Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials

Background: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeACmucin) do not benefit from neoadjuvant chemotherapy. Methods: OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeACmucin) or non-mucinous adenocarcinoma (OeACnon-mucin). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed. Results: Overall, 7.3% and 9.6% OeAC were classified as OeACmucin in OE02 and OE05, respectively. In OE02, the frequency of OeACmucin was similar in S and CS-patients. Patients with OeACmucin treated with surgery alone had a poorer overall survival compared with OeACnon-mucin patients (hazard ratio: 2.222, 95% confidence interval: 1.08–4.56, P = 0.025). Patients with OeACmucin treated with neoadjuvant chemotherapy and surgery had similar survival as OeACnon-mucin patients in test and validation cohort. Conclusions: This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy

The Significance of Family History Status in Relation to Neuropsychological Test Performance and Cerebral Glucose Metabolism Studied with Positron Emission Tomography in Older Alcoholic Patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66033/1/j.1530-0277.1998.tb03622.x.pd

Canonical A-to-I and C-to-U RNA Editing Is Enriched at 3′UTRs and microRNA Target Sites in Multiple Mouse Tissues

RNA editing is a process that modifies RNA nucleotides and changes the efficiency and fidelity of the central dogma. Enzymes that catalyze RNA editing are required for life, and defects in RNA editing are associated with many diseases. Recent advances in sequencing have enabled the genome-wide identification of RNA editing sites in mammalian transcriptomes. Here, we demonstrate that canonical RNA editing (A-to-I and C-to-U) occurs in liver, white adipose, and bone tissues of the laboratory mouse, and we show that apparent non-canonical editing (all other possible base substitutions) is an artifact of current high-throughput sequencing technology. Further, we report that high-confidence canonical RNA editing sites can cause non-synonymous amino acid changes and are significantly enriched in 3′ UTRs, specifically at microRNA target sites, suggesting both regulatory and functional consequences for RNA editing

Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials.

BACKGROUND: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeACmucin) do not benefit from neoadjuvant chemotherapy. METHODS: OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeACmucin) or non-mucinous adenocarcinoma (OeACnon-mucin). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed. RESULTS: Overall, 7.3% and 9.6% OeAC were classified as OeACmucin in OE02 and OE05, respectively. In OE02, the frequency of OeACmucin was similar in S and CS-patients. Patients with OeACmucin treated with surgery alone had a poorer overall survival compared with OeACnon-mucin patients (hazard ratio: 2.222, 95% confidence interval: 1.08-4.56, P = 0.025). Patients with OeACmucin treated with neoadjuvant chemotherapy and surgery had similar survival as OeACnon-mucin patients in test and validation cohort. CONCLUSIONS: This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy

Breast Cancer's Microarray Data: Pattern Discovery Using Nonnegative Matrix Factorizations.

One challenge in microarray analysis is to discover and capture valuable knowledge to understand biological processes and human disease mechanisms. Nonnegative Matrix Factorization (NMF) – a constrained optimization mechanism which decomposes a data matrix in terms of additive combination of non-negative factors– has been demonstrated to be a useful tool to reduce the dimension of gene expression data and to identify potentially interesting genes which explain latent structure hidden in microarray data. In this paper, we detail how to use Nonnegative Matrix Factorization based on generalized Kullback-Leibler divergence to analyze gene expression profile data related to the cell line of mammary cancer MCF-7 and to pharmaceutical compounds connected to the metabolism of arachidonic acid. NMF technique is able to reduce the dimension of the considered genes-compounds matrix from thousands of genes to few metagenes and to extract information about the drugs that more affect these genes. We provide an experimental framework illustrating the technical steps one has to perform to use NMF to discover useful patterns from microarray data. In fact, the results obtained by NMF method could be used to select and characterize therapies that can be effective on biological functions involved in the neoplastic transformation process and to perform further biological investigations

Q-matrix Extraction from Real Response Data Using Nonnegative Matrix Factorizations

In this paper we illustrate the use of Nonnegative Matrix Factorization (NMF) to analyze real data derived from an e-learning context. NMF is a matrix decomposition method which extracts latent information from data in such a way that it can be easily interpreted by humans. Particularly, the NMF of a score matrix can automatically generate the so called Q-matrix. In an e-learning scenario, the Q-matrix describes the abilities to be acquired by students to correctly answer evaluation exams. An example on real response data illustrates the effectiveness of this factorization method as a tool for EDM