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Michael S Lee, Bert H O'Neil
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies, with differences in prognosis and effective therapies. Traditionally, NETs have been characterized by tumor grade, site of primary tumor, functional status, and presence of underlying familial syndrome. However, increased feasibility and utilization of next-generation sequencing and other methodologies have revealed new genomic and epigenetic aberrations. In the last decade, treatment options available for metastatic well-differentiated gastroenteropancreatic (GEP) NETs have expanded, with approval of antiangiogenic and mTOR-directed targeted therapies, and our armamentarium of active therapies is likely to further increase...
October 2016: Journal of Gastrointestinal Oncology
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
Hailong Zhao, Shuying Wang, Chengwei Song, Yunhong Zha, Li Li
BACKGROUND: The prognostic value of the status of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation measured by pyrosequencing assay (PSQ) among glioblastoma (GBM) patients was examined in meta-analysis. METHODS: Eligible studies that reported the association between the status of MGMT promoter methylation by PSQ and prognostic value of GBM patients from three electronic databases, like PubMed, EMBASE, and Cochrane library were involved in meta-analysis...
October 12, 2016: World Journal of Surgical Oncology
Josa M Frischer, Christine Marosi, Adelheid Woehrer, Johannes A Hainfellner, Karin Ute Dieckmann, Helmut Eiter, Wei-Te Wang, Ammar Mallouhi, Adolf Ertl, Engelbert Knosp, Martin Filipits, Klaus Kitz, Brigitte Gatterbauer
BACKGROUND: We evaluated Gamma Knife radiosurgery (GKRS) as a treatment option for patients with recurrent glioblastoma. PATIENTS AND METHODS: 42 patients with histopathologically diagnosed recurrent grade IV tumor were treated with GKRS. All patients had undergone standard multimodal first-line treatment. The average time from diagnosis to GKRS was 17.0 months. The median target volume was 5.1 cm3. The median margin dose was 10 Gy and the median central dose 20 Gy...
October 8, 2016: Stereotactic and Functional Neurosurgery
Tamotsu Sugai, Wataru Habano, Ryo Takagi, Hiroo Yamano, Makoto Eizuka, Noriyuki Arakawa, Yayoi Takahashi, Eiichiro Yamamoto, Keisuke Kawasaki, Syunichi Yanai, Kazuyuki Ishida, Hiromu Suzuki, Takayuki Matsumoto
BACKGROUND: Colorectal laterally spreading tumors (LSTs) are classified into LST-Gs and LST-NGs, according to macroscopic findings. In the present study, we determined the genetic and epigenetic alterations within colorectal LSTs and protruding adenomas. METHODS: A crypt isolation method was used to isolate DNA from tumors and normal glands of 73 macroscopically verified colorectal LSTs (histologically defined adenomas; 38 LST-Gs and 35 LST-NGs) and 36 protruding adenomas...
October 4, 2016: Journal of Gastroenterology
Uta Duppel, Matthias Woenckhaus, Christian Schulz, Johannes Merk, Wolfgang Dietmaier
Aberrant promoter methylation of tumor relevant genes frequently occurs in early steps of carcinogenesis and during tumor progression. Epigenetic alterations could be used as potential biomarkers for early detection and for prediction of prognosis and therapy response in lung cancer. The present study quantitatively analyzed the methylation status of known and potential gatekeeper and tumor suppressor genes [O-6-methylguanine-DNA methyltransferase (MGMT), Ras association domain family member 1A (RASSF1A), Ras protein activator like 1 (RASAL1), programmed cell death 4 (PDCD4), metastasis suppressor 1 (MTSS1) and tumor suppressor candidate 3 (TUSC3)] in 42 lung cancers and in corresponding non-malignant bronchus and lung tissue using bisulfite-conversion independent methylation-quantification of endonuclease-resistant DNA (MethyQESD)...
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
Jörg Fahrer, Bernd Kaina
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is causally linked to dietary habits, notably the intake of processed and red meat. Processed and red meat contain dietary carcinogens, including heterocyclic aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce various N-methylated DNA adducts and O(6)-methylguanine (O(6)-MeG), which are removed by base excision repair (BER) and O(6)-methylguanine-DNA methyltransferase (MGMT), respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed from DNA by nucleotide excision repair (NER)...
October 6, 2016: Food and Chemical Toxicology
Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Guy Kantor, Martin J B Taphoorn, Mohamed Ben Hassel, Christian Hartmann, Gail Ryan, David Capper, Johan M Kros, Sebastian Kurscheid, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frederic Dhermain, Jacoline E Bromberg, Loic Feuvret, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Nicolas Dif, Carmen Balana, Jose Bravo-Marques, Paul M Clement, Christine Marosi, Tzahala Tzuk-Shina, Robert A Nordal, Jeremy Rees, Denis Lacombe, Warren P Mason, Roger Stupp
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration...
September 26, 2016: Lancet Oncology
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
J K Molitoris, Y J Rao, S N Badiyan, H R Gittleman, J Barnholtz-Sloan, S M Bentzen, J Huang, M P Mehta
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
C W Wee, E Kim, I H Kim, I A Kim
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Yang Yuan, Mao Yunhe, Wang Xiang, Liu Yanhui, Liang Ruofei, Luo Jiewen, Mao Qing
BACKGROUND: Tumor location, which serves as a prognostic factor for high-grade gliomas, may reflect the molecular and genetic phenotype of tumor initiate cells and thus predict tumor origin. Therefore, the purpose of this study was to combine radiographic atlases and tumor biomarkers through a voxel-based neuroimaging approach. METHODS: Preoperative MRIs were collected from 65 newly diagnosed patients with histologically confirmed high-grades gliomas. These samples were analyzed for TP53 mutations and MMP-9...
November 2016: Clinical Neurology and Neurosurgery
Haley Gittleman, Daniel Lim, Michael W Kattan, Arnab Chakravarti, Mark R Gilbert, Andrew B Lassman, Simon S Lo, Mitchell Machtay, Andrew E Sloan, Erik P Sulman, Devin Tian, Michael A Vogelbaum, Tony J C Wang, Marta Penas-Prado, Emad Youssef, Deborah T Blumenthal, Peixin Zhang, Minesh P Mehta, Jill S Barnholtz-Sloan
BACKGROUND: Glioblastoma (GBM) is the most common primary malignant brain tumor. Nomograms are often used for individualized estimation of prognosis. This study aimed to build and independently validate a nomogram to estimate individualized survival probabilities for patients with newly diagnosed GBM, using data from 2 independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. METHODS: This analysis included information on 799 (RTOG 0525) and 555 (RTOG 0825) eligible and randomized patients with newly diagnosed GBM and contained the following variables: age at diagnosis, race, gender, Karnofsky performance status (KPS), extent of resection, O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status, and survival (in months)...
September 23, 2016: Neuro-oncology
Jane Shen-Gunther, Chiou-Miin Wang, Graham M Poage, Chun-Lin Lin, Luis Perez, Nancy A Banks, Tim Hui-Ming Huang
BACKGROUND: The Pap smear has remained the foundation for cervical cancer screening for over 70 years. With advancements in molecular diagnostics, primary high-risk human papillomavirus (hrHPV) screening has recently become an accepted stand-alone or co-test with conventional cytology. However, both diagnostic tests have distinct limitations. The aim of this study was to determine the association between HPV genotypes and cellular epigenetic modifications in three grades of cervical cytology for screening biomarker discovery...
2016: Clinical Epigenetics
Chiara Cremolini, Filippo Pietrantonio
In metastatic colorectal cancer, the optimization of upfront treatment and the continuum of care based on patients' exposure to multiple treatment lines have reached a plateau of efficacy. Therefore, a paradigm shift is ongoing towards precision medicine and personalized treatments based on the specific molecular features of the disease. In this perspective, the improved knowledge of disease biology coming from the lab has prompted a rapid translation from bench to bedside of newer targeted strategies. Here, we focus on the most promising biomarkers already included or close to adoption in daily clinical practice...
September 20, 2016: Tumori
Thomas B Brunner
This article aims to review the rationale behind the combination of radiotherapy and chemotherapy. Theoretical concepts describing the principles of the joint effects of chemoradiotherapy are reviewed. Preclinical and clinical evidence are collected and summarised demonstrating the co-operation between the two modalities which form the mainstay of the treatment of most solid tumours. Initially, the evolution of chemoradiotherapy was mostly empirically driven which is true for both, the early studies and the experimental investigations, rather than relying on scientific rationale...
August 2016: Best Practice & Research. Clinical Gastroenterology
Tao Fu, Anup Sharmab, Fei Xie, Yanliang Liu, Kai Li, Weiwei Wan, Stephen B Baylin, Christopher L Wolfgang, Nita Ahuja
BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. METHODS: Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations...
2016: PloS One
Daniel Xia, David A Reardon, Jacqueline L Bruce, Neal I Lindeman
The methylation status of the promoter of the O(6)-methylguanine DNA methyltransferase gene (MGMT) is an established prognostic and predictive biomarker of glioblastoma (GBM). At the Center for Advanced Molecular Diagnostics, MGMT testing is performed by methylation-specific PCR with multiple replicates, leading to three types of reportable results: methylated, unmethylated, and inconsistently methylated. An inconsistently methylated result is reported when a methylated peak is seen in some but not all of the PCR replicates from a single DNA sample...
September 14, 2016: Journal of Molecular Diagnostics: JMD
Philipp Kickingereder, David Bonekamp, Martha Nowosielski, Annekathrin Kratz, Martin Sill, Sina Burth, Antje Wick, Oliver Eidel, Heinz-Peter Schlemmer, Alexander Radbruch, Jürgen Debus, Christel Herold-Mende, Andreas Unterberg, David Jones, Stefan Pfister, Wolfgang Wick, Andreas von Deimling, Martin Bendszus, David Capper
Purpose To evaluate the association of multiparametric and multiregional magnetic resonance (MR) imaging features with key molecular characteristics in patients with newly diagnosed glioblastoma. Materials and Methods Retrospective data evaluation was approved by the local ethics committee, and the requirement to obtain informed consent was waived. Preoperative MR imaging features were correlated with key molecular characteristics within a single-institution cohort of 152 patients with newly diagnosed glioblastoma...
September 16, 2016: Radiology
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