PURPOSE A major factor limiting the effective clinical management of colorectal cancer (CRC) is resistance to chemotherapy. Therefore, the identification of novel, therapeutically targetable mediators of resistance is vital. EXPERIMENTAL DESIGN We used a CRC disease-focused microarray platform to transcriptionally profile chemotherapy-responsive and nonresponsive pretreatment metastatic CRC l...

BACKGROUND The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. METHODS Rats were trained to drink 10% ethanol, implanted with br...

Like galanin, the 60-amino-acid peptide, galanin-like peptide (GALP), has orexigenic actions, demonstrated by an acute increase in feeding after central injection in rodents. However, in contrast to galanin, GALP causes a prolonged rise in core body temperature and a reduction in body weight over 24 h. In an attempt to identify potential explanations for the observed differences between GALP an...

Over long periods, feeding and metabolism are tightly regulated at the central level. The total amount of nutrients ingested is thought to result from a delicate balance between orexigenic and anorexigenic factors expressed and secreted by specialized hypothalamic neuronal populations. We have developed a system of perifused hypothalamic neurons to characterize the relationships existing betwee...

There is a large body of pre-clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In-vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele...

Damage-induced neuronal endopeptidase (DINE) is a novel metallopeptidase and is expressed in response to various neuronal injuries. The expression regulation of DINE mRNA in the dorsal root ganglia (DRGs) after sciatic nerve injury is examined. A substantial increase of DINE mRNA expression was observed in relatively small-sized DRG neurons after nerve injury. The expression was observed in iso...

The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothalamus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal. The administration of es...

In the present thesis, the aim was to probe the distribution and functions of galanin type 2 receptor (GalR2) in the rodent brain. In order to overcome the lack of a reliable antibody to localize GalR2 by immunohistochemistry, we generated a construct which expresses GalR2 tagged with enhanced GFP (EGFP). We first studied the trafficking and function of this fusion protein in cell lines, includ...