Trichobezoars in praomys (mastomys) natalensis

We have in a rat model studied the role of gastric neuroendocrine cells in the regulation of gastric function and growth and given indication for an important role of these cells in physiology and human carcinogenesis. Because of the high incidence of spontaneous tumors in the glandular stomach of mastomys (Praomys (mastomys) natalensis), we wanted to investigate if mastomys might be an useful model for our further studies.Tumors. were recognized in several organs of our mastomys, but not in the stomach. However, a high incidence oftrichobezoars was observed in the stomach and intestine, and obstruction from thesewas the cause of illness and death for many of them.Multiple factors are involved in the formation of bezoars. and these are discussed in relation to the occurrence in our mastomys colony

Cheese-induced body weight gain is not accompanied by an increase of gastric cells producing leptin, ghrelin, gastrin, or pancreastatin in mice

The stomach is a source of several circulating peptides/hormones, such as gastrin, pancreastatin, leptin and ghrelin, which are thought to play important roles in the regulation of food intake and body growth. The present study was undertaken in mice in order to examine the effects of diet composition on the body weight gain and the gastric cells that produce these peptides/hormones.Both young and adult female mice (BALB/cABBom strain) were given a standard pelleted dry diet, with or without cheese ad libitum, during a 7 week period. The diet supplement consisted either of carbohydrate- free white cheese containing 27% fat or sweet-tasting but sucrose-free Norwegian “brown cheese” containing 29% fat and 39% carbohydrate, mainly lactose. The total intake of the various types of food and the change in body weight were recorded. At the end of the observation period, blood samples were obtained for determination of gastric hormone levels by radioimmunoassay, and the stomachs were removed for examination of hormone producing cells by immunohistochemistry.The young mice increased their body weight more than the adult mice. In the groups offered white cheese, both young and adult mice increased their body weight more than the animals kept on the standard diet alone. In contrast, the “brown cheese” supplement led to a relative overweight only in adult mice. Despite the changes in body weight gain, there were no differences with respect to the circulating levels of gastrin, leptin or ghrelin, and to the numbers of cells stained with antibodies to pancreastatin (including ECL cells and G cells), leptin (subpopulation of chief cells) and ghrelin (A-like cells) in all groups.Body weight gain was increased in both young and adult mice by a white cheese diet supplement, whereas ‘brown cheese’ produced overweight only in adult mice. The increased body weight gain was not accompanied by an icrease of gastric cells producing leptin, ghrelin, gastrin, or pancreastatin

Clear Cell Renal Cancer, a Tumour with Neuroendocrine Features Originating from the Erythropoietin-Producing Cell

The dominating type of kidney cancer is the clear cell renal cell cancer (ccRCC), hitherto been thought to develop from proximal tubule cells. However, the ability of tubule cells to proliferate is at best controversial. ccRCCs show many peculiarities like erythrocytosis due to erythropoietin overproduction and a combination of early metastases and sometimes apparent dormancy and late recurrence, features in common with neuroendocrine tumours (NETs). We have shown that most ccRCCs express erythropoietin and the neuroendocrine marker neuron-specific enolase, and other neuroendocrine markers in a percentage of the cancers. Missense mutation in von Hippel–Lindau (VHL) factor is rather specific for ccRCC found in familial and sporadic forms. The function of VHL factor is together with other proteins to destroy hypoxia-inducible factors (HIFs), central in adaptation to hypoxia. Lack of functioning VHL factor results in continuous overstimulation of the erythropoietin-producing cell to release erythropoietin and parallelly to proliferate, and in long-term mutations and malignant transformation. Thus, ccRCC occurs about 30 years later in sporadic cases compared with familial von Hippel–Lindau syndrome, reflecting the time necessary for two versus one genetic change. Embryologically, there are many arguments favouring neural crest origin of the erythropoietin-producing cell

Morphology of G Cells in Hypergastrinemic Cotton Rats

In a strain of inbred cotton rats, 25-50% of females develop spontaneous gastric hypochlorhydria and  hypergastrinemia. Hypergastrinemic animals develop ECL cell derived gastric carcinomas located in the  oxyntic mucosa, thus being an interesting animal model for studying the role of gastrin in gastric carcinogenesis.  The response to gastric hypoacidity in cotton rats as regards the level of hypergastrinemia is far  more pronounced than in the more commonly used laboratory rat. It is unknown whether the pronounced  hypergastrinemic response in cotton rats is due to a greater population of G cells or a greater capacity of  hormone synthesis in each G cell. The aim of the study was therefore to examine G cell population and  ultrastructure in normogastrinemic and hypergastrinemic cotton rats by the use of immunhistochemical  methods applied on both light- and electron-microscopy. Five hypergastrinemic vs. five normogastrinemic  cotton rats were compared. Cotton rats with gastric hypochlorhydria have a 55-fold increase in serum gastrin levels and a 6-fold  increase in G cell number, but this is not accompanied by significant changes in G cell ultrastructure. The  lack of ultrastructural changes in these activated G cells indicates that previously reported changes in  chronic stimulated G cells are just one of several ways G cells are activated.

Animal Models to Study the Role of Long-Term Hypergastrinemia in Gastric Carcinogenesis

Patients with chronic hypergastrinemia due to chronic atrophic gastritis or gastrinomas have an increased risk of developing gastric malignancy, and it has been questioned whether also patients with hypergastrinemia caused by long-term use of acid inhibiting drugs are at risk. Gastric carcinogenesis in humans is affected by numerous factors and progresses slowly over years. When using animal models with the possibility of intervention, a complex process can be dissected by studying the role of hypergastrinemia in carcinogenesis within a relatively short period of time. We have reviewed findings from relevant models where gastric changes in animal models of long-term hypergastrinemia have been investigated. In all species where long-term hypergastrinemia has been induced, there is an increased risk of gastric malignancy. There is evidence that hypergastrinemia is a common causative factor in carcinogenesis in the oxyntic mucosa, while other cofactors may vary in the different models

Involvement of NF-κB/IL-6 Pathway in the Processing of Colorectal Carcinogenesis in Colitis Mice

publishedVersio

Classification of tumours

Tumours are classified according to the most differentiated cells with the exception of carcinomas where a few tumour cells show neuroendocrine differentiation. In this case these cells are regarded as redifferentiated tumour cells, and the tumour is not classified as neuroendocrine. However, it is now clear that normal neuroendocrine cells can divide, and that continuous stimulation of such cells results in tumour formation, which during time becomes increasingly malignant. To understand tumourigenesis, it is of utmost importance to recognize the cell of origin of the tumour since knowledge of the growth regulation of that cell may give information about development and thus possible prevention and prophylaxis of the tumour. It may also have implications for the treatment. The successful treatment of gastrointestinal stromal tumours by a tyrosine kinase inhibitor is an example of the importance of a correct cellular classification of a tumour. In the future tumours should not just be classified as for instance adenocarcinomas of an organ, but more precisely as a carcinoma originating from a certain cell type of that organ

Tumor classification should be based on biology and not consensus: Re-defining tumors based on biology may accelerate progress, an experience of gastric cancer

Abstract: Malignant tumors are a consequence of genetic changes mainly occurring during cell division, sometimes with a congenital component. Therefore, accelerated cell divisions will necessarily predispose individuals, whether due to conditions of chronic cell destruction or hormonal overstimulation. It has been postulated that two genetic hits are necessary for the development of malignancy (Knudson). The correct view is probably that the number of genetic changes needed depends on the role the mutated genes have in proliferation and growth control. Hormones should accordingly be regarded as complete carcinogens. In this review based upon experience of gastric cancer where gastrin is central in the pathogenesis, it is argued that oxyntic atrophy—and not metaplasia as postulated by Correa—is the central precancer change in gastric mucosa. Moreover, the target cell of gastrin, the enterochromaffin-like (ECL) cell, is central in gastric carcinogenesis and most probably the cell of origin of gastric carcinomas of the diffuse type according to Lauren (a classification probable in accordance with biology). The distinction between adenocarcinomas and neuroendocrine carcinomas based upon a certain percentage of cancer cells with neuroendocrine differentiation is questioned. To make progress in the treatment of cancer, a correct classification system and knowledge of the pathogenesis are necessary