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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

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

Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1.
In this study, we found that infection with the oncolytic H-1 parvovirus decreased HIF-1α protein levels in pancreatic cancer cells under CoCl2 or hypoxia. The H-1 virus-induced decrease of HIF-1α was regulated by a proteasome-mediated pathway. Suppression of VHL, an E3 ligase and a critical regulator of HIF-1α, or enforced expression of UCP, an E2 ubiquitin-conjugating enzyme, failed to inhibit the H-1 virus-induced decrease of HIF-1α. Furthermore, siRNA-mediated suppression of RACK1, another regulator of HIF-1α, did not prevent H-1 viral infection from lowering HIF-1α protein levels. Although decrease of HIF-1α wa...
Source: International Journal of Oncology - March 9, 2015 Category: Cancer & Oncology Authors: Cho IR, Kaowinn S, Moon J, Soh J, Kang HY, Jung CR, Oh S, Song H, Koh SS, Chung YH Tags: Int J Oncol Source Type: research

Energy Metabolism in a Matched Model of Radiation Resistance for Head and Neck Squamous Cell Cancer.
In this study, we investigated the reprogramming of the energy metabolism in radiosensitive and radioresistant head and neck squamous cell carcinomas (HNSCC) using a preclinical matched model of radiation resistance. Our investigation found that radioresistant rSCC-61 cells: 1. They display increased glucose uptake and decreased fatty acid uptake; 2. They deviate from the classical Warburg effect by diverting the glycolytic flux into the pentose phosphate pathway; 3. They are more dependent on glucose than glutamine metabolism to support growth; 4. They have decreased mitochondrial oxidative phosphorylation; 5. They have e...
Source: Radiation Research - March 4, 2015 Category: Physics Authors: Mims J, Bansal N, Bharadwaj MS, Chen X, Molina AJ, Tsang AW, Furdui CM Tags: Radiat Res Source Type: research

Hypoxia-induced autophagy confers resistance of breast cancer cells to ionizing radiation.
Authors: He WS, Dai XF, Jin M, Liu CW, Rent JH Abstract Hypoxia is a hallmark of solid tumors, which presents a major obstacle to the effectiveness of radiation therapy. However, the function and the importance of molecular response have not been well defined. In the present study, hypoxia-induced autophagy and its effect on the response of breast cancer cells to ionizing radiation were examined. Results showed that hypoxic exposure induced a marked accumulation of autophagosomes accompanied by mRNA induction of the autophagy-related genes Beclin-1, Atg5, Atg7, and Atg12. The elevated autophagic activity was associ...
Source: Oncology Research - December 1, 2014 Category: Cancer & Oncology Tags: Oncol Res Source Type: research

Ionizing Radiation Sensitizes Breast Cancer Cells to Bcl-2 Inhibitor, ABT-737, through Regulating Mcl-1.
Abstract Breast-conserving surgery followed by radiation therapy has become the standard of care for early stage breast cancer. However, there are some patients that develop a local failure. We have previously shown that Bcl-2 overexpression was associated with an increased risk of local recurrence in patients with early stage breast cancer. The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. siRNAs were employed to silence myel...
Source: Radiation Research - November 19, 2014 Category: Physics Authors: Wu H, Schiff DS, Lin Y, Neboori HJ, Goyal S, Feng Z, Haffty BG Tags: Radiat Res Source Type: research

Silencing of insulin-like growth factor-1 receptor enhances the radiation sensitivity of human esophageal squamous cell carcinoma in vitro and in vivo
Conclusions: The results of the current study suggest that IGF-1r knockdown may enhance the radiation sensitivity of ESCC and increase the therapeutic effects of radiation both in vitro and in vivo. These results provide strong evidence that the targeted application of siRNA will enable the development of new therapeutic strategies for the clinical treatment of ESCC patients.
Source: BioMed Central - November 3, 2014 Category: Journals (General) Authors: Hui ZhaoXiaomeng Gu Source Type: research

Rt-40 * the down-regulation of h-ferritin as an adjuvant therapy in human glioma
This study supports the potential of H-ferritin siRNA as an adjuvant therapy in glioma treatment.
Source: Neuro-Oncology - November 3, 2014 Category: Cancer & Oncology Authors: Pang, M., Liu, X., Madhankumar, A. B., Slagle-Webb, B., Connor, J. Tags: RADIATION THERAPY (CLINICAL AND/OR LABORATORY RESEARCH) Source Type: research

The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype
Conclusions: Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolism.
Source: BMC Cancer - October 1, 2014 Category: Cancer & Oncology Authors: Bárbara SousaAna RibeiroAna NobreNair LopesDiana MartinsCéline PinheiroAndré VieiraAndré AlbergariaRené GerhardFernando SchmittFátima BaltazarJoana Paredes Source Type: research

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