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https://www.readbyqxmd.com/read/28449469/cd90-positive-cells-exhibit-aggressive-radioresistance-in-esophageal-squamous-cell-carcinoma
#1
Yuandong Wang, Chi Zhang, Hongcheng Zhu, Junwei Tang, Shu Zhang, Jinhua Luo, Xinchen Sun
BACKGROUND: Cancer stem cells (CSCs) are widely abundant and considered to be an important factor in therapy resistance. They are also promising potential targets for conquering tumors. We explored the effects of radiation on stem cell-like tumor cells via the candidate marker CD90 to provide new ideas for the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). METHODS: We constructed CD90 overexpression ESCC cells by lentiviral transfection and observed differences of toxicity, proliferation, clone number, apoptosis, migration, invasion, and in vivo tumor formation after irradiation...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28445939/epigenetic-therapy-with-inhibitors-of-histone-methylation-suppresses-dna-damage-signaling-and-increases-glioma-cell-radiosensitivity
#2
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/28444219/dna-methylation-of-a-novel-pak4-locus-influences-ototoxicity-susceptibility-following-cisplatin-and-radiation-therapy-for-pediatric-embryonal-tumors
#3
Austin L Brown, Kayla L Foster, Philip J Lupo, Erin C Peckham-Gregory, Jeffrey C Murray, M Fatih Okcu, Ching C Lau, Surya P Rednam, Murali Chintagumpala, Michael E Scheurer
Background: Ototoxicity is a common adverse side effect of platinum chemotherapy and cranial radiation therapy; however, individual susceptibility is highly variable. Therefore, the objective of this study was to conduct an epigenome-wide association study to identify differentially methylated CpG sites associated with ototoxicity susceptibility among cisplatin-treated pediatric patients with embryonal tumors. Methods: Samples were collected for a discovery (n=62) and a replication cohort (n=18) of medulloblastoma and primitive neuroectodermal tumor patients...
April 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#4
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439080/ets-related-gene-mediated-androgen-receptor-aggregation-and-endoplasmic-reticulum-stress-in-prostate-cancer-development
#5
Taduru L Sreenath, Shiela S Macalindong, Natallia Mikhalkevich, Shashwat Sharad, Ahmed Mohamed, Denise Young, Talaibek Borbiev, Charles Xavier, Rishita Gupta, Muhammad Jamal, Kevin Babcock, Shyh-Han Tan, Marja T Nevalainen, Albert Dobi, Gyorgy Petrovics, Isabell A Sesterhenn, Inger L Rosner, Charles J Bieberich, Peter Nelson, Valeri Vasioukhin, Shiv Srivastava
Mechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#6
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434073/direct-downregulation-of-b-cell-translocation-gene-3-by-microrna-93-is-required-for-desensitizing-esophageal-cancer-to-radiotherapy
#7
Hujun Cui, Shengqiang Zhang, Hongbo Zhou, Ling Guo
BACKGROUND: Esophageal squamous carcinoma (ESC) is one of the most fatal malignancies worldwide with increasing occurrences yet poor outcome. MicroRNAs were reported to play roles in ESC. AIMS: We aimed to understand how miRNAs affect the radiotherapy resistance of ESC. METHODS: MicroRNA assays, real-time PCR, and Western blot were performed for expression analysis of miR-93 and BTG3. Luciferase activity assay was conducted with mutated B-cell translocation gene 3 (BTG3) 3'-UTR sequence in the 3' end of luciferase sequence with miR-93 inhibitor...
April 22, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28432589/expression-and-function-of-abcg2-and-xiap-in-glioblastomas
#8
Ivette F Emery, Archana Gopalan, Stephanie Wood, Kin-Hoe Chow, Chiara Battelli, Joshy George, Hagen Blaszyk, Jeffrey Florman, Kyuson Yun
Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28430578/involvement-of-polo-like-kinase-1-plk1-in-quiescence-regulation-of-cancer-stem-like-cells-of-the-gastric-cancer-cell-lines
#9
Lin Zhu, Sheng Xing, Li Zhang, Jian-Min Yu, Cheng Lin, Wei-Jun Yang
Cancer stem cells (CSCs) have been hypothesized to initiate tumor growth and be resistant to chemoradiotherapy, and these processes appear to be closely related to CSC quiescence. Here, a CSC-like cell population with a high level of CD44 expression was obtained from the human gastric cancer cell lines MKN45 and MKN74. Using a PKH26-labeling retention assay, quiescent CSC-like cells with low levels of Ki67 and PCNA expression were found in spheres formed in serum-free medium, and exhibited resistance to drug and radiation treatments...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428886/vaccination-with-inhibin-%C3%AE-provides-effective-immunotherapy-against-testicular-stromal-cell-tumors
#10
Robert Aguilar, Justin M Johnson, Patrick Barrett, Vincent K Tuohy
BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors. METHODS: To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428190/in-vivo-detection-of-egfrviii-in-glioblastoma-via-perfusion-magnetic-resonance-imaging-signature-consistent-with-deep-peritumoral-infiltration-the-%C3%AF-index
#11
Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M O'Rourke, Christos Davatzikos
<br />The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma non-invasively, using routine clinically-acquired imaging...
April 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28427834/doped-silica-fibre-thermoluminescence-measurements-of-radiation-dose-in-the-use-of-223-ra
#12
Bradley, S F Abdul Sani, A S Siti Shafiqah, S M Collins, R P Hugtenburg, H A Abdul Rashid, Nurul Najua Zulkepely, M J Maah
Using tailor-made sub-mm dimension doped-silica fibres, thermoluminescent dosimetric studies have been performed for α-emitting sources of (223)RaCl2 (the basis of the Bayer Healthcare product Xofigo®). The use of (223)RaCl2 in the palliative treatment of bone metastases resulting from late-stage castration-resistant prostate cancer focuses on its favourable uptake in metabolically active bone metastases. Such treatment benefits from the high linear energy transfer (LET) and associated short path length (<100µm) of the α-particles emitted by (223)Ra and its decay progeny...
April 14, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28427152/radioligand-therapy-of-metastatic-prostate-cancer-using-177lu-psma-617-after-radiation-exposure-to-223ra-dichloride
#13
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with 177Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with 223Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of 177Lu-PSMA-617 after exposure to more cycles of 223Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with 223Ra...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426877/knockdown-of-hnrnpk-leads-to-increased-dna-damage-after-irradiation-and-reduces-survival-of-tumor-cells
#14
Nadine Wiesmann, Judith Strozynski, Carina Beck, Nadine Zimmermann, Simone Mendler, Rita Gieringer, Irene Schmidtmann, Jürgen Brieger
Radiotherapy is an important treatment option in the therapy of multiple tumor entities among them head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by the development of radiation resistances. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and represents a potential target for radio sensitization of tumor cells. In this study, we analyzed the impact of hnRNPK on the DNA damage response after gamma irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA damage levels in irradiated cells...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28423669/the-novel-long-non-coding-rna-talnec2-regulates-tumor-cell-growth-and-the-stemness-and-radiation-response-of-glioma-stem-cells
#15
Shlomit Brodie, Hae Kyung Lee, Wei Jiang, Simona Cazacu, Cunli Xiang, Laila M Poisson, Indrani Datta, Steve Kalkanis, Doron Ginsberg, Chaya Brodie
Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423611/the-stem-cell-cancer-stem-cell-marker-aldh1a3-regulates-the-expression-of-the-survival-factor-tissue-transglutaminase-in-mesenchymal-glioma-stem-cells
#16
Kelly E Sullivan, Kathy Rojas, Richard A Cerione, Ichiro Nakano, Kristin F Wilson
Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423594/the-hypoxia-activated-prodrug-evofosfamide-in-combination-with-multiple-regimens-of-radiotherapy
#17
Katarzyna J Nytko, Ivo Grgic, Sabine Bender, Janosch Ott, Matthias Guckenberger, Oliver Riesterer, Martin Pruschy
The promising treatment combination of ionizing radiation (IR) with a hypoxia-activated prodrug (HAP) is based on biological cooperation. Here we investigated the hypoxia-activated prodrug evofosfamide in combination with different treatment regimens of IR against lung A549- and head&neck UT-SCC-14-derived tumor xenografts. DNA damage-related endpoints and clonogenic cell survival of A549 and UT-SCC-14 carcinoma cells were probed under normoxia and hypoxia.Evofosfamide (TH-302) induced DNA-damage and a dose-dependent antiproliferative response in A549 cells on cellular pretreatment under hypoxia, and supra-additively reduced clonogenic survival in combination with IR...
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/28422161/impact-of-low-temperature-overcast-and-rainy-weather-during-the-reproductive-growth-stage-on-lodging-resistance-of-rice
#19
Fei Weng, Wujun Zhang, Xiaoran Wu, Xia Xu, Yanfeng Ding, Ganghua Li, Zhenghui Liu, Shaohua Wang
The objectives of this study were to explore the mechanism by which the lodging resistance of the rice population during the late growth period responds to low-temperature, overcast and rainy weather during the reproductive growth stage. Field experiments were conducted using indica rice Yliangyou2 (lodging-resistance variety), IIyou084 (lodging-susceptible variety) and japonica rice Wuyunjing23 (lodging-resistance variety) and W3668 (lodging- susceptible variety) in 2013 (high temperature and strong radiation during the rice reproductive growth stage), 2012 and 2014 (low temperature and weak radiation during rice reproductive growth stage)...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419357/stereoelectroencephalography-using-magnetic-resonance-angiography-for-avascular-trajectory-planning-technical-report
#20
Krasimir Minkin, Kaloyan Gabrovski, Marin Penkov, Yuri Todorov, Rositsa Tanova, Yoana Milenova, Kiril Romansky, Petia Dimova
BACKGROUND: Stereoelectroencephalography (SEEG) requires high-quality angiographic studies because avascular trajectory planning is a prerequisite for the safety of this procedure. Some epilepsy surgery groups have begun to use computed tomography angiography and magnetic resonance T1-weighted sequence with contrast enhancement for this purpose. OBJECTIVE: To present the first series of patients with avascular trajectory planning of SEEG based on magnetic resonance angiography (MRA)...
April 13, 2017: Neurosurgery
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