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https://www.readbyqxmd.com/read/28453697/prediction-of-overall-survival-in-stage-ii-and-iii-colon-cancer-beyond-tnm-system-a-retrospective-pooled-biomarker-study
#1
R Dienstmann, M J Mason, F A Sinicrope, A I Phipps, S Tejpar, A Nesbakken, S A Danielsen, A Sveen, D D Buchanan, M Clendenning, C Rosty, B Bot, S R Alberts, J Milburn Jessup, R A Lothe, M Delorenzi, P A Newcomb, D Sargent, J Guinney
Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28449420/cytological-features-of-warthin-like-papillary-thyroid-carcinoma-a-case-report-with-review-of-previous-cytology-cases
#2
Archana George Vallonthaiel, Shipra Agarwal, Deepali Jain, Rajni Yadav, Nishikant A Damle
Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC...
April 27, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/28448514/a-new-gtf2i-braf-fusion-mediating-mapk-pathway-activation-in-pilocytic-astrocytoma
#3
Tajana Tešan Tomić, Josefin Olausson, Annica Wilzén, Magnus Sabel, Katarina Truvé, Helene Sjögren, Sándor Dósa, Magnus Tisell, Birgitta Lannering, Fredrik Enlund, Tommy Martinsson, Pierre Åman, Frida Abel
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection...
2017: PloS One
https://www.readbyqxmd.com/read/28445987/context-dependent-mir-204-and-mir-211-affect-the-biological-properties-of-amelanotic-and-melanotic-melanoma-cells
#4
Marianna Vitiello, Andrea Tuccoli, Romina D'Aurizio, Samanta Sarti, Laura Giannecchini, Simone Lubrano, Andrea Marranci, Monica Evangelista, Silvia Peppicelli, Chiara Ippolito, Ivana Barravecchia, Elena Guzzolino, Valentina Montagnani, Michael Gowen, Elisa Mercoledi, Alberto Mercatanti, Laura Comelli, Salvatore Gurrieri, Lawrence W Wu, Omotayo Ope, Keith Flaherty, Genevieve M Boland, Marc R Hammond, Lawrence Kwong, Mario Chiariello, Barbara Stecca, Gao Zhang, Alessandra Salvetti, Debora Angeloni, Letizia Pitto, Lido Calorini, Giovanna Chiorino, Marco Pellegrini, Meenhard Herlyn, Iman Osman, Laura Poliseno
Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway.By performing small RNA sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#5
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445541/iqgap1-is-an-oncogenic-target-in-canine-melanoma
#6
Becky H Lee, Poornima H Neela, Michael S Kent, Ashley M Zehnder
Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28445138/killer-cell-immunoglobulin-like-receptor-2dl4-is-expressed-in-and-suppresses-the-cell-growth-of-langerhans-cell-histiocytosis
#7
Yusuke Takei, Chiyuki Ueshima, Tatsuki R Kataoka, Masahiro Hirata, Akihiko Sugimoto, Mariyo Rokutan-Kurata, Koki Moriyoshi, Kazuo Ono, Ichiro Murakami, Sanju Iwamoto, Hironori Haga
Killer cell immunoglobulin-like receptor (KIR) 2DL4 (CD158d) is a receptor for human leukocyte antigen-G. The function of KIR2DL4 has been reported in human natural killer cell lymphoma and mastocytosis, but not in Langerhans cell histiocytosis (LCH). Herein, we examined the expression and function of KIR2DL4 in LCHs. In pathological specimens, 27 of 36 LCH cases (75.0%) were immunohistochemically positive for KIR2DL4. Its expression was independent of age, gender, location, multi- or single-system, and the status of BRAFV600E immunostaining...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444112/incidence-course-and-management-of-toxicities-associated-with-cobimetinib-in-combination-with-vemurafenib-in-the-cobrim-study
#8
B Dréno, A Ribas, J Larkin, P A Ascierto, A Hauschild, L Thomas, J-J Grob, D O Koralek, I Rooney, J J Hsu, E F McKenna, G A McArthur
The combination of cobimetinib plus vemurafenib is well tolerated in patients with advanced BRAFV600-mutated melanomaAEs generally occur early and are manageable through patient monitoring, dose modification, and supportive careThe favourable safety profile and significantly improved patient outcomes support the use of cobimetinib plus vemurafenib as a standard of care for initial treatment.
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#9
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423208/combined-activity-of-temozolomide-and-the-mtor-inhibitor-temsirolimus-in-metastatic-melanoma-involves-dkk1
#10
Heike Niessner, Corinna Kosnopfel, Tobias Sinnberg, Daniela Beck, Kathrin Krieg, Ines Wanke, Konstantinos Lasithiotakis, Michael Bonin, Claus Garbe, Friedegund Meier
The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in patients with BRAF-mutant melanoma, but its effects are limited by the onset of drug resistance. In the case of resistance, chemotherapy can still be applied as second line therapy. However, it yields low response rates and strategies are urgently needed to potentiate its effects. In a previous study, we showed that the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity of melanoma cells to chemotherapeutic drugs (1)...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28421232/clinical-spectrum-quality-of-life-braf-mutation-status-and-treatment-of-skin-involvement-in-adult-langerhans-cell-histiocytosis
#11
Etienne Crickx, Jean-David Bouaziz, Gwenaël Lorillon, Mathilde de Menthon, Florence Cordoliani, Emmanuell Bugnet, Martine Bagot, Michel Rybojad, Samia Mourah, Abdellatif Tazi
Langerhans cell histiocytosis is a rare histiocytic disorder for which skin involvement and management are poorly described in adults. The aim of this retrospective monocentric study in a national reference centre is to describe the clinical characteristics, quality of life, BRAF mutation status and outcomes of skin involvement in adult patients with Langerhans cell histiocytosis. Twenty-five patients (14 females, mean age 47 years) were included, with a median follow-up of 33 months (range 4-420 months). Patients experienced poor dermatological quality of life despite low body surface involvement...
April 19, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28418885/development-of-11c-vemurafenib-employing-a-carbon-11-carbonylative-stille-coupling-and-preliminary-evaluation-in-mice-bearing-melanoma-tumor-xenografts
#12
Paul Slobbe, Albert D Windhorst, Kevin Adamzek, Marije Bolijn, Robert C Schuit, Daniëlle A M Heideman, Guus A M S van Dongen, Alex J Poot
Over the last decade kinase inhibitors have witnessed tremendous growth as anti-cancer drugs. Unfortunately, despite their promising clinical successes, a large portion of patients does not benefit from these targeted therapeutics. Vemurafenib is a serine/threonine kinase inhibitor approved for the treatment of melanomas specifically expressing the BRAFV600E mutation. The aim of this study was to develop vemurafenib as PET tracer to determine its potential for identification of tumors sensitive to vemurafenib treatment...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416767/the-molecular-heterogeneity-of-sporadic-colorectal-cancer-with-different-tumor-sites-in-chinese-patients
#13
Junjie Peng, Dan Huang, Graeme Poston, Xiaoji Ma, Renjie Wang, Weiqi Sheng, Xiaoyan Zhou, Xiaoli Zhu, Sanjun Cai
PURPOSE: To assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC). MATERIALS AND METHODS: In this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415756/human-melanoma-cells-resistant-to-mapk-inhibitors-can-be-effectively-targeted-by-inhibition-of-the-p90-ribosomal-s6-kinase
#14
Corinna Kosnopfel, Tobias Sinnberg, Birgit Sauer, Heike Niessner, Anja Schmitt, Elena Makino, Andrea Forschner, Stephan Hailfinger, Claus Garbe, Birgit Schittek
The clinical availability of small molecule inhibitors specifically targeting mutated BRAF marked a significant breakthrough in melanoma therapy. Despite a dramatic anti-tumour activity and improved patient survival, rapidly emerging resistance, however, greatly limits the clinical benefit. The majority of the already described resistance mechanisms involve a reactivation of the MAPK signalling pathway. The p90 ribosomal S6 kinase (RSK), a downstream effector of the MAPK signalling cascade, has been reported to enhance survival of melanoma cells in response to chemotherapy...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401596/successful-retreatment-with-combined-braf-mek-inhibition-in-metastatic-brafv600-mutated-melanoma
#15
Valerie C Amann, Dorothée Hoffmann, Joanna Mangana, Reinhard Dummer, Simone M Goldinger
BACKGROUND: The combination treatment with BRAF- and MEK-inhibitors is amongst the current standard of care for stage IIIC/IV BRAF-mutated melanoma. However, therapeutic options are limited once patients have progressed upon both targeted and immunotherapy. OBJECTIVE: To investigate whether retreatment with BRAF- and MEK-inhibitor combination is an option for patients with metastatic BRAF-mutated melanoma upon previous progression on kinase inhibitors. METHODS: Two patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF- and MEK-inhibitor combination after progression on targeted therapy and subsequent immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies...
April 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28368402/sox2-is-not-required-for-melanomagenesis-melanoma-growth-and-melanoma-metastasis-in-vivo
#16
V Cesarini, E Guida, F Todaro, S Di Agostino, V Tassinari, S Nicolis, R Favaro, S Caporali, P M Lacal, E Botti, A Costanzo, P Rossi, E A Jannini, S Dolci
Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRaf(V600E) mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28362711/ectopic-thyroid-tissue-immunohistochemistry-and-molecular-analysis
#17
Diana M Lin, Sara Javidiparsijani, Alexandra Vardouniotis, Lela Buckingham, Swathi B Reddy, Paolo Gattuso
Ectopic thyroid tissue is rare and controversial. Some experts consider it to always be metastatic thyroid carcinoma, whereas others consider it benign as long as it is restricted to few follicles without cytoarchitectural features of papillary thyroid carcinoma. Immunohistochemistry (IHC) and molecular studies have not yet been performed to further characterize this entity. We retrospectively searched our pathology files for all ectopic thyroid inclusions and reviewed clinicopathologic characteristics and concurrent thyroid pathologic findings...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28351223/identification-of-three-novel-fusion-oncogenes-sqstm1-ntrk3-afap1l2-ret-and-ppfibp2-ret-in-thyroid-cancers-of-young-patients-in-fukushima
#18
Keita Iyama, Michiko Matsuse, Norisato Mitsutake, Tatiana Rogounovitch, Vladimir Saenko, Keiji Suzuki, Mai Ashizawa, Chiyo Ookouchi, Satoshi Suzuki, Hiroshi Mizunuma, Toshihiko Fukushima, Shinichi Suzuki, Shunichi Yamashita
BACKGROUND: The BRAF(V600E) mutation is the most frequent genetic abnormality in adult papillary thyroid carcinomas (PTCs). On the other hand, various chromosomal rearrangements are more prevalent in childhood and adolescent PTCs. The aim of the present study was to identify novel rearrangements in PTCs from young patients. METHODS: Among 63 postoperative specimens of childhood and adolescent PTCs, which had been discovered by the thyroid ultrasound screening program in Fukushima, nine samples without prevalent known oncogenes, BRAF(V600E), RAS, RET/PTC1, RET/PTC3, and ETV6/NTRK3, were analyzed in the current study by quantitative real-time reverse transcription polymerase chain reaction to screen for novel fusion genes by comparing transcript expression between extracellular and kinase domains of ALK, NTRK1, NTRK3, and RET...
April 25, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28323782/controversies-in-intrapatient-melanoma-brafv600e-mutation-status
#19
Erica Riveiro-Falkenbach, Angel Santos-Briz, Juan J Ríos-Martín, José L Rodríguez-Peralto
Therapies targeting the BRAF oncogene have improved the overall and disease-free survival of patients with advanced melanomas. An unresolved issue in clinical practice is the existence (or not) of BRAF-mutated and BRAF-nonmutated tumors in individual patients (intrapatient BRAF mutation heterogeneity), which may serve as a mechanism of resistance to BRAF inhibitors or lead to diagnostic problems. Different research groups have reported differing results after analyzing the BRAF mutation statuses of multiple melanoma tumors...
April 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28295484/who-2016-classification-changes-and-advancements-in-the-diagnosis-of-miscellaneous-primary-cns-tumours
#20
Felix Sahm, David E Reuss, Caterina Giannini
This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal non-meningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding "hybrid nerve sheath tumours" to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term solitary SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells...
March 12, 2017: Neuropathology and Applied Neurobiology
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