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https://www.readbyqxmd.com/read/29348875/radiosensitization-of-the-pi3k-inhibitor-hs-173-through-reduction-of-dna-damage-repair-in-pancreatic-cancer
#1
Jung Hee Park, Kyung Hee Jung, Soo Jung Kim, Zhenghuan Fang, Hong Hua Yan, Mi Kwon Son, Juyoung Kim, Yeo Wool Kang, Ji Eun Lee, Boreum Han, Joo Han Lim, Soon-Sun Hong
Activation of PI3K/AKT pathway occurs frequently in tumors and is correlated with radioresistance. The PI3K/AKT pathway can be an important target for improvement of radiotherapy. Although adding of chemotherapy to radiation therapy regimen enhances survival in patients with locally advanced pancreatic cancer, more effective therapies for increasing radiosensitivity are urgently needed. In this study, we investigated whether the novel PI3K inhibitor HS-173 could attenuate radiation-induced up-regulation of DNA damage repair processes and assessed its efficacy as a radio- and chemo-sensitizer...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348437/first-experimental-proof-of-proton-boron-capture-therapy-pbct-to-enhance-protontherapy-effectiveness
#2
G A P Cirrone, L Manti, D Margarone, G Petringa, L Giuffrida, A Minopoli, A Picciotto, G Russo, F Cammarata, P Pisciotta, F M Perozziello, F Romano, V Marchese, G Milluzzo, V Scuderi, G Cuttone, G Korn
Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy's superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346681/optimal-number-and-sizes-of-the-doses-in-fractionated-radiotherapy-according-to-the-lq-model
#3
C Bruni, F Conte, F Papa, C Sinisgalli
We address a non-linear programming problem to find the optimal scheme of dose fractionation in cancer radiotherapy. Using the LQ model to represent the response to radiation of tumour and normal tissues, we formulate a constrained non-linear optimization problem in terms of the variables number and sizes of the dose fractions. Quadratic constraints are imposed to guarantee that the damages to the early and late responding normal tissues do not exceed assigned tolerable levels. Linear constraints are set to limit the size of the daily doses...
January 15, 2018: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/29345285/the-epitranscriptome-m6a-writer-mettl3-promotes-chemo-and-radioresistance-in-pancreatic-cancer-cells
#4
Kosuke Taketo, Masamitsu Konno, Ayumu Asai, Jun Koseki, Masayasu Toratani, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii, Kazuhiko Ogawa
N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m6A epitranscriptomics, indicating its crucial roles in the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m6A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m6A is significant for each of the numerous genes remain unclear...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344296/cdk16-phosphorylates-and-degrades-p53-to-promote-radioresistance-and-predicts-prognosis-in-lung-cancer
#5
Jie Xie, Yan Li, Ke Jiang, Kaishun Hu, Sheng Zhang, Xiaorong Dong, Xiaofang Dai, Li Liu, Tao Zhang, Kunyu Yang, Kai Huang, Junjie Chen, Shaojun Shi, Yu Zhang, Gang Wu, Shuangbing Xu
Rationale: Radioresistance is considered the main cause of local relapse in lung cancer. However, the molecular mechanisms of radioresistance remain poorly understood. This study investigates the role of CDK16 in radioresistance of human lung cancer cells. Methods: The expression levels of CDK16 were determined by immunohistochemistry in lung cancer tissues and adjacent normal lung tissues. Immunoprecipitation assay and GST pulldown were utilized to detect the protein-protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase assay...
2018: Theranostics
https://www.readbyqxmd.com/read/29344203/mucin-1-promotes-radioresistance-in-hepatocellular-carcinoma-cells-through-activation-of-jak2-stat3-signaling
#6
Feng-Tao Yi, Qi-Ping Lu
Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29341150/effect-of-akt-activation-and-experimental-pharmacological-inhibition-on-responses-to-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#7
F C Koyama, C M Lopes Ramos, F Ledesma, V A F Alves, J M Fernandes, B B Vailati, G P São Julião, A Habr-Gama, J Gama-Rodrigues, R O Perez, A A Camargo
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. METHODS: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal verge...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29336987/the-in-vitro-radiosensitizer-potential-of-resveratrol-on-mcf-7-breast-cancer-cells
#8
Isabel Cristina da Costa Araldi, Fernando Primitivo Romero Bordin, Francine Carla Cadoná, Fernanda Barbisan, Verônica Farina Azzolin, Cibele Ferreira Teixeira, Tadeu Baumhardt, Ivana Beatrice Mânica da Cruz, Marta Maria Medeiros Frescura Duarte, Liliane de Freitas Bauermann
Radiation therapy is commonly applied in breast cancer (BC) patients. However, radioresistance and side effects are limiting factors of this practice. Therefore, studying substances that can enhance the radiation effect and, at the same time, protect normal cells is very relevant. Thus, the aim of this work was to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A high cytotoxic and antiproliferative effect was observed in the treatment with 10 μM of RV + 3 Gy ionizing radiation (IR)...
January 11, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29331678/microrna-320-enhances-radiosensitivity-of-glioma-through-down-regulation-of-sirtuin-type-1-by-directly-targeting-forkhead-box-protein-m1
#9
Tengfei Li, Ji Ma, Xinwei Han, Yongxu Jia, Huifeng Yuan, Shaofeng Shui, Dong Guo
Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively...
January 10, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29328411/dna-methylation-enzyme-inhibitor-rg108-suppresses-the-radioresistance-of-esophageal-cancer
#10
Yao Ou, Quan Zhang, Yiting Tang, Zhonghua Lu, Xujing Lu, Xifa Zhou, Changmin Liu
Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca‑109 and TE‑1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca‑109 cells were inoculated into nude mice to establish tumors...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#11
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29322791/targeting-rad50-increases-sensitivity-to-radiotherapy-in-colorectal-cancer-cells
#12
C Chen, Y Wang, J F Mei, S S Li, H X Xu, H P Xiong, X H Wang, X He
Radiotherapy resistance remains the major factor limiting the radiotherapy efficacy in colorectal cancer. The Mre11-RAD50-Nbs1 (MRN) complex is known to play a critical role in the DNA double strand breaks (DSBs) repair pathways and thus facilitates radioresistance. Targeting MRN function can sensitize cancer cells to irradiation in some malignancies. In this study, we stably knocked down RAD50 protein in colorectal cancer (CRC) cell lines, HCT116 and DLD1, and evaluated their response to irradiation as well as the DSB repair dynamics...
2018: Neoplasma
https://www.readbyqxmd.com/read/29320576/targeting-dna-repair-with-pnkp-inhibition-sensitizes-radioresistant-prostate-cancer-cells-to-high-let-radiation
#13
Pallavi Srivastava, Asitikantha Sarma, Chandra Mohini Chaturvedi
High linear energy transfer (LET) radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator...
2018: PloS One
https://www.readbyqxmd.com/read/29318915/the-overexpression-of-pxn-promotes-tumor-progression-and-leads-to-radioresistance-in-cervical-cancer
#14
Qiuli Liu, Jing Wang, Mei Tang, Ling Chen, Xiaowei Qi, Juan Li, Jinjin Yu, Haifeng Qiu, Yuan Wang
AIM: We aim to investigate the functions of PXN in cervical cancer. MATERIALS & METHODS: PXN protein was investigated by immunohistochemistry in a panel of cervical cancer. A series of in vitro and in vivo assays were used to explore the efficacy of PXN. RESULTS: PXN was significantly upregulated in cervical cancer, which associated with tumor stage, poor differentiation, lymphovascular space invasion and lymphatic metastasis. Knockdown of PXN notably impaired cellular growth and colony formation by suppressing Bcl-2 and inducing marked apoptosis...
January 10, 2018: Future Oncology
https://www.readbyqxmd.com/read/29316943/are-prognostic-indices-for-brain-metastases-of-melanoma-still-valid-in-the-stereotactic-era
#15
Harun Badakhshi, Fidelis Engeling, Volker Budach, Pirus Ghadjar, Sebastian Zschaeck, David Kaul
BACKGROUND: Malignant melanoma brain metastases (MBM) are the third most common cause for brain metastases (BM). Historically Whole-brain radiotherapy (WBRT) was considered the goldstandard of treatment even though melanoma cells are regarded as very radioresistant. Therapeutic possibilities have fundamentally changed since the availability of stereotactic radiotherapy (SRT), where it is possible to apply high ablative doses in a very precise manner. In this work we analyze prognostic factors of overall survival (OS) after SRT in patients with MBM and evaluate the applicability of popular prognostic indices that mainly stem from the WBRT-era...
January 10, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29311662/evidence-for-a-radiation-responsive-p53-gateway-contributing-significantly-to-the-radioresistance-of-lepidopteran-insect-cells
#16
Ashish Kumar, Sudhir Chandna
Recently, we have demonstrated that microRNA-31 (miR-31) overexpression is inherent to radiation-induced cell death in the highly radioresistant Sf9 insect cells, and regulates pro-apoptotic Bax translocation to mitochondria. In the present study, we report that at sub-lethal radiation doses for Sf9 cells, miR-31 is significantly downregulated and is tightly regulated by an unusual mechanism involving p53. While ectopic overexpression of a well-conserved Sfp53 caused typical apoptosis, radiation-induced p53 accumulation observed selectively at sub-lethal doses failed to induce cell death...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29307045/a-comparison-of-cell-survival-and-heat-shock-protein-expression-after-radiation-in-normal-dermal-fibroblasts-microvascular-endothelial-cells-and-different-head-and-neck-squamous-carcinoma-cell-lines
#17
Dominique Muschter, Fabian Geyer, Richard Bauer, Tobias Ettl, Stephan Schreml, Frank Haubner
OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) shows increased radioresistance due to the manipulation of homeostatic mechanisms like the heat shock response. This study intended to comparatively analyze effects of ionizing radiation on different HNSCC cell lines (PCI) and normal human dermal fibroblasts (NHFs) and human dermal microvascular endothelial cells (HDMECs) to uncover differences in radiation coping strategies. MATERIALS AND METHODS: Proliferation (BrdU assay), apoptosis (caspase 3/7) and intracellular protein expression of heat shock protein (HSP)-70, and phosphorylated and total HSP27, determined by enzyme-linked immunosorbent assay (ELISA), were analyzed after exposure to increasing doses of ionizing radiation (2, 6, and 12 Gray, Gy)...
January 6, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29305710/ecto-5-nucleotidase-cd73-contributes-to-the-radiosensitivity-of-t24-human-bladder-cancer-cell-line
#18
Fabrícia Dietrich, Fabrício Figueiró, Eduardo Cremonese Filippi-Chiela, Angélica Regina Cappellari, Liliana Rockenbach, Alain Tremblay, Patrícia Boni de Paula, Rafael Roesler, Aroldo Braga Filho, Jean Sévigny, Fernanda Bueno Morrone, Ana Maria Oliveira Battastini
PURPOSE: Trimodal therapy is a reasonable bladder-preserving option to radical cystectomy. However, many tumors are radioresistive. In this sense, the identification of new prognostic and predictive biomarkers that allow the selection of patients with better responses to radiation therapy would improve outcomes. With the aim of using ecto-5'-nucleotidase/CD73 as a predictive biomarker, the role of this enzyme in the context of radiotherapy in T24 human bladder cancer cell line was investigated...
January 5, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29301323/programming-of-cell-resistance-to-genotoxic-and-oxidative-stress
#19
REVIEW
Ilya O Velegzhaninov, Vitaly A Ievlev, Yana I Pylina, Dmitry M Shadrin, Olesya M Vakhrusheva
Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increase the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, which can be used for manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review, we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance...
January 2, 2018: Biomedicines
https://www.readbyqxmd.com/read/29299738/recursive-partitioning-analysis-is-predictive-of-overall-survival-for-patients-undergoing-spine-stereotactic-radiosurgery
#20
Ehsan H Balagamwala, Jacob A Miller, Chandana A Reddy, Lilyana Angelov, John H Suh, Muhammad B Tariq, Erin S Murphy, Kailin Yang, Toufik Djemil, Anthony Magnelli, Alireza M Mohammadi, Sherry Soeder, Samuel T Chao
Spine stereotactic radiosurgery (SRS) offers excellent radiographic and pain control for patients with spine metastases. We created a prognostic index using recursive partitioning analysis (RPA) to allow better patient selection for spine SRS. Patients who underwent single-fraction spine SRS for spine metastases were included. Primary histologies were divided into favorable (breast/prostate), radioresistant (renal cell/sarcoma/melanoma) and other. Cox proportional hazards regression was done to identify factors associated with overall survival (OS)...
January 3, 2018: Journal of Neuro-oncology
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