Biology subjects

Arellano, C.

Publications and source records attributed to Arellano, C..

3 recordsLinked to original sources

bioRxiv2024

Tumor-associated macrophages confer resistance to chemotherapy (Trifluridine/Tipiracil) in digestive cancers by overexpressing Thymidine Phosphorylase

Pyrimidine analogs are part of the first-line chemotherapy regimen for gastrointestinal cancers. Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. Despite its promise, in the current study, we report that macrophage-specific overexpression of thymidine phosphorylase results in macrophage-induced chemoresistance to TAS-102 that is insensitive to tipiracil inhibition. In addition, we demonstrate the human specificity of this mechanism, as mouse macrophages do not express significant levels of thymidine phosphorylase. To study the importance of macrophages in chemoresistance to trifluridine, we developed a humanized mouse model with tumor-implanted human macrophages and demonstrated their important role in treatment resistance to pyrimidine analogs. We also showed in human colorectal cancer that macrophages represent a major source of thymidine phosphorylase expression leading to chemoresistance. SignificanceThymidine phosphorylase overexpression in TAMs confers chemoresistance to TAS-102 in digestive cancers.

pathology↗

bioRxiv2019

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

Vibrio cholerae is a human pathogen, which is transmitted by the consumption of contaminated food or water. V. cholerae strains belonging to the serogroups O1 and O139 can cause cholera outbreaks and epidemics, a severe life-threatening diarrheal disease. In contrast, serogroups other than O1 and O139, denominated as non-O1/non-O139, have been mainly associated with sporadic cases of moderate or mild diarrhea, bacteremia and wound infections. Here we investigated the virulence determinants and phylogenetic origin of a non-O1/non-O139 V. cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018. We found that this outbreak strain lacks the classical virulence genes harboured by O1 and O139 strains, including the cholera toxin (CT) and the toxin-coregulated pilus (TCP). However, this strain carries genomic islands (GIs) encoding Type III and Type VI secretion systems (T3SS/T6SS) and antibiotic resistance genes. Moreover, we found these GIs are wide distributed among several lineages of non-O1/non-O139 strains. Our results suggest that the acquisition of these GIs may enhance the virulence of non-O1/non-O139 strains that lack the CT and TCP-encoding genes. Our results highlight the pathogenic potential of these V. cholerae strains. DATA SUMMARYSequence data were submitted to GenBank under the accession number SRLP00000000. The authors confirm that all supporting data and protocols have been provided within the article or through supplementary data files. Data statementAll supporting data, code and protocols have been provided within the article or through supplementary data files. Four supplementary tables are available with the online version of this article.

microbiology↗

bioRxiv2019

Differences in proteome response to cold acclimation in Zoysia japonica cultivars with different levels of freeze tolerance

Zoysiagrasses (Zoysia spp.) are warm season turfgrasses primarily grown in the southern and transition zones of the United States. An understanding of the physiological changes that zoysiagrasses undergo during cold acclimation may shed light on physiological phenotypic traits useful in selection of freeze tolerant genotypes. We investigated the relationship between cold acclimation, protein expression, and freeze tolerance in cold-acclimated (CA) and non-acclimated (NCA) plants of Zoysia japonica Steud. cultivars Meyer (freeze-tolerant) and Victoria (freeze-susceptible). Freeze tolerance was assessed using chambers reaching -6, -8, -10, and -12{degrees}C. Additionally, meristematic tissues from the grass crowns of Meyer and Victoria were harvested for proteomic analysis after a four week cold acclimation period. Freeze testing indicated that cold acclimation accounted for a 1.9-fold increase in plant survival compared to the non-acclimation treatment. Overall, proteomic analysis identified 62 protein spots having at least a twofold change in abundance under cold acclimation. Nine and 22 unique protein spots were identified for Meyer and Victoria, respectively, with increased abundance (up-regulated) or decreased abundance (down-regulated). In addition, 23 shared protein spots were found among the two cultivars having differential expression in response to cold acclimation. In Meyer, protein response to cold acclimation was primarily upregulated, while in Victoria, protein response was primarily downregulated. These cold acclimation responsive proteins were found to be involved primarily in transcription, metabolism, protein destination and storage, and energy production. As identified through MALDI-TOF/TOF mass spectrometry followed matching of protein homologues against the NCBI Arabidopsis database, major proteins of interest for their association with cold acclimation were LEA 3, MAPK, SOD, GAST1, Phytochrome A, ATP synthase, AGP, PLD, and PSII. Further investigation of these proteins and their functional categories may contribute to increase our understanding of the differences in freezing tolerance among zoysiagrass germplasm.

physiology↗