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)

A questionnaire on the treatment of anogenital warts was sent to 150 consultants in genitourinary medicine, 78 (52%) were returned completed. A wide range of treatments were used; podophyllin was the commonest first line treatment of multiple penile (60.3%), perianal (57.7%) and vulval (61.5%) warts. Cryotherapy was a popular choice for intrameatal warts (65.3%), small numbers of vulval warts (33.3%) and as second line therapy for penile (35.9%) and perianal (33.3%) warts. Vaginal warts were treated with podophyllin (39.7%) or cryotherapy (29.5%). Various combinations of podophyllin, trichloroacetic acid and cryotherapy were used (2.6%-24.3%) although there is no evidence this offers benefit over single therapy. Podophyllin is frequently used despite side effects, a poor clearance rate and in vaginal warts, difficult access. Initial therapy with more time-consuming procedures such as cryotherapy or electrocautery may be of benefit to selected patients.
Int J STD AIDS
PMID:Treatment of anogenital warts in genitourinary clinics in England and Wales. 128 22

The 1-nitroacridine nitracrine [NC,1-nitro-9-(dimethylaminopropyl-amino)acridine] is a potent hypoxia-selective cytotoxic agent in culture, but lacks activity against hypoxic tumor cells in vivo at therapeutically accessible doses. To clarify reasons for this failure in vivo the metabolism of NC was investigated in stirred suspension cultures of Chinese hamster ovary cells, in EMT-6 spheroids, and in mice. One major low molecular weight metabolite (identical to that generated by NaBH4/Pd/C reduction) was observed in hypoxic (less than 10 ppm O2) single cell suspensions, while [G-3H-acridinyl]NC formed trichloroacetic acid- and acetonitrile-insoluble macromolecular adducts (MA) at a rate seven-fold higher than in aerobic (20% O2) cultures. Formation of these adducts correlated with cytotoxicity under air or nitrogen, and hence may provide a dosimeter for NC-induced damage. Autoradiographic investigation of the distribution of MA in spheroids equilibrated with 5% O2 showed that the label was restricted to the outer cell layers rather than being localized in the hypoxic central region. Thus metabolic activation is probably too rapid, even in well-oxygenated cells, to allow adequate distribution to hypoxic microenvironments in tumors. In mice, levels of MA were higher in liver, kidney, spleen and lung than in Lewis lung tumors, indicating that oxygen concentration does not exert a dominant influence on relative rates of metabolic activation in vivo. The development of nitroacridines with useful hypoxic selectivity in vivo will require identification of analogs for which reductive metabolism is more completely inhibited at oxygen concentrations found in normal tissues.
...
PMID:Reductive metabolism and hypoxia-selective toxicity of nitracrine. 374 44

The investigation of mechanism of synergistic action with SYN and ECZ was performed using C. albicans SC5314 so that SYN was confirmed to show strong synergistic effects against Candida sp. in particular with addition of extremely small quantities under the MICs of imidazole antimycotics such as ECZ, MCZ and CTZ. The synergistic effect of antifungal activity against C. albicans SC5314 with a combination of SYN and ECZ (SYN + ECZ) showed fungistatic action. Effect of SYN + ECZ on osmotic resistance was not recognized and protoplast was not observed under a microscope. Accordingly, SYN + ECZ was considered not to take part in cell wall synthesis directly. For effect of SYN + ECZ on release of intracellular components, slow release of 260 nm-absorbing substances was occurred, so that SYN + ECZ was seemed not to affect cytoplasmic membrane damage directly. Also, it was suggested clearly that SYN + ECZ affected lipid metabolism and glycolysis including TCA cycle from the investigation on antagonism by growth recovery of C. albicans SC5314 by 106 kinds of substances such as fatty acids, isoprenoids, phospholipids, vitamins, amino acids, nucleic acid-related substances and TCA cycle-related substances. From the above results, it was suggested that the mechanism of synergistic action with SYN and ECZ against C. albicans SC5314 was due to affect the different reactions in lipid metabolism and the similar reactions in glycolysis including TCA cycle, respectively, in consideration of respective mechanism of actions of SYN alone and ECZ alone. A part of this work was presented at the Annual Meeting of the Agricultural Chemical Society of Japan, 1981 (Kyoto).
...
PMID:Studies on the mechanism of synergistic action with synergisidin and imidazole antimycotics. 703 86

Our previous studies have shown that the Galbeta1-3GalNAcalpha- (Thomsen-Friedenreich antigen)-binding lectin from the common edible mushroom Agaricus bisporus (ABL) reversibly inhibits cell proliferation, and this effect is a consequence of inhibition of nuclear localization sequence-dependent nuclear protein import after ABL internalization [Yu, L.G., Fernig, D.G., White, M.R.H., Spiller, D.G., Appleton, P., Evans, R.C., Grierson, I., Smith, J.A., Davies, H., Gerasimenko, O.V., Petersen, O.H., Milton, J.D. & Rhodes, J.M. (1999) J. Biol. Chem. 274, 4890-4899]. Here, we have investigated further the intracellular trafficking and fate of ABL after internalization in HT29 human colon cancer cells. Internalization of 125I-ABL occurred within 30 min of the lectin being bound to the cell surface. Subcellular fractionation after pulse labelling of the cells with 125I-ABL for 2 h at 4 degrees C followed by culture of the cells at 37 degrees C demonstrated a steady increase in radioactivity in a crude nuclear extract. The radioactivity in this extract reached a maximum after 10 h and declined after 20 h. Release of ABL from the cell, after pulse labelling, was assessed using both fluorescein isothiocyanate-labelled ABL and 125I-ABL and was slow, with a t1/2 of 48 h. Most of the 125I-ABL both inside cells and in the medium remained intact, as determined by trichloroacetic acid precipitation and SDS/PAGE, and after 48 h only 22 +/- 2% of ABL in the medium and 14 +/- 2% inside the cells was degraded. This study suggests that the reversibility of the antiproliferative effect of ABL is associated with its release from cells after internalization. The internalization and subsequent slow release, with little degradation of ABL, reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells.
...
PMID:Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells. 1072 53

Euglena gracilis cell was extracted sequentially with CSK-Triton buffer, RSB-Magik solution and DNase-As solution. DGD embedment-free electron microscopy showed that in the extracted nucleus there was a residual non-chromatin fibrous network. That it could not be removed by hot trichloroacetic acid further supported the idea that it was a non-histone, non-chromatin fibrous protein network, and should be the internal network of the nuclear matrix. After the sequential extraction, the nuclear membrane was removed, leaving behind a layer of lamina; the chromatin was digested and eluted from the dense chromosomes and residual chromosomal structures that should be chromosomal scaffold were revealed. Western blot analysis with antiserum against rat lamins showed that nuclear lamina of the cell possessed two positive polypeptides, a major one and a minor one, which had molecular masses similar to lamin B and lamin A, respectively. Comparing these data with those of the most primitive eukaryote Archezoa and of higher eukaryotes, it was suggested that the lower unicellular eukaryote E. gracilis already had the nuclear matrix structure, and its nuclear matrix (especially the lamina) might represent a stage of evolutionary history of the nuclear matrix.
...
PMID:The nuclear matrix of Euglena gracilis (euglenophyta): a stage of nuclear matrix evolution? 1087 33

Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between -235 and -310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem. 273, 21856-21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions -169 to -193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing -169/-193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis.
...
PMID:Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. 1153 40

Genital warts are one of the most commonly reported sexually transmitted diseases worldwide. A variety of treatment options are available but few have been assessed in large-scale, randomized, placebo-controlled trials. Provider-applied surgical and non-surgical treatments have traditionally been the therapies of choice. Surgical therapies, including cryotherapy, electrotherapy, laser surgery and surgical excision, are generally equivalent in terms of wart clearance rates, but are associated with high rates of wart recurrence. Trichloroacetic acid is a widely used non-surgical therapy, but little is known about its efficacy, and it is associated with unpleasant side-effects. The patient-applied treatments imiquimod and podophyllotoxin are newer therapy choices which are more acceptable to both patients and practitioners. The wart clearance rates for these two treatments are similar, although imiquimod is associated with lower recurrence rates. In the face of increasing pressures on genitourinary clinic services, patient-applied home therapy represents an attractive option for the treatment of genital warts.
Int J STD AIDS 2004 Jun
PMID:Critical appraisal of commonly used treatment for genital warts. 1518 77

This was a cross-sectional survey that collected data relating to management of anogenital warts (AGW) during a single-patient visit only at genitourinary medicine clinics. Single-agent use of cryotherapy, podophyllotoxin and trichloroacetic acid (TCA) were the most common treatment modalities, accounting for over two-thirds of all modalities used. Podophyllin, alone or in combination with other agents, was used for about 20% of first-line treatments. Podophyllin was included in about 15% of all treatment modalities. Guidelines for the management of AGW continue to recommend the use of podophyllin, but this may need to be modified in the light of recent publications. Podophyllin, TCA, podophyllotoxin or combinations of these agents are commonly used to treat keratinized warts. About 11% of all treatments involved a combination of two or more agents.
Int J STD AIDS 2005 Mar
PMID:A cross-sectional survey of treatment choices for anogenital warts. 1582 21

To determine whether an educational event can affect treatment choice for ano-genital warts, genitourinary medicine clinicians attending a wart management lecture were shown 14 photographs of genital warts of differing morphology at different sites and asked to choose their preferred method of treatment. Study questionnaires were completed pre-lecture and repeated after the lecture and discussion. Podophyllin was chosen significantly less frequently and cryotherapy more frequently post-lecture for certain wart types. Podophyllotoxin was favoured for multiple small penile and posterior fourchette warts, whereas imiquimod was chosen predominantly for large or bulky lesions. Trichloracetic acid was infrequently chosen as a treatment option (<6% of respondents). This study has shown that clinicians attending a lecture on the management of ano-genital warts do change their treatment choice for certain clinical scenarios. Whether opting for a particular treatment in a lecture setting translates to altered practice in the clinical setting requires further study.
Int J STD AIDS 2007 Aug
PMID:Treatment of ano-genital warts: the effect of an educational event on practitioner choice. 1768 14

Chronic myeloid leukemia (CML) is a clonal disorder characterized by proliferation of hematopoietic cells that possess the BCR-ABL fusion gene resulting in the production of a 210 kDa chimeric tyrosine kinase protein. CML, when left untreated, progresses to a blast phase during which the disease turns aggressive and shows poor response to known treatment regimens. We have studied a Siddha herbal agent, Semecarpus anacardium Linn. nut milk extract (SA) for its antileukemic activity and its effect on the changes in energy metabolism in leukemic mice. Leukemia was induced in BALB/c mice by tail vein injection of BCR-ABL(+) 12B1 murine leukemia cell line. This resulted in an aggressive leukemia, similar to CML in blast crisis, myeloid subtype, confirmed by histopathological study and RT-PCR for the p210 mRNA in the peripheral blood, spleen and liver. Leukemia-bearing mice showed a significant increase in lipid peroxides, glycolytic enzymes, a decrease in gluconeogenic enzymes and significant decrease in the activities of TCA cycle and respiratory chain enzymes as compared to control animals. SA treatment was compared with standard drug imatinib mesylate. SA administration to leukemic animals resulted in clearance of the leukemic cells from the bone marrow and internal organs on histopathological examination and this was confirmed by RT-PCR for the p210 mRNA. Treatment with SA significantly reversed the changes seen in the levels of the lipid peroxides, the glycolytic enzymes, the gluconeogenic enzymes and the mitochondrial enzymes. These effects are probably due to the flavonoids, polyphenols and other compounds present in SA which result in total regression of leukemia and correction of the alterations in energy metabolism. Study of animals treated with SA alone did not reveal any adverse effects. On the basis of the observed results, SA can be considered as a readily accessible, promising and novel antileukemic chemotherapeutic agent.
...
PMID:Restoration of energy metabolism in leukemic mice treated by a siddha drug--Semecarpus anacardium Linn. nut milk extract. 1835 58


1 2 3 Next >>

---