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    Lack of Sunlight Exposure Influence on Primary Glioblastoma Survival
    (ASIAN PACIFIC ORGANIZATION CANCER PREVENTION, 2014-01-01) Mutlu, Hasan; Akca, Zeki; Erden, Abdulsamet; Aslan, Tuncay; Ucar, Kadir; Kaplan, Bunyamin; Buyukcelik, Abdullah
    Background: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary brain tumor diagnoses are GBM, of which 95\% are primary lesions. In this study, we aimed to evaluate whether more sunlight exposure has an effect on survival of patients with primary GBM. Materials and Methods: A total of 111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40) and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients with primary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival (PFS) and overall survival (OS). Results: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups, respectively (p=0.10) and the repsective OS values were 13.3 and 9.4 months (p=0.13). We did not found any significant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapy and palliative chemotherapy between the groups. Conclusions: We found that more sunlight exposure had no impact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationship between sunlight and GBM.
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    Treatment of glioblastoma by photodynamic therapy with the aid of synthesized silver nanoparticles by green chemistry from Citrus aurantium
    (MARMARA UNIV, 2021-01-01) Erdogan, Omer; Abbak, Muruvvet; Demirbolat, Gulen Melike; Aksel, Mehran; Pasa, Salih; Donmez Yalcin, Gizem; Cevik, Ozge
    Blood brain barrier is very important to provide treatment locally for the treatment of glioblastoma. The use of nanoparticles has shown promise for glioblastoma treatments in recent years. In this study, the effect of the combined treatment of silver nanoparticles (AgNPs) synthesized from Citrus aurantium with photodynamic therapy (PDT) was investigated on U87 glioblastoma cells. AgNPs were characterized by FTIR, zeta potential and SEM images. U87 cells were treated with AgNPs (10 mu g/mL) and/or PDT (0.5 mJ/cm(2)) at 24 h. Cells antiproliferative effect, migration levels, colony formation capability, Bax and Bcl-2 protein/gene expression, and caspase-3 activity levels as apoptotic markers were measured. AgNPs size were found at 141 +/- 3 nm and 18.1 +/- 1.3 mV as zeta potential. It was found that cell proliferation, migration and Bcl-2 protein/gene levels decreased, and Bax protein/ gene levels and caspase-3 activity increased via AgNPs and PDT combined treatment. As a result, nanoparticles synthesized from Citrus aurantium are eco-friendly and their size can cross the blood brain barrier. If AgNPs is used with PDT, it may be a new therapy for clinically treatment of glioblastoma in the future.
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    In Vitro Effects of Mesenchymal Stem Cells and Various Agents on Apoptosis of Glioblastoma Cells
    (TURKISH NEUROSURGICAL SOC, 2019-01-01) Tanrikulu, Bahattin; Ziyal, Ibrahim; Bayri, Yasar
    AIM: To investigate a new anti-tumor treatment method using stem cells transfected with specific genes and proteins that induce apoptosis in tumor cells. MATERIAL and METHODS: We used glioblastoma (GBM) cells and human adipose tissue-derived mesenchymal stem cells (AD-MSCs) in this study. The AD-MSCs were transfected with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To overcome apoptosis resistance in tumor cells, we used suberoylanilide hydroxamic acid (SAHA) as the histone deacetylase inhibitor and embelin as the X-linked inhibitor of apoptosis protein (XIAP). In addition, we silenced the XIAP gene on GBM cells with the shXIAP plasmid. Following the determination of half-maximal effective concentration (EC50\%) doses of SAHA and embelin, GBM cells were incubated with them for 24 hours. XIAP-silenced and XIAP-non-silenced GBM cells were cultured with TRAIL-non-transfected and TRAIL-transfected stem cells for 24 hours. Viability and cell cycle analysis of all groups were determined using annexin V/propidium iodide and cell cycle method via flow cytometry. RESULTS: TRAIL-transfected AD-MSCs, XIAP silencing, embelin, and SAHA induced apoptosis in GBM cells and decreased their proliferation, whereas TRAIL-non-tranfected AD-MSCs did not. CONCLUSION: Engineered stem cell therapies and molecular studies show promise in developing combination therapies for effective treatment of GBM.
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    Limited field adaptive radiotherapy for glioblastoma: changes in target volume and organ at risk doses
    (KOREAN SOC THERAPEUTIC RADIOLOGY \& ONCOLOGY, 2022-01-01) Senkesen, Oznur; Tezcanli, Evrim; Abacioglu, Mehmet Ufuk; Ozen, Zeynep; Cone, Derya; Kucucuk, Halil; Goksel, Evren Ozan; Arifoglu, Alptekin; Sengoz, Meric
    Objective: This study aimed to investigate the tumor volume changes occurring during limited-field radiotherapy (RT) for glioblastoma patients and whether a volume-adapted boost planning approach provided any benefit on tumor coverage and normal tissue sparing. Materials and Methods: Twenty-four patients underwent simulation with magnetic resonance (MR) and computed tomography (CT) scans prior to RT (MR\_initial, CT\_initial) and boost treatment (MR\_adapt, CT\_adapt). For the boost phase, MR\_initial and MR\_adapt images were used to delineate GTV(2) and GTV(2\_adapt), respectively. An initial boost plan (Plan\_initial) created on CT\_initial for PTV2 was then reoptimized on CT\_adapt by keeping the same optimization and normalization values. Plan\_adapt was generated on CT\_adapt for PTV(2\_adapt )volume. Dose volume histogram parameters for target volumes and organs-at-risk were compared using these boost plans generated on CT\_adapt. Plan\_initial and Plan\_adaptive boost plans were summed with the first phase plan and the effect on the total dose was investigated. Results: Target volume expansion was noted in 21 0 /c, of patients while 791b had shrinkage. The average difference for the initial and adaptive gross tumor volume (G1V), clinical target volume (CTV), and planning target volume (PTV) volumes were statistically significant. Maximum dose differences for brainstem and optic chiasm were significant. Healthy brain tissue V-10 and ipsilateral optic nerve maximum doses were found to decrease significantly in Plan\_adaptive. Conclusion: Results of this study confirm occurrence of target volume changes during RT for glioblastoma patients. An adaptive plan can provide better normal tissue sparing for patients with lesion shrinkage and avoid undercoverage of treatment volumes in case of target volume expansion especially when limited-fields are used.
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    Oxamate targeting aggressive cancers with special emphasis to brain tumors
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2022-01-01) Altinoz, Meric A.; Ozpinar, Aysel
    Cancer is one of the main causes of human mortality and brain tumors, including invasive pituitary adenomas, medulloblastomas and glioblastomas are common brain malignancies with poor prognosis. Therefore, the development of innovative management strategies for refractory cancers and brain tumors is important. In states of mitochondrial dysfunction - commonly encountered in malignant cells - cells mostly shift to anaerobic glycolysis by increasing the expression of LDHA (Lactate Dehydrogenase-A) gene. Oxamate, an isosteric form of pyruvate, blocks LDHA activity by competing with pyruvate. By blocking LDHA, it inhibits protumorigenic cascades and also induces ROS (reactive oxygen species)-induced mitochondrial apoptosis of cancer cells. In preclinical studies, oxamate blocked the growth of invasive pituitary adenomas, medulloblastomas and glioblastomas. Oxamate also increases temozolomide and radiotherapy sensitivity of glioblastomas. Oxamate is highly polar, which may preclude its clinical utilization due to low penetrance through cell membranes. However, this obstacle could be overcome with nanoliposomes. Moreover, different oxamate analogs were developed which inhibit LDHC4, an enzyme also involved in cancer progression and germ cell physiology. Lastly, phenformin, an antidiabetic agent, exerts anticancer effects via complex I inhibition in the mitochondria and leading the overproduction of ROS. Oxamate combination with phenformin reduces the lactic acidosis-causing side effect of phenformin while inducing synergistic anticancer efficacy. In sum, oxamate as a single agent and more efficiently with phenformin has high potential to slow the progression of aggressive cancers with special emphasis to brain tumors.