Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Galactosyltransferase (GT) (EC 2.4.1.38) was purified to homogeneity from human ovarian tumor effusion fluid and normal human serum by chromatography on alpha-lactalbumin and anti-human immunoglobulin affinity (to selectively absorb contaminating IgG) columns. Both preparations showed a single, broad band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis centered at a molecular weight of 48,000, but nondenaturing polyacrylamide gel electrophoresis of GT isolated from tumor effusion fluid revealed the presence of a series of oligomeric proteins possessing GT activity, which were barely detectable in normal human serum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of N-glycanase- and O-glycanase-treated GT revealed that each endoglycanase removed carbohydrate with an approximate molecular weight of 3,000, revealing the presence of both N-linked and O-linked oligosaccharide substitutions on GT. Purified GT (containing a mixture of GT isoenzymes) was used to immunize BALB/c mice for monoclonal antibody (MAb) preparation. Four of the MAb isolated reacted with GT. MAb 3872 (patent pending; an IgG1) was determined to be specific for a cancer-associated GT isoenzyme (GT-II) by immunostaining of Western blots and nondenaturing polyacrylamide gel electrophoresis of GT specifically eluted from a MAb 3872 affinity column. Two 125I-labeled cyanogen bromide peptides (Mr 8,400 and 7,400) prepared from 125I-GT were specifically bound and eluted from a MAb 3872 affinity column, demonstrating that the MAb 3872 GT-II-specific antigenic epitope resides on these peptides. MAb 3872 was immobilized on 1,1'-carbonyldiimidazole-activated trisacryl GF-2000 and used to specifically assay serum GT-II levels in 29 individual normal human serum samples and 77 serum samples from 38 patients with advanced ovarian tumors. The normal serum GT-II level was found to be 85.3 +/- 30.9 milliunits/ml, with a range of 17 to 160 milliunits/ml. Of the 38 tumor patients, 33 showed GT-II values in excess of 200 milliunits/ml, with a range of 216 to 8,469 milliunits/ml. Serial samples obtained from the ovarian tumor patients suggested that the serum GT-II level reflected the tumor burden of the patient.
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PMID:Characterization and immunoassay of human tumor-associated galactosyltransferase isoenzyme II. 313 19

Cachectin/tumor necrosis factor (TNF) is a macrophage product which may have a role in cancer cachexia. Recombinant human cachectin/TNF (Cetus Corporation) was administered i.p. twice daily to male F344 rats at varying, nonlethal dosages for either 5 or 10 days, and daily rat food intake and body weight were measured. There was a dose-dependent cachectin/TNF-induced decline in food intake and body weight gain over the treatment period. However, after 1 day rats became tolerant to these effects and increased food intake and gained body weight despite receiving cachectin/TNF. Rats were subsequently inoculated with a transplantable methylcholanthrene-induced sarcoma, and survival was measured. Rats previously treated with high-dose (either 100 or 200 micrograms/kg/day) cachectin/TNF survived significantly longer following tumor inoculation than did control rats given saline or rats given 10 micrograms/kg/day of cachectin/TNF. Analysis of tumor growth curves and tumor weight indicated that high-dose cachectin pretreatment did not retard tumor growth. Analysis of food intake and tumor burden following tumor inoculation indicated that high-dose cachectin pretreatment decreased the reduction in food intake associated with progressive tumor growth and allowed rats to withstand a greater tumor burden at death. Rats immunized with low-dose human cachectin/TNF developed high IgG titers against human TNF, but failed to demonstrate the same protection against a methylcholanthrene-induced tumor challenge as rats made tolerant with repetitive twice daily high-dose cachectin/TNF. The observation of reduced cancer-associated anorexia and increased survival of tumor-bearing rats associated with previous tolerance to exogenous cachectin/TNF strengthens the contention that endogenously produced cachectin may be a factor in the pathogenesis of cancer anorexia in the tumor-bearing rat. The mechanism of this tolerance is unclear but does not appear to be a humoral immune response.
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PMID:Cachectin/tumor necrosis factor: a possible mediator of cancer anorexia in the rat. 316 53

Approximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically-related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P less than 0.05 or P less than 0.01) effects were consistent with the number expected by chance alone. Thus, cage-related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current studies.
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PMID:Do cage effects influence tumor incidence? An examination of laboratory animal carcinogenicity studies utilizing Fischer 344 rats. 318 92

Lectin histochemistry has permitted an assessment of the glycoconjugate expression in colorectal polyps (Table 8). The T-antigen, a cancer-associated antigen, is expressed in colorectal adenomatous polyps. The apparent expression of T-antigen is related to the methodology used for its detection. FITC-PNA does not bind to glycoconjugates in the normal colon, however it is a sensitive marker for glycoconjugates secreted by colorectal cancers. The binding of FITC-PNA in adenomatous polyps is related to size and histology. The use of biotinylated PNA (followed by avidin-biotin-peroxidase) or PNA:anti-PNA is a more sensitive technique, and the result is that binding may be seen in the normal colon as well as most neoplastic lesions. The use of polyclonal and monoclonal antibodies to the T-antigen are more specific than the PNA:anti-PNA technique. Binding of PAb and MAb anti-T-antigen to colorectal polyps is related to the size of the polyp for both probes, and binding is also related to the degree of dysplasia for the MAb. The future of this work may be directed at an attempt to determine whether a family of closely related antigens are expressed in colorectal neoplasia with varying degrees of affinity for different probes of the T-antigen.
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PMID:Lectin histochemistry in colorectal polyps. 318 74

Phosphohexose isomerase (PHI) derived from human gastrointestinal tumor tissue was isolated by specific elution from a cation exchanger. The identity of three PHI variants in the purified preparation could be demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing analysis. By preparative IEF the variants could be resolved to high homogeneity. The monomer of the common major variant with a pI of 9.1 revealed a molecular weight of 60,000, whereas for the cancer-associated variants with a pI of 8.9 and 8.6, a molecular weight of 57,000 and 56,000, respectively, was determined. The results obtained support the hypothesis that those variants are due to a specific intracellular cleavage of the enzyme in the malignant cells. Since it has been shown that the Mr 56,000 protein neuroleukin exhibits a strikingly high degree of homology with PHI (M. Chaput et al., Nature (Lond.), 332: 454-455, 1988; P. Faik et al., Nature (Lond.), 332: 455-456, 1988), the described specific cleavage of PHI might be responsible for the conversion of an enzyme to a trophic factor.
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PMID:Purification and characterization of phosphohexose isomerase from human gastrointestinal carcinoma and its potential relationship to neuroleukin. 319 76

In an attempt to quantify the nonrandomness of primary neoplasia-associated acquired chromosomal aberrations in humans, we have retrieved information from a computerized data base on the chromosomal abnormalities of 9069 human neoplasms. By restricting the survey to the 1985 cases with a solitary structural rearrangement, we attempted to limit the analysis to only those aberrations that were most likely to represent pathogenetically important, primary changes. The breakpoints of the primary abnormalities thus identified clustered to 71 bands. It furthermore turned out that 27 of the 41 oncogene sites known with reasonable precision (i.e., localized within one or two bands) coincide with bands consistently involved in neoplasia-associated rearrangements. These comparisons add to the evidence that acquired, cancer-associated chromosomal aberrations are nonrandom in distribution, that only a limited number of genomic sites are consistently involved in primary neoplasia-associated aberrations, and that the concordance between the breakpoints of primary aberrations and the location of cellular oncogenes is greater than predicted by chance.
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PMID:Consistent involvement of only 71 of the 329 chromosomal bands of the human genome in primary neoplasia-associated rearrangements. 319 87

In hypernephroma an overall diagnostic sensitivity of 72% and a specificity of 87% was found for the serum tumor marker phosphohexose isomerase (PHI). Both in early stage disease and in well differentiated tumors a sensitivity of about 60% was reached. In contrast the sensitivity of three other glycolytic enzymes tested was found to be less than 20%. Since the cancer induced elevation of PHI activity in the tumor was found to be comparable to those of the other test enzymes, elevated PHI serum activities cannot be attributed to overproportional PHI synthesis and unspecific cell-lysis. In 6 of 10 cases studied differences in the PHI isozyme pattern between the tumor and the normal tissue were found suggesting the occurrence of cancer associated structural alterations of PHI.
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PMID:Phosphohexose isomerase in hypernephroma. Significance as serum tumor marker, comparison to other glycolytic enzymes and isozyme patterns in normal and tumor tissue. 320 49

We have cytogenetically analyzed short-term cultures from an in situ squamous cell carcinoma of the skin (Bowen's disease). The following mosaic tumor karyotype was found: 46,XX, -1, +der(1)(pter----p22::q11----cen----p22:), -9, +der(9)t(1;9)(q11; p24)/46,XX,t(3;6) (q21;p21)/46,XX,t(5;14)(q13;q24),t(7;18)(q32;q11)/46,XX,t(8;11)(p22;q13) /46, XX,t(8;11) (p22;q13),t(15;17) (q13;q24)/46,XX,t(12;15)(q12;p11). None of the rearrangements correspond to previously known cancer-associated abnormalities. Two of the clones are obviously related, and it is reasonable to assume that the t(15;17) developed as an evolutionary change in a cell that already contained t(8;11)(p22;q13). Since five clones without cytogenetic similarities were found in this in situ skin carcinoma, we suggest that the tumor was of polyclonal origin. It is impossible to decide whether all, or indeed any, of the visible abnormalities constitute pathogenetically essential primary changes, or merely represent chromosomal markers of secondary importance in tumorigenesis.
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PMID:Multiple unrelated clonal chromosome abnormalities in an in situ squamous cell carcinoma of the skin. 259 69

Mice bearing the S-180 sarcoma displayed a depression of liver catalase and cytochrome P-450-dependent enzymes (ethoxycoumarin deethylase, ED) from day 6 following tumor implantation. Injection of serum obtained from tumor-bearing mice into normal mice caused depression of liver ED suggesting that a circulating factor was involved. Tumor-bearing mice did not show any significant change in serum triglycerides and food intake. By contrast, injection of endotoxin, interleukin-1 (IL-1) or tumor necrosis factor (TNF) caused not only a depression in liver ED but also a marked increase in serum triglycerides. To study the possible analogies between cancer-associated circulating factor and monokines, we studied the effect of dexamethasone (a known inhibitor of monokine synthesis) on liver ED activity in tumor-bearing mice. Dexamethasone (DEX) treatment increased (up to 60%) liver ED activity in tumor-bearing mice. We conclude that: (i) a circulating factor is involved in cancer-associated ED depression; (ii) that this mediator is not necessarily identical to TNF or IL-1 and (iii) that DEX reverses the depression of liver ED in cancer, possibly by inhibiting the synthesis, or the effects, of this factor.
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PMID:Depression of liver drug metabolism in sarcoma-bearing mice. Evidence for a circulating factor and dissociation from lipolytic activity. 326 84

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.
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PMID:Protein A immunoadsorption in the treatment of malignant disease. 327 21


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