Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Programa Nacional de Apoio à Atenção Oncológica (Pronon)Associacao Beneficiente Alzira Denise Hertzog Silva (ABADHS)CIPE AC Camargo Canc Ctr, Med Genom Lab, Sao Paulo, BrazilUniv Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, BrazilUniv Sao Paulo, Cursode Posgrad Bioinformat, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Pelv Surg, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Pathol, Sao Paulo, BrazilUniv Fed Sao Paulo, Coll Med, Dept Gynecol, Lab Mol Gynecol, Sao Paulo, BrazilHosp Sirio Libane, Ctr Oncol Mol, Sao Paulo, BrazilUniv Sao Paulo, Food Res Ctr FoRC, Fac Ciencias Farmaceut, Dept Alimentos & Nutr Expt, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Clin Oncol, Sao Paulo, BrazilAC Camargo Canc Ctr, Lab Computat Biol & Boinformat, Sao Paulo, BrazilVirginia Tech, Biocomplex Inst, Blacksburg, VA USAUniv Sao Paulo, Fac Med, Inst Psychiat, Lab Neurosci LIM Alzira Denise Hertzog Silva 27, Sao Paulo, BrazilLaboratory of Molecular Gynecology, Department of Gynecology, Medicine College, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilFAPESP: 2015/01507-7FAPESP: 2013/07914-8CAPES: 88887.062078/2014-00CAPES: 3385/2013PRONON: 25000.055.167/2015-23Web of Scienc

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Composição química de sementes de azevém em resposta ao retardamento da secagem e ao armazenamento Chemical composition of ryegrass seeds in response to drying delay and storage

O objetivo deste trabalho foi avaliar as alterações na composição química de sementes de azevém anual (Lolium multiflorum Lam.), cultivar Comum-RS, em resposta ao retardamento da secagem (0, 6, 12, 18, 24, 36 e 48 horas) e ao armazenamento (zero, quatro e oito meses), e correlacionar tais alterações com a qualidade fisiológica. A secagem foi retardada por meio do acondicionamento das sementes em caixas de poliestireno, contendo cada uma 24 kg de sementes, e realizada sobre piso de concreto, à sombra, por 12 horas, completando-a em estufa com circulação de ar. O retardamento da secagem por até 14 horas não comprometeu a qualidade fisiológica das sementes. Quando as sementes foram armazenadas por quatro e oito meses, os teores de proteína solúvel apresentaram correlação positiva com a germinação. A qualidade fisiológica das sementes correlacionou-se de forma negativa com o teor de aminoácidos e positiva com o teor de açúcares solúveis. O retardamento da secagem aumentou o teor de aminoácidos e reduziu açúcares solúveis, amido solúvel, proteína solúvel e peso de mil sementes. Durante o armazenamento houve aumento dos teores de aminoácidos, amido solúvel e proteína solúvel, e a redução de açúcares solúveis e peso de mil sementes.<br>The objective of this experiment was to evaluate changes in the chemical composition of annual ryegrass (Lolium multiflorum Lam.), cv. Comum-RS, seeds, in response to drying delay (0, 6, 12, 18, 24, 36 e 48 hours) and storage (zero, four and eight months) and to correlate these changes with physiological quality. Drying was delayed by conditioning seeds in polystyrene boxes, containing 24 kg of seeds each one, and was done on a shadowy concrete floor for 12 hours, being completed in an oven with circulation of forced air. Drying delay up to 14 hours did not compromise physiological quality of seeds. When seeds were stored for four and eight months, contents of soluble protein showed positive correlation with germination. Seeds physiological quality correlated negatively with aminoacids contents and positively with soluble sugars. Drying delay increased aminoacids contents and decreased contents of soluble sugars, soluble starch and soluble protein, and 1,000-seeds weight. Storage increased aminoacids, soluble starch and soluble protein contents and decreased soluble sugars content and 1,000-seeds weight