tbuckley/cabot-search huggingface dataset:
Intermittent Hypoxia: Potential Factor of Resistance to Endocrine Therapy.
Authors: W. Yin, G. Liu, G. Di, Z. Shen, Z. Shao
Journal: Cancer Research (2009)

Abstract Background: It has been reported that intermittent hypoxia, which is likely more prevalent than acute hypoxia in breast cancers, can cause persistent depression of estrogen receptor alpha (ER-α) expression in breast cell lines. However, it remains suspension whether intermittent hypoxia may be associated with resistance to endocrine therapy.Material and methods: The role of intermittent hypoxia in resistance to endocrine therapy was investigated in ER-α positive breast cell lines and animal models.Results: We observed that intermittent hypoxia promoted cancer cell proliferation in vitro and in vivo compared with normoxia. At both mRNA and protein levels, intermittent hypoxia induced down-regulation of ER-α and factor inhibiting HIF-1 (FIH) as well as up-regulation of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA-IX). ER-α positive breast cancer cells under normoxic condition were capable of an intact response to ICI 182,780 (Tocris), whereas the inhibitory effect of ICI 182,780 (Tocris) was significantly reduced in those after intermittent hypoxia. Such effect was further validated with fulvestrant (Astrazeneca) in the animal models. To clarify whether intermittent hypoxia was associated with resistance to endocrine therapy, the expression of HIF-1α, a critical regulator of hypoxia-related pathway, was blocked by a reformed type of small interfering RNA (siRNA), stealth RNAi (Invitrogen), which can reduce the cytotoxic interferon response unlike conventional siRNA. Interestingly, knock-down of HIF-1α did result in the restoration of not only the ER-α expression but also the response to endocrine therapy, which was reproducible with administration of Bortezomib, a proteasome inhibitor of HIF-1α.Discussion: These data provide functional evidence that intermittent hypoxia may confer resistance to endocrine therapy in breast cancers through the crosstalk between HIF-1α and ER-α signaling, which holds a promise to overcome endocrine resistance. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5148.
Abstract 765: DDX31 regulates p53 tumor suppressive activity in renal cell carcinomas.
Authors: Toyomasa Katagiri, Tomoya Fukawa, Taisuke Matsuo, Hiro-omi Kanayama
Journal: Cancer Research (2013)

Abstract Renal cell carcinoma (RCC) is the most common cancer of the kidney, and up to 30% of patients with RCC present with metastatic disease, yet its oncogenic origins are poorly understood. At an early stage, RCC can be cured by surgical resection, which is the most effective treatment for localized RCC tumors .Moreover, cytokine therapies, such as interleukin-2 or IFN-a, are widely used as a first-line treatment for metastatic disease. Therefore, it is highly important to develop a new molecular target agent(s) against RCC. However, these treatments can be associated with severe toxicity. Therefore, it is highly important to develop a new molecular target agent(s) against RCC. To identify therapeutic targets for cancer and understand the detailed molecular mechanism of carcinogenesis, we analyzed the expression profiling of clear cell RCC (ccRCC), which is a major histologic type of RCC, and identified DEAD (Asp-Glu-Ala-Asp) box polypeptide 31 (DDX31), a novel member of the DEAD box protein family, which is frequently up-regulated in the vast majority of human RCCs. Immunohistochemistry analysis indicated that DDX31 positivity was an independent prognostic factor for RCC patients. RNAi-mediated knockdown of DDX31 significantly suppressed RCC cell growth. Concordantly, expressing exogenous DDX31 promoted the growth of HEK293 cells. We also found that endogenous DDX31 interacted and colocalized with nucleophosmin (NPM1), involved in ribosome biogenesis and regulation of p53–HDM2 pathway, in nucleoli. Knockdown of DDX31 or NPM1 decreased pre-ribosome RNA biogenesis. Interestingly, in DDX31-knockdown cells, NPM1 was translocated from nucleoli to the nucleoplasm or cytoplasm, and then bound to HDM2, which prevented HDM2 from interacting with the p53 protein, resulting in p53 stabilization by inhibiting p53 ubiquitination. Our findings suggest that the DDX31–NPM1 complex plays critical roles in cell proliferation of RCC. Citation Format: Toyomasa Katagiri, Tomoya Fukawa, Taisuke Matsuo, Hiro-omi Kanayama. DDX31 regulates p53 tumor suppressive activity in renal cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 765. doi:10.1158/1538-7445.AM2013-765
Detection of Osseous Metastasis by 18F-NaF/18F-FDG PET/CT Versus CT Alone
Authors: Srinath C. Sampath, Srihari C. Sampath, Camila Mosci, Amelie M. Lutz, Juergen K. Willmann, Erik S. Mittra, Sanjiv S. Gambhir, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2014)

Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis.Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard.Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT.Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.
OP34 * TARGETING RAD51 TO RADIOSENSITISE GLIOBLASTOMA STEM CELLS
Authors: H. King, A. Wright, A. Patel, S. Short
Journal: Neuro-Oncology (2014)

INTRODUCTION: The capacity of a sub-population of stem-like cells (Glioma stem cells, GSC) to withstand treatment is thought to play a major role in tumour recurrence. It is becoming increasingly apparent that these GSC express elevated levels of DNA repair proteins including the homologous recombination protein Rad51. We have investigated whether targeting Rad51 is a viable mehod of radio-sensitising GSC. METHOD: Patient derived GSC were characterised for repair protein levels using western blot and IF microscopy when cells were cultured in stem cell permissive media and in differentiating conditions (exposure to BMP-4 and/or serum). The expression of Rad51 and its co-expression with stem cell markers in tumour samples was determined using IHC. We used 2 pharmacological inhibitors of Rad51 (RI-1 and B02) on undifferentiated cells to investigate the effect of inhibition on sensitivity to clinically relevant radiation doses RESULTS: Levels of Rad51 were elevated in GSC compared to normal human astrocytes. Differentiation of these cells reduces the expression of Rad51 in parallel with the stem cell markers SOX2 and Nestin. Rad51 was also found to preferentially co-localise with Nestin in tumour samples. The Rad51 inhibitors reduced Rad51 foci formation following irradiation in GSC without affecting γH2AX foci. Both inhibitors caused radiosensitisation when combined with single radiation doses between 1 and 5 Gy, with dose modifying factors of between 1.33 and 1.46 CONCLUSION: The increased expression of Rad51 in GSC and the ability of Rad51 inhibitors to radiosensitise these cells suggest that Rad51 may be a specific target for GSC and that targeting this repair pathway may lead to improved response to radiotherapy in GBM.
Abstract 2019: Molecular pathways involved in docetaxel (D)-resistance hormone-independent prostate cancer (HIPC) cells
Authors: Mercedes Marín-Aguilera, Jordi Codony-Servat, Susana G. Kalko, Pere Gascón, Begoña Mellado
Journal: Cancer Research (2010)

Abstract Background: D-based chemotherapy is the standard therapy of metastatic HIPC. However, only approximately 50% of patients respond to this treatment and most of them eventually develop resistance to the therapy. The molecular events that lead to D-resistance in HIPC are not well established. Objectives: To determine the main molecular pathways responsible for D-resistance in two different HIPC cells lines. Methodology: DU-145 and PC3 cell lines were converted to D-resistant cells (DU-145R and PC3R, respectively) by means of exposing parental cells to increasing doses of D. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these four cell lines. Genes, pathways and networks, commonly deregulated in both DU-145R and PC3R cells respect their parental cell lines, were analyzed in detail. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. Results: Differential expression of 321 genes (P&amp;lt;0.05 Bonferroni corrected and logFC&amp;gt;1.2) was found to be common in DU-145R and PC3R cells. Pathway and network analysis showed that these genes were particularly involved in cellular growth and proliferation, gene expression, cellular movement, cellular development, cell death and cell cycle. Other related functions are infection mechanism, cellular assembly and organization, tissue morphology, antigen presentation and cell-mediated immune response. RT-PCR confirmed differential expression in genes related with epithelial-mesenquimal transition (e-CADHERIN, α-CATENIN, VIMENTIN, SNAIL and TWIST), NFkB related genes (IL-6, IL-8, c-REL, P50 and P65) and ErbB signalling pathway family genes (EGFR and HER3). Conclusions: These data reveals a set of gene networks involved in HIPC D-resistance. Key genes from these networks should be investigated further as new targets for potential therapeutic development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2019.
Abstract 4765: Investigation of omega-3 docosahexaenoic acid (DHA)-induced apoptosis in human triple negative breast cancer
Authors: Ailian Xiong, Weiping Yu, Bob G. Sanders, Kimberly Kline
Journal: Cancer Research (2011)

Abstract Omega-3 fatty acid enriched diets especially diets rich in docosahexaenoic acid (DHA) have long been associated with a lower incidence of a variety of cancers. Both in vivo and in vitro studies have indicated that DHA exerts anticancer actions via inducing tumor cells to undergo programmed cell death or decreasing cell proliferation. In this study, we investigated the anticancer actions of DHA in human triple negative breast cancer (TNBC) cells in vitro. Data indicate that DHA induces apoptosis in MDA-MB-231 and BT-20 human p53 mutant TNBC cells by activating both intrinsic and extrinsic death-mediating pathways. Activation of apoptosis is associated with induction of endoplasmic reticulum (ER) stress, and increased levels of phosphorylated JNK (pJNK), and CHOP and DR5 protein levels; as well as, reduced levels of pIκB and NF-κB downstream mediators: c-FLIP, Survivin and Bcl-2. DHA induces ROS generation and antioxidants, RRR-alpha tocopherol (αT) and N-acetyl-Cysteine (NAC) block DHA-induced apoptosis, ER stress and upregulation of pJNK/CHOP/DR5. Taken together, our data demonstrate that DHA induces apoptosis in p53 mutant TNBC via activation of ROS mediated ER stress and suppression of NF-kB mediated anti-apoptotic factors. Since p53 mutant TNBCs are associated with poor prognosis and limited treatment options, these studies suggest DHA may be a successful adjuvant treatment strategy. Research is supported by the Clayton Foundation for Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4765. doi:10.1158/1538-7445.AM2011-4765
Abstract LB-19: The Smac mimetic LBW242 induces apoptosis in melanoma in a TLR-3-dependent and TNFR-independent manner
Authors: Kevin T. McHenry, Elena Jacobson, Jerry Donovan, Kymberly Levine, Jingxin Zhang, David E. Fisher, Leigh Zawel, Dale Porter
Journal: Cancer Research (2011)

Abstract Toll-like Receptor-3 (TLR-3), a pattern recognition receptor family member, has been shown to activate immune system pathways; however, it has also been shown to induce apoptosis in certain cancer cells. Combination of the synthetic TLR-3 ligand, poly I:C, with the Smac mimetic LBW242, an inhibitor of apoptosis protein (IAP) antagonist, has been shown to potently induce apoptosis in melanoma cells which are insensitive to either single agent. To better elucidate the mechanism responsible for this combination induced cell death, we performed a pooled shRNA screen. We identified receptor interacting protein kinase-1 (RIPK1) and as an important component of this process. Constitutive knockdown of RIPK1 prevents the LBW242 and poly I:C combination induced apoptosis. The IAP proteins cIAP1 and cIAP2 have been shown previously to regulate Caspase-8 activation downstream of Tumor Necrosis Factor Receptor-1 (TNFR1). Interestingly, we found that the combination induced apoptosis was independent of TNF signaling. Utilizing both gain of function and loss of function studies, we found that expression of TLR-3 is necessary for the combination induced apoptosis in melanoma cells. Taken together, our data indicate that the combination of the Smac mimetic LBW242 and TLR-3 agonist poly I:C induces a novel type of TLR-3 dependent apoptosis in melanoma cells that is independent of TNFR1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-19. doi:10.1158/1538-7445.AM2011-LB-19
788 RAPID VIRAL RESPONSE IN PRISON INMATES TREATED FOR CHRONIC HEPATITIS DUE TO HCV WITH PEGINTERFERON alfa-2a PLUS RIBAVIRIN. SUBANALYSIS OF PERSEO STUDY
Authors: J.J. Anton Basanta, A. Marco Mouriño, P. Sainz de la Hoya, J. de Juan Ramirez, F. Inmaculada, C Alia, G Almada, F Amaya, JJ Antón, M Bedia, J Borrego, E Campo, A Carreño, A da Silva, J de Juan, JR Díaz, J Domingo, I Faraco, V Ferrer, C Gallego, J García-Guerrero, C Gutierrez, AM Herrero, C Hoyos, G Jiménez-Gala'n, JM Laine, E Leandro, C López, A Marco, R Muros, F Paniagua, J Pérez de los Cobos, A Pérez-Valenzuela, R Planella, E Pozo, JR Rebolledo, F Ruíz, P Saíz de la Hoya, P Sánchez-Arrobas, C Sarriera, C Solé, J Trujols, LC Vasallo, M Veiras, C Yllobre, J Zúñiga
Journal: Journal of Hepatology (2013)
Hormone Replacement Therapy: Some Answers...More Questions
Authors: Elaine Blume
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Hormone Replacement Therapy: Some Answers...More Questions Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Pages 389–390, https://doi.org/10.1093/jnci/84.6.389 Published: 18 March 1992
Abstract 725: eIF4E/4eBP-1 as predictive factor(s) of response to EGFR targeted drug in head and neck cancer
Authors: Sébastien Vergez, Christelle Tavergnier, Philippe Rochaix, Thomas Filleron, Stéphan Vagner, Pierre R. Canal, Chatelut Etienne, Jean-Pierre Delord, Ben Allal
Journal: Cancer Research (2012)

Abstract Purpose: There is a clinical need to identify predictive markers of the response to epidermal growth factor receptor (EGFR) inhibitors in patients with head and neck squamous cell carcinoma (HNSCC). In breast cancer, the resistance to targeted therapies against HER2 implicates the reactivation of the PI3K/Akt/mTOR pathway and eIF4E overexpression. The axis eIF4E/4eBP-1 is one of the major downstream effector of the PI3K/Akt/mTOR pathway. The aim of this study was to further investigate these markers in the response to preclinical and clinical EGFR inhibitors used in HNSCC, cell lines and patients. Experimental Design: We studied the effects of cetuximab using human HNSCC cell lines (CAL33 and CAL166) on proliferation, survival pathways, eIF4E and 4eBP activities and expression by western blot or immunohistochemistry in initial biopsies of patients treated for an HNSCC with cetuximab used in combination with radiotherapy or cisplatin (n=28). Results: The HNSCC cell lines have an opposite effect under cetuximab treatment. Whereas the CAL33 are not sensitive, the CAL166 shows a moderate cytostatic effect allowing us to determine an IC20 of 5,56 +/− 0.37 µg/mL. In the CAL33 cell lines cetuximab doesn't significantly modify the 4eBP phosphorylation level. On the contrary in CAL166 cetuximab induces the inhibition of the 4eBP phosphorylation level corroborating the cytostatic effect previously observed. More over, in patients the combination Cetuximab / radiotherapy or cisplatin shows, in the initial biopsie examination in the non-responder group, a significant higher level of eIF4E. Conclusion: The couple eIF4E expression levels and/or activities appeared to be determinant to discriminate the response to the EGFR targeted inhibitor in HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 725. doi:1538-7445.AM2012-725
THU0406 Mortality Due to Low-Impact Fractures of the Proximal Femur in Senior Age Group
Authors: T. A. Raskina, J. V. Averkieva, E. Malyuta
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fractures of a hip are the most serious complication of osteoporosis, causing high rates of mortality, an invalidization, high cost of treatment and rehabilitation. <h3>Objectives</h3> To study the mortality due to low-traumatic fractures of the proximal femur in senior age group of Kemerovo town during the observation period: 0-6 months, 7-12 months, 13-24 months after injury. <h3>Methods</h3> Mortality is analyzed among 432 patients (328 women and 104 men) aged 50 and older, observed in the trauma departments of Kemerovo town from 01 January 2004 to 31 December 2008. Information about fractures and their outcomes was obtained from medical documentations data of the specialized trauma departments (cases history, maps of drop-out patients from an in-patient department), a telephone survey, data registration of registry offices. <h3>Results</h3> In the first 6 months 95 patients died (22,0%) of 432 patients in the period from 7 to 12 months - 42 (12,46%) of 337 patients, between 13 and 24 months from the date of hip fracture - 47 (16,21%) of the 295 patients remained under observation. Found that the mortality in the first 6 months after hip fracture was significantly higher than in the follow-up period 7-12 months (Χ ² = 14,28; p&lt;0.0001), and between 13-24 months (Χ ² = 2,1 p = 0,04). Fatality periods 7-12 months and 13-24 months were not significantly different (Χ ² = 1,04; p = 0.25). In the analysis of mortality by gender the following results were obtained: for 6 months 73 patients died (22,25%) of the 328 women, in the period of 7-12 months - 31 (12,15%) of the 255 female patients, in the period of 13-24 months – 36 female patients (16,07%) of the 224 women remaining under the observation. Noted that the mortality rate in women was significantly higher in the first 6 months after injury than in 7-12 months (Χ ² = 6,3; p &lt;0,001), and after 13-24 months (Χ ² = 2,21; p = 0,04). No significant differences in the comparative analysis of mortality in women in the period of 7-12 months and 13-24 months were found (p = 0,21). Men's mortality in the studying period of observation was as follows: for the first 6 months 22 men died (21,15%) of 104 patients, in the period of 7-12 months mortality increase was 11 men (13,41%) of 82 patients, in the period of 13-24 months – 11 men (15,49%) of 71 patients. Statistically significant differences in all periods of observation were not found: for 0-6 months and 7-12 months (Χ ² = 1,2; p = 0,17), for 7-12 months and 13-24 months (Χ ² = 0,46 p = 0,7) for 0-6 months and 13-24 months (Χ ² = 0,9; p = 0,3). <h3>Conclusions</h3> Thus, these results indicate a significantly higher mortality during the first 6 months after hip fracture among women. No statistically significant differences in mortality among men were found. <h3>Disclosure of Interest</h3> None Declared
Abstract 21: Quantification of Total Myocyte Regeneration Following Intracoronary Cardiosphere-Derived Cell (icCDC) Treatment in Swine with Chronic Myocardial Ischemia
Authors: Brian R Weil, Amanda Ribbeck, Gen Suzuki, Merced M Leiker, James A Fallavollita, John M Canty
Journal: Circulation Research (2014)

Objective: icCDCs improve function of ischemic myocardium and increase cardiomyocyte nuclear density but the extent to which this is explained by an increase in nuclei per cell vs. the formation of new myocytes is unclear. We aimed to address this issue and quantify new myocyte formation throughout the left ventricle (LV) after global icCDC treatment in swine with hibernating myocardium. Methods: Swine with a chronic LAD stenosis (N=29) received either ~35 x 10 6 icCDCs or no treatment. Regional function (echocardiography) and myocyte morphometric indices were assessed 1 month later. Transverse and longitudinal tissue sections were used to measure regional myocyte nuclear density, diameter, length, and nuclei/cell, from which myocyte volume and myocytes per gram of myocardium were calculated. Results: icCDC-mediated improvements in regional function were accompanied by an increase in myocyte nuclear density without a change in the number of nuclei/cell (Table). Compared with untreated animals, icCDC-treated animals exhibited a reduction in myocyte volume and a reciprocal increase in the number of myocytes per gram of tissue. Anatomic LV hypertrophy did not occur, however, as LV mass/body mass ratio was not different between groups (untreated: 2.5 ± 0.1 vs. icCDCs: 2.3 ± 0.1). Conclusion: These data demonstrate that icCDCs produce significant myocyte regeneration throughout the regionally ischemic heart that is dissociated from alterations in LV mass. Changes in myocyte nuclear density do not reflect an altered number of nuclei/cell and quantitative estimates suggest that intracoronary delivery of CDCs to the entire LV increases the number of myocytes by ~25% in just 4 weeks.