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.
Int J Cancer 1975 Jun 15
PMID:Origin and partial characterization of Fc receptor-bearing cells found within experimental carcinomas and sarcomas. 115 Mar 46

Patients with renal transplants that survive the first year often ask about the chance of long-term function. We studied 1850 patients with primary transplants from June 7, 1963 to September 1, 1988 who had graft survival of greater than 1 year. Patients were grouped by donor type, diabetic status, and whether or not they received cyclosporine (CsA). Half-life (T1/2) was used to compare long-term survival rates. We determined the long-term graft survival inclusive and exclusive of death with function (DwF) in order to study all patients and to direct attention to immunologic losses. Pre-CsA, DwF was the major cause of graft loss in each cohort. Cause of DwF was cardiovascular (49%), infection (26%), and cancer (14%). The percentage of patients experiencing DwF was much higher in the pre-CsA group vs. the CsA group: HLA-identical living related donor, 16% vs. 3%; non-HLA-identical LRD, 22% vs. 5%; and cadaver donors, 26% vs. 11%. T1/2 for 711 transplants to diabetics (DM) was 9.01 +/- .54 years, while for transplants to 1139 nondiabetics (NDM) T1/2 was 13.57 +/- .68 (P less than .05). When DwF is excluded (DwFex) DM T1/2 = 23.5 +/- 2.69 and NDM T1/2 = 22.2 +/- 1.55 (NS). Overall, for HLA-identical transplants (n = 297) T1/2 = 26.13 +/- 3.35 and DwFex T1/2 = 104.3 +/- 28.93. Nonidentical LRD (n = 845) T1/2 = 11.25 +/- .61 and DwFex T1/2 = 19.37 +/- 1.55. For CAD (n = 701) T1/2 = 9.10 +/- .54 and DwFex T1/2 = 17.49 +/- 1.65. Comparing pre- and post-CsA cohorts, CsA has not resulted in significant improvement in long-term graft survival by T1/2 analysis with DwFex. It appears that overall long-term graft survival has improved with the introduction of CsA. Much of the improvement may be attributed to better first year graft survival and a reduction in cases of DwF. DM patients have an equal opportunity for long-term graft survival if they do not die from other causes. Excluding DwF, especially as an older population is transplanted, is important in determining chances of immunologic loss. Use of this type of analysis suggests that long-term outlook for 1-year graft survivors is excellent.
 ...
PMID:Long-term outlook for renal transplant recipients with one-year function. "Doctor, what are my chances"? 198 80

Azimexon [2-cyanaziridinyl-2-carbamoyl-aziridinyl-1-propane] is a derivative of 2-cyanaziridine. Azimexon is an immunostimulant which shows therapeutic effects in tumor models and experimental infections in mice in vitro, enhances T lymphocyte transformation in vitro and increases phagocytosis of latex particles by mouse peritoneal cells. In cancer patients it increases blood active T rosettes, increases T4/T8 ratio and is used in the treatment of melanomas. The crystal structure analysis of azimexon has been undertaken to study the conformation of the molecule in the solid state as a first step in the investigation of a possible structure-function relationship of immunomodulators. Crystals of azimexon are triclinic, space group P1, with a = 6.342(2), b = 6.804(1), c = 13.106(2) A, alpha = 75.17(1), beta = 89.17(2), gamma = 83.26(2) degrees, V = 542.8 A3, Z = 2, D0 = 1.18 g cm-3 and Dc = 1.189 g cm-3. The structure was solved using CAD-4 data by multisolution techniques and refined to a final R value of 0.057. There are two independent molecules in the asymmetric unit with very different conformations relating the two aziridine rings in the molecule. The mean lengths of C-N and C-C in the aziridine rings are 1.461 and 1.494 A and the configuration of the ring nitrogen is pyramidal. The mean C-C-N and C-N-C bond angles in the ring are 59.2 and 60.6 degrees respectively. The two molecules, which differ significantly in the relative orientation of their aziridine rings, are linked by hydrogen bonding involving the amino group of one molecule as the donor and the cyano nitrogen and carbamoyl oxygen of the other molecule as the acceptor. There are a number of C-H...O and C-H...N interactions in the structure. The mode of action of azimexon is unknown. It has been suggested that azimexon may alkylate DNA. The knowledge of the three-dimensional structure should facilitate distance geometry calculations that would determine which modes of crosslinking would be possible. The end-to-end distances between the two ends of the molecule is 9.0 A which is of the same order as the intrastrand distances in the DNA double helix. The present structural work of azimexon strongly indicates that azimexon crosslinks with DNA using its two reactive groups at its ends. Further study is necessary in order to determine which modes of crosslinking would be possible.
 ...
PMID:Structural studies of immunomodulators. Part 2: Crystal structure and conformation of azimexon (BM 12.531) an immunostimulant and an anti-tumor drug. 235 66

Two distinct calcium-sensitive cell-cell adhesion molecules were identified in human epithelial tissues and carcinomas using two monoclonal antibodies raised against vulvar epidermoid carcinoma A-431 and human mammary carcinoma MCF-7 and selected on the basis of their activities to disrupt cell-cell adhesion. In immunoblot analysis, these antibodies, designated NCC-CAD-299 and HECD-1, detected main bands of Mr 118,000 and 124,000, respectively. Purified tryptic fragments of the antigen recognized by NCC-CAD-299 showed cross-reactivity with a rabbit antiserum against mouse P-cadherin, indicating that this molecule was the human homologue of P-cadherin. On the other hand, the antigen recognized by HECD-1 showed essentially the same tissue distribution pattern as E-cadherin in the mouse, suggesting that this molecule is the human homologue of E-cadherin. Availability of these monoclonal antibodies to human P- and E-cadherin allowed us to examine their distributions in human tissues immunohistochemically. Both antigens were detected in epithelial tissues, but they showed distributions that were distinct from each other. The antigen recognized by HECD-1 was expressed in almost all epithelial tissues, while distribution of the other one recognized by NCC-CAD-299 was restricted to the basal or lower layers of stratified epithelia in which both antigens were coexpressed. Moreover, immunohistochemical examination of 44 lung carcinomas showed that both molecules were coexpressed in all of them, and suggested that expression of P-cadherin was closely related to the differentiation of carcinoma cells.
Cancer Res 1989 Apr 15
PMID:Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. 270 54

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.
Cancer Chemother Pharmacol 1983
PMID:Combination chemotherapy for the treatment of Hodgkin's disease in relapse. Results with lomustine (CCNU), melphalan (Alkeran), and vindesine (DVA) alone (CAD) and in alternation with MOPP and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV). 619 13

Fifty consecutive adults with sarcoma were treated with Adriamycin (45 mg/m2) on day 1, cyclophosphamide (500 mg/m2) on day 2, and DTIC (400 mg/m2) on days 1 and 2 (CAD). Of the 23 patients with measurable metastatic disease, 4 patients (17%) had a complete response, 9 patients (39%) had a partial response, 5 patients (22%) had stabilization, but 5 patients (22%) did not respond. The actuarial survival of complete and partial responders was 31.5 months compared to 5.5 months for non-responders (P < .005). Chemotherapy doses were escalated to a median lowest white count of 700 cells/mm3. Acute gastrointestinal toxicity and alopecia occurred in all patients. CAD differed from previously reported combinations by omission of vincristine, a two-day dose schedule and dose rate intensification. CAD is recommended for patients with metastatic sarcoma.
Cancer 1980 Oct 15
PMID:Successful treatment of metastatic sarcomas with cyclophosphamide, adriamycin, and DTIC (CAD). 742 76

In a phase III randomized trial of adjuvant chemotherapy for gastric cancer, interinstitutional differences were analyzed. A trial of three regimens: mitomycin C, 5-fluorouracil(5-FU) and CA (MFC) + continuous oral 5-FU (Group C); MFC + continuous oral UFT(tegafur and uracil) (Group B); and MF + UFT (Group C) after operation was conducted in 466 patients with gastric cancer (stage II and III) at four hospitals in Japan (CIH, CAD, ACC and NCC). Patients were stratified by the institution, stage, and tumor size (8 cm ><). The 5-year survival rates were in the order of Group A (79.0%) > B (70.0%) > C (61.0%) (P = 0.1228) in total, A (95.0%) > B (80.0%) > C (58.0%) (P < 0.05) at CAD (82 patients), A > C > B at CIH (215), C > A > B at ACC (95), and B > A > C at NCC (78). The survival rate of patients with S2(serosal exposure), 8 cm < and N0-1 cancer was higher at CIH than at the other institutions. The interinstitutional differences in patient characteristics and surgical technique were more powerful than the differences among the three groups.
 ...
PMID:Randomized study with mitomycin C + 5-fluorouracil+cytosine arabinoside (MFC)+5-fluorouracil, MFC+tegafur and uracil (UFT), and MF+UFT in advanced gastric cancer: interinstitutional differences in a multicenter study in Japan. 766 68

Transforming growth factor beta 1 (TGF-beta 1) regulates a multitude of diverse biological functions in mammalian cells, and there is good evidence that aberrant expression of this growth factor can play an important role in mechanisms of malignant progression. We show that a TGF-beta 1-overexpressing mouse 10T1/2 cell line transfected with a TGF-beta 1 sequence that allows the synthesis of bioactive growth factor exhibits reduced sensitivity to the cytotoxic effects of the drug N-(phosphonacetyl)-L-aspartate (PALA) in colony-forming experiments. Furthermore, six independent 10T1/2 TGF-beta 1-transfected cell lines containing TGF-beta 1 gene expression under the control of a zinc sulfate-responsive metallothionein promoter were selected. In all cases, sensitivity to PALA cytotoxic effects was significantly reduced when cells were cultured under conditions that led to elevated levels of TGF-beta 1 gene expression when compared to cells containing basal levels of this growth factor. Fluctuation analysis to determine the rate of PALA resistance was performed with several TGF-beta 1-transfected cell lines in which growth factor expression was regulated by the metallothionein promoter. We observed significantly higher rates of PALA resistance/cell/generation in cell populations expressing high levels of TGF-beta 1 than in the same cells expressing relatively low levels of this growth factor. The only mechanism known for PALA resistance in mouse cells involves the amplification of the gene coding for the protein target of PALA, CAD, a multifunctional polypeptide containing carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase. Southern blot analysis of colonies that survived normally cytotoxic concentrations of PALA exhibited CAD gene amplification. In total, these observations indicate that aberrant expression of TGF-beta 1 gene expression decreases the genetic stability of 10T1/2 cells, leading to increased rates of drug resistance and elevated gene amplification potential. The results of this study indicate a new malignancy related function for TGF-beta 1 alterations and suggest a novel role for aberrant expression of this growth factor in mechanisms of drug resistance and tumor progression.
Cancer Res 1995 Apr 15
PMID:Drug resistance and gene amplification potential regulated by transforming growth factor beta 1 gene expression. 771 85

Fischer rat embryo fibroblasts subjected to temporary anoxia followed by an aerobic recovery period show genomic instability in the form of highly elevated CAD gene amplification rates. As revealed by flow cytometric analysis this is associated with DNA breakage in vivo, followed by repair during the recovery period. Such genomic instability parallels expression of a M(r) 29,000/31,000 endonuclease; this enzyme requires no added divalent metal ion and has a pH optimum of about 6.5. The same endonuclease was found to be expressed within healing wounds and in four of ten human colorectal cancers but was not seen in eight normal colorectal tissue samples. Our results indicate that DNA breakage resulting from endogenous endonuclease activity can have a substantial effect in modulating genomic instability.
Cancer Res 1995 Mar 01
PMID:An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. 786 98

Normal and SV40-infected human fibroblasts were grown in the presence of the drug N-(phosphonoacetyl)-L-aspartate (PALA) and examined for evidence of genetic instability. Both cell populations were precrisis and showed a normal, diploid karyotype at early passage. In contrast to the normal IMR-90 cells, which showed growth arrest and did not form colonies in PALA, the SV40-infected IMR-90 cells formed colonies at a very high frequency and continued to cycle in the drug. The drug-resistant colonies senesced after continued growth in culture, indicating that this change in ability to amplify preceded immortalization. This is the first observation of mortal human cells overcoming the drug-induced growth arrest. Although all previously isolated PALA-resistant colonies demonstrated CAD gene amplification as the mechanism of the drug-resistant phenotype, these SV40-infected human cells also showed alternative mechanisms, including increases in gene copy number by aneuploidy and formation of an isochromosome 2p.
Cancer Res 1993 Oct 15
PMID:Multiple mechanisms of N-(phosphonoacetyl)-L-aspartate drug resistance in SV40-infected precrisis human fibroblasts. 840 85


1 2 3 4 5 6 7 8 9 10 Next >>