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https://www.readbyqxmd.com/read/28339824/a-phase-i-trial-of-the-mek-inhibitor-selumetinib-azd6244-in-pediatric-patients-with-recurrent-or-refractory-low-grade-glioma-a-pediatric-brain-tumor-consortium-pbtc-study
#1
Anuradha Banerjee, Regina I Jakacki, Arzu Onar-Thomas, Shengjie Wu, Theodore Nicolaides, Tina Young Poussaint, Jason Fangusaro, Joanna Phillips, Arie Perry, David Turner, Michael Prados, Roger J Packer, Ibrahim Qaddoumi, Sridharan Gururangan, Ian F Pollack, Stewart Goldman, Lawrence A Doyle, Clinton F Stewart, James M Boyett, Larry E Kun, Maryam Fouladi
Background.: Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG. Methods.: Selumetinib was administered orally starting at 33 mg/m2/dose b.i.d., using the modified continual reassessment method. Pharmacokinetic analysis was performed during the first course...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28332309/effects-of-mir-145-5p-through-nras-on-the-cell-proliferation-apoptosis-migration-and-invasion-in-melanoma-by-inhibiting-mapk-and-pi3k-akt-pathways
#2
Sha Liu, Guozhen Gao, Dexiong Yan, Xiangjun Chen, Xingwei Yao, Shuzhong Guo, Guirong Li, Yu Zhao
We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS. After transfecting miR-145-5p mimics, miR-145-5p inhibitors, NRAS cDNA and NRAS siRNA into CHL-1, VMM917 and SK-mel-28 cells, functional assays were used to detect the proliferation, apoptosis, invasion and migration, including MTT, flow cytometry, Transwell and wound healing assays...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#3
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28323937/tert-braf-and-nras-in-primary-thyroid-cancer-and-metastatic-disease
#4
Miguel Melo, Adriana Gaspar da Rocha, Rui Batista, João Vinagre, Maria João Martins, Gracinda Costa, Cristina Ribeiro, Francisco Carrilho, Valeriano Leite, Cláudia Lobo, José Manuel Cameselle-Teijeiro, Bruno Cavadas, Luísa Pereira, Manuel Sobrinho-Simões, Paula Soares
Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNM) and distant metastases. Design and patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTC) (n=180), including 196 LNM and 56 distant metastases...
March 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28315738/pulmonary-sarcomatoid-carcinomas-commonly-harbor-either-potentially-targetable-genomic-alterations-or-high-tumor-mutational-burden-as-observed-by-comprehensive-genomic-profiling
#5
Alexa B Schrock, Shuyu D Li, Garrett M Frampton, James Suh, Eduardo Braun, Ranee Mehra, Steven Buck, Jose A Bufill, Nir Peled, Nagla Abdel Karim, Cynthia Hsieh, Manuel Doria, James Knost, Rong Chen, Sai-Hong Ignatius Ou, Jeffrey S Ross, Philip J Stephens, Paul Fishkin, Vincent A Miller, Siraj M Ali, Balazs Halmos, Jane J Liu
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1...
March 15, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28314271/identification-of-methylation-profiles-of-cancer-related-genes-in-circulating-tumor-cells-population
#6
Anna Lyberopoulou, Michail Galanopoulos, Gerasimos Aravantinos, George E Theodoropoulos, Evangelos Marinos, Efstathios P Efstathopoulos, Maria Gazouli
BACKGROUND: We performed an epigenetic analysis of the first exon of the hVIM gene and the SFRP2 in circulating tumor cells (CTCs) and correlation with the corresponding primary colorectal cancer (CRC) tissue. PATIENTS AND METHODS: CTCs detection in 52 colorectal cancer patients was managed by a multi-marker immunomagnetic method with the use of quantum dots (QDs). To determine methylation levels we used high-resolution melting (HRM) technology. RESULTS: In the case of VIM we found 76...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28301874/veph1-expression-decreases-vascularisation-in-ovarian-cancer-xenografts-and-inhibits-vegfa-and-il8-expression-through-inhibition-of-akt-activation
#7
Premalatha Shathasivam, Alexandra Kollara, Thomasina Spybey, Soyeon Park, Blaise Clarke, Maurice J Ringuette, Theodore J Brown
BACKGROUND: VEPH1 is amplified in several cancers including ovarian but its impact on tumour progression is unknown. Previous work has shown that VEPH1 inhibits TGFβ signalling while its Drosophila ortholog increases tissue growth, raising the possibility that VEPH1 could impact tumour growth or progression. METHODS: A CRISPR approach was used to disrupt VEPH1 expression in ovarian cancer ES-2 cells, while VEPH1-negative SKOV3 cells were stably transfected with VEPH1 cDNA...
March 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28299583/braf-plus-mek-targeted-drugs-a-new-standard-of-treatment-for-braf-mutant-advanced-melanoma
#8
Paola Queirolo, Francesco Spagnolo
BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients...
March 15, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28297754/-clinicopathologic-characteristics-of-head-and-neck-carcinoma-showing-thymus-like-element
#9
X J Cui, C Y Zhang, P Su, B Lyu, Y B Ren, X S Fan, X F Zhang, Y Wang, Y H Song, Z Y Liu
Objective: To investigate clinicopathological features of carcinoma showing thymus-like elements (CASTLE) in the head and neck regions. Methods: Clinicopathological data of 7 patients with CASTLE in the head and neck regions were retrospectively reviewed.Immunohistochemical staining and in situ hybridization for EBER were performed. BRAF(V600E) mutation was examined by ARMS method in 6 cases. Results: There were 5 females and 2 males with age between 49 and 78 years (average of 65.6 years). All tumors were solitary nodular lesions with an infiltrative border, including 6 intrathyroid tumors and 1 extrathyroid tumor in the laryngeal pharynx...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28293477/braf-v600e-immunohistochemistry-in-a-large-series-of-glial-and-glial-neuronal-tumors
#10
Quentin Breton, Hélène Plouhinec, Delphine Prunier-Mirebeau, Blandine Boisselier, Sophie Michalak, Philippe Menei, Audrey Rousseau
INTRODUCTION: Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma [PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a diagnostic clue to these entities. Targeted therapies against BRAF-V600 protein have shown promising results in GNT. The aim of this study was to assess the utility of BRAF-V600E immunohistochemistry (IHC, clone VE1) in daily practice in a series of 140 glial, and GNT compared to molecular biology (MB) techniques. METHODS: We performed BRAF-V600E IHC on all 140 cases...
March 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28292978/validating-a-fully-automated-real-time-pcr-based-system-for-use-in-the-molecular-diagnostic-analysis-of-colorectal-carcinoma-a-comparison-with-ngs-and-ihc
#11
Richard Colling, Lai Mun Wang, Elizabeth Soilleux
BACKGROUND: Molecular testing is increasingly needed in colorectal carcinoma (CRC) and the current clinically relevant mutations are in BRAF, KRAS and NRAS. This study aimed to further validate a new alternative polymerase chain reaction (PCR) platform (Idylla, Biocartis) against existing next-generation sequencing (NGS) and immunohistochemistry (IHC) assays. METHODS: 56 Idylla tests were performed on 43 CRC cases, in a total of 74 comparisons against an NGS panel (Ion Torrent) and the VE1 (anti-BRAF) antibody IHC...
March 14, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28283079/molecular-investigation-of-the-direct-anti-tumour-effects-of-nonsteroidal-anti-inflammatory-drugs-in-a-panel-of-canine-cancer-cell-lines
#12
R Yoshitake, K Saeki, M Watanabe, N Nakaoka, S M Ong, M Hanafusa, N Choisunirachon, N Fujita, R Nishimura, T Nakagawa
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as effective adjunctive anti-tumour agents in human and veterinary medicine. However, the molecular mechanisms associated with their anti-tumour effects and correlations with the expression of cyclooxygenase (COX) and related molecules in tumours remain controversial. The objective of this study was to compare the expression profiles of COX and related molecules with NSAID sensitivity and to explore the molecular mechanisms of anti-tumour effects...
March 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28277101/radiosurgery-stereotactic-radiotherapy-in-combination-with-immunotherapy-and-targeted-agents-for-melanoma-brain-metastases
#13
Elisabetta Trino, Cristina Mantovani, Serena Badellino, Umberto Ricardi, Andrea Riccardo Filippi
The clinical landscape of advanced melanoma drastically changed after the introduction of both targeted therapies and immunotherapy. This rapid development in systemic therapies led to a change in the management of patients with brain metastases, with the subsequent need to re-assess the role of local therapies, in particular stereotactic radiosurgery (SRS). Areas covered: In this non-systematic review, we report on the current knowledge on the use of SRS in combination with immunotherapy and BRAF/MEK inhibitors for patients with melanoma brain metastases, as well as ongoing trials in this field...
March 1, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28267766/association-of-smad4-mutation-with-patient-demographics-tumor-characteristics-and-clinical-outcomes-in-colorectal-cancer
#14
Amir Mehrvarz Sarshekeh, Shailesh Advani, Michael J Overman, Ganiraju Manyam, Bryan K Kee, David R Fogelman, Arvind Dasari, Kanwal Raghav, Eduardo Vilar, Shanequa Manuel, Imad Shureiqi, Robert A Wolff, Keyur P Patel, Raja Luthra, Kenna Shaw, Cathy Eng, Dipen M Maru, Mark J Routbort, Funda Meric-Bernstam, Scott Kopetz
SMAD4 is an essential mediator in the transforming growth factor-β pathway. Sporadic mutations of SMAD4 are present in 2.1-20.0% of colorectal cancers (CRCs) but data are limited. In this study, we aimed to evaluate clinicopathologic characteristics, prognosis, and clinical outcome associated with this mutation in CRC cases. Data for patients with metastatic or unresectable CRC who underwent genotyping for SMAD4 mutation and received treatment at The University of Texas MD Anderson Cancer Center from 2000 to 2014 were reviewed...
2017: PloS One
https://www.readbyqxmd.com/read/28264791/more-than-5000-patients-with-metastatic-melanoma-in-europe-per-year-do-not-have-access-to-recommended-first-line-innovative-treatments
#15
L Kandolf Sekulovic, K Peris, A Hauschild, A Stratigos, J-J Grob, P Nathan, R Dummer, A-M Forsea, C Hoeller, H Gogas, L Demidov, C Lebbe, C Blank, J Olah, L Bastholt, D Herceg, B Neyns, R Vieira, J Hansson, P Rutkowski, I Krajsova, M Bylaite-Bucinskiene, I Zalaudek, J Maric-Brozic, N Babovic, M Banjin, K Putnik, G Weinlich, V Todorovic, K Kirov, J Ocvirk, A Zhukavets, M Kukushkina, L De La Cruz Merino, A Ymeri, M Risteski, C Garbe
BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF)...
March 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28258479/prevalence-and-clinicopathologic-molecular-characteristics-of-mismatch-repair-deficient-colorectal-cancer-in-the-under-50-year-old-japanese-population
#16
Okihide Suzuki, Hidetaka Eguchi, Noriyasu Chika, Takehiko Sakimoto, Keiichiro Ishibashi, Kensuke Kumamoto, Jun-Ichi Tamaru, Tetsuhiko Tachikawa, Kiwamu Akagi, Tomio Arai, Yasushi Okazaki, Hideyuki Ishida
PURPOSE: To clarify the prevalence and clinicopathologic/molecular characteristics of mismatch repair (MMR)-deficient colorectal cancer in the young Japanese population. METHODS: Immunohistochemical analyses for MMR proteins (MLH1, MSH2, MSH6, and PMS2) were performed in formalin-fixed paraffin-embedded sections prepared from the resected CRC specimens of 119 consecutive patients aged <50 years old, who underwent resection of the primary tumor at our institution between 1996 and 2015...
March 3, 2017: Surgery Today
https://www.readbyqxmd.com/read/28251966/-scanning-for-kras-nras-braf-and-pik3ca-mutations-by-dna-melting-analysis-with-taqman-probes
#17
I V Botezatu, I O Panchuk, A M Stroganova, A I Senderovich, V N Kondratova, V P Shelepov, A V Lichtenstein
Scanning for mutations by DNA melting analysis (DMA) is based on asymmetric PCR followed by the melting of duplexes formed by single-stranded amplicons with TaqMan probes. The method is optimally suited for clinical genetic testing; it is easy to perform, high-throughput, and sensitive. The detection limit of mutant alleles by the DMA method is about 3%, which is much higher than the sensitivity of Sanger sequencing. In addition, the DMA method is realized in a closed-tube format, while 2-h assay is carried out in a single tube without any intermediate or additional procedures thereby minimizing the risk of cross contamination of the samples...
January 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28248716/intraepithelial-melanoma-in-the-stomach-after-treatment-with-immune-checkpoint-blockade-therapy
#18
Elina Shustef, Carlos A Torres-Cabala, Jonathan L Curry, Michael T Tetzlaff, Priyadharsini Nagarajan, Doina Ivan, Victor G Prieto, Phyu P Aung
Melanoma is the most common tumor to metastasize to the gastrointestinal tract, commonly affecting the small intestine, colon, and anorectum. Primary mucosal melanoma can arise in any gastrointestinal site, most frequently affecting anorectal mucosa. Melanoma involving the gastric mucosa, specifically, is exceedingly rare and carries a poor prognosis with a median survival of 5 months. The presence of atypical melanocytes exclusively within gastric epithelium has not been previously described. We report a case of a 52-year-old man with widespread BRAFV600E mutant metastatic melanoma who was referred to our institution for immune checkpoint antibody-blockade therapy...
February 23, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28245430/man2a1-fer-fusion-gene-is-expressed-by-human-liver-and-other-tumor-types-and-has-oncogenic-activity-in-mice
#19
Zhang-Hui Chen, Yan P Yu, Junyan Tao, Silvia Liu, George Tseng, Michael Nalesnik, Ronald Hamilton, Rohit Bhargava, Joel B Nelson, Arjun Pennathur, Satdarshan P Monga, James D Luketich, George K Michalopoulos, Jian-Hua Luo
BACKGROUND & AIMS: Human tumors and liver cancer cell lines express the product of a fusion between the first 13 exons in the mannosidase α class 2A member 1 gene (MAN2A1) and the last 6 exons in the FER tyrosine kinase gene (FER), called MAN2A1-FER. We investigated whether MAN2A1-FER is expressed by human liver tumors and its role in liver carcinogenesis. METHODS: We performed reverse transcription polymerase chain reaction analyses of 102 non-small cell lung tumors, 61 ovarian tumors, 70 liver tumors, 156 glioblastoma multiform samples, 27 esophageal adenocarcinomas, and 269 prostate cancer samples, as well as 10 nontumor liver tissues and 20 nontumor prostate tissues, collected at the University of Pittsburgh...
February 25, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28236768/survival-of-patients-with-melanoma-brain-metastasis-treated-with-stereotactic-radiosurgery-and-active-systemic-drug-therapies
#20
Ee Siang Choong, Serigne Lo, Martin Drummond, Gerald B Fogarty, Alexander M Menzies, Alexander Guminski, Brindha Shivalingam, Kathryn Clarke, Georgina V Long, Angela M Hong
INTRODUCTION: With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy. METHOD: A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted...
February 22, 2017: European Journal of Cancer
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