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Hai-Xia Li, Jin-Hua Zheng, Liang Ji, Guan-Yao Liu, Yv-Kun Lv, Dan Yang, Zheng Hu, He Chen, Feng-Min Zhang, Wenwu Cao
Low-intensity ultrasound (LIUS) combined with chemotherapy is an innovative modality for cancer treatment, but its effect on orthotopic carcinoma remains unknown. Our previous study revealed that LIUS enhanced the growth inhibitory effects of several chemotherapeutic drugs in nude mice with transplanted tumors. In the present study, we used 7,12-dimethylbenz(alpha)anthracene to induce orthotopic tongue carcinogenesis in hamsters. We used the first-line chemotherapy drug for tongue cancer, carboplatin (CBP) in combination with LIUS to investigate the synergistic effect...
February 13, 2018: Oncology Reports
Xingguo Song, Li Xie, Minghui Chang, Xinran Geng, Xingwu Wang, Thomas C Chen, Xianrang Song
The DNA repair enzyme O6-methylguanin-DNA-methltransferase (MGMT) is able to remove products of alkylating agent such as O6-meG and emerges as a central determinant of cancer resistance to temozolomide (TMZ). Temozolomide-perillyl alcohol conjugate (TMZ-POH), a novel TMZ analog developed based on the conjugation of TMZ and POH, displayed strong anticancer potency in multiple cancer types, but seemed not to experience the chemoresistance even in cells with high MGMT expression unlike TMZ and other alkylating agents...
February 9, 2018: Cell Death & Disease
Shun Hirasawa, Min Cho, Tarsis F Brust, Jeremy J Roach, Laura M Bohn, Ryan A Shenvi
Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its C8 epimer, so much so that epimerization is completely supressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR...
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
Andrej Pala, Anne Lea Schmitz, Andreas Knoll, Max Schneider, Michal Hlavac, Ralph König, Christian Rainer Wirtz, Jan Coburger
OBJECTIVES: At present, there is no standard therapy approved for recurrent glioblastoma (rGB). In particular, the counselling of patients with an unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter GB remains a challenge. Our aim was to compare the overall survival (OS) and progression free survival (PFS) in patients treated surgically and non-surgically at the time of GB recurrence. This was evaluated with particular reference to the impact of recurrent surgery for patients with unmethylated MGMT promoter rGB...
February 5, 2018: Clinical Neurology and Neurosurgery
Caroline Happold, Thierry Gorlia, L Burt Nabors, Sara C Erridge, David A Reardon, Christine Hicking, Martin Picard, Roger Stupp, Michael Weller
Glioblastomas are malignant brain tumors with poor prognosis. Lately, data from clinical studies assessing the role of co-medications in different cancer types suggested reduced mortality and potential anti-tumor activity for statins, angiotensin-I converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (sartans). Here, we analysed the association of co-treatment with statins, ACEI or sartans with outcome in a cohort of 810 patients enrolled in the phase III CENTRIC and phase II CORE trials on the role of the integrin antagonist, cilengitide, in newly diagnosed glioblastoma with or without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation...
February 8, 2018: Journal of Neuro-oncology
Beom Ryong Kang, Anne J Anderson, Young Cheol Kim
Root-knot nematodes (Meloidogyne spp.) are parasites that attack many field crops and orchard trees, and affect both the quantity and quality of the products. A root-colonizing bacterium, Pseudomonas chlororaphis O6, possesses beneficial traits including strong nematicidal activity. To determine the molecular mechanisms involved in the nematicidal activity of P. chlororaphis O6, we constructed two mutants; one lacking hydrogen cyanide production, and a second lacking an insecticidal toxin, FitD. Root drenching with wild-type P...
February 2018: Plant Pathology Journal
Juliana Guimarães Santos, Wanise Maria Souza Da Cruz, Axel H Schönthal, Marcela D'alincourt Salazar, Cristina Asvolinsque Pantaleão Fontes, Thereza Quirico-Santos, Clovis Orlando Da Fonseca
It has been hypothesized that persistent ketotic hypoglycemia represents a potential therapeutic strategy against high-grade gliomas. Perillyl alcohol (POH) is a non-toxic, naturally-occurring, hydroxylated monoterpene that exhibits cytotoxicity against temozolomide-resistant glioma cells, regardless of O6-methylguanine-methyltransferase promoter methylation status. The present study aimed to evaluate the toxicity and therapeutic efficacy of intranasal POH when administered in combination with a ketogenic diet (KD) program for the treatment of patients with recurrent glioblastoma...
January 2018: Oncology Letters
Belinda Kramer, Radhika Singh, Jessica Wischusen, Rebecca Velickovic, Amanda Rush, Shiloh Middlemiss, Yu-Wooi Ching, Ian Edward Alexander, Geoffrey B McCowage
Gene transfer targeting haematopoietic stem cells (HSC) in children has shown sustained therapeutic benefit in the treatment of genetic diseases affecting the immune system, most notably in the severe combined immuno-deficiencies affecting T cell function. The HSC compartment has also been successfully targeted using gene transfer in children with genetic diseases affecting the central nervous system, such as metachromatic leukodystrophy and adrenoleukodystrophy. The HSC is also a target for genetic modification in strategies aiming to confer drug resistance to chemotherapy agents so as to reduce off-target toxicity, and to allow for chemotherapy dose escalation with the possibility of enhanced therapeutic benefit...
January 31, 2018: Human Gene Therapy
Dipika Gupta, Bo Lin, Ann Cowan, Christopher D Heinen
The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear. This has important implications for understanding how MMR repairs O6-methylguanine/thymidine (MeG/T) mismatches created upon exposure to DNA alkylating agents. If MeG/T lesion recognition by MMR initiates mismatch excision, the reinsertion of a mismatched thymidine during resynthesis could initiate futile repair cycles...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hyun-Wook Lee, Sung-Hyun Park, Mao-Wen Weng, Hsiang-Tsui Wang, William C Huang, Herbert Lepor, Xue-Ru Wu, Lung-Chi Chen, Moon-Shong Tang
E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Almadani A, Dixit S, Rowland-Hill C, Achawal S, Rajaraman Cr, Gerry Go, R Highley, Hussain Masood, Baker L, Gill L, Morris H, Hingorani M
The management of elderly patients with glioblastoma-multiforme (GBM) remains poorly defined with many experts advocating best supportive care in view of limited evidence on efficacy of more aggressive treatment protocols. There is randomised evidence (NORDIC and NA-O8 studies) to support the use of surgery followed by adjuvant monotherapy with either radiotherapy (RT) using hypo-fractionated regimes (e.g. 36 Gy in 6 fractions OR 40 Gy in 15 fractions) or chemotherapy with temozolomide (TMZ) in patients expressing methylation of promoter for O6-methylguanine-DNA methyltransferase (MGMT) enzyme...
January 29, 2018: British Journal of Radiology
Brennan Ashwood, Luis A Ortiz-Rodríguez, Carlos E Crespo-Hernández
S6-Methylthioinosine and O6-methylguanosine are byproducts resulting from the enzymatic reactions of sulfur-substituted prodrugs in cells and from the interaction of alkylating agents with cellular DNA, respectively. Their photochemistry has not been investigated, and it is currently unknown whether light absorption by these byproducts may pose any threat to the cell. In this contribution, their photoinduced processes upon absorption of UVB radiation are reported using broadband transient absorption spectroscopy...
January 26, 2018: Faraday Discussions
Paweł Kiczmer, Alicja Prawdzic Seńkowska, Joanna Katarzyna Strzelczyk, Błażej Szydło, Krzysztof Biernacki, Tadeusz Osadnik, Łukasz Krakowczyk, Zofia Ostrowska
Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and 242 healthy individuals...
January 25, 2018: Acta Biochimica Polonica
Lei Zhang, Yoshitaka Matsushita, Yoshio Katsuya, Masahiko Tanaka, Kazunari Yamaura, Alexei A Belik
We prepared a quadruple perovskite CeCuMn6O12 under high-pressure and high-temperature conditions at 6 GPa and about 1670 K and investigated its structural, magnetic and transport properties. CeCuMn6O12 crystallizes in space group Im-3 above T CO  =  297 K; below this temperature, it adopts space group R-3 with the 1:3 (Mn4+:Mn3+) charge and orbital orders. Unusual compressed Mn3+O6 octahedra are realized in CeCuMn6O12 similar to CaMn7O12 with the  -Q 3 Jahn-Teller distortion mode. Below about 90 K, structural instability takes place with phase separation and the appearance of competing phases; and below 70 K, two R-3 phases coexist...
January 23, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Inas Fawzy Gaballah, Sawsan Farouk Helal, Basma Hussein Mourad
Wood dust is known to be a human carcinogen, with a considerable risk of lung cancer. The increased cancer risk is likely induced through its genotoxic effects resulting from oxidative DNA damage. This study aimed at assessing the genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening tool for early prediction of lung cancer among wood workers. The study was carried out in the carpentry section of a modernized factory involved with the manufacture of wooden furniture in Greater Cairo, Egypt...
January 23, 2018: International Journal of Occupational and Environmental Health
Ye Zhou, Shengnan Sun, Shibo Xi, Yan Duan, Thirumany Sritharan, Yonghua Du, Zhichuan J Xu
Mn-Co containing spinel oxides are promising, low-cost electrocatalysts for the oxygen reduction reaction (ORR). Most studies are devoted to the design of porous Mn-Co spinels or to strongly coupled hybrids (e.g., MnCo2 O4 /N-doped-rmGO) to maximize the mass efficiency. The lack of analyses by metal oxide intrinsic activity (activity normalized to catalysts' surface area) hinders the development of fundamental understanding of the physicochemical principles behind the catalytic activities. A systematic study on the composition dependence of ORR in ZnCox Mn2-x O4 (x = 0...
January 22, 2018: Advanced Materials
Alexander S G Micko, Romana Höftberger, Adelheid Wöhrer, Matthias Millesi, Engelbert Knosp, Stefan Wolfsberger
PURPOSE: Despite the established role of O6-methyl-guanine-DNA methyltransferase (MGMT) as a marker for temozolomide response, consensus of the most reliable method to assess MGMT expression in pituitary adenomas is still missing. Currently, immunohistochemistry (IHC) assessment of formaldehyde fixed tissue samples is most widely used in a semiquantitative description. As formaldehyde fails to completely preserve nucleic acids, RCL2, an alcohol-based formaldehyde-free fixative, has been proposed as a more reliable alternative in terms of cell stability...
January 17, 2018: Pituitary
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
Zhikuan Yang, Danping Wei, Feifei Liu, Jing Liu, Xiaoming Wu, Malcolm F G Stevens, Tracey D Bradshaw, Ying Luo, Jihong Zhang
The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels...
January 13, 2018: Journal of Cellular Biochemistry
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