Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiretina antibodies have been found in the serum samples of four patients with cancer experiencing concomitant loss of vision (cancer-associated retinopathy [CAR] syndrome). These immunoglobulins bound an antigen from normal pooled retina having a molecular weight of 23,000 daltons, which we describe as the CAR antigen. No corresponding antibodies could be found in serum samples obtained from patients with cancer not experiencing vision loss, from patients having retinitis pigmentosa, or from normally sighted individuals who did not have cancer. The early detection of rising antibody titers against the CAR antigen could prove important in the identification of patients likely to suffer from CARs.
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PMID:Cancer-associated retinopathy. 295 Aug 46

The monoclonal antibody-defined CAR-3 antigen is a new carcinoma associated marker which is expressed on a mucin-like molecule. Serum concentrations of CAR-3 were assayed in 181 patients with carcinomas of different organs, 20 patients with non-carcinomatous malignancies, 123 patients with inflammatory diseases and 150 healthy controls. Serum levels of CAR-3 were significantly increased in 51% of the patients with pancreatic carcinomas, in 60% of patients with biliary tract carcinomas and in about 15% of the patients with carcinomas of the digestive apparatus. Sera from patients with breast carcinomas were negative, as well as sera from patients with melanomas or sarcomas. CAR-3 values in samples from patients with chronic pancreatitis were constantly negative, as were samples from healthy donors. Significant concentrations of CAR-3 were detected in 20% of the sera from patients with acute pancreatitis and in 15% of the sera from patients with cirrhosis. Because of its high specificity for pancreatic carcinomas compared to chronic pancreatitis, CAR-3 seems a promising marker for distinguishing between neoplastic and chronic inflammatory diseases of the pancreas, whose differential diagnosis is difficult.
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PMID:The monoclonal antibody-defined CAR-3 antigen is a serological marker associated with pancreatic carcinoma. 297 86

To avoid non-specific binding of intact ricin-antibody conjugates, we prepared a new blocked thioether-linked ricin-antibody IT, in which the galactose binding site of ricin had lost the ability to bind to galactosidic residues of Sepharose 6B gel. As carrier agent, the monoclonal antibody AR-3, which defines the CAR-3 tumour-associated antigenic determinant expressed selectively on different human carcinoma cell lines, was used. Purification of the new conjugate was performed in three sequential steps: (1) by HPLC gel filtration on TSK G3000SW to remove the unconjugated ricin: (2) by affinity chromatography on Affi-Gel Blue to separate the free antibody from the conjugate and (3) by affinity chromatography on Sepharose 6B to separate the galactose-binding IT from the non-binding moiety. The cytotoxicity of the blocked and non-blocked thioether-linked IT was compared with that of classical ricin-antibody IT conjugated via SPDP and that of ricin A chain IT. The comparison was made on two different target cell lines (KATO III human gastric carcinoma and HT-29 human colorectal carcinoma) versus two control cell lines (HL-60 promyelocytic pre-leukaemic and COLO38 melanoma). The results showed that the blocked thioether IT displayed a more selective toxicity to target cells than the non-blocked IT and was much more potent than the ricin A chain conjugate.
Cancer Immunol Immunother 1988
PMID:Comparison of blocked and non-blocked ricin-antibody immunotoxins against human gastric carcinoma and colorectal adenocarcinoma cell lines. 326 8

Primary "idiopathic" amyloidosis is usually related to immunoglobulin light chain (AL) associated with immunocytic dyscrasias, while secondary "reactive" amyloidosis (AA) is related to serum amyloid A protein (SAA) and typically occurs with chronic inflammation, malignancy, or familial Mediterranean fever. In the present study, amyloid fibril protein extracted from frozen and paraffin-embedded tissue from a patient (CAR) with primary systemic amyloidosis proved to be AA protein by immunohistochemical, immunochemical, and amino terminal sequence. Extracts from both frozen and formalin-fixed paraffin-embedded kidney and spleen yielded similar monomers and dimers of the AA protein. The additional high-molecular-weight bands and a distinct 12,000-dalton fragment in the amyloid protein extracted from the formalin-fixed paraffin-embedded lung suggest that different processing of proteins, ie, by polymerization and/or degradation, may occur in different organs.
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PMID:Primary amyloidosis A. Immunohistochemical and biochemical characterization. 342 91

The Southwest Oncology Group (SWOG) performed a randomized study (SWOG 7518, CAR 2) of chemotherapy using ten courses of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) plus low-dose bleomycin (LDB), versus three courses of combined therapy, MOPP + LDB plus radiotherapy (XRT) from October, 1974, to April 1980, in pathologic stage III Hodgkin's disease. The present report includes data on 136 registered patients, of whom 112 are fully or partially evaluable. At this preliminary analysis, complete remission rates are 82% for chemotherapy alone and 82% for combined treatment. There are no statistically significant differences in survival or relapse-free survival between the two treatment programs, and no specific trends for stage IIIA versus IIIB. The estimated 3-year survival rate for all patients was 82%. Toxicities are comparable when considering the highest grades. There was one case of acute myeloblastic leukemia on combined treatment. Preliminary evidence suggests that patients with nodular sclerosis histologic type are more likely to relapse on chemotherapy alone than on combined treatment.
Recent Results Cancer Res 1982
PMID:A Southwest Oncology Group: chemotherapy versus chemotherapy plus radiotherapy in treatment of stage III Hodgkin's disease. 617 4

Mature data from four clinical trials conducted by the Southwest Oncology Group from 1971 to 1978 for patients with all stages of Hodgkin's disease (HD) are reviewed in this paper. In the RAC #1 trial of stage I and II HD we demonstrated that involved-field radiotherapy plus six courses of MOPP chemotherapy improved relapse-free survival compared to standard radiotherapy alone (P = 0.12), especially in patients with B symptoms (P less than 0.03) or mediastinal disease (P = 0.08). However, at present, there is no significant difference in overall survival. In the CAR #1 study for patients with pathologic stage IIB, IIIA, and IIIB HD, we demonstrated that three or four courses of MOPP before radiotherapy produced a 90% complete remission (CR) rate, with 70% of the patients remaining free of disease at 5 years. In the CAR #2 study for patients with pathologic stage IIIA or IIIB disease, we demonstrated that chemotherapy alone (MOPP-bleomycin) was as effective as combined modality treatment (MOPP-bleomycin plus radiotherapy) in terms of CR rate (85% versus 89%, respectively), relapse-free survival, and survival. For advanced stages of HD we added doxorubicin to our MOPP-bleomycin schedule and demonstrated that MOP-BAP produced a 77% CR rate compared to 67% for MOPP-bleomycin (P = 0.10). Moreover, MOP-BAP produced consistently superior CR rates and survival in patients with more prognostically favorable presentations of HD. Our new ongoing study (MOPP #6) incorporates many of the concepts derived from these earlier clinical investigations.
Cancer Treat Rep 1982 Apr
PMID:Conclusions from clinical trials of the Southwest Oncology Group. 617 21

This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer. 763 59

Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion of the vasoconstrictor vasopressin does not result in sustained vasoconstriction, and this may limit the benefit of vasopressin in infusional chemotherapy. We have assessed whether loss of vasopressin-induced vasoconstriction is mediated by nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an animal hepatic tumour model, by laser Doppler flowmetry. The response to regionally infused vasopressin and the nitric oxide inhibitor N-nitro-L-arginine methyl ester (L-NAME) were assessed over a 30 min infusion period. The vasopressin-induced vasoconstrictor effect diminished after 15 min despite continued infusion. Vasoconstriction was significantly prolonged when L-NAME was infused in addition to vasopressin. The increase in tumour to normal blood flow ratio was greater over the infusion period when L-NAME was co-administered with vasopressin. Our results suggest that the loss of vasopressin-induced vasoconstriction seen in liver parenchyma after regional infusion is prevented by the nitric oxide synthase inhibitor L-name and may be mediated by nitric oxide.
Br J Cancer 1995 May
PMID:Nitric oxide inhibition sustains vasopressin-induced vasoconstriction. 773 17

Effects of NG-nitro-L-arginine methyl ester (L-NAME; an inhibitor of nitric oxide (NO) synthase) and/or L-arginine (substrate of NO synthase) on pulmonary metastasis of murine melanoma and Lewis lung carcinoma cells were investigated. L-NAME, L-arginine or both L-NAME and L-arginine was injected i.p. into mice 5, 3, and 1 h before and 1, 3, 5, and 7 h after the injection of tumor cells into mice via a tail vein. The administration of L-NAME (9.3 mumol/mouse) alone or L-arginine alone (46.5 or 186 mumol/mouse) potentiated pulmonary metastasis of highly and poorly metastatic B16 melanoma cells. L-NAME alone also increased the number of pulmonary metastasis of Lewis lung carcinoma cells, but L-arginine (185 mumol/mouse) did not. However, the combination of L-NAME and L-arginine increased the number of pulmonary metastasis of both the melanoma and Lewis lung carcinoma cells synergistically. L-NAME or L-arginine administration enhanced the retention of B16 melanoma cells in the lungs examined 24 h after the tumor cell injection. Synergistic effect of L-NAME and L-arginine was also seen in the tumor cell retention. The present results suggest that the metastatic potentials of the tumor cells do not simply correlate to NO production in vivo.
Cancer Lett 1994 Nov 25
PMID:Effects of NG-nitro-L-arginine and/or L-arginine on experimental pulmonary metastasis in mice. 795 64

Immunotoxins have been extensively studied for the treatment of neoplasias; their intracavitary administration could be useful for the therapy of tumors confined to the pleural or peritoneum spaces. To study the feasibility of this "locoregional" treatment, a pharmacokinetic study of immunotoxins delivery is necessary. Ricin, a plant toxin extracted from the seeds of Ricinus communis, has often been used in immunoconjugates for its high activity; nevertheless, appropriate strategies have been necessary to limit the aspecific toxicity. We previously prepared a AR-3-ricin immunotoxin lacking the ability to bind galactosidic cell surface residues, a so-called sterically blocked immunotoxin. The monoclonal antibody AR-3, an IgG1 specific to the CAR-3 antigen, was able to recognize human colorectal adenocarcinomas. Preclinical trials in nude mice, intraperitoneally grafted with the target neoplasia, showed that this immunotoxin suppressed tumor growth without showing any undesirable ricin toxicity. In the present work we report the pharmacokinetic properties of this immunotoxin, showing the in vivo stability and a relatively long blood survival. With a biodistribution study in tumor-bearing mice, we demonstrate that in tumor-invaded tissues, the concentration of the specific AR-3-ricin immunotoxin was higher and progressively increased in a multiple-dose regimen. In contrast, an irrelevant immunotoxin behaved differently because it did not show specific tumor uptake. Moreover the pharmacokinetic data reported in this work improve the potential for "locoregional" treatment of malignancy with blocked immunotoxins.
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PMID:Pharmacokinetics of an antibody-ricin conjugate administered intraperitoneally to mice. 804 6


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