Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of experiments using 131I-labelled monoclonal antibody (131I-MoAb) were described. The experiments were staged on nude male mice with transplanted human colon adenocarcinoma of the 34th generation (RTK-12). Tumor sizes by the time of 131I-MoAb administration varied from 1 to 3 cm. 131I-MoAb specific radioactivity was 456.6 kBq/micrograms in the volume of 0.3 ml. The same amount of 131I-Na was administered to control animals. Scanning on the Scintimat-2F (Siemens) was performed 1, 2, 3 and 4 days after injection of 131I-MoAb. Three days before scanning 0.2% KI was added to the drinking water. Some animals were decapitated on the 2nd-3rd day for radiometry of organs and tissues. After the injection of 131I-MoAb 10-fold less than the CEA serum concentration and with specific radioactivity of 370-444 kBq its tumor accumulation in 48 h was 10-15-fold higher than that in the surrounding tissues resulting in better tumor scans. Intensive dehalogenation of 131I-MoAb in vivo and related 131I accumulation in the thyroid and adrenal glands (in the medullary layer) required the administration of stable iodine not only before but also after injection of the radioactive agent.
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PMID:[Immuno-scanning of human colon cancer xenografts using a labeled monoclonal antibody to the carcinoembryonic antigen]. 334 4

This report presents the ultrastructural features of a congenital epulis. The granular cells of the epulis were packed with numerous membrane bound cytoplasmic granules containing particles, small vesicles, and electron-dense materials. These granules were negative in immunohistochemical reaction for CEA (DAKO PAP KIT). Cytoplasmic organelles such as mitochondria, rough surfaced endoplasmic reticulum, and Golgi apparatus, were absent. Nuclei were markedly indented. Occasionally, banded intracellular collagen fibrils were observed within the cytoplasm. Some of these fibrils were surrounded by a limiting membrane, whereas others appeared to lie free in the cytoplasm. The collagen fibrils were also seen within a deep invagination of the cell surface. There was no basal lamina around the granular cells. Sporadically, mast cells with many granules containing lamellar formations were found between the granular cells. These observations support the idea that granular cells of the congenital epulis are derived from mesenchymal cells, probably fibroblasts.
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PMID:Ultrastructure of the congenital epulis. 641 6

Epithelial differentiation antigens have been correlated with morphologic differentiation of neoplastic urothelium. Moreover, epidermal growth factor, which is a polypeptide regulating growth and differentiation of normal and neoplastic cells, is found in high concentrations in the urine while its receptors (EGFR) have been identified in bladder tumors. The aim of this study was to investigate the immunohistochemical expression of cytokeratin, epithelial membrane antigen (EMA), CEA and EGFR in transitional cell bladder carcinomas (TCC) and to define any correlation of their expression with tumor grade, stage and patient survival. Twenty-four biopsy specimens obtained from patients with TCC were studied retrospectively. There were 23 men and 1 woman with a mean follow-up of 64 months. Eight biopsy specimens, which represented tumor recurrences of 4 patients, were also included in our material. The immunohistochemical avidin-biotin complex method was performed on paraffin sections for the detection of cytokeratin and EGFR with monoclonal antibodies as well as CEA with a polyclonal antibody. Cytokeratin was detected in 83.5% of the TCC, EMA in 62% and CEA in 70%. The expression of the epithelial differentiation antigens in TCCs was heterogenous, showing an increased incidence in high-grade and high-stage TCC. The CEA expression in TCC demonstrated a statistically significant correlation with patient survival (p < 0.02). EGFR was detected in 50% of the TCC. Although not statistically significant, a trend was found for a higher percentage of EGFR detection in high-grade TCC. EGFR expression was significantly associated with tumor stage and patient survival (p < 0.01 and p < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epithelial differentiation antigens and epidermal growth factor receptors in transitional cell bladder carcinoma: correlation with prognosis. 754 21

The Distribution pattern and proportion of the positive cells of proliferating cell nuclear antigen (PCNA) were examined immunohistochemically to study the proliferative activities of 33 cases of carcinoma found at the confluence of the main hepatic ducts. Expressions of CEA, CA19-9 and EGF receptor (R) were further examined with serial histological sections and comparatively analyzed with the result of PCNA staining and the clinico-pathological features of the carcinoma. PCNA positive cancer cells were observed in greatest abundance at the deeply infiltrated region of the carcinoma. CEA and CA19-9 were also expressed most strongly in this region and a stromal staining pattern was predominant. However, negative or apical staining patterns of CEA and CA19-9 were more frequent in the surface or the lateral spreading regions of the carcinoma, where the PCNA positive cancer cells were fewer in number. EGFR expression was rarely observed in the present study.
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PMID:[Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) in carcinoma at the confluence of the main hepatic ducts and its relationship to expression of CEA, CA19-9 and EGF receptor]. 809 56

The aim of the present study was to assess the clinical value of five serum tumour markers AFP, CA 15-3, CEA, TPS and Neu oncoprotein (p 185) in the diagnosis of breast cancer. The serum values were measured in a prospective series of patients with breast cancer (n = 233), benign breast disease (n = 176) and healthy control subjects (n = 215). The cut-off levels (90% specificity) were determined for each test. Using these cut-off levels the diagnostic sensitivity of the CEA test was 0.23, for the AFP test it was 0.16, for the CA 15-3 test 0.27, for the TPS test 0.18 and for the Neu oncoprotein test 0.19 in detecting breast cancer. Correlation coefficients (Pearson's) were statistically significant between CEA and CA 15-3, and between CA 15-3 and Neu oncoprotein measurements in breast cancer patients. In patients with benign breast disease the serum levels of AFP, CA 15-3, CEA and TPS correlated with age, being somewhat higher in older patients. Similarly, in population controls higher age correlated with higher levels of AFP, CA 15-3, Neu and TPS. In breast cancer patients there was no correlation between the age at diagnosis and any of the measured markers. The only marker statistically significantly associated with the stage of breast cancer was CA 15-3. In conclusion, our results indicate that serum CEA, AFP, CA 15-3, TPS and Neu oncoprotein are only of limited value in the diagnosis of breast cancer.
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PMID:Serum tumour markers CEA, AFP, CA 15-3, TPS and Neu in diagnosis of breast cancer. 913 78

A better understanding of immune recognition of cells has led to identification of potential new targets on tumor cells. Noticeable successes in melanoma have been immunization with the GM2 ganglioside vaccine, and the identification of novel antigens such as MAGE, BAGE and GAGE recognized by T cells cloned from cancer patients with regressing disease. However, the unexpected finding that other antigens recognized by these T cells were overexpressed normal differentiation antigens such as tyrosinase. Pmel 17 and Melan A have led to vaccines developed against differentiation antigens expressed in other solid tumors. Monoclonal antibody, anti-idiotype and antigen based vaccines for colorectal target antigens 17-1A, CEA and 791Tgp72 are all in clinical development. Similarly HER2/neu and mucin overexpression in breast cancer represent promising targets. Mutations in tumor oncogenes or suppressor genes which lead to malignant transformation can also present tumor-specific antigens. The most effective vaccines against infectious disease are live viruses. The development of DNA vaccines which act like viruses in entering cells and show continuous production of antigens offers great potential for the future.
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PMID:Cancer vaccines. 939 16

Six loci--CALR, EPOR, JUNB, JUND, CEA, and PRKCG--were assigned to bovine chromosomes using PCR-based hybrid somatic cell analysis. The five genes other than CALR are comparative mapping anchor loci. This study, together with the previous assignment of three anchor loci--INSR, LDLR, APOE--and four other genes--AMH, GPI, RYR1, LHB--defines the conserved synteny relationship between human chromosome 19 and cattle chromosomes 7 and 18. Genes on HSA 19p13.3-13.2 are conserved in cattle chromosome 7, while those on HSA19-q13.1-13.4 are conserved in cattle chromosome 18. In contrast, homologous genes from HSA19 are located on four different mouse chromosomes, namely MMU10, MMU8, MMU9, and MMU7. This is further evidence that syntenic conservation between cattle and human generally exceeds that observed between human and mouse.
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PMID:Comparative mapping of anchor loci from HSA19 to cattle chromosomes 7 and 18. 941 94

One approach to development of specific cancer immunotherapy relies on the induction of cytotoxic T lymphocytes (CTL) specific for tumor-associated antigens (TAA). Induction of TAA-specific CTL could be used towards the eradication of established tumors, or to prevent their dissemination or recurrence after primary treatment. The present study identifies a set of CTL epitopes from TAA frequently found on solid epithelial tumors such as breast, lung and gastro-intestinal tumors. Specifically, HLA-A2.1 binding peptides from the MAGE2, MAGE3, HER-2/neu and CEA antigens were tested for their capacity to elicit in vitro anti-tumor CTL using lymphocytes from normal volunteers and autologous dendritic cells as antigen-presenting cells. A total of 6 new epitopes (MAGE2[10(157)], MAGE3[9(112)], CEA[9(691)], CEA[9(24)], HER2[9(435)] and HER2[9(5)]) were identified which were capable of specifically recognizing tumor cell lines lines expressing HLA-A2.1 and the corresponding TAA. In one case (CEA[9(24)]), induction of vigorous anti-tumor CTL responses required epitope engineering to increase HLA-A2.1 binding affinity. Finally, most of the newly identified epitopes (5 out of 6) were found to be highly crossreactive with other common HLA alleles of the A2 supertype (A2.2, A2.3, A2.6 and A6802), thus demonstrating their potential in providing broad and non-ethnically biased population coverage. The results are discussed in the context of the development of multi-epitope-based therapies with broad applicability for patients suffering from commonly found tumors.
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PMID:The multi-epitope approach for immunotherapy for cancer: identification of several CTL epitopes from various tumor-associated antigens expressed on solid epithelial tumors. 954 34

A new cancer cell line (KKP) was established from an ascitic effusion of an advanced gastric adenocarcinoma, intestinal type. The line has been maintained in continuous monolayer culture with a doubling time of 48 hours for more than 2 years. KKP cells, whose ultrastructural features are presented, showed an aneuploid DNA content, a modal number of 53 chromosomes, and the presence of one double minute chromosome. The karyotype showed trisomies of chromosomes 7, 12, 13, and 14, tetrasomy of chromosome 18, a reciprocal translocation [t(1;20)(q21;p11.2)], and a [t(4;?)] rearrangement. No amplification or rearrangements were evident in the c-MYC, c-ERB B2, H-RAS, INT-2, HST-1, c-MOS, and K-RAS genes, whereas somatic rearrangements were present in the sequences corresponding to c-MET and cyclin E genes by Southern blotting analysis. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of P53 and RB genes did not reveal alterations or point mutations in the SSCP pattern of conformers. The chemosensitivity pattern assay of the KKP cell line indicated that it was sensitive to cisplatin, etoposide, and doxorubicin and resistant to 4'-hydroperoxycyclophosphamide. The clinical history of the patient from whom the cell line was derived is reported and compared with the results observed in the cell line in vitro. High levels of the tumor-associated antigens CEA (carcinoembryonic antigen) and CA19-9 were evident in the KKP cytosol, whereas the KKP spent culture medium maintained the same low levels of CEA and CA 19-9 found in the patient's serum. This new cell line may represent a useful tool for studying the biology of gastric cancer and for planning new therapeutic approaches.
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PMID:Molecular genetics and in vitro sensitivity of a new human cell line, KKP, from a gastric adenocarcinoma. 968 29

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.
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PMID:Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study. 985 98


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