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Qiushi Sun, Yuan Liu, Bo Liu, Yingying Liu
BACKGROUND: Patients with colorectal cancer (CRC) who are sensitive to epidermal growth factor antibodies inevitably acquire drug resistance. This study aimed to determine the usefulness of liquid biopsies for prognosis and clinical correlation. MATERIALS AND METHODS: For liquid biopsy tests, we extracted blood from 140 CRC patients with matched tumor samples. Circulating tumor cells (CTCs) and tumor DNA (ctDNA) were extracted before surgery and treatment. Samples were quantified and tested for mutations in KRAS, NRAS and BRAF...
March 2018: American Journal of the Medical Sciences
Yang Zou, Jiang-Yan Zhou, Jiu-Bai Guo, Li-Qun Wang, Yong Luo, Zi-Yu Zhang, Fa-Ying Liu, Jun Tan, Feng Wang, Ou-Ping Huang
Endometriosis is a potential premalignant disorder. The underlying molecular aberrations, however, are not fully understood. A recent exome sequencing study found that 25% (10/39) of deep infiltrating endometriosis harbored cancer driver gene mutations. However, it is unclear whether these mutations also exist in ovarian endometriosis. Here, a total of 101 ovarian endometriosis samples were analyzed for the presence of these gene mutations, including KRAS, PPP2R1A, PIK3CA and ARID1A. In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed...
March 9, 2018: Mutation Research
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Jingyi Li, Jie Xu, Lynne V Abruzzo, Guilin Tang, Shaoying Li, M James You, Gary Lu, Elias J Jabbour, Qi Deng, Carlos E Bueso-Ramos, L Jeffrey Medeiros, C Cameron Yin
We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17-76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia. Flow cytometry analysis showed myeloid lineage with blasts positive for CD13, CD33, CD34, CD38, CD117 and HLA-DR. Interestingly, aberrant CD7 expression was detected in 12/14 cases, and myeloperoxidase was either negative (3/15) or positive in only a small subset of the blasts (12/15)...
February 16, 2018: Oncotarget
Meenakshi Mehrotra, Rajesh R Singh, Sanam Loghavi, Dzifa Yawa Duose, Bedia A Barkoh, Carmen Behrens, Keyur P Patel, Mark J Routbort, Scott Kopetz, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Rajyalakshmi Luthra
A suitable clinical-grade platform is required for detection of somatic mutations with high sensitivity in cell-free DNA (cfDNA) of patients with solid tumors. In this study, we evaluated in parallel ultra-deep NGS with MassARRAY and allele-specific droplet digital PCR (ddPCR) for cfDNA genotyping and correlated cfDNA yield and mutation status with overall survival (OS) of patients. We assessed plasma samples from 46 patients with various advanced metastatic solid tumors and known mutations by deep sequencing using an Ampliseq cancer hotspot panel V2 on Ion Proton...
February 13, 2018: Oncotarget
Sarah D Cramer, Julie A Hixon, Caroline Andrews, Ross J Porter, Gisele O L Rodrigues, Xiaolin Wu, Tim Back, Kelli Czarra, Helen Michael, Maggie Cam, Jack Chen, Dominic Esposito, Emilee Senkevitch, Vijay Negi, Peter D Aplan, Wenqing Li, Scott K Durum
No abstract text is available yet for this article.
February 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Marcel Wiesweg, Henning Reis, Tobias Köster, Moritz Goetz, Karl Worm, Thomas Herold, Andreas Paul, Alexander Dechêne, Brigitte Schumacher, Peter Markus, Isabel Virchow, Karina Kostbade, Nathalie Wolf, Gregor Zaun, Martin Metzenmacher, Kurt W Schmid, Martin Schuler, Stefan Kasper
BACKGROUND: Deregulation of signal transduction pathways plays a critical role in oncogenesis of colorectal cancer (CRC) and directly affects sensitivity to targeted therapies. Against this background we developed a comprehensive biomarker profiling program including markers of downstream signaling to study their association with clinical outcomes. PATIENTS AND METHODS: A prospectively studied cohort of 160 patients with metastatic CRC was included. Standard diagnostic workup included mutational analyses of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
February 17, 2018: Clinical Colorectal Cancer
Li Sun, Zhicheng Xiong, Chengbo Han
In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC...
February 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Carmine Pinto, Maurizio Di Bisceglie, Francesca Di Fabio, Annamaria Bochicchio, Tiziana Latiano, Stefano Cordio, Gerardo Rosati, Carlo Aschele, Antonella Marino, Francesca Bergamo, Sara Bustreo, Luca Frassineti, Fortunato Ciardiello, Angela Damato, Stefania Giaquinta, Daniela Baldari, Luca Boni
BACKGROUND: Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment. MATERIALS AND METHODS: Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, KRAS wild-type status, and negative circumferential radial margin...
March 9, 2018: Oncologist
Girish Gulab Meshram, Neeraj Kaur, Kanwaljeet Singh Hura
Giant congenital melanocytic nevi (GCMN) are a rare occurrence. Gain-of-function mutation in the NRAS gene is found to be associated with GCMN, causing abnormal proliferation of embryonic melanoblasts. The two major complications associated with GCMN are malignant melanoma and neurocutaneous melanosis. Treatment of GCMN has conventionally been surgical. However, the role of NRAS inhibitors and inactivation of nevus tissue by high hydrostatic pressure are being explored. We present a case of a 1-day-old neonate born with GCMN, along with a review of the literature...
January 2018: Case Reports in Dermatology
Giulia M Ravaioli, Emi Dika, Martina Lambertini, Marco A Chessa, Pier A Fanti, Annalisa Patrizi
Acral lentiginous melanoma (ALM) is the most common type of malignant melanoma (MM) in Asians, Afro-Americans and Middle-Easterns. It represents 1.5-10% of all MM cases, being the most common histological type of MM arising on palms, soles and nail apparatus, which is more generically defined as acral MM. To date no risk factors have been officially established, however a history of trauma may be involved in the pathogenesis of acral MM. This shows heterogeneous clinical features and frequently presents with advanced stage and aggressive behaviour, often as a result of misdiagnosis or delayed identification...
March 6, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression...
March 7, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
Irina A Tikhonova, Nicola Huxley, Tristan Snowsill, Louise Crathorne, Jo Varley-Campbell, Mark Napier, Martin Hoyle
BACKGROUND: Combination therapies with cetuximab (Erbitux® ; Merck Serono UK Ltd) and panitumumab (Vectibix® ; Amgen UK Ltd) are shown to be less effective in adults with metastatic colorectal cancer who have mutations in exons 2, 3 and 4 of KRAS and NRAS oncogenes from the rat sarcoma (RAS) family. OBJECTIVE: The objective of the study was to estimate the cost effectiveness of these drugs in patients with previously untreated RAS wild-type (i.e. non-mutated) metastatic colorectal cancer, not eligible for liver resection at baseline, from the UK National Health Service and Personal Social Services perspective...
March 1, 2018: PharmacoEconomics
Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L McQuade, Roger J Liang, Mingguang Liu, Whijae Roh, Dzifa Y Duose, Fernando Cl Carapeto, Jun Li, Jessica Lf Teh, Andrew E Aplin, Merry Chen, Jianhua Zhang, Alexander J Lazar, Michael A Davies, P Andrew Futreal, Rodabe N Amaria, David Y Zhang, Jennifer A Wargo, Lawrence N Kwong
Combined MEK and CDK4/6 inhibition (MEKi+CDK4i) has shown promising clinical outcomes in NRAS mutant melanoma patients. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi+CDK4i therapy but subsequently developed resistance. Whole exome sequencing and functional validation identified an acquired PIK3CAE545K mutation as conferring drug resistance. We demonstrate that PIK3CAE545K pre-existed in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multi-region sampling due to PIK3CAE545K being non-uniformly distributed...
March 1, 2018: Cancer Discovery
Jessica L F Teh, Phil F Cheng, Timothy J Purwin, Neda Nikbakht, Prem Patel, Inna Chervoneva, Adam Ertel, Paolo M Fortina, Ines Kleiber, Kim HooKim, Michael A Davies, Lawrence N Kwong, Mitch P Levesque, Reinhard Dummer, Andrew E Aplin
Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein...
March 1, 2018: Cancer Discovery
Weijie Li, Linda D Cooley, Keith August
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive childhood leukemia characterized by an excess proliferation of cells of granulocytic and monocytic lineages. The WHO classifies JMML with the myelodysplastic/myeloproliferative neoplasms. Myelodysplasia in JMML is usually minimal to mild. Auer rods have never been reported in JMML. We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis...
December 5, 2017: Pathology, Research and Practice
Kabir Mody, Tanios Bekaii-Saab
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide but associated mortality has declined in recent decades. Genomic profiling of the disease has resulted in the definition of subsets of patients-for example, KRAS, NRAS, or BRAF mutated; Her2 amplified; and mismatch repair deficient-which has enabled personalization of therapeutic decision making. These subsets are guiding drug development and combination therapy approaches using both targeted therapies and immunotherapies. Further refinement based on molecular discoveries and the emergence of newer technologies to enable new discoveries allow for great optimism for the future on behalf of patients with colon cancer...
April 2018: Surgical Oncology Clinics of North America
Christina Wu
Systemic treatments for patients with colon cancer has expanded broadly beyond 5-fluorouracil based chemotherapy. For early stage colon cancer patients who are considering adjuvant chemotherapy, multiple factors such as the risk of disease recurrence, absolute survival benefit of chemotherapy, treatment toxicity, and patient comorbid medical conditions must be taken into account. In the metastatic setting, biomarkers such as KRAS/NRAS/BRAF mutation, microsatellite instability status, and left- versus right-sided colon cancer have helped oncologists to tailor systemic treatment regimens, which include chemotherapy, targeted therapy, and immunotherapy...
April 2018: Surgical Oncology Clinics of North America
Xin Liu, Xianping Lv, Qiankun Yang, Huifang Jin, Wenpeng Zhou, Qingxia Fan
MicroRNAs have been reported to play an important role in diverse biological processes and progression of various cancers. MicroRNA-29a has been observed to be downregulated in human lung cancer tissues, but the function of microRNA-29a in lung cancer has not been well investigated. In this study, we demonstrated that the expression levels of microRNA-29a were significantly downregulated in 38 pairs of lung cancer tissues when compared to adjacent normal tissues. Overexpression of microRNA-29a inhibited the activity of cell proliferation and colony formation of lung cancer cells, H1299 and A549...
January 1, 2018: Technology in Cancer Research & Treatment
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