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https://www.readbyqxmd.com/read/28346397/the-process-and-regulatory-components-of-inflammation-in-brain-oncogenesis
#1
REVIEW
A G M Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide, Kalkunte S Srivenugopal
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers...
March 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28339723/leveraging-molecular-datasets-for-biomarker-based-clinical-trial-design-in-glioblastoma
#2
Shyam K Tanguturi, Lorenzo Trippa, Shakti H Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I Lindeman, Azra H Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y Wen, Keith L Ligon, Brian M Alexander
Background.: Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. Methods.: We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP)...
February 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28328619/evaluation-of-o6-methylguanine-dna-methyltransferase-as-a-predicting-factor-of-response-to-temozolomide-based-chemotherapy-in-well-differentiated-metastatic-pancreatic-neuroendocrine-tumors
#3
Paul Girot, Clotilde Dumars, Jean-François Mosnier, Léa Muzellec, Hélène Senellart, Fanny Foubert, François-Xavier Caroli-Bosc, Estelle Cauchin, Nicolas Regenet, Tamara Matysiak-Budnik, Yann Touchefeu
OBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy...
March 21, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28324304/management-of-elderly-patients-with-glioblastoma
#4
REVIEW
Patrick Roth, Dorothee Gramatzki, Michael Weller
PURPOSE OF REVIEW: Glioblastoma represents one of the major challenges in neurooncology and approximately half of the patients are 60 years or older. We summarize the particular situation of elderly glioblastoma patients with a focus on therapeutic considerations. RECENT FINDINGS: Favorable molecular markers such as mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are virtually absent in glioblastomas in elderly patients. Treatment options are similar to the situation in young patients and comprise surgical resection, radiation therapy, and alkylating chemotherapy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28316990/diagnostic-and-therapeutic-biomarkers-in-glioblastoma-current-status-and-future-perspectives
#5
REVIEW
Wojciech Szopa, Thomas A Burley, Gabriela Kramer-Marek, Wojciech Kaspera
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3-5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#6
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28314302/kras-mutant-status-may-be-associated-with-distant-recurrence-in-early-stage-rectal-cancer
#7
Michail Sideris, Jane Moorhead, Salvador Diaz-Cano, Amyn Haji, Savvas Papagrigoriadis
BACKGROUND/AIM: Total mesorectal excision combined with neo-adjuvant chemoradiotherary (CRT) and adjuvant chemotherapy, has been the standard treatment of locally advanced rectal cancer (LARC). Although TNM (Tumor, Node, Metastasis) classification for malignant Tumors is still the cornerstone in rectal cancer staging, there has been an effort to identify molecular biomarkers with additional prognostic or predictive value. MATERIALS AND METHODS: We retrospectively analyzed molecular biomarkers on prospectively collected histological specimens and clinical data from a cohort of 135 consecutive rectal cancer cases who underwent radical excision in a tertiary center between 2011-2014 (males=87, females=48, age range=22-89 years, mean=64,67 years, SD=13...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314286/safety-and-tolerance-of-d-l-methadone-in-combination-with-chemotherapy-in-patients-with-glioma
#8
Julia Onken, Claudia Friesen, Peter Vajkoczy, Martin Misch
BACKGROUND/AIM: D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy. PATIENTS AND METHODS: The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303493/the-effect-of-molecular-diagnostics-on-the-treatment-of-glioma
#9
REVIEW
Nancy Ann Oberheim Bush, Nicholas Butowski
PURPOSE OF REVIEW: This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. RECENT FINDINGS: Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28302331/novel-recursive-partitioning-analysis-classification-for-newly-diagnosed-glioblastoma-a-multi-institutional-study-highlighting-the-mgmt-promoter-methylation-and-idh1-gene-mutation-status
#10
Chan Woo Wee, Eunji Kim, Nalee Kim, In Ah Kim, Tae Min Kim, Yu Jung Kim, Chul-Kee Park, Jin Wook Kim, Chae-Yong Kim, Seung Hong Choi, Jae Hyoung Kim, Sung-Hye Park, Gheeyoung Choe, Soon-Tae Lee, Jong Hee Chang, Se Hoon Kim, Chang-Ok Suh, Il Han Kim
BACKGROUND AND PURPOSE: To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. METHODS AND MATERIALS: Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42...
March 13, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28298550/limited-role-for-extended-maintenance-temozolomide-for-newly-diagnosed-glioblastoma
#11
Dorothee Gramatzki, Philipp Kickingereder, Bettina Hentschel, Jörg Felsberg, Ulrich Herrlinger, Gabriele Schackert, Jörg-Christian Tonn, Manfred Westphal, Michael Sabel, Uwe Schlegel, Wolfgang Wick, Torsten Pietsch, Guido Reifenberger, Markus Loeffler, Martin Bendszus, Michael Weller
OBJECTIVE: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. METHODS: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression...
March 15, 2017: Neurology
https://www.readbyqxmd.com/read/28296618/short-course-radiation-plus-temozolomide-in-elderly-patients-with-glioblastoma
#12
James R Perry, Normand Laperriere, Christopher J O'Callaghan, Alba A Brandes, Johan Menten, Claire Phillips, Michael Fay, Ryo Nishikawa, J Gregory Cairncross, Wilson Roa, David Osoba, John P Rossiter, Arjun Sahgal, Hal Hirte, Florence Laigle-Donadey, Enrico Franceschi, Olivier Chinot, Vassilis Golfinopoulos, Laura Fariselli, Antje Wick, Loic Feuvret, Michael Back, Michael Tills, Chad Winch, Brigitta G Baumert, Wolfgang Wick, Keyue Ding, Warren P Mason
Background Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown. Methods We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma...
March 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#13
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278076/adenovirus-based-strategies-enhance-antitumor-capability-through-p53-mediated-downregulation-of-mgmt-in-uveal-melanoma
#14
Xun Li, Ling Yuan, Jianfeng Zhao, Hui Yang, Yunzhi Yang, Yanfei Zhang, Biyun Cun
Uveal melanoma (UM) is an intractable disease with a low survival rates, despite adequate local treatment, as a result of its metastatic characteristics. Thus, new therapeutic strategies, including combinations of novel gene therapy and traditional chemotherapy, are under investigation to improve long-term prognosis. Dacarbazine or DTIC, an alkylating agent which results in DNA methylation, is most commonly used to treat melanoma but the response is very limited. The O6-methylguanine DNA methyl transferase (MGMT), a DNA repair protein, is involved in chemoresistance in DTIC treatment...
February 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28275120/role-of-mgmt-methylation-status-at-time-of-diagnosis-and-recurrence-for-patients-with-glioblastoma-clinical-implications
#15
Alba A Brandes, Enrico Franceschi, Alexandro Paccapelo, Giovanni Tallini, Dario De Biase, Claudio Ghimenton, Daniela Danieli, Elena Zunarelli, Giovanni Lanza, Enrico Maria Silini, Carmelo Sturiale, Lorenzo Volpin, Franco Servadei, Andrea Talacchi, Antonio Fioravanti, Maria Pia Foschini, Stefania Bartolini, Annalisa Pession, Mario Ermani
BACKGROUND: MGMT methylation status represents a powerful prognostic factor in newly diagnosed glioblastoma (GBM). Recently, its role in recurrent tumors has also been suggested; however, few data investigating the stability of this biomarker during the clinical course of the disease are available. In this study, we evaluated the rate of change of MGMT methylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM. METHODS: We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion...
March 8, 2017: Oncologist
https://www.readbyqxmd.com/read/28267302/cytomorphology-of-metastatic-pituitary-carcinoma-to-the-bone
#16
Christopher M Chandler, Xiaoqi Lin
Metastatic pituitary carcinoma to bone is rare. In this report, we present a case of a 59-year-old female with recurrent pituitary adenoma of the sparsely granulated somatotroph subtype with metastasis to a few bony sites 10 years later. Needle core biopsy (NCB) with touch preparations was performed on a 5 mm lesion in left ilium. Diff-Quik stained NCB touch preparation slides showed a few loosely cohesive epithelial polygonal cells that were arranged in nests or acini, or singly, had scant vacuolated cytoplasm and eccentrically located round nuclei (plasmacytoid) with slight nuclear pleomorphism, fine granular chromatin, conspicuous nucleoli, and smooth nuclear membrane...
March 7, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/28266716/the-prognostic-value-of-mgmt-promoter-methylation-in-glioblastoma-a-meta-analysis-of-clinical-trials
#17
Maryam Moradi, Afsane Bahrami, Soodabeh ShahidSales, Marjan Joodi, Mona Joudi Mashhad, Seyed Mahdi Hassanian, Kazem Anvari, Amir Avan
The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) is suggested to be associated with resistance to alkylating agents such as Temozolomide which is being used in treatment of patients with glioblastoma (GBM). Therefore we evaluated the associations between MGMT promoter methylation and prognosis of patients with glioblastoma (GBM). Data were extracted from publications in Embase, PubMed, and the Cochrane Library. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained and 4097 subjects were enrolled...
March 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28260500/current-therapeutic-alternatives-and-new-perspectives-in-glioblastoma-multiforme
#18
Claudia Andrea Quezada Monrás, Rody San Martín, Sebastián Muñoz, Ignacio Niechi, Jake Howden, Daniel Alejandro Uribe, José Ignacio Erices, Ángelo Sebastián Torres Arévalo
BACKGROUND: In the last two decades, there have been significant technological advances in the early detection of brain tumors. However, no notable improvements have been observed in the treatment of Glioblastoma Multiforme (GBM), the most common brain neoplasm coupled with the worst prognosis. GBM is characterized by an extensive resistance to a broad spectrum of anti-tumor drugs. This property is the result of a phenomenon known as Multiple Drug Resistance (MDR), which significantly limits non-invasive alternative therapies...
March 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28254081/learning-mri-based-classification-models-for-mgmt-methylation-status-prediction-in-glioblastoma
#19
Vasileios G Kanas, Evangelia I Zacharaki, Ginu A Thomas, Pascal O Zinn, Vasileios Megalooikonomou, Rivka R Colen
BACKGROUND AND OBJECTIVE: The O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation has been shown to be associated with improved outcomes in patients with glioblastoma (GBM) and may be a predictive marker of sensitivity to chemotherapy. However, determination of the MGMT promoter methylation status requires tissue obtained via surgical resection or biopsy. The aim of this study was to assess the ability of quantitative and qualitative imaging variables in predicting MGMT methylation status noninvasively...
March 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28241740/hinokitiol-induces-dna-demethylation-via-dnmt1-and-uhrf1-inhibition-in-colon-cancer-cells
#20
Jung Seon Seo, Young Ha Choi, Ji Wook Moon, Hyeon Soo Kim, Sun-Hwa Park
BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co...
February 27, 2017: BMC Cell Biology
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