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Mona Pazhouhi, Reyhaneh Sariri, Arezou Rabzia, Mozafar Khazaei
OBJECTIVES: Glioblastoma multiforme (GBM) is one of the most lethal forms of human cancer and temozolomide (TMZ) is currently part of the standard treatment for this disease. Combination therapy using natural substances can enhance the anti-cancer activity of TMZ. The purpose of this study was to evaluate the effect of TMZ in combination with thymoquinone (TQ) on human GBM cell line (U87MG). MATERIALS AND METHODS: The cell line was treated with TMZ and/or TQ. Cell viability was assessed using trypan blue and MTT assay...
August 2016: Iranian Journal of Basic Medical Sciences
Eugene J Vaios, Brian V Nahed, Alona Muzikansky, Amir T Fathi, Jorg Dietrich
OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS])...
October 14, 2016: Journal of Neurosurgery
Tomokazu Aoki, Yoshiki Arakawa, Tetsuya Ueba, Masashi Oda, Namiko Nishida, Yukinori Akiyama, Tetsuya Tsukahara, Koichi Iwasaki, Nobuhiro Mikuni, Susumu Miyamoto
The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m(2)/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m(2)/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated...
October 11, 2016: Neurologia Medico-chirurgica
Xingliang Dai, Cheng Ma, Qing Lan, Tao Xu
Glioma is still difficult to treat because of its high malignancy, high recurrence rate, and high resistance to anticancer drugs. An alternative method for research of gliomagenesis and drug resistance is to use in vitro tumor model that closely mimics the in vivo tumor microenvironment. In this study, we established a 3D bioprinted glioma stem cell model, using modified porous gelatin/alginate/fibrinogen hydrogel that mimics the extracellular matrix. Glioma stem cells achieved a survival rate of 86.92%, and proliferated with high cellular activity immediately following bioprinting...
October 11, 2016: Biofabrication
Abdolali Amiri, Phuong Uyen Le, Alexandre Moquin, Gayane Machkalyan, Kevin Petrecca, John W Gillard, Nathan Yoganathan, Dusica Maysinger
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches are standard treatments but not effective in long term. In this study we tested the treatment with acetazolamide (ATZ), an inhibitor of CAIX, alone or combined with TMZ. The experiments were performed in 2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor stem cells (BTSC)...
October 1, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Thais Torquato Sales, Fernando Francisco Borges Resende, Natália Lemos Chaves, Simoneide Souza Titze-De-Almeida, Sônia Nair Báo, Marcella Lemos Brettas, Ricardo Titze-De-Almeida
Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various types of cancer cell overexpress the ether à go-go 1 (Eag1) potassium channel. Therefore, the present study examined the role of Eag1 in the cell damage caused by TMZ on the U87MG glioblastoma cell line...
October 2016: Oncology Letters
Taiichi Saito, Kazuhiko Sugiyama, Fusao Ikawa, Fumiyuki Yamasaki, Minoru Ishifuro, Takeshi Takayasu, Ryo Nosaka, Yoshihiro Muragaki, Takakazu Kawamata, Kaoru Kurisu
OBJECTIVE: The current standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). We hypothesized that the permeability surface area product (PS) from a perfusion CT (PCT) study is associated with sensitivity to TMZ. The aim of this study was to determine whether PS values were correlated with prognosis of GBM patients who received the standard treatment protocol. METHODS: This study included 36 patients with GBM that were newly diagnosed between October 2005 and September 2014 and who underwent preoperative PCT study and the standard treatment protocol...
September 27, 2016: World Neurosurgery
Doo-Sik Kong, Do-Hyun Nam, Shin-Hyuk Kang, Jae Won Lee, Jong-Hee Chang, Jeong-Hoon Kim, Young-Jin Lim, Young-Cho Koh, Yong-Gu Chung, Jae-Min Kim, Choong-Hyun Kim
PURPOSE: Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas. EXPERIMENTAL DESIGN: In this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group)...
September 27, 2016: Oncotarget
Yasuharu Akasaki, Tetsuro Kikuchi, Sadamu Homma, Shigeo Koido, Toshifumi Ohkusa, Tetsunori Tasaki, Kazumi Hayashi, Hideo Komita, Nobuyuki Watanabe, Yuta Suzuki, Yohei Yamamoto, Ryosuke Mori, Takao Arai, Toshihide Tanaka, Tatsuhiro Joki, Takaaki Yanagisawa, Yuichi Murayama
BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol...
September 29, 2016: Cancer Immunology, Immunotherapy: CII
YiHan Wu, Li Dong, SaRuLa Bao, MeiLing Wang, YongLi Yun, RunXiu Zhu
Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). Romidepsin (FK228), a histone deacetylase inhibitor, is a promising new class of antineoplastic agent with the capacity to induce growth arrest and/or apoptosis of cancer cells. However, combination of the two drugs in glioma remains largely unknown. In the present study, we evaluated the combinatory effects of FK228 with TMZ in glioma, and its molecular mechanisms responsible for these effects...
September 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Chigang Du, Junquan Ren, Rui Zhang, Tao Xin, Zhongmin Li, Zhiti Zhang, Xinghua Xu, Qi Pang
BACKGROUND MGMT methylation status can influence the therapeutic effect and prognosis of glioblastoma (GBM). There are conflicting results from studies evaluating the efficacy of bevacizumab (BV) when it is combined with temozolomide (TMZ) and radiotherapy (RT) in patients diagnosed with GBM with different MGMT methylation status. MATERIAL AND METHODS Data were extracted from publications in PubMed, Embase, and The Cochrane Library, with the last search performed March 23, 2016. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Koji Yoshimoto, Akiko Kada, Daisuke Kuga, Ryusuke Hatae, Hideki Murata, Yojiro Akagi, Kunihiro Nishimura, Ryota Kurogi, Ataru Nishimura, Nobuhiro Hata, Masahiro Mizoguchi, Tetsuro Sayama, Koji Iihara
We conducted this study to clarify the current trends and healthcare resource usage in the treatment of inpatients with primary malignant brain tumors. The Diagnostic Procedure Combination (DPC) data of all inpatients treated between 2013 and 2014 in the 370 core and branch hospitals enrolled in the Japanese Neurosurgical Society training program were collected. DPC is a discharge abstract and administrative claims database of inpatients. We assessed 6,142 primary, malignant brain tumor patients. Patient information, diagnostic information, treatment procedure, and healthcare resource usage were analyzed...
September 27, 2016: Neurologia Medico-chirurgica
Georgia Kourlaba, George Gourzoulidis, George Andrikopoulos, Konstantinos Tsioufis, Alexandra Beletsi, Nikos Maniadakis
BACKGROUND: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. METHODS: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective...
September 27, 2016: BMC Health Services Research
Andreas F Hottinger, Monika E Hegi, Brigitta G Baumert
PURPOSE OF REVIEW: The management of patients suffering from low-grade gliomas (LGGs) remains a challenge in absence of a definite curative therapy. The median survival is highly variable, from 2 years (high-risk disease) to over 15 years (low risk). The aim of this review is to provide a practical step-by-step evaluation of the available treatment options for patients with LGGs. RECENT FINDINGS: Next to clinical prognostic markers, both the isocitrate dehydrogenase (IDH) mutation status and the status of 1p/19q codeletion are key prognostic factors for the optimal management of patients with LGG...
September 26, 2016: Current Opinion in Neurology
Mathieu Seyfrid, Viola Marschall, Simone Fulda
Small-molecule inhibitors of Inhibitor of Apoptosis proteins such as Smac mimetics have been reported to provide a promising tool to sensitize glioblastoma (GBM) cells to cytotoxic therapies including chemotherapeutic drugs. However, the underlying molecular mechanisms of action have not yet been fully unraveled. In the present study, we therefore investigated the role of reactive oxygen species (ROS) in the regulation of Smac mimetic/temozolomide (TMZ)-induced cell death in GBM cells. Here, we show that the Smac mimetic BV6 and TMZ act in concert to stimulate the production of both cytosolic and mitochondrial ROS...
November 2016: Anti-cancer Drugs
Masahide Matsuda, Tetsuya Yamamoto, Eiichi Ishikawa, Hiroyoshi Akutsu, Shingo Takano, Akira Matsumura
Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy...
September 23, 2016: Neurologia Medico-chirurgica
Rui Pinheiro, Cláudia Braga, Gisela Santos, Maria R Bronze, Maria J Perry, Rui Moreira, Dora Brites, Ana S Falcão
Glioblastoma (GBM) is the most common and aggressive type of brain tumor in adults. The triazene Temozolomide (TMZ), an alkylating drug, is the classical chemotherapeutic agent for gliomas, but has been disappointing against the highly invasive and resistant nature of GBM. Hybrid compounds may open new horizons within this challenge. The multicomponent therapeutic strategy here used resides on a combination of two repurposing drugs acting by different but potentially synergistic mechanisms, improved efficacy, and lower resistance effects...
October 11, 2016: ACS Chemical Neuroscience
Andreas F Hottinger, Patricia Pacheco, Roger Stupp
Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM...
October 2016: Neuro-oncology
Anam Khan, Syed Sarim Imam, Mohammed Aqil, Abdul Ahad, Yasmin Sultana, Asgar Ali, Khalid Khan
The aim of the present work was to investigate the efficacy of temozolomide nanostructured lipid carriers (TMZ-NLCs) to enhance brain targeting via nasal route administration. The formulation was optimized by applying a four-factor, three-level Box-Behnken design. The developed formulations and the functional relationships between their independent and dependent variables were observed. The independent variables used in the formulation were gelucire (X1), liquid lipid/total lipid (X2), Tween 80 (X3), and sonication time (X4), and their effects were observed with regard to size (Y1), % drug release (Y2), and drug loading (Y3)...
October 3, 2016: Molecular Pharmaceutics
Lan B Hoang-Minh, Loic P Deleyrolle, Nariaki S Nakamura, Alexander K Parker, Regina T Martuscello, Brent A Reynolds, Matthew R Sarkisian
A better understanding of the molecules implicated in the growth and survival of glioblastoma (GBM) cells and their response to temozolomide (TMZ), the standard-of-care chemotherapeutic agent, is necessary for the development of new therapies that would improve the outcome of current GBM treatments. In this study, we characterize the role of pericentriolar material 1 (PCM1), a component of centriolar satellites surrounding centrosomes, in GBM cell proliferation and sensitivity to genotoxic agents such as TMZ...
October 2016: Translational Oncology
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