Modulation of 5-fluorouracil host-toxicity and chemotherapeutic efficacy against human colon tumors by 5-(Phenylthio)acyclouridine, a uridine phosphorylase inhibitor

The development and progression of colon cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.

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Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice

Gastroenterology ◽

10.1053/j.gastro.2015.08.051 ◽

2015 ◽

Vol 149 (7) ◽

pp. 1860-1871.e8 ◽

Cited By ~ 19

Author(s):

Junjie Zhao ◽

Katarzyna Bulek ◽

Muhammet F. Gulen ◽

Jarod A. Zepp ◽

Georgio Karagkounis ◽

...

Keyword(s):

Colon Cancer ◽

Human Colon ◽

Dominant Negative ◽

Colon Tumors ◽

Dominant Negative Form ◽

Negative Form

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Expression of multiple isoforms of protein kinase C in normal human colon mucosa and colon tumors and decreased levels of protein kinase C β and η mRNAs in the tumors

Molecular Carcinogenesis ◽

10.1002/mc.2940110405 ◽

1994 ◽

Vol 11 (4) ◽

pp. 197-203 ◽

Cited By ~ 33

Author(s):

Sadyuki Doi ◽

Cebra Goldstein ◽

Hubert Hug ◽

I. Bernard Weinstein

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Human Colon ◽

Colon Mucosa ◽

Colon Tumors ◽

Kinase C ◽

Normal Human

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Down-regulation of MTUS1 in human colon tumors

Oncology Reports ◽

10.3892/or_00000621 ◽

2009 ◽

Vol 23 (1) ◽

Cited By ~ 4

Author(s):

Zuern

Keyword(s):

Human Colon ◽

Down Regulation ◽

Colon Tumors

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Variation in cytosolic protein expression between human colon tumors that differ with regard to differentiation class.

Clinical Chemistry ◽

10.1093/clinchem/34.1.71 ◽

1988 ◽

Vol 34 (1) ◽

pp. 71-75 ◽

Cited By ~ 20

Author(s):

T J Nalty ◽

C W Taylor ◽

L C Yeoman

Keyword(s):

Human Colon ◽

Human Colon Cancer ◽

Two Dimensional Gel Electrophoresis ◽

Colon Tumors ◽

Marker Proteins ◽

Isoelectric Points ◽

Molecular Masses ◽

Poorly Differentiated ◽

Differentiation Marker ◽

Individual Differentiation

Abstract Using a combination of two-dimensional gel electrophoresis, silver staining, and a 16-quadrant grid system, we established a set of composite patterns for the colon tumor cytosol proteins of well, moderately, and poorly differentiated tumors. These composite patterns were found to be characteristic of the three individual differentiation classes for colon tumors. The apparent relative molecular masses (Mr) of the resolved proteins ranged from 14,000 to 105,000 and their isoelectric points from pH 5.2 to 8.4. Although the vast majority of the proteins identified in the composite patterns were common, a comparison based upon these patterns revealed two qualitative and seven quantitative protein differences. The qualitative differences were identified by apparent Mr X 10(-3)/pI coordinates of 73/7.2 and 66/6.2. Quantitative differences were identified by Mr X 10(-3)/pI coordinates of 71/6.0, 59/6.7, 57/6.7, 56/5.4, 52/6.1, 30/5.8, and 18/6.2. These cytosolic differentiation marker proteins may facilitate the diagnosis, staging, and monitoring of human colon cancer.

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