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)

Pathological modification in secretory IgA values as well as in circadian rhythms were found in tracheotomized patients in both nasal and tracheo-bronchial secretions. The protective role of the mucosal immune system in addition to the frequency of severe infectious respiratory diseases in laryngectomized patients justifies the efforts of clinicians to prevent and treat such modifications. Mucoregulatory drugs have a peculiar role in these therapeutical attempts. Forty tracheotomized subjects with neoplastic disease were studied. Twenty received SCMC-Lys as a mucoregulatory drug. IgA 7S, 11S and albumin values in nasal and tracheo-bronchial secretions, were evaluated at surgery, 15 and then 40 days later. In accordance with clinical data, an improvement in local antibody production, damaged by tracheostomy, was found in the treated group. The influence of SCMS-Lys on SIgA production, whose evaluation was made by means of an original, highly selective and sensitive Immuno-IsoElectroFocusing procedure, seems to encourage the use of mucoregulatory drugs in laryngectomized patients.
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PMID:[Local immunity following treatment with S-carboxymethylcysteine-lysine in tracheotomy patients]. 141 21

Degradation products of peptidoglycan, the universal bacterial cell wall constituent, were previously found in animal tissues and urine. Reassessment and quantitative analysis of available data lead to an original concept, i.e. that eukaryotic cells synthesize peptidoglycan. We present a model in which this endogenously synthesized peptidoglycan is essential for the processes of eukaryotic cell division and sleep induction in animals. Genes for peptidoglycan metabolism, like those for lysine biosynthesis in plants, are probably inherited from endosymbiotic bacteria, the ancestors of mitochondria and chloroplasts. Corollaries of this concept, i.e. roles for peptidoglycan metabolism in tumor formation and in the biological clock, are supported by abundant evidence. We propose that many interactions between bacteria and eukaryotes are conditioned by their common genetic heritage.
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PMID:Endogenous synthesis of peptidoglycan in eukaryotic cells; a novel concept involving its essential role in cell division, tumor formation and the biological clock. 142 43

A rapid separation of polyamines and some related amino acids in cultured tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection is demonstrated. 60 cm x 75 microns I.D. fused-silica capillary was used for the separation and quinine sulfate was used as a background electrolyte (BGE). Several polyamines (putrescine, spermidine and spermine), amino acids (lysine, arginine, histidine) and simple cations (K+, Na+) were easily separated in less than 10 min. Using the indirect photometric detection method, femtomole amounts of polyamines extracted from the tumor cells were detected from nanoliter injection volumes, and the signal response was linear over two orders of magnitude.
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PMID:Indirect photometric detection of polyamines in biological samples separated by high-performance capillary electrophoresis. 143 36

Two model peptides rich in boron and prepared by Merrifield syntheses, dansyl.(nido-CB)2, (1) and dansyl.(nido-CB)10.Lys.Ac (2), where nido-CB represents the alpha-amino acid [nido-7-CH3-8-(CH2)3CH-(NH2)COOH-7,8-C2B9H10]-, were conjugated with the anti-CEA mAb T84.66 using peptide active ester reagents. The dansyl groups provided a means of fluorimetric analysis of mAb conjugates which was augmented by conventional amino acid analyses for nido-CB. The conjugate of 1 contained an average of 63 B atoms per mAb molecule. The mAb conjugate of 2 was chromatographically separated into a strongly fluorescent high molecular weight aggregated fraction (HMW) and a less intensely fluorescent monomeric fraction. Both fractions retained immunoreactivity. The HMW species contained an average of ca. 490 B atoms/mAb molecule, as determined by amino acid analysis. Biodistribution data were collected using nude mice bearing LS174T xenografts and 125I-labeled mAb conjugates. While the lightly B-loaded dipeptide conjugate gave biodistribution results which resembled those of native T84.66 mAb, the undecapeptide conjugate displayed greatly enhanced liver uptake and decreased tumor accretion. These results suggest that as the boron-containing burden on the supporting immunoprotein is greatly increased, as in the case of the T84.66-2 conjugate, loss of circulating conjugate to liver effectively competes with the desired tumor localization. Means which might be taken to circumvent this difficulty have been described elsewhere (ref 15).
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PMID:Carboranyl peptide-antibody conjugates for neutron-capture therapy: preparation, characterization, and in vivo evaluation. 152 Jul 28

Gene and protein expression of Y-79 retinoblastoma cells growing on poly(D-lysine) is switched from a photoreceptor-like to a conventional neuron-like pathway by the basement membrane glycoprotein laminin. Unlike other cell systems where laminin influences differentiation, Y-79 cells can neither attach to nor chemotactically respond to laminin. However, laminin increases attachment to poly(D-lysine). The laminin effects therefore seem to occur via an adhesion- and chemotaxis-independent mechanism. Moreover, these tumor cells do not exhibit high-affinity laminin binding, having only a single binding site of intermediate affinity. Laminin-Sepharose affinity chromatography of Y-79 cell surface proteins labeled with 125I revealed a single major radiolabeled 100-kDa protein eluted by 20 mM EDTA, with an electrophoretic behavior different from that of integrins. No other proteins were eluted under more stringent conditions. This material, which we call LBM-100 (100-kDa laminin-binding molecule), may be a "differentiative" laminin-binding protein through which laminin influences gene expression and development independently of attachment.
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PMID:Laminin-induced retinoblastoma cell differentiation: possible involvement of a 100-kDa cell-surface laminin-binding protein. 153 53

In an attempt to improve bifunctional chelate labelling of Mab, we investigated the use of a polyamino acid backbone for multiple DTPA substitutions. Poly-L-lysine (PL) (3.8 Kd, n = 25) was partially acetylated with MADTPA to yield 11 moles of DPTA per mole of PL. The average numbers of DTPA on PL were directly quantified with MADTPA-C-14. The remaining epsilon amino groups on PL-DTPA (I) were measured with TNBS reagent. A selective maleimide derivatization of (I) with S-SMPB yielded (II), which contains 2.3 moles of maleimide groups per mole of (I). The sulfhydryl activation of Mab-TP41.2F(ab')2 with 2-Iminothiolane hydrochloride produced (III), containing 1.3 moles of sulfhydryl groups per mole of Mab. Compounds (II) and (III) were combined to form a single thioether-spaced chain linkage of Mab-PL-DTPA (IV), which was subsequently chelated with 111In to yield (V), which was the compound of interest. Indium-111-PL-DTPA (VI) and 111In-DTPA-MabTP41.2F(ab')2 (VII) also were prepared for control studies. Direct cell binding assay revealed the mean immunoreactivity of (V) to be 79.4% and that of (VII) to be 39.5%. In a biodistribution study on melanoma tumor-bearing athymic mice at 4, 24, and 48 hr postinjection, the tumor/blood and tumor/liver ratios at 48 hr were 11.6 and 1.2 for (V), compared to 3.7 and 0.13, respectively, with (VII). Thus, the PL configuration for radiolabeled antibodies seems to result in decreased hepatic accumulation and retained tumor activity. The findings suggest that further studies of this new compound are warranted.
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PMID:Reduced hepatic accumulation of radiolabeled monoclonal antibodies with indium-111-thioether-poly-L-lysine-DTPA-monoclonal antibody-TP41.2F(ab')2. 155 42

Renal mesenchymal tumors induced in F344 rats with methyl(methoxymethyl)nitrosamine (DMN-OMe) have previously been shown by our laboratory to contain transforming Ki-ras sequences, activated most commonly by a variety of codon 12 mutations. Further sequence analysis of the one DMN-OMe-induced tumor with transforming Ki-ras sequences detected by NIH 3T3 transfection assay but with no mutation in codon 12 detected by selective oligonucleotide hybridization has now revealed an activating point mutation in codon 63. The observed GAG----AAG transition in codon 63, which replaces glutamic acid with lysine, was the only detectable mutation in exon 1 and 2 hotspot regions of Ki-ras in this tumor. The same mutation was also detected in Ki-ras sequences derived from first- and second-cycle transformants in NIH 3T3 transfection assays. Although random mutagenesis studies of cloned Ha-ras sequences by Fasano et al. (Proc Natl Acad Sci USA 81:4008-4012, 1984) had already indicated that GAG----AAG mutations in codon 63 of ras are transforming, this is the first demonstration of the natural occurrence of this particular activating mutation in a tumor.
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PMID:Activating point mutation in Ki-ras codon 63 in a chemically induced rat renal tumor. 155 12

The function of the pituitary-gonadal axis in normal (immunocompetent) and nude (immunocompromised) mice, like that of other species, can be suppressed by luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists administered by continuous release systems and, therefore, nude mice provide a valuable model for investigation of the effects of LH-RH analogues on growth of xenografts of human cancers. To extend our findings further, we treated male nude mice bearing xenografts of human prostate adenocarcinoma PC-82, for 42 days, with sustained release formulations (microcapsules or microgranules) of the agonist [D-Trp6]LH-RH, the antagonist [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH- RH (SB-75), or the somatostatin analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160). At necropsy, in mice given microcapsules releasing 25 micrograms/day of [D-Trp6]-LH-RH, tumor weight and volume were significantly decreased, compared with control mice, and weights of testes, ventral prostate, and seminal vesicles were also reduced in this group. In mice which received microgranules liberating 50 micrograms/day of antagonist SB-75, there was a greater decrease in tumor weight and volume than that produced by the agonist and a significant reduction in the weight of the testes and accessory sex organs. Histological parameters also demonstrated significant tumor inhibition, with the best results being obtained by treatment with the antagonist SB-75. The tumor inhibition induced by SB-75 was demonstrated to be due to decreased cellular proliferation, with enhanced cellular death (i.e., apoptosis) of the PC-82 cells. Microcapsules releasing 50 micrograms/day of RC-160 decreased tumor weight and volume by 23% and 28%, respectively, but this reduction was not significant. Serum levels of testosterone were decreased by 90% in mice given the LH-RH agonist and by 94% in response to the antagonist SB-75. Serum levels of prostate-specific antigen were significantly lower in mice treated with LH-RH analogues, with the antagonist SB-75 causing a greater reduction. A ratio of prostate-specific antigen to tumor weight suggests that levels of serum prostate-specific antigen may be correlated with tumor mass. Using sensitive multipoint micromethods, one class of binding sites for LH-RH, with a dissociation constant of 7.8 +/- 1.2 nM and a maximal binding capacity of 126.4 +/- 23.1 fmol/mg protein, was found in the control tumors. Tumors from mice treated with either LH-RH agonist or antagonist, but not somatostatin analogue RC-160, showed a significant reduction in maximal binding capacity for LH-RH, compared to control tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sustained release formulations of luteinizing hormone-releasing hormone antagonist SB-75 inhibit proliferation and enhance apoptotic cell death of human prostate carcinoma (PC-82) in male nude mice. 156 23

The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.
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PMID:Somatic mutations in the neurofibromatosis 1 gene in human tumors. 156 47

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.
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PMID:Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects. 159 17


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