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R Gautier

Publications and source records attributed to R Gautier.

At least 37 records · Page 2Linked to original sources
PubMed1991

Oncofetal mucin M1 epitope family: characterization and expression during colonic carcinogenesis.

The gastric mucin M1 antigens, markers associated with colonic carcinogenesis, have been characterized by new antimucin monoclonal antibodies (MAbs). These MAbs, obtained against mucins isolated from a human ovarian mucinous cyst (MAbs 19M1, 21M1 and 45M1) and from a pancreatic adenocarcinoma (MAb 96RA), were compared with 5 other anti-M1 mucin MAbs described previously, which characterized the a, b, c, d and e mucin M1 epitopes. Using immunoperoxidase, these new MAbs exclusively stained the surface gastric epithelium of normal human gastro-intestinal tract and reacted with fetal, precancerous and cancerous colonic mucosa, but not with normal colon. Immunoradiofixation studies showed that these new MAbs are directed against 3 epitopes (f, g and h) which are different from the a, b, c, d and e mucin M1 epitopes, though present on the same a immunoreactive high-molecular-weight components (greater than 1,000 kDa) with a density of 1.4 by CsCl-density-gradient ultracentrifugation. M1 antigenicity is characterized by a family of 8 different M1 epitopes which were destroyed with beta-mercaptoethanol (except for the f epitope), sensitive to a 5 hr trypsin treatment and resistant to 5 mM periodate (except for the h epitope). Some epitopes (b, c and d) showed increasing immunoreactivity after 20 mM periodate treatment, suggesting cryptic location. In rat-colon adenocarcinomas, M1 mucin epitopes were masked but could be decrypted using high periodate treatment, similar to normal rat gastric mucosa, thus suggesting the absence of drastic changes in the saccharide coat of the peptide mucin portion bearing M1 epitopes. Cryptic location, periodate resistance, sensitivity to protease and conformational behavior strongly suggest that the peptidic core of gastric (or fetal colonic) mucin plays a role in M1 immunoreactivity. Indeed, the resurgence of M1 antigens during colonic carcinogenesis is due to re-expression of the peptide core of gastric (or fetal colonic) mucins.

Animals↗
PubMed1990

Evidence of mucin M1 antigens in seminal plasma and normal cells of human prostatic urethra in relation to embryonic development and tumors.

By employing immunoperoxidase methodology, using monoclonal antibodies against the peptide core of gastric mucins (M1 antigens), we demonstrate the presence of M1 mucin-producing cells that are associated with the prostatic urethral epithelium and located mainly in the veru montanum area near the prostatic ductal and utriculus junctions. The significance of these M1 cells is not yet clear. Using an immunoradiometric assay, these M1 mucins were found predominantly in the prostatic fraction obtained from seminal plasma. By chromatography on Sepharose 6B and 2B and cesium chloride gradient centrifugation, we demonstrate that high-molecular-weight components (greater than 10(7) Da) show a density of 1.45 g/ml, similar to mucins, and are immunochemically related to peptidic gastric M1 mucins. The particular location of these M1 antigens in prostatic adult urethra and their fetal expression in cloacal structures suggest that, in males, the prostatic urethral epithelium includes some remnant cells from the enteric cloaca. Finally, the presence of mucin-containing cells in the prostatic urethra could possibly explain the histogenesis of the rare benign villous tumors and primary mucinous adenocarcinomas arising from the prostatic urethral epithelium.

Adult↗
PubMed1989

Induction of rat intestinal carcinogenesis with single doses, low and high repeated doses of 1,2-dimethylhydrazine.

We investigated seven different procedures for chemical induction of rat colonic carcinogenesis using: repeated high doses (i) weekly 10 x 15 mg/kg, (ii) quarterly 8 x 15 mg/kg; repeated low doses (iii) weekly 27 x 1.5 mg/kg, (iv) quarterly 8 x 5 mg/kg, (v) quarterly 8 x 1 mg/kg; and single injections of 1,2-dimethylhydrazine (DMH) at (vi) 1 x 40 mg/kg or (vii) 1 x 20 mg/kg. Rats had typical histological precancerous lesions of the colon (dysplasia) and intestinal carcinomas in the six groups receiving a total dose of more than 8 mg/kg DMH. With doses of greater than 120 mg/kg, rats had more cancers, particularly intestinal carcinomas and significantly reduced survival. Rats receiving a single injection of 20 or 40 mg/kg also had histological lesions and colonic carcinomas. The group receiving a 40 mg/kg total dose in a single injection had a significantly higher frequency of colonic lesions per rat and a higher incidence of rats with colonic lesions than groups receiving the same total dose but fractionated. Control rats and groups injected with an 8 mg/kg total dose had no cancers, nor pre-cancerous histological lesions. Thus the carcinogenesis is dose-related, but for the same final dose a single injection gives more histological colonic lesions than several recurrent injections; however, the number of colonic carcinomas and the survival did not vary. This lack of correlation between the number of dysplasia and the number of adenocarcinomas may indicate that dysplasia is not always the precursor lesion of adenocarcinoma. With repeated low doses, we obtained colonic adenocarcinomas after a long period of latency in old rats, thus producing an experimental model with characteristics similar to those found in humans.

1,2-Dimethylhydrazine↗
PubMed1988

Immunochemical characterization of mucins. Polypeptide (M1) and polysaccharide (A and Leb) antigens.

Seven monoclonal antibodies (MAbs) reacting with high-molecular-mass components (greater than 20,000 kDa) isolated from an ovarian mucinous cyst of an A Le(a-b+) patient are described. By the use of immunoradiometric methods, these MAbs characterized seven different epitopes associated with components having a density of 1.45 g/ml by CsCl-density-gradient ultracentrifugation, like mucins. Two MAbs reacted with A and Lewis blood-group antigens respectively (polysaccharide epitopes). The five other MAbs characterized five M1 epitopes (called a, b, c, d and e), mainly associated with components of more than 20,000 kDa and 2000 kDa. They were completely destroyed by papain and 2-mercaptoethanol treatment (polypeptide epitopes). Moreover, timed trypsin digestion of native mucin resulted in a progressive loss of M1 activity and degraded these mucins into smaller M1-positive fragments. The a and c epitopes were partially degraded from relatively high-molecular-mass fragments (2000 kDa to 500 kDa) into a 100 kDa fragment. The b and d epitopes were completely degraded into smaller fragments ranging from 100 kDa to 40 kDa. The e epitope was completely destroyed by trypsin. These different pathways of M1 antigen degradation suggest the occurrence of different epitopes located in separate regions of the mucin molecules.

Antibodies, Monoclonal↗
PubMed1988

Ectopic expression of the Y (Ley) antigen defined by monoclonal antibody 12-4LE in distal colonic adenocarcinomas.

Monoclonal antibody (MAb) 12-4LE reacts specifically with the alpha Fuc(1-2) beta Gal(1-4) [alpha Fuc(1-3)]GlcNAc-R synthetic oligosaccharide and consequently characterizes the Y (Ley) antigen. In normal individuals, this MAb reacts more strongly on samples from blood group O persons, indicating that the Y structure is better recognized when terminal A or B sugars are not added to the Y structure. In fetal and normal adult gastrointestinal tract, this antibody reacts with the epithelium of stomach, small intestine and proximal colon, but not of distal colon. In the adult, cells from the surface epithelium of the gastric, small intestinal and cecal mucosae express the Y antigen according to the secretor phenotype of each individual, thus characterizing the so-called "upward differentiation" pattern. In contrast, mucus cells of the pylorus and duodenal Brünner glands, as well as Paneth cells, always express the Y antigen irrespective of secretor phenotype, thereby characterizing the so-called "downward differentiation" pattern. Proximal fetal colonic mucosa has the same genetic control as the downward differentiation pattern of the adult. Distal fetal colonic mucosa is negative with anti-Y, as in the adult. Y antigen was not expressed in hyperplastic (10 cases), juvenile (5 cases) or adenomatous (43 cases) polyps, except for some spreading villous adenomas in which rare Y-positive foci could be observed but which were not specifically associated with dysplastic glands. Polyps from familiar polyposis did not express this antigen. In adenocarcinomas, the Y antigen was expressed in 41/45 (91%) of distal tumors and 15/35 (43%) of cecal tumors, independently of ABO phenotype. The ectopic expression of this Y antigen on distal colon adenocarcinomas may be a useful tool in the detection of distal colonic carcinomas.

ABO Blood-Group System↗
PubMed1988

A new mucin-associated oncofetal antigen, a marker of early carcinogenesis in rat colon.

We report the characterization of an IgG2a monoclonal antibody, (MAb) 660, prepared against rat gastric high molecular weight glycoproteins. By immunoperoxidase staining, MAb 660 reacted only with the mucous cells of surface gastric epithelium and with a few duodenal goblet cells close to the pylorus in normal adult rats. In fetuses, it reacted with intestinal and colonic goblet cells. The adult colon was always negative. The MAb 660 stained 100% (30 of 30) of chemically induced colonic carcinomas and 100% (7 of 7) of duodenal carcinomas. Several weeks before the appearance of tumors, histologically normal glands, then hyperplasia and dysplasia were precociously stained with MAb 660. The tissue distribution was different from that of blood group related antigens and M1 fucomucins. The recognized antigen was not sensitive to neuraminidase treatment. After electrophoresis in polyacrylamide gel, staining with periodic acid-Schiff reagent and Western blotting showed that the MAb 660 recognized an epitope associated with high molecular weight glycoproteins. This epitope was unaffected by beta-mercaptoethanol reduction-periodate treatment and neuraminidase and trypsin digestion. However, trypsin digestion performed after beta-mercaptoethanol reduction destroyed the 660 epitope. These data suggest that the antibody could recognize the peptide moiety of the mucin rather than its carbohydrate moiety. Thus, the new antigen identified by MAb 660 is a mucin-type glycoprotein with an oncofetal behavior in the rat colon and is precociously expressed by precancerous colonic mucosa.

Animals↗
PubMed1988

Rat colonic carcinogenesis after ureterosigmoidostomy: pathogenesis and immunohistological study.

A group of 44 rats underwent the equivalent of a ureterosigmoidostomy (US), while a second group of 18 rats underwent a pediculated graft (PG) of urothelial tissue in the sigmoid wall. Histological lesions were observed in the colon near the bladder colon junction in US rats exclusively. These lesions included dysplasias (5/23), cystic glands (4/23) and 10 neoplasms (9/23), three of which were adenomas, showing elements of juvenile polyp and tubular adenoma in one case. The seven other tumors showed typical histological features of colonic adenocarcinomas, but no frank evidence of parietal tumoral invasion was observed and their cancerous nature was questionable. It is probably a true carcinogenesis since we induced the same histological changes as those in the mucosae adjacent to colonic adenocarcinomas after human US surgery. Moreover, by immunoperoxidase using antibodies against mucus associated antigens (M1 and M3C antigens) we demonstrated that US rat carcinogenesis differs from dimethylhydrazine (DMH) rat carcinogenesis. Furthermore, our results suggest that urine may be an important factor in inducing this type of US carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1987

Monoclonal antibody against sialylated Lewis(a) antigen.

We isolated hybridoma cells, which secreted monoclonal antibody (MAb) 121 SLE, an IgM showing the following reactivities: (1) by immunodiffusion, MAb 121 SLE and MAb NS 19-9 (a monoclonal antibody directed against a sialylated Lewis(a) antigen called CA 19-9) showed an identical precipitin line with mucin preparation containing this CA 19-9; (2) by immunoradiometric assay, MAb 121 SLE totally inhibited fixation of radiolabelled MAb NS 19-9; (3) by immunoperoxidase, MAb 121 SLE stained the normal gastrointestinal mucosa of Le-positive individuals exclusively, and this staining disappeared after neuraminidase treatment, as observed using MAb NS 19-9. However, the pattern of the staining obtained with MAb 121 SLE differed slightly from that given by MAb 19-9 on the different positive areas of the gastrointestinal mucosae. These differences principally concerned the number of positive epithelial cells and the intensity of their staining; (4) moreover, antibodies against idiotype determinant of NS 19-9 antibody did not react with the antibody 121 SLE. We concluded that MAb 121 SLE is different from the MAb NS 19-9. However, both these antibodies were associated with the same molecular sialylated Lewis(a) structure.

Animals↗
PubMed1986

Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae.

We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALeb patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status. They did not stain normal colonic mucosae, but did stain fetal and precancerous colonic mucosae. Using serial sections, each anti-M1 MAb stained the same goblet cells in fetal and precancerous colon. Extensive search of other normal tissues showed that M1 antigens were restricted to the epithelium embryologically derived from the foregut (gastric and bronchial epithelium) and from Müllerian ducts (mucus cells of endocervix and prostatic utriculus). Some differences in the reactivities of the various anti-M1 MAb were observed in subesophageal, subtracheal, and endocervical mucus cells, suggesting that each anti-M1 MAb characterized a different M1 epitope. A mixture of these five anti-M1 MAbs allowed the estimation of M1 mucus modification in the precancerous colonic mucosae with a sensitivity near to that obtained with polyclonal anti-M1 antibodies. Papain and mercaptoethanol treatments destroyed the M1 epitopes, at variance with the A- or Lewis-related antigens. Our results therefore suggest that the expression of M1 epitopes in precancerous colonic mucosae cannot be due exclusively to alterations in mucin glycosylation but may be related to the reexpression of antigens associated with native gastric mucin which is normally produced by the fetal colon during the sixth month of gestation.

Adolescent↗
PubMed1986

Fetal and ectopic mucous markers expressed by distal and proximal rat colonic carcinomas.

Using immunohistochemistry, seven markers associated with mucous glycoproteins were studied in rat colonic mucosa during fetal and adult life and in carcinomas. These included: blood group A antigen, terminal fucose, sulfated and sialylated groups, M3 intestinal, M3C colonic and M1 gastric antigens. It was found that colonic carcinomas expressed normal adult markers, fetal markers and an ectopic marker. The differentiation of goblet cells was not the same in distal and proximal colon. Finally, this differentiation shared numerous analogies with that of human colonic goblet cells.

ABO Blood-Group System↗
PubMed1984

Abnormal pattern of mucus-associated M1 antigens in histologically normal mucosa adjacent to colonic adenocarcinomas.

Apparently normal mucosae adjacent to colon adenocarcinomas were studied by cutting strips of mucosa from the entire length of 120 surgical specimens (94 located on the distal colon and 26 on the proximal colon). These mucosae were coiled into "Swiss rolls." Their mucus alterations were mapped by immunoperoxidase using antibodies against M1 antigens, oncofetal markers associated with precancerous colonic mucosa. We demonstrated mucus modifications in patches of mucosa at a distance from frank tumors. The extent of these alterations was not related to invasion by the adjacent carcinoma according to Dukes' classification. However, these mucus modifications were more frequently observed on the distal than on the proximal side, were more often found adjacent to mucinous hyperplasia or adenoma, and were observed in 8 of 10 mucosae bearing metachronous or synchronous distal colonic adenocarcinomas. Our results suggest that the M1 modifications characterizing an early stage of carcinogenesis could have a putative prognostic value in estimating the risk for metachronous distal colonic adenocarcinomas.

Adenocarcinoma↗