Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transformation of hematopoietic cells by the p210bcr/abl tyrosine kinase appears to require the expression of a functional MYC protein, suggesting that simultaneous targeting of BCR-ABL and c-myc might be a rational strategy for attempting treatment of Phil-adelphia leukemia. To test this hypothesis, severe combined immunodeficiency mice injected with Philadelphia leukemic cells were treated systemically with equal doses of bcr-abl or c-myc antisense oligodeoxynucleotides (ODNs) or with both ODNs in combination. Compared with the mice treated with individual agents, the disease process was much slower in the group treated with both ODNs, as revealed by flow cytometry, clonogenic assay, and reverse transcriptase-polymerase chain reaction analysis to detect leukemic cells in mouse tissue cell suspensions, and by enumeration of liver metastases. The retardation of the disease process was positively correlated with a markedly increased survival of leukemic mice treated with both ODNs. These data demonstrate the therapeutic potential of targeting multiple cooperating oncogenes.
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PMID:Leukemia treatment in severe combined immunodeficiency mice by antisense oligodeoxynucleotides targeting cooperating oncogenes. 750 9

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL-1 beta production by liver macrophages, and the produced IL-1 beta activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.
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PMID:An in vivo study of hepatic and splenic interleukin-1 beta mRNA expression following oral PSK or LEM administration. 785 92

Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.
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PMID:Parathyroid hormone-related protein in an esophageal squamous cell carcinoma with tumor-induced hypercalcemia. 904 Feb 21

We have examined the expression of c-met mRNA in tissue from 27 colorectal cancers and ten liver metastases using the reverse transcriptase-polymerase chain reaction method. The expression of c-met mRNA in these tissues was quantified and the copy number of c-met mRNA to 10(8.0) copies of beta-actin mRNA was calculated. Mean copy numbers of c-met mRNA in cancer tissue and normal mucosa were 10(5.5) and 10(4.5) respectively. The c-met expression of cancer was significantly higher than that of normal mucosa (P < 0.0001). In 20 of 22 samples in which c-met expression of both tumor and corresponding normal tissue were examined, c-met was overexpressed in the cancer tissue. No correlation was found between c-met expression and the clinicopathologic background. The mean copy numbers of c-met mRNA in the tissue from the ten liver metastases and normal liver were 10(6.1) and 10(6.2) respectively. Although c-met expression in metastatic tissue was higher than that in the primary cancer tissue, the increase was not statistically significant. In three of four patients with synchronous liver metastases, c-met was overexpressed in the metastatic tissue compared with that in the corresponding primary cancer tissue. These results show that c-met is overexpressed in both primary colorectal cancer and liver metastases and suggest that c-met plays a role in the development of colorectal cancer liver metastases.
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PMID:Expression of c-met proto-oncogene in primary colorectal cancer and liver metastases. 943 98

We studied the metastatic properties of human tumor cells and tumor cell dissemination in a xenograft tumor model for human colorectal carcinoma in athymic rats which shows a reproducible pattern of metastases similar to the clinical situation. Such a model is also attractive for evaluating several therapeutic approaches. The tumor cell lines HT-29 and WiDr which are derived from the same colorectal tumor and exhibit a similar tumorigenic potential after subcutaneous injection were injected into the portal venous system of 4-week-old male nude rats. After injection of WiDr cells no liver metastases were observed; however, 50% of the rats developed liver metastases 4-12 weeks after injection of HT-29. Immunostaining of the liver cryosections at different times after injection revealed a total disappearance of WiDr cells within the first 12 h. A subpopulation of HT-29 (HT29-b) with increased metastatic activity was isolated by double selection and recultivation of cells from induced liver metastases. After a 6- to 12-week period rats injected with HT-29b showed a pattern of metastases with additional lung metastases and in some cases peritoneal carcinosis. In addition to immunohistochemistry cytokeratin 20 reverse transcriptase-polymerase chain reaction was confirmed to be a sensitive and specific tool for the detection of disseminated tumor cells in different compartments.
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PMID:A human carcinoma model in athymic rats reflecting solid and disseminated colorectal metastases. 992 49

We recently reported that p.o. administration of the new synthetic bacterial lipopeptide JBT-3002 can protect mice from irinotecan (CPT-11)-induced intestinal injury, but the mechanism was not known. Because interleukin-15 (IL-15) is associated with maintenance of intestinal epithelial cell integrity, we examined whether p.o. administration of JBT-3002 elevates expression of this monocyte-derived cytokine. Four daily i.p. injections of 100 mg/kg CPT-11 were effective against liver metastases produced by CT-26 murine colon cancer cells, but severe damage to the intestinal epithelium and early death of the mice also resulted. Three consecutive daily p.o. doses of JBT-3002 prior to i.p. injection of irinotecan prevented the undesirable side effects of irinotecan without reducing its ability to eradicate liver metastases. Immunohistochemical analyses of the intestines of mice treated with JBT-3002 and CPT-11 demonstrated an increase in the number of dividing cells in the crypts and enhanced expression of IL-15 in lamina propria cells; the increase correlated with increased expression of the IL-15 gene as determined by semiquantitative reverse transcriptase-PCR. In vitro studies demonstrated that JBT-3002 induced expression of IL-15 in peritoneal macrophages but not in normal intestinal epithelial cells (IEC-6). Moreover, the presence of IL-15 decreased irinotecan-mediated cytotoxicity of IEC-6 epithelial cells. These data show that the p.o. administration of JBT-3002 induces expression of IL-15 by macrophages in the lamina propria, which can prevent irinotecan-induced injury to the intestinal mucosa.
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PMID:Oral administration of the immunomodulator JBT-3002 induces endogenous interleukin 15 in intestinal macrophages for protection against irinotecan-mediated destruction of intestinal epithelium. 1047 99

The matrix metalloproteinase matrilysin has been implicated in the progression of gastrointestinal and other cancers. The aim of this study was to examine matrilysin mRNA expression and determine whether it is correlated with K-ras mutations and/or progression of pancreatic carcinoma. Using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 11 pancreatic cancer cell lines and 70 pancreatic adenocarcinoma tissues for matrilysin mRNA expression. The results were correlated with clinicopathological characteristics and K-ras mutations. Significant amounts of matrilysin mRNA were detected in six of the eight cell lines with K-ras mutations but not in the three cell lines with wild-type K-ras. Matrilysin mRNA was detected in 57 (81.4% ) of the 70 tumor tissues and in all of the eight liver metastases, but not in any of the adjacent non-tumorous tissues. Matrilysin expression was significantly correlated with the size of tumor, tumor spreading, lymph node metastasis, advanced pathologic tumor-node- metastasis stage and K-ras mutations. The relative amounts of matrilysin mRNA in tumor tissues increased with increase in tumor stage and were highest in liver metastatic tumor tissues. Our results suggest that matrilysin, the expression of which is correlated with K-ras mutations, plays a key role in tumor growth and progression of pancreatic carcinoma.
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PMID:Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas. 1140 48

The features and functions of prostatic neuroendocrine (NE) cells remain ill-defined. Neuroendocrine differentiation (NED) in adenocarcinoma of the human prostate (CaP) is associated with more aggressive disease, but the underlying mediators are poorly understood. We examined these issues in transgenic mice that utilize regulatory elements from the cryptdin-2 gene (Defcr2) to express simian virus 40 large T antigen (TAg) in prostatic NE cells. CR2-TAg mice develop prostatic intraepithelial neoplasia at 8 weeks of age, 1 week after the onset of TAg expression. An invasive phase follows 2-4 weeks later, with lymph node, liver, lung, brain, and bone metastases appearing within 16 weeks. DNA microarray studies revealed 122 mRNAs that were increased >/=2-fold in duplicate assays of 16-week-old CR2-TAg versus normal prostates. Thirty two transcripts encode proteins associated with neurons and endocrine cells (e.g. basic helix loop helix, SRY-related high mobility group box and sine-oculis homeobox transcription factors, Hu RNA-binding proteins, neuronatin, Racgap1, collapsin response mediator protein-1, synaptotagmin-1, proprotein convertase, and secretogranins). Follow-up studies of candidate mediators and biomarkers of differentiation/growth in the microarray data set involved real time quantitative reverse transcriptase-PCR assays of laser capture microdissected NE cells from CR2-TAg prostates plus liver metastases, and immunohistochemical comparisons of transgenic mouse prostates and 35 human CaP samples. Our findings include (a) expression of the bHLH mouse achaete-scute homolog (mASH1) in normal and CR2-TAg NE cells and foci of NED in human CaP, (b) glutamic acid decarboxylase and its product (gamma-aminobutyric acid) in neoplastic NE cells juxtaposed next to cohorts of normal gamma-aminobutyric acid receptor expressing secretory cells (a potential route for paracrine interactions between these two epithelial lineages), and (c) aromatic l-amino-acid decarboxylase, but not its dopamine/serotonin products, in CR2-TAg NE cells and NED. These results underscore the value of CR2-TAg mice for characterizing normal NE cell biology and tumorigenesis.
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PMID:Molecular characterization of a metastatic neuroendocrine cell cancer arising in the prostates of transgenic mice. 1222 43

Deoxycytidine kinase (dCK) is required for the phosphorylation of several deoxyribonucleoside analogues that are widely employed as chemotherapeutic agents. Examples include cytosine arabinoside (Ara-C) and 2-chlorodeoxyadenosine (CdA) in the treatment of acute myeloid leukaemia (AML) and gemcitabine to treat solid tumours. In this study, expression of dCK mRNA was measured by a competitive template reverse transcriptase polymerase chain reaction (CT RT-PCR) in seven cell lines of different histological origin, 16 childhood and adult AML samples, 10 human liver samples and 11 human liver metastases of colorectal cancer origin. The enzyme activity and protein expression levels of dCK in the cell lines were closely related to the mRNA expression levels (r=0.75, P=0.026 and r=0.86, P=0.007). In AML samples, dCK mRNA expression ranged from 1.16 to 35.25 (x10(-3)xdCK/beta-actin). In the cell line panel, the range was 2.97-56.9 (x10(-3)xdCK/beta-actin) of dCK mRNA expression. The enzyme activity in liver metastases was correlated to dCK mRNA expression (r=0.497, P=0.05). In the liver samples, these were not correlated. dCK mRNA expression showed only a 36-fold range in liver while a 150-fold range was observed in the liver metastases. In addition, dCK activity and mean mRNA levels were 2.5-fold higher in the metastases than in the liver samples. Since dCK is associated with the sensitivity to deoxynucleoside analogues and because of the good correlation between the different dCK measurements in malignant cells and tumours, the CT-RT PCR assay will be useful in the selection of patients that can be treated with deoxycytidine analogues.
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PMID:Expression of deoxycytidine kinase in leukaemic cells compared with solid tumour cell lines, liver metastases and normal liver. 1262 50

When injected subcutaneously, mouse plasmacytoma (MOPC315) grew rapidly in situ, and metastatic cells became detectable first in the lymph nodes (LNs) and bone marrow, and later in the liver and lungs. We studied MOPC315 cell migration by tracking metastatic cells labelled with green fluorescent protein (GFP). We measured the levels of their chemokine receptor mRNA (by semiquantitative and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), because chemokines can regulate organ predilection of metastasis. Freshly sorted metastatic cells and tumour cell lines derived from the liver of BALB/c mice overexpressed functional CCR6 and CCR7 molecules compared with primary tumour. Preincubation with the CCR6 ligand (CCL20) induced liver-sorted tumour cells to preferentially colonize the liver, demonstrating an association between liver metastasis and CCR6 expression in the mouse. Because the liver is a common site for metastasis, second only to draining LNs, we wished to ascertain whether this finding could be generalized, i.e. whether other cancers can use the similar mechanism of metastasis to the liver, and whether it holds true for humans. We found that CCR6 is overexpressed in small liver metastases of colon, thyroid and ovarian carcinomas compared with normal liver. Because human liver constitutively expresses CCL20, it could attract and select CCR6+ cancer cells. We suggest that chemotaxis via CCR6 might be a common mechanism by which malignant cancers metastasize to the liver. As metastasis in patients with cancer poses the biggest peril for survival, inhibition of CCR6 signalling, either during or after medical or surgical treatment, might be useful in preventing liver metastasis.
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PMID:Liver metastasis of cancer facilitated by chemokine receptor CCR6. 1279 Oct 91


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