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Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
Hailong Li, Jiye Li, Gang Cheng, Jianning Zhang, Xuezhen Li
PURPOSE: This study aimed to investigate the potential association between IDH mutation and O(6)-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy. METHODS: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis...
October 12, 2016: Clinical Neurology and Neurosurgery
Shigeo Ohba, Yuichi Hirose
Glioblastomas are the most aggressive of all gliomas and have the worst prognosis, with 5-year survival rates of less than 10%. Temozolomide (TMZ) is a DNA-methylating agent. Now that TMZ is available, the standard treatment is to resect as much of the tumor as possible without inducing unacceptable neurologic deficits, followed by treatment with radiation and TMZ. TMZ has also been used for maintenance therapy. Recently, bevacizumab, which is a monoclonal antibody to vascular endothelial growth factor, has been used for the initial treatment of glioblastomas and for the treatment of recurrent glioblastomas...
October 14, 2016: Current Medicinal Chemistry
Liang Leng, Xiaojun Zhong, Guan Sun, Wen Qiu, Lei Shi
Temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM) as it can effectively inhibit the growth of GBM for some months; however, this cancer type is still incurable. The existence of glioma stem cells (GSCs) is thought to be responsible for the invariable recurrence of GBM after treatment, but GSCs are insensitive to TMZ. Our recent research showed that demethoxycurcumin (DMC), a component of curcumin, was superior to TMZ in its ability to inhibit proliferation and induce apoptosis of GSCs in vitro...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Andreas Maus, Godefridus J Peters
Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer's biology is a key for the development of more effective therapy approaches...
October 17, 2016: Amino Acids
Jianheng Wu, Linfan Li, Guangyuan Jiang, Hui Zhan, Nannan Wang
Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues...
October 12, 2016: International Journal of Oncology
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
Heather Marion Ames, Ming Yuan, Maria Adelita Vizcaíno, Wayne Yu, Fausto J Rodriguez
Low-grade (WHO I-II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and have an important role in cancer, including brain tumors...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Steven J Isakoff, Shannon Puhalla, Susan M Domchek, Michael Friedlander, Bella Kaufman, Mark Robson, Melinda L Telli, Véronique Diéras, Hyo Sook Han, Judy E Garber, Eric F Johnson, David Maag, Qin Qin, Vincent L Giranda, Stacie P Shepherd
Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609)...
October 14, 2016: Future Oncology
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
Mohamad Chehimi, Mathieu Boone, Cyril Chivot, Hervé Deramond, Jean-Marc Constans, Mony Chenda Ly, Bruno Chauffert
There is no effective treatment for recurrent glioblastoma (GB) when temozolomide-based radiochemotherapy fails. In theory, intra-arterial (IA) delivery of cytotoxic agents could achieve higher drug concentrations in tumors compared to intravenous injection. Moreover, choosing a highly lipid-soluble drug could make the most of the first-pass effect. Here, we evaluated idarubicin (IDA), a lipophilic anthracycline, in an in vitro assay using four human GB cell lines and compared it with 11 other drugs previously used for the IA treatment of brain tumors...
May 2016: Case Reports in Oncology
Veronica Villani, Roberta Merola, Antonello Vidiri, Alessandra Fabi, Mariantonia Carosi, Diana Giannarelli, Laura Marucci, Marta Maschio, Carmine M Carapella, Andrea Pace
PURPOSE: To explore the efficacy and toxicity of an extended schedule of temozolomide (50 mg/mq 1 week on/1 week off) in a population of newly diagnosed low-grade gliomas (LGG). METHODS: Primary endpoints were progression-free survival (PFS) at 12 and 24 months and response rate evaluated with Response Assessment in Neuro-Oncology Criteria. Secondary endpoints were clinical benefit (reduction of seizures frequency), reduction of steroid, and modifications of Karnofsky Performance Status...
September 22, 2016: Tumori
Stefano M Priola, Felice Esposito, Salvatore Cannavò, Alfredo Conti, Rosaria V Abbritti, Valeria Barresi, Sergio Baldari, Francesco Ferraù, Antonino Germanò, Francesco Tomasello, Filippo F Angileri
BACKGROUND: Although pituitary adenomas are considered benign lesions, a small group may exhibit a clinically aggressive behavior, sometimes independently from the classic markers of aggressiveness, including the Ki67 labeling index and/or p53 expression. METHODS: We selected 7 subjects harboring a pituitary tumor with clinical features of aggressiveness. Patients underwent a full preoperative and postoperative endocrinological and neuroradiological work-up. Two were non-functioning, two PRL-secreting, two ACTH-secreting, and one a GH-secreting adenoma...
October 3, 2016: World Neurosurgery
Junko Murai, Ying Feng, Guoying K Yu, Yuanbin Ru, Sai-Wen Tang, Yuqiao Shen, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models...
September 27, 2016: Oncotarget
Chuan He Yang, Yinan Wang, Michelle Sims, Chun Cai, Ping He, Junming Yue, Jinjun Cheng, Frederick A Boop, Susan R Pfeffer, Lawrence M Pfeffer
MicroRNAs (miRNAs) play critical roles in regulating cancer cell proliferation, migration, survival and sensitivity to chemotherapy. The potential application of using miRNAs for cancer prognosis holds great promise but miRNAs with predictive value remain to be identified and underlying mechanisms of how they promote or suppress tumorigenesis are not completely understood. Here, we show a strong correlation between miR203 expression and brain cancer patient survival. Low miR203 expression is found in subsets of brain cancer patients, especially glioblastoma...
October 2, 2016: Oncotarget
Katharina Koch, Rudolf Hartmann, Friederike Schröter, Abigail Kora Suwala, Donata Maciaczyk, Andrea Caroline Krüger, Dieter Willbold, Ulf Dietrich Kahlert, Jaroslaw Maciaczyk
Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target the most aggressive subtype of glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible for tumor initiation, progression, and relapse. Furthermore, they have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT) thereby inducing tumor dissemination and chemo resistance...
September 29, 2016: Oncotarget
Lin Lin, Guangzhi Wang, Jianguang Ming, Xiangqi Meng, Bo Han, Bo Sun, Jinquan Cai, Chuanlu Jiang
Gliomas are the most common primary intracranial malignant tumors in adults. Surgical resection followed by optional radiotherapy and chemotherapy is the current standard therapy for glioma patients. Vimentin, a protein of intermediate filament family, could maintain the cellular integrity and participate in several cell signal pathways to modulate the motility and invasion of cancer cells. The purpose of the present research was to identify the relationship between vimentin expression and clinical characteristics and detect the prognostic and predictive ability of vimentin in patients with glioma...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Raita Fukaya, Masatoki Ozaki, Dai Kamamoto, Yukina Tokuda, Tokuhiro Kimura, Masahito Fukuchi, Koji Fujii
The prognosis of recurrent and disseminated glioblastoma is very poor. Bevacizumab is an effective established therapy for recurrent glioblastoma following treatment with radiotherapy plus temozolomide. However, the efficacy of bevacizumab is limited to prolonging progression-free survival, without significant prolongation of the overall survival. We herein report a case of glioblastoma in a 32-year-old female patient with encephalocraniocutaneous lipomatosis (ECCL) that had disseminated following surgical resection and subsequent treatment with temozolomide and radiation therapy...
October 2016: Molecular and Clinical Oncology
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