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Tatiana V Beketova, Mikhail Y Volkov, Evgeniy A Naryshkin, Tatiana M Novoselova, Evgeniy L Nasonov
Recent advances in pharmacology have greatly expanded the drug repertoire for treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystemic disorder, a type of the ANCA-associated vasculitis. Important features of this disease are eosinophilia and anti-myeloperoxidase ANCA presence in around 30-70% of patients. Primary therapy of EGPA includes steroids and cytotoxic drugs, e.g., cyclophosphamide, azathioprine, or methotrexate...
March 21, 2018: Clinical Rheumatology
Y J Xue, J Wu, Y X Zuo, Y P Jia, A D Lu, L P Zhang
Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
J J Zhao, Y L Zhang, S J Zhang, J Zhou, F K Yu, Y L Zu, H F Zhao, Z Li, Y P Song
Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
F Yang, W Z Cai, X D Yang, S N Chen, X W Tang, A N Sun, D P Wu, W Q Qian, H Y Qiu
Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph+ ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Yingjun Deng, Xin Li, Jinxin Feng, Xiangliang Zhang
CML is a myeloproliferative disease which expresses an active tyrosine kinase, BCR/ABL. As a specific inhibitor of BCR-ABL tyrosine kinase, imatinib becomes the first choice for treatment of CML due to its high efficacy and low toxicity. However, the development of imatinib resistance limits the long-term treatment benefit. so, we aimed to investigate the roles of miR-202 in the regulation of imatinib sensitivity in CML cell lines and the possible mechanisms involved. We found miR-202 was downregulated in seven CML cell lines by qRT-PCR analysis...
March 20, 2018: Bioscience Reports
Jeanne M Sisk, Matthew B Frieman, Carolyn E Machamer
Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions...
March 20, 2018: Journal of General Virology
Dong-Wook Kim, Susanne Saussele, Loretta A Williams, Hesham Mohamed, Yuanxin Rong, Teresa Zyczynski, Javier Pinilla-Ibarz, Elisabetta Abruzzese
Chronic, low-grade adverse events are common in patients with chronic myeloid leukemia who are treated with imatinib. These events may decrease patient quality of life and adherence, and may ultimately contribute to a suboptimal response. Alternative, second-generation tyrosine kinase inhibitors, such as dasatinib, are available with the potential to reduce adverse events, improve tolerability, and support long-term treatment goals. We present the final, primary analysis of DASPERSE/CA180-400 (NCT01660906), an open-label, multicenter, phase IV study designed to determine whether chronic, low-grade nonhematologic adverse events in imatinib-treated patients improve after switching to dasatinib, without affecting efficacy...
March 20, 2018: Annals of Hematology
Ningshu Huang, Zhenglan Huang, Miao Gao, Zhenhong Luo, Fangzhu Zhou, Lin Liu, Qing Xiao, Xin Wang, Wenli Feng
BACKGROUND: The bcr-abl fusion gene is the pathological origin of chronic myeloid leukemia (CML) and plays a critical role in the resistance of imatinib. Thus, bcr-abl disruption-based novel therapeutic strategy may warrant exploration. In our study, we were surprised to find that the characteristics of bcr-abl sequences met the design requirements of zinc finger nucleases (ZFNs). METHODS: We constructed the ZFNs targeting bcr-abl with high specificity through simple modular assembly approach...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
Qun Dai, Yu-Qing Ge
Platycodin D(PD) has a significantly inhibitory effect on multiple malignant tumors, and can inhibit the proliferation of leukemia cells K562 and induce apoptosis. However, its effect in improving the sensitivity of drug-resistant cells to imatinib and their molecular mechanism remained unclear. To investigate the effect and mechanism of PD alone or combined with imatinib (IM) in inhibiting CML imatinib resistant cell line K562/R, the cell proliferation was examined by CCK8 assay to reveal the effect of PD on the inhibitory function of imatinib...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Marcel Trautmann, Sebastian Huss, Wolfgang Hartmann, Eva Wardelmann
No abstract text is available yet for this article.
2018: Translational Gastroenterology and Hepatology
Hitoshi Kameyama, Tatsuo Kanda, Yosuke Tajima, Yoshifumi Shimada, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Toshifumi Wakai
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. However, rectal GIST is rare, the incident rate of it is approximately 5% of all GISTs. Rectal GIST symptoms generally include bleeding and/or pain and occasionally, urinary symptoms. Immunohistochemical evaluation finds that most rectal GIST tumors are CD117 (KIT) positive, and are sometimes CD34, platelet-derived growth factor receptor alpha (PDGFRA), smooth muscle actin, S-100, or vimentin positive...
2018: Translational Gastroenterology and Hepatology
Yuki Tanisaka, Shomei Ryozawa, Masanori Kobayashi, Maiko Harada, Tsutomu Kobatake, Kumiko Omiya, Hirotoshi Iwano, Shin Arai, Kouichi Nonaka, Yumi Mashimo
Lymphadenopathy may be difficult to diagnose using imaging results alone. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) may help to diagnose and determine the appropriate management of lymphadenopathy. EUS-FNA has been used as a safe and less invasive method for obtaining pathologic specimens from extraluminal lesions using endoscopic ultrasound. The present study evaluated the usefulness of EUS-FNA for lymphadenopathy. Between July 2013 and December 2016, 72 patients undergoing EUS-FNA for lymphadenopathy that could not be diagnosed solely using imaging were included...
April 2018: Oncology Letters
Yan Chen, Yao Cheng, Pengxuan Zhao, Shasha Zhang, Minsi Li, Chuanchuan He, Xiaojuan Zhang, Tan Yang, Ruicong Yan, Peng Ye, Xiang Ma, Guangya Xiang
Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity...
March 15, 2018: International Journal of Pharmaceutics
Steven A Rosenzweig
Resistance to chemotherapeutic drugs exemplifies the greatest hindrance to effective treatment of cancer patients. The molecular mechanisms responsible have been investigated for over 50 years and have revealed the lack of a single cause, but instead, multiple mechanisms including induced expression of membrane transporters that pump drugs out of cells (multidrug resistance (MDR) phenotype), changes in the glutathione system, and altered metabolism. Treatment of cancer patients/cancer cells with chemotherapeutic agents and/or molecularly targeted drugs is accompanied by acquisition of resistance to the treatment administered...
2018: Advances in Cancer Research
Fevzi F Yalniz, Mohammad H Murad, Stephanie J Lee, Steven Z Pavletic, Nandita Khera, Nilay D Shah, Shahrukh K Hashmi
Given the increasing incidence of cGVHD and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost effectiveness analysis (CEA) for the frequently utilized agents in SR-cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis (ECP), pomalidomide and methotrexate...
March 14, 2018: Biology of Blood and Marrow Transplantation
Qinghong Zheng, Xiaohong Peng, Hai Yu
BACKGROUND: Apart from the known anesthetic and antiarrhythmic effects, recent studies also highlight the anticancer activities of local anesthetics. In line with the findings, our work shows that ropivacaine, an amide-linked local anesthetic drug, targets chronic myeloid leukemia (CML) via inhibiting PI3K/Akt/mTOR. MATERIALS AND METHODS: The effects of ropivacaine in CML cell lines and primary stem or progenitor cells were investigated using apoptosis, proliferation and colony formation assays...
March 2018: American Journal of the Medical Sciences
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
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