Project description:Normal human colorectal mucosa was sampled at points along the colon. Experiment Overall Design: Normal human colorectal mucosa, cecum, ascending, transverse, sigmoid and rectum
Project description:We applied numerical ecology methods to data produced with a human intestinal tract-specific phylogenetic microarray (the Aus-HIT Chip) to examine the biogeography of mucosa-associated bacteria along the human colon. The microbial DNA associated with matched biopsy tissue samples taken from the cecum, transverse colon, sigmoid colon and rectum of 10 healthy patients was examined. Consistent with previous studies, the profiles revealed a marked inter-subject variability; however, the numerical ecology methods of analysis allowed the subtraction of the subject effect from the data and revealed, for the first time, evidence of a longitudinal gradient for specific microbes along the colorectum: with Streptococcus, Comamonadaceae, Enterococcus and Lactobacillus in greatest abundance at the cecum, with a gradual decline in their relative abundance through to the rectum. Conversely, the analyses suggest that members of the Enterobacteriaceae increase in relative abundance towards the rectum. These differences were validated by quantitative PCR. We were also able to identify significant differences in the profiles, especially for the Streptococci, on the basis of gender. The results derived by these multivariate analyses are biologically intuitive, and suggestive that the biogeography of the colonic mucosa can be monitored for changes via cross-sectional and/or inception cohort studies. 10 patients, 5 males and 5 females. Four different locations along the colorectum.
Project description:We applied numerical ecology methods to data produced with a human intestinal tract-specific phylogenetic microarray (the Aus-HIT Chip) to examine the biogeography of mucosa-associated bacteria along the human colon. The microbial DNA associated with matched biopsy tissue samples taken from the cecum, transverse colon, sigmoid colon and rectum of 10 healthy patients was examined. Consistent with previous studies, the profiles revealed a marked inter-subject variability; however, the numerical ecology methods of analysis allowed the subtraction of the subject effect from the data and revealed, for the first time, evidence of a longitudinal gradient for specific microbes along the colorectum: with Streptococcus, Comamonadaceae, Enterococcus and Lactobacillus in greatest abundance at the cecum, with a gradual decline in their relative abundance through to the rectum. Conversely, the analyses suggest that members of the Enterobacteriaceae increase in relative abundance towards the rectum. These differences were validated by quantitative PCR. We were also able to identify significant differences in the profiles, especially for the Streptococci, on the basis of gender. The results derived by these multivariate analyses are biologically intuitive, and suggestive that the biogeography of the colonic mucosa can be monitored for changes via cross-sectional and/or inception cohort studies.
Project description:Helminth infection may have the potential to suppress intestinal inflammation in inflammatory bowel diseases. Ulcerative colitis is more common in developed countries than in developing countries endemic for helminth infections. There are animal models, as well as clinical trials, suggesting therapeutic effects of experimental helminth infection. Here, we provide a comprehensive molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Genes involved in carbohydrate and lipid metabolism were upregulated in helminth-colonized tissue, while tissues with active colitis showed upregulation of proinflammatory genes such as IL-17, IL13RA2, and CHI3L1. T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through TH2 cytokines and IL-22. By better understanding the physiological effects of helminth infection, new therapies for ulcerative colitis could be identified. This is the first (out of three) series of arrays from this patient from a colonoscopy in 2007 when the patient had mild proctitis in the rectum and worms in the ascending and transverse colon. We analyzed 14 HEEBO arrays on which were hybridized RNA amplified from pinch biopsies collected from different regions of the colon. 3 samples were from the ascending colon, which was colonized by worms at the time. 2 samples were from the transverse colon, which was also colonized by worms at the time. 4 samples were from the sigmoid colon, which appeared normal at the time. 3 samples were from the rectum, which showed signs of proctitis and was inflamed at the time. 2 samples were from the terminal ileum, which was unaffected by worms or colitis.
Project description:Gene expression was analyzed in terms of canonical molecular changes and clinicopathological features to elucidate alternative or subordinate pathways during colorectal tumorigenesis and tumor growth. Eighty-four sporadic colorectal cancer patients, standardized by tumor location, were consecutively enrolled. Representative molecular changes including APC, TP53, Wnt, RAF, and mismatch repair defect (MMR) were recorded for each sample. Keywords: disease state analysis; sub-type analysis within colorectal cancers 84 samples from colorectal patients were analyzed. Paired tumor and adjacent normal tissues from the same patient were used for hybridization onto custom-made, 21k dual channel cDNA arrays. We prepared a similar number of samples from each of the three tumor locations (ascending 27, descending 29, and rectum 28) and recorded for each sample important molecular changes such as APC, TP53, RAF, WNT, and MMR mutations.
Project description:Identification of differentially expressed microRNAs in Colorectal Cancer Distant metastasis is the major determinant of patient outcome in colorectal cancer and microRNAs have emerged as an increasingly important class of molecules which can regulate several steps of the metastatic cascade. By systematically analysing the miR expression profiles of resected metastasis-, corresponding primary tumor- and normal tissues of colorectal cancer patients, we were able to delineate a miR-signature indicative of the metastatically critical microRNA landscape. 9 colorectal cancer patients were profiled comprising 5 patients with tissues from the primary tumor, normal mucosa, secondary metastasis and the background tissue in which the metastasis ocurred. In the remaining 4 patients, one of these four tissue entitities is missing. One patient had two synchronous primary tumors, one in the colon and the other in the rectum.
Project description:Comparing to matched normal mucosa, WTX was lost in most of human colorectal cancers (Zhang et al., 2016). We analyzed the microRNA expression profiling among WTX low human colorectal cancer tissues and matched adjacent WTX high normal colorectal mucosa. The aimed to identify the unique signature of miRNAs which related to WTX loss in human colorectal cancers.
Project description:Comparing to matched normal mucosa, WTX was lost in most of human gastric cancers (Zhang et al., 2016). We analyzed the microRNA expression profiling among WTX low human colorectal cancer tissues and matched adjacent WTX high normal colorectal mucosa. The aimed to identify the unique signature of miRNAs which related to WTX loss in human colorectal cancers.