pharmacolo... more Pharmacogenetics is the study of the cause of various individual responses to the same pharmacologic therapy. Genetic alterations in a single nucleotide in the genes responsible for transport and metabolism of an immunosuppression drug may modify patient response. Although pharmacogenetics is of interest, its clinical relevance remains to be demonstrated. The objective of the present study was to evaluate the effect of single-nucleotide polymorphisms (SNPs) in renal transplant recipients and their donors relative to blood concentrations of tacrolimus in the first 2 weeks posttransplantation. Seventy-one blood samples each from renal transplant recipients and their donors were analyzed using a genetic analysis system (MassARRAY; Sequenom, Inc, San Diego, California) in an attempt to characterize the more relevant SNPs of the ABCB1 and CYP3A5 genes for correlation with recipient trough concentrations of drug. Two-way analysis of variance and Bonferroni post hoc tests were used. In agreement with theoretical predictions, the wild-type genotype in ABCB1 SNPs (CC) tended to stabilize drug concentrations within the therapeutic range, whereas the T variant induced a mean increase in blood concentrations of more than 60%. These findings are in agreement with statistical tests that compared mean concentrations in various recipient-donor populations and found significant differences between them (P&amp;amp;amp;amp;amp;lt;.001) in CC vs TT, and P&amp;amp;amp;amp;amp;lt;.01 in CT vs TT). Donor genotype did not seem to be relevant. However, further studies are required to achieve more robust conclusions.

Current Drug Metabolism, Mar 28, 2018

Background: Anthracyclines in combination with cytarabine have been the standard therapy for acut... more Background: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. Methods: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity. Results: Polymorphisms in the main enzymes of anthracyclines metabolism (CBR, AKR, NQO1, NOS3) have been related to lower enzymatic activity and higher cardiotoxicity. Moreover, variant alleles in the genes of carcinogens and chemotherapy neutralizing enzymes (GST, SULT, NADP(H) oxidase) have been associated with ROS generation and drug efficacy, influencing the survival rates and cardiac toxicities. In addition, genetic variability in the transporters of anthracyclines could affect the intake in cells, including influx (SLC28A3, SLC22A12, SLCO1B1) and efflux transporters (ABCB1, ABCC1, ABCC3, ABCG2). Conclusion: The knowledge of the role of pharmacogenetics in anthracyclines metabolism could explain the differences observed in their disposition in leukemic cells. These genetic variants are proposed biomarkers in clinical practice in order to individualize chemotherapy schemes, potentially increasing the effectiveness and reducing the toxicities.