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At least 937 records · Page 52Linked to original sources
PubMed1989

c-myc protooncogene expression in mouse erythroleukemia cells.

Murine erythroleukemia (MEL) cells are erythroid progenitors whose programs of erythroid differentiation has been interrupted by transformation with the Friend virus complex. As a result of the ability of certain chemicals such as dimethylsulfoxide (DMSO) to induce terminal erythroid differentiation, the cells have been used as a model for understanding the molecular basis of cellular differentiation. Recent work on MEL cells as well as other differentiating systems indicates that expression of cellular protooncogenes is implicated in chemically mediated differentiation. In MEL cells the expression of the c-myc protooncogene undergoes unusual biphasic changes following inducer treatment. Levels of c-myc mRNA decrease 10- to 20-fold between 1 and 2 hr and are then reexpressed between 12 and 24 hr. These changes occur as a result of complex transcriptional and posttranscriptional regulatory events. Recent DNA transfection experiments, in which MEL cells were transfected with myc expression vectors, indicate that both the early decrease in c-myc expression and its subsequent reexpression are important events in the differentiation pathway. The work on MEL cells, as well as on other models of differentiation, is directed at understanding the molecular basis of leukemogenic transformation and cellular differentiation. The ability of c-myc, as well as other protooncogenes, to influence both of these events indicates that cellular protooncogenes play a central role in their regulation.

Animals↗
PubMed2001

[The value of marker antigens TPS, SCC and CEA in diagnosis, evaluation of histologic type and clinical disease progression in patients with cervical carcinoma].

Pretreatment values TPS, SCC and CEA were measured in 84 patients with cervical carcinoma in order to evaluate the usefulness of markers in diagnosis, estimation of the histological type, estimation of stage of disease and grade of cellular differentiation. TPS was raised in 78.4%, SCC was raised in 71.8% and CEA was raised in 32.4% patients with cervical carcinoma. The frequency of increased results and absolute value of TPS and SCC levels showed tendency to significant increase with the stage of disease and to the grade of cellular differentiation. The highest sensitivities TPS and SCC were observed in patients with carcinoma planoepitheliale macrocellulare akeratodes, CEA in adenocarcinoma clarocellulare. These results suggest that TPS especially in the combination with SCC may be useful in the diagnosis and estimation of stage of disease of patients with cervical carcinoma.

Adenocarcinoma↗
PubMed1973

Role of the mitochondrial genome during early development in mice. Effects of ethidium bromide and chloramphenicol.

The role of the mitochondrial genome in early development and differentiation was studied in mouse embryos cultured in vitro from the two to four cell stage to the blastocyst (about 100 cells). During this period the mitochondria undergo morphological differentiation: progressive enlargement followed by an increase in matrix density, in number of cristae, and in number of mitochondrial ribosomes. Mitochondrial ribosomal and transfer RNA synthesis occurs from the 8 to 16 cell stage on and contributes to the establishment of a mitochondrial protein-synthesizing system. Inhibition of mitochondrial RNA- and protein-synthesis by 0.1 microg/ml of ethidium bromide or 31.2 microg/ml of chloramphenicol permits essentially normal embryo development and cellular differentiation. Mitochondrial morphogenesis is also nearly normal except for the appearance of dilated and vesicular cristae in blastocyst mitochondria. Such blastocysts are capable of normal postimplantation development when transplanted into the uteri of foster mothers. Higher concentrations of these inhibitors have general toxic effects and arrest embryo development. It is concluded that mitochondrial differentiation in the early mouse embryo occurs through the progressive transformation of the preexisting mitochondria and is largely controlled by the nucleocytoplasmic system. Mitochondrial protein synthesis is required for the normal structural organization of the cristae in blastocyst mitochondria. Embryo development and cellular differentiation up to the blastocyst stage are not dependent on mitochondrial genetic activity.

Animals↗
PubMed2002

Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity.

Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids, 2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta-isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6), 4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide (7), 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oic acid methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were evaluated for their potential as cancer chemopreventive agents, by measuring antiproliferative activity in Col2 cells and induction of cellular differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds were then investigated for their ability to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay. Among these isolates, 5 and 6 showed significant antiproliferative activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly inhibited (63.0% at 10 microg/mL) lesion formation in the mouse mammary organ culture assay. The chemical structures of 1-3 were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were determined by Mosher ester methodology.

Animals↗
PubMed1996

Malignant fibrous histiocytoma: histomorphological pattern or tumor type.

During the past years MFH has obviously been used as a diagnostic waste basket for hard to classify tumours of all kinds. Immunohistochemistry revealed insights into cellular differentiation of neoplastic proliferations, also raising new questions because of unexpected antigen expression, as, for instance, cytokeratins in MFH. Thus, a number of tumours originally diagnosed as MFH could be reclassified, i.e., as leiomyosarcoma, melanoma or anaplastic carcinoma. Nevertheless, there remain a certain number of sarcomas which lack any evidence of special cellular differentiation. These proliferations of primitive mesenchymal or fibroblastic cells, often with a typical histological, storiform pattern, qualify as MFH. Using these strict criteria, the diagnosis of MFH will become rarer, though not obsolete (like hemaugioperizytoma years ago!).

Histiocytoma, Benign Fibrous↗
PubMed1986

The effects of different steroids on costal and epiphyseal cartilage of fetal and adult rats.

The effects of different doses of various steroids on growth, and on costal and epiphyseal chondrocytes, have been studied in prenatal, immature, and adult Long-Evans rats using histochemical techniques, and both light and electron microscopy. Both prenatal and postnatal treatments have been employed. The steroids used were cortisone (CA), betamethasome (BM), and, in the prenatal group only, dexamethasone (DM). Body weight is reduced in all treated rats (except the low dose of CA) by day 17 of gestation, with greater weight reductions occurring in rats receiving the higher dose level of each steroid. In rats treated prenatally or neonatally, and sacrificed postnatally on days 39-43 or days 116-127, body weights, and tibial and tail lengths, are less than in correspondingly aged controls, thus showing a persistence of the effects of treatment. Costal and epiphyseal cartilages in prenatal rats show cellular, synthetic, and ultrastructural alterations induced by treatment with glucocorticoids but the responses are not necessarily comparable. Except for the low dose of DM, the higher doses of each steroid are more effective in inhibiting, or altering, growth and cellular differentiation in the developing fetuses. Surprisingly, a low dose of DM has a more devastating effect on the cells and extracellular matrix of both costal and epiphyseal cartilage, than do higher dose-levels of the various steroids. Low doses of CA and BM are also effective in inhibiting or altering growth and cellular differentiation, but their effectiveness is largely limited to 17 days of gestation. The order of effect of the various doses of the different steroids on fetal cartilage, listed in decreasing order of severity, is as follows: 0.12 DM, 0.24 DM, 0.42 BM, 50 CA, with 25 CA and 0.18 BM being approximately equal and only slightly different from control cartilages. The effect of prenatal or neonatal glucocorticoid treatment on chondrocytes is minimal in the 30-43 days, or 116-127 day, postnatal groups. In immature and adult rats, cortisone affects the chondrocytes more deleteriously than does betamethasone, and a 5.0 mg dose of CA seems to affect chondrocytes, body weight, and tibial and tail lengths more than 0.2 or 7.5 mg doses.

Animals↗
PubMed1997

The correlation of membranous glycoprotein-gp-170, cytoplasmic glutathione and glucose-6-phosphate dehydrogenase levels with multidrug resistance in transitional cell carcinoma cell lines of the urinary tract.

The expression of membranous glycoprotein gp-170, cytoplasmic glutathione (GSH) and energy-related glucose-6-phosphate dehydrogenase (G-6-PD) in cultured normal urothelial cells and transitional cell carcinoma (TCC) cell lines was analyzed by flow cytometric and enzymatic methods. The chemosensitivity of these tumor cells to four major types of anticancer drugs, including cisplatin, thiotepa, methotrexate, 5-fluorouracil, adriamycin and vinblastine, was correlated with biological activities in TCC cell lines. The TCC cell lines displayed a general sensitivity to anticancer drugs with a low incidence of highly resistant cell lines (23%). The expression of multidrug resistance was not related to cellular differentiation or invasiveness of cancer cells. Only 24% of TCC cell lines had an elevated expression of gp-170, but their expression was not related to drug resistance. Increased cytoplasmic GSH and G-6-PD was observed in over 90 per cent of TCC cell lines, but no correlation with drug resistance and cellular differentiation was observed. The biological activities of GSH and G-6-PD were not related to the drug resistance of TCC. The low expression rate of gp-170 in TCC cells indicates that other mechanisms should be involved in the development of MDR in TCC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells.

BACKGROUND & AIMS: Regulatory cytokines mediate intestinal epithelial cell (IEC) participation in mucosal immune responses. The aim of this study was to investigate the expression of secretory and intracellular isoforms of interleukin 1 receptor antagonist (IL-1Ra) in human primary IECs and carcinoma-derived cell lines. METHODS: Primary IECs were isolated from patients with Crohn's disease or ulcerative colitis and from normal controls. Isoform-specific IL-1Ra messenger RNA (mRNA) and protein were assessed by reverse-transcription polymerase chain reaction and Western blot analysis. Expression during cellular differentiation was determined by in situ immunohistochemistry on sequentially released, native IECs and in vitro differentiated cell lines. Intracellular IL-1Ra I function was analyzed by permanent transfection of Caco-2 cells. RESULTS: Intracellular IL-1Ra I protein accumulated in surface IECs with extension to the crypts during inflammation. Secretory IL-1Ra and intracellular IL-1Ra II mRNA, but not the corresponding protein, was detected. Transcription of intracellular IL-1Ra I mRNA was significantly up-regulated with inflammation and in vitro by phorbol myristate acetate and interleukin 1beta. In vitro differentiated cells had higher constitutive intracellular IL-1Ra I protein content. Intracellular IL-1Ra I expression in Caco-2 cells decreased IL-1beta-stimulated interleukin 8 secretion. CONCLUSIONS: Native human IECs and certain cell lines constitutively express intracellular IL-1Ra type I, which is up-regulated by inflammation, inflammatory stimuli, and cellular differentiation. Constitutive expression of this anti-inflammatory cytokine may contribute to mucosal protection.

Cell Differentiation↗
PubMed2004

Ageing and exposure to oxidative stress in vivo differentially affect cellular levels of PrP in mouse cerebral microvessels and brain parenchyma.

The biological function of cellular prion protein PrPc has not been established, despite in vitro studies suggesting antioxidant activity or link to signal transduction pathways. In this study, mice were exposed to hyperoxia to establish whether oxidative stress affected prion expression in vivo. C57Bl/6J mice aged 6, 18, and 24 months, maintained under normoxic conditions, exhibited age-related increases in PrPc in both cerebral microvessels and in microvessel-depleted brain homogenate. We demonstrate that PrPc is differentially affected by exposure to hyperoxia in vivo for 1 (24 h) or 2 (48 h) days, or for 1 day hyperoxia, followed by 1 day normoxia. Brain parenchymal cells from 6-month-old mice exposed to 1 day hyperoxia showed elevation of a glycosylated approximately 36 kDa form, whereas in 24-month-old mice cellular prion level was substantially reduced. Extending hyperoxia from 1 to 2 days resulted in significantly reduced PrPc level, regardless of age. Parenchymal PrPc is substantially elevated in 6-month-old mice, but declines in 18- and 24-month-old animals following 1 day hyperoxia. By contrast, PrPc content in cerebral microvessels from 6-month-old mice declined after a 2 day exposure to hyperoxia, while microvessels from 24-month-old brains showed elevated prion levels 24 h after hyperoxia. Moreover, unglycosylated 25-30 kDa PrPc, and a previously undescribed 50-64 kDa band containing at least some glycosylated protein, predominated in microvessels with lesser content of the glycosylated approximately 36 kDa form. Cellular content of these unglycosylated forms was correlated with age, while the response to hyperoxia was evident in both unglycosylated and glycosylated forms of the protein following 1 and 2 day exposures. The observed elevation of the 25-30 and 50-64 kDa bands of microvessel PrPc is not sustainable following 1 day hyperoxia, but returns to near normoxic levels within 24 h after hyperoxia. We also show in a knockout mouse for methionine sulfoxide reductase (MsrA), the enzyme responsible for reducing methionine sulfoxide back to methionine, and a regulator of cellular antioxidant defence, that following hyperoxia brain PrPc in the null mutant is elevated relative to PrPc content in the parent strain. Our results show up-regulated PrPc expression or reduced turnover in response to age-related, and hyperoxia-induced oxidative stress.

Aging↗
PubMed1997

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts.

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF, thereby demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (KD 451-709 pM; receptors/cell 2306-13645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.

3T3 Cells↗
PubMed1994

Arabidopsis COP8, COP10, and COP11 genes are involved in repression of photomorphogenic development in darkness.

Wild-type Arabidopsis seedlings are capable of following two developmental programs: photomorphogenesis in the light and skotomorphogenesis in darkness. Screening of Arabidopsis mutants for constitutive photomorphogenic development in darkness resulted in the identification of three new loci designated COP8, COP10, and COP11. Detailed examination of the temporal morphological and cellular differentiation patterns of wild-type and mutant seedlings revealed that in darkness, seedlings homozygous for recessive mutations in COP8, COP10, and COP11 failed to suppress the photomorphogenic developmental pathway and were unable to initiate skotomorphogenesis. As a consequence, the mutant seedlings grown in the dark had short hypocotyls and open and expanded cotyledons, with characteristic photomorphogenic cellular differentiation patterns and elevated levels of light-inducible gene expression. In addition, plastids of dark-grown mutants were defective in etioplast differentiation. Similar to cop1 and cop9, and in contrast to det1 (deetiolated), these new mutants lacked dark-adaptive change of light-regulated gene expression and retained normal phytochrome control of seed germination. Epistatic analyses with the long hypocotyl hy1, hy2, hy3, hy4, and hy5 mutations suggested that these three loci, similar to COP1 and COP9, act downstream of both phytochromes and a blue light receptor, and probably HY5 as well. Further, cop8-1, cop10-1, and cop11-1 mutants accumulated higher levels of COP1, a feature similar to the cop9-1 mutant. These results suggested that COP8, COP10, and COP11, together with COP1, COP9, and DET1, function to suppress the photomorphogenic developmental program and to promote skotomorphogenesis in darkness. The identical phenotypes resulting from mutations in COP8, COP9, COP10, and COP11 imply that their encoded products function in close proximity, possibly with some of them as a complex, in the same signal transduction pathway.

Arabidopsis↗
PubMed2005

THY-1 induction is associated with up-regulation of fibronectin and thrombospondin-1 in human ovarian cancer.

We recently identified THY-1 as a putative tumor suppressor gene for human ovarian cancer. To understand the carcinogenic role of THY-1, and its downstream effects on cancer cells, a THY-1 inducible system was established in the human ovarian cancer cell line SKOV-3 based on the tetracycline (tet) regulating system. To establish an inducible system for Thy-1 expression, two plasmids, pUHD172-1neo and pTEP4mThy-1, which are neomycin and hygromycin resistant were co-transfected into the ovarian carcinoma cell line, SKOV-3. The inducibility of Thy-1 expression in the SKOV-3 cell line by doxycycline (dox) was determined by northern blot analysis, immunocytochemistry, and flow cytometry. A time course study revealed that Thy-1 expression is induced 3 hours post dox exposure. Expression was reversible such that 12 hours post the removal of dox almost no Thy-1 could be detected. Furthermore, 2 genes, Fibronectin (FN) and Thrombospondin (TSP-1) involved in cellular differentiation and the regulation of tumor angiogenesis, respectively, were found to be up-regulated upon THY-1 induction. In contrast, the gene SPARC was found to be independent of Thy-1 expression. This study supports the hypothesis that THY-1 plays a critical role in regulating downstream genes associated with the regulation of ovarian tumor growth and cellular differentiation.

Doxycycline↗
PubMed1979

"The diencephalon of Ptilocercus lowii (pen-tailed tree-shrew)".

The pen-tailed tree-shrew (Ptilocercus lowii) has been regarded by Le Gros Clark (1926), and Martin (1968) to possess more primitive morphological and to a certain extent, neuro-anatomical characteristics than the other tree-shrew species belonging to the sub-family Tupaiinae. Investigations have been carried out on the diencephalon of Ptilocercus lowii which has not been completely done by Le Gros Clark and other workers since 1926, to find out whether the diencephalon has actually undegone any phylogenetic changes that should be more advanced than those of the Insectivora or remain more primitive than that of the Tupaiinae. The diencephalic structure that show the most significant phylogenetic features which differe Ptilocerecus from Tupaia are observed in the anterior, dorsolateral and ventrolateral thalamic groups, and the geniculate bodies. The nucleus anteroventralis is, by comparison, much smaller and poorly differentiated from the nucleus anteromedialis. The nucleus anterodorsalis is also comparably large and does not reach the dorsal surface of the thalamus as it does in the primates. The midline nuclei do not show any significant differences, except the notably larger size of nucleus parataenialis in Ptilocercus. The nucleus mediodoralis is small and indifferentiated although it does show some incipient signs of cellular differentiation. The nucleus centralis lateralis is well developed; its inferior (ventral) part is larger than its superior part which is the better developed of the two parts in the tupaiids and primates. The nucleus centrum medianum appears to be very small and forms only a lateral extension of the nucleus parafascicularis. The ventrolateral thalamic group basically consists of nuclei ventrales anterior, lateralis and posterior without intermediate or transitional zones as found in Tupaia and Primates. The nucleus pretectalis is the largest and the best developed of all the elements of the posterior thalamic nuclear group. The lateral geniculate nucleus is not differentiated into laminae like that in Tupaia and Primates; it is merely a homogeneous structure that appears to be smaller in size that the pregeniculate and medial geniculate nuclei. The medial geniculate nucleus is large in proportional size of the whole thalamus and appears to be well differentiated cellularly into several small parts. No remarkable changes are noted in the epithalamus, subthalamus and hypothalamus. However, the nucleus ventromedialis appears to be the most outstanding structure in the infundibular region of the hypothalamus. The mammillary region is of a simpler construction in Ptilocercus than in Tupaia; it does not protrude from the ventral surface of the hypothalamus. In the light of these findings, the phyletic status of Ptilocercus in the family Tupaiidae is discussed.

Animals↗
PubMed2006

Expression and regulation of the mu opioid peptide receptor in TPA-differentiated HL-60 promyelocytic leukemia cells.

Cellular differentiation of immune cells involves an array of molecular events responsible for their commitment to cellular maturation. Treatment of HL-60 promyelocytic leukemia cells with 12-o-tetradecanoyl-phorbol-13-acetate (TPA) induces the cells to differentiate into monocyte/macrophage-like cells. In this study, following TPA treatment, there was a significant increase in mu opioid peptide receptor (MOPR) mRNA levels in the differentiated HL-60 cells as measured by quantitative-competitive RT-PCR (QC-RT-PCR) and real-time RT-PCR. Morphine's inhibition of forskolin-induced intracellular cAMP confirmed the functionality of the MOPR. TPA-induced differentiation also significantly enhanced the binding activities of two transcriptional factors, AP-1 and NFkB. Prolonged treatment of the TPA-differentiated HL-60 cells with morphine down-regulated MOPR mRNA expression and decreased the binding activities of AP-1 and NFkB, both of which were naloxone reversible. Thus, the direct correlation between AP-1 and NFkB binding activities and MOPR expression in HL-60 cells following TPA-induced differentiation as well as in TPA-differentiated HL-60 cells given prolonged treatment with morphine suggests that transcriptional factors, such as AP-1 and NFkB, may play a role in the molecular mechanisms underlying regulation of MOPR expression in immune cells.

Analgesics, Opioid↗
PubMed1990

Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon-gamma.

The regulation of carcinoembryonic antigen (CEA) expression by recombinant human interferon-gamma (IFN-gamma) was studied in a series of 7 human colorectal tumor cell lines at various stages of differentiation. Two of the colorectal cell lines were poorly differentiated and did not constitutively express CEA. IFN-gamma treatment, however, induced CEA expression in one of those lines (i.e., DLD-1) as evidenced by the appearance of CEA-related mRNA transcripts, as well as the cell surface expression of the antigen as measured by flow cytometry and radioimmunoassay. In the highly differentiated colorectal tumor cell lines, IFN-gamma treatment resulted in no detectable change in CEA content in whole cell extracts or in the percentage of cells positive for cell surface CEA expression. In fact, IFN-gamma treatment of the highly differentiated LS174T cell line not only failed to alter CEA expression, but also failed to induce class II human leukocyte antigen expression. Therefore, the highly differentiated LS174T cell line and the poorly differentiated MIP cell line represent colorectal tumor cell types that are unresponsive to the ability of IFN-gamma to induce alterations in tumor (i.e., CEA) or normal (i.e., class I and class II human leucocyte antigen) surface antigen expression. The most responsive of human colorectal tumor cells to the ability of IFN-gamma to alter CEA expression were the moderately differentiated cell lines (i.e., HT-29, WiDr, etc.). IFN-gamma treatment of those cell types increased the CEA content in cell extracts by 300-400%, and increased the percentage of cells positive for surface CEA expression from 30-45% to greater than 80%. The effect of IFN-gamma treatment on 2',5'-oligoadenylate synthetase (2'-5' A) activity was also studied using 4 of the 7 colorectal cell lines. Constitutive 2'-5' A activity varied approximately 14-fold and was not correlated with degree of cellular differentiation. IFN-gamma treatment increased 2'-5' A activity in all 4 colorectal tumor cells tested. In particular, the ability to enhance 2'-5' A activity in the MIP and LS174T cells, 2 colorectal tumor cell types that previously were shown to be unresponsive to IFN-gamma-mediated changes in their antigenic phenotype, clearly separates cellular events regulating 2'-5' A activity from those involved in regulating cell surface antigen expression. The findings also suggested that the regulation of CEA expression by IFN-gamma is not related to the degree of cellular differentiation and, furthermore, provide some insight into which human tumor cell populations may be the most amenable to tumor antigen augmentation by IFN-gamma in an adjuvant setting with a monoclonal antibody.

2',5'-Oligoadenylate Synthetase↗
PubMed1995

[Survival of patients with upper urothelial tumor].

OBJECTIVE: A descriptive analysis of 35 patients with transitional cell carcinoma of the upper urinary tract is presented. The actuarial survival was analyzed to determine which circumstances associated with superficial bladder cancer had a prognostic significance. METHODS: The records of 35 patients with upper urothelial tumor diagnosed from 1987 to 1993 were retrospectively analyzed. A descriptive statistical analysis was performed on all the variables. Correlation was determined by Pearson's Xi2 test, Yates' and Fisher's exact test. McNemar's test was used to determine which diagnostic method had the highest yield. The actuarial survival data were analyzed with the Kaplan-Meier and Mantel-Haenzel test. RESULTS: Patient mean age was 67.74 yrs, mean follow up was 26.83 months, 40% were ureteral tumors, 25.7% were pelvic tumors, 60.6% were superficial tumors and 62.6% were GI and GII, 48.5% were associated with bladder tumors and no correlation was found between the grade and stage of bladder relapses and the upper urinary tract tumors. Intravenous urography demonstrated function was abolished in 45.5%. Cytology gave the highest diagnostic yield (84.6%). Nephroureterectomy with perimeatal cystectomy was the surgical technique most frequently used (57.1%). To date, 71.4% of the patients have survived. Significantly women demonstrated the most undifferentiated cellular grade (p < 0.001), although no prognostic value was found for sex. 95% of the patients with non-infiltrating tumor stages and 95% of the patients with GI-GII tumors survived, whereas 61.5% of the patients with infiltrating tumors and 58.3% of those with GIII tumors did not survive (p < 0.002). Evidently, the grade of cellular differentiation and the stage of infiltration were interrelated (p < 0.002). Analysis of the actuarial survival data showed that the probability of survival after 24 months (mean follow up) was 67.07% and the probability of reaching 74 months (maximum follow up) was 60.04%. CONCLUSIONS: After a comparative analysis of the survival with the Mantel-Haenzel test, it was found that the grade of cellular differentiation (p < 0.001) and stage of infiltration (p < 0.01) had significant differences in the survival curves.

Actuarial Analysis↗
PubMed1997

Transcription factors and induction in Xenopus laevis embryos.

Studies with amphibian embryos have contributed major insights into the molecular basis of induction processes and the formation of germ layers during vertebrate embryogenesis. Primary signals that have been identified as growth factors or growth factor-related ligands act as inducing factors on their target cells and, by a change of the genetic program, evoke a specification of the cellular differentiation pathways. While at present the signal transduction mechanisms leading from the ligands via cognate receptors to the nuclei are still poorly understood, there is growing information on transcription factors which are activated upon induction. They govern the expression of other regulatory molecules and co-ordinate the expression of cell type-specific structural genes. Meanwhile, it is generally accepted that development and cellular differentiation in all multicellular organisms depends upon a cascade of evolutionarily conserved transcription factors. Striking structural similarities within their DNA-binding domains allow many of these factors to be subdivided into different transcription factor families. Most of the basic knowledge on these factors emerged from the pioneering work done with Drosophila embryos which was greatly facilitated by the availability of numerous mutants. Despite the fact that Drosophila development until the blastoderm stage proceeds in a multinuclear syncytium and thus is significantly different from that in vertebrate organisms, the primary structures of many embryonic transcription factors have been conserved in higher organisms. This especially holds true for the various DNA binding motifs and it facilitated the isolation and characterization of vertebrate homologues to factors previously identified in lower organisms.

Animals↗
PubMed2003

Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation.

Decidualization of endometrial stromal cells is a prerequisite for human implantation and occurs in vivo in response to progesterone and involves activation of the protein kinase A (PKA) pathway. The objective of this study was to determine the molecular signatures and patterns of gene expression during stimulation of this pathway with an analog of cAMP. Endometrial stromal cells from two subjects were treated with or without 8-Br-cAMP (1 mM) for 0, 2, 12, 24, 36, and 48 h and were processed for microarray analysis, screening for 12,686 genes and ESTs. Most abundantly upregulated genes included neuropeptides, immune genes, IGF family members, cell cycle regulators, extracellular matrix proteases, cholesterol trafficking, cell growth and differentiation, hormone signaling, and signal transduction. Most abundantly downregulated genes included activator of NF-kappaB, actin/tropomyosin/calmodulin binding protein, cyclin B, IGFBP-5, alpha1 type XVI collagen, lipocortin III, l-kynurenine hydrolase, frizzle-related protein, and cyclin E2. RT-PCR validated upregulation of IGFBP-1, preprosomatostatin, and IL-11, and Northern analysis validated their kinetic upregulation. RT-PCR confirmed downregulation of IGFBP-5, cyclin B, and TIL-4. K-means analysis revealed four major patterns of up- and downregulated genes, and genes within each ontological group were categorized into these four kinetic patterns. Within each ontological group different patterns of temporal gene expression were observed, indicating that even genes within one functional category are regulated differently during activation of the PKA pathway in human endometrial stromal cells. Overall, the data demonstrate kinetic reprogramming of genes within specific functional groups and changes in genes associated with nucleic acid binding, cell proliferation, decreased G protein signaling, increased STAT pathway signaling, structural proteins, cellular differentiation, and secretory processes. These changes are consistent with cAMP modulating early events (0-6 h) primarily involving cell cycle regulation, subsequent events (12-24 h) involving cellular differentiation (including changes in morphology and secretory phenotype), and late events (24-48 h) mediating more specialized function, including immune modulators, in the human endometrial stromal cell.

8-Bromo Cyclic Adenosine Monophosphate↗