Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solitary cerebellar metastatic tumors are rarely reported in the literature. We reviewed 240 posterior fossa tumors treated in the past eight years. There were 11 cases of solitary metastases in the cerebellum. The primary tumor was lung cancer in five cases and breast carcinoma in two cases; the remaining three cases had colon cancer, nasopharyngeal carcinoma (NPC) and Ewing's sarcoma, respectively. All patients underwent craniectomy and gross total excision of the tumor. Seven patients survived less than one year, two cases died in the second year, and one case of NPC survived for more than two years. The only survival is a case of Ewing's sarcoma who underwent surgery 14 months ago. The symptoms and signs of all patients improved satisfactorily after surgery. Four patients received postoperative irradiation to the posterior fossa and two cases of lung cancer had a thoracotomy for the primary lung lesion; however, the survival period was not prolonged. We suggest that a cancer patient or a patient in the fifth to seventh decades of life presenting headache, gait disturbance and vomiting should promptly undergo a computed tomography (CT) scan of the head. In selected cases, surgical intervention for solitary metastatic tumors in the tiny posterior fossa may be the best initial treatment. Adjuvant therapies should then be added according to the type of tumor.
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PMID:Solitary cerebellar metastases: analysis of 11 cases. 136 66

Double-label immunofluorescence was used to monitor basement-membrane composition and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases. Cryostat sections were stained with polyclonal anti-laminin anti-serum combined with monoclonal antibodies (MAbs) to all major basement-membrane components (laminin, entactin/nidogen, collagen type IV and large heparan sulfate proteoglycan), as well as to keratin 8. In all adenocarcinomas, including mucinous, basement membranes were altered more at the invasive front than in the parenchyma. The degree of this alteration was inversely correlated with the level of tumor differentiation. An uncoordinated loss of basement membrane components (dissociation of markers), previously described by us in rat colon adenocarcinomas, was also found in human tumors. In the great majority of adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the presence of fibrillar deposits of basement-membrane components, mainly of collagen type IV and/or heparan sulfate proteoglycan. This reaction was never observed in polyps and may be derived from myofibroblasts reported to accumulate in colon cancer stroma. The combined use of antibodies to basement-membrane components and to a specific keratin may constitute an adequate immunohistochemical test for the presence of invasion, and may be useful in the histologic analysis of polyps, especially in dubious cases.
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PMID:Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies. 137

Second generation antibodies to mammary mucins were produced by immunizing mice with a peptide with a sequence deduced from that of the MUC1 complementary DNA sequence (PAHGVTSAPDTRPAPGSTAP). Four monoclonal antibodies (BCP7-10) were produced which gave different reactions. BCP8 was similar in tissue reactivity (by immunoperoxidase staining) to anti-breast cancer or anti-human milk fat globule membranes (HMFG) antibodies and reacted strongly with most breast cancers and a proportion of other adenocarcinomas, whether formalin fixed or fresh, and reacted less strongly with some normal tissues. The three other antibodies (BCP7, BCP9, BCP10) reacted only with fresh tissues or a single cell line (LS174T of colon cancer origin) and gave variable weak reactions. Like many anti-mucin antibodies BCP8 reacted with HMFG, but more strongly with deglycosylated HMFG; analysis with peptides by enzyme-linked immunosorbent assay indicated reactivity with an epitope contained in the amino acid motif PDTR and using the pepscan method, the minimum epitope was DTR. MAbs BCP7, BCP9, and BCP10 did not react with HMFG; substantial reactions were obtained with deglycosylated HMFG for BCP7 and weaker reactions with BCP9 and BCP10. The finding that BCP7 reacted with breast cancer tissues and deglycosylated HMFG suggested that the epitope recognized by BCP7 was masked in native form and exposed in cancer, indicating that BCP7 could be a useful agent for analyzing differences between normal and cancer mucins. The amino acid epitopes for these antibodies were VTSA (BCP7), GSTAP (BCP9), and RPAP (BCP10). For BCP8, amino acid substitution analysis of SAPDTR indicated that substitutions were poorly tolerated (except Q for T and L/Y for R), contrasting with the substitution analysis of anti-mucin antibody reactions where virtually any amino acid can be substituted for T, indicating that in the native state T (threonine) may be O-glycosylated. The use of synthetic peptides to produce antibodies similar to those produced using crude mucins or tumor extracts represents a major advance in the production of antitumor reagents.
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PMID:Second generation anti-MUC1 peptide monoclonal antibodies. 137 8

Expression and cellular localization of brush-border enzymes (aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase) in normal human colon, colonic polyps and malignant intestinal tumors were investigated with a panel of monoclonal antibodies reacting with either native or denatured proteins. The enzymes were detected on cryostat sections by indirect immunofluorescence staining, or affinity-purified and analyzed by gel electrophoresis and immunoblotting. Dipeptidylpeptidase IV, lactase and maltase were absent from all samples examined, while aminopeptidase N (APN) was detected at the basal membrane of the epithelial cells in most specimens of colon obtained from individuals free of intestinal tumors. In contrast, APN was frequently localized at the luminal membrane of the surface epithelium in large-intestinal mucosa distal to tumors, adenomas and hyperplastic polyps, and from members of hereditary colon cancer syndrome families. APN was also expressed in colonic tumors, where it was present in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas examined. No correlation was found between tumor-cell invasiveness (classified by "Dukes" stage) and expression or cellular location of aminopeptidase N. Histologically, all positive tumors were moderately or well differentiated. These results suggest that aminopeptidase N is normally expressed in adult human colon, but epithelial cells in the large and small intestine differ in their ways of sorting this enzyme intracellularly and eventually inserting it into different aspects of their surface membrane, a process which may be altered at an early stage of carcinogenesis.
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PMID:Expression and different polarity of aminopeptidase N in normal human colonic mucosa and colonic tumors. 137 88

Cytogenetic analyses of human colon cancer cells have revealed non-random deletions in chromosome arm 8p, among other chromosomal changes. By using 8p-specific DNA probes we could identify allelic loss in 87% of colon cancer cell lines. Corresponding analyses in direct preparations of colon tumor tissues revealed a minimal value of 40% of allelic loss but were obstructed in many instances by contaminating normal tissue. These findings add to the number of non-random genetic alterations occurring during colon carcinogenesis.
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PMID:Deletions in the short arm of chromosome 8 are present in up to 90% of human colorectal cancer cell lines. 138 68

The purpose of this study was to determine whether nm23 steady-state mRNA expression levels correlate with metastatic potential of mouse K-1735 melanoma cells, human KM12 colon cancer cells, and human SN12 renal cancer cells. Since neoplasms are heterogeneous and contain subpopulations of cells with different metastatic potentials, we analyzed multiple sets of nonmetastatic and metastatic clones isolated from each neoplasm. In addition, we also examined nine somatic cell hybrids produced by the fusion of nonmetastatic and metastatic K-1735 clones. In the mouse melanoma, we found heterogeneity in nm23-1 steady-state expression levels among the clones and hybrids that did not correlate with their metastatic phenotype. Clones isolated from human colon or renal carcinomas expressed similar levels of nm23-HI regardless of metastatic potential in nude mice. All of the human tumor cells were heterozygous for the nm23-HI-specific allelic DNA fragments, with no allelic deletions or gross alterations detected. Since the failure of tumor cells to produce metastasis can be due to multiple deficiencies, these data stress the importance of using independent clones with different metastatic potentials for the analysis of gene regulation of this process.
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PMID:Expression level of the nm23 gene in clonal populations of metastatic murine and human neoplasms. 139 7

Complementary DNA clones encoding four different mucin core peptides have been isolated. However, the expression of these mucin genes in the colon has not been systematically studied. The present investigation used Northern blot analysis to study the expression of MUC1, MUC2, MUC3, and MUC4 mRNA in paired normal and cancerous colonic tissues, and nine colon cancer cell lines. Results were correlated with the clinicopathological features of the tumors and with the immunohistochemical expression of several carbohydrate tumor-associated antigens that may reside on mucins. MUC1 mRNA was expressed in all colonic tissues, and levels in paired normal and cancer tissues were similar in most cases. MUC2 and MUC3 mRNAs were expressed in both normal and cancer tissues, but levels were often decreased in the cancers. MUC4 mRNA was present in normal mucosa with comparable or sometimes greater expression in cancers. There was no apparent correlation between the expression of any particular mucin gene or pattern of mucin genes and the site, stage, or histological type of tumor. In addition, the expression of mucin-associated carbohydrate antigens did not correlate with any individual mucin gene or group of mucin genes. In colon cancer cell lines all four MUC genes were expressed rather weakly or not at all. These results indicate that the human colon expresses a broad repertoire of mucin genes which are differentially regulated in malignancy. Whether this differential regulation of mucin genes affect the behavior of the tumor and results in the altered glycosylation commonly seen in these requires further investigation.
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PMID:Mucin gene expression in colonic tissues and cell lines. 139 23

Aberrant crypts are putative preneoplastic lesions that have been proposed as intermediate biomarkers for colon cancer. The goals of these studies were to determine (i) if the colon cancer chemopreventive agent, sodium phytate, when started 1 week after a single dose of carcinogen, has any effect on the development of aberrant crypt foci (ACF) in treated rats; and (ii) if ACF at an early time period under these conditions correlate with the later formation of tumors in similarly treated animals. The number of ACF with four or more crypts was greater (P = 0.02, Mann-Whitney test) in rats with tumors compared with rats without tumors killed at 36 weeks after the injection of azoxymethane (AOM); the total number of ACF was not significantly different in these two groups. The incidence of tumors in F344 rats treated with AOM without phytate was 83% (10/12) compared to 25% (3/12) in rats treated with AOM plus phytate (P = 0.0045, two-tail Fisher's exact test). The finding of more (P = 0.005, Mann-Whitney test) ACF with four or more crypts in rats without phytate than in rats with phytate at 12 weeks after the injection of AOM is consistent with the hypothesis that the development of larger ACF (with four or more crypts) is predictive of the tumor incidence. These results validate the use of this parameter, i.e. ACF with four or more crypts, as an intermediate biomarker for tumor incidence in this system.
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PMID:Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate. 139 32

The Hybrid Spheroid assay is based on packaging tumor cells into agglomerates of non-proliferating, but metabolically active, HeLa cells. These agglomerates provide an in vivo-like environment for entrapped test cells. Clonogenicity is determined by varying the number of test cells per hybrid spheroid so that some, but not all, spheroids give rise to macrocolonies. From the fraction of noncolony forming spheroids and the Poisson distribution, the average number of clonogens per spheroid can be calculated. The clonogenicity and radiation survival curves of cells derived from human tumors (of the maxilla, tongue, larynx, mouth floor, lung, breast, ovary, and colon) were so determined. Plating efficiency was increased in these normally poorly plating tumor cells, thus enabling survival measurements which are not practical using conventional methods. The Hybrid Spheroid assay has also been applied to determine the chemosensitivity of colon cancer cells.
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PMID:The hybrid spheroid clonogenic assay for the intrinsic radio- and chemo-sensitivities of human tumors. 139 38

Splenic tissues derived from patients with gastric cancer were implanted into mice with severe combined immunodeficiency (SCID) and then the mice were challenged with COLO-205, a human colon cancer cell line. Production of human immunoglobulin G (IgG) reactive against the COLO-205 cells was detected by enzyme-linked immunosorbent assay in sera from the reconstituted and tumor-bearing SCID mice. The titers of the reactive IgG relative to total IgG in the sera of SCID mice began to increase from one week after implantation of the tumor cells, and became 10- to 100-fold higher than that in the donor's serum by 3-4 weeks. This model using implantation of human cancer cells in SCID mice reconstituted with human splenic tissues would facilitate further studies of human cancer immunology.
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PMID:Production of human immunoglobulin G reactive against human cancer in tumor-bearing mice with severe combined immunodeficiency reconstituted with human splenic tissues. 139 26


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