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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
#1
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/28299358/a-novel-potentially-targetable-tmem106b-braf-fusion-in-pleomorphic-xanthoastrocytoma
#2
Susan J Hsiao, Matthias A Karajannis, Daniel Diolaiti, Mahesh M Mansukhani, Julia Glade Bender, Andrew L Kung, James H Garvin
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining for BRAF V600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence of BRAF V600E, but identified copy-number alterations (including loss of the tumor suppressor CDKN2A) and a novel TMEM106B-BRAF fusion...
March 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28297754/-clinicopathologic-characteristics-of-head-and-neck-carcinoma-showing-thymus-like-element
#3
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/28297625/genomics-of-hairy-cell-leukemia
#4
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28293988/molecular-profiling-of-papillary-thyroid-carcinoma-in-korea-with-high-prevalence-of-braf-v600e-mutation
#5
Seung Eun Lee, Tae Sook Hwang, Yoon-La Choi, Wook Youn Kim, So Duk Lim, Young Bum Yoo, Suk Kyeong Kim
BACKGROUND: BRAF V600E mutation in PTC is particularly prevalent in Korea and a considerable number of BRAF-wild PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC (NIE-FVPTC) has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features...
March 15, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28293477/braf-v600e-immunohistochemistry-in-a-large-series-of-glial-and-glial-neuronal-tumors
#6
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/28292959/multiepitope-tissue-analysis-reveals-sppl3-mediated-adam10-activation-as-a-key-step-in-the-transformation-of-melanocytes
#7
Christian Ostalecki, Jung-Hyun Lee, Jochen Dindorf, Lena Collenburg, Stephan Schierer, Beate Simon, Stefan Schliep, Elisabeth Kremmer, Gerold Schuler, Andreas S Baur
The evolution of cancer is characterized by the appearance of specific mutations, but these mutations are translated into proteins that must cooperate to induce malignant transformation. Using a systemic approach with the multiepitope ligand cartography (MELC) technology, we analyzed protein expression profiles (PEPs) in nevi and BRAF(V600E)-positive superficial spreading melanomas (SSMs) from patient tissues to identify key transformation events. The PEPs in nevi and SSMs differed predominantly in the abundance of specific antigens, but the PEPs of nevi- and melanoma-associated keratinocytes gradually changed during the transformation process...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292178/antisense-oligonucleotides-internally-labeled-with-peptides-show-improved-target-recognition-and-stability-to-enzymatic-degradation
#8
Maria Taskova, Charlotte S Madsen, Knud J Jensen, Lykke Haastrup Hansen, Birte Vester, Kira Astakhova
Specific target binding and stability in diverse biological media is of crucial importance for applications of synthetic oligonucleotides as diagnostic and therapeutic tools. So far, these issues have been addressed by chemical modification of oligonucleotides and by conjugation with a peptide, most often at the terminal position of the oligonucleotide. Herein, we for the first time systematically investigate the influence of internally attached short peptides on the properties of antisense oligonucleotides...
March 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28282860/strategies-for-overcoming-resistance-in-tumours-harboring-braf-mutations
#9
REVIEW
Nourah Mohammad Obaid, Karen Bedard, Weei-Yuarn Huang
The development of resistance to previously effective treatments has been a challenge for health care providers and a fear for patients undergoing cancer therapy. This is an unfortunately frequent occurrence for patients undergoing targeted therapy for tumours harboring the activating V600E mutation of the BRAF gene. Since the initial identification of the BRAF mutation in 2002, a series of small molecular inhibitors that target the BRAFV600E have been developed, but intrinsic and acquired resistance to these drugs has presented an ongoing challenge...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28281551/molecular-correlates-and-rate-of-lymph-node-metastasis-of-non-invasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features-and-invasive-follicular-variant-papillary-thyroid-carcinoma-the-impact-of-rigid-criteria-to-distinguish-non-invasive-follicular
#10
Uiju Cho, Ozgur Mete, Min-Hee Kim, Ja Seong Bae, Chan Kwon Jung
Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28263969/activated-mek-cooperates-with-cdkn2a-and-pten-loss-to-promote-the-development-and-maintenance-of-melanoma
#11
H Yang, D A Kircher, K H Kim, A H Grossmann, M W VanBrocklin, S L Holmen, J P Robinson
The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAF(V600E) mutations. Although the initial response to these inhibitors can be dramatic, sometimes causing complete tumor regression, the majority of melanomas eventually become resistant. Mitogen-activated protein kinase kinase (MEK) mutations are found in primary melanomas and frequently reported in BRAF melanomas that develop resistance to targeted therapy; however, melanoma is a molecularly heterogeneous cancer, and which mutations are drivers and which are passengers remains to be determined...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28260510/prediction-of-activities-of-braf-v600e-inhibitors-by-sw-mlr-and-ga-mlr-methods
#12
Parinaz Pargolghasemi, Mir Saleh Hoseininezhad-Namin, Aiyoub Parchehbaf Jadid
BACKGROUND: quantitative structure-activity relationship(QSAR) models couldprovide both statistical significanceand useful chemical insights for drug design. The QSARmethod has found applications for predicting diverse properties of organic compounds, including antiviral activities, toxicities and biological activities. In this work, a quantitative structure-activity relationship was utilized for prediction of allosteric BRAF (V600E) inhibitory activities. METHODS: A data set which contains 54 molecules was classified to training and test sets...
March 3, 2017: Current Computer-aided Drug Design
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
#13
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/28257096/expression-of-autophagy-related-proteins-in-different-types-of-thyroid-cancer
#14
Hye Min Kim, Eun-Sol Kim, Ja Seung Koo
Thyroid cancer is common type of malignant tumor in humans, and the autophagy status of such tumors may vary according to subtype. This study aimed to investigate the expression and implications of the major autophagy-related molecules light chain (LC) 3A, LC3B, p62, and BNIP-3 in human thyroid carcinoma. Tissue microarrays were constructed from 555 thyroid cancers (papillary thyroid carcinoma (PTC): 342; follicular carcinoma (FC): 112; medullary carcinoma (MC): 70; poorly differentiated carcinoma (PDC): 23; and anaplastic carcinoma (AC): 8) and 152 follicular adenomas (FAs)...
March 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28255242/braf-v600-mutations-in-solid-tumors-other-than-metastatic-melanoma-and-papillary-thyroid-cancer-or-multiple-myeloma-a-screening-study
#15
Allen L Cohn, Bann-Mo Day, Sarang Abhyankar, Edward McKenna, Todd Riehl, Igor Puzanov
BACKGROUND: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma harboring activating BRAF(V600) mutations for enrollment in a vemurafenib clinical study. METHODS: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAF(V600) mutations by bidirectional direct Sanger sequencing...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28253394/clinical-and-radiologic-responses-to-cladribine-for-the-treatment-of-erdheim-chester-disease
#16
Gaurav Goyal, Mithun V Shah, Timothy G Call, Mark R Litzow, William J Hogan, Ronald S Go
Importance: While cladribine is best known for the treatment of hairy cell leukemia and other lymphoid cancers, it also has activity against myeloid neoplasms, such as Erdheim-Chester disease (ECD). Objective: To assess the efficacy of cladribine (2-chloro-2'-deoxyadenosine) in the treatment of ECD. Design, Setting, and Participants: This study was a single-institution retrospective medical record review from January 1, 1998, to April 6, 2016, at a tertiary academic medical center...
March 2, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28249088/braf-v600e-mutation-in-involuting-nevus-in-a-patient-treated-with-vemurafenib
#17
José Francisco Millán-Cayetano, Inés Fernández-Canedo, Nuria Blázquez-Sánchez, Rafael Fúnez-Liébana, Magdalena de Troya-Martín
No abstract text is available yet for this article.
March 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28247222/update-from-the-4th-edition-of-the-world-health-organization-classification-of-head-and-neck-tumours-mucosal-melanomas
#18
Michelle D Williams
The updated edition of The World Health Organization Classification of Tumours of the Head and Neck includes discussions on mucosal melanoma of both the sinonasal and oral cavity. Since the prior edition, sinonasal origin is now recognized as the most common site of occurrence of mucosal melanoma in the head and neck (66%) with oral cavity representing 25% of cases. Histologic features of mucosal melanomas vary widely from spindled, epithelioid, and pleomorphic to rhabdoid, plasmacytoid and undifferentiated...
March 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28242553/design-synthesis-and-evaluation-of-derivatives-based-on-pyrimidine-scaffold-as-potent-pan-raf-inhibitors-to-overcome-resistance
#19
Lu Wang, Qing Zhang, Gaoyuan Zhu, Zhimin Zhang, Yanle Zhi, Li Zhang, Tianxiao Mao, Xiang Zhou, Yadong Chen, Tao Lu, Weifang Tang
Simutaneous targeting all Raf isoforms offers the prospect of enhanced efficacy as well as reduced potential for resistance. Described herein is the discovery and characterization of a series of pyrimidine scaffold with DFG-out conformation as potent Pan-Raf inhibitors. Among them, I-41 with excellent Pan-Raf potency demonstrates inhibitory activity against BRaf(WT) phenotypic melanoma and BRaf(V600E) phenotypic colon cells. The western blot results for the Erk inhibition in human melanoma SK-Mel-2 cell lines showed I-41 inhibited the proliferation of SK-Mel-2 cell lines without paradoxical activation of Erk, which supported I-41 may become a good candidate compound to overcome the resistance of melanoma against the current BRaf(V600E) inhibitor therapy...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#20
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
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