GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Corticotropin-Releasing Hormone (CRH) Expression and Protein Kinase A Mediated CRH Receptor Signalling in an Immortalized Hypothalamic Cell Line (2003)
    Oxford, UK : Blackwell Science, Ltd
    Journal of neuroendocrinology 15 (2003), S. 0 
    Details
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Corticotropin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays an important role in the stress response in the hypothalamus. We describe the development of an immortalized hypothalamic cell line which expresses CRH. We hypothesized that this cell line would possess the relevant characteristics of parvocellular CRH-expressing neurones such as glucocorticoid receptor (GR) expression and vasopressin (VP) coexpression. For production of hypothalamic cells, embryonic day 19 rat pup hypothalami were dissected and dissociated into tissue culture dishes. They were immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene at 3 days of culture and then screened for expression of CRH following dilution cloning. One cell line was chosen (IVB) which exhibited CRH-like immunoreactivity (CRH-LI) and expressed CRH, VP and CRH1 receptor RNA via the reverse transcriptase-polymerase chain reaction. In addition, the cell line expressed the neuronal marker, microtubule-associated protein-2. We verified that the CRH-LI from IVB cell lysates coeluted with CRH standard via reversed-phase high-performance liquid chromatography (HPLC). Furthermore, oxidation of the lysate converted its HPLC profile to that identical with oxidized CRH standard. In addition, IVB cells exhibited high affinity binding to CRH. Incubation of IVB cells with CRH lead to increases in cAMP levels and protein kinase A activity in a concentration-dependent manner. Incubation of IVB cells with CRH also resulted in increases in phospho-cyclic-AMP response element binding protein (CREB) imunostaining as detected by immunocytochemical analysis. Finally, CRH treatment of IVB cell lines has been linked to CREB-mediated gene expression as determined via the PathDetect CREB trans-reporting system. The characteristics of IVB cells, such as CRH and VP coexpression, GR expression and a biologically active CRH-R1-mediated signalling pathway, suggest that this neuronal cell line may serve as model of parvocellular CRH neurones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2826.2003.01026.x
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Effect of Repeated Lipopolysaccharide Administration on Tissue Cytokine Expression and Hypothalamic-Pituitary-Adrenal Axis Activity in Rats (2001)
    Oxford, UK : Blackwell Science, Ltd
    Journal of neuroendocrinology 13 (2001), S. 0 
    Details
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of chronic immune challenge on cytokine expression and hypothalamic-pituitary-adrenal axis (HPA) axis responses to stress were studied in Wistar rats after administration of increasing doses of lipopolysaccharide (LPS). Repeated LPS (R-LPS) decreased body weight and increased adrenal weight and pituitary pro-opiomelanocortin mRNA levels. LPS injection increased plasma adrenocorticotropic hormone (ACTH) and corticosterone but the effect was attenuated in R-LPS. Plasma corticosterone but not ACTH responses to restraint were also reduced in R-LPS. Basal and restraint-stimulated corticotropin releasing hormone (CRH) mRNA levels were lower in R-LPS, but responses to a new LPS injection were similar to controls. In contrast, type 1 CRH receptor (CRH-R1) mRNA responses to both LPS and restraint were blunted in R-LPS. Vasopressin mRNA levels in parvocellular neurones were higher in R-LPS, and increased further after restraint but not after a new LPS injection. Glucocorticoid receptor (GR) levels in the paraventricular nucleus (PVN) increased after a single LPS or R-LPS (24 h after the last injection) but declined after a new injection in R-LPS. Interleukin (IL)-1β and IL-6 mRNAs increased in the pituitary, spleen and circumventricular organs after single or R-LPS, suggesting that cytokines may contribute to the activation of the HPA axis though pathways from the circumventricular organs as well as paracrine effects in the pituitary. The data show that (i) adaptation of the HPA axis during repeated LPS injection involves increases in vasopressin : CRH expression ratios in parvocellular neurones; (ii) that hypothalamic CRH and vasopressin responses to acute stimulation are independent of CRH-R1 expression in the PVN; and (iii) there is a dissociation between pituitary and adrenal responses to acute stress suggesting a decrease of adrenal sensitivity to ACTH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2826.2001.00684.x
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    facet.materialart.
    Unknown
    CHFR Expression Predicts Taxane Sensitivity (2013)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2013-03-16
    Description: Purpose: Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non–small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival with taxane-based first-line chemotherapy in advanced stage NSCLC. Methods: We studied a cohort of 41 patients (median age 63 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. CHFR expression by immunohistochemistry (score 0–4) was correlated with clinical outcome using chi-square test and Cox proportional models. A cutoff score of "3" was determined by receiver operator characteristics analysis for "low" CHFR expression. Results were validated in an additional 20 patients who received taxane-based chemotherapy at Emory University Hospital and the Atlanta VAMC. Results: High expression (score = 4) of CHFR is strongly associated with adverse outcomes: the risk for progressive disease after first-line chemotherapy with carboplatin–paclitaxel was 52% in patients with CHFR-high versus only 19% in those with CHFR-low tumors ( P = 0.033). Median overall survival was strongly correlated with CHFR expression status (CHFR low: 9.9 months; CHFR high: 6.2 months; P = 0.002). After multivariate adjustment, reduced CHFR expression remained a powerful predictor of improved overall survival (HR = 0.24; 95% CI, 0.1–0.58%; P = 0.002). In the validation set, low CHFR expression was associated with higher likelihood of clinical benefit ( P = 0.03) and improved overall survival ( P = 0.038). Conclusions: CHFR expression is a novel predictive marker of response and overall survival in NSCLC patients treated with taxane-containing chemotherapy. Clin Cancer Res; 19(6); 1603–11. ©2013 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Early Detection of Pancreatic Cancer (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-07-02
    Description: Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. Cancer Res; 74(13); 3381–9. ©2014 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    CDO1 Promoter Methylation and Clear-Cell Renal Cell Cancer (2015)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2015-08-04
    Description: Purpose: In this era of molecular diagnostics, prediction of clear-cell renal cell cancer (ccRCC) survival requires optimization, as current prognostic markers fail to determine individual patient outcome. Epigenetic events are promising molecular markers. Promoter CpG island methylation of cysteine dioxygenase type 1 ( CDO1 ), which was identified as prognostic marker for breast cancer, is studied as a potential marker for ccRCC survival. Experimental Design: We collected primary tissues of 365 ccRCC cases identified within the prospective Netherlands Cohort Study (NLCS). In this population-based series, CDO1 promoter methylation was observed in 124 of 324 (38.3%) patients with successful methylation-specific PCR analysis. Kaplan–Meier curves and Wilcoxon tests were used to evaluate 10-year ccRCC-specific survival. Cox regression analysis was used to obtain crude and multivariate HRs and 95% confidence intervals (CI). The relative prognostic value of multivariate models with and without CDO1 promoter methylation was compared using likelihood-ratio tests. Results: Patients with CDO1 promoter methylation have a significantly poorer survival than those without (Wilcoxon P = 0.006). Differences in survival were independent of other prognostic factors, including age and sex (HR, 1.66; 95% CI, 1.12–2.45) and TNM stage, tumor size, and Fuhrman grade (HR, 1.89; 95% CI, 1.25–2.85). Multivariate models performed better with than without CDO1 promoter methylation status (likelihood-ratio P = 0.003). Survival curves were validated in an independent series of 280 ccRCC cases from The Cancer Genome Atlas (TCGA; Wilcoxon P 〈 0.001). Conclusions: CDO1 promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis. Clin Cancer Res; 21(15); 3492–500. ©2015 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Inactivation of CDO1 and Resistance to Anthracyclines (2013)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2013-06-15
    Description: Purpose: Genome-wide DNA methylation analyses have identified hundreds of candidate DNA-hypermethylated genes in cancer. Comprehensive functional analyses provide an understanding of the biologic significance of this vast amount of DNA methylation data that may allow the determination of key epigenetic events associated with tumorigenesis. Experimental Design: To study mechanisms of cysteine dioxygenase type 1 ( CDO1 ) inactivation and its functional significance in breast cancer in a comprehensive manner, we screened for DNA methylation and gene mutations in primary breast cancers and analyzed growth, survival, and reactive oxygen species (ROS) production in breast cancer cells with restored CDO1 function in the context of anthracycline treatment. Results: DNA methylation-associated silencing of CDO1 in breast cancer is frequent (60%), cancer specific, and correlates with disease progression and outcome. CDO1 function can alternatively be silenced by repressive chromatin, and we describe protein-damaging missense mutations in 7% of tumors without DNA methylation. Restoration of CDO1 function in breast cancer cells increases levels of ROS and leads to reduced viability and growth, as well as sensitization to anthracycline treatment. Priming with 5-azacytidine of breast cancer cells with epigenetically silenced CDO1 resulted in restored expression and increased sensitivity to anthracyclines. Conclusion: We report that silencing of CDO1 is a critical epigenetic event that contributes to the survival of oxidative-stressed breast cancer cells through increased detoxification of ROS and thus leads to the resistance to ROS-generating chemotherapeutics including anthracyclines. Our study shows the importance of CDO1 inactivation in breast cancer and its clinical potential as a biomarker and therapeutic target to overcome resistance to anthracyclines. Clin Cancer Res; 19(12); 3201–11. ©2013 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    Driver Genes in Pancreatic Cancer (2012)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2012-11-16
    Description: Purpose: Genetic alterations of KRAS , CDKN2A , TP53 , and SMAD4 are the most frequent events in pancreatic cancer. We determined the extent to which these 4 alterations are coexistent in the same carcinoma, and their impact on patient outcome. Experimental Design: Pancreatic cancer patients who underwent an autopsy were studied ( n = 79). Matched primary and metastasis tissues were evaluated for intragenic mutations in KRAS , CDKN2A , and TP53 and immunolabeled for CDKN2A, TP53, and SMAD4 protein products. The number of altered driver genes in each carcinoma was correlated to clinicopathologic features. Kaplan–Meier estimates were used to determine median disease free and overall survival, and a Cox proportional hazards model used to compare risk factors. Results: The number of genetically altered driver genes in a carcinoma was variable, with only 29 patients (37%) having an alteration in all 4 genes analyzed. The number of altered driver genes was significantly correlated with disease free survival ( P = 0.008), overall survival ( P = 0.041), and metastatic burden at autopsy ( P = 0.002). On multivariate analysis, the number of driver gene alterations in a pancreatic carcinoma remained independently associated with overall survival ( P = 0.046). Carcinomas with only 1 to 2 driver alterations were enriched for those patients with the longest survival (median 23 months, range 1 to 53). Conclusions: Determinations of the status of the 4 major driver genes in pancreatic cancer, and specifically the extent to which they are coexistent in an individual patients cancer, provides distinct information regarding disease progression and survival that is independent of clinical stage and treatment status. Clin Cancer Res; 18(22); 6339–47. ©2012 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-02-16
    Description: Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone. Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML). Results: A total of 99 patients received veliparib 10–100 mg orally twice daily on days 1–8, 1–14, or 1–21 along with continuous infusion topotecan 1.0–1.2 mg/m 2 /d + carboplatin 120–150 mg/m 2 /d on days 3–7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m 2 /d + carboplatin 150 mg/m 2 /d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage–induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27–0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34 + leukemia cells, with greater phosphorylation in cells from responders. Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899–907. ©2016 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Myeloid Leukemia (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-02-02
    Description: Purpose: In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies. Experimental Design: Patients received veliparib [20–200 mg once a day on day 1 and twice daily on days 4–12 in cycle 1 (days 1–8 in cycle ≥2)] and temozolomide [150–200 mg/m 2 daily on days 3–9 in cycle 1 (days 1–5 in cycle ≥2)] every 28 to 56 days. Veliparib pharmacokinetics and pharmacodynamics [ability to inhibit poly(ADP-ribose) polymer (PAR) formation and induce H2AX phosphorylation] were assessed. Pretreatment levels of MGMT and PARP1 protein, methylation of the MGMT promoter, and integrity of the Fanconi anemia pathway were also examined. Results: Forty-eight patients were treated at seven dose levels. Dose-limiting toxicities were oral mucositis and esophagitis lasting 〉7 days. The MTD was veliparib 150 mg twice daily with temozolomide 200 mg/m 2 daily. The complete response (CR) rate was 17% (8/48 patients). Veliparib exposure as well as inhibition of PAR polymer formation increased dose proportionately. A veliparib-induced increase in H2AX phosphorylation in CD34 + cells was observed in responders. Three of 4 patients with MGMT promoter methylation achieved CR. Conclusions: Veliparib plus temozolomide is well tolerated, with activity in advanced AML. Further evaluation of this regimen and of treatment-induced phosphorylation of H2AX and MGMT methylation as potential response predictors appears warranted. Clin Cancer Res; 23(3); 697–706. ©2016 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Systemic Therapy of Pancreatic Cancer with 3-Bromopyruvate (2014)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2014-12-16
    Description: Purpose: This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: The presence of the β-CD–3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC 50 ) of β-CD–3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro . An orthotopic luc MiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy. Results: β-CD–3-BrPA and free 3-BrPA demonstrated an almost identical IC 50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo , animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA. Conclusion: The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD–3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered. Clin Cancer Res; 20(24); 6406–17. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...