FGF Receptors: Cancer Biology and Therapeutics.

FGF Receptors: Cancer Biology and Therapeutics.

Med Res Rev. 2013 May 21;

Authors: Katoh M, Nakagama H

Abstract
Fibroblast growth factors (FGFs) are involved in a variety of cellular processes, such as stemness, proliferation, anti-apoptosis, drug resistance, and angiogenesis. Here, FGF signaling network, cancer genetics/genomics of FGF receptors (FGFRs), and FGFR-targeted therapeutics will be reviewed. FGF signaling to RAS-MAPK branch and canonical WNT signaling cascade mutually regulate transcription programming. FGF signaling to PI3K-AKT branch and Hedgehog, Notch, TGF?, and noncanonical WNT signaling cascades regulate epithelial-to-mesenchymal transition (EMT) and invasion. Gene amplification of FGFR1 occurs in lung cancer and estrogen receptor (ER)-positive breast cancer, and that of FGFR2 in diffuse-type gastric cancer and triple-negative breast cancer. Chromosomal translocation of FGFR1 occurs in the 8p11 myeloproliferative syndrome and alveolar rhabdomyosarcoma, as with FGFR3 in multiple myeloma and peripheral T-cell lymphoma. FGFR1 and FGFR3 genes are fused to neighboring TACC1 and TACC3 genes, respectively, due to interstitial deletions in glioblastoma multiforme. Missense mutations of FGFR2 are found in endometrial uterine cancer and melanoma, and similar FGFR3 mutations in invasive bladder tumors, and FGFR4 mutations in rhabdomyosarcoma. Dovitinib, Ki23057, ponatinib, and AZD4547 are orally bioavailable FGFR inhibitors, which have demonstrated striking effects in preclinical model experiments. Dovitinib, ponatinib, and AZD4547 are currently in clinical trial as anticancer drugs. Because there are multiple mechanisms of actions for FGFR inhibitors to overcome drug resistance, FGFR-targeted therapy is a promising strategy for the treatment of refractory cancer. Whole exome/transcriptome sequencing will be introduced to the clinical laboratory as the companion diagnostic platform facilitating patient selection for FGFR-targeted therapeutics in the era of personalized medicine.

PMID: 23696246 [PubMed - as supplied by publisher]

pan Akt inhibitor selleck chemicals akt2 inhibitor selleck chemicals Akt inhibitor selleckchem

Luteolin and fisetin inhibit the effects of lipopolysaccharide obtained from Porphyromonas gingivalis in human gingival fibroblasts.

Related Articles

Luteolin and fisetin inhibit the effects of lipopolysaccharide obtained from Porphyromonas gingivalis in human gingival fibroblasts.

Mol Biol Rep. 2013 Jan;40(1):477-85

Authors: Guti�rrez-Venegas G, Contreras-S�nchez A

Abstract
Periodontitis is an inflammatory process of infectious origin that affects the gums and, in severe cases, destroys connective tissue, leading to loss of the dental organ. Gram-negative Porphyromonas gingivalis bacteria are recovered from patients with chronic periodontitis. The polysaccharide obtained from these bacteria induces the expression of interleukin (IL)-1 beta, tumor necrosis factor, and IL-6. Flavonoids are molecules that participate in the control of inflammatory processes. We studied the role of the flavonoids fisetin, luteolin, myricetin, and morin in inhibiting the activation of mitogen-activated protein kinase (MAPK) and AKT as well as their role in lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) transcription. All four of these flavonoids were found to inhibit MAPK and AKT. Fisetin and luteolin blocked the activation of MAPK and AKT to levels below basal levels. All of these flavonoids also blocked LPS-mediated COX-2 expression.

PMID: 23054013 [PubMed - indexed for MEDLINE]

akt3 inhibitor selleckchem Akt inhibitor selleck chemical specific Akt inhibitor

Image-based high-throughput screening for inhibitors of angiogenesis.

Related Articles

Image-based high-throughput screening for inhibitors of angiogenesis.

Methods Mol Biol. 2013;931:139-51

Authors: Evensen L, Link W, Lorens JB

Abstract
Automated multicolor fluorescence microscopy facilitates high-throughput quantitation of cellular parameters of complex, organotypic systems. In vitro co-cultured vascular cells form capillary-like networks that model facets of angiogenesis, making it an attractive alternative for anti-angiogenic drug discovery. We have adapted this angiogenesis assay system to a high-throughput format to enable automated image-based high-throughput screening of live primary human vascular cell co-cultures with chemical libraries for anti-angiogenic drug discovery. Protocols are described for setup of a fluorescence-based co-culture assay, live cell image acquisition, image analysis of morphological parameters, and screening data handling.

PMID: 23027002 [PubMed - indexed for MEDLINE]

Caspase-1 inhibitor ATP-competitive Caspase inhibitor selleck chemical ATP-competitive Caspase inhibitor

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

AKT Inhibitors selleck chemicals reversible Akt inhibitor akt2 inhibitor

Image-based high-throughput screening for inhibitors of angiogenesis.

Related Articles

Image-based high-throughput screening for inhibitors of angiogenesis.

Methods Mol Biol. 2013;931:139-51

Authors: Evensen L, Link W, Lorens JB

Abstract
Automated multicolor fluorescence microscopy facilitates high-throughput quantitation of cellular parameters of complex, organotypic systems. In vitro co-cultured vascular cells form capillary-like networks that model facets of angiogenesis, making it an attractive alternative for anti-angiogenic drug discovery. We have adapted this angiogenesis assay system to a high-throughput format to enable automated image-based high-throughput screening of live primary human vascular cell co-cultures with chemical libraries for anti-angiogenic drug discovery. Protocols are described for setup of a fluorescence-based co-culture assay, live cell image acquisition, image analysis of morphological parameters, and screening data handling.

PMID: 23027002 [PubMed - indexed for MEDLINE]

akt3 inhibitor Akt3 inhibitor selleck chemical specific Akt inhibitor selleck chemical

Re: genome sequencing identifies a basis for everolimus sensitivity.

Related Articles

Re: genome sequencing identifies a basis for everolimus sensitivity.

J Urol. 2013 Jul;190(1):61-2

Authors: Wood DP

PMID: 23759603 [PubMed - in process]

A66

Re: genome sequencing identifies a basis for everolimus sensitivity.

Related Articles

Re: genome sequencing identifies a basis for everolimus sensitivity.

J Urol. 2013 Jul;190(1):61-2

Authors: Wood DP

PMID: 23759603 [PubMed - in process]

A66 Bufexamac JNK INHIBITOR selleck chemical

Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer.

Related Articles

Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer.

Toxicol Appl Pharmacol. 2013 Jun 5;

Authors: Li Y, Zhao H, Wang Y, Zheng H, Yu W, Chai H, Zhang J, Falck JR, Guo AM, Yue J, Peng R, Yang J

Abstract
Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2'-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B4 (LTB4). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser(241)), phospho-Akt (Thr(308)), phospho-Bad (Ser(136)), and Bcl-xL expression, thereby activating caspase cascades and eventually cleaving poly (ADP-ribose) polymerase (PARP). Conversely, addition of exogenous eicosanoids, including PGE2, LTB4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr(308)). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer.

PMID: 23747687 [PubMed - as supplied by publisher]

jnk inhibitor ii selleck chemical Elvitegravir A66

Divers models of divalent cation interaction to calcium-binding proteins: techniques and anthology.

Related Articles

Divers models of divalent cation interaction to calcium-binding proteins: techniques and anthology.

Methods Mol Biol. 2013;963:15-35

Authors: Cox JA

Abstract
Intracellular Ca(2+)-binding proteins (CaBPs) are sensors of the calcium signal and several of them even shape the signal. Most of them are equipped with at least two EF-hand motifs designed to bind Ca(2+). Their affinities are very variable, can display cooperative effects, and can be modulated by physiological Mg(2+) concentrations. These binding phenomena are monitored by four major techniques: equilibrium dialysis, fluorimetry with fluorescent Ca(2+) indicators, flow dialysis, and isothermal titration calorimetry. In the last quarter of the twentieth century reports on the ion-binding characteristics of several abundant wild-type CaBPs were published. With the advent of recombinant CaBPs it became possible to determine these properties on previously inaccessible proteins. Here I report on studies by our group carried out in the last decade on eight families of recombinant CaBPs, their mutants, or truncated domains. Moreover this chapter deals with the currently used methods for quantifying the binding of Ca(2+) and Mg(2+) to CaBPs.

PMID: 23296602 [PubMed - indexed for MEDLINE]

jnk inhibitor ii selleck jnk inhibitor ii selleck chemical Elvitegravir

Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer.

Related Articles

Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer.

Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):E1301-10

Authors: Knight JF, Lesurf R, Zhao H, Pinnaduwage D, Davis RR, Saleh SM, Zuo D, Naujokas MA, Chughtai N, Herschkowitz JI, Prat A, Mulligan AM, Muller WJ, Cardiff RD, Gregg JP, Andrulis IL, Hallett MT, Park M

Abstract
Triple-negative breast cancer (TNBC) accounts for ?20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Met(mt)) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Met(mt) mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Met(mt), significantly increased tumor penetrance over Met(mt) or Trp53 loss alone. Unlike Met(mt) tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Met(mt) tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC.

PMID: 23509284 [PubMed - in process]

Bufexamac JNK INHIBITOR selleck chemical JNK INHIBITOR

A Multiparametric Clinical and Echocardiographic Score to Risk Stratify Patients with Chronic Systolic Heart Failure: Derivation and Testing.

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A Multiparametric Clinical and Echocardiographic Score to Risk Stratify Patients with Chronic Systolic Heart Failure: Derivation and Testing.

Echocardiography. 2013 Jun 6;

Authors: Fontanive P, Miccoli M, Simioniuc A, Angelillis M, Bello VD, Baggiani A, Bongiorni MG, Marzilli M, Dini FL

Abstract
Although echo Doppler and biomarkers are the most common examinations performed worldwide in heart failure (HF), they are rarely considered in risk scores. In outpatients with chronic HF and left ventricular ejection fraction (LVEF) ?45%, data on clinical status, echo Doppler variables, aminoterminal pro-type B natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and drug therapies were combined to build up a multiparametric score. We randomly selected 250 patients to produce a derivation cohort and 388 patients were used as a testing cohort. Follow-up lasted 29���23�months. The univariable predictors that entered into the multivariable Cox model were as follows: furosemide daily dose >25�mg, inability to tolerate angiotensin converting enzyme (ACE) inhibitors, inability to tolerate ?-blockers, age >75�years, New York Heart Association (NYHA) >2, eGFR<60�mL/min, NT-proBNP plasma levels above the median, tricuspid plane systolic excursion (TAPSE) ?14�mm, LV end-diastolic volume index (LVEDVi) >96�mL/m(2) , moderate-to-severe mitral regurgitation (MR) and LVEF <30%. The scores of prognostic factors were obtained with the respective odds ratio divided by the lower odd ratio: 4 points for furosemide dose, 3 points for age, NT-proBNP, LVEDVi, TAPSE, 2 points for inability to tolerate ?-blockers, inability to tolerate ACE inhibitors, NYHA, eGFR<60�mL/min, moderate-to-severe MR, 1 point for LVEF. The multiparametric score predicted all-cause mortality either in the derivation cohort (68.4% sensitivity, 79.5% specificity, area under the curve [AUC] 78.7%) or in the testing cohort (73.7% sensitivity, 71.3% specificity, AUC 77.2%). All-cause mortality significantly increased with increasing score both in the derivation and in the testing cohort (P�<�0.0001). In conclusion, this multiparametric score is able to predict mortality in chronic systolic HF.

PMID: 23742144 [PubMed - as supplied by publisher]

jnk jnk inhibitor ii selleck jnk inhibitor ii selleck chemical

FGF Receptors: Cancer Biology and Therapeutics.

FGF Receptors: Cancer Biology and Therapeutics.

Med Res Rev. 2013 May 21;

Authors: Katoh M, Nakagama H

Abstract
Fibroblast growth factors (FGFs) are involved in a variety of cellular processes, such as stemness, proliferation, anti-apoptosis, drug resistance, and angiogenesis. Here, FGF signaling network, cancer genetics/genomics of FGF receptors (FGFRs), and FGFR-targeted therapeutics will be reviewed. FGF signaling to RAS-MAPK branch and canonical WNT signaling cascade mutually regulate transcription programming. FGF signaling to PI3K-AKT branch and Hedgehog, Notch, TGF?, and noncanonical WNT signaling cascades regulate epithelial-to-mesenchymal transition (EMT) and invasion. Gene amplification of FGFR1 occurs in lung cancer and estrogen receptor (ER)-positive breast cancer, and that of FGFR2 in diffuse-type gastric cancer and triple-negative breast cancer. Chromosomal translocation of FGFR1 occurs in the 8p11 myeloproliferative syndrome and alveolar rhabdomyosarcoma, as with FGFR3 in multiple myeloma and peripheral T-cell lymphoma. FGFR1 and FGFR3 genes are fused to neighboring TACC1 and TACC3 genes, respectively, due to interstitial deletions in glioblastoma multiforme. Missense mutations of FGFR2 are found in endometrial uterine cancer and melanoma, and similar FGFR3 mutations in invasive bladder tumors, and FGFR4 mutations in rhabdomyosarcoma. Dovitinib, Ki23057, ponatinib, and AZD4547 are orally bioavailable FGFR inhibitors, which have demonstrated striking effects in preclinical model experiments. Dovitinib, ponatinib, and AZD4547 are currently in clinical trial as anticancer drugs. Because there are multiple mechanisms of actions for FGFR inhibitors to overcome drug resistance, FGFR-targeted therapy is a promising strategy for the treatment of refractory cancer. Whole exome/transcriptome sequencing will be introduced to the clinical laboratory as the companion diagnostic platform facilitating patient selection for FGFR-targeted therapeutics in the era of personalized medicine.

PMID: 23696246 [PubMed - as supplied by publisher]

jnk inhibitor ii selleck jnk inhibitor ii selleck chemical Elvitegravir

Image-based high-throughput screening for inhibitors of angiogenesis.

Related Articles

Image-based high-throughput screening for inhibitors of angiogenesis.

Methods Mol Biol. 2013;931:139-51

Authors: Evensen L, Link W, Lorens JB

Abstract
Automated multicolor fluorescence microscopy facilitates high-throughput quantitation of cellular parameters of complex, organotypic systems. In vitro co-cultured vascular cells form capillary-like networks that model facets of angiogenesis, making it an attractive alternative for anti-angiogenic drug discovery. We have adapted this angiogenesis assay system to a high-throughput format to enable automated image-based high-throughput screening of live primary human vascular cell co-cultures with chemical libraries for anti-angiogenic drug discovery. Protocols are described for setup of a fluorescence-based co-culture assay, live cell image acquisition, image analysis of morphological parameters, and screening data handling.

PMID: 23027002 [PubMed - indexed for MEDLINE]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

Chromosome Res. 2013 Jun 5;

Authors: Liew GM, Foulk MS, Gerbi SA

Abstract
The steroid hormone ecdysone induces DNA amplification and subsequent DNA puff formation in late fourth larval instar salivary gland polytene chromosomes of the fungus fly, Sciara coprophila. Previous in vitro studies on DNA puff II/9A in Sciara demonstrated that the ecdysone receptor (ScEcR-A) efficiently binds an ecdysone response element adjacent to the origin recognition complex binding site within the II/9A amplification origin, implying a role for ScEcR-A in amplification. Here, we extrapolate the molecular details from locus II/9A to the rest of the genome using immunofluorescence with a ScEcR-A-specific antibody. ScEcR-A binds all DNA puff sites just as amplification begins and persists throughout the processes of amplification, transcription, and puffing. Ecdysone injections into pre-amplification stage larvae prematurely induce both DNA amplification and ScEcR-A binding to DNA puff sites. These data are consistent with a direct role for ScEcR-A in DNA amplification.

PMID: 23737076 [PubMed - as supplied by publisher]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

Chromosome Res. 2013 Jun 5;

Authors: Liew GM, Foulk MS, Gerbi SA

Abstract
The steroid hormone ecdysone induces DNA amplification and subsequent DNA puff formation in late fourth larval instar salivary gland polytene chromosomes of the fungus fly, Sciara coprophila. Previous in vitro studies on DNA puff II/9A in Sciara demonstrated that the ecdysone receptor (ScEcR-A) efficiently binds an ecdysone response element adjacent to the origin recognition complex binding site within the II/9A amplification origin, implying a role for ScEcR-A in amplification. Here, we extrapolate the molecular details from locus II/9A to the rest of the genome using immunofluorescence with a ScEcR-A-specific antibody. ScEcR-A binds all DNA puff sites just as amplification begins and persists throughout the processes of amplification, transcription, and puffing. Ecdysone injections into pre-amplification stage larvae prematurely induce both DNA amplification and ScEcR-A binding to DNA puff sites. These data are consistent with a direct role for ScEcR-A in DNA amplification.

PMID: 23737076 [PubMed - as supplied by publisher]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

Non-small cell lung cancer - genetic predictors.

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Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

Non-small cell lung cancer - genetic predictors.

Related Articles

Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

Elvitegravir A66 Bufexamac

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

Non-small cell lung cancer - genetic predictors.

Related Articles

Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

Elvitegravir A66 Bufexamac

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

A66 Bufexamac JNK INHIBITOR selleck chemical

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

jnk inhibitor ii selleck jnk inhibitor ii selleck chemical Elvitegravir

Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood-brain barrier and metal homeostasis in cerebral cortex of rat brain: an in vivo &in vitro study.

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Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood-brain barrier and metal homeostasis in cerebral cortex of rat brain: an in vivo &in vitro study.

Toxicology. 2013 Jun 3;

Authors: Mitra S, Gera R, Siddiqui WA, Khandelwal S

Abstract
Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30mg/kg)was administered and the animals were sacrificed on day3 and day7. Blood-brain barrier permeability remained disrupted significantly till day7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 & NF-?B) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca(2+) inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT assay), signifying specific roles of Ca(2+) and ROS. Significance of p38 signaling was evaluated on pro-apoptotic proteins by using SB203580, a selective p38 inhibitor. Our data collectively illustrates that TBTC can disrupt BBB, induce oxidative stress, cause cell death and initiate neurodegeneration in rat brain.

PMID: 23743147 [PubMed - as supplied by publisher]

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Non-small cell lung cancer - genetic predictors.

Related Articles

Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

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Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

Elvitegravir A66 Bufexamac

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

JNK INHIBITOR selleck chemical JNK INHIBITOR jnk

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Related Articles

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

J Proteome Res. 2013 Jan 4;12(1):455-69

Authors: Hrabakova R, Kollareddy M, Tyleckova J, Halada P, Hajduch M, Gadher SJ, Kovarova H

Abstract
Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53(+/+) and p53(-/-) phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease.

PMID: 23151231 [PubMed - indexed for MEDLINE]

jnk inhibitor ii selleck chemical Elvitegravir A66

FGF Receptors: Cancer Biology and Therapeutics.

FGF Receptors: Cancer Biology and Therapeutics.

Med Res Rev. 2013 May 21;

Authors: Katoh M, Nakagama H

Abstract
Fibroblast growth factors (FGFs) are involved in a variety of cellular processes, such as stemness, proliferation, anti-apoptosis, drug resistance, and angiogenesis. Here, FGF signaling network, cancer genetics/genomics of FGF receptors (FGFRs), and FGFR-targeted therapeutics will be reviewed. FGF signaling to RAS-MAPK branch and canonical WNT signaling cascade mutually regulate transcription programming. FGF signaling to PI3K-AKT branch and Hedgehog, Notch, TGF?, and noncanonical WNT signaling cascades regulate epithelial-to-mesenchymal transition (EMT) and invasion. Gene amplification of FGFR1 occurs in lung cancer and estrogen receptor (ER)-positive breast cancer, and that of FGFR2 in diffuse-type gastric cancer and triple-negative breast cancer. Chromosomal translocation of FGFR1 occurs in the 8p11 myeloproliferative syndrome and alveolar rhabdomyosarcoma, as with FGFR3 in multiple myeloma and peripheral T-cell lymphoma. FGFR1 and FGFR3 genes are fused to neighboring TACC1 and TACC3 genes, respectively, due to interstitial deletions in glioblastoma multiforme. Missense mutations of FGFR2 are found in endometrial uterine cancer and melanoma, and similar FGFR3 mutations in invasive bladder tumors, and FGFR4 mutations in rhabdomyosarcoma. Dovitinib, Ki23057, ponatinib, and AZD4547 are orally bioavailable FGFR inhibitors, which have demonstrated striking effects in preclinical model experiments. Dovitinib, ponatinib, and AZD4547 are currently in clinical trial as anticancer drugs. Because there are multiple mechanisms of actions for FGFR inhibitors to overcome drug resistance, FGFR-targeted therapy is a promising strategy for the treatment of refractory cancer. Whole exome/transcriptome sequencing will be introduced to the clinical laboratory as the companion diagnostic platform facilitating patient selection for FGFR-targeted therapeutics in the era of personalized medicine.

PMID: 23696246 [PubMed - as supplied by publisher]

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The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

Chromosome Res. 2013 Jun 5;

Authors: Liew GM, Foulk MS, Gerbi SA

Abstract
The steroid hormone ecdysone induces DNA amplification and subsequent DNA puff formation in late fourth larval instar salivary gland polytene chromosomes of the fungus fly, Sciara coprophila. Previous in vitro studies on DNA puff II/9A in Sciara demonstrated that the ecdysone receptor (ScEcR-A) efficiently binds an ecdysone response element adjacent to the origin recognition complex binding site within the II/9A amplification origin, implying a role for ScEcR-A in amplification. Here, we extrapolate the molecular details from locus II/9A to the rest of the genome using immunofluorescence with a ScEcR-A-specific antibody. ScEcR-A binds all DNA puff sites just as amplification begins and persists throughout the processes of amplification, transcription, and puffing. Ecdysone injections into pre-amplification stage larvae prematurely induce both DNA amplification and ScEcR-A binding to DNA puff sites. These data are consistent with a direct role for ScEcR-A in DNA amplification.

PMID: 23737076 [PubMed - as supplied by publisher]

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Non-small cell lung cancer - genetic predictors.

Related Articles

Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

Elvitegravir A66 Bufexamac

Non-small cell lung cancer - genetic predictors.

Related Articles

Non-small cell lung cancer - genetic predictors.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 May 29;

Authors: Koudelakova V, Kneblova M, Trojanec R, Drabek J, Hajduch M

Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer that is the leading cause of cancer-related mortality worldwide. Several predictive markers have been found in NSCLC patients to date but only a few are currently used for tailored therapy. METHODS AND RESULTS: PubMed and Web of Science online databases were used to search review and original articles on the most important predictive markers in NSCLC. CONCLUSION: EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib). Other markers, such as KRAS mutation, EGFR T790M mutation and C-MET amplification, are responsible for resistance to these inhibitors. Overcoming of this resistance as well as discovery of new potential markers and inhibitors is the main goal of ongoing research and clinical trials in NSCLC.

PMID: 23733083 [PubMed - as supplied by publisher]

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Short-term acetaminophen consumption enhances the exercise-induced increase in Achilles peritendinous IL-6 in humans.

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Short-term acetaminophen consumption enhances the exercise-induced increase in Achilles peritendinous IL-6 in humans.

J Appl Physiol. 2013 Jun 6;

Authors: Gump BS, McMullan DR, Cauthon DJ, Whitt JA, Del Mundo JD, Letham T, Kim PJ, Friedlander GN, Pingel J, Langberg H, Carroll CC

Abstract
Through an unknown mechanism the cyclooxygenase (COX) inhibitor acetaminophen (APAP) alters tendon mechanical properties in humans when consumed during exercise. Interleukin-6 (IL-6) is produced by tendon during exercise and is a potent stimulator of collagen synthesis. In non-tendon tissue, IL-6 is upregulated in presence of COX-inhibitors and may contribute to alterations in extracellular matrix turnover, possibly due to inhibition of prostaglandin E2 (PGE2). We evaluated the effects of APAP on IL-6 and PGE2 in human Achilles peritendinous tissue after 1-hour of treadmill exercise. Subjects were randomly assigned to a placebo (n=8, 26�1 y) or APAP (n=8, 25�1 y) group. Each subject completed a non-exercise and exercise experiment consisting of 6-hours of microdialysis. Drug (APAP, 1000 mg) or placebo was administered in a double-blind manner during both experiments. PGE2 and IL-6 were determined via enzyme immunoassay and APAP via high performance liquid chromatography. In subjects given APAP, peritendinous APAP levels increased to 4.08�0.65 ?g?ml(-1) (p<0.05). PGE2 did not increase with exercise in either group (p>0.05), nor was PGE2 significantly reduced in the APAP group. IL-6 levels increased with exercise in both groups (p<0.05), but this increase was greater in the APAP group (p<0.05). Our findings suggest that APAP enhances tendon IL-6 production after exercise. Peak levels of APAP obtained in the peritendinous space were 2-fold lower than values reported in plasma or skeletal muscle.. These findings provide insight into the effects of APAP on tendon and provide novel information on the kinetics of APAP in tendon tissue after oral APAP consumption.

PMID: 23743397 [PubMed - as supplied by publisher]

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The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

The ecdysone receptor (ScEcR-A) binds DNA puffs at the start of DNA amplification in Sciara coprophila.

Chromosome Res. 2013 Jun 5;

Authors: Liew GM, Foulk MS, Gerbi SA

Abstract
The steroid hormone ecdysone induces DNA amplification and subsequent DNA puff formation in late fourth larval instar salivary gland polytene chromosomes of the fungus fly, Sciara coprophila. Previous in vitro studies on DNA puff II/9A in Sciara demonstrated that the ecdysone receptor (ScEcR-A) efficiently binds an ecdysone response element adjacent to the origin recognition complex binding site within the II/9A amplification origin, implying a role for ScEcR-A in amplification. Here, we extrapolate the molecular details from locus II/9A to the rest of the genome using immunofluorescence with a ScEcR-A-specific antibody. ScEcR-A binds all DNA puff sites just as amplification begins and persists throughout the processes of amplification, transcription, and puffing. Ecdysone injections into pre-amplification stage larvae prematurely induce both DNA amplification and ScEcR-A binding to DNA puff sites. These data are consistent with a direct role for ScEcR-A in DNA amplification.

PMID: 23737076 [PubMed - as supplied by publisher]

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