Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, there has been much interest in the use of radionuclide conjugated monoclonal antibodies for the treatment of human malignancies. One way to potentially maximize the therapeutic effectiveness of radioimmunotherapy would be to sensitize tumor cells to the radiation dose delivered by the antibody. Since radioimmunotherapy can potentially treat disseminated disease, including micrometastasis, we chose to study a halogenated pyrimidine radiosensitizer, a class of compounds that affect nonhypoxic cells. 5-Iododeoxyuridine, administered with pyrimidine metabolism modulators, increased the therapeutic effectiveness of radioimmunotherapy, resulting in individual cures of human tumors growing in BALB/c nu/nu (nude) mice. 5-Iododeoxyuridine was administered with N-(phosphonacetyl)-L-aspartic acid and 5-fluoro-deoxycytidine plus tetrahydrouridine. This drug treatment was combined with radioimmunotherapy using 131I conjugated to a monoclonal antibody, Mc5. Mc5 binds to a mucin component of the human milk fat globule. This antigen is expressed on the surface of MX-1 cells, the transplantable human tumor used in this study. Tumor-bearing mice treated with both the drug protocol and 131I-Mc5 (540 microCi, 10 microCi/micrograms) showed a regression in average tumor volume. The average tumor volume was reduced below the initial size at treatment for 50 days; two of five cures were obtained. Neither cures nor regressions were observed with either the drug or antibody treatments alone. Our results indicate the potential for increasing the therapeutic effectiveness of radioimmunotherapy of human solid tumors with halogenated pyrimidines.
 ...
PMID:5-Iododeoxyuridine increases the efficacy of the radioimmunotherapy of human tumors growing in nude mice. 163 46

B1 and B3 are two newly isolated monoclonal antibodies that react uniformly with the surface of many mucinous carcinomas of the colon, stomach, and ovary but with a limited number of normal tissues, among which are glands of the stomach, epithelia of the trachea and bladder, differentiated epithelium of the esophagus, and small bowel mucin. They also react uniformly with many human tumor cell lines, including MCF7, MDA-MB-468, and HTB20 (breast), A431 (epidermoid), HT29 (colon), HTB33 (cervical), and DU145 (prostate). Immunoprecipitation experiments indicate that B1 and B3 react with epitopes present on a large number of glycoproteins, ranging in molecular weight from greater than 200,000 to less than 40,000. Using a panel of 37 different carbohydrate residues attached to albumin to form neoglycoproteins, it was found that B1 reacts with Ley and H-type 2 and B3 reacts with Ley, di-Lex, and tri-Lex antigens. Thus, each antibody reacts with a distinct portion of a carbohydrate residue. Because of the limited reactivity of these antibodies with normal tissues, they merit evaluation in the treatment of cancer.
Cancer Res 1991 Jul 15
PMID:Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. 164 44

The inaccessibility of radiolabeled antibody to poorly vascularized regions of solid tumors may reduce the therapeutic efficacy of these macromolecules. Theoretical mathematical models have predicted that increasing the protein dose administered would reduce the heterogeneity of radioantibody distribution. This investigation was undertaken to evaluate this hypothesis in experimental animal models. We have utilized the technique of macroautoradiography to demonstrate an increase in tumor penetration of the lower-affinity 125I-labeled NP-4 or higher-affinity Immu-14 anti-carcinoembryonic antigen (anti-CEA) mAbs into small (60.25-0.4 g) and large (0.8-1.5 g) GW-39 and LS174T human colonic xenografts, grown subcutaneously in the nude mouse, when 400 micrograms unlabeled antibody is administered simultaneously with 10 micrograms (100 microCi) radioantibody. Further increases in protein to 800 micrograms result in a reduction in total tumor uptake of the antibody. These in a reduction in total tumor uptake of the antibody. These differences in mAb distribution could be visualized as early as 1 day after antibody injection. Improved mAb penetration was also achieved for the Mu-9 anti-CSAp (anti-mucin) antibody using 800 micrograms unlabeled antibody. An irrelevant antibody (AFP-7-31) was found to be homogeneously distributed 3 days after injection, even at a low protein dose. Attempts to improve mAb penetration by increasing the protein dose in the GS-2 colorectal tumor, a model that has low NP-4 accretion as a result physiological barriers separating antibody from antigen, were not successful. These results suggest that a more homogeneous distribution of radioantibody can be achieved by carefully selecting a dose of unlabeled antibody to coadminister. Work is currently in progress to determine the effect of improved tumor distribution of radioantibody on the therapeutic potential of a single dose of radioantibody.
Cancer Immunol Immunother 1991
PMID:The effect of antibody protein dose on the uniformity of tumor distribution of radioantibodies: an autoradiographic study. 165 55

A comparative study was undertaken among mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma and normal salivary glands using lectin affinity histochemical method. It was found that the positive rate was highest in mucoepidermoid carcinoma (P less than 0.05); Among the 4 kinds of lectins used PNA and UEA had different distributions and contents in cancer and control groups (P less than 0.05). The mucoid substances in the cancer tissue were mixed mucin, similar to those in the normal salivary gland. However, there was more mixed mucin in the former than in the latter. This method is useful in diagnosis of salivary gland carcinoma. The relation of glucoprotein content on the cancer cell surface and carcinogenesis is discussed.
 ...
PMID:[Preliminary study on lectin affinity histochemistry for diagnosis and histogenesis of salivary gland carcinoma]. 165 18

The occurrence of a point mutation on the 12th and 13th codons of the Ki-ras oncogene has been investigated in 99 colorectal carcinomas in relation to 3 histological parameters: extent of differentiation, occurrence of a mucinous component within the tumor, and presence of peripheral adenomatous polyp remnants. The mutation frequency increased with each parameter: from 13% (2/15) to 44% (37/84) with differentiation, from 33% (26/79) to 65% (13/20) with mucinous character, and from 27% (15/56) to 56% (24/43) with the presence of polyp remnants. The frequency was highest in well-differentiated mucinous tumors with adenomatous remnants 83% (5/6). We suggest that Ki-ras mutation is preferentially involved in carcinomas that have developed from adenoma and that the mutation preserves differentiation and mucin secretion in these cancer cells.
Int J Cancer 1991 Sep 09
PMID:Association of Ki-ras mutation with differentiation and tumor-formation pathways in colorectal carcinoma. 165 68

The mucin alterations associated with the progress of cellular atypia of the colorectal mucosa were investigated by light and electron microscopy using lectin-histochemical technique with DBA and PNA. The samples showing positive staining in the more than one-third areas of the colonic epithelial mucosa were scored as positive reaction. The DBA positive reaction was found 100%, 95.8% and 45.7% in the normal mucosa, adenoma and carcinoma, respectively. On the other hand, the PNA positive cases increased with the grade of malignancy; 18.2%, 58.5% and 97.1% respectively. The DBA binding sites were found in the mucin of the goblet cells of the normal and adenomatous epithelia. The PNA positive sites were localized in the supranuclear portion of the normal mucosa and adenoma while in the epithelia of the carcinoma the PNA positive areas were found in the intraglandular substance and cell apex. With the electron microscopy the PNA binding sites were detected in the cis cistern of Golgi apparatus in the normal and adenomatous epithelia and in the apical membrane in the epithelia of the carcinoma. It is suggested that the PNA binding activity is a useful marker to detect the adenomas with the high risk of malignant transformation.
 ...
PMID:[A study of binding sites of lectins in colorectal adenomas and carcinomas: the optical and electron microscopical findings]. 165 99

In order to investigate the early cellular changes in liver associated with furan cholangiocarcinogenesis, young adult male Fischer 344 rats were administered furan by gavage once a day, 5 days a wk for 2 to 3 wk at doses ranging from 15 to 60 mg/kg of body weight per day. The most conspicuous feature observed in the liver of animals receiving the higher doses of furan was a rapidly developed cholangiofibrosis characterized by the presence of bile ductular hyperplasia, intestinal metaplasia, and fibrosis. Moreover, this lesion was found to be almost exclusively localized to the caudate liver lobe, which by morphometric analysis was further determined to be largely replaced by cholangiofibrotic tissue. Both the hyperplastic bile ductular epithelial cells and the intestinal-like epithelial cells in these areas selectively exhibited a strongly positive immunohistochemical staining for cytokeratin 19 and were supported by well-developed basement membranes enriched in both laminin and type IV collagen. However, in contrast to the hyperplastic bile ductules, electron microscopy of the metaplastic intestinal glands revealed them to be composed mostly of columnar epithelial cells with well-developed striated borders, less numerous mucin-secreting goblet cells, and occasional neuroendocrine-like cells, thus closely resembling in their cellular composition that of intestinal mucosa. These metaplastic glands also showed a more heterogeneous pattern of staining for both gamma-glutamyl transpeptidase and the placental form of glutathione S-transferase than did the hyperplastic bile ductules. At the 60-mg/kg/day furan dose, cholangiolar-like structures composed of biliary epithelial cells and ductular hepatocytic cells at different stages of morphological differentiation were also observed. Phenotypically, the biliary epithelial and "ductular hepatocytes" of these cholangioles shared a common basement membrane containing laminin and type IV collagen, as well as a luminal plasma membrane gamma-glutamyl transpeptidase. On the other hand, only the biliary epithelial cells of the newly appearing mixed cell cholangioles stained positive for cytokeratin 19. Interestingly, unlike hepatocarcinogen-induced oval cells, alpha-fetoprotein expression was not detected in any of the cell types comprising the furan-induced cholangiofibrotic tissue. These results support a novel in vivo model for investigating cell lineages in the development in liver of intestinal metaplasia, "ductular hepatocytes," and cholangiofibrosis in relation to intrahepatic cholangiocarcinogenesis.
Cancer Res 1991 Oct 15
PMID:Phenotypic characterization of metaplastic intestinal glands and ductular hepatocytes in cholangiofibrotic lesions rapidly induced in the caudate liver lobe of rats treated with furan. 165 60

Pancreatic tumors were induced in guinea fowls inoculated with virus strain Pts-56. Sequential high-resolution light microscopic and ultrastructural studies revealed consecutive occurrence of alterations in the pancreas of the infected birds. From the second month p.i., there were nonobligatory, unspecific focal degenerative changes in acinar units that were replaced by tubular complexes, lined with centroacinar-like cells. From the third month, proliferation of ductule structures with mucin-producing or mucin-nonproducing epithelium occurred, giving rise to cystic and papillary adenomas. From the fourth to sixth months, pancreatic adenocarcinomas and poorly differentiated carcinomas arose. The cells of the serous adenomas ultrastructurally resembled the normal pancreatic centroacinar and ductular cells with their regular glandular arrangement on basal lamina, elongated nuclei with finely dispersed heterochromatin, scanty cytoplasmic organelles, microvilli, and occasional cilium. The cells of the mucinous tumors showed similarities to ductal cells with their darker cytoplasmic matrix, larger number of small mitochondria, microfilaments, vesicles, mucin granules, and extensive interdigitations. The cells of the pancreatic carcinomas revealed irregularities in glandular formation, nuclear polymorphism, low cytodifferentiation, and ultrastructural abnormalities, but in most cases retained basic fine structural similarities to the epithelium of the pancreatic ductal system. The present results indicate that the centroacinar cell is the cell of origin of the broad spectrum of pancreatic neoplasms with various differentiation and malignancy induced in guinea fowl by virus strain Pts-56.
 ...
PMID:Virus-induced pancreatic cancer in guinea fowl. An electron-microscopical study. 166 71

A new human cholangiocarcinoma cell line (HuCCA-1) was established from cholangiocarcinoma (CCA) tissue fragments surgically removed from a Thai patient with intrahepatic bile duct cancer. The growth medium used for the primary cell culture was Ham's F12 supplemented with 10% fetal bovine serum (FBS) and 10 ng/ml epithelial growth factor (EGF). Approximately one month later, the cells were subcultured in Ham's F12 supplemented with only 10% FBS. The population doubling time was approximately 55 hr. Staining of the cells for cytokeratin and mucin confirmed that the cells were mucin-secreting tumor of epithelial cell origin. The supernatant fluid secreted a number of non-specific tumor markers including CA125 and traces of MCA and AFP. The ability of the HuCCA-1 cell line to synthesize specific marker that may have potential in the diagnosis of cholangiocarcinoma is now being investigated.
 ...
PMID:Establishment and characterization of a cholangiocarcinoma cell line from a Thai patient with intrahepatic bile duct cancer. 166 51

Morphologic and histochemical analysis was performed on 33 carcinomas with mucin-secreting areas that were identified among 100 carcinomas from radical prostatectomy specimens. The most common mucin-secreting pattern was Gleason grade 3, which usually showed distinctive luminal distention. The "colloid carcinoma" pattern with mucinous lakes was the only histologic pattern that was unique to mucinous areas. Its frequent association with cribriform Gleason grade 4 carcinoma suggests that it is a variant of grade 4 cancer, whose deviant appearance is a consequence of mucus hypersecretion. Collagenous stromal micronodules, found in 13 cases, are a previously undescribed and distinctive pattern thought to be a stromal reaction to contact with acidic extraluminal mucin. In grade 3 carcinoma, glands that secreted into the stroma rather than the gland lumen accounted for the stromal mucin, which appeared to lead to micronodule formation. In the grade 4 "colloid cancer" pattern, collagenous micronodules sometimes completely obliterated mucinous lakes, isolating residual cribriform glands in a "pseudo-grade 3" pattern. Lectin histochemical staining showed similar sialated and/or sulfated acidic mucin in all cases. Immunohistochemical staining showed downregulation of several differentiation antigens accompanying the alteration to mucinous differentiation.
 ...
PMID:Mucinous differentiation in prostatic adenocarcinoma. 166 88


<< Previous 1 2 3 4 5 6 7 8 9 10