211 research outputs found
Sustainable Copper Electrochemical Stripping onto a Paper-Based Substrate for Clinical Application
Concomitant mutations G12D and G13D on the exon 2 of the KRAS gene. Two cases of women with colon adenocarcinoma
Colorectal cancer (CRC) is rapidly increasing representing the second most frequent cause of cancer-related deaths. From a clinical-molecular standpoint the therapeutically management of CRC focuses on main alterations found in the RAS family protein, where single mutations of KRAS are considered both the hallmark and the target of this tumor. Double and concomitant alterations of KRAS are still far to be interpreted as molecular characteristics which could potentially address different and more personalized treatments for patients. Here, we firstly describe the case of two patients at different stages (pT2N0M0 and pT4cN1cM1) but similarly showing a double concurrent mutations G12D and G13D in the exon 2 of the KRAS gene, normally mutually exclusive. We also evaluated genetic testing of dihydropyrimidine dehydrogenase (DPYD) and microsatellite instability (MSI) by real-time PCR and additional molecular mutations by next generation sequencing (NGS) which resulted coherently to the progression of the disease. Accordingly, we reinterpreted and discuss the clinical history of both cases treated as single mutations of KRAS but similarly progressing towards a metastatic asset. We concluded that double mutations of KRAS cannot be interpreted as univocal genomic alterations and that they could severely impact the clinical outcome in CRC, requiring a tighter monitoring of patients throughout the time.Abstract: Colorectal cancer (CRC) is rapidly increasing representing the second most frequent cause
of cancer-related deaths. From a clinical-molecular standpoint the therapeutically management
of CRC focuses on main alterations found in the RAS family protein, where single mutations of
KRAS are considered both the hallmark and the target of this tumor. Double and concomitant
alterations of KRAS are still far to be interpreted as molecular characteristics which could potentially
address different and more personalized treatments for patients. Here, we firstly describe the case
of two patients at different stages (pT2N0M0 and pT4cN1cM1) but similarly showing a double
concurrent mutations G12D and G13D in the exon 2 of the KRAS gene, normally mutually exclusive.
We also evaluated genetic testing of dihydropyrimidine dehydrogenase (DPYD) and microsatellite
instability (MSI) by real-time PCR and additional molecular mutations by next generation sequencing
(NGS) which resulted coherently to the progression of the disease. Accordingly, we reinterpreted and
discuss the clinical history of both cases treated as single mutations of KRAS but similarly progressing
towards a metastatic asset. We concluded that double mutations of KRAS cannot be interpreted
as univocal genomic alterations and that they could severely impact the clinical outcome in CRC,
requiring a tighter monitoring of patients throughout the time
Purification and characterization of a Cys-Gly hydrolase from the gastropod mollusk, Patella caerulea
A magnesium-dependent cysteinyl-glycine hydrolyzing enzyme from the gastropod mollusk Patella caerulea was purified to electrophoretic homogeneity through a simple and rapid purification protocol. The molecular masses of the native protein and the subunit suggest that the enzyme has a homohexameric structure. Structural data in combination with kinetic parameters determined with Cys-Gly and compared with Leu-Gly as a substrate, indicate that the purified enzyme is a member of the peptidase family M17. The finding that an enzyme of the peptidase family M17 is responsible also in mollusks for the breakdown of Cys-Gly confirms the important role of this peptidase family in the glutathione metabolism
Comparative transcriptome analysis of the interaction between Actinidia chinensis var. chinensis and Pseudomonas syringae pv. Actinidiae in absence and presence of acibenzolar-S-methyl
Background: Since 2007, bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has become a pandemic disease leading to important economic losses in every country where kiwifruit is widely cultivated. Options for controlling this disease are very limited and rely primarily on the use of bactericidal compounds, such as copper, and resistance inducers. Among the latter, the most widely studied is acibenzolar-S-methyl. To elucidate the early molecular reaction of kiwifruit plants (Actinidia chinensis var. chinensis) to Psa infection and acibenzolar-S-methyl treatment, a RNA seq analysis was performed at different phases of the infection process, from the epiphytic phase to the endophytic invasion on acibenzolar-S-methyl treated and on non-treated plants. The infection process was monitored in vivo by confocal laser scanning microscopy. Results: De novo assembly of kiwifruit transcriptome revealed a total of 39,607 transcripts, of which 3360 were differentially expressed during the infection process, primarily 3 h post inoculation. The study revealed the coordinated changes of important gene functional categories such as signaling, hormonal balance and transcriptional regulation. Among the transcription factor families, AP2/ERF, MYB, Myc, bHLH, GATA, NAC, WRKY and GRAS were found differentially expressed in response to Psa infection and acibenzolar-S-methyl treatment. Finally, in plants treated with acibenzolar-S-methyl, a number of gene functions related to plant resistance, such as PR proteins, were modulated, suggesting the set-up of a more effective defense response against the pathogen. Weighted-gene coexpression network analysis confirmed these results. Conclusions: Our work provides an in-depth description of the plant molecular reactions to Psa, it highlights the metabolic pathway related to acibenzolar-S-methyl-induced resistance and it contributes to the development of effective control strategies in open field
Could a chimeric condition be responsible for unexpected genetic syndromes? The role of the single nucleotide polymorphism-array analysis
Hyaluronan preconditioning of monocytes/macrophages affects their angiogenic behavior and regulation of TSG-6 expression in a tumor type-specific manner
Hyaluronan is a glycosaminoglycan normally present in the extracellular matrix in most tissues. Hyaluronan is a crucial player in many processes associated with cancer, such as angiogenesis, invasion and metastasis. However, little has been reported regarding the action of hyaluronan on monocytes/macrophages in tumor angiogenesis and its consequences on tumor development. In the present study, we investigated the effects of hyaluronan of different sizes on human monocytes/macrophages angiogenic behavior in colorectal and breast carcinoma. In vitro, treatment of monocytes/macrophages with lysates and conditioned media from a breast, but not from colorectal, carcinoma cell line plus high molecular weight hyaluronan induced: i) an increased expression of angiogenic factors VEGF, IL‐8, FGF‐2 and MMP‐2, ii) increased endothelial cell migration and iii) a differential expression of hyaluronan‐binding protein TSG‐6. Similar results were observed in monocytes/macrophages derived from breast cancer patients treated with tumor lysates. Besides, macrophages primed with high molecular weight hyaluronan and inoculated in human breast cancer xenograft tumor increased blood vessel formation and diminished TSG‐6 levels. In contrast, the effects triggered by high molecular weight hyaluronan on monocytes/macrophages in breast cancer context were not observed in the context of colorectal carcinoma. Taken together, these results indicate that the effect of high molecular weight hyaluronan as an inductor of the angiogenic behavior of macrophages in breast tumor context is in part consequence of the presence of TSG‐6.Fil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Icardi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Caon, Ilaria. Università degli Studi dell’Insubria; ItaliaFil: Brandone, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Doctor Abraham Felix Piñeyro.; ArgentinaFil: Giannoni, Ana Paula. No especifíca;Fil: Saturno, Maria Virginia. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Passi, Alberto. Università degli Studi dell’Insubria; ItaliaFil: García, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin
Hyaluronan metabolism is associated with DNA repair genes in breast and colorectal cancer: Screening of potential progression markers using qPCR
In this work, we compared mRNA levels of Hyaluronan (HA) metabolism members and BRCA genes, known to be involved in the tumoral process, between tumor and non-tumor adjacent tissue and its correlation with previously proposed biomarkers (ER, PR, HER2 and KI67) in order to assess their value as a progression biomarkers. We show alteration in HA metabolism in colorectal but not breast cancer. However, we found a decrease in Hyaluronidase 1 HYAL1 levels in the breast but not colorectal cancer. We also show lower HA levels in tumor compared with normal tissue that could indicate a possible influence of tumor on its surrounding "normal" tissue. In both breast and colorectal cancer, CD44 and BRCA2 showed a strong positive correlation. Besides, our results show first indicators that qPCR of the analyzed genes could be used as an easy and low cost procedure for the evaluation of molecular markers we propose here.Fil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Vitale, Daiana Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Icardi, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Romano, María Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Brandone, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Doctor Abraham Felix Piñeyro.; ArgentinaFil: Giannoni, Ana Paula. Clínica Centro, Junín; ArgentinaFil: Cristina, Silvia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin
Plant Microbiome and Its Link to Plant Health: Host Species, Organs and Pseudomonas syringae pv. actinidiae Infection Shaping Bacterial Phyllosphere Communities of Kiwifruit Plants
Pseudomonas syringae pv. actinidiae (Psa) is the causal agent of the bacterial canker, the most devastating disease of kiwifruit vines. Before entering the host tissues, this pathogen has an epiphytic growth phase on kiwifruit flowers and leaves, thus the ecological interactions within epiphytic bacterial community may greatly influence the onset of the infection process. The bacterial community associated to the two most important cultivated kiwifruit species, Actinidia chinensis and Actinidia deliciosa, was described both on flowers and leaves using Illumina massive parallel sequencing of the V3 and V4 variable regions of the 16S rRNA gene. In addition, the effect of plant infection by Psa on the epiphytic bacterial community structure and biodiversity was investigated. Psa infection affected the phyllosphere microbiome structures in both species, however, its impact was more pronounced on A. deliciosa leaves, where a drastic drop in microbial biodiversity was observed. Furthermore, we also showed that Psa was always present in syndemic association with Pseudomonas syringae pv. syringae and Pseudomonas viridiflava, two other kiwifruit pathogens, suggesting the establishment of a pathogenic consortium leading to a higher pathogenesis capacity. Finally, the analyses of the dynamics of bacterial populations provided useful information for the screening and selection of potential biocontrol agents against Psa
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