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Vivek Subbiah, Oliver Holmes, Kyle Gowen, Daniel Spritz, Behrang Amini, Wei-Lien Wang, Alexa B Schrock, Funda Meric-Bernstam, Ralph Zinner, Sarina Piha-Paul, Maria Zarzour, Julia A Elvin, Rachel L Erlich, David L Stockman, Jo-Anne Vergilio, James H Suh, Philip J Stephens, Vincent Miller, Jeffrey S Ross, Siraj M Ali
Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients...
October 21, 2016: Oncology
Zhong Ni, Xiting Wang, Tianchen Zhang, Rong Zhong Jin
Anaplastic lymphoma kinase (ALK) has become as an important target for the treatment of various human cancers, especially non-small-cell lung cancer. A mutation, F1174C, suited in the C-terminal helix αC of ALK and distal from the small-molecule inhibitor ceritinib bound to the ATP-binding site, causes the emergence of drug resistance to ceritinib. However, the detailed mechanism for the allosteric effect of F1174C resistance mutation to ceritinib remains unclear. Here, molecular dynamics (MD) simulations and binding free energy calculations [Molecular Mechanics/Generalized Born Surface Area (MM/GBSA)] were carried out to explore the advent of drug resistance mutation in ALK...
October 11, 2016: Computational Biology and Chemistry
Daniel B Costa
No abstract text is available yet for this article.
October 20, 2016: Cell Cycle
Gabriela Abrego, Julio García, Bruce Gilbert, Scott Forseen, Michael Toscano
Primary bone lymphoma (PBL) is an uncommon extra nodal disease that represents about 1-3% of lymphoma cases. Imaging findings are variable and non-specific. Computed tomography may demonstrate lytic lesions with sequestra and periosteal reaction. On magnetic resonance imaging, lesions are T1WI hypointense and T2WI hyperintense, related to peritumoral edema or bone marrow replacement. Rarely lesions may have associated fibrosis and show a more hypointense signal pattern on T2WI. After administration of contrast, PBL tends to enhance avidly...
September 2016: Journal of Radiology Case Reports
Tongtong Zhang, Junling Li
BACKGROUND: It has been proven that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and KRAS are common driver genes in non-small cell lung cancer (NSCLC). Molecular targeted therapy increases the overall response rate and progression-free survival (PFS) of patients with EGFR-sensitive mutation or echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. However, target and targeted drugs for lung squamous cell carcinoma to indicate clinical therapy remain to be confirmed...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Yoko Kojima, Koji Okudela, Mai Matsumura, Takahiro Omori, Tomohisa Baba, Akimasa Sekine, Tetsukan Woo, Shigeaki Umeda, Tamiko Takemura, Hideaki Mitsui, Takehisa Suzuki, Yoko Tateishi, Tae Iwasawa, Hiromasa Arai, Michihiko Tajiri, Takashi Ogura, Yoichi Kameda, Munetaka Masuda, Kenich Ohashi
AIMS: To investigate the pathological features of idiopathic interstitial pneumonia (IIP) - associated pulmonary adenocarcinoma. METHODS: Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected. We here further focused on adenocarcinomas that developed in the honeycomb lesions. Adenocarcinomas in the IIP group were subdivided into two groups, one group included tumors connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group) and the other included tumors unrelated to honeycomb lesions (the NH-IIP group)...
October 19, 2016: Histopathology
Weisheng Xu, Kamal K Khurana, Jamie Tull, Charlene Maciak, Shengle Zhang
BACKGROUND: Anaplastic lymphoma kinase (ALK) gene rearrangement analysis by fluorescence in situ hybridization (FISH) is one of the standard molecular tests for targeted therapy of lung adenocarcinoma. However, insufficient cell block cellularity may impede molecular testing. A recent study showed that Diff-Quik (DQ) stained cytology smear is suitable for ALK by FISH. AIMS: The aim of our study was to observe the impact of destaining intervals on the quality of FISH signals and determine if DQ smears without destaining would allow FISH analysis...
July 2016: Journal of Cytology
Yoon Jin Cha, Hye Ryun Kim, Hyo Sup Shim
BACKGROUND: Clinical outcomes of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer according to ALK fusion variants are not clear. We aimed to investigate the prevalence of ALK fusion variants and to compare clinical outcomes according to ALK fusion variants. METHODS: A retrospective analysis was conducted on patients with advanced ALK-rearranged adenocarcinoma treated with chemotherapy and ALK inhibitors. ALK rearrangement was identified by fluorescence in situ hybridization and confirmed by immunohistochemistry...
October 19, 2016: Journal of Translational Medicine
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
Elisabet Cuyàs, Almudena Pérez-Sánchez, Vicente Micol, Javier A Menendez, Joaquim Bosch-Barrera
The signal transducer and activator of transcription 3 (STAT3) has been suggested to play a prominent role in mediating non-small-cell lung cancer (NSCLC) resistance to some tyrosine kinase inhibitor (TKI)-mediated therapies. Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways...
October 18, 2016: Cell Cycle
Masato Chiba, Yosuke Togashi, Shuta Tomida, Hiroshi Mizuuchi, Yu Nakamura, Eri Banno, Hidetoshi Hayashi, Masato Terashima, Marco A De Velasco, Kazuko Sakai, Yoshihiko Fujita, Tetsuya Mitsudomi, Kazuto Nishio
Several receptor tyrosine kinases (RTKs) including EGFR, ALK, and MET have been identified as therapeutic targets in non-small cell lung cancer (NSCLC). Among the downstream pathways of RTKs, the MAPK pathway is particularly important for cancer cell proliferation, differentiation, and survival. In this study, the effects of MEK inhibitors (trametinib and PD0325901) in several NSCLC cell lines with driver gene alterations, especially RTK genes, were tested in vitro using an MTT assay, and a wide range of sensitivities was found...
October 17, 2016: International Journal of Oncology
John D Hainsworth, F Anthony Greco
BACKGROUND: Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP). OBJECTIVE: We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors. METHODS: We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc...
March 2016: Drugs—Real World Outcomes
Noriyoshi Masuoka, Kulwadee Tamsampaoloet, Warinthorn Chavasiri, Isao Kubo
Anacardic acid C15:3 and cardol C15:3 sigmoidally suppressed superoxide anion (O2-) generation using xanthine oxidase. To study this suppression activity, anacardic acids, cardanols and cardols having different numbers of double bonds in alk(en)yl chains were prepared. The O2- scavenging activity and H2O2 formation from O2- using PMS-NADH were examined. Anacardic acids and cardols indicated sigmoidal O2- scavenging activity but cardanols did not. The O2- scavenging activity of anacardic acid C15:3 was weaker than the suppression activity using xanthine oxidase, but the scavenging activity of cardol C15:3 was quite similar to the suppression using xanthine oxidase...
September 2016: Heliyon
Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
In January 2003, a 55-year old, non-smoking woman visited our hospital to undergo treatment for T4N0M0 pulmonary adenocarcinoma of the left lung. Until death in October 2015, she received over 20 lines of treatment including a second line therapy with gefitinib, which showed long response. In March 2014, she noticed the left axillar lymph node swelling. Aspiration cytology of the lymph node revealed the presence of adenocarcinoma harboring EGFR exon 19 deletion (Ex19del) but not T790M. Concomitant ALK translocation of variant 1 was also detected...
2016: Respiratory Medicine Case Reports
Corey J Langer, Shirish M Gadgeel, Hossein Borghaei, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Yang Ge, Harry Raftopoulos, Leena Gandhi
BACKGROUND: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC...
October 10, 2016: Lancet Oncology
Srividya Srinivasamaharaj, Bilal Khameze Salame, Jorge Rios-Perez, Goetz Kloecker, Cesar A Perez
The identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor. Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor...
October 17, 2016: Expert Review of Anticancer Therapy
A S Mansfield, S J Murphy, F R Harris, S I Robinson, R S Marks, S H Johnson, J B Smadbeck, G C Halling, E S Yi, D Wigle, G Vasmatzis, J Jen
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy...
October 14, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Jacob A Miller, Elizabeth E Bennett, Roy Xiao, Rupesh Kotecha, Samuel T Chao, Michael A Vogelbaum, Gene H Barnett, Lilyana Angelov, Erin S Murphy, Jennifer S Yu, Manmeet S Ahluwalia, John H Suh, Alireza M Mohammadi
BACKGROUND: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN...
September 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Zenggang Pan, Shimin Hu, Min Li, Yi Zhou, Young S Kim, Vishnu Reddy, Jennifer N Sanmann, Lynette M Smith, Mingyi Chen, Zifen Gao, Huan-You Wang, Ji Yuan
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK LBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma with characteristic ALK rearrangements. Diagnosis of ALK LBCL can be challenging because of its rarity, unique morphologic characteristics, and unusual immunophenotypic features, which significantly overlap with other hematologic and nonhematologic neoplasms. The purpose of this study is to further explore the clinicopathologic features of ALK LBCL to ensure the awareness and accurate diagnosis of this entity...
October 12, 2016: American Journal of Surgical Pathology
Manjima Dhar, Edward Pao, Corinne Renier, Derek E Go, James Che, Rosita Montoya, Rachel Conrad, Melissa Matsumoto, Kyra Heirich, Melanie Triboulet, Jianyu Rao, Stefanie S Jeffrey, Edward B Garon, Jonathan Goldman, Nagesh P Rao, Rajan Kulkarni, Elodie Sollier-Christen, Dino Di Carlo
Circulating tumor cells (CTCs) have a great potential as indicators of metastatic disease that may help physicians improve cancer prognostication, treatment and patient outcomes. Heterogeneous marker expression as well as the complexity of current antibody-based isolation and analysis systems highlights the need for alternative methods. In this work, we use a microfluidic Vortex device that can selectively isolate potential tumor cells from blood independent of cell surface expression. This system was adapted to interface with three protein-marker-free analysis techniques: (i) an in-flow automated image processing system to enumerate cells released, (ii) cytological analysis using Papanicolaou (Pap) staining and (iii) fluorescence in situ hybridization (FISH) targeting the ALK rearrangement...
October 14, 2016: Scientific Reports
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