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Sanja Dacic, Liza C Villaruz, Shira Abberbock, Alyssa Mahaffey, Pimpin Incharoen, Marina N Nikiforova
Break-apart ALK FISH probe is the FDA approved approach for detection of ALK rearrangements in lung carcinoma patients who may benefit from ALK kinase inhibitors. The FISH assay can be technically challenging and difficult to interpret. ALK immunohistochemistry and next generation sequencing have been proposed as alternative approaches. In this study, we compared various ALK -FISH patterns to next -generation sequencing (NGS) for gene fusion detection, ALK immunohistochemistry (IHC) and tumor responses to crizotinib...
October 17, 2016: Oncotarget
Masaru Ide, Shinichi Koba, Naoko Sueoka-Aragane, Akemi Sato, Yuri Nagano, Takuya Inoue, Noriyuki Misago, Yutaka Narisawa, Shinya Kimura, Eisaburo Sueoka
: BRAF gene mutations have been observed in 30-50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011...
October 21, 2016: Pathology Oncology Research: POR
Marta Polkowska, Edyta Czepielewska, Małgorzata Kozłowska-Wojciechowska
Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach...
December 2016: Current Treatment Options in Oncology
Teresa Delgado-Goni, Maria Falck Miniotis, Slawomir Wantuch, Harold G Parkes, Richard Marais, Paul Workman, Martin O Leach, Mounia Beloueche-Babari
Understanding the impact of BRAF signaling inhibition in human melanoma on key disease mechanisms is important for developing biomarkers of therapeutic response and combination strategies to improve long term disease control. This work investigates the downstream metabolic consequences of BRAF inhibition with vemurafenib, the molecular and biochemical processes that underpin them, their significance for antineoplastic activity and potential as non-invasive imaging response biomarkers.(1)H NMR spectroscopy showed that vemurafenib decreases the glycolytic activity of BRAF mutant (WM266...
October 7, 2016: Molecular Cancer Therapeutics
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAFV600E mutations activate MAP kinase signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer (CRC). In BRAFV600E mutant CRCs, treatment failure may be related to BRAFV600E -mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using CRC cell lines isogenic for BRAF. BRAFV600E -induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1...
October 7, 2016: Molecular Cancer Therapeutics
Meinolf Karthaus, Ralf-Dieter Hofheinz, Laurent Mineur, Henry Letocha, Richard Greil, Josef Thaler, Eva Fernebro, Kelly S Oliner, Michael Boedigheimer, Brian Twomey, Ying Zhang, Gaston Demonty, Claus-Henning Köhne
BACKGROUND: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC). METHODS: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression. RESULTS: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease...
October 20, 2016: British Journal of Cancer
E Matyja, W Grajkowska, K Stępień, E Naganska
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection...
2016: Folia Neuropathologica
Xiaoyan Kang, Nan Zhu, Xia Song
In recent years, targeted drugs occupy a pivotal position in the treatment of non-small cell lung cancer (NSCLC), drugs targeting epidermal growth factor receptor (EGFR) has been widely used in clinical practice, it is of milestone significance. V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors targeted at BRAF gene have obviously clinical efficacy to specific advantages populations with little side-effect, and be well tolerated. It is discovered recently that drug resistance also exists in BRAF inhibitors like other targeted drugs, the mechanism of drug resistance is being studied...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Zhen Huo, Tao Lu, Zhiyong Liang, Fan Ping, Jie Shen, Jingjing Lu, Wenbing Ma, Dachun Zhao, Dingrong Zhong
BACKGROUND: Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAF(V600E) mutations and treatments of isolated HPLCH. METHODS: We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes...
October 19, 2016: Diagnostic Pathology
Sergio Pina-Oviedo, Carlos A Torres-Cabala, Roberto N Miranda, Michael T Tetzlaff, Selina Singh, Ronald P Rapini, Victor G Prieto, Phyu P Aung
Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 10/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis...
October 18, 2016: American Journal of Dermatopathology
Mohammad Adawi, Bishara Bisharat, Abdalla Bowirrat
BACKGROUND: Erdheim-Chester disease (ECD) is an uncommon aggressive, multisystem form of non-Langerhans' cell histocytosis, which was firstly reported by Jakob Erdheim and William chester in 1930. The disease pathological features encompass an aberrant multiplication, overproduction and accumulation of white blood cells called histiocytes within multiple tissues and organs. Herein, we present a case of ECD owing to the rarity of this disease (roughly 550 cases have been described in the literature to date)...
October 2016: Medicine (Baltimore)
Lea Bottlaender, Marie Perier-Muzet, Véronique Lapras, Luc Thomas, Stephane Dalle
BRAF inhibitors (vemurafenib and dabrafenib) are nowadays commonly prescribed in BRAF-mutant metastatic melanoma and allow improvement of the overall survival and progression-free survival. They are, however, accompanied by many adverse effects which mainly affect the skin. We observed on computed tomographic scans in three different patients after 3 months of treatment, the onset of osteosclerotic lesions. In parallel, the computed tomographic scans showed a significant reduction in all of the previously identified metastases in all patients...
October 18, 2016: Melanoma Research
Qiangfeng Wang, Huanxia Yang, Lingjiao Wu, Jian Yao, Xiaohua Meng, Han Jiang, Cheng Xiao, Fusheng Wu
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription PCR (qRT-PCR) were used to detect and verify, respectively, changes to the transcriptomic profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathological characteristics was analysed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs...
October 19, 2016: Thyroid: Official Journal of the American Thyroid Association
Florian Rouaud, Jean-Luc Boucher, Anny Slama-Schwok, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite the spectacular achievements of targeted therapies (BRAF inhibitors) or immuno-therapies (anti-CTLA4 or anti-PD1), most patients with melanoma will need additional treatments. Here we used a photoactive NADPH analogue called NS1 to induce cell death by inhibition of NADPH oxidases NOX in melanoma cells, including melanoma cells isolated from patients. In contrast, healthy melanocytes growth was unaffected by NS1 treatment...
October 14, 2016: Oncotarget
Weibin Wang, Helen Kang, Yinu Zhao, Irene Min, Brian Wyrwas, Maureen Moore, Lisong Teng, Rasa Zarnegar, Xuejun Jiang, Thomas J Fahey
CONTEXT: The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anti-cancer therapy induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. OBJECTIVE: In this study, we investigate if autophagy is activated in vemurafenib treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
Naftali Stern
As both the rate of hypertension and cancer rise with age, concomitant hypertension in patients receiving treatment for cancer is very common. Increase in blood pressure during cancer treatment requires careful clinical assessment. Distinction between discontinuation or malabsorption of antihypertensive treatment due to factors such as nausea/vomiting/diarrhea and anti-cancer drug specific effects must be first made. De-novo hypertension during cancer treatment is likely related to anticancer drugs per se. Classical chemotherapeutic agents such as cyclophosphamide, cisplatin and busulfan have been previously linked to rising blood pressure...
September 2016: Journal of Hypertension
Alessia Nottegar, Fabrizio Tabbò, Claudio Luchini, Matteo Brunelli, Emilio Bria, Nicola Veronese, Antonio Santo, Sara Cingarlini, Eliana Gilioli, Chiara Ogliosi, Albino Eccher, Licia Montagna, Serena Pedron, Claudio Doglioni, Maria G Cangi, Giorgio Inghirami, Marco Chilosi
Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Clara Ugolini, Nicla Borrelli, Cristina Niccoli, Rossella Elisei, David Viola, Paolo Vitti, Paolo Miccoli, Fulvio Basolo
CONTEXT: Yes-associated protein-1 (YAP-1) is a player of the Hippo pathway and is involved in regulating cell proliferation. YAP-1 is overexpressed in papillary and anaplastic thyroid cancers. However, a correlation between YAP-1 expression and outcome in thyroid carcinoma has not been conclusively demonstrated. OBJECTIVE: This study was designed to clarify whether YAP-1 may be considered a marker of worse prognosis and outcome in thyroid cancer. DESIGN: A large series of cases of thyroid cancer with a long follow-up were investigated for YAP-1 expression...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Shih-Ping Cheng, Po-Sheng Yang, Ming-Nan Chien, Ming-Jen Chen, Jie-Jen Lee, Chien-Liang Liu
BACKGROUND AND OBJECTIVES: The induction of tumor-associated carbohydrate antigen results from altered glycosylation in transformed cells. Globo H is a hexasaccharide glycosphingolipid overexpressed on malignancies of epithelial origin and has become an attractive vaccine target. We aimed to investigate the expression patterns and prognostic value of Globo H in thyroid neoplasms. METHODS: Globo H expression was examined by immunohistochemical analysis using commercial and in-house tissue microarrays...
October 18, 2016: Journal of Surgical Oncology
Siavash Rahimi, Iolia Akaev, Costa Repanos, Peter A Brennan, Jean Daniel Dubois
Primary lingual intestinal-type adenocarcinomas are extremely rare with only a few cases described. A case with immunohistochemical expression of Androgen Receptor (AR) which was treated solely by chemo-radiotherapy is reported herein. A 54-year-old male was referred with symptoms of fullness in his tongue. Clinical examination showed an asymmetry of the tongue with a hard mass palpable within the middle of the tongue. Biopsy showed intestinal-type adenocarcinoma. The tumour showed positive staining with cytokeratin 7, cytokeratin 20, CDX2, AR, β-catenin and was mismatch repair proteins (MMR) proficient...
October 17, 2016: Head and Neck Pathology
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