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V Moreno

Publications and source records attributed to V Moreno.

At least 19 recordsLinked to original sources
PubMed2022

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Humans↗
PubMed2006

Kinase-dependent, retinoic acid receptor-independent up-regulation of cyclooxygenase-2 by all-trans retinoic acid in human mesangial cells.

BACKGROUND AND PURPOSE: Preliminary results in human mesangial cells (MC) suggested that all-trans retinoic acid (ATRA) increased the expression of COX-2 and the production of prostaglandin E2 (PGE2), a PG with anti-inflammatory effects in MC. The aim of this work is to confirm that ATRA increases the expression of COX-2 in MC and to examine the mechanisms involved. EXPERIMENTAL APPROACH: Cultured MC were treated with ATRA. COX expression and kinase activity were analyzed by Western blot. Transcriptional mechanisms were analyzed by Northern blot, RT-PCR and promoter assays. KEY RESULTS: COX-2 and COX-1 expression and PGE2 production were increased by ATRA. COX-2 played a role in PGE2 production as production was only partially inhibited by COX-1 inhibitor SC-560. COX-2 up-regulation by ATRA was due to transcriptional mechanisms as pre-incubation with actinomycin D abolished it and ATRA increased the expression of COX-2 mRNA and the activity of a human COX-2 promoter construct, whereas post-transcriptional mechanisms were not found. Retinoic acid receptors (RAR) were not involved in the up-regulation of COX-2 by ATRA since it was not inhibited by RAR-pan-antagonists and the RAR-pan-agonist TTNPB did not up-regulate COX-2. Instead ATRA might act through a sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) since up-regulation of COX-2 was prevented by inhibition of the activation of ERK1/2 with PD098059. Also ERK1/2, as well as downstream signalling proteins from ERK1/2, remained phosphorylated when COX-2 increased 24 h later. CONCLUSIONS AND IMPLICATIONS: These results highlight the relevance of RAR-independent mechanisms to the biological effects of ATRA.

Cells, Cultured↗
PubMed2006

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Adenocarcinoma↗
PubMed2006

Increasing salt tolerance in the tomato.

In this paper, a number of strategies to overcome the deleterious effects of salinity on plants will be reviewed; these strategies include using molecular markers and genetic transformation as tools to develop salinity-tolerant genotypes, and some cultural techniques. For more than 12 years, QTL analysis has been attempted in order to understand the genetics of salt tolerance and to deal with component traits in breeding programmes. Despite innovations like better marker systems and improved genetic mapping strategies, the success of marker-assisted selection has been very limited because, in part, of inadequate experimental design. Since salinity is variable in time and space, experimental design must allow the study of genotype x environment interaction. Genetic transformation could become a powerful tool in plant breeding, but the growing knowledge from plant physiology must be integrated with molecular breeding techniques. It has been shown that the expression of several transgenes promotes a higher level of salt tolerance in some species. Despite this promising result, the development of a salt-tolerant cultivar by way of transgenesis has still not been achieved. Future directions in order to overcome the present limitations are proposed. Three cultural techniques have proved useful in tomato to overcome, in part, the effects of salinity: treatment of seedlings with drought or NaCl ameliorates the adaptation of adult plants to salinity; mist applied to tomato plants grown in Mediterranean conditions improves vegetative growth and yield in saline conditions; and grafting tomato cultivars onto appropriate rootstocks could reduce the effects of salinity.

Breeding↗
PubMed2005

Morphological criteria to distinguish cell death induced by apoptotic and necrotic treatments.

We present a comparative study of apoptotic and necrotic morphology (light and scanning electron microscopy), induced by well known experimental conditions (photodynamic treatments, etoposide, hydrogen peroxide, freezing-thawing and serum deprivation) on cell cultures. Our results indicate that morphological criteria (apoptotic cell rounding and shrinkage, and appearance of membrane bubbles in early necrosis) allow to distinguish these cell death mechanisms, and also show that, independently of the damaging agents, the necrotic process occurs in a characteristic sequence (coalescence of membrane bubbles in a single big one that detaches from cells remaining on the substrate).

Apoptosis↗
PubMed2004

Connective tissue growth factor mediates high glucose effects on matrix degradation through tissue inhibitor of matrix metalloproteinase type 1: implications for diabetic nephropathy.

High glucose concentration inhibits matrix degradation and affects the activities of the enzymes responsible, the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Connective tissue growth factor (CTGF) expression is increased in diabetic nephropathy and is a downstream mediator of TGF-beta actions. However, whether CTGF regulates matrix degradation and the mechanism of effect in diabetes has not been reported. Human mesangial cells were cultured in media containing 5 or 25 mM glucose and, in some experiments, with recombinant human (rh)CTGF (0-1000 ng/ml) and/or appropriate neutralizing antibodies. Matrix degradation was inhibited by rhCTGF in a dose-dependent manner, and the decrease in matrix degradation caused by high glucose and by TGF-beta was significantly attenuated by addition of CTGF-neutralizing antibody (by 40.2 and 69.1%, respectively). Similar to 25 mM glucose, addition of rhCTGF increased MMP-2, TIMP-1, and TIMP-3 mRNA by 2.5-, 2.1-, and 1.6-fold, respectively (P < 0.05) but had no effect on membrane-type (MT)1-MMP or TIMP-2. Addition of TIMP-1 antibody to conditioned medium abolished the decrease in degradation caused by rhCTGF and partially prevented (by 79%) the glucose-induced inhibition of matrix degradation. In vivo studies of glomeruli from diabetic and control rats showed that intensive insulin treatment prevented the increase in expression of CTGF and TIMP-1 and attenuated the decreased matrix degradation seen in diabetes. In summary, CTGF inhibits matrix degradation by increasing TIMP-1 expression, and by this action it contributes to the inhibition of matrix breakdown by high glucose, implying that CTGF has a role in the reduced matrix degradation observed in diabetic nephropathy.

Animals↗
PubMed2004

Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer.

Inflammation plays a key role in the development of colorectal cancers. We have investigated the relationship between PTGS2 (COX2) polymorphisms and colorectal cancer risk in a hospital based case-control study. We recruited 292 patients with colorectal cancer and 274 controls from new patients admitted to Bellvitge Hospital, Barcelona, Spain, from 1996 to 1998. Subjects responded to a questionnaire on risk factors. Genotypes of the eight more frequent polymorphisms of PTGS2 were determined. Two polymorphisms are located in the promoter sequence, one in the untranslated region of exon 1, one in exon 3, one in intron 5, two in the untranslated region of exon 10, and one downstream of the last polyadenylation (poly-A) signal. Associations were analysed with logistic regression models assuming a dominant effect for rare variants to increase statistical power. An association was detected between colorectal cancer and a polymorphism in the untranslated region of exon 10 of PTGS2, with an odds ratio (OR) of 2.49, 95% confidence interval (CI) of 1.17-5.32, P=0.01. A nearby polymorphism downstream of the last poly-A signal also showed a nonsignificant increase in risk (OR 2.17, 95% CI 0.99-4.78, P=0.05). Analysis of haplotypes confirmed that individuals with these variants were at increased risk of colorectal cancer (OR compared to the most frequent haplotype: 2.17, 95% CI 0.97-4.84, P=0.06) Interactions between PTGS2 genotype and use of nonsteroidal anti-inflammatory drugs and risk of colorectal cancer were also explored.

Adult↗
PubMed2004

Comparative study between the interaction of dephosphorylated amifostine (WR-1065) and amoxicilline with pBR322 in absence and presence of cisplatin by AFM.

The effect of the amoxicilline as a possible cisplatin-action protector on pBR322 DNA has been visually studied by atomic force microscopy in comparison with the modifications caused by the controversed cisplatin protector amifostine. Incubation of amoxicilline with the plasmid DNA showed aggregation and compaction of DNA. Cisplatin incubated in the same conditions with DNA produced kinks and super-coiling of the circular form. In the case of previous treatment of DNA with amoxicilline, the characteristic effect of cisplatin is only partially observed. The amoxicilline seemed to control the action of cisplatin on DNA. The initial effect of dephosphorylated amifostine (WR-1065) when this protector was incubated with the plasmid was also the formation of aggregates and the compaction of DNA. However, addition of cisplatin successively after 1 and 2 h showed the characteristic modification caused by cisplatin but only in a decreasing percentage of molecules of DNA. Both molecules, amoxicilline and WR-1065 seem to control the strong direct action of cisplatin on DNA. This effect can justify the role as protecting agent of amifostine on side effects caused by cisplatin and can open new possibilities to other agents like amoxicilline.

Amifostine↗
PubMed2004

Pd(II) and Pt(II) complexes with aromatic diamines: study of their interaction with DNA.

Pd(II) and Pt(II) new complexes with simple aromatic diamines were synthesised and characterised with the aim of studying their possible antitumour activity. The aromatic diamines chosen were 2,3-diaminotoluene (2,3 dat), 3,4-diaminotoluene (3,4 dat), 4,5-diaminoxylene (4,5 dax) and 2,3-diaminophenol (2,3 dap). The complexes, of formulae cis-[MCl(2)(diamine)], were characterised by elemental analysis, conductivity measurements, 1H, 13C(1H) and 195Pt NMR spectroscopy. The X-ray crystal structure was also resolved for the palladium complexes with 2,3-diaminotoluene and 4,5-diaminoxylene. The DNA adduct formation of the eight new complexes synthesised was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the four platinum complexes against the cisplatin resistant tumour cell line A2780cisR.

Animals↗
PubMed2004

In-plane electronic speckle pattern of interference (ESPI) with optical fibre system applied to the study of the human jaw.

The standard illumination set-up for measurement of in-plane displacement in electronic speckle pattern of interference (ESPI) requires the use of two oblique coherent beams for the illumination of the object. These two beams define a direction in the plane perpendicular to the optical axis in which the displacement can be measured, while in the perpendicular direction the interferometer has no sensitivity. In this paper, a new ESPI system for the measurement of in-plane displacements is used. The novelty presented by this assembly is the use of optical fibres to split and guide the light beams. In this way, it is possible to vary with great precision and ease the direction of the projected beams and, consequently, the direction of the plane in which the displacements undergone by the object can be studied. This set-up makes possible the study of objects with complex geometries, which have deformations with unknown symmetry. We present results obtained with this interferometer applied to the study of the mechanical behaviour of the human jaw.

Algorithms↗
PubMed2003

The expression of the Saccharomyces cerevisiae HAL1 gene increases salt tolerance in transgenic watermelon [Citrullus lanatus (Thunb.) Matsun. & Nakai.].

An optimised Agrobacterium-mediated gene transfer protocol was developed in order to obtain watermelon transgenic plants [Citrullus lanatus (Thunb.) Matsun. & Nakai.]. Transformation efficiencies ranged from 2.8% to 5.3%, depending on the cultivar. The method was applied to obtain genetically engineered watermelon plants expressing the Saccharomyces cerevisiae HAL1 gene related to salt tolerance. In order to enhance its constitutive expression in plants, the HAL1 gene was cloned in a pBiN19 plasmid under control of the 35S promoter with a double enhancer sequence from the cauliflower mosaic virus and the RNA4 leader sequence of the alfalfa mosaic virus. This vector was introduced into Agrobacterium tumefaciens strain LBA4404 for further inoculation of watermelon half-cotyledon explants. The introduction of both the neomycin phosphotransferase II and HAL1 genes was assessed in primary transformants (TG1) by polymerase chain reaction analysis and Southern hybridisation. The expression of the HAL1 gene was determined by Northern analysis, and the diploid level of transgenic plants was confirmed by flow cytometry. The presence of the selectable marker gene in the expected Mendelian ratios was demonstrated in TG2 progenies. The TG2 kanamycin-resistant plantlets elongated better and produced new roots and leaves in culture media supplemented with NaCl compared with the control. Salt tolerance was confirmed in a semi-hydroponic system (EC=6 dS m(-1)) on the basis of the higher growth performance of homozygous TG3 lines with respect to their respective azygous control lines without the transgene. The halotolerance observed confirmed the inheritance of the trait and supports the potential usefulness of the HAL1 gene of S. cerevisiae as a molecular tool for genetic engineering of salt-stress protection in other crop species.

Blotting, Northern↗
PubMed2002

The ploidy level of transgenic plants in Agrobacterium-mediated transformation of tomato cotyledons ( Lycopersicon esculentum Mill.) is genotype and procedure dependent [corrected].

A protocol avoiding the feeder-layer cell system was optimized for Agrobacterium-mediated transformation of tomato cotyledonary explants. Over 500 transgenic plants from five tomato cultivars were regenerated in 15 independent experiments. Depending on both genotype and procedure, transformation frequencies ranged from 1.8% to 11.3%. The optimal transformation rate was obtained by inoculating explants with a bacterial suspension in exponential growth ( D(600) = 10(2)-10(3) cells/ml) and transferring cotyledon explants to fresh selective regeneration medium every 3 weeks. The ploidy level of both tomato genotypes used as explant source and primary transformants, was studied by flow cytometry. The inbred lines and cultivars were diploid but a polysomatic pattern in the cotyledon explant was confirmed. The rate of tetraploid transgenic plants ranged from 24.5% to 80% and depended on both the genotype and the transformation procedure. Surprisingly, the percentages of transformed plants with higher ploidy levels were not related to the proportion of 4C and 8C nuclei in the cotyledonary tissue. For some genotypes the optimisation of the transformation rate resulted in an increase of tetraploid transgenic plants. Results obtained in this work indicate the convenience of checking the ploidy level of the primary transformants before performing basic studies or introducing tomato transgenic material in a breeding program.

Cotyledon↗
PubMed2002

Study of the modifications caused by cisplatin, transplatin, and Pd(II) and Pt(II) mepirizole derivatives on pBR322 DNA by atomic force microscopy.

Modifications of the structure of pBR322 DNA caused by interaction with cisplatin, transplatin and Pd(II) and Pt(II) mepirizole derivatives were studied. The compounds were incubated with the plasmid DNA for 24 h at 37 degrees C and then observed with an atomic force microscope. Circular DNA was used because the small tertiary structural changes are easy to monitor. Likewise, its superhelical nature mimics DNA better than certain forms of intracellular DNA such as chromatin. AFM images clearly reveal that the complexes induce changes in the topological forms of fully relaxed pBR322 DNA. Most of the compounds produce a more compact DNA structure with modified writhing number. Analysis of gel migration of the relaxed pBR322 DNA incubated with the platinum complexes provides complementary information, which is in good agreement with AFM results.

Antineoplastic Agents↗
PubMed2002

Pd(II)- and Pt(II)-cimetidine complexes. Crystal structure of trans-[Pt(N,S-cimetidine)(2)]Cl(2)(*)12H(2)O.

The influence of cimetidine on patients under cisplatin treatment for cancer is controversial. It has moderate or no effects on several types of cancer and its effects on the nephrotoxicity induced by cisplatin are uncertain. To examine the binding properties and antiproliferative effects of the known anticancer noble metals, cimetidine (cim) was complexed to platinum(II) and palladium(II). The crystal structure of the Pt-cim compound shows two molecules of cimetidine coordinated to the metal through thioether sulfur and imidazolic nitrogen whereas spectroscopic studies in solution for Pd-cim reveal that the ratio of the metal to cimetidine is 1:1 with identical coordination environments. To determine the antitumor activity of the drugs, the interaction of the metallic complexes and free cimetidine with DNA was assessed. Their cytotoxic activity was compared with that of cisplatin.

Animals↗
PubMed2002

The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen.

Many works have dealt with the study of the allergenic relevance of profilin from allergenic extracts, mainly derived from pollens and vegetable foods. Olive pollen extracts also contain a profilin allergen (Ole e 2). This protein has been characterized in detail, so the amino-acid sequence of three isoforms and the structural model of one of them are already known. The prevalence of Ole e 2 for olive allergenic patients has been evaluated by different in vivo and in vitro methods, and the results compared with those obtained for another pollen profilins.

Allergens↗
PubMed2002

Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen.

BACKGROUND: An association between Helicobacter pylori infection and heart disease has been suggested. A potential mechanism may be inflammation-induced atherogenic changes of lipoproteins, but epidemiological studies have provided conflicting results. METHODS: In a prospective multicentre study, 830 patients submitted for endoscopy and H. pylori testing were evaluated. Of the 686 H. pylori-positive patients, 487 received and 199 did not receive eradication treatment. Serum lipids and plasma fibrinogen were measured at baseline in all patients and 3 months later in those initially positive for H. pylori. RESULTS: H. pylori had no influence on baseline lipid or fibrinogen levels. Increases in high-density lipoprotein cholesterol were observed in 368 patients who received eradication treatment and in 193 untreated patients: 0.06 mmol/L (P=0.000) and 0.07 mmol/L (P=0.009), respectively. Similar minor increases in total cholesterol and triglycerides occurred in both groups. Lipid changes were related to symptom relief and a reduction in smoking. Eradication therapy was associated with a minor decrease in plasma fibrinogen irrespective of the resolution of infection. CONCLUSIONS: H. pylori has no influence on blood lipids or fibrinogen. Both the eradication of infection and symptomatic treatment without eradication are associated with minor lipid changes related to symptom relief and lifestyle modifications. Thus, the inflammatory changes associated with H. pylori are unlikely to affect lipoprotein or fibrinogen metabolism.

Adult↗