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Total 78 results found since Jan 2013.

Application of bifurcation theory and siRNA-based control signal to restore the proper response of cancer cells to DNA damage
Publication date: 7 November 2016 Source:Journal of Theoretical Biology, Volume 408 Author(s): Emilia Kozłowska, Krzysztof Puszynski Many diseases with a genetic background such as some types of cancer are caused by damage in the p53 signaling pathway. The damage changes the system dynamics providing cancer cells with resistance to therapy such as radiation therapy. The change can be observed as the difference in bifurcation diagrams and equilibria type and location between normal and damaged cells, and summarized as the changes of the mathematical model parameters and following changes of the eigenvalues of Jacobian mat...
Source: Journal of Theoretical Biology - August 23, 2016 Category: Biology Source Type: research

Sodium valproate prevents radiation-induced injury in hippocampal neurons via activation of the Nrf2/HO-1 pathway
Conclusions: ROS generation after radiation exposure contributes to DNA damage in the zebrafish brain. VPA inhibits ROS generation by activating the Nrf2/HO-1 pathway, which improves cognitive behavior following radiation-induced neuronal injury.
Source: Neuroscience - June 25, 2016 Category: Neuroscience Source Type: research

Abstract P3-06-15: Notch3 as a predictor of GSI sensitivity in distinct subtypes of triple negative breast cancer
Conclusions: GSI acts through Notch3 in two TNBC subtypes and combination of chemotherapy with Notch inhibition results in a better outcome as compared to either drug alone. Future experiments would elucidate the role of Notch3 inhibition in targeting cancer stem cells post chemotherapy treatment in different subtypes of TNBC.Citation Format: Shah D, Osipo C. Notch3 as a predictor of GSI sensitivity in distinct subtypes of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Shah, D., Osipo, C. Tags: Poster Session Abstracts Source Type: research

Cyclin D1 silencing suppresses tumorigenicity, impairs DNA double strand break repair and thus radiosensitizes androgenindependent prostate cancer cells to DNA damage.
Authors: Marampon F, Gravina GL, Ju X, Vetuschi A, Sferra R, Casimiro MC, Pompili S, Festuccia C, Colapietro A, Gaudio E, Di Cesare E, Tombolini V, Pestell RG Abstract Patients with hormone-resistant prostate cancer (PCa) have higher biochemical failure rates following radiation therapy (RT). Cyclin D1 deregulated expression in PCa is associated with a more aggressive disease: however its role in radioresistance has not been determined. Cyclin D1 levels in the androgen-independent PC3 and 22Rv1 PCa cells were stably inhibited by infecting with cyclin D1-shRNA. Tumorigenicity and radiosensitivity were investigated u...
Source: Oncotarget - December 26, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Systemic PSMA-Targeted IR Sensitization
Radiation therapy is a highly effective tool for treating all stages of prostate cancer, from curative approaches in localized disease to palliative care and enhanced survival for patients with distant bone metastases. The therapeutic index of these approaches may be enhanced with targeted radiation-sensitizing agents. Aptamers are promising nucleic acid delivery agents for short interfering RNAs (siRNA) and short hairpin RNAs (shRNA). We have previously developed a radiation-sensitizing RNA aptamer–shRNA chimera that selectively delivers DNA-PK targeting shRNAs to prostate-specific membrane antigen (PSMA) positive c...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Ni, X., Zhang, Y., Zennami, K., Castanares, M., Mukherjee, A., Raval, R. R., Zhou, H., DeWeese, T. L., Lupold, S. E. Tags: Large Molecule Therapeutics Source Type: research

MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells.
Abstract Maternal Embryonic Leucine Zipper Kinase (MELK), a Ser/Thr protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The oncogenic function of MELK is attributed to its capacity to disable critical cell-cycle checkpoints and reduce replication stress. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing. Here, we have explored the biological function of MELK using MELK-T1, a novel and selective small-molecule inhibitor. Strikingly, MELK-T1 triggered a rapid and proteasome-dependent degradation of the MELK protein. Treatment of MCF-7 breast adenoca...
Source: Bioscience Reports - October 2, 2015 Category: Biomedical Science Authors: Beke L, Kig C, Linders JT, Boens S, Boeckx A, Van Heerde E, Parade M, De Bondt A, Van Den Wyngaert I, Bashir T, Ogata S, Meerpoel L, Van Eynde A, Johnson CN, Beullens M, Brehmer D, Bollen M Tags: Biosci Rep Source Type: research

Abstract 3303: Radioresistance in glioma stem cells driven by Rad51 dependent homologous recombination repair
We examined co-expression of stem cell markers with RAD51 protein at whole population level using western blotting, immunocytochemistry and RT-PCR in cultured cells and immunohistochemistry in tumor material. Single cell expression was analysed using the Fluidigm C1 platform. We examined the effect of two specific inhibitors of RAD51 (B02, RI-1) on the same cell pairs in vitro and used the γH2AX assay to assess differences in repair kinetics. We used subcutaneous models of glioma to evaluate the effect of one of these agents (RI-1) on tumour growth delay with and without fractionated radiation doses in vivo.Primary glioma...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: King, H., Payne, H., Brend, T., Patel, A., Wright, A., Englu, T., Stead, L., Wurdak, H., Short, S. C. Tags: Tumor Biology Source Type: research

Abstract 3326: Targeting lysophosphatidic acid receptor 1 (LPAR1) radiosensitizes poor prognosis cancers
Therapies for poor prognosis cancers, such as lung cancer and glioblastoma, are limited due to radio-resistance and tumor recurrence. Development of molecular targeted therapy can serve as a potential method to improve the efficacy of radiation therapy in both glioblastoma and lung cancer. Ionizing radiation (IR) can activate a series of pro-survival pathways which contributes to the pathogenesis of cancer cells. Among these pathways, cytosolic phospholipase A2 (cPLA2) is an integral component which is activated by IR. Following activation, cPLA2 cleaves arachidonic acid to form phosphatidylcholine (PC) and yields lysophos...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Khudanyan, A., Dadey, D., Karvas, R., Kotipatruni, R., Hallahan, D., Thotala, D. Tags: Tumor Biology Source Type: research

Abstract 3338: Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma
In conclusion, we have developed a new small molecule inhibitor of MRK/ZAK that radio-sensitizes medulloblastoma cells. We hypothesize that combining radio-therapy with M443 will allow us to lower the radiation dose while maintaining therapeutic efficacy, thereby minimizing radiation-induced side effects.Citation Format: Rosamaria Ruggieri, Daniel Markowitz, Caitlin Powell, Nhan Tran, Magimairajanissai Vanan, Mingzu He, Yousef Al-Abed, Marc Symons. Pharmacological inhibition of MRK/ZAK kinase for the treatment of medulloblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ruggieri, R., Markowitz, D., Powell, C., Tran, N., Vanan, M., He, M., Al-Abed, Y., Symons, M. Tags: Tumor Biology Source Type: research

Abstract 20: Honokiol radiosensitizes squamous cells carcinoma of head and neck by down-regulation of survivin
Conclusions: Survivin is a negative prognostic factor in SCCHN, and is involved in DNA damage response and repair induced by IR in SCCHN cells. Down regulation of survivin by honokiol enhances the efficacy of IR, and may provide a novel therapeutic approach to improve the efficacy of radiotherapy in SCCHN. (This research was supported by the National Cancer Institute award P50 CA128613, and GCC Distinguished Cancer Scholar to Dong M. Shin, Zhuo (Georgia) Chen, and Jonathan J Beitler)Citation Format: Xu Wang, Jonathan J. Beitler, Wen Huang, Guoqing Qian, Kelly Magliocca, Jun Zhang, Sreenivas Nannapaneni, Sungjin Kim, Zhengj...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, X., Beitler, J. J., Huang, W., Qian, G., Magliocca, K., Zhang, J., Nannapaneni, S., Kim, S., Chen, Z., Nabil, S. F., Chen, Z. G., Arbiser, J. L., Shin, D. M. Tags: Molecular and Cellular Biology Source Type: research

Radiosensitization and downregulation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) upon inhibition of mitogen/extracellular signal-regulated kinase (MEK) in malignant melanoma cells.
CONCLUSION: Our results indicate that pharmacological interference with MAPK signaling increases vulnerability of NRAS-mutant malignant melanoma cells to ionizing radiation along with downregulation of endogenous hnRNP K and point towards a possible use for combined MEK inhibition and localized radiation therapy of MM in the NRAS-mutant setting where BRAF inhibitors offer no clinical benefit. PMID: 26136337 [PubMed - as supplied by publisher]
Source: Oncotarget - July 5, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Gene interference strategies as a new tool for the treatment of prostate cancer
Abstract Prostate cancer (PCa) is one of the most common cancer in men. It affects older men and the incidence increases with age; the median age at diagnosis is 67 years. The diagnosis of PCa is essentially based on three tools: digital rectal exam, serum concentration of prostate specific antigen, and transrectal ultrasound-guided biopsy. Currently, the therapeutic treatments of this cancer are different and range from the prostatectomy to hormonal therapy, to radiation therapy, to immunotherapy, and to chemotherapy. However, additional efforts are required in order to find new weapons for the treatment of meta...
Source: Endocrine - June 7, 2015 Category: Endocrinology Source Type: research

RNF8 plays an important role in the radioresistance of human nasopharyngeal cancer cells in vitro.
Authors: Wang M, Chen X, Chen H, Zhang X, Li J, Gong H, Shiyan C, Yang F Abstract Tumor residue or recurrence is common after radiation therapy for nasopharyngeal cancer (NPC) since the tumor cells can repair irradiation-induced DNA damage. The ubiquitination cascade mediates the assembly of repair and signaling proteins at sites of DNA double-strand breaks (DSBs). Ring finger protein 8 (RNF8) is an E3 ubiquitin ligase that triggers ubiquitination at the site of DSBs. The present study aimed to identify whether and how RNF8 small interfering RNA (siRNA) treatment enhances the radiosensitivity of irradiated human ...
Source: Oncology Reports - May 9, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

B-cell receptor-guided delivery of peptide-siRNA complex for B-cell lymphoma therapy
Conclusions: Peptide-siRNA complex can be suitable tool for both selective peptide-driven cell targeting and gene silencing. In this setting, the improvement of this strategy is expected to provide a safe and non-invasive approach for the delivery of therapeutic molecules.
Source: Cancer Cell International - May 7, 2015 Category: Cancer & Oncology Authors: Nunzia MigliaccioCamillo PalmieriImmacolata RuggieroGiuseppe FiumeNicola MartucciIris ScalaIleana QuintoGiuseppe ScalaAnnalisa LambertiPaolo Arcari Source Type: research

TR-04 * NANOPARTICLE siRNA DELIVERY VEHICLES INHIBIT DNA REPAIR AND SENSITIZE PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY
Source: Neuro-Oncology - April 23, 2015 Category: Cancer & Oncology Authors: Kievit, F., Stephen, Z., Wang, K., Dayringer, C., Silber, J., Ellenbogen, R., Zhang, M. Tags: TRANSLATIONAL THERAPEUTICS Source Type: research