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https://read.qxmd.com/read/30776452/pravastatin-reverses-established-radiation-induced-cutaneous-and-subcutaneous-fibrosis-in-patients-with-head-and-neck-cancer-results-of-the-biology-driven-phase-ii-clinical-trial-pravacur
#1
Celine Bourgier, Anne Auperin, Sofia Rivera, Pierre Boisselier, Benoit Petit, Philippe Lang, Nathalie Lassau, Patrice Taourel, Raphael Tetreau, David Azria, Jean Bourhis, Eric Deutsch, Marie-Catherine Vozenin
PURPOSE: The "xxx" phase II trial (NCTxxx) assessed the efficacy of pravastatin as anti-fibrotic agent in patients with established cutaneous and subcutaneous radiation-induced fibrosis (RIF) after head and neck squamous cell carcinoma (HNSCC) radiotherapy and/or radio-chemotherapy. METHODS AND MATERIALS: The main inclusion criteria were: patients with HNSCC in remission, with grade ≥2 cutaneous and subcutaneous neck RIF (NCI-CTCAE v4.0); no current treatment with statins or fibrates...
February 15, 2019: International Journal of Radiation Oncology, Biology, Physics
https://read.qxmd.com/read/30774379/effects-of-combined-inhibition-of-stat3-and-vegfr2-pathways-on-the-radiosensitivity-of-non-small-cell-lung-cancer-cells
#2
Chenxi Hu, Wei Zhuang, Yun Qiao, Bin Liu, Liang Liu, Kaiyuan Hui, Xiaodong Jiang
Purpose: The goals of this study were to determine the effects of combined inhibition of STAT3 and vascular endothelial growth factor receptor 2 (VEGFR2) pathways on the radiosensitivity of non-small-cell lung cancer (NSCLC) cells, and to assess the underlying mechanisms. Methods: The expressions of VEGFR2, STAT3, related signaling molecules, hypoxia-inducible factor 1-alpha (HIF-1α), and cyclin D1 were determined by Western blotting. Radiosensitivity was assessed using the colony-forming assay, and cell cycle and cell death were analyzed by flow cytometry...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30771458/rlip-an-existential-requirement-for-breast-carcinogenesis
#3
REVIEW
Sharad S Singhal, Ravi Salgia, Sulabh Singhal, David Horne, Sanjay Awasthi
Breast cancer (BC) is the most common cancer among women worldwide. Due to its complexity in nature, effective BC treatment can encounter many challenges. The human RALBP1 gene encodes a 76-kDa splice variant protein, RLIP (ral-binding protein1, RalBP1), a stress-protective mercapturic acid pathway (MAP) transporter protein, that also plays a key role in regulating clathrin-dependent endocytosis (CDE) as a Ral effector. Growing evidence shows that targeting RLIP may be an effective strategy in cancer therapy, as RLIP is over-expressed in multiple cancers and is known to induce resistance to apoptosis and chemotherapeutic drugs...
February 13, 2019: Biochimica et biophysica acta. Reviews on cancer
https://read.qxmd.com/read/30771428/usp39-regulates-dna-damage-response-and-chemo-radiation-resistance-by-deubiquitinating-and-stabilizing-chk2
#4
Jinhuan Wu, Yuping Chen, Guohe Geng, Lei Li, Ping Yin, Somaira Nowsheen, Yunhui Li, Chenming Wu, Jiaqi Liu, Fei Zhao, Wootae Kim, Qin Zhou, Jinzhou Huang, Guijie Guo, Chao Zhang, Xinyi Tu, Xiumei Gao, Zhenkun Lou, Kuntian Luo, Haixuan Qiao, Jian Yuan
The serine/threonine kinase, CHK2 (checkpoint kinase 2), is a key mediator in DNA damage response and a tumor suppressor, which is implicated in promoting cell cycle arrest, apoptosis and DNA repair. Accumulating evidence suggests that these functions are primarily exerted through phosphorylation downstream factors such as p53 and BRCA1. Recent studies have shown that ubiquitination is an important mode of regulation of CHK2. However, it remains largely unclear whether deubiquitinases participate in regulation of CHK2...
February 13, 2019: Cancer Letters
https://read.qxmd.com/read/30770789/plod3-suppression-exerts-an-anti-tumor-effect-on-human-lung-cancer-cells-by-modulating-the-pkc-delta-signaling-pathway
#5
Jeong-Hwa Baek, Hong Shik Yun, Gyoo Taik Kwon, Janet Lee, Ju-Young Kim, Yunhui Jo, Jae-Min Cho, Chang-Woo Lee, Jie-Young Song, Jiyeon Ahn, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells...
February 15, 2019: Cell Death & Disease
https://read.qxmd.com/read/30767202/fractionated-ionizing-radiation-facilitates-interferon-%C3%AE-signaling-and-anticancer-activity-in-lung-adenocarcinoma-cells
#6
Szu-Yuan Wu, Chia-Ling Chen, Po-Chun Tseng, Chi-Yun Chiu, Yung-En Lin, Chiou-Feng Lin
Fractionated ionizing radiation (FIR) is a radiotherapy regimen that is regularly performed as part of lung cancer treatment. In contrast to the growth inhibition caused by DNA damage, immunomodulation in post-irradiated cancer cells is not well documented. Interferon (IFN)-γ confers anticancer activity by triggering both growth inhibition and cytotoxicity. This study investigated the priming effects of FIR with immunomodulation on the anticancer IFN-γ. Cell morphology, cell growth, and cytotoxicity were observed in FIR-treated A549 lung adenocarcinoma...
February 14, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30764514/moscatilin-inhibits-growth-of-human-esophageal-cancer-xenograft-and-sensitizes-cancer-cells-to-radiotherapy
#7
Wun-Ke Chen, Chien-An Chen, Chih-Wen Chi, Li-Hui Li, Chin-Ping Lin, Hui-Ru Shieh, Ming-Ling Hsu, Chun-Chuan Ko, Jeng-Jong Hwang, Yu-Jen Chen
Esophageal cancer prognosis remains poor in current clinical practice. We previously reported that moscatilin can induce apoptosis and mitotic catastrophe in esophageal cancer cells, accompanied by upregulation of polo-like kinase 1 (Plk1) expression. We aimed to validate in vitro activity and Plk1 expression in vivo following moscatilin treatment and to examine the treatment's radiosensitizing effect. Human esophageal cancer cells were implanted in nude mice. Moscatilin was intraperitoneally (i.p.) injected into the mice...
February 5, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30764513/reprogramming-of-energy-metabolism-in-response-to-radiotherapy-in-head-and-neck-squamous-cell-carcinoma
#8
REVIEW
Alfredo Cruz-Gregorio, Imelda Martínez-Ramírez, José Pedraza-Chaverri, Marcela Lizano
Head and neck cancer (HNC) is the sixth cause of cancer-related death worldwide. Head and neck squamous cells carcinoma (HNSCC) is the most frequent subtype of HNC. The development of HNSCC is associated to alcohol consumption, smoking or infection by high-risk human Papillomavirus (HR-HPV). Although the incidence of cancers associated with alcohol and tobacco has diminished, HNSCC associated with HR-HPV has significantly increased in recent years. However, HPV-positive HNSCC responds well to treatment, which includes surgery followed by radiation or chemoradiation therapy...
February 5, 2019: Cancers
https://read.qxmd.com/read/30763552/the-lnt-model-for-cancer-induction-is-not-supported-by-radiobiological-data
#9
REVIEW
Bobby R Scott, Sujeenthar Tharmalingam
The hallmarks of cancer have been the focus of much research and have influenced the development of risk models for radiation-induced cancer. However, natural defenses against cancer, which constitute the hallmarks of cancer prevention, have largely been neglected in developing cancer risk models. These natural defenses are enhanced by low doses and dose rates of ionizing radiation, which has aided in the continuation of human life over many generations. Our natural defenses operate at the molecular, cellular, tissue, and whole-body levels and include epigenetically regulated (epiregulated) DNA damage repair and antioxidant production, selective p53-independent apoptosis of aberrant cells (e...
January 21, 2019: Chemico-biological Interactions
https://read.qxmd.com/read/30763548/re-evaluation-of-the-linear-no-threshold-lnt-model-using-new-paradigms-and-modern-molecular-studies
#10
REVIEW
Sujeenthar Tharmalingam, Shayenthiran Sreetharan, Antone L Brooks, Douglas R Boreham
The linear no-threshold (LNT) model is currently used to estimate low dose radiation (LDR) induced health risks. This model lacks safety thresholds and postulates that health risks caused by ionizing radiation is directly proportional to dose. Therefore even the smallest radiation dose has the potential to cause an increase in cancer risk. Advances in LDR biology and cell molecular techniques demonstrate that the LNT model does not appropriately reflect the biology or the health effects at the low dose range...
November 29, 2018: Chemico-biological Interactions
https://read.qxmd.com/read/30763546/review-of-the-evidence-for-thresholds-for-dna-reactive-and-epigenetic-experimental-chemical-carcinogens
#11
REVIEW
Tetyana Kobets, Gary M Williams
In the deliberations over many years on the question of thresholds for the carcinogenicity of chemicals, the dominant paradigm has been the linear no-threshold (LNT) model, derived from concepts formulated in radiation mutagenicity. Based on the analogy with radiation, the key mechanistic assumption underlying the assessment of the dose-effect of chemical-induced carcinogenicity has been that any dose, no matter how low, can lead to induction of mutations, which will result in some risk of neoplasia. The LNT assumption, however, was never well founded and, its application to chemical carcinogens, does not allow for differences in their disposition or mechanisms of action...
November 28, 2018: Chemico-biological Interactions
https://read.qxmd.com/read/30763392/discrimination-of-breast-cancer-from-benign-tumours-using-raman-spectroscopy
#12
Fiona M Lyng, Damien Traynor, Thi Nguyet Que Nguyen, Aidan D Meade, Fazle Rakib, Rafif Al-Saady, Erik Goormaghtigh, Khalid Al-Saad, Mohamed H Ali
Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million cases and 522,000 deaths in 2012. Breast cancer is diagnosed by histopathological examination of breast biopsy material but this is subjective and relies on morphological changes in the tissue. Raman spectroscopy uses incident radiation to induce vibrations in the molecules of a sample and the scattered radiation can be used to characterise the sample. This technique is rapid and non-destructive and is sensitive to subtle biochemical changes occurring at the molecular level...
2019: PloS One
https://read.qxmd.com/read/30760304/low-dose-radiation-regulates-braf-induced-thyroid-cellular-dysfunction-and-transformation
#13
Neha Kaushik, Min-Jung Kim, Nagendra Kumar Kaushik, Jae Kyung Myung, Mi-Young Choi, Jae-Hyeok Kang, Hyuk-Jin Cha, Cha-Soon Kim, Seon-Young Nam, Su-Jae Lee
BACKGROUND: The existence of differentiated thyroid cells is critical to respond radioactive iodide treatment strategy in thyroid cancer, and loss of the differentiated phenotype is a trademark of iodide-refractive thyroid disease. While high-dose therapy has been beneficial to several cancer patients, many studies have indicated this clinical benefit was limited to patients having BRAF mutation. BRAF-targeted paired box gene-8 (PAX8), a thyroid-specific transcription factor, generally dysregulated in BRAF-mutated thyroid cancer...
February 13, 2019: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/30753262/randomized-double-blind-placebo-controlled-trial-evaluating-oral-glutamine-on-radiation-induced-oral-mucositis-and-dermatitis-in-head-and-neck-cancer-patients
#14
Chih-Jen Huang, Ming-Yii Huang, Pen-Tzu Fang, Frank Chen, Yu-Tsang Wang, Chung-Ho Chen, Shyng-Shiou Yuan, Chun-Ming Huang, Kuei-Hau Luo, Hung-Yi Chuang, Yen-Yun Wang, Hsin-Hua Lee
Background: Glutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT). Objectives: The aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT. Methods: This was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital...
February 9, 2019: American Journal of Clinical Nutrition
https://read.qxmd.com/read/30753097/radiation-induced-dna-damage-response-and-resistance-in-colorectal-cancer-stem-like-cells
#15
Kumari Anuja, Amit Roy Chowdhury, Arka Saha, Souvick Roy, Arabinda Kumar Rath, Madhabananda Kar, Birendranath Banerjee
PURPOSE: Radiation therapy is an integral part of current treatment modality for colorectal cancer. Recent studies have revealed the presence of cancer stem-like cells (CSCs) population, in different tumors are responsible for therapeutic resistance and disease relapse, including colorectal cancer with poorer survival rate. Hence, characterization of effect of Ionizing Radiation (IR) in colorectal cancer may serve to explain possible mechanisms. MATERIAL AND METHODS: Parental HCT116 and HCT-15cells and derived clonospheres were irradiated and dose was optimized based on cell survival assay and cell cycle analysis...
February 12, 2019: International Journal of Radiation Biology
https://read.qxmd.com/read/30747221/downregulation-of-bag%C3%A2-1-in-t47d-cells-promotes-resistance-to-tamoxifen-via-activation-of-the-pi3k-akt-mtor-signaling-pathway
#16
Su Lu, Yiyi Du, Fang Cui, Xinyi Feng, Yuanyuan Ma, Hong Liu
Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely used endocrine therapy for patients with ER‑positive breast cancer. However, ~30% of tamoxifen‑treated breast cancers do not initially respond to tamoxifen, and neither do they eventually develop tamoxifen resistance. Bcl‑2‑associated athanogene 1 (BAG‑1) is a multifunctional protein that interacts with a wide range of molecules to protect cells from apoptosis otherwise induced by cytotoxic drugs, growth factor withdrawal, radiation and stress...
January 22, 2019: Oncology Reports
https://read.qxmd.com/read/30746122/radon-induced-mitochondrial-dysfunction-in-human-bronchial-epithelial-cells-and-epithelial-mesenchymal-transition-with-long-term-exposure
#17
Qian Xu, Lijun Fang, Bin Chen, Hong Zhang, Qianqian Wu, Hongbo Zhang, Aiqing Wang, Jian Tong, Shasha Tao, Hailin Tian
Radon is a naturally occurring radionuclide, which has a wide environmental distributed. It emits multiple high linear energy transfer (LET) alpha particles during radiative decay, and has been regarded as a human carcinogen by the International Agency for Research on Cancer. Currently, residential radon exposure is considered as the second highest cause of lung cancer and the leading cause among nonsmokers. Radon exposure leads to genomic instability, which causes the accumulation of multiple genetic changes and leads to cancer development...
January 1, 2019: Toxicology Research
https://read.qxmd.com/read/30745832/polydatin-increases-radiosensitivity-by-inducing-apoptosis-of-stem-cells-in-colorectal-cancer
#18
Qiu Chen, Ya-Nan Zeng, Ke Zhang, Ying Zhao, Yong-You Wu, Gen Li, Hui-Ying Cheng, Meng Zhang, Feng Lai, Jin-Bing Wang, Feng-Mei Cui
This study aimed to investigate the radiosensitizing effect of polydatin (PD) on colorectal cancer (CRC) and its underlying mechanism. The C57BL/6 mouse model of CRC was induced by treatment with azoxymethane (AOM)/dextran sodium sulfate (DSS) and then divided into four groups: control, PD alone, IR alone, and combination of PD and IR. Radiation therapy (200 cGy/min, 10Gy) was performed in mice in the experimental groups for once a week with a total of four times. Thirty minutes before IR, mice were intraperitoneally injected with PD at the dose of 25mg/kg...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30745071/cardioprotective-strategies-to-prevent-breast-cancer-therapy-induced-cardiotoxicity
#19
REVIEW
Allison Padegimas, Suparna Clasen, Bonnie Ky
Breast cancer is the most common malignancy affecting females, with over 260,000 new cases annually and over 3.1 million survivors in the United States alone. Exposure to potentially cardiotoxic therapies, including anthracyclines, trastuzumab, and radiation therapy, coupled with host factors, place patients at increased risk for the development of cardiovascular disease (CVD) compared to non-cancer controls. Overall survival outcomes are significantly worse in patients who develop CVD, and in certain breast cancer populations, cardiovascular death exceeds the risk of cancer death in the long-term...
January 29, 2019: Trends in Cardiovascular Medicine
https://read.qxmd.com/read/30743222/effect-of-177-lu-ipsma-on-viability-and-dna-damage-of-human-glioma-cells-subjected-to-hypoxia-mimetic-conditions
#20
Erika Azorín-Vega, Liliana Aranda-Lara, Eugenio Torres-García, Juan Antonio Santiago-Bañuelos
The therapeutic potential of 177 Lu-iPSMA on hypoxic cancer cells has not been yet demonstrated. The aim of this work was to evaluate the radiation dose effect of 177 Lu-iPSMA on viability and DNA damage in U87MG human glioma cells subjected to hypoxia-mimetic conditions. U87MG cells treated with 177 Lu-iPSMA were incubated with CoCl2 in order to induce hypoxia-mimetic conditions. The cytotoxic and genotoxic effect was evaluated with an in vitro viability test and a neutral comet assay. 177 Lu-iPSMA decreased the cell viability and induced DNA double strand breaks in U87MG human glioma cells under hypoxia-mimetic conditions...
January 28, 2019: Applied Radiation and Isotopes
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