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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
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Rüveyda Dok, Karin Haustermans, Ruth J Muschel
Limited data exists regarding the combination of Hedgehog signaling (Hh) inhibition and radiotherapy, even though there are several indications that this might be a promising treatment strategy. In this study, we evaluated the combination of two Hh inhibitors, the SMO inhibitor GDC-0449 and the GLI inhibitor GANT61 with radiotherapy in different prostate cancer (PCa) models. In vitro, GANT61 was able to sensitize 22Rv1 PCa cells but not PC3 and DU145 PCa cells. The lack of radiosensitization in the latter cell lines was shown to be dependent on the presence of mutated p53...
October 5, 2016: Oncotarget
Hongqing Zhuang, Jing Bai, Joe Y Chang, Zhiyong Yuan, Ping Wang
OBJECTIVE: To investigate the effects of mTOR inhibition on drug resistance in lung adenocarcinoma after combined radiation and erlotinib therapy. RESULTS: Combined radiation and erlotinib therapy produced clear radiosensitization effects both in vitro and in vivo; however, tumor cells remained drug resistant. Additionally, combined radiation and erlotinib therapy significantly increased p-AKT and p-P70 levels. After mTOR inhibition, the number of surviving cells significantly decreased compared with that before inhibition, and the in vivo growth curve was significantly reduced...
October 4, 2016: Oncotarget
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
Gen Li, Anqing Wu, Dandan Qi, Fengmei Cui, Yanan Zeng, Fang Xie, Hongya Wu, Yongping Gu, Qiu Chen, Xueguang Zhang
Immediate medical intervention is required after pelvic tumor radiotherapy to protect the radiosensitive intestine and also to mitigate tumor growth. Toll-like receptors (TLRs) have been shown to promote tissue repair processes. Here, we analyzed the effect observed upon combining the TLR2 agonist, peptidoglycan (PGN), with radiation therapy on tumors as well as intestinal tissue, both in vitro and in vivo. In contrast to radiotherapy alone, PGN when combined with ionizing radiation (IR) elicited enhanced antitumor effects and also reduced the IR-induced intestinal damage...
September 30, 2016: Oncotarget
Shin-Ichi Bando, Osamu Hatano, Hiroshi Takemori, Nobuo Kubota, Ken Ohnishi
PURPOSE: This study examined the enhancing effects of syringetin on the radiosensitivity of normal and cancer cells, and the related mechanism. MATERIALS AND METHODS: We used normal human lung and mouse fibroblasts as well as human lung and mouse cancer cells derived from the above normal fibroblasts. Cell radiosensitivity was measured using a colony formation assay. Apoptosis was analyzed with DAPI staining and Western blots. DNA lesions were analyzed with γH2AX immunofluorescent staining...
October 6, 2016: International Journal of Radiation Biology
Mehdi Mousavi, Hassan Ali Nedaei, Samideh Khoei, Samira Eynali, Karim Khoshgard, Mostafa Robatjazi, Rasoul Iraji Rad
PURPOSE: Gold nanoparticles (GNP) have significant potential as radiosensitizer agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the radiosensitization effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. MATERIALS AND METHODS: The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential...
October 5, 2016: International Journal of Radiation Biology
Ying Xu, Dongming Wu, Yuanchun Fan, Peigeng Li, Hongfei Du, Jiao Shi, Dan Wang, Xiaoping Zhou
The recombinant protein flagellin A (FlaA) N/C, derived from the flagellin protein of Legionella pneumophila, has been shown to increase the expression of cytoprotective cytokines, activate the nuclear factor-κB (NF-κB) signaling pathway, and increase the survival of mice following total body irradiation. Determi ning whether FlaA N/C has a sensitizing effect on tumor radiation or a direct tumoricidal effect is critical for its application as an effective radiation protection agent. The present study investigated the molecular mechanism underlying the tumor radiosensitivity of FlaA N/C...
October 2016: Oncology Letters
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