Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GB16, GB18, GB19 and GB22 are mouse monoclonal antibodies produced against full-term human placental microvilli. These antibodies reacted predominantly with the apical surface of the syncytiotrophoblast from first-trimester and full-term placentae, and also reacted with several cell lines derived from non-haematopoietic tissues by immunofluorescence. The radioiodinated BeWo (choriocarcinoma) cell surface proteins were immunoprecipitated with these four antibodies and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The results demonstrated that the immunoprecipitates migrated at 180 and 90 kilodaltons under non-reducing and reducing conditions, respectively. Using enzyme-linked immunosorbent assay, the antigens recognized by GB16, GB18, GB19, and GB22 were able to bind human transferrin. Immunoabsorption studies showed that these four antibodies bound to the same molecule as OKT9, an antibody to the transferrin receptor. Moreover, the reactivities of these antibodies with HL-60 (promyelocytic leukaemia) cells diminished following dimethyl sulphoxide-induced differentiation by flow cytometric analysis. These data indicate that these four antibodies recognize the transferrin receptor. By competition assay, GB18 bound to an epitope different from those recognized by GB16, GB19 and GB22. In addition, GB22 displayed significant growth inhibition against the activated lymphocytes and Daudi cells, but not against HL-60 or Jurkat cells. These data suggest that these four monoclonal anti-transferrin receptor antibodies will provide additional means to investigate the physiological roles played by the transferrin receptor.
Placenta
PMID:Monoclonal antibodies (GB16, GB18, GB19, GB22) raised against human placental microvilli recognize the transferrin receptor. 343 58

After delivery of a healthy female child from a mother suffering from acute lymphatic leukaemia (35th week of gestation) the placenta was examined by light and electron microscopy. Morphologically, the villi in this placenta from a case of maternal acute lymphatic leukaemia differed from those in a normal placenta in the following respects: 1. The frequent occurrence of fibrinoid deposits on the free surface of the syncytiotrophoblast and the pronounced formation of syncytial cytoplasmic protrusions. 2. Dilatation of syncytial rough endoplasmic reticulum, numerous syncytial knots and numerous autophagosomes. 3. An excessive number of villous cytotrophoblastic cells. 4. Thickening of the trophoblastic basement membrane. 5. Bulbous endothelial cells with cytoplasm in fetal capillaries. 6. Strands of basement membrane-like material within the villous stroma. 7. Phagocytosis of nucleus-containing cells by the syncytiotrophoblast. 8. Cells with an abundant number of microtubular bundles within the villous stroma. It is suggested that phagocytosis of nucleus-containing cells (tumour cells?) by the syncytium could play a role in the prevention of transplacental metastasis.
Placenta
PMID:Structural aspects of a placenta from a case of maternal acute lymphatic leukaemia. 657 31

The purpose of this study was to identify the presence of placental neutral metalloendopeptidase (NEP; enkephalinase; EC 3.4.24.11) in human normotensive and pre-eclamptic pregnancy. The localization of NEP in placentae from normotensive, chronic hypertensive and pre-eclamptic pregnancies was carried out on fresh frozen tissues by using a monoclonal primary antibody developed against human common acute lymphoblastic leukaemia antigen (CD10) together with the avidin-biotin-peroxidase method. In placentae from normotensive, chronic hypertensive and superimposed pre-eclamptic pregnancies, intense staining was found in the extravillous trophoblast, and also in fibroblasts of the chorionic plate and stem villi. Light to moderate staining was noted in the villous-associated trophoblast and in some cells from the villous core. In cases of pre-eclampsia, very intense staining was detected not only on the surface, but also in the cytoplasm of the villous-associated trophoblast. The increased expression of placental NEP in pre-eclampsia suggests that this enzyme may be involved in the regulation of the local concentration of circulating biologically active peptides at the fetomaternal interface, and thus could be implicated in the pathophysiological changes of this syndrome.
Placenta 1995 Jul
PMID:Increased immunohistochemical expression of neutral metalloendopeptidase (enkephalinase; EC 3.4.24.11) in villi of the human placenta with pre-eclampsia. 747 14

We investigated the functional expression of the plasma membrane serotonin transporter and the vesicular monoamine transporter in choriocarcinoma cells and normal trophoblasts. The RBL 2H3 cells, a rat basophilic leukaemia cell line, which express both transporters were used for comparison. The choriocarcinoma cells JAr and BeWo were found to possess the plasma membrane serotonin transporter as assessed by the presence of serotonin transport activity in intact cells that was Na(+)-dependent and was sensitive to inhibition by tricyclic and non-tricyclic antidepressants. The activity of the vesicular monoamine transporter in these cells was determined by measuring serotonin transport in digitonin-permeabilized cells. The transport in permeabilized cells was very slow, was not stimulated by ATP and was insensitive to inhibition by reserpine. Under similar conditions, the vesicular monoamine transporter activity was demonstrable in RBL cells, which was stimulated by ATP and was inhibitable by reserpine, bafilomycin A1 (an inhibitor of the V-type H(+)-pump) and carbonyl cyanide p-trifluoromethoxy phenylhydrazone (a protonophore which dissipates transmembrane H+ gradients). In corroboration with these findings, mRNA transcripts hybridizable to the vesicular monoamine transporter cDNA probe were detectable in RBL cells but not in JAr choriocarcinoma cells. Similarly, there was no evidence for the expression of the vesicular monoamine transporter as assessed by Northern blot analysis in normal trophoblasts which were maintained in culture to differentiate to form multinucleated syncytial cells. It is concluded that the trophoblasts and choriocarcinoma cells express the plasma membrane serotonin transporter but not the vesicular monoamine transporter.
Placenta 1996 May
PMID:Functional expression of the plasma membrane serotonin transporter but not the vesicular monoamine transporter in human placental trophoblasts and choriocarcinoma cells. 876 63

Leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6) are candidate embryo-maternal signalling molecules which are present within the uterine luminal micro-environment. We examined the relative expression of the mRNAs encoding LIF and IL-6, as well as the LIF-binding subunit (LIFR-beta) of the LIF receptor and, as a potential downstream cytokine-responsive gene, beta(2)-microglobulin (beta(2)m), in porcine peri-implantation conceptuses, and in placenta and endometrium during early and mid-pregnancy. Peri-implantation spherical and filamentous conceptuses expressed LIFR-beta and beta(2)m mRNAs with no LIF mRNA present. Rapid development in days 11/12 spherical conceptuses to the filamentous stage was accompanied by transiently increased IL-6 gene expression. The corresponding endometrium, in contrast, expressed LIF in addition to these other mRNAs. LIFR-beta, IL-6 and beta(2)m, but not LIF mRNAs, were expressed in the Jag-1 cell line, an in vitro model for porcine day 14 trophoblast. The greatest steady-state amounts of LIF, LIFR-beta and IL-6 mRNAs in both the endometrium and placenta were evident at the post-implantation stages (days 30 and 60>day 18 of pregnancy). Treatment of porcine endometrial explants with human recombinant (hr)LIF or hrIL-6 resulted in no change in, or diminished, the presence of endometrial beta(2)m mRNA, respectively. Addition of LIF to peri-implantation conceptus explant cultures, in contrast, induced beta(2)m mRNA synthesis. These results highlight the potential importance of both the endometrium and placenta as sources, as well as targets, of these cytokines throughout pregnancy. Cytokine modulation of beta(2)m, a known in vitro mitogen, may constitute one mechanism for local control of trophoblast and endometrial proliferation.
Placenta 2000 May
PMID:Pregnancy-dependent expression of leukaemia inhibitory factor (LIF), LIF receptor-beta and interleukin-6 (IL-6) messenger ribonucleic acids in the porcine female reproductive tract. 1083 69

Approximately 1 per 1,000-1,500 pregnancies is complicated by maternal malignancies. Metastatic involvement of the products of conception is a rare event. There have been 62 cases of placental and/or fetal metastatic involvement originating from maternal cancer reported since 1866. Only 14 cases of lung cancer associated with pregnancy have been documented. We report on an additional case involving the products of conception, and the management of lung cancer in pregnancy is discussed based on an extensive review of the literature. The case of a 29-year-old woman presenting during the 31(st) week of gestation with metastatic non small-cell lung cancer to the placenta, liver and bone is described. The mother was delivered by caesarean section of a healthy baby girl during her 32(nd) week of gestation. The mother's postpartum course was complicated by disseminated pulmonary and bony metastases and malignant pericardial and pleural effusions causing the patient's death within 1 month after lung cancer was diagnosed. Malignancies spreading to the products of conception are melanoma (32%), leukemia and lymphomas (15%), breast cancer (13%), lung cancer (11%), sarcoma (8%), gastric cancer (3%) and gynecologic cancers (3%), reflecting malignancies with a high incidence in women of reproductive age. All lung cancers were diagnosed with widely disseminated, inoperable neoplastic disease, including distant metastases in 46%. The mean age was 35.1 years (range, 30-45 years) and 60% of patients had a history of tobacco use. The mean survival was 7.5 months (range: 1-42 months). Placenta involvement was present in 7 out of 15 cases. Fetal involvement was reported in only one case. Because there is no evidence of a direct adverse effect of pregnancy on the course of lung cancer, we recommend delivery at a time when enough fetal maturity can be assumed and the subsequent treatment of the mother.
 ...
PMID:Lung cancer during pregnancy involving the products of conception and a review of the literature. 1276 92

Aberrant activity of the signal transducer and activator of transcription 3 (Stat3) is believed to be essential for neoplastic cell behaviour and thus for the malignancy of tumor cells [Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000;19:2474-88]. Extravillous trophoblast cells resemble malignancies in their invasive and destructive features, excluding the fact of sequential restriction to the first trimester of pregnancy. Trophoblast cells from term placentas have reduced invasive capacity [Hohn HP, Denker HW. Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells. Cells Tissues Organs 2002;172:218-36]. Constitutively activated Stat3 DNA-binding activity in choriocarcinoma cells, carcinomatous derivates of trophoblast cells, have been reported to correlate with its invasiveness [Corvinus FM, Fitzgerald JS, Friedrich K, Markert UR. Evidence for a correlation between trophoblast invasiveness and STAT3 activity. Am J Reprod Immunol 2003;50:316-21]. Here we demonstrate using RNAi that Stat3 activation is necessary in the invasive phenotype of trophoblast cells and can be controlled via Leukemia Inhibitory Factor (LIF). LIF provides a soluble extracellular signal that stimulates invasion in trophoblast and Jeg-3 choriocarcinoma cells. Loss of LIF-mediated invasion in these cells subsequent to STAT3 knock-down strongly suggests that STAT3 plays a crucial role in mediating this invasion.
Placenta 2005 Apr
PMID:Trophoblast invasion: tuning through LIF, signalling via Stat3. 1583 65

Homeodomain (HDM) proteins encoded by homeobox (HBX) genes represent a large family of transcriptional factors that control differentiation and development in certain cell types. DLX4 is a member of Distal-less (DLX) family of HBX genes. Recent studies have demonstrated that abnormal expression of DLX4 is present in several types of human tumors, such as breast cancer, leukemia and colon cancer. In the present study, we investigated DLX4 mRNA and protein expression in both normal placental tissues and human choriocarcinoma cell lines. Also, using RNA interference (RNAi) technique, we knocked down the expression of DLX4 and examined apoptosis in JEG-3 cells. Our studies demonstrated that DLX4 RNAi inhibited DLX4 mRNA expression and decreased DLX4 protein mass specifically and effectively, potentially enhancing apoptosis. Moreover, we examined expression of caspase-3 and caspase-8, and found that both caspases were increased after DLX4 knockdown. However, DLX4 RNAi did not influence Bax expression in JEG-3 cells. In conclusion, this study suggests that DLX4 may be involved in the survival of human choriocarcinoma cells, which may be mediated by the inhibition of apoptosis. The detailed mechanism needs further investigation.
Placenta
PMID:Inhibition of DLX4 promotes apoptosis in choriocarcinoma cell lines. 1597 50