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Xuechao Liu, Haibo Qiu, Peng Zhang, Xingyu Feng, Tao Chen, Yong Li, Kaixiong Tao, Guoxin Li, Xiaowei Sun, Zhiwei Zhou, On Behalf Of China Gastrointestinal Stromal Tumor Study Group Cn-Gist
Objective: We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Methods: Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Results: Of the included patients, 1,375 (53...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Qian Li, Xiao-Ji Lin, Hui Chen, Jian Gong, Zhen Li, Xiang-Nan Chen
More than 90% of patients with chronic myeloid leukemia (CML) have the chromosomal translocation t(9;22)(q34;q11), while 5-8% of patients have complex variant translocations that have previously been thought not to affect the efficacy of imatinib therapy. The present study reports a patient with CML in B-lymphoid blast crisis who had a rare three-way Philadelphia (Ph) variant t(3;9;22)(p21;q34;q11), in addition to isodicentric Ph chromosomes. The patient was initially treated with imatinib for >2 months with a very poor response...
April 2018: Oncology Letters
Ching-Yuan Kuo, Po-Nan Wang, Wen-Li Hwang, Cheng-Hwai Tzeng, Li-Yaun Bai, Jih-Luh Tang, Ming-Chih Chang, Sheng-Fung Lin, Tsai-Yun Chen, Yeu-Chin Chen, Tran-Der Tan, Chih-Yi Hsieh, Chinjune Lin, Clinton Lai, Darko Miljkovic, Cheng-Shyong Chang
Background: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. Methods: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs...
March 2018: Therapeutic Advances in Hematology
Daniel Giglio, Lucie Podmolikova, Gunnar Tobin
Currently, we have assessed the neuronal control of the urinary bladder in radiation cystitis and whether interstitial cells contribute to the condition. Fourteen days following bladder irradiation (20 Gy) rats were sedated and the urinary bladder was cut in two sagittal halves where electrical field stimulation (EFS; 5-20 Hz) was applied on the pelvic nerve afferents or stretch (80 mN) on one half of the urinary bladder, while contractions were registered on the contralateral half of the urinary bladder in the absence and presence of increasing doses of imatinib (1-10 mg/kg; inhibitor of c-kit+ interstitial cells), atropine (1 mg/kg; to block muscarinic M3 receptors) or PPADS (2 mg/kg; to block P2X1 purinoceptors)...
March 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Khadega A Abuelgasim, Hinna Rehan, Maha Alsubaie, Nasser Al Atwi, Mohammed Al Balwi, Saeed Alshieban, Areej Almughairi
BACKGROUND: Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases...
March 11, 2018: Journal of Medical Case Reports
G Mulkerrin, N M Hogan, M Sheehan, M R Joyce
INTRODUCTION: Gastrointestinal Stromal Tumors (GISTs) are a rare slow growing malignancy, accounting for less than 1% of all gastrointestinal (GI) tract tumors. These tumors are usually discovered incidentally by endoscopy, surgery or radiology. However on occasions they may present with significant symptoms including GI blood loss. This case report discusses an atypical presentation of a GIST in a 57-year-old female. CASE PRESENTATION: A 57-year-old woman presented to the emergency department following one episode of melena...
March 1, 2018: International Journal of Surgery Case Reports
Naoya Uchida, Juan J Haro-Mora, Selami Demirci, Atsushi Fujita, Lydia Raines, Matthew M Hsieh, John F Tisdale
A reliable cell line capable of robust in vitro erythroid differentiation would be useful to investigate red blood cell (RBC) biology and genetic strategies for RBC diseases. K562 cells are widely utilized for erythroid differentiation; however, current differentiation methods are insufficient to analyze globin proteins. In this study, we sought to improve erythroid differentiation from K562 cells to enable protein-level globin analysis. K562 cells were exposed to a variety of reagents including hemin, rapamycin, imatinib, and/or decitabine (known erythroid inducers), and cultured in basic culture media or erythropoietin-based differentiation media...
March 7, 2018: Experimental Hematology
Lindsey M Charo, Adam M Burgoyne, Paul T Fanta, Hitendra Patel, Juliann Chmielecki, Jason K Sicklick, Michael T McHale
Gastrointestinal stromal tumors (GISTs) are rare in pregnancy, with only 11 reported cases. Adjuvant imatinib therapy, which targets the most common driver mutations in GIST ( KIT and PDGFRA) , is recommended for patients with high-risk GIST, but it has known teratogenicity in the first trimester. A 34-year-old G3P2 woman underwent exploratory laparotomy at 16 weeks' gestation for a presumed adnexal mass. Surgical findings included normal adnexa and a 14-cm solid small bowel mass. The mass was resected en bloc with a segment of jejunum followed by a primary anastomosis...
March 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Lucas Souto Nacif, Daniel R Waisberg, Rafael Soares Pinheiro, Fabiana Roberto Lima, Vinicius Rocha-Santos, Wellington Andraus, Luiz Carneiro D'Albuquerque
BACKGROUND: There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. CASE PRESENTATION: A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure...
March 10, 2018: Journal of Medical Case Reports
Lunming Liu, Weifeng Shen, Zhihui Zhu, Jinxiong Lin, Qingxia Fang, Yeping Ruan, Huajun Zhao
Fulvestrant is the FDA-approved "pure anti-estrogen" agent for malignant breast cancer therapy. But endocrine resistance causes drug failure. A new approach is desired for fulvestrant-resistant breast cancer (FRBC) therapy. This study aims to find an effective approach to inhibit FRBC for patients with advanced breast cancer. MTT assay was first performed to detect the effect of inhibitors of c-ABL (imatinib) and EGFR (lapatinib) on FRBC cells. Microarray analysis was carried out to identify microRNA which is significantly changed between parental and FRBC cells...
March 6, 2018: Biochemical and Biophysical Research Communications
Małgorzata Janeczko-Czarnecka, Maryna Krawczuk-Rybak, Irena Karpińska-Derda, Maciej Niedźwiecki, Katarzyna Musioł, Magdalena Ćwiklińska, Katarzyna Drabko, Katarzyna Mycko, Tomasz Ociepa, Katarzyna Pawelec, Danuta Januszkiewicz-Lewandowska, Marek Ussowicz, Blanka Rybka, Renata Ryczan-Krawczyk, Andrzej Kołtan, Grażyna Karolczyk, Agnieszka Zaucha-Prażmo, Wanda Badowska, Krzysztof Kałwak
BACKGROUND: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Elias Jabbour, Maral DerSarkissian, Mei Sheng Duh, Nora McCormick, Wendy Y Cheng, Lisa J McGarry, Ariadne Souroutzidis, Hui Huang, Susan O'Brien, Farhad Ravandi, Hagop M Kantarjian
INTRODUCTION: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib). PATIENTS AND METHODS: We identified 26 Ph+ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib...
February 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
F Belal, F Ibrahim, Z A Sheribah, H Alaa
In this paper, novel univariate and multivariate regression methods along with model-updating technique were developed and validated for the simultaneous determination of quaternary mixture of imatinib (IMB), gemifloxacin (GMI), nalbuphine (NLP) and naproxen (NAP). The univariate method is extended derivative ratio (EDR) which depends on measuring every drug in the quaternary mixture by using a ternary mixture of the other three drugs as divisor. Peak amplitudes were measured at 294nm, 250nm, 283nm and 239nm within linear concentration ranges of 4...
February 21, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Tânia Patrícia Almeida, Joana Ferreira, Ariane Vettorazzi, Amaia Azqueta, Eduardo Rocha, Alice Abreu Ramos
In the present study, we evaluate the in vitro cytotoxicity of fucoxanthin (Fx) on two human leukemia cell lines, K562 and TK6, alone and in combination with the conventional anticancer drugs imatinib (Imat) and doxorubicin (Dox). For the purpose, we assessed the cytotoxic and proliferation effects by cell count, induction of DNA damage by comet assay, and cell death by nuclear condensation, annexin V staining, coupled with propidium iodide uptake, and protein expression of Bax, caspase-3, and Bcl-2 (western blot)...
February 16, 2018: Environmental Toxicology and Pharmacology
Massimo Breccia, Robin Foà
PURPOSE OF REVIEW: Discontinuation of tyrosine kinase inhibitors (TKIs) in chronic phase chronic myeloid leukemia (CP-CML) patients has become a reality. Treatment-free remission (TFR) is the term that identifies success after discontinuation. RECENT FINDINGS: Several trials have demonstrated that with imatinib about 40% of patients discontinuing treatment in deep and stable molecular response remain disease-free. Second-generation TKIs have improved the rate of deep molecular responses and allowed to increase the percentage of patients attempting treatment discontinuation...
March 6, 2018: Current Oncology Reports
Houfu Liu, Yan Chen, Liang Huang, Xueying Sun, Tingting Fu, Shengqian Wu, Xiaoyan Zhu, Wei Zhen, Jihong Liu, Gang Lu, Wei Cai, Ting Yang, Wandong Zhang, Xiaohong Yu, Zehong Wan, Jianfei Wang, Scott G Summerfield, Kelly Dong, Georg C Terstappen
Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration of 11 small molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular weight of 3826 daltons, in rats. Each drug was administered as constant rate intravenous infusion for 6 h (small molecules) or 24 h (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements...
March 6, 2018: Journal of Pharmacology and Experimental Therapeutics
Kenji Nakano, Shunji Takahashi
Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib's approval as a treatment for gastrointestinal stromal tumors (GISTs) has been a great achievement...
March 5, 2018: International Journal of Molecular Sciences
Valentina Indio, Annalisa Astolfi, Giuseppe Tarantino, Milena Urbini, Janice Patterson, Margherita Nannini, Maristella Saponara, Lidia Gatto, Donatella Santini, Italo F do Valle, Gastone Castellani, Daniel Remondini, Michelangelo Fiorentino, Margaret von Mehren, Giovanni Brandi, Guido Biasco, Michael C Heinrich, Maria Aabbondanza Pantaleo
Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha ( PDGFRA ) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein-ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course...
March 4, 2018: International Journal of Molecular Sciences
Alexander Bartelt, Friederike Behler-Janbeck, F Timo Beil, Till Koehne, Brigitte Müller, Tobias Schmidt, Markus Heine, Laura Ochs, Tayfun Yilmaz, Martin Dietrich, Jan P Tuckermann, Michael Amling, Joachim Herz, Thorsten Schinke, Joerg Heeren, Andreas Niemeier
Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption...
2018: Bone Research
Elaine Silveira, Isadora Pontes Cavalcante, Jean Lucas Kremer, Pedro Omori Ribeiro de Mendonça, Claudimara Ferini Pacicco Lotfi
Background: New drugs for adrenocortical carcinoma (ACC) are needed because most patients undergo rapid disease progression despite surgery and adjuvant therapy with mitotane. In this study, we aimed to investigate the in vitro effects of different chemotherapy drugs, alone or combined with mitotane, on the viability of adrenocortical carcinoma cells. Methods: Everolimus, sunitinib, zoledronic acid, imatinib and nilotinib cytotoxicity, alone or combined with mitotane were tested on ACC H295R cells in monolayer or spheroid cultures using MTS assays and confocal microscopy...
2018: Cancer Cell International
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