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

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The NF-kappaB family of transcription factors regulates diverse cellular functions such as immune response and cell growth and development, and has been reported to be constitutively active in a variety of mammary carcinoma cell lines. However, its role in normal mammary gland development has not been addressed. In our study, we detected developmentally regulated NF-kappaB activity in the mammary gland of mice. During pregnancy, DNA binding activity of NF-kappaB p50/p65 increased until day 16 postcoitum and decreased with the onset of lactation, most likely due to reduced p50 and p65 protein levels in the nucleus. Cotransfection experiments performed with 293 cells revealed an inhibition of the prolactin receptor/JAK2/STAT5 pathway by NF-kappaB. In HC11 cells, NF-kappaB p50/p65 activity was inversely correlated with prolactin-induced STAT5 tyrosine phosphorylation, expression of endogenous beta-casein gene, and of a transfected beta-casein gene promoter reporter construct. This indicates a negative cross talk between NF-kappaB and the prolactin receptor/JAK2/STAT5 activation pathway, which occurs at the level of STAT5 tyrosine phosphorylation. Our results provide evidence for a role of NF-kappaB in normal mammary gland development, and indicate its function as a negative regulator of beta-casein gene expression during pregnancy by interfering with STAT5 tyrosine phosphorylation.
...
PMID:Activation of NF-kappaB p50/p65 is regulated in the developing mammary gland and inhibits STAT5-mediated beta-casein gene expression. 1083 38

A model lung tumor system has been developed in mice for the evaluation of vascular targeted radioimmunotherapy. In this model, EMT-6 mammary carcinoma tumors growing in the lung are treated with 213Bi, an alpha particle emitter, which is targeted to lung blood vessels using a monoclonal antibody. Smaller tumors (< 100 microm in diameter) are cured, but larger tumors undergo a period of regression and then regrow and ultimately prove lethal. The goal of this work was to determine if external imaging with MRI or CT could be used routinely to monitor the growth/ regression of lung tumors in live mice. To attempt to evaluate individual tumors in vivo, animals were initially imaged with magnetic resonance imaging (MRI). High resolution MRI images could be obtained only after sacrifice when lungs were not moving. In contrast, high resolution computed tomography (CT) produced evaluable images from anesthetized animals. Serial CT images (up to 5/animal) were collected over a 17 day period of tumor growth and treatment. When tumored animals became moribund, animals were sacrificed and lungs were inflated with fixative, embedded in paraffin, and then sectioned serially to compare the detection of tumors by high resolution CT with detection by histology. CT proved most useful in detecting lung tumors located in the hilar area and least useful in detecting serosal surface and anterior lobe tumor foci. Overall, CT images of live animals revealed tumors in approximately 2/3 of cases detected in histologic serial sections when relatively few tumors were present per lung. Detection of lesions and their resolution post therapy were complicated due to residual hemorrhagic, regressing tumor nodules and the development of lung edema both of which appeared as high density areas in the CT scans. We conclude that the microCT method used could identify some lung tumors as small as 100 microm in diameter; however, no concrete evaluation of therapy induced regression of the tumors could be made with CT analyses alone.
...
PMID:High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: correlation with histology. 1084 15

The use of Lectins to identify oligosaccharides in mucin substances has been increased by the role played by cell surface carbohydrates in invasion and metastasis processes. We studied in this work normal endometrial tissue, with benign and malignant entities in search for the presence of the Galactose beta 1-3 N Acetylgalactosamine(Gal beta 1-3 GalNAC alpha and Galactose beta 1-3 N Acetylgalactosamine (Gal beta 1-3 alpha and beta) using the Lectins: Agaricus bisporus (ABL) and Arachis hipogea (PNA) respectively. The specific control were baths with galactose for PNA and with porcine stomach mucin for ABL. The use of these two Lectins allowed to differentiate substances bonded or non bonded to Sialic Acid, since PNA fails to label when the oligosaccharide is bonded to this acid Sialic. Significant differences were noticed on the bonding patterns of both Lectins on tissues with benign, malignant and normal entities. In this latter case the labelling was always continuous in both Lectins whereas it was irregular in the carcinoma.
...
PMID:[Differential expression of mucin carbohydrates in human endometria]. 1088 4

PTEN is one of the most commonly mutated tumor suppressor genes in human cancer. PTEN mutations have been implicated in the development of a variety of human neoplasia, including high-grade glioblastoma, prostate, breast, endometrial, and thyroid carcinoma. Germ-line mutations of PTEN cause Cowden's syndrome (CS), a multiple hamartoma condition resulting in increased susceptibility for the development of cancer. When more than 6 months old, pten+/- mice develop a range of tumors, partially resembling the spectrum of neoplasia observed in CS patients. One-half (32 of 65) of pten+/- females developed breast tumors, whereas all (65 of 65) of the females had endometrial hyperplasia, and there was a high incidence (14 of 65) of endometrial cancer. Hamartoamous tumors of the gastrointestinal tract, as well as prostate and adrenal neoplasia, were also frequently observed. Significantly, the spectrum of neoplasia observed in pten+/- mice partially overlaps with the types of tumors frequently detected in CS patients. The majority of tumors in pten+/- mice exhibit loss of heterozygosity at the pten locus, which indicates the importance for loss of PTEN function in tumor formation. Consistent with the role of PTEN in negative regulation of PKB/Akt phosphorylation and activity, pten loss of heterozygosity is accompanied by hyperphosphorylation of PKB/Akt in tumors. Taken together, our results establish pten+/- mice as an excellent animal model system for the investigation of PTEN-related hamartoma syndromes, as well as the role of PTEN in breast and endometrial carcinogenesis.
...
PMID:High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice. 1091 75

Several alpha particle emitting radioisotopes have been studied for use in radioimmunotherapy. Ac-225 has the potential advantages of a relatively long half life of 10 days, and a yield of 4 alpha emissions in its decay chain with a total energy release of approximately 28 MeV. A new, 12 coordination site chelating ligand, HEHA, has been chemically modified for coupling to targeting proteins without loss of chelating ability. HEHA was coupled with MAb 201B which binds to thrombomodulin and accumulates efficiently in murine lung. Ac-225 was bound to the HEHA-MAb 201B conjugate and injected into BALB/c mice bearing lung tumor colonies of EMT-6 mammary carcinoma. Biodistribution data at 1 and 4 h postinjection indicated that, as expected, 225Ac was delivered to lung efficiently (> 300% ID/g). The 225Ac was slowly released from the lung with an initial t1/2 = 49 h, and the released 225Ac accumulated in the liver. Injection of free HEHA was only partially successful in scavenging free 225Ac. In addition to the slow release of 225Ac from the chelate, data indicated that decay daughters of 225Ac were also released from the lung. Immediately after organ harvest, the level of 213Bi, the third alpha-decay daughter, was found to be deficient in the lungs and to be in excess in the kidney, relative to equilibrium values. Injected doses of 225Ac MAb 201B of 1.0 microCi, delivering a minimum calculated absorbed dose of about 6 Gy to the lungs, was effective in killing lung tumors, but also proved acutely radiotoxic. Animals treated with 1.0 microCi or more of the 225Ac radioconjugate died of a wasting syndrome within days with a dose dependent relationship. We conclude that the potential for 225Ac as a radioimmunotherapeutic agent is compromised not only by the slow release of 225Ac from the HEHA chelator, but most importantly by the radiotoxicity associated with decay daughter radioisotopes released from the target organ.
...
PMID:Evaluation of 225Ac for vascular targeted radioimmunotherapy of lung tumors. 1094 28

This study reports a case of papillary carcinoma with vesicular components showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22 and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22 changes as the sole abnormality were seen. The main abnormal clone lacked the whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell population with a der(17)t(?17;22). Some of these chromosome 22 alterations have been described in other solid tumors such as meningiomas and neurinomas, suggesting a common genetic pathway of tumor progression occurring in a multistep process. Chromosome 22 changes do not seem to be involved in pure papillary thyroid tumors and therefore could be related to the maintenance of a follicular-type histological pattern.
...
PMID:Structural and numerical aberrations of chromosome 22 in a case of follicular variant of papillary thyroid carcinoma revealed by conventional and molecular cytogenetics. 1095 38

Interleukin 1beta (IL-1beta) suppresses the IL-6-dependent induction of type II acute-phase response genes, but the underlying mechanism for this suppression remains uncertain. Here we report that treatment of human hepatocullular carcinoma HepG2 cells with IL-1beta inhibited the IL-6-dependent binding of signal transducer and activator of transcription factor (STAT)1, but not that of STAT3, to the high-affinity serum-inducible element ('SIE'). Furthermore, IL-1beta selectively down-regulated the IL-6-induced tyrosine phosphorylation of STAT1 without affecting the level of STAT1 or tyrosine phosphorylation of STAT3. Kinase assays in vitro indicated that the inhibition of STAT1 phosphorylation by IL-1beta was not due to an upstream blockade of Janus kinase (JAK1 or JAK2) activation. However, pretreatment with the proteasome inhibitor MG132 under conditions that prevented the IL-1beta-dependent activation of the nuclear factor NF-kappaB also blocked the inhibitory effect of IL-1beta on IL-6-activated STAT1. In related experiments, the protein tyrosine phosphatase inhibitor Na(3)VO(4) also antagonized the inhibitory effect of IL-1beta on the activation of STAT1 by IL-6. Taken together, these findings indicate that, by using a proteasome-dependent mechanism, IL-1beta concomitantly induces NF-kappaB activation and dephosphorylates IL-6-activated STAT1; the latter might partly account for the inhibition by IL-1beta of the IL-6-dependent induction of type II acute-phase genes.
...
PMID:Cross-talk between interleukin 1beta (IL-1beta) and IL-6 signalling pathways: IL-1beta selectively inhibits IL-6-activated signal transducer and activator of transcription factor 1 (STAT1) by a proteasome-dependent mechanism. 1110 3

A systematic review was conducted to determine the effectiveness of health education interventions to promote sexual risk reduction behaviours amongst women in order to reduce transmission of human papillomavirus (HPV), a leading agent in the development of cervical cancer. A comprehensive search was conducted to identify relevant studies. Studies were included in the review if they evaluated educational interventions targeting women only and measured the impact on either a behavioural outcome such as condom use for sexual intercourse, partner reduction or abstinence, or a clinical outcome such as incidence of a STD. Thirty studies met the inclusion criteria for the review; all had the primary aim of preventing HIV and other STDs rather than cervical cancer. Ten of the 30 studies were considered to provide the strongest evidence for a causal relationship between the intervention and the change in outcomes measured. Each of these 10 most rigorous studies showed a statistically significant positive effect on sexual risk reduction, typically with increased use of condoms for vaginal intercourse. This positive effect was generally sustained up to 3 months after intervention. It was concluded that educational interventions targeting socially and economically disadvantaged women in which information provision is complemented by sexual negotiation skill development can encourage at least short-term sexual risk reduction behaviour. This effect has the potential to reduce the transmission of HPV and thus possibly reduce the incidence of cervical carcinoma.
...
PMID:Cervical cancer and sexual lifestyle: a systematic review of health education interventions targeted at women. 1114 74

The human GH (hGH) antagonist B2036 combines a single amino acid substitution impairing receptor binding site 2 (G120K) with eight additional amino acid substitutions that improve binding site 1 affinity. B2036 does not bind, activate, or antagonize the human PRL receptor and therefore is suitable to determine cellular effects mediated specifically through the hGH receptor. We have used this hGH receptor specific antagonist in MCF-7 cells stably transfected with either the hGH gene (MCF-hGH) or a translation deficient hGH gene (MCF-MUT) to determine whether the effects of autocrine hGH on mammary carcinoma cell behavior are mediated via the hGH receptor. Enhanced JAK2 tyrosine phosphorylation observed in MCF-hGH cells compared with MCF-MUT cells is abrogated by B2036 as is the autocrine hGH stimulated increase in total cell number and DNA synthesis. Interestingly, autocrine hGH functions as a potent inhibitor of apoptosis induced by serum withdrawal compared with exogenously added hGH, and the protection against apoptosis afforded by autocrine hGH is abrogated by B2036. B2036 also inhibited autocrine hGH stimulated transcriptional activation mediated by either STAT5, CHOP (p38 MAP kinase specific) or Elk-1 (p44/42 MAP kinase specific). Finally, B2036 inhibited the autocrine hGH-dependent enhancement of the rate of mammary carcinoma cell spreading on a collagen matrix. Thus, the effects of autocrine hGH on human mammary carcinoma cell behavior are mediated via the hGH receptor.
...
PMID:The effects of autocrine human growth hormone (hGH) on human mammary carcinoma cell behavior are mediated via the hGH receptor. 1115 49

We have derived a cell line, RE1, from a pre-implantation rat blastocyst, resembling morphologically the L2 cell line from a parietal yolk sac carcinoma of the rat, as well as parietal endoderm cell lines of the mouse. The sub-cellular organization and epithelial characteristics of RE1 cells are described. The cells express cytokeratins of simple epithelia, and vimentin; and demonstrate synthesis of proteins of the extracellular matrix, such as laminin and collagen IV. Extensive Reichert's-like basement membrane is formed by RE1 cells when grown in suspension as aggregates. Cells have a microvillous surface morphology and abundant, rough endoplasmic reticulum which is swollen with apparent secretory material. These morphological and cytochemical features are characteristic of parietal endoderm cells in vivo, and the RE1 cell line is deduced to be rat parietal endoderm. In addition, RE1 cells were examined for expression of stage-specific embryonic antigens: cells reacted with antibody against SSEA-1/TEC-1 and EMA-1, constituting the first observation of parietal endoderm cells expressing the respective epitopes. RE1-cell monolayers did not generate transepithelial resistances or potential differences in vitro, consistent with their formation of leaky epithelia. Our observations on RE1-cell morphology and ultrastructure are consistent with the occurrence of epithelial-mesenchyme transitions in culture.
...
PMID:Parietal endoderm cell line from a rat blastocyst. 1116 60


<< Previous 1 2 3 4 5 6 7 8 9 10

---