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https://www.readbyqxmd.com/read/28449496/the-mechanisms-of-radioresistance-in-esophageal-squamous-cell-carcinoma-and-current-strategies-in-radiosensitivity
#1
REVIEW
Guang-Zong Chen, Hong-Cheng Zhu, Wang-Shu Dai, Xiao-Ning Zeng, Jin-Hua Luo, Xin-Chen Sun
Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death worldwide. Surgery is the primary form of treatment, but the survival is poor, especially for patients with locally advanced esophageal cancer. Radiotherapy has been a critical treatment option that may be combined with chemotherapy in patients with unresectable esophageal cancer. However, resistance to chemoradiotherapy might result in treatment failures and cancer relapse. This review will mainly focus on the possible cellular mechanisms and tumor-associated microenvironmental (TAM) factors that result in radioresistance in patients with esophageal cancer...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446130/a-comparison-of-pediatric-and-adult-ct-organ-dose-estimation-methods
#2
Yiming Gao, Brian Quinn, Usman Mahmood, Daniel Long, Yusuf Erdi, Jean St Germain, Neeta Pandit-Taskar, X George Xu, Wesley E Bolch, Lawrence T Dauer
BACKGROUND: Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation...
April 26, 2017: BMC Medical Imaging
https://www.readbyqxmd.com/read/28445939/epigenetic-therapy-with-inhibitors-of-histone-methylation-suppresses-dna-damage-signaling-and-increases-glioma-cell-radiosensitivity
#3
Ozge Gursoy-Yuzugullu, Chelsea Carman, Rodolfo Bortolozo Serafim, Marios Myronakis, Valeria Valente, Brendan D Price
Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442922/inhibition-of-pcsk9-protects-against-radiation-induced-damage-of-prostate-cancer-cells
#4
Si-Shun Gan, Jian-Qing Ye, Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating low-density lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28437549/poor-utility-of-gonadal-shielding-for-pediatric-pelvic-radiographs
#5
Mark C Lee, Jessica Lloyd, Matthew J Solomito
Plain pelvic radiographs are commonly used for a variety of pediatric orthopedic disorders. Lead shielding is typically placed over the gonads to minimize radiation exposure to these sensitive tissues. However, misplaced shielding can sabotage efforts to protect patients from excessive radiation exposure either by not covering radiosensitive tissues or by obscuring anatomic areas of interest, prompting repeat radiographic examinations. The goal of this study was to determine the incidence of misplaced shielding for pelvic radiographs obtained for pediatric orthopedic evaluation...
April 24, 2017: Orthopedics
https://www.readbyqxmd.com/read/28435470/downregulation-of-sirt7-by-5-fluorouracil-induces-radiosensitivity-in-human-colorectal-cancer
#6
Ming Tang, Xiaopeng Lu, Chaohua Zhang, Changzheng Du, Linlin Cao, Tianyun Hou, Zhiming Li, Bo Tu, Ziyang Cao, Yinglu Li, Yongcan Chen, Lu Jiang, Hui Wang, Lina Wang, Baohua Liu, Xingzhi Xu, Jianyuan Luo, Jiadong Wang, Jin Gu, Haiying Wang, Wei-Guo Zhu
5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy to treat human cancers, but the underlying mechanisms of this combination treatment remain unclear. Here, we report that NAD(+)-dependent deacetylase sirtuin-7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal cancer cells sensitive to radiation. We found that SIRT7 downregulation was mediated via a Tat-binding Protein 1 (TBP1) proteasome-dependent pathway. Specifically, TBP1 was dephosphorylated at tyrosine 381 upon 5-FU treatment, which enhanced its direct interaction with SIRT7 and targeted it for degradation...
2017: Theranostics
https://www.readbyqxmd.com/read/28434660/reduced-dose-radiotherapy-for-human-papillomavirus-associated-squamous-cell-carcinoma-of-the-oropharynx-a-single-arm-phase-2-study
#7
Allen M Chen, Carol Felix, Pin-Chieh Wang, Sophia Hsu, Vincent Basehart, Jordan Garst, Phillip Beron, Deborah Wong, Michael H Rosove, Shyam Rao, Heather Melanson, Edward Kim, Daphne Palmer, Lihong Qi, Karen Kelly, Michael L Steinberg, Patrick A Kupelian, Megan E Daly
BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1...
April 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28432740/novel-3q27-2-qter-deletion-in-a-patient-with-diamond-blackfan-anemia-and-immunodeficiency-case-report-and-review-of-literature
#8
Ebba Alkhunaizi, Brett Schrewe, Reza Alizadehfar, Catherine Vézina, Grant S Stewart, Nancy Braverman
3q27.2-qter deletion syndromes feature an overlapping set of terminal and interstitial deletions with variable congenital malformations. Diamond-Blackfan anemia (DBA) is etiologically heterogeneous disorder in which one cause is dominant mutations of the RPL35A gene on 3q29. We report a child with a 3q27.2-qter deletion that contains the RPL35A gene. She had clinical and laboratory features consistent with DBA and as well, an unexplained immunodeficiency disorder. Given these unusual findings, we reviewed other patients in the literature with overlapping genomic deletions...
April 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28431753/eef2k-promotes-progression-and-radioresistance-of-esophageal-squamous-cell-carcinoma
#9
Hongcheng Zhu, Hongmei Song, Guangzong Chen, Xi Yang, Jia Liu, Yangyang Ge, Jing Lu, Qin Qin, Chi Zhang, Liping Xu, Xiaoke Di, Jing Cai, Jianxin Ma, Shu Zhang, Xinchen Sun
OBJECTIVES: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively...
April 18, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28430589/ier5-as-a-promising-predictive-marker-promotes-irradiation-induced-apoptosis-in-cervical-cancer-tissues-from-patients-undergoing-chemoradiotherapy
#10
Yang Liu, Ming Tian, Hui Zhao, Yue He, Fengshuang Li, Xiunan Li, Xinping Yu, Kuke Ding, Pingkun Zhou, Yumei Wu
PURPOSE: To define the role of immediate-early 5 (IER5) gene as a promising biomarker in predicting the radiosensitivity and prognosis of cervical cancer patients receiving cisplatin-based concurrent chemoradiotherapy (DDP-CCRT). RESULTS: Our investigations found that IER5 level was markedly elevated in cervical cancer patients after being treated with irradiation, which indicated IER5 was closely dose induced. By contrast, the correlation between IER5 and radiosensitivity cannot be confirmed by the present study...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429022/dependence-of-gold-nanoparticle-radiosensitization-on-cell-geometry
#11
Wonmo Sung, Sung-Joon Ye, Aimee L McNamara, Stephen J McMahon, James Hainfeld, Jungwook Shin, Henry M Smilowitz, Harald Paganetti, Jan Schuemann
The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing (1) the cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and (4) the photon energy...
April 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#12
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427800/the-effect-of-optune%C3%A2-tumor-treating-fields-transducer-arrays-on-skin-radiation-dose-during-radiotherapy
#13
Edward Bender, Kevin Kozak, Steven Howard, Lori Hayes, John Bayouth, H Ian Robins
A Phase 3 clinical study demonstrated that the addition of 200kHz Tumor Treating Fields (TTF) to temozolomide in the post-radiation (RT) phase of therapy in newly diagnosed glioblastoma increases progression free and overall survival (resulting in FDA and European Union approval). Preclinical studies have demonstrated the ability of TTF to act as a radiosensitizer, suggesting concurrent TTF and RT may have clinical utility. The removal and replacement of TTF transducer arrays from the scalps of patients on a daily basis, i...
April 17, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28427529/primary-central-nervous-system-lymphoma
#14
REVIEW
Giovanni Citterio, Michele Reni, Gemma Gatta, Andrés José Maria Ferreri
Primary CNS lymphomas (PCNSL) represent a subgroup of malignancies with specific characteristics, aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumour burden and/or histological type. Despite a high chemo- and radiosensitivity, remissions are frequently shortlasting, mainly because the blood brain-barrier limits the access of many drugs to the CNS. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity, raising the question of how to balance therapy intensification with side-effects control...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427525/precision-medicine-for-early-breast-cancer-radiotherapy-opening-up-new-horizons
#15
REVIEW
Jacques Bernier
So far most efforts put forth to test the value of predictive and prognostic tools in the field of breast radiotherapy remained globally disappointing, or at least below the convincing levels reached for systemic therapy. Nevertheless the addition of predictive tools to the clinical armament tends to prevail over the use of the sole prognostic factors, also in radiotherapy. A number of predictive assays, clinically validated or not, have recently elicited significant associations between molecular profiles and tumor biological aggressiveness and/or radiosensitivity levels...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#16
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28423589/role-of-microrna-21-in-radiosensitivity-in-non-small-cell-lung-cancer-cells-by-targeting-pdcd4-gene
#17
Li-Peng Jiang, Chun-Yan He, Zhi-Tu Zhu
This study aims to explore the effects of microRNA-21 (miR-21) on radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer tissues and adjacent normal tissues were collected from 97 NSCLC patients who received a standard radiotherapy regimen. TUNEL assay was applied to determine cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western blotting...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423495/afatinib-radiosensitizes-head-and-neck-squamous-cell-carcinoma-cells-by-targeting-cancer-stem-cells
#18
Muzafar A Macha, Satyanarayana Rachagani, Asif Khurshid Qazi, Rahat Jahan, Suprit Gupta, Anery Patel, Parthasarathy Seshacharyulu, Chi Lin, Sicong Li, Shuo Wang, Vivek Verma, Shosei Kishida, Michiko Kishida, Norifumi Nakamura, Toshiro Kibe, William M Lydiatt, Russell B Smith, Apar K Ganti, Dwight T Jones, Surinder K Batra, Maneesh Jain
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418119/endoplasmic-reticulum-stress-pathway-perk-eif2%C3%AE-confers-radioresistance-in-oropharyngeal-carcinoma-by-activating-nf-%C3%AE%C2%BAb
#19
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumours, as well as in the regulation of radio- and chemoresistance in many malignancies. ERS signalling pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2 (eIF2α) may induce aberrant activation of nuclear factor-κB (NF-κB). Our previous study showed that NF-κB confered radioresistance in lymphoma cells. However, whether PERK-eIF2α regulates radioresistance in oropharyngeal carcinoma through NF-κB activation is unknown...
April 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28415784/misregulation-of-dna-damage-repair-pathways-in-hpv-positive-head-and-neck-squamous-cell-carcinoma-contributes-to-cellular-radiosensitivity
#20
Catherine M Nickson, Parisa Moori, Rachel J Carter, Carlos P Rubbi, Jason L Parsons
Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy and improved survival rates in comparison to HPV-negative forms of the disease. However the cellular mechanisms responsible for this characteristic difference are unclear. Here, we have investigated the contribution of DNA damage repair pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV-negative OPSCC cells, which correlates with reduced efficiency for the repair of ionising radiation (IR)-induced DNA double strand breaks (DSB)...
March 16, 2017: Oncotarget
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