46 research outputs found
Production of two highly abundant 2-methyl-branched fatty acids by blooms of the globally significant marine cyanobacteria Trichodesmium erythraeum
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gosselin, K. M., Nelson, R. K., Spivak, A. C., Sylva, S. P., Van Mooy, B. A. S., Aeppli, C., Sharpless, C. M., O’Neil, G. W., Arrington, E. C., Reddy, C. M., & Valentine, D. L. Production of two highly abundant 2-methyl-branched fatty acids by blooms of the globally significant marine cyanobacteria Trichodesmium erythraeum. ACS Omega, 6(35), (2021): 22803–22810, https://doi.org/10.1021/acsomega.1c03196.The bloom-forming cyanobacteria Trichodesmium contribute up to 30% to the total fixed nitrogen in the global oceans and thereby drive substantial productivity. On an expedition in the Gulf of Mexico, we observed and sampled surface slicks, some of which included dense blooms of Trichodesmium erythraeum. These bloom samples contained abundant and atypical free fatty acids, identified here as 2-methyldecanoic acid and 2-methyldodecanoic acid. The high abundance and unusual branching pattern of these compounds suggest that they may play a specific role in this globally important organism.This work was funded with grants from the National Science Foundation grants OCE-1333148, OCE-1333162, and OCE-1756254 and the Woods Hole Oceanographic Institution (IR&D). GCxGC analysis made possible by WHOI’s Investment in Science Fund
Heterosexual couples and prostate cancer support groups: a gender relations analysis.
Introduction: Men diagnosed with prostate cancer (PCa) can receive supportive care from an array of sources including female partners and prostate cancer support groups (PCSGs). However, little is known about how heterosexual gender relations and supportive care play out among couples who attend PCSGs. Distilling such gender relation patterns is a key to understanding and advancing supportive care for men who experience PCa and their families
Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer
The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%–25% of all cancers. In particular, approximately 30%–40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer
626 Anti-ERBB2 SI- and sh-RNAs Suppress Cell Growth in ERBB2-Overexpressing Upper Gastrointestinal Adenocarcinomas
TP53 and let-7a micro-RNA regulate K-Ras activity in HCT116 colorectal cancer cells.
Recent reports have indicated that KRAS and TP53 mutations predict response to therapy in colorectal cancer. However, little is known about the relationship between these two common genetic alterations. Micro-RNAs (miRNAs), a class of noncoding RNA implicated in cellular processes, have been increasingly linked to KRAS and TP53. We hypothesized that lethal-7a (let-7a) miRNA regulates KRAS through TP53. To investigate the relationship between KRAS, TP53, and let-7a, we used HCT116 KRAS(mut) human colorectal cancer cells with four different genotypic modifications in TP53 (TP53(-/-), TP53(+/-), TP53(mut/+), and TP53(mut/-) ). Using these cells we observed that K-Ras activity was higher in cells with mutant or knocked out TP53 alleles, suggesting that wild-type TP53 may suppress K-Ras activity. Let-7a was present in HCT116 KRAS(mut) cells, though there was no correlation between let-7a level and TP53 genotype status. To explore how let-7a may regulate K-Ras in the different TP53 genotype cells we used let-7a inhibitor and demonstrated increased K-Ras activity across all TP53, thus corroborating prior reports that let-7a regulates K-Ras. To assess potential clinical implications of this regulatory network, we examined the influence of TP53 genotype and let-7a inhibition on colon cancer cell survival following chemoradiation therapy (CRT). We observed that cells with complete loss of wild-type TP53 alleles ((-/-) or (-/mut)) were resistant to CRT following treatment with 5-fluorouracil and radiation. Further increase in K-Ras activity with let-7a inhibition did not impact survival in these cells. In contrast, cells with single or double wild-type TP53 alleles were moderately responsive to CRT and exhibited resistance when let-7a was inhibited. In summary, our results show a complex regulatory system involving TP53, KRAS, and let-7a. Our results may provide clues to understand and target these interactions in colorectal cancer
Massive Intra-Abdominal Imatinib-Resistant Gastrointestinal Stromal Tumor in a 21-Year-Old Male
Gastrointestinal stromal tumors (GISTs) in adolescence are far less common than adult GISTs and have varied GIST genotypes that present diagnostic and therapeutic challenges. Here, we discuss a 21-year-old male with diagnosis of unresectable, imatinib-resistant GIST. At initial evaluation, a neoadjuvant treatment approach was recommended. As such, the patient received imatinib over the course of one year. Unfortunately, the GIST increased in size, and a subsequent attempt at surgical resection was aborted fearing infiltration of major vascular structures. The patient was then referred to our institution, at which time imatinib therapy was discontinued. Surgical intervention was again considered and the patient underwent successful resection of massive intra-abdominal GIST with total gastrectomy and Roux-en-Y esophagojejunostomy. Since pediatric GISTs are typically resistant to imatinib, we performed genotype analysis of the operative specimen that revealed KIT mutations associated with imatinib sensitivity and resistance. Given the sequencing data and operative findings, the patient was started postoperatively on sunitinib. This case illustrates the importance of understanding both adult and pediatric GISTs when implementing appropriate treatment regimens. Since the genotype of GISTs dictates phenotypic behavior, mutational analysis is an important component of care especially for adolescents whose disease may mirror the pediatric or adult population
W1760 Human Tissue Slice Model for Evaluating Conditionally Replicative Oncolytic Adenovirus Specificity to Pancreatic Cancer
K-Ras activity is increased in cells with let-7a inhibition.
<p>Cell lysates were collected following 72 h incubation and subjected to a Raf-pull down assay which measures K-Ras activity. Data shown represents three experiments done in triplicate. Error bars show SD. *p<0.05.</p