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https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#1
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#2
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209515/cell-type-specific-role-of-the-rna-binding-protein-nono-in-the-dna-double-strand-break-response-in-the-mouse-testes
#3
Shuyi Li, Feng-Jue Shu, Zhentian Li, Lahcen Jaafar, Shourong Zhao, William S Dynan
The tandem RNA recognition motif protein, NONO, was previously identified as a candidate DNA double-strand break (DSB) repair factor in a biochemical screen for proteins with end-joining stimulatory activity. Subsequent work showed that NONO and its binding partner, SFPQ, have many of the properties expected for bona fide repair factors in cell-based assays. Their contribution to the DNA damage response in intact tissue in vivo has not, however, been demonstrated. Here we compare DNA damage sensitivity in the testes of wild-type mice versus mice bearing a null allele of the NONO homologue (Nono (gt))...
February 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#4
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208747/multinucleated-giant-cancer-cells-produced-in-response-to-ionizing-radiation-retain-viability-and-replicate-their-genome
#5
Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W Wang, Piyush Kumar, David Murray
Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21(WAF1) (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202528/distinct-levels-of-radioresistance-in-lgr5-colonic-epithelial-stem-cells-versus-lgr5-small-intestinal-stem-cells
#6
Guoqiang Hua, Chu Wang, Yan Pan, Zhaoshi Zeng, Sang Gyu Lee, Maria Laura Martin, Adriana Haimovitz-Friedman, Zvi Fuks, Philip B Paty, Richard N Kolesnick
While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic epithelial stem cells (CESC) markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells (CBC) (D0 6.0±0.3 Gy vs. 1.3±0.1, respectively; p0...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28195448/mitochondrion-anchoring-photosensitizer-with-aggregation-induced-emission-characteristics-synergistically-boosts-the-radiosensitivity-of-cancer-cells-to-ionizing-radiation
#7
Chris Y Y Yu, Huae Xu, Shenglu Ji, Ryan T K Kwok, Jacky W Y Lam, Xiaolin Li, Sunil Krishnan, Dan Ding, Ben Zhong Tang
The first mitochondrion-anchoring photosensitizer that specifically generates singlet oxygen ((1) O2 ) in mitochondria under white light irradiation that can serve as a highly effective radiosensitizer is reported here, significantly sensitizing cancer cells to ionizing radiation. An aggregation-induced emission luminogen (AIEgen), namely DPA-SCP, is rationally designed with α-cyanostilbene as a simple building block to reveal AIE, diphenylamino (DPA) group as a strong electron donating group to benefit red emission and efficient light-controlled (1) O2 generation, as well as a pyridinium salt as the targeting moiety to ensure specific mitochondrial localization...
February 13, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28195253/diagnostic-role-of-detecting-hpv-in-a-fnac-of-metastatic-laterocervical-lymph-node-in-a-case-of-occult-hpv-related-head-and-neck-squamous-cell-carcinoma
#8
A Ginori, F Scaramuzzino, M A G Munezero Butorano, A Barone, A Disanto
Human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCC) are radiosensitive tumors and have a better prognosis than the conventional keratinizing HNSCC. Despite extensive radiographic and clinical evaluation in approximately 3% to 5% of patients who present with cervical lymph node metastases, the primary tumor remains occult. The lack of a clinically identifiable primary tumor usually leads to more aggressive therapy, which can result in higher morbidity. Herein, we report a case of a patient with an occult HPV-related HNSCC, diagnosed detecting HPV in a fine needle aspiration cytology (FNAC) of metastatic laterocervical lymph nodes...
June 2016: Pathologica
https://www.readbyqxmd.com/read/28194032/tumour-specific-pi3k-inhibition-via-nanoparticle-targeted-delivery-in-head-and-neck-squamous-cell-carcinoma
#9
Aviram Mizrachi, Yosi Shamay, Janki Shah, Samuel Brook, Joanne Soong, Vinagolu K Rajasekhar, John L Humm, John H Healey, Simon N Powell, José Baselga, Daniel A Heller, Adriana Haimovitz-Friedman, Maurizio Scaltriti
Alterations in PIK3CA, the gene encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3Kα), are frequent in head and neck squamous cell carcinomas. Inhibitors of PI3Kα show promising activity in various cancer types, but their use is curtailed by dose-limiting side effects such as hyperglycaemia. In the present study, we explore the efficacy, specificity and safety of the targeted delivery of BYL719, a PI3Kα inhibitor currently in clinical development in solid tumours. By encapsulating BYL719 into P-selectin-targeted nanoparticles, we achieve specific accumulation of BYL719 in the tumour milieu...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193559/dual-functional-mesoporous-silicon-nanoparticles-enhance-the-radiosensitivity-of-vpa-in-glioblastoma
#10
Hailong Zhang, Wei Zhang, Yong Zhou, Yuhua Jiang, Shupeng Li
Radiotherapy is a critical strategy and standard adjuvant approach to glioblastoma treatment. One of the major challenges facing radiotherapy is to minimize radiation damage to normal tissue without compromising therapeutic effects on cancer cells. Various agents and numerous approaches have been developed to improve the therapeutic index of radiotherapy. Among them, radiosensitizers have attracted much attention because they selectively increase susceptibility of cancer cells to radiation and thus enhance biological effectiveness of radiotherapy...
February 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28187100/prognostic-significance-of-the-standardized-uptake-value-of-pretherapeutic-18f-labeled-2-fluoro-2-deoxyglucose-positron-emission-tomography-computed-tomography-in-patients-with-locally-advanced-cervical-cancer
#11
Ajit Gubbi, Shimoni Kacheria, Sarfraz Ahmad, Nicole M Stavitzski, James E Kendrick
OBJECTIVES: To determine the prognostic significance of the pretreatment and posttreatment maximum standardized uptake value (SUVmax) of F-labeled 2-fluoro-2-deoxyglucose positron emission tomography (PET)/computed tomography imaging in patients with stage IB2-IVA cervical cancer. METHODS: This was a retrospective review of cervical cancer patients with International Federation of Gynecology and Obstetrics stages IB2-IVA, from March 2008 to April 2014. All patients had pretreatment and posttreatment PET imaging and received primary whole pelvic radiation therapy with concurrent radiosensitizing chemotherapy, followed by intracavitary brachytherapy...
March 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28186989/inhibiting-dna-pkcs-in-a-non-homologous-end-joining-pathway-in-response-to-dna-double-strand-breaks
#12
Jun Dong, Tian Zhang, Yufeng Ren, Zhenyu Wang, Clifton C Ling, Fuqiu He, Gloria C Li, Chengtao Wang, Bixiu Wen
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185938/folate-targeted-nanoparticle-delivery-of-androgen-receptor-shrna-enhances-the-sensitivity-of-hormone-independent-prostate-cancer-to-radiotherapy
#13
Xinjun Zhang, Nianli Liu, ZhiYing Shao, Hui Qiu, Hong Yao, JiaYin Ji, Jianshe Wang, Wenchao Lu, Ronald C Chen, Longzhen Zhang
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro...
February 6, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28184999/rosiglitazone-enhances-radiosensitivity-by-inhibiting-repair-of-dna-damage-in-cervical-cancer-cells
#14
Zhengzhe An, Jae-Ran Yu, Woo-Yoon Park
Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated...
February 9, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28184943/analysis-of-chromosomal-radiosensitivity-of-healthy-brca2-mutation-carriers-and-non-carriers-in-brca-families-with-the-g2-micronucleus-assay
#15
Annelot Baert, Julie Depuydt, Tom Van Maerken, Bruce Poppe, Fransiska Malfait, Tim Van Damme, Sylvia De Nobele, Gianpaolo Perletti, Kim De Leeneer, Kathleen B M Claes, Anne Vral
Breast cancer risk drastically increases in individuals with a heterozygous germline BRCA1 or BRCA2 mutation, while it is estimated to equal the population risk for relatives without the familial mutation (non-carriers). The aim of the present study was to use a G2 phase-specific micronucleus assay to investigate whether lymphocytes of healthy BRCA2 mutation carriers are characterized by increased radiosensitivity compared to controls without a family history of breast/ovarian cancer and how this relates to healthy non-carrier relatives...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28184930/resveratrol-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cells-by-downregulating-e2f1
#16
Yuhui Tan, Xianli Wei, Wenyin Zhang, Xiaolan Wang, Kun Wang, Biaoyan Du, Jianyong Xiao
Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28180110/assessing-tumor-oxygenation-for-predicting-outcome-in-radiation-oncology-a-review-of-studies-correlating-tumor-hypoxic-status-and-outcome-in-the-preclinical-and-clinical-settings
#17
REVIEW
Florence Colliez, Bernard Gallez, Bénédicte F Jordan
Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28179317/hypofractionated-palliative-radiotherapy-with-concurrent-radiosensitizing-chemotherapy-for-advanced-head-and-neck-cancer-using-the-quad-shot-regimen
#18
Mauricio E Gamez, Manuj Agarwal, Kenneth S Hu, John N Lukens, Louis B Harrison
AIM: To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. MATERIALS AND METHODS: We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. RESULTS: All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28170128/effect-of-the-histone-deacetylase-inhibitor-resminostat-on-head-and-neck-squamous-cell-carcinoma-cell-lines
#19
Elisabeth Enzenhofer, Lorenz Kadletz, Isabella Stanisz, Ulana Kotowski, Rudolf Seemann, Rainer Schmid, Dietmar Thurnher, Gregor Heiduschka
BACKGROUND: Carcinogenesis is determined by various epigenetic events, such as histone deacetylation. The purpose of this study was to investigate the effect of the new histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma (HNSCC) cell lines. METHODS: The cytotoxicity of resminostat and cisplatin on HNSCC cell lines SCC25, CAL27, and FaDu was determined using CCK-8 cell proliferation assay and combination index analysis. Cells were irradiated with 2 to 8 Gray...
February 7, 2017: Head & Neck
https://www.readbyqxmd.com/read/28164103/nanodiamonds-and-nanoparticles-as-tumor-cell-radiosensitizers-promising-results-but-an-obscure-mechanism-of-action
#20
COMMENT
Martin Falk
No abstract text is available yet for this article.
January 2017: Annals of Translational Medicine
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