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https://www.readbyqxmd.com/read/28642964/metastasis-of-breast-cancer-cells-to-the-bone-lung-and-lymph-nodes-promotes-resistance-to-ionizing-radiation
#1
Takamitsu Hara, Manabu Iwadate, Kazunoshin Tachibana, Satoshi Waguri, Seiichi Takenoshita, Nobuyuki Hamada
BACKGROUND: Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant. MATERIALS AND METHODS: A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times...
June 22, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28642840/cytolethal-distending-toxin-enhances-radiosensitivity-in-prostate-cancer-cells-by-regulating-autophagy
#2
Hwai-Jeng Lin, Hsin-Ho Liu, Chia-Der Lin, Min-Chuan Kao, Yu-An Chen, Chuan Chiang-Ni, Zhi-Pei Jiang, Mei-Zi Huang, Chun-Jung Lin, U-Ging Lo, Li-Chiung Lin, Cheng-Kuo Lai, Ho Lin, Jer-Tsong Hsieh, Cheng-Hsun Chiu, Chih-Ho Lai
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28640996/a-polyoxometalate-based-radiosensitization-platform-for-treating-hypoxic-tumor-by-attenuating-radio-resistance-and-enhancing-radiation-response
#3
Yuan Yong, Chunfang Zhang, Zhanjun Gu, Jiangfeng Du, Zhao Guo, Xinghua Dong, Jiani Xie, Guangjin Zhang, Xiangfeng Liu, Yuliang Zhao
Radioresistance is one of the undesirable impediments in hypoxia tumor, which sharply diminishes therapeutic effectiveness of radiotherapy and eventually results in the failure of their treatments. An attractive strategy for attenuating radioresistance is developing an ideal radiosensitization system with admirable radiosensitization capacity to attenuate tumor hypoxia and reinforce radiotherapy response in hypoxia tumor. Therefore, we describe the development of Gd-containing polyoxometalates-conjugated chitosan (GdW10@CS nanosphere) as a radiosensitization system for simultanous extrinsic and intrinsic radiosensitization, by generating overabundance cytotoxic reactive oxygen species (ROS) using high energy X-ray stimulation and mediating the hypoxia-inducible factor-1a (HIF-1a) siRNA to down-regulate HIF-1α expression and suppress the broken double-stranded DNA self-healing...
June 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28638454/downregulation-of-mitochondrial-single-stranded-dna-binding-protein-ssbp1-induces-mitochondrial-dysfunction-and-increases-the-radiosensitivity-in-non-small-cell-lung-cancer-cells
#4
You Wang, Liu Hu, Ximei Zhang, Hong Zhao, Hui Xu, Yuehua Wei, Huangang Jiang, Conghua Xie, Yunfeng Zhou, Fuxiang Zhou
Radiotherapy is one of the major therapeutic strategies for human non-small cell lung cancer (NSCLC), but intrinsic radioresistance of cancer cells makes a further improvement of radiotherapy for NSCLC challenging. Mitochondrial function is frequently dysregulated in cancer cells for adaptation to the changes of tumor microenvironment after exposure to radiation. Therefore, targeting mitochondrial biogenesis and bioenergetics is an attractive strategy to sensitize cancer cells to radiation therapy. In this study, we found that downregulation of single-strand DNA-binding protein 1 (SSBP1) in H1299 cells was associated with inducing mitochondrial dysfunction and increasing radiosensitivity to ionizing radiation...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28636807/targeting-protein-for-xenopus-kinesin-like-protein-2-knockdown-enhances-radiation-sensitivity-of-human-lung-squamous-carcinoma-cell
#5
Jie Yang, Feng Gao, Xinjian Xu, Yuxiang Wang, Shuchai Zhu
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been demonstrated to be associated with the tumorigenesis of many cancers. In the present study, we investigated the role and preliminary mechanism of TPX2 in the resistance of lung squamous carcinoma to radiation therapy. The results showed that SK-MES-1R and NCI-H226R cells were more resistant to X-ray irradiation than the parental cells (SK-MES-1 and NCI-H226). Moreover, TPX2 was upregulated in the radioresistant cells compared with the parental cells...
June 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28631740/radiotherapy-for-renal-cell-carcinoma-renaissance-of-an-overlooked-approach
#6
REVIEW
Shankar Siva, Gargi Kothari, Alexander Muacevic, Alexander V Louie, Ben J Slotman, Bin S Teh, Simon S Lo
Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC...
June 20, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28627761/biological-effects-of-hydrogen-peroxide-administered-intratumorally-with-or-without-irradiation-in-murine-tumors
#7
Taiki Takaoka, Yuta Shibamoto, Masayuki Matsuo, Chikao Sugie, Taro Murai, Yasutaka Ogawa, Akifumi Miyakawa, Yoshihiko Manabe, Takuhito Kondo, Koichiro Nakajima, Dai Okazaki, Takahiro Tsuchiya
Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used...
June 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28627706/the-wnt-inhibitor-lgk-974-enhances-radiosensitivity-of-hepg2-cells-by-modulating-nrf2-signaling
#8
Dan Tian, Ying Shi, Dexi Chen, Qiang Liu, Feiyue Fan
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of antioxidant and detoxification activities that can eliminate reactive oxygen species (ROS) produced via irradiation. However, Nrf2 overexpression in liver cancer cells may cause both radioresistance and chemoresistance. Reducing Nrf2 levels can enhance the radiosensitivity of HepG2 cells. Wingless/int-3A (Wnt3A) is a Wnt family protein that mainly activates the canonical Wnt signaling pathway. Recent studies showed that the Axin1-GSK-3β protein complex, a component of the canonical Wnt signaling pathway, can capture Nrf2 and facilitate its ubiquitination and proteasomal degradation in the cytoplasm...
June 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624789/pediatric-and-adult-glioblastoma-radiosensitization-induced-by-pi3k-mtor-inhibition-causes-early-metabolic-alterations-detected-by-nuclear-magnetic-resonance-spectroscopy
#9
Alice Agliano, Geetha Balarajah, Daniela M Ciobota, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Martin O Leach, Nada M S Al-Saffar
Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. In this study, we show that NVP-BEZ235, a dual PI3K/mTOR inhibitor, potentiates the effects of irradiation in both adult and pediatric glioblastoma cell lines, resulting in early metabolic changes detected by nuclear magnetic resonance (NMR) spectroscopy. NVP-BEZ235 radiosensitises cells to X ray exposure, inducing cell death through the inhibition of CDC25A and the activation of p21cip1(CDKN1A)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621688/radioresistance-of-mesenchymal-glioblastoma-initiating-cells-correlates-with-patient-outcome-and-is-associated-with-activation-of-inflammatory-program
#10
Elisabetta Stanzani, Fina Martínez-Soler, Teresa Martín Mateos, Noemi Vidal, Alberto Villanueva, Miquel Angel Pujana, Jordi Serra-Musach, Núria de la Iglesia, Pepita Giménez-Bonafé, Avelina Tortosa
Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and Glioblastoma-Initiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro model and addressed molecular programs activated in GICs after RT. Established GICs heterogeneously expressed several GICs markers and displayed a mesenchymal signature. Upon fractionated RT, GICs reported higher radioresistance compared to non-GICs and showed lower α- and β-values, according to the Linear Quadratic Model interpretation of the survival curves...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620444/clinical-utility-of-pretreatment-prediction-of-chemoradiotherapy-response-in-rectal-cancer-a-review
#11
REVIEW
Byong Chul Yoo, Seung-Gu Yeo
Approximately 20% of all patients with locally advanced rectal cancer experience pathologically complete responses following neoadjuvant chemoradiotherapy (CRT) and standard surgery. The utility of radical surgery for patients exhibiting good CRT responses has been challenged. Organ-sparing strategies for selected patients exhibiting complete clinical responses include local excision or no immediate surgery. The subjects of this tailored management are patients whose presenting disease corresponds to current indications of neoadjuvant CRT, and their post-CRT tumor response is assessed by clinical and radiological examinations...
March 2017: EPMA Journal
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#12
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28612593/2-methoxyestradiol-promotes-radiosensitivity-of-esophageal-squamous-cell-carcinoma-by-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#13
Yanrong Lu, Jia Song, Zhabihula Baerxiaguli, Zengyan Li, Min Wu, Jinrong Zhang
Background: Acquired radioresistance remains a primary obstacle to improving survival of patients with esophageal cancer(EC). Factors related to hypoxia play crucial roles in such radioresistance, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiogenic factor with G-patch and FHA domains 1 (AGGF1). However, evidence clarifying the role of AGGF1 in EC is limited. We here aimed to investigate the effects of 2-methoxyestradiol(2ME2) on the radiosensitivity of EC...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28611417/direct-evidence-for-cell-adhesion-mediated-radioresistance-cam-rr-on-the-level-of-individual-integrin-%C3%AE-1-clusters
#14
Laura Babel, Miriam Grunewald, Robert Lehn, Markus Langhans, Tobias Meckel
The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as "cell-adhesion-mediated-radio-resistance" (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609167/hdr-brachytherapy-decreases-proliferation-rate-and-cellular-progression-of-a-radioresistant-human-squamous-cell-carcinoma-in-vitro
#15
Jony M Geraldo, Sérgio Scalzo, Daniela S Reis, Thiago L Leão, Silvia Guatimosim, Luiz O Ladeira, Lídia M Andrade
PURPOSE: To investigate the effects of HDR brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters. MATERIALS AND METHODS: An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated two times up to 1100cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay...
June 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28607587/impact-of-cd44-expression-on-radiation-response-for-bladder-cancer
#16
Chun-Te Wu, Wei-Yu Lin, Ying-Hsu Chang, Wen-Cheng Chen, Miao-Fen Chen
Background Identification of potential factors that can stratify tumors' response to specific therapies will aid in the selection of cancer therapy. Radioresistance is the major obstacles to positive outcomes in bladder cancer patients after definite chemotherapy. CD44, a cancer stem cell surface marker, is relevant in treatment resistance. In the present study, we examined the role of CD44 in bladder cancer. Methods We retrospectively analyzed the clinical outcomes of 85 bladder cancer patients treated with definite chemoradiotherapy, and correlated the expressions of CD44 with IL-6 and treatment response...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28607172/tweety-homologue-1-drives-brain-colonization-of-gliomas
#17
Erik Jung, Matthias Osswald, Jonas Blaes, Benedikt Wiestler, Felix Sahm, Torsten Schmenger, Gergely Solecki, Katrin Deumelandt, Felix T Kurz, Ruifan Xie, Sophie Weil, Oliver Heil, Carina Thomé, Miriam Gömmel, Mustafa Syed, Peter Häring, Peter E Huber, Sabine Heiland, Michael Platten, Andreas von Deimling, Wolfgang Wick, Frank Winkler
Early and progressive colonization of the healthy brain is one hallmark of diffuse gliomas, including glioblastomas. Recently we have discovered ultra-long (> ten to hundreds of microns) membrane protrusions (tumor microtubes, TMs) that are extended by glioma cells. TMs were associated with the capacity of glioma cells to effectively invade the brain, and proliferate. Moreover, TMs were also used by some tumor cells to interconnect to one large, resistant multicellular network. Here, we performed a correlative gene expression microarray and in vivo imaging analysis, and identified novel molecular candidates for TM formation and function...
June 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28604998/role-of-radiotherapy-in-the-treatment-of-renal-cell-cancer-updated-and-critical-review
#18
Vincenzo Fusco, Salvatore Parisi, Barbara d'Andrea, Michele Troiano, Maria Antonietta Clemente, Franco Morelli, Rocchina Caivano, Giuseppe Guglielmi
PURPOSE: The growing incidence of renal cell carcinoma (RCC) raises many questions about the management of these patients. The late clinical presentation, the presence of locally advanced or metastatic disease at diagnosis, the difficulty of radical surgical excision, and radioresistance make it one of the more challenging tumors to treat. The primary objective of this article is to propose an updated and critical review of the role of radiotherapy (RT) in the treatment of RCC. METHODS: This literature review is based on data from meta-analyses and randomized, prospective, and retrospective studies...
June 6, 2017: Tumori
https://www.readbyqxmd.com/read/28598290/delayed-growth-suppression-and-radioresistance-induced-by-long-term-continuous-gamma-irradiation
#19
Hiroo Nakajima, Chiharu Furukawa, Young-Chae Chang, Hiromitsu Ogata, Junji Magae
Biological response to ionizing radiation depends not only on the type of radiation and dose, but also on the duration and dose rate of treatment. For a given radiation dose, the biological response may differ based on duration and dose rate. We studied the properties of two human cell lines, M059K glioma and U2OS osteosarcoma, continuously exposed to γ rays for long time periods of more than five months. Growth inhibition in both cell lines was dependent on total dose when exposed to acute radiation over several minutes, whereas prolonged growth inhibition was dependent on dose rate after continuous irradiation over several months...
June 9, 2017: Radiation Research
https://www.readbyqxmd.com/read/28592117/mechanisms-regulating-radiosensitivity-of-glioma-stem-cells
#20
Y Liu, Y Shen, T Sun, W Yang
Malignant glioblastoma (GBM) has become a very common and difficult brain tumor given its low cure rate and high recurrence rate. GBMs are resistant to treatments because glioma stem cells (GSCs)/glioma-initiating cells (GICs), a specific subpopulation of GBM, possess properties of tumor stem cells, such as unlimited proficiency, self-renewal, differentiation and resistance to chemotherapy and radiotherapy, and exhibit a very strong DNA repair capability. Radiotherapy has become a preponderant treatment, and researchers have found many significant tumor microenvironmental factors and valuable signaling pathways regulating the GSC radioresistance, including NOTCH, Wnt/β-catenin, Hedgehog, STAT3, and PI3K/AKT/mTOR...
June 8, 2017: Neoplasma
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