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Review article: gall-bladder motor function in diabetes mellitus.

Although some controversy exists, diabetic patients generally are thought to have a two- to threefold increased risk of cholesterol gallstones. From previous studies there is no convincing evidence for a supersaturated bile in diabetics, whereas several reports indicate that impaired gall-bladder emptying could be one of the important factors in the increased incidence of gallstones in diabetics. However, studies of gall-bladder motility in diabetics have yielded conflicting results, probably because of substantial heterogeneity in the patients studied, emptying stimulus and technique used to assess gall-bladder motor function. The mechanism of the gall-bladder emptying abnormality in diabetics is not completely understood, although it has been proposed that it could represent a manifestation of denervation caused by visceral neuropathy. Based on normal post-prandial cholecystokinin release, it can be ruled out that impaired cholecystokinin release is the mechanism responsible for reduced gall-bladder emptying in diabetics. Other possible explanations for impaired gall-bladder contraction in diabetics include a decreased sensitivity of the smooth muscle of the gall-bladder to plasma cholecystokinin, and/or decreased cholecystokinin receptors on the gall-bladder wall.

Cholecystokinin↗

Hepatobiliary cystadenocarcinoma with cystadenoma elements of the gall bladder in an old man.

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.

Aged↗

Free amino Acid contents of stem and phylloxera gall tissue cultures of grape.

Free amino acid constituents were determined of grape stem and Phylloxera leaf gall callus in tissue culture. Fast, medium and slow growing single cell clones of, respectively, stem and gall origins were grown on a mineral salt-sucrose medium supplemented with coconut milk and alpha-naphthaleneacetic acid. Stem and gall clones showed qualitative similarities and quantitative variations in the amino acids and nitrogenous constituents. Nineteen amino acids, glucosamine, ethanolamine, sarcosine, methionine sulfoxides and ammonia were identified. Two free polypeptides accounted for over 30% of the amino compounds in the stem and gall callus tissues which were not found in the intact plant parts. Stem clones of different growth rates grown on agar showed generally an excess of amino acid constituents over gall tissues of similar growth rates, except for the free polypeptides. Fast growing stem clones grown on agar medium contained lower amounts of certain amino acids than the fast growing gall clones, but when grown in liquid medium they contained higher amounts of these acids than the gall clones. The total and nonsoluble nitrogen of stem clones were higher than in the gall clones. Tissue cultures differed from the original plant parts with respect to their free polypeptides and high amino acid contents.

Journal Article↗

Evolution of gall morphology and host-plant relationships in willow-feeding sawflies (Hymenoptera: Tenthredinidae).

There are over 200 species of nematine sawflies that induce galls on willows (Salix spp.). Most of the species are mono- or oligophagous, and they can be separated into seven or eight different groups based on the type of gall that they induce. We studied the evolution of different gall types and host plant associations by reconstructing the phylogeny of five outgroup and 31 ingroup species using DNA sequence data from the mitochondrial cytochrome b gene. Maximum-parsimony and maximum-likelihood analyses resulted in essentially the same phylogeny with high support for important branches. The results show that: (1) the galling species probably form a monophyletic group; (2) true closed galls evolved only once, via leaf folders; (3) with the possible exception of leaf rollers, all gall type groups are mono- or paraphyletic; (4) similar gall types are closer on the phylogeny than would be expected by a random process; (5) there is an apparent evolutionary trend in galling site from the leaf edge towards the more central parts of the host plant; and (6) many willow species have been colonized several times, which excludes the possibility of parallel cladogenesis between willows and the gallers; however, there are signs of restrictions in the evolution of host use. Many of the patterns in the evolutionary history of nematine gallers have also been observed in earlier studies on other insect gallers, indicating convergent evolution between the independent radiations.

Animals↗

Effect of calcitonin on gall-bladder volume in man.

The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.

Adult↗

Differences in c-fos gene product expression in cancers of the gall-bladder and biliary tract.

The c-fos gene encodes a 55 kDa nuclear protein product that complexes to a cellular protein, p39. The pattern of expression of c-fos is particularly complex with increased expression of the protein observed in undifferentiated cultured cells while reduced expression is found during terminal differentiation. The expression of c-fos gene was studied by immunohistochemistry in carcinoma of the gall-bladder (n = 13), biliary tract (n = 5) and ampulla of Vater (n = 9). Non-malignant conditions investigated include chronic cholecystitis (n = 11), gall-bladder dysplasia (n = 3) and adenoma (n = 1), and ampullary carcinoma in situ (n = 3). Strong positive granular cytoplasmic immunostaining for c-fos oncoprotein was present in most gall-bladder adenocarcinomas (n = 11; 85%). The single gall-bladder adenoma and only one of the dysplasia cases were positive. Most of the cases of chronic cholecystitis showed either absent or only focal to patchy and weak to moderate c-fos immunoreactivity in the deeper glands and Rokitansky-Aschoff sinuses but not in the superficial epithelium. None of the biliary tract and ampullary tumors showed immunostaining for c-fos. The difference in c-fos immunoreactivity between gall-bladder carcinoma and chronic cholecystitis was statistically significant (P = 0.0002; chi 2 test with continuity correction). In conclusion, c-fos protein may be important in the development of gall-bladder neoplasia with increased c-fos immunoreactivity in gall-bladder carcinoma but not in chronic cholecystitis, biliary tract and ampullary neoplasms. These findings suggest that gall-bladder carcinoma may arise from a different genetic basis compared to biliary tract and ampullary cancers.

Adenoma↗

Differential expression of pine and Cronartium quercuum f. sp. fusiforme genes in fusiform rust galls.

Cronartium quercuum f. sp. fusiforme is the causative agent of fusiform rust disease of southern pines in the United States. This disease is characterized by the formation of woody branch and stem galls. Differential display was used to identify pine genes whose expression is altered by C. quercuum f. sp. fusiforme infection and to identify C. quercuum f. sp. fusiforme genes that are expressed in fusiform rust galls. Six pine cDNAs that appeared to be differentially expressed in galled and healthy stems and 13 C. quercuum f. sp. fusiforme cDNAs expressed in galled tissues were identified. A probe that hybridizes specifically to C. quercuum f. sp. fusiforme 18S rRNA was used to estimate that 14% of the total RNA in fusiform rust galls was from C. quercuum f. sp. fusiforme. This finding was used to calibrate gene expression levels in galls when comparing them to expression levels in uninfected pines or in isolated C. quercuum f. sp. fusiforme cultures. According to Northern analysis and reverse transcriptase PCR analysis, all six of the pine clones were expressed at lower levels in galls than in healthy tissues. Seven of the nine C. quercuum f. sp. fusiforme clones that were assayed were expressed at higher levels in galls than in axenic culture. A number of the cDNAs encode proteins that are similar to those that play roles in plant development, plant defense, or fungal stress responses.

Basidiomycota↗

Resistance to chenodeoxycholic acid (CDCA) treatment in obese patients with gall stones.

In most patients with radiolucent gall stones who were given chenodeoxycholic acid (CDCA) in doses of 13-15 mg/kg body weight/day the bile became unsaturated in cholesterol, and their gall stones dissolved. The patients whose stones did not dissolve were significantly heavier and fatter than the responders, which suggested that obese patients might be "resistant" to the effects of CDCA. To test this hypothesis, 32 consecutive patients presenting for medical treatment of gall stones had their ideal body weight (IBW) and estimated body fat mass calculated. The eight most obese and the eight least obese patients were then selected, and their fasting bile lipid responses to CDCA 13-15 mg/kg/day were measured. The very obese patients were also given larger doses, and any changes in bile lipid composition were studied in relation to subsequent gall-stone dissolution.Before treatment the obese patients had a higher mean biliary cholesterol saturation index than the non-obese patients, and this difference was maintained during treatment with the normal dose of CDCA: the bile in the obese patients remained supersaturated while that in the non-obese became unsaturated with cholesterol. When the obese patients were given larger doses of CDCA their bile ultimately became unsaturated in cholesterol. Gall stones dissolved partially or completely in five of the eight non-obese patients after 6-18 months of 13-15 mg CDCA/kg/day, but none of the obese patients showed any response after comparable periods of treatment with this standard dose. With increased doses and unsaturated bile, however, three of the obese patients showed partial gall-stone dissolution after 3-12 months' treatment and one showed complete gall-stone dissolution after three years' treatment.These results suggest that when giving CDCA to patients with gall stones, larger than normal doses (some 18-20 mg/kg/day) should be prescribed. Alternatively the lipid composition of the patients' bile should be monitored by duodenal intubation and the CDCA dose increased until the bile becomes unsaturated in cholesterol.

Adult↗

Chemical and physical properties of gall stones in South Australia: implications for dissolution treatment.

Of 406 consecutive patients with gall-bladder stones, 387 were treated by cholecystectomy and 19 were treated with chenodeoxycholic acid. The gall stones found in 356 of the 387 patients at operation were analysed chemically for cholesterol and calcium, physically for number, size, and mass, and radiologically before cholecystectomy for stone lucency. Gall stones rich in cholesterol (greater than 80% by weight) were present in 75% of patients, while pigment stones (less than 25% cholesterol) were found in 12% of patients. Out of the 406 gall-stone patients, 77 (19%) had functioning gall bladders which contained radiolucent stones 1.5 cm or less in diameter, thereby fulfilling the criteria which are used by most clinicians in selecting patients for dissolution therapy of cholesterol gall stones. The stones of 61 of these patients were available for chemical analysis and 52 (85%) were rich in cholesterol. Using the more stringent criterion for stone size of 1 cm or less in diameter, only 11% of patients had stones suitable for dissolution treatment. Taking into account other factors such as lack of compliance with treatment, obesity, and calcium salts in gall stones, it appears that no more than 10% of gall-stone patients presenting to a general hospital could be successfully treated with chenodeoxycholic acid.

Adult↗

Pathogenesis of the impaired gall bladder contraction of coeliac disease.

We have investigated the possibility that the abnormally decreased gall bladder contraction after meals in patients with coeliac disease might result in part from an abnormality in the gall bladder response to endogenous cholecystokinetic hormones--for example, cholecystokinin and motilin--rather than solely from decreased secretion of such hormones. Eight patients with untreated coeliac disease and nine controls received intravenous infusions of the pure synthetic cholecystokinin analogue caerulein, 2-16 ng/kg/hour. Gall bladder emptying was measured on a minute-by-minute basis using 99mTc-HIDA scans. In the patients with coeliac disease, gall bladder emptying was greatly decreased (34.6 +/- 9.9 v 61.5 +/- 7.5% at 60 minutes, p less than 0.02), and a much greater dose of caerulein was needed to initiate gall bladder contraction (3.80 +/- 1.08 v 1.49 +/- 0.56 ng/kg, p less than 0.02). These results suggest that the abnormal gall bladder contraction in coeliac disease is not simply because of impaired release of cholecystokinin. Although mechanical factors secondary to the increased gall bladder size in patients with coeliac disease might to some extent account for the findings, the alternative explanation is that the gall bladder muscle is for some reason resistant to the action of cholecystokinetic agents. A similar phenomenon affecting the pancreas might contribute to the abnormally decreased pancreatic secretion found in coeliac disease.

Adult↗

Gall bladder emptying in normal subjects--a data base for clinical cholescintigraphy.

Biliary excretion scintigraphy with a cholagogic test meal may be used to assess patients with suspected disorders of gall bladder motility. The interpretation of results is frustrated, however, by the lack of information about the range of normal responses in a form suitable for comparative analysis. We present the results of 41 gall bladder emptying studies on 32 normal healthy subjects (14 men, 18 women) 30 minutes after intravenous injection of 74 MBq 99Tcm-EHIDA. Gall bladder emptying was provoked by the ingestion of 300 ml milk. Gamma camera scintigraphy was used to plot gall bladder activity against time. Gall bladder emptying occurred within 10 minutes in all men and 12/18 women (p = 0.02). Gall bladder ejection fractions were significantly greater in women (p less than 0.05). Duplicate studies in nine subjects showed good reproducibility (r = 0.959). A plot of mean and (m + 2 SD) values of gall bladder activity against time has been derived. The data provide an estimate of normal gall bladder emptying response, which may be used to aid interpretation of clinical studies.

Adult↗

CCK receptor antagonism by loxiglumide and gall bladder contractions in response to cholecystokinin, sham feeding and ordinary feeding in man.

The postprandial contractions of the gall bladder result from the interaction of neurohormonal factors but their relative contribution is unknown. This study was designed to determine the role of cholecystokinin (CCK) in gall bladder contractions using a highly selective and potent CCK-receptor antagonist, CR-1505 (loxiglumide) in healthy men either infused with exogenous CCK in graded doses (1.56-50 pmol/kg/h) or subjected to modified sham feeding (MSF) and ordinary feeding tests. The gall bladder volume measured by real time ultrasonography showed dose dependent decrease in the gall bladder volume in 10 subjects when CCK8 was infused iv in graded doses reaching about 15% at 1.56 pmol/kg/h and 91% at 50 pmol/kg/h. Close correlation between the decrease in gall bladder volume and the dosage of CCK or the increments in plasma CCK-bioactivity was observed. After pretreatment with loxiglumide, CCK resulted in similar increments in plasma CCK-bioactivity but failed to affect the gall bladder volume at CCK doses up to 6.25 pmol/kg/h and caused only 53% reduction at 50 pmol/kg/h. Modified sham feeding and real feeding reduced the volume of gall bladder by 20% and 70%, respectively and loxiglumide decreased these values to 15% and 30%, respectively. This study provides evidence that loxiglumide is highly potent and selective CCK antagonist and that endogenous CCK plays an important role both in the postprandial contractions of gall bladder.

Adolescent↗

Effect of octreotide on fasting gall bladder emptying, antroduodenal motility, and motilin release in acromegaly.

Subcutaneous octreotide (Sandostatin) injections lead to gall stone formation in 13-50% of acromegaly patients during one year of therapy. This study explored the effects of octreotide on interdigestive gall bladder emptying, antroduodenal motility, and motilin release. Ambulatory antroduodenal manometry was performed in six acromegaly patients before and after two months of octreotide therapy (100 micrograms thrice daily, subcutaneously). Ultrasonographic gall bladder volume measurements and plasma motilin concentrations were obtained during two migrating motor complex (MMC) cycles. Before octreotide treatment, nine of 26 phase III activities started in the antrum and 17 of 26 in the duodenum whereas during treatment 47 of 48 of phase III activity started in the duodenum (p < 0.05). Before treatment, interdigestive gall bladder emptying (mean (SEM) 39.9 (4.0)% of maximal fasting volume) and plasma motilin peaks preceded antral phase III but not duodenal phase III. During octreotide therapy no significant motilin fluctuation or gall bladder emptying was seen. Fasting gall bladder volume increased from 40.9 (9.1) ml before to 68.0 (14.8) ml (p < 0.05) during octreotide treatment. In conclusion, two months' treatment with octreotide increases the number of duodenal phase III like activity and virtually abolishes antral phase III, plasma motilin peaks, and interdigestive gall bladder emptying. These effects might contribute to the high risk of gall stone formation during longterm octreotide treatment.

Acromegaly↗

Increased gall bladder volume in primary sclerosing cholangitis.

BACKGROUND: The diagnosis of primary sclerosing cholangitis (PSC) requires invasive procedures such as liver biopsy and endoscopic retrograde cholangiography (ERC). Sonographic measurement of fasting gall bladder volume, which has been reported to be enlarged in PSC, could serve as a non-invasive screening test. METHODS: Fasting gall bladder volume was studied in patients with PSC (n = 24), primary biliary cirrhosis (PBC, n = 13), liver cirrhosis due to other causes (n = 18), ulcerative colitis (n = 15), and healthy controls (n = 23). Meal induced gall bladder emptying was studied in patients with PSC, patients with PBC, and healthy controls. RESULTS: In patients with PSC gall bladder volume was greatly enlarged (72.9 (SEM 3.7) ml) compared with healthy controls (25.4 (1.7) ml, and patients with PBC (30.9 (2.7) ml), liver cirrhosis (31.3 (4.0) ml) or ulcerative colitis (25.8 (2.0) ml) (p < 0.0005 v all). In four patients with PSC the gall bladder wall was irregularly thickened (> 4 mm) as previously described in PSC. Postprandial residual fractions (% of fasting volume) were comparable between patients with PSC (17.5 (3.7)%) and those with PBC (23.6 (7.1%) and healthy controls (12.7 (2.3)%) Although gall bladder emptying seems normal, increased biliary pressure in patients with PSC cannot be excluded. CONCLUSION: Apart from wall thickening, patients with PSC often present with enlargement of the gall bladder. Sonographic determination of fasting gall bladder volume may be a useful, non-invasive, and easy to perform tool in the evaluation of patients suspected of having PSC.

Adolescent↗

Morphogenesis of galls induced by Baccharopelma dracunculifoliae (Hemiptera: Psyllidae) on Baccharis dracunculifolia (Asteraceae) leaves.

The commonest insect gall on Baccharis dracunculifolia (Asteraceae) leaves is induced by Baccharopelma dracunculifoliae (Hemiptera, Psyllidae). The gall-inducing insect attacks young leaves in both the unfolded and the fully expanded stages. Four developmental phases were observed in this type of gall: 1) A folding phase, during which the leaf lamina folded upward alongside the midrib and the edges of the upper portion of the leaf approached each other, forming a longitudinal slit. A single chamber was formed on the adaxial surface of the leaf; 2) A swelling phase, in which the folded leaf tissues thickened and the edges of the leaf drew closer together, narrowing the slit. In this phase the gall matured, turning succulent, fusiform and pale green. The single nymphal chamber was lined with white wax and was able to house from one to several nymphs; 3) A dehiscence phase, characterized by the opening of the slit to release inducers; and 4) A senescence phase, when the gall turned dark and dry. The dermal system of the mature gall was composed of a single-layered epidermis. The mesophyll was swollen, and the swelling was due mainly to hyperplasia of the parenchyma. The vascular tissues along the midrib vein were conspicuous and the perivascular fibers resembled parenchymal cells. The hypertrophied secretory cavities contained low lipophylic content. This gall does not form nutritive tissue, but salivary sheaths left by the inducers were observed near the parenchyma, vascular bundles and secretory cavities. This study complements our current knowledge of gall biology and sheds further light on the plasticity of plant tissues stimulated by biotic factors.

Animals↗

Comparative anatomy of gall development on Gypsophila paniculata induced by bacteria with different mechanisms of pathogenicity.

Galls induced on Gypsophila paniculata by Pantoea agglomerans pv. gypsophilae (Pag) and Agrobacterium tumefaciens (At), bacteria with different mechanisms of pathogenicity, were compared morphologically and anatomically. The pathogenicity of Pag is dependent on the presence of an indigenous plasmid that harbors hrp gene cluster, genes encoding Hop virulence proteins and biosynthetic genes for auxin (IAA) and cytokinins (CKs), whereas that of At involves host transformation. The Pag-induced gall was rough, brittle and exhibited limited growth, in contrast to the smooth, firm appearance and continuous growth of the At-induced gall. Anatomical analysis revealed the presence of cells with enlarged nuclei and multiple nucleoli, giant cells and suberin deposition in Pag that were absent from At-induced galls. Although circular vessels were observed in both gall types, they were more numerous and the vascular system was more organized in At. An aerenchymal tissue was observed in the upper part of the galls. Ethylene emission from Pag galls, recorded 6 days after inoculation, was eight times as great as that from non-infected controls. In contrast, a significant decrease in ethylene production was observed in Gypsophila cuttings infected with Pag mutants deficient in IAA and CK production. The results presented are best accounted for by the two pathogens having distinct pathogenicity mechanisms that lead to their differential recognition by the host as non-self (Pag) and self (At).

Caryophyllaceae↗

Lipid metabolism by the gall-bladder. I. The in situ uptake and metabolism of lysophosphatidylcholine.

Accumulation of lysophosphatidylcholine in gall-bladder bile is involved in the pathogenesis of acute cholecystitis. [1-14C]oleoyl- or [1-14C]palmitoyl-lysophosphatidylcholine was thus instilled in the in situ guinea pig gall-bladder and the absorption and metabolism of the lipid were determined. We found that, after 6 h instillation, 53% of the oleoyl derivative was adsorbed by the gall-bladder, whereasee only 37% of the palmitoyl derivative was absorbed. Although some differences in the metabolism of these two lipids were observed, a major portion of the absorbed radioactivity was found in the gall-bladder wall as phosphatidylcholine. To determine the mechanism of phosphatidylcholine formation from lysophosphatidylcholine by the gall-bladder mucosa, we used lysophosphatidylcholine which was labelled in the fatty acid moiety with 14C and in the choline moiety with 3H. Our data suggest that the mechanism of phosphatidylcholine formation from lysophosphatidylcholine involved acylation with an acyl donor other than a second molecule of lysophosphatidylcholine. We hypothesize that this mechanism as well as others described serve to prevent accumulation of lysophosphatidylcholine within the gall-bladder lumen and thus prevent damage to the gall-bladder mucosa.

1-Acylglycerophosphocholine O-Acyltransferase↗

Expression of MDR1 mRNA and encoding P-glycoprotein in archival formalin-fixed paraffin-embedded gall bladder cancer tissues.

The aim of this study was to examine the expression of P-glycoprotein (Pgp) and MDR1 mRNA, in gall bladder carcinoma, a chemo-resistant tumour. 26 cases of gall bladder cancer and nine samples of normal gall bladder archival paraffin blocks were investigated for the presence of Pgp protein with immunohistochemistry (IHC) and MDR1 RNA by reverse transcription-polymerase chain reaction (RT-PCR). Monoclonal antibodies JSB-1 and UIC-2, recognising separate epitopes of Pgp, were used for IHC. For RT-PCR, total RNA was extracted from paraffin-embedded tissue. After RT, the samples were subjected to nested PCR (NPCR) using primers specific for the MDR1 gene, and evaluated by electrophoresis. In gall bladder carcinoma, the percentage of positive cases expressing Pgp (77% for JSB-1, 69% for UIC-2) and MDR1 mRNA (52%) was significantly higher than those in normal gall bladder. In earlier TNM stages Pgp and MDR1 mRNA were more frequently expressed (non-significant) than in advanced stages. The results of this study suggested that overexpression of MDR1 mRNA and Pgp in gall bladder carcinoma tissue probably is a very important reason why gall bladder cancer is generally not responsive to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗