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https://www.readbyqxmd.com/read/28822335/specificity-protein-1-modulated-superoxide-dismutase-2-enhances-temozolomide-resistance-in-glioblastoma-which-is-independent-of-o-6-methylguanine-dna-methyltransferase
#1
Kwang-Yu Chang, Tsung-I Hsu, Che-Chia Hsu, Shan-Yin Tsai, Jr-Jiun Liu, Shao-Wen Chou, Ming-Sheng Liu, Jing-Ping Liou, Chiung-Yuan Ko, Kai-Yun Chen, Jan-Jong Hung, Wen-Chang Chang, Cheng-Keng Chuang, Tzu-Jen Kao, Jian-Ying Chuang
Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants derived from MGMT-negative GBM clinical samples and cell lines were studied, revealing there to be increased specificity protein 1 (Sp1) expression associated with reduced reactive oxygen species (ROS) accumulation following TMZ treatment...
August 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28821714/gadd45a-plays-a-protective-role-against-temozolomide-treatment-in-glioblastoma-cells
#2
Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811386/trimetazidine-protects-retinal-ganglion-cells-from-acute-glaucoma-via-the-nrf2-ho-1-pathway
#3
Peixing Wan, Wenru Su, Yingying Zhang, Zhidong Li, Caibin Deng, Yehong Zhuo
Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuro-inflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses anti-oxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28806010/blastomycosis-and-histoplasmosis-in-a-patient-with-glioblastoma-receiving-temozolomide
#4
Aiham H Jbeli, John Yu
Malignant glioblastoma multiform (GBM) is the most common primary malignancy of the brain in the U.S. Temozolomide (TMZ) is the cornerstone of management along with surgical resection and radiotherapy. Because of the reduction in the CD4+ lymphocyte count as a side effect of TMZ use, this patient population is under risk for opportunistic infections like Pneumocystis jiroveci. A male patient with newly diagnosed glioblastoma multiform presented with non-productive cough and chest pain. Before presentation, the patient received the standard therapy including surgical resection, radiation and TMZ...
October 2016: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28800752/a-type-i-combi-targeting-approach-for-the-design-of-molecules-with-enhanced-potency-against-brca1-2-mutant-and-o6-methylguanine-dna-methyltransferase-mgmt-expressing-tumour-cells
#5
Zhor Senhaji Mouhri, Elliot Goodfellow, Bertrand Jean-Claude
BACKGROUND: Mutations of the DNA repair proteins BRCA1/2 are synthetically lethal with the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), which when inhibited, leads to cell death due to the absence of compensatory DNA repair mechanism. The potency of PARP inhibitors has now been clinically proven. However, disappointingly, acquired resistance mediated by the reactivation of wild type BRCA1/2 has been reported. In order to improve their efficacy, trials are ongoing to explore their combinations with temozolomide (TMZ)...
August 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28791452/long-term-daily-temozolomide-with-dose-dependent-efficacy-in-mgmt-promotor-methylation-negative-recurrent-high-grade-astrocytoma
#6
Zhengqiu Zhou, Tracy A Howard, John L Villano
Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day...
August 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28777020/direct-medical-costs-of-treatment-in-newly-diagnosed-high-grade-glioma-among-commercially-insured-us-patients
#7
Shan Jiang, Kala Hill, Dipen Patel, A Reginald Waldeck, Marc Botteman, Abdalla Aly, Andrew D Norden
AIM: This analysis assessed the direct medical costs of newly-diagnosed, temozolomide (TMZ)-treated glioblastoma (GBM) from the perspective of a US commercial setting. MATERIALS AND METHODS: The analysis included subjects identified from the IMS PharMetrics LifeLink Plus™ claims database from January 1, 2008 to August 31, 2014 who were ≥18 years of age, had ≥1 malignant brain cancer diagnosis, had brain surgery ≤90 days prior to TMZ initiation, had TMZ treatment, and were continuously enrolled for ≥12 months pre-diagnosis and ≥1 month post-diagnosis...
August 16, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28776671/%C3%AE-asarone-inhibited-cell-growth-and-promoted-autophagy-via-p53-bcl-2-bclin-1-and-p53-ampk-mtor-pathways-in-human-glioma-u251-cells
#8
Nanbu Wang, Qinxin Zhang, Laiyu Luo, Baile Ning, Yongqi Fang
Glioma is the most common type of primary brain tumor and has an undesirable prognosis. Autophagy plays an important role in cancer therapy, but it's effect is still not definite. P53 is an important tumor suppressor gene and protein that is closely to autophagy. Our aim was to study the effect of β-asarone on inhibiting cell proliferation in human glioma U251 cells and to detect the effect of the inhibition on autophagy through the P53 signal pathway. For cell growth, the cells were divided into four groups: the model, β-asarone, temozolomide (TMZ) and co-administration groups...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28767406/effect-of-trimetazidine-on-preventing-contrast-induced-nephropathy-in-diabetic-patients-with-renal-insufficiency
#9
Ziliang Ye, Haili Lu, Qiang Su, Xinhua Xian, Lang Li
BACKGROUND: Our study sought to assess the effect of trimetazidine (TMZ) on preventing contrast-induced nephropathy (CIN) in diabetic patients with renal insufficiency. MATERIALS AND METHODS: 106 diabetic patients with renal insufficiency who were undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) were enrolled in this study. Standard hydration was administered to both groups (the TMZ group and the control group). In the TMZ group, patients were orally administered TMZ for 48 hours before and 24 hours after CAG and/or PCI...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766920/temozolomide-alone-or-in-combination-with-doxorubicin-as-a-rescue-agent-in-37-cases-of-canine-multicentric-lymphoma
#10
E Treggiari, J W Elliott, S J Baines, L Blackwood
Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group...
August 2, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28765947/acid-ceramidase-confers-radioresistance-to-glioblastoma-cells
#11
Ninh B Doan, Ha S Nguyen, Mona M Al-Gizawiy, Wade M Mueller, Roger A Sabbadini, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine‑1-phosphate (Sph-1P)...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28756593/serial-changes-in-lymphocyte-subsets-in-patients-with-newly-diagnosed-high-grade-astrocytomas-treated-with-standard-radiation-and-temozolomide
#12
Jian L Campian, Anna F Piotrowski, Xiaobu Ye, Frances T Hakim, Jeremy Rose, Xiao-Yi Yan, Yao Lu, Ronald Gress, Stuart A Grossman
The immune system plays a significant role in cancer prevention and outcome. In high grade astrocytomas (HGA), severe lymphopenia is associated with shortened survival due to tumor progression. This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ...
July 29, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28747713/overcoming-blood-brain-barrier-with-a-dual-purpose-temozolomide-loaded-lactoferrin-nanoparticles-for-combating-glioma-serp-17-12433
#13
Sonali Kumari, Saad M Ahsan, Jerald M Kumar, Anand K Kondapi, Nalam M Rao
Targeted delivery of drugs to the brain is challenging due to the restricted permeability across the blood brain barrier (BBB). Gliomas are devastating cancers and their positive treatment outcome using Temozolomide (TMZ) is limited due to its short plasma half-life, systemic toxicity and limited access through the blood-brain barrier (BBB). Nanoparticles made of Lactoferrin (Lf) protein, have been shown to enhance the pharmacological properties of drugs. Here, we report the specific ability of Lf nanoparticles to cross BBB and target over-expressed Lf receptors on glioma for enhanced TMZ delivery...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744879/procarbazine-lomustine-and-vincristine-for-recurrent-high-grade-glioma
#14
REVIEW
Saurabh Parasramka, Goutham Talari, Myrna Rosenfeld, Jing Guo, John L Villano
BACKGROUND: Recurrent high-grade glioma (HGG) carries an extremely poor prognosis. There is no current standard of care or guideline-based recommendations. Nitrosourea-based multidrug chemotherapy or PCV - procarbazine, lomustine (CCNU) and vincristine - is one of the treatment options at recurrence. There has been no meta-analysis which looks at the benefits and harms of PCV chemotherapy in adults with recurrent HGG. OBJECTIVES: To assess the effectiveness and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy with other interventions in adults with recurrent high-grade glioma...
July 26, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28742502/temozolomide-therapy-for-resistant-prolactin-secreting-pituitary-adenomas-and-carcinomas-a-systematic-review
#15
REVIEW
Mussa H Almalki, Nora Nasser Aljoaib, Maha Jurais Alotaibi, Bayan Saloum Aldabas, Tayba Saleh Wahedi, Maswood H Ahmad, Fahad Alshahrani
Pituitary tumors represent 10-15% of all intracranial tumors; of these, prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to dopamine agonists (DA) as first-line therapy. However, treatment resistance remains a concern. Temozolomide (TMZ) is an oral alkylating agent that has shown promise in treating aggressive pituitary adenomas and carcinomas that are resistant to other therapies. To date, no control trials have been undertaken and only single case reports of pituitary tumors treated with TMZ have been published...
April 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28739174/inhibition-of-mitochondrial-fission-prevents-hypoxia-induced-metabolic-shift-and-cellular-proliferation-of-pulmonary-arterial-smooth-muscle-cells
#16
Valentina Parra, Roberto Bravo-Sagua, Ignacio Norambuena-Soto, Carolina P Hernández-Fuentes, Andrés G Gómez-Contreras, Hugo E Verdejo, Rosemarie Mellado, Mario Chiong, Sergio Lavandero, Pablo F Castro
Inhibition of mitochondrial fission prevents hypoxia-induced metabolic shift and cellular proliferation of pulmonary arterial smooth muscle cells. Valentina Parra, Roberto Bravo-Sagua, Ignacio Norambuena-Soto, Carolina P. Hernández-Fuentes, Andrés G. Gómez-Contreras, Hugo E. Verdejo, Rosemarie Mellado, Mario Chiong, Sergio Lavandero, Pablo F. Castro. Chronic hypoxia exacerbates proliferation of pulmonary arterial smooth muscle cells (PASMC), thereby reducing the lumen of pulmonary arteries. This leads to poor blood oxygenation and cardiac work overload, which are the basis of diseases such as pulmonary artery hypertension (PAH)...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28732990/combination-of-sonodynamic-with-temozolomide-inhibits-c6-glioma-migration-and-promotes-mitochondrial-pathway-apoptosis-via-suppressing-nhe-1-expression
#17
Lei Chen, Damin Cong, Yongzhe Li, Dan Wang, Qingsong Li, Shaoshan Hu
Temozolomide (TMZ) was used for clinical postoperative or non-surgical chemotherapy patients. However, its effect remains unsatisfactory and gradually discovered that the presence of chemoresistance. To explore more effective therapy using TMZ, we investigate the effects of combination of application of TMZ together with Sonodynamic therapy (SDT), which is based on the ultrasonic activation of a sonosensitizer, with low toxicity, noninvasive, deeper penetrability and a promising approach for treating malignant glioma by inducing apoptosis on glioma cells in vitro...
November 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28731079/a-polymeric-temozolomide-nanocomposite-against-orthotopic-glioblastoma-xenograft-tumor-specific-homing-directed-by-nestin
#18
Suma Prabhu, Jayant Sastri Goda, Srinivas Mutalik, Bhabani Shankar Mohanty, Pradip Chaudhari, Sharada Rai, Nayanabhirama Udupa, Bola Sadashiva Satish Rao
The development of effective therapeutic strategies for glioblastoma faces challenges such as modulating the blood brain barrier (BBB) for drug influx and selectively targeting tumor cells. Nanocarrier drug delivery strategies are functionalized to enhance vascular permeability. We engineered superparamagnetic iron oxide nanoparticle (SPION) based polymeric nanocomposites (84.37 ± 12.37 nm / 101.56 ± 7.42 nm) embedding temozolomide (TMZ) targeted against glioblastoma by tagging an antibody against nestin, a stem cell marker, and transferrin / polysorbate-80 to permeate the BBB...
August 3, 2017: Nanoscale
https://www.readbyqxmd.com/read/28726172/combined-treatment-for-non-small-cell-lung-cancer-and-breast-cancer-patients-with-brain-metastases-with-whole-brain-radiotherapy-and-temozolomide-a-systematic-review-and-meta-analysis
#19
REVIEW
Jingru Tian, Yien Luo, Juanjuan Xiang, Jingqun Tang
Brain metastasis is the leading cause of death among advanced non-small cell lung cancer (NSCLC) and breast cancer patients. The standard treatment for brain metastases is radiotherapy. The combination of radiotherapy and chemotherapy has been tested. However, the management of brain metastases has yet to be successful. Here, we aimed to determine the efficacy and safety of whole brain radiotherapy (WBRT) alone or in combination with temozolomide (TMZ) in NSCLC and breast cancer patients with brain metastases...
July 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28718668/olea-europaea-leaf-extract-improves-the-efficacy-of-temozolomide-therapy-by-inducing-mgmt-methylation-and-reducing-p53-expression-un-glioblastoma
#20
Gulcin Tezcan, Berrin Tunca, Hilal Demirci, Ahmet Bekar, Mevlut Ozgur Taskapilioglu, Hasan Kocaeli, Unal Egeli, Gulsah Cecener, Sahsine Tolunay, Ozgur Vatan
Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation...
July 18, 2017: Nutrition and Cancer
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