Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sandwich method was developed for the detection of carcinoembryonic antigen (CEA) and CEA-like molecules and immunoglobulin G (IgG) containing immune complexes (CEA-IgG-IC) in human sera. Rabbit anti-CEA ( Dako , FRG) was adsorbed to polypropylene tubes. CEA-like molecules and IgG containing immune complexes bound to the solid phase. They were detected by binding peroxidase-labelled anti-IgG antibodies and quantified by measuring the optical density (OD) at 492 nm after oxidation of orthophenylene diamine. Sera of 68 controls had a mean OD 492 of 1.19 +/- 0.26 (means +/- SD). An extinction of more than 1.97 (means + 3 SD) was judged as elevated. Fourteen of 69 patients after surgical treatment of colorectal carcinoma showed elevated OD 492 up to a value of 3.92. In five patients with benign diseases of colon or rectum normal values were found. In 7 of 41 patients without recurrence or metastases CEA-IgG-IC were elevated although the CEA was normal, and in one case both parameters were elevated. In four of 22 patients with tumor progression CEA-IgG-IC and CEA were elevated, whereas in two cases only CEA-IgG-IC were found.
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PMID:[Demonstration of circulating CEA or CEA-like antigens and immunoglobulin G containing immune complexes in colorectal carcinoma]. 637 76

We followed 67 patients with superficial bladder cancer (TA, T1) for 12-48 months (mean, 26.8 months) after surgical removal of the tumors. Every 3-4 months, when the patients came for cystoscopic control, we evaluated serum and urinary carcinoembryonic antigen (CEA), urinary cytology, serum rheumatoid factors, and urinary IgG, IgA, and IgM concentrations. The purpose was to look for markers or prognostic factors in patients with superficial bladder carcinoma other than characteristics of the excised tumors themselves. We emphasized data that can be obtained on patient follow-up. Our results were correlated with tumor recurrence and tumor progression rates. In contrast with other reports, only urinary immunoglobulins (especially IgG) proved to have prognostic value. However, urinary CEA and (even more so) urinary cytology are fairly good tumor markers: they were positive when the bladder tumors were present and, in the case of recurrence, before recurrent tumors were visible.
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PMID:The value of urinary cytology, serum and urinary carcinoembryonic antigen, rheumatoid factors, and urinary immunoglobulin concentration as tumor markers or prognostic factors in predicting progression of superficial bladder cancer. 665 25

Seven consecutive ascitic tumors were obtained over a 9-month period from a patient with serous adenocarcinoma of the ovary. The tumor cell populations were analyzed for cellular proliferation (labeling index, agar clonogenicity, and self-renewal capacity), for cell differentiation (cell surface expression of carcinoembryonic antigen and histochemical stain for fat accumulation), and for karyotypic changes. Evidence is presented of increased aggressiveness of proliferative features together with a decreasing proportion of cells with differentiated features. Parallel temporal changes were documented in density-volume characteristics of the tumor cell population, from small, high-density to large, low-density cells. The only karyotypic change identified over this period was the loss of one X-chromosome and the increased frequency of cells containing double minute bodies. The progressive characteristics described in this human tumor are not, therefore, associated with gross chromosomal changes. The accumulation of double minute chromosome bodies may be associated with a low-dose methotrexate exposure or with the tumor progression.
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PMID:Tumor progression studied by analysis of cellular features of serial ascitic ovarian carcinoma tumors. 684 99

The mouse biliary glycoprotein 1 gene (bgp1) encodes several multifunctional glycoprotein isoforms. These glycoproteins represent members of the carcinoembryonic antigen (CEA) family which belongs to the immunoglobulin superfamily. The Bgp1 glycoproteins function as cell adhesion molecules and receptors for the mouse hepatitis viruses. In contrast to CEA, whose overexpression has been correlated with cancer progression, the human and mouse Bgp proteins are generally down-regulated upon tumor formation. In this study, we report on the mouse bgp1 gene organization and transcriptional activation. We have isolated phage and cosmid clones encompassing the entire bgp1 coding region. This gene consists of nine exons, some of which are subjected to alternative splicing producing a minimum of four splice variants. A comparison of the murine bgp1 proximal promoter with the human BGP and mouse cea10/bgp3 genes revealed sequence conservation of 66% and 95%, respectively. RNase protection assays and primer extension analyses indicated that the mouse bgp1 transcriptional start site is positioned 240 nucleotides upstream of the ATG translational initiation codon, which is 140 nucleotides further upstream than in any other CEA family member. The bgp1 promoter is transcriptionally active in reporter gene activation in vitro transfection studies and in vivo using a bgp1-containing cosmid clone. We identified three putative AP-2 or AP-2-like sites and an upstream stimulatory factor (USF) recognition sequence within the proximal mouse bgp1 promoter region at positions similar to those used by the human BGP promoter region. These data suggest that the regulation of the mouse and human BGP genes may follow some common spatial and temporal expression. Interestingly, the bgp1 proximal promoter and coding region are also well conserved throughout evolution.
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PMID:Characterization and transcriptional activity of the mouse biliary glycoprotein 1 gene, a carcinoembryonic antigen-related gene. 762 60

Blood tissue polypeptide specific antigen (TPS) concentration was serially measured by IRMA radioimmunodetective procedure in hormonally treated prostate cancer patients with Stage Do-D1 tumor (20 subjects free of bone lesions) and Stage D2 disease (20 subjects with bone metastases). Monoclonal antibody against the principle M3-TPA epitope was used in this TPS assay. Serum TPS values were compared with respective blood prostate specific antigen (PSA), prostatic acid phosphatase (PAP), carcinoembryonic antigen (CEA) and testosterone levels in a retrospective manner. A control group included healthy men, patients with benign prostatic hypertrophy (BPH), subjects with inflammation of the prostate, and men with diabetes. PSA is reported to be a quantitative calibration for prostate cancer load in untreated patients, especially during early stages of the disease. In hormonally treated, advanced, and dedifferentiated prostatic carcinoma this serotest fails to reflect properly both tumor status and response to treatment. In Stage Do-D1 patients TPS concentrations remain normal or become slightly elevated even during local tumor progression. This finding is in accord with the slow proliferation of nonaggressive primary tumors. Circulating TPS concentrations are elevated in progressive metastatic patients, in the majority of Stage D2 subjects with stable disease and even in some of these patients during partial tumor remission. This latter result may be attributed not only to the heterogeneity of the advanced prostatic cancer but also to the actual tumor response to treatment, since serum PSA level fails to reflect properly the outcome of hormonal treatment. There is some evidence that an abrupt elevation in serum TPA level in such patients is a consequence of NK cell-mediated lysis of circulating tumor cells, thus giving rise to a simultaneous and rapid delivery of intracellular TPS into the bloodstream. Prostatic inflammation elevates TPS concentrations only slightly, while diabetes, even during a proper treatment, raises TPS concentration more intensely. In patients with BPH normal or slightly increased TPS values were measured. The results ot these preliminary investigations seem to open the way for further prospective studies.
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PMID:Serial measurements of tissue polypeptide specific antigen (TPS), PSA, PAP and CEA serotest values in treated patients with primary and metastatic prostate cancer. 768 62

The purpose of this study was to determine if proton irradiation can increase the localization of radiolabeled monoclonal antibodies (MAb) in subcutaneous (s.c.) or intracranial (i.c.) human lung tumors xenotransplanted in athymic rats. Rats with carcinoembryonic antigen (CEA)-expressing (NCI-H441) tumors were irradiated using 3 different proton time-dose regimens, followed by 111In-ZCE025, an anti-CEA MAb, which was injected 2 hr after the last dose of irradiation, and the animals were euthanized 3 days later for biodistribution and other assays. Proton irradiation at 10 gray (Gy) as a single dose or in 2 Gy fractions given on 5 consecutive days increased the uptake of 111In-ZCE025 into s.c. tumors by 292% and 182%, respectively, compared to nonirradiated controls. No enhancement in radiolabeled MAb delivery was seen after hemibrain irradiation in animals with i.c. tumors. Histopathological examination of both implantation sites showed a viable poorly differentiated adenocarcinoma with a decrease in blood vessel density, a decrease in mitotic activity, and an increase in areas of necrosis following irradiation as compared with adjacent nonirradiated tissue. CEA expression was generally maintained in vivo in that the marker was detectable in the tumor, plasma, and cerebrospinal fluid. Oxygen radical production by peripheral blood cells from s.c. and i.c. tumor-bearing rats exhibited strikingly different patterns of responsiveness. I.c. injected animals were 24% lighter than their s.c. injected counterparts, but no neurological signs of tumor progression were noted. The results indicate that proton irradiation can be used effectively to increase the delivery of radiolabeled MAb to s.c. implanted human lung tumor xenografts. However, in order to accomplish this in the brain, other radiation time-dose schedules and treatments may be needed.
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PMID:Pilot study of monoclonal antibody localization in subcutaneous and intracranial lung tumor xenografts after proton irradiation. 787 72

Octreotide (SMS 201-995), a long-acting somatostatin analogue, has been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. We analyzed the efficacy of octreotide treatment in 22 patients (14 men, 8 women) with histologically verified ductal pancreatic cancer. All patients had advanced tumor stages (stage III: 13 patients; stage IV: 9 patients). Octreotide was given by self-administered subcutaneous injection (3 x 100 micrograms/day). When there was evidence of tumor progression, the dose of octreotide was increased to 3 x 200 micrograms/day. A monthly follow-up, including clinical status, CT scan or ultrasonography, and tumor marker carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 determination was carried out. There were no severe side effects apart from slight burning sensation at the injection site. No partial or complete remission was seen. Eighteen patients showed tumor progression with a median survival time of 17 weeks (range 3-42 weeks). In three patients a "no change" evaluation with a median survival time of 46 weeks (range 40-68 weeks) was registered. In these three patients the serum tumor markers CA 19-9 and CEA did not show an increase to more than twice the baseline value during this time. One patient discontinued the octreotide treatment because of tumor progression. The results of the analysis indicate that low-dose octreotide treatment is not effective in patient suffering from advanced tumor stages of pancreatic cancer.
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PMID:Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer. 830 89

The expression of nucleoside diphosphate (NDP) kinase/nm23 has been reported to be inversely related to metastasizing potential of experimental cells and human breast cancer. In the present study, levels of NDP kinase/nm23 gene product in curatively resected human pancreatic adenocarcinomas were examined immunohistochemically using anti-NDP kinase antibody. Immunoreactivity for NDP kinase varied between tumors. Of 31 pancreatic tumors examined, 17 (55%; positive staining group) showed strong immunoreactivity for the NDP kinase, while 14 (45%; negative staining group) showed low or no immunoreactivity. Positive staining was associated with higher incidence of lymph node metastasis (13/17; 77%) and perineural invasion (13/17; 77%) than negative staining (5/14, 36%, P < 0.03; 4/14, 29%, P < 0.01, respectively). Positive staining was also associated with shorter overall survival and relapse-free survival than negative staining (P < 0.01, P < 0.01, respectively). No significant difference in age, sex, size, location of tumor, serum carcinoembryonic antigen (CEA) level, or histological type was found between the two groups. These results showed that, in contrast to the reports on breast cancer, NDP kinase/nm23 expression in human pancreatic cancer is positively associated with lymph node metastasis or perineural invasion and with poor prognosis. These, together with other previous reports, suggest that NDP kinase may play an important role in cancer progression or aggressiveness by altering its expression in a tissue-specific manner.
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PMID:Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer: an association with lymph node metastasis and tumor invasion. 838 29

We report a case of transitional cell carcinoma of the renal pelvis with extremely high serum levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). A 69-year-old woman was admitted with gross hematuria. Imaging diagnosis revealed a tumor in the left renal pelvis and multiple liver and bone metastases. Serum levels of CA19-9 and CEA were 2,557 U/ml (normal < 36) and 523 ng/ml (normal < 3.8), respectively. She died of cancer progression 3 weeks after admission. An autopsy diagnosis was transitional cell carcinoma of the left renal pelvis. No abnormal findings were recognized in the gastrointestinal organs. Cancer cells showed a positive immunohistochemical staining for both CA19-9 and CEA.
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PMID:[A case of transitional cell carcinoma of renal pelvis with extremely high serum levels of CA19-9 and CEA]. 928 96

Experimental studies in nude mice with human colon-carcinoma grafts demonstrated the therapeutic efficiency of F(ab')2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I-labeled F(ab')2 fragments (131I-F(ab')2) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with 131I-F(ab')2, doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of 131I-F(ab')2 in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophils and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia. The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of 131I-F(ab')2 from the anti-CEA Mab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity.
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PMID:Phase-I/II radio-immunotherapy study with Iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab')2 in patients with non-resectable liver metastases from colorectal cancer. 946 65


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