Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of murine connective and epithelial tissue tumors, including the SAD/2 and FS9 fibrosarcomas, the TA3/Ha and CAD/2 mammary carcinomas and a primary methylcholanthrene-induced sarcoma, were found to contain a high proportion of cells with receptors for the Fc portion of immunoglobulin G ("Fc receptors"). Experiments were undertaken to assess whether these cells were neoplastic, or whether they represented the infiltration into the tumor of non-malignant host cells such as macrophages or lymphocytes. It was found that long-term established in vitro cell lines of the TA3/Ha SAD/2 and CAD/2 tumors were entirely negative for the Fc receptor, whereas injection of these cells led to the formation of tumors containing a high proportion of Fc receptor-bearing cells. Many of these cells were actively phagocytic as assessed by ingestion of iron filings or antibody-coated erythrocytes. Injection of Fc receptor-negative cultured tumor cells into F1 hybrids, in which host cells could be distinguished from the tumor cells by anti-H2 sera, revealed that many or all of the Fc receptor-bearing cells in the resultant tumor were of host origin. In contrast to its effect on normal spleen cells, anti-theta serum treatment also partially inhibited Fc rosettes, suggesting a T-lymphocyte origin for some of the Fc receptor-bearing cells. Since almost all cells with potential anti-tumor activity bear Fc receptors, it is suggested that an index of host cell infiltration of carcinomas and sarcomas can quickly and easily be ascertained by enumeration of Fc receptor-bearing cells.
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PMID:Origin and partial characterization of Fc receptor-bearing cells found within experimental carcinomas and sarcomas. 115 Mar 46

The expression of phenylpropanoid and related genes was investigated in bm1, bm2, bm3, and bm4 near-isogenic maize plants at the 4-5 leaf stage using a gene-specific cell wall macro-array. The bm3 mutant, which is mutated in the caffeic acid O-methyltransferase (COMT) gene, exhibited the lowest number of differentially expressed genes. Although no other phenylpropanoid gene had an altered expression, two distinct OMT and two cytochrome P450 genes were overexpressed suggesting the activation of alternative hydroxylation/methylation pathways. The bm1 mutant had the highest number of differentially expressed genes, all of which were under-expressed. Bm1 mutant plants were affected not only in cinnamyl alcohol dehydrogenase (bm1 related CAD) gene expression as expected, but also in the expression of other CAD/SAD gene family members and several regulatory genes including MYB, ARGONAUTE and HDZip. As originally believed, the bm1 mutation could be localized at the CAD locus, but more probably in a gene that regulates the expression of the CAD gene family. The profile of under-expressed genes in the bm2 mutant is nearly similar to that of bm1. These genes fell under several functional categories including phenylpropanoid metabolism, transport and trafficking, transcription factors and regulatory genes. As the bm2 mutant exhibited a lower guaiacyl (G) unit lignin content, the bm2 mutation could affect a regulatory gene involved, perhaps indirectly, in the regulation, conjugation or transport of coniferaldehyde, or the establishment of G-rich maize tissues. The pattern of gene expression in bm4 plants, characterized by the over-expression of phenylpropanoid and methylation genes, suggests that the bm4 mutation likely also affects a gene involved in the regulation of lignification.
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PMID:Differential expression of phenylpropanoid and related genes in brown-midrib bm1, bm2, bm3, and bm4 young near-isogenic maize plants. 1722 26

The acid-sensitive PEGylated doxorubicin (DOX) with exact chemical structure was designed and prepared as a potential tumor intracellular microenvironment-responsive drug delivery system. First, the insensitive succinic anhydride-functionalized DOX (i.e., SAD) and acid-sensitive cis-aconitic anhydride-modified DOX (i.e., CAD) were synthesized through the ring-opening reaction. Subsequently, the insensitive and acid-sensitive PEGylated DOX (i.e., mPEG-SAD and mPEG-CAD) was prepared by the condensation reaction between the terminal hydroxyl group of mPEG and the carboxyl group in SAD and CAD, respectively. The obtained mPEG-SAD and mPEG-CAD could spontaneously self-assemble into micelles in phosphate-buffered saline at pH 7.4 with diameters of about 100 nm. The DOX release of mPEG-CAD micelle could be accelerated by the decrease of pH from 7.4, 6.8, to 5.5 in relation to that of mPEG-SAD micelle. On the other hand, the result of the cellular proliferation inhibition test indicated that mPEG-CAD micelle exhibited favorable antiproliferative activity in vitro. In addition, the selective intratumoral accumulation and antitumor efficacy of mPEG-CAD micelle were significantly better than those of free DOX and mPEG-SAD. More importantly, the prodrug micelles exhibited upregulated security in vivo as compared to free DOX. Overall, the mPEG-CAD micelle with enhanced antitumor efficacy and decreased side effects was a fascinating prospect for the clinical chemotherapy of malignancy.
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PMID:Preclinical evaluation of antitumor activity of acid-sensitive PEGylated doxorubicin. 2541 51

The reversible PEGylation endows antitumor drugs with various fascinating advantages, including prolonged circulation time in blood, enhanced accumulation in tumor tissue, increased cellular uptake, and promoted intracellular drug release, to improve the therapeutic efficacy and security. Here, the obtained succinic anhydride (SA)-functionalized DOX (SAD) (i.e., insensitive succinic anhydride-functionalized doxorubicin (DOX)) and aconitic anhydride (CA)-modified DOX (CAD) (i.e., acid-sensitive cis-aconitic anhydride-modified DOX) are conjugated to the terminal of poly(ethylene glycol) (PEG) yielding the unresponsive SAD-PEG-SAD and pH-responsive CAD-PEG-CAD prodrugs, respectively. The prepared prodrugs can self-assemble into micelles in aqueous solution. Both micelles are sufficiently stable at normal physiological pH (i.e., 7.4), while CAD-PEG-CAD micelle gradually swells and finally disassembles at intratumoral (i.e., 6.8) and especially endosomal pHs (i.e., 5.5). DOX release from CAD-PEG-CAD at pH 7.4 is efficiently inhibited, whereas it is significantly accelerated by the rapid cleavage of amide bond at pH 5.5. In addition, CAD-PEG-CAD exhibits more efficient cellular uptake and potent cytotoxicity in vitro, as well as improved tissue distribution and superior tumor suppression in vivo than free DOX and SAD-PEG-SAD. More importantly, the PEGylated DOX exhibits favorable security in vivo. In brief, the smart CAD-PEG-CAD with enhanced antitumor efficacy and decreased side effects shows as a promising powerful platform for the clinical chemotherapy of malignancy.
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PMID:pH-Responsive Reversible PEGylation Improves Performance of Antineoplastic Agent. 2564 3