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Xia Wang, Qing Li, Hua Jin, Hua Zou, Wei Xia, Nan Dai, Xiao-Yan Dai, Dong Wang, Cheng-Xiong Xu, Yi Qing
Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells...
October 18, 2016: Oncotarget
Eun Ho Kim, Mi-Sook Kim, Kyung-Hee Lee, Jae-Soo Koh, Won-Gyun Jung, Chang-Bae Kong
To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone...
September 27, 2016: Oncotarget
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
Antonin Levy, Etienne Bardet, Benjamin Lacas, Jean-Pierre Pignon, Julien Adam, Ludovic Lacroix, Xavier Artignan, Pierre Verrelle, Cécile Le Péchoux
BACKGROUND: Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer. PATIENTS AND METHODS: This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status...
October 18, 2016: Oncotarget
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0161700.].
2016: PloS One
Meysam Khosravifarsani, Ali Shabestani Monfared, Sajad Borzoueisileh
INTRODUCTION: Radiosensitivity is an inherent trait, associated with a raised reaction to ionizing radiation on the human body. In radiotherapy and radiation protection fields, individualization of the patient's treatment is one of the main topics. With the goal of determining biomarkers capable of anticipating normal tissue side reactions, we studied the association between the Rh factor and radiosensitivity. METHODS: This experimental study was carried out from January to June 2014 among 50 normal responders with A blood group (25Rh+ and 25Rh-) between the ages of 22 and 23 in Babol, Iran...
August 2016: Electronic Physician
Peidang Liu, Haizhen Jin, Zhirui Guo, Jun Ma, Jing Zhao, Dongdong Li, Hao Wu, Ning Gu
Radiotherapy performs an important function in the treatment of cancer, but resistance of tumor cells to radiation still remains a serious concern. More research on more effective radiosensitizers is urgently needed to overcome such resistance and thereby improve the treatment outcome. The goal of this study was to evaluate and compare the radiosensitizing efficacies of gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) on glioma at clinically relevant megavoltage energies. Both AuNPs and AgNPs potentiated the in vitro and in vivo antiglioma effects of radiation...
2016: International Journal of Nanomedicine
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
Qiao Jin, Xiang Jun Li, Pei Guo Cao
OBJECTIVES: Although low-dose radiotherapy (RT) that involves low collateral damage is more suitable for hepatocellular carcinoma (HCC) than traditional high-dose RT, but to achieve satisfactory therapeutic effect with low-dose RT, it is necessary to sensitize HCC cells to irradiation. This study was aimed to determine whether radiosensitivity of HCC cells can be enhanced using miR-26b by targeting erythropoietin producing human hepatocelluar A2 (EphA2). MATERIALS AND METHODS: The levels of miR-26b and EphA2 expression in multiple HCC cell lines were assessed by qPCR and western blotting, respectively, and compared with those in a hepatic cell line...
August 2016: Iranian Journal of Basic Medical Sciences
Manabu Koike, Yasutomo Yutoku, Aki Koike
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair processes, especially nonhomologous DNA-end joining (NHEJ), is critical for developing next-generation radiotherapies and chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, such as human Ku70 and Ku80, might play critical roles in controlling NHEJ activity. XRCC4-like factor (XLF) is a core NHEJ factor and plays a key role in the Ku-dependent NHEJ repair process in human cells...
October 14, 2016: Journal of Veterinary Medical Science
Sheldon Greer, Tieran Han, Cristina Dieguez, Nicola McLean, Rafael Saer, Isildinha Reis, Joe Levi, Victor E Marquez
Enzymatic activity from tumor and adjacent normal tissue of 200 patients involving deoxycytidine kinase (dCK), uridine/cytidine kinase (U/CK), cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD) was quantified. . Patients with brain (17), colon (24), and breast (30) tumors, 53, 67, and 73%, respectively, had an elevated T/N value (Specific Activity of tumor/ Specific Activity of normal tissue) involving dCK and dCMPD suggesting chemo therapy with 5-fluorodeoxycytidine (5-FdC) alone or in combination with thymidine plus deoxytetrahydrouridine, or with the radiosensitizer, 5-chlorodeoxycytidine (5-CldC) plus tetrahydrouridine (H4U)...
October 13, 2016: Anti-cancer Agents in Medicinal Chemistry
Michael M Im, Sheryl A Flanagan, Jeffrey J Ackroyd, Brendan Knapp, Aaron Kramer, Donna S Shewach
Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (≥24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage...
October 14, 2016: Radiation Research
Tosol Yu, Bong Jun Cho, Eun Jung Choi, Ji Min Park, Dan Hyo Kim, In Ah Kim
Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification...
October 12, 2016: Oncotarget
Ameer L Elaimy, Aarif Ahsan, Katherine Marsh, William B Pratt, Dipankar Ray, Theodore S Lawrence, Mukesh K Nyati
Heat shock protein 90 is a chaperone that plays an essential role in the stabilization of a large number of signal transduction molecules, many of which are associated with oncogenesis. An Hsp90 isoform (Hsp90α) has been shown to be selectively phosphorylated on two N-terminal threonine residues (threonine 5 and 7) and is involved in the DNA damage response and apoptosis. However, the kinase that phosphorylates Hsp90α after ionizing radiation (IR) and its role in post-radiation DNA repair remains unclear...
October 11, 2016: Oncotarget
Constantin Dreher, Christian Scholz, Mira Pommer, Stephan Brons, Hannah Prokesch, Swantje Ecker, Jürgen Debus, Oliver Jäkel, Stephanie E Combs, Daniel Habermehl
BACKGROUND: The aim of the thesis is to improve treatment plans of carbon ion irradiation by integrating the tissues' specific [Formula: see text]-values for patients with locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS: Five patients with LAPC were included in this study. By the use of the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) treatment plans with carbon ion beams have been created. Dose calculation was based on [Formula: see text]-values for both organs at risk (OAR) and the tumor...
2016: PloS One
Yuichiro Matsuoka, Hideki Nakayama, Ryoji Yoshida, Akiyuki Hirosue, Masashi Nagata, Takuya Tanaka, Kenta Kawahara, Junki Sakata, Hidetaka Arita, Hikaru Nakashima, Satoru Shinriki, Daiki Fukuma, Hidenao Ogi, Akimitsu Hiraki, Masanori Shinohara, Ryo Toya, Ryuji Murakami
BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. METHODS: Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro...
October 13, 2016: British Journal of Cancer
E Benedetti, M d'Angelo, A Ammazzalorso, G Gravina, C Laezza, A Antonosante, G Panella, B Cinque, L Cristiano, A C Dhez, C Astarita, R Galzio, M G Cifone, R Ippoliti, R Amoroso, E Di Cesare, A Giordano, A Cimini
Glioblastoma is the most-common cancer in the brain and with an increasing incidence. Despite major advances in the field, there is no curative therapy for GB to date. Many solid tumors, including GB, experienced metabolic reprogramming in order to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. PPARs, member of the steroid hormone receptor superfamily, are particularly involved in the control of energetic metabolism, particularly lipid metabolism, which has been reported deregulated in gliomas...
October 13, 2016: Journal of Cellular Physiology
E Yu, H Ueta, H Kimura, Y Kitazawa, Y Sawanobori, K Matsuno
Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication, with no presently available animal model and no preventive measure. To develop a rat LT-GvHD model, we preconditioned hosts with sublethal irradiation plus reduction of NK cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared to those in the peripheral counterpart, graft CD4(+) CD25(-) passenger T cells showed lower alloreactivities in mixed leukocyte culture. Immunohistology revealed that donor CD4(+) T cells migrated and formed clusters with host dendritic cells in secondary lymphoid organs, with early expansion and subsequent accumulation in target organs...
October 12, 2016: American Journal of Transplantation
Leonard N Zinman, Alex J Vanni
Primary urethral cancer (PUC) is a rare, but devastating genitourinary tumor that affects men and women. Although most PUC are localized, proximal PUC frequently presents with locally advanced disease, with 30% to 40% having lymph node metastasis. Single modality surgical or radiation therapy has dismal results. Multimodal therapy with cisplatin-based chemotherapy and consolidation surgery has greatly improved the local recurrence and overall survival rates for this aggressive disease. In locally advanced squamous cell carcinoma of the urethra, radiotherapy combined with radiosensitizing chemotherapy is an option for genital preservation...
November 2016: Urologic Clinics of North America
Thomas Altmann, Andrew R Gennery
DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. DNA ligase IV is part of the non-homologous end joining mechanism, required to repair DNA double stranded breaks. Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events such as DNA replication and meiosis or extracellular events including damage by reactive oxygen species and ionising radiation...
October 7, 2016: Orphanet Journal of Rare Diseases
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