Ramon Messeguer - Academia.edu (original) (raw)
Papers by Ramon Messeguer
PLOS Computational Biology
Deciphering the mechanisms of regulation of metabolic networks subjected to perturbations, includ... more Deciphering the mechanisms of regulation of metabolic networks subjected to perturbations, including disease states and drug-induced stress, relies on tracing metabolic fluxes. One of the most informative data to predict metabolic fluxes are 13 C based metabolomics, which provide information about how carbons are redistributed along central carbon metabolism. Such data can be integrated using 13 C Metabolic Flux Analysis (13 C MFA) to provide quantitative metabolic maps of flux distributions. However, 13 C MFA might be unable to reduce the solution space towards a unique solution either in large metabolic networks or when small sets of measurements are integrated. Here we present parsimonious 13 C MFA (p 13 CMFA), an approach that runs a secondary optimization in the 13 C MFA solution space to identify the solution that minimizes the total reaction flux. Furthermore, flux minimization can be weighted by gene expression measurements allowing seamless integration of gene expression data with 13 C data. As proof of concept, we demonstrate how p 13 CMFA can be used to estimate intracellular flux distributions from 13 C measurements and transcriptomics data. We have implemented p 13 CMFA in Iso2Flux, our in-house developed isotopic steady-state 13
Journal of inorganic biochemistry, Jan 15, 2018
Journal of Organometallic Chemistry
Plant Systematics and Evolution, 1998
The genus Cheirolophus is a good example of a genus with a western Mediterranean distribution, wi... more The genus Cheirolophus is a good example of a genus with a western Mediterranean distribution, with an important centre of speciation in Macaronesia. We carried out an electrophoretic study on representatives of Iberian-North African species of Cheirolophus as well as species from the Canaries. In addition, some species of the genera Centaurea, Crupina and Serratula were examined. Our results show high genetic identities between taxa and low genetic diversity in Cheirolophus from the Canaries. This is the same pattern found in plants from other oceanic archipelagos and it suggests a recent colonization of the Canaries by the genus Cheirolophus. The Iberian species exhibit high genetic identities, suggesting that the genus as a whole is younger than has been suggested. Cluster analysis shows little correlation between accepted taxonomic delimitation of the species of Cheirolophus and isozyme variation, which points towards very recent speciation in the genus; not only in the Canarian species, but also in the continental group. On the other hand, cluster analysis reinforces the segregation of Cheirolophus as a genus distinct from Centaurea and supports a closer relationship to the genus Serratula. Cheirolophus was described by CASSINI (1817) on the basis of the Linnean species Centaurea sempervirens L. The genus was not widely accepted, as has been the case with many others described by CASSlM. BOISSmR (1839-1845) included in bis genus Ptosimopappus Bolss. all species of Centaurea sect. Cheirolophus, together with species of Centaurea sectt. Microlophus and Ptosimopappus. As happened with the suggestion of CASSINI (1817), this classification was not widely accepted and Cheirolophus was generally considered a section of Centaurea. HOLUB (1973) and DOSTÄL (1975) recognized Cheirolophus at the generic level. Nowadays, even authors who maintain a very broad concept of Centaurea (e.g. BREMER 1994), also segregate Cheirolophus as a distinct genus. The evidence for the maintenance of this genus is substantial. The most peculiar features that isolate Cheirolophus from Centaurea are the anatomy of the achenes, pollen type (Serratula type in the classification of WAGEYITZ 1955) and a geographic distribution limited to the western Mediterranean and Macaronesia.
Plant Mol Biol, 1993
ABSTRACT The sequence of an -tubulin from Prunus amygdalus has been obtained by cDNA cloning. Whe... more ABSTRACT The sequence of an -tubulin from Prunus amygdalus has been obtained by cDNA cloning. When this sequence is compared to that of the Tub1 gene from maize it shows a very high degree of similarity, much higher than any of the -tubulin sequences reported so far from plants. The expression of this gene is high in the stages of seed development where a high divisional activity is present. It is preferentially expressed in the radicular tissues as it is gene Tub1 in maize. Southern analysis indicates that this gene may from a subfamily of -tubulin genes having similar sequence and tissue specificity and existing at least in maize and in Prunus.
Scientia Horticulturae, 1987
Plant Physiology and Biochemistry, May 1, 1999
The plant hormone abscisic acid (ABA) is necessary for the regulation of several aspects during s... more The plant hormone abscisic acid (ABA) is necessary for the regulation of several aspects during seed development and for the response to environmental stresses such as desiccation, salt and cold. An important part of the physiological response to ABA is achieved through gene expression. Although different signal molecules have been identified, the signal transduction pathway from ABA perception to the induction of specific genes is not very well established yet. In particular, phosphorylation and dephosphorylation events have been identified as important in ABA signalling. A great effort has been focused on analysing the promoters of ABA-responsive genes in order to identify cis-and transacting elements that mediate transcriptional regulation. Many different proteins accumulate in response to water deficit, some of them with a clear function in protecting the cells against dehydration. Other proteins, whose function is not completely understood, include LEA proteins that accumulate during late embryogenesis and in response to ABA.
Dalton transactions (Cambridge, England : 2003), Jan 3, 2015
The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives ... more The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH2CH(CH3)C10H6}(L)] [L = SOMe2 ( or ), L = PPh3 ( or ), L = P(4-FC6H4)3 (), L = P(CH2)3N3(CH2)3 ()], cycloplatinated cationic complexes [Pt{(R)-NH2CH(CH3)C10H6}{L}]Cl [L = Ph2PCH2CH2PPh2 (), L = (C6F5)2PCH2CH2P(C6F5)2 ()] and the Pt(ii) coordination compound trans-[PtCl2{(R)-NH2CH(CH3)C10H6}2] (). The X-ray molecular structure of is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/...
Carcinogenesis, Jan 26, 2015
The members of the human Regulators of Calcineurin (RCAN) protein family are endogenous regulator... more The members of the human Regulators of Calcineurin (RCAN) protein family are endogenous regulators of the calcineurin (CN)- cytosolic nuclear factor of activated T-cells (NFATc) pathway activation. This function is explained by the presence of a highly conserved CIC motif in RCAN proteins, which has been shown to compete with NFATc for the binding to CN and therefore are able to inhibit NFATc dephosphorylation and activation by CN. Very recently, emerging roles for NFATc proteins in transformation, tumor angiogenesis and metastasis have been described in different cancer cell types. In the present work, we report that the overexpression of RCAN3 dramatically inhibits tumor growth and tumor angiogenesis in an orthotopic human breast cancer model. We suggest that RCAN3 exerts these effects in a CN dependent manner, as mutation of the CIC motif in RCAN3 abolishes the tumor suppressor effect. Moreover, the expression of the EGFP-R3(178-210) peptide, spanning the CIC motif of RCAN3, is a...
Plant molecular biology, 1993
The sequence of an alpha-tubulin from Prunus amygdalus has been obtained by cDNA cloning. When th... more The sequence of an alpha-tubulin from Prunus amygdalus has been obtained by cDNA cloning. When this sequence is compared to that of the Tub alpha 1 gene from maize it shows a very high degree of similarity, much higher than any of the alpha-tubulin sequences reported so far from plants. The expression of this gene is high in the stages of seed development where a high divisional activity is present. It is preferentially expressed in the radicular tissues as it is gene Tub alpha 1 in maize. Southern analysis indicates that this gene may form a subfamily of alpha-tubulin genes having similar sequence and tissue specificity and existing at least in maize and in Prunus.
Journal of Organometallic Chemistry, 2014
ABSTRACT The study of the reactivity of the novel pyrazole derivative [1-{MeOe(CH2)(2)-}-3,5-PH2-... more ABSTRACT The study of the reactivity of the novel pyrazole derivative [1-{MeOe(CH2)(2)-}-3,5-PH2-(C3HN2)] (1) with Na-2[PdCl4] or Pd(OAc)(2) under different experimental conditions has allowed us to isolate and characterize the trans-isomers of [Pd{[1-{MeOe(CH2)(2)-}-3,5-PH2-(C3HN2)]}(2)(X)(2)] [X = Cl (2) or OAc (3)] and the di-m-ligand bridged cyclopalladated complexes [Pd{kappa(2),C,N[1-{MeOe(CH2)(2)-}-3-(C6H4), 5-Ph-(C3HN2)]}(mu-X)](2) [X = OAc (4) or Cl (5)]. Further treatment of compounds 4 or 5 with PPh3 in CH2Cl2 produced the bridge splitting and the formation of [Pd{kappa(2),C,N[1-{MeOe(CH2)(2)-}-3-(C6H4), 5-Ph-(C3HN2)]}X(PPh3)] [X = OAc (6) or Cl (7)]. The cytotoxic assessment of the free ligand (1) and the Pd(II) complexes on the two breast cancer cell lines MCF7 and MDA-MB231 reveals that: a) compound 1 is less active than its analogue [1-{Me2N-(CH2)(2)-}-3,5-Ph(2)e(C3HN2)] (Ic) and b) palladacycles 4-7 showed a remarkable cytotoxic activity in the MDA-MB231 cell line (with IC50 values in the range 9.1-14.4 mu M).
Oncogenesis, 2014
Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prog... more Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood. We showed that extracellular S100P stimulates pancreatic carcinoma BxPC3 cell line by promoting cell proliferation. We also demonstrated that S100P induces, in this cell line, the phosphorylation of IkBa and the secretion of matrix metalloproteinase 9 (MMP-9). In addition, treatment with S100P protected cells from injuries induced by the cytotoxic agent Gemcitabine. On the basis of these results, we developed function-blocking anti-S100P monoclonal antibodies (mAbs) that abolished all of its in vitro activities. Furthermore, in vivo treatment with the candidate 2H8 antibody decreased tumor growth and liver metastasis formation in a subcutaneous and orthotopic BxPC3 tumor model. We conclude here that a therapeutic strategy blocking the extracellular activity of S100P by means of specific mAbs could be an attractive therapeutic approach as a single agent or in combination with target-directed or chemotherapeutic drugs to treat pancreatic cancer.
Organometallics, 2014
ABSTRACT The cyclopalladation of a series of symmetric diimines with the formula (RC6H4CHNZ)2, w... more ABSTRACT The cyclopalladation of a series of symmetric diimines with the formula (RC6H4CHNZ)2, where Z = CH2 or (CH2)2OCH2 and R = p-Cl, p-OMe, p-NO2, and o-Cl, is described. Optimal conditions to obtain the dimetalated compounds were found to be palladium(II) acetate, in toluene, at 60 °C and with a reaction time of 2−4 h. The reactivity of the dimetalated compounds with monodentate, bidentate, and bis(monodentate) Lewis bases was also studied. The cytotoxic activity of some selected compounds was evaluated against a panel of adenocarcinoma cell lines (colon HCT116 and breast MCF7 and MDA-MB231). Compounds containing the fragment NCH2CH2OCH2CH2OCH2CH2N exhibited a remarkable cytotoxic activity in the three cancer cells assayed, but complexes containing the NCH2CH2N fragment showed no activity. It seems that the length and flexibility of the central saturated chain in the imine molecule, as well as its lipophilicity and hydrophilicity, explain the different cytotoxicity of the two series of coordination compounds here reported.
European journal of medicinal chemistry, 2014
Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a... more Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively. Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity over A549 cells mainly through the induction of apoptosis (38 and 31-fold increase in early apoptotic cells, respectively).
Journal of inorganic biochemistry, 2014
The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition... more The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1-4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1-5 was in between the ranges of activity ...
Annals of Surgery, 2014
The aim of this study was to investigate the effect of postoperative peritoneal infection on prol... more The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer. Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may enhance tumor progression features of residual cancer cells. Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008-March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n=47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n=47).In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serum and peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities. Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140±85 vs control: 94±30; P=0.016) and cell invasion (infection: 117±31 vs control: 103±16; P=0.024) capacities of cancer cell lines. With serum samples, these effects were only observed in cell migration assays (infection: 98±28 vs control: 87±17; P=0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P=0.032). Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors.
TAG Theoretical and Applied Genetics, 2001
A map with 51 markers (46 RFLPs and five isozymes) was constructed using an interspecific F 2 pop... more A map with 51 markers (46 RFLPs and five isozymes) was constructed using an interspecific F 2 population between 'Garfi' almond (Prunus amygdalus Batsch.) and 'Nemared' peach [Prunus persica (L.) Batsch.]. This map was developed by selecting markers covering most of the distance of the eight linkage groups from previously constructed Prunus maps. The markers studied in this population mapped to seven linkage groups instead of the eight expected in Prunus. Markers belonging to groups 6 and 8 in previous maps formed a single group in the 'Garfi'×'Nemared' F 2 and several marker pairs placed in different groups in other maps exhibited tight linkages. The study of pollen fertility and chromosome behavior during meiosis in the F 1 generation allowed us to confirm the hypothesis that a reciprocal translocation exists between 'Garfi' and 'Nemared'. Based on independent evidence of linkage between markers and pollen fertility data in the F 2 population, we concluded that the breakpoint of the reciprocal translocation was placed between markers AC50 and AG26A in group 6 and between markers AG112A and FG230A in group 8.
TAG Theoretical and Applied Genetics, 1998
A map with 246 markers (11 isozymes and 235 RFLPs) was constructed using an interspecific F popul... more A map with 246 markers (11 isozymes and 235 RFLPs) was constructed using an interspecific F population between almond (cv Texas) and peach (cv Earlygold). RFLPs were obtained using 213 probes from the genomic and cDNA libraries of different species (almond, peach, P. ferganensis, cherry, plum and apple), including 16 almond probes which correspond to known genes. All markers were distributed in eight linkage groups, the same as the basic chromosome number of the genus, covering a total distance of 491 cM. The average map density was 2.0 cM/marker and only four gaps of 10 cM or more were found; the two largest gaps were 12 cM each. This map was compared with one constructed previously with an intraspecific almond population sharing 67 anchor loci. Locus order was nearly identical and distances were not significantly different. A large proportion of the mapped loci (46%) had skewed segregations; in approximately half of them, the distortion was due to an excess of heterozygotes. One of the distorted regions Communicated by M. A. Saghai Maroof
Theoretical and Applied Genetics, 1995
Inheritance and linkage studies were conducted with seven isozyme genes and 120 RFLPs in the F 1 ... more Inheritance and linkage studies were conducted with seven isozyme genes and 120 RFLPs in the F 1 progeny of a cross between almond cultivars 'Ferragnes' and 'Tuono'. RFLPs were detected using 57 genomic and 43 cDNA almond clones. Eight of the cDNA probes corresponded to known genes (extensin, prunin (2), ~-tubulin, endopolygalacturonase, oleosin, actin depolymerizing factor and phosphoglyceromutase). Single-copy clones were found more frequently in the cDNA (65%) than in the genomic libraries (26%). Two maps were elaborated, one with the 93 loci heterozygous in 'Ferragnes' and another with the 69 loci heterozygous in 'Tuono'. Thirty-five loci were heterozygous in both parents and were used as bridges between both maps. Most of the segregations (91%) were of the 1:1 or 1 : 1 : 1 : 1 types, and data were analyzed as if they derived from two backcross populations. Eight linkage groups covering 393 cM in 'Ferragnes' and 394 in 'Tuono' were found for each map. None of the loci examined in either map was found to be unlinked. Distorted segregation ratios were mainly concentrated in two linkage groups of the 'Ferragnes' map.
PLOS Computational Biology
Deciphering the mechanisms of regulation of metabolic networks subjected to perturbations, includ... more Deciphering the mechanisms of regulation of metabolic networks subjected to perturbations, including disease states and drug-induced stress, relies on tracing metabolic fluxes. One of the most informative data to predict metabolic fluxes are 13 C based metabolomics, which provide information about how carbons are redistributed along central carbon metabolism. Such data can be integrated using 13 C Metabolic Flux Analysis (13 C MFA) to provide quantitative metabolic maps of flux distributions. However, 13 C MFA might be unable to reduce the solution space towards a unique solution either in large metabolic networks or when small sets of measurements are integrated. Here we present parsimonious 13 C MFA (p 13 CMFA), an approach that runs a secondary optimization in the 13 C MFA solution space to identify the solution that minimizes the total reaction flux. Furthermore, flux minimization can be weighted by gene expression measurements allowing seamless integration of gene expression data with 13 C data. As proof of concept, we demonstrate how p 13 CMFA can be used to estimate intracellular flux distributions from 13 C measurements and transcriptomics data. We have implemented p 13 CMFA in Iso2Flux, our in-house developed isotopic steady-state 13
Journal of inorganic biochemistry, Jan 15, 2018
Journal of Organometallic Chemistry
Plant Systematics and Evolution, 1998
The genus Cheirolophus is a good example of a genus with a western Mediterranean distribution, wi... more The genus Cheirolophus is a good example of a genus with a western Mediterranean distribution, with an important centre of speciation in Macaronesia. We carried out an electrophoretic study on representatives of Iberian-North African species of Cheirolophus as well as species from the Canaries. In addition, some species of the genera Centaurea, Crupina and Serratula were examined. Our results show high genetic identities between taxa and low genetic diversity in Cheirolophus from the Canaries. This is the same pattern found in plants from other oceanic archipelagos and it suggests a recent colonization of the Canaries by the genus Cheirolophus. The Iberian species exhibit high genetic identities, suggesting that the genus as a whole is younger than has been suggested. Cluster analysis shows little correlation between accepted taxonomic delimitation of the species of Cheirolophus and isozyme variation, which points towards very recent speciation in the genus; not only in the Canarian species, but also in the continental group. On the other hand, cluster analysis reinforces the segregation of Cheirolophus as a genus distinct from Centaurea and supports a closer relationship to the genus Serratula. Cheirolophus was described by CASSINI (1817) on the basis of the Linnean species Centaurea sempervirens L. The genus was not widely accepted, as has been the case with many others described by CASSlM. BOISSmR (1839-1845) included in bis genus Ptosimopappus Bolss. all species of Centaurea sect. Cheirolophus, together with species of Centaurea sectt. Microlophus and Ptosimopappus. As happened with the suggestion of CASSINI (1817), this classification was not widely accepted and Cheirolophus was generally considered a section of Centaurea. HOLUB (1973) and DOSTÄL (1975) recognized Cheirolophus at the generic level. Nowadays, even authors who maintain a very broad concept of Centaurea (e.g. BREMER 1994), also segregate Cheirolophus as a distinct genus. The evidence for the maintenance of this genus is substantial. The most peculiar features that isolate Cheirolophus from Centaurea are the anatomy of the achenes, pollen type (Serratula type in the classification of WAGEYITZ 1955) and a geographic distribution limited to the western Mediterranean and Macaronesia.
Plant Mol Biol, 1993
ABSTRACT The sequence of an -tubulin from Prunus amygdalus has been obtained by cDNA cloning. Whe... more ABSTRACT The sequence of an -tubulin from Prunus amygdalus has been obtained by cDNA cloning. When this sequence is compared to that of the Tub1 gene from maize it shows a very high degree of similarity, much higher than any of the -tubulin sequences reported so far from plants. The expression of this gene is high in the stages of seed development where a high divisional activity is present. It is preferentially expressed in the radicular tissues as it is gene Tub1 in maize. Southern analysis indicates that this gene may from a subfamily of -tubulin genes having similar sequence and tissue specificity and existing at least in maize and in Prunus.
Scientia Horticulturae, 1987
Plant Physiology and Biochemistry, May 1, 1999
The plant hormone abscisic acid (ABA) is necessary for the regulation of several aspects during s... more The plant hormone abscisic acid (ABA) is necessary for the regulation of several aspects during seed development and for the response to environmental stresses such as desiccation, salt and cold. An important part of the physiological response to ABA is achieved through gene expression. Although different signal molecules have been identified, the signal transduction pathway from ABA perception to the induction of specific genes is not very well established yet. In particular, phosphorylation and dephosphorylation events have been identified as important in ABA signalling. A great effort has been focused on analysing the promoters of ABA-responsive genes in order to identify cis-and transacting elements that mediate transcriptional regulation. Many different proteins accumulate in response to water deficit, some of them with a clear function in protecting the cells against dehydration. Other proteins, whose function is not completely understood, include LEA proteins that accumulate during late embryogenesis and in response to ABA.
Dalton transactions (Cambridge, England : 2003), Jan 3, 2015
The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives ... more The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH2CH(CH3)C10H6}(L)] [L = SOMe2 ( or ), L = PPh3 ( or ), L = P(4-FC6H4)3 (), L = P(CH2)3N3(CH2)3 ()], cycloplatinated cationic complexes [Pt{(R)-NH2CH(CH3)C10H6}{L}]Cl [L = Ph2PCH2CH2PPh2 (), L = (C6F5)2PCH2CH2P(C6F5)2 ()] and the Pt(ii) coordination compound trans-[PtCl2{(R)-NH2CH(CH3)C10H6}2] (). The X-ray molecular structure of is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/...
Carcinogenesis, Jan 26, 2015
The members of the human Regulators of Calcineurin (RCAN) protein family are endogenous regulator... more The members of the human Regulators of Calcineurin (RCAN) protein family are endogenous regulators of the calcineurin (CN)- cytosolic nuclear factor of activated T-cells (NFATc) pathway activation. This function is explained by the presence of a highly conserved CIC motif in RCAN proteins, which has been shown to compete with NFATc for the binding to CN and therefore are able to inhibit NFATc dephosphorylation and activation by CN. Very recently, emerging roles for NFATc proteins in transformation, tumor angiogenesis and metastasis have been described in different cancer cell types. In the present work, we report that the overexpression of RCAN3 dramatically inhibits tumor growth and tumor angiogenesis in an orthotopic human breast cancer model. We suggest that RCAN3 exerts these effects in a CN dependent manner, as mutation of the CIC motif in RCAN3 abolishes the tumor suppressor effect. Moreover, the expression of the EGFP-R3(178-210) peptide, spanning the CIC motif of RCAN3, is a...
Plant molecular biology, 1993
The sequence of an alpha-tubulin from Prunus amygdalus has been obtained by cDNA cloning. When th... more The sequence of an alpha-tubulin from Prunus amygdalus has been obtained by cDNA cloning. When this sequence is compared to that of the Tub alpha 1 gene from maize it shows a very high degree of similarity, much higher than any of the alpha-tubulin sequences reported so far from plants. The expression of this gene is high in the stages of seed development where a high divisional activity is present. It is preferentially expressed in the radicular tissues as it is gene Tub alpha 1 in maize. Southern analysis indicates that this gene may form a subfamily of alpha-tubulin genes having similar sequence and tissue specificity and existing at least in maize and in Prunus.
Journal of Organometallic Chemistry, 2014
ABSTRACT The study of the reactivity of the novel pyrazole derivative [1-{MeOe(CH2)(2)-}-3,5-PH2-... more ABSTRACT The study of the reactivity of the novel pyrazole derivative [1-{MeOe(CH2)(2)-}-3,5-PH2-(C3HN2)] (1) with Na-2[PdCl4] or Pd(OAc)(2) under different experimental conditions has allowed us to isolate and characterize the trans-isomers of [Pd{[1-{MeOe(CH2)(2)-}-3,5-PH2-(C3HN2)]}(2)(X)(2)] [X = Cl (2) or OAc (3)] and the di-m-ligand bridged cyclopalladated complexes [Pd{kappa(2),C,N[1-{MeOe(CH2)(2)-}-3-(C6H4), 5-Ph-(C3HN2)]}(mu-X)](2) [X = OAc (4) or Cl (5)]. Further treatment of compounds 4 or 5 with PPh3 in CH2Cl2 produced the bridge splitting and the formation of [Pd{kappa(2),C,N[1-{MeOe(CH2)(2)-}-3-(C6H4), 5-Ph-(C3HN2)]}X(PPh3)] [X = OAc (6) or Cl (7)]. The cytotoxic assessment of the free ligand (1) and the Pd(II) complexes on the two breast cancer cell lines MCF7 and MDA-MB231 reveals that: a) compound 1 is less active than its analogue [1-{Me2N-(CH2)(2)-}-3,5-Ph(2)e(C3HN2)] (Ic) and b) palladacycles 4-7 showed a remarkable cytotoxic activity in the MDA-MB231 cell line (with IC50 values in the range 9.1-14.4 mu M).
Oncogenesis, 2014
Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prog... more Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood. We showed that extracellular S100P stimulates pancreatic carcinoma BxPC3 cell line by promoting cell proliferation. We also demonstrated that S100P induces, in this cell line, the phosphorylation of IkBa and the secretion of matrix metalloproteinase 9 (MMP-9). In addition, treatment with S100P protected cells from injuries induced by the cytotoxic agent Gemcitabine. On the basis of these results, we developed function-blocking anti-S100P monoclonal antibodies (mAbs) that abolished all of its in vitro activities. Furthermore, in vivo treatment with the candidate 2H8 antibody decreased tumor growth and liver metastasis formation in a subcutaneous and orthotopic BxPC3 tumor model. We conclude here that a therapeutic strategy blocking the extracellular activity of S100P by means of specific mAbs could be an attractive therapeutic approach as a single agent or in combination with target-directed or chemotherapeutic drugs to treat pancreatic cancer.
Organometallics, 2014
ABSTRACT The cyclopalladation of a series of symmetric diimines with the formula (RC6H4CHNZ)2, w... more ABSTRACT The cyclopalladation of a series of symmetric diimines with the formula (RC6H4CHNZ)2, where Z = CH2 or (CH2)2OCH2 and R = p-Cl, p-OMe, p-NO2, and o-Cl, is described. Optimal conditions to obtain the dimetalated compounds were found to be palladium(II) acetate, in toluene, at 60 °C and with a reaction time of 2−4 h. The reactivity of the dimetalated compounds with monodentate, bidentate, and bis(monodentate) Lewis bases was also studied. The cytotoxic activity of some selected compounds was evaluated against a panel of adenocarcinoma cell lines (colon HCT116 and breast MCF7 and MDA-MB231). Compounds containing the fragment NCH2CH2OCH2CH2OCH2CH2N exhibited a remarkable cytotoxic activity in the three cancer cells assayed, but complexes containing the NCH2CH2N fragment showed no activity. It seems that the length and flexibility of the central saturated chain in the imine molecule, as well as its lipophilicity and hydrophilicity, explain the different cytotoxicity of the two series of coordination compounds here reported.
European journal of medicinal chemistry, 2014
Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a... more Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively. Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity over A549 cells mainly through the induction of apoptosis (38 and 31-fold increase in early apoptotic cells, respectively).
Journal of inorganic biochemistry, 2014
The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition... more The antitumor, antibacterial and antioxidant activity, DNA interaction and cathepsin B inhibition of cyclo-ortho-palladated and -platinated compounds [Pd(C,N)]2(μ-X)2 [X=OAc (1), X=Cl (2)] and trans-N,P-[M(C,N)X(PPh3)] [M=Pd, X=OAc (3), M=Pd, X=Cl (4), M=Pt, X=Cl (5)] are discussed [(C,N)=cyclo-ortho-metallated benzophenone imine]. The cytotoxicity of compound 5 has been evaluated towards human breast (MDA-MB-231 and MCF-7) and colon (HCT-116) cancer cell lines and that of compounds 1-4 towards the HCT-116 human colon cancer cell line. These cytotoxicities have been compared with those previously reported for compounds 1-4 towards MDA-MB-231 and MCF-7 cancer cell lines. Compound 3 and 4 were approximately four times more active than cisplatin against the MDA-MB-231 and MCF-7 cancer cell lines, and compound 5, was approximately four times more potent than cisplatin against the HCT-116 cancer cell line. The antibacterial activity of compounds 1-5 was in between the ranges of activity ...
Annals of Surgery, 2014
The aim of this study was to investigate the effect of postoperative peritoneal infection on prol... more The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer. Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may enhance tumor progression features of residual cancer cells. Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008-March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n=47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n=47).In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serum and peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities. Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140±85 vs control: 94±30; P=0.016) and cell invasion (infection: 117±31 vs control: 103±16; P=0.024) capacities of cancer cell lines. With serum samples, these effects were only observed in cell migration assays (infection: 98±28 vs control: 87±17; P=0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P=0.032). Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors.
TAG Theoretical and Applied Genetics, 2001
A map with 51 markers (46 RFLPs and five isozymes) was constructed using an interspecific F 2 pop... more A map with 51 markers (46 RFLPs and five isozymes) was constructed using an interspecific F 2 population between 'Garfi' almond (Prunus amygdalus Batsch.) and 'Nemared' peach [Prunus persica (L.) Batsch.]. This map was developed by selecting markers covering most of the distance of the eight linkage groups from previously constructed Prunus maps. The markers studied in this population mapped to seven linkage groups instead of the eight expected in Prunus. Markers belonging to groups 6 and 8 in previous maps formed a single group in the 'Garfi'×'Nemared' F 2 and several marker pairs placed in different groups in other maps exhibited tight linkages. The study of pollen fertility and chromosome behavior during meiosis in the F 1 generation allowed us to confirm the hypothesis that a reciprocal translocation exists between 'Garfi' and 'Nemared'. Based on independent evidence of linkage between markers and pollen fertility data in the F 2 population, we concluded that the breakpoint of the reciprocal translocation was placed between markers AC50 and AG26A in group 6 and between markers AG112A and FG230A in group 8.
TAG Theoretical and Applied Genetics, 1998
A map with 246 markers (11 isozymes and 235 RFLPs) was constructed using an interspecific F popul... more A map with 246 markers (11 isozymes and 235 RFLPs) was constructed using an interspecific F population between almond (cv Texas) and peach (cv Earlygold). RFLPs were obtained using 213 probes from the genomic and cDNA libraries of different species (almond, peach, P. ferganensis, cherry, plum and apple), including 16 almond probes which correspond to known genes. All markers were distributed in eight linkage groups, the same as the basic chromosome number of the genus, covering a total distance of 491 cM. The average map density was 2.0 cM/marker and only four gaps of 10 cM or more were found; the two largest gaps were 12 cM each. This map was compared with one constructed previously with an intraspecific almond population sharing 67 anchor loci. Locus order was nearly identical and distances were not significantly different. A large proportion of the mapped loci (46%) had skewed segregations; in approximately half of them, the distortion was due to an excess of heterozygotes. One of the distorted regions Communicated by M. A. Saghai Maroof
Theoretical and Applied Genetics, 1995
Inheritance and linkage studies were conducted with seven isozyme genes and 120 RFLPs in the F 1 ... more Inheritance and linkage studies were conducted with seven isozyme genes and 120 RFLPs in the F 1 progeny of a cross between almond cultivars 'Ferragnes' and 'Tuono'. RFLPs were detected using 57 genomic and 43 cDNA almond clones. Eight of the cDNA probes corresponded to known genes (extensin, prunin (2), ~-tubulin, endopolygalacturonase, oleosin, actin depolymerizing factor and phosphoglyceromutase). Single-copy clones were found more frequently in the cDNA (65%) than in the genomic libraries (26%). Two maps were elaborated, one with the 93 loci heterozygous in 'Ferragnes' and another with the 69 loci heterozygous in 'Tuono'. Thirty-five loci were heterozygous in both parents and were used as bridges between both maps. Most of the segregations (91%) were of the 1:1 or 1 : 1 : 1 : 1 types, and data were analyzed as if they derived from two backcross populations. Eight linkage groups covering 393 cM in 'Ferragnes' and 394 in 'Tuono' were found for each map. None of the loci examined in either map was found to be unlinked. Distorted segregation ratios were mainly concentrated in two linkage groups of the 'Ferragnes' map.