Changes in composition of mucin in the mucosa adjacent to carcinoma of the colon as compared with the normal: A biochemical investigation

Filipe, M. I.; Cooke, K B

doi:10.1136/jcp.27.4.315

Cited by 75 publications

(18 citation statements)

References 36 publications

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“…If this hypothesis is correct, then they may play an important role in the immunological reaction to tumour specific antigens in the control of tumour growth (Baldwin, 1970). In fact, we have found greater amounts of neuraminidase sensitive neuraminic acids in the mucosa around carcinoma in man (Filipe and Cooke, 1974) and they are more abundant in our most invasive tumours (Filipe and Branfoot, 1974). In DMH treated rats we have also observed that the amount of sialomucins present in the focal areas of dysplasia varies during the progress of the experiment, possibly reflecting the immunological status of the host and thus affecting the tumour growth potential.…”

Section: Discussionmentioning

confidence: 63%

“…The histochemical changes in the composition of the goblet cell mucin consist of an increase in sialomucins as compared with the normal mucosa in which sulphomucins predominate. The higher level of sialic acids is accompanied by a rise in neuraminidase-sensitive sialic acids (Filipe and Cooke, 1974), a feature described in the human foetal gut mucin (Lev and Orlic, 1974).…”

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confidence: 99%

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Mucous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study

Filipe¹

1975

Br J Cancer

178

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Summary.-Our previous studies, in specimens of large intestine resected for carcinoma, have shown abnormal patterns of mucous secretion in areas of apparently " normal " mucosa, where goblet cells produce mainly sialomucins as compared with the true normal colonic mucosa in which sulphomucins predominate. In the present work, large bowel cancer was induced in rats by the administration of 1,2-dimethylhydrazine-2HCl (DMH). We attempted to study the sequential histological and secretory abnormalities which developed in the colonic epithelium during carcinogenesis, and to correlate these changes with those described above in the human. The microscopical and histological lesions observed in the colonic mucosa of DMH treated rats confirmed the findings of other authors and resembled the human colorectal cancer. The earliest changes detected were small foci of hyperplasia accompanied from the 6th week onwards by several foci of dysplasia. Carcinoma in situ appeared at the 15th week and finally invasive carcinoma developed from the 19th week onwards. Changes in the type of mucous secretion, with predominance of sialomucins, were observed in the majority of the areas showing mild to moderate dysplasia whilst the surrounding normal epithelium produced sulphated material. Mucous depletion was a common feature in areas of severe dysplasia and carcinoma.These findings correlated well with the similar variations in the mucin composition observed in human colonic mucosa in carcinoma and further supported our previous hypothesis that mucin changes characterized by an increase in sialomucins might reflect early malignant transformation. If this hypothesis proved to be correct, the use of a simple method for the identification of mucins in large bowel biopsies would be of great help in detecting early malignancy.

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Section: Discussionmentioning

confidence: 63%

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confidence: 99%

Mucous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study

Filipe¹

1975

Br J Cancer

178

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“…In the present study, multifocal expression of the BGP was observed in the colorectal mucosa adjacent to 'de novo' carcinoma. The BGP foci may be involved in the 'transitional mucosa' (Filipe and Cooke, 1974) as mentioned earlier, because the similar histologic characteristics to transitional mucosa such as crypt distortion and basal cell hyperplasia were observed in the BGP foci. The sites of BGP expression in tubules usually localized in the generative zone, where a carcinoma is supposed to arise from (Ming et al, 1967;Nagayo, 1975;Oohara et al, 1982;Shimada et al, 1984Shimada et al, , 1992Matsuzaki et al, 1998).…”

Section: Discussionmentioning

confidence: 58%

“…These results indicate that the BGP focus may contribute to the carcinogenesis of the 'de novo' carcinoma. Adjacent mucosa around existing carcinoma, the so-called 'transitional mucosa' (Filipe and Cooke, 1974), has been advocated as a distinct entity which is indicative of premalignant changes such as high proliferative activity (Wang et al, 1992) or K-ras mutation (Zhang et al, 1998) in the crypt stem cell. These observations support the contention that a malignant field change exists in transitional mucosa adjacent to a colorectal carcinoma.…”

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confidence: 99%

Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human ‘de novo’ colorectal carcinomas

et al. 2001

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‘de novo’ carcinogenesis has been advocated besides ‘adenoma carcinoma sequence’ as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of ‘de novo’ carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the ‘de novo’ carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa ( P < 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of ‘de novo’ colorectal carcinogenesis. © 2001Cancer Research Campaign http://www.bjcancer.com

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“…The concentrations of sialic acid and hexosamines are higher in mucin secreted by transitional mucosa that is immediately adjacent to colon tumor than the mucin secreted by normal mucosa. 36 At colonic pH, sialic acid will remain deprotonated and will carry a negative charge. The free carboxyl group of calcium alginate will also be deprotonated at the said pH and thereby repel the negatively charged sialic acid moieties.…”

Section: In Vitro Mucoadhesive Propertiesmentioning

confidence: 99%

The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

Thakral¹,

Ray²,

Bar‐Shalom³

et al. 2011

IJN

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The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib.

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Changes in composition of mucin in the mucosa adjacent to carcinoma of the colon as compared with the normal: A biochemical investigation

Cited by 75 publications

References 36 publications

Mucous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study

Mucous secretion in rat colonic mucosa during carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study

Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human ‘de novo’ colorectal carcinomas

The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

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