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Answers
Educational section
143
Answers (to self-assessment exercise on p. 138) 1. That is correct. Three isoforms have been isolated interacting through two types of surface protein receptors (ETA and ETB). 2.
That is not correct. A variety of cancer cells have been shown (h7 vitro and hl vivo) to synthesize and secrete ET-I.
3.
Endothelin has a multi-functional role in a variety of cells and tissues. For example, it is thought to be mitogenic for certain tumour cells (eg melanoma cells).
4.
There is evidence for both selective distribution of ET receptors on tumour cells (eg ETA and meningioma cells) and selective interaction with the different isoforms (eg ETA predominantly for ET-I and ETB for all three isoforms equally).
5.
This is not entirely correct. There is evidence that it works through a signal transduction pathway to the nucleus. Although the precise mode of action is unclear, studies with cells in vitro demonstrate that following interaction with surface receptors it activates phospholipase C with production of inositol triphosphate and 1,2-diacylglycerol leading to increased intracellular Ca ++ and expression of various proto-oncogenes (eg c-fos, c-myc).
6.
There is some evidence to suggest that endothelin may be important as an angiogenic factor in tumour growth. For example, ET-binding sites have been shown to be located on stromal blood vessels within and surrounding colorectal cancers.
7.
Unfortunately, early tumour recurrence and limited hepatic donors have not provided the solution to this difficult problem.
8.
A review of the published literature, as well as the practice of the Hanover Unit, suggests that liver transplantation may be considered for specific tumour types. For example, unresectable early stage hepatocellular and proximal bile duct carcinomas may be suitable tumour types. Also, some uncommon entities (fibrolamella~ carcinoma, epithelioid haemangioendothelioma and hepatoblastoma) are worth considering.
9.
There appears to be little benefit in hepatic resection and transplantation for secondary hepatic deposits from most of the common tumours, in particular colorectal cancer. However, some patients with liver metastases from neuroendocrine tumours may derive benefit from such radical therapy.
10.
There is some evidence to support such a therapeutic approach, but the data for this approach are based on retrospective reviews. Donor organ shortage and, as yet, ill-defined multimodality treatments make it difficult to assess such an approach in a randomized controlled trial.
143
Answers (to self-assessment exercise on p. 138) 1. That is correct. Three isoforms have been isolated interacting through two types of surface protein receptors (ETA and ETB). 2.
That is not correct. A variety of cancer cells have been shown (h7 vitro and hl vivo) to synthesize and secrete ET-I.
3.
Endothelin has a multi-functional role in a variety of cells and tissues. For example, it is thought to be mitogenic for certain tumour cells (eg melanoma cells).
4.
There is evidence for both selective distribution of ET receptors on tumour cells (eg ETA and meningioma cells) and selective interaction with the different isoforms (eg ETA predominantly for ET-I and ETB for all three isoforms equally).
5.
This is not entirely correct. There is evidence that it works through a signal transduction pathway to the nucleus. Although the precise mode of action is unclear, studies with cells in vitro demonstrate that following interaction with surface receptors it activates phospholipase C with production of inositol triphosphate and 1,2-diacylglycerol leading to increased intracellular Ca ++ and expression of various proto-oncogenes (eg c-fos, c-myc).
6.
There is some evidence to suggest that endothelin may be important as an angiogenic factor in tumour growth. For example, ET-binding sites have been shown to be located on stromal blood vessels within and surrounding colorectal cancers.
7.
Unfortunately, early tumour recurrence and limited hepatic donors have not provided the solution to this difficult problem.
8.
A review of the published literature, as well as the practice of the Hanover Unit, suggests that liver transplantation may be considered for specific tumour types. For example, unresectable early stage hepatocellular and proximal bile duct carcinomas may be suitable tumour types. Also, some uncommon entities (fibrolamella~ carcinoma, epithelioid haemangioendothelioma and hepatoblastoma) are worth considering.
9.
There appears to be little benefit in hepatic resection and transplantation for secondary hepatic deposits from most of the common tumours, in particular colorectal cancer. However, some patients with liver metastases from neuroendocrine tumours may derive benefit from such radical therapy.
10.
There is some evidence to support such a therapeutic approach, but the data for this approach are based on retrospective reviews. Donor organ shortage and, as yet, ill-defined multimodality treatments make it difficult to assess such an approach in a randomized controlled trial.