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Lymphoma multidrug resistance

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https://www.readbyqxmd.com/read/29057047/stabilizing-a-tubulysin-antibody-drug-conjugate-to-enable-activity-against-multidrug-resistant-tumors
#1
Leanna R Staben, Shang-Fan Yu, Jinhua Chen, Gang Yan, Zijin Xu, Geoffrey Del Rosario, Jeffrey T Lau, Luna Liu, Jun Guo, Bing Zheng, Josefa Dela Cruz-Chuh, Byoung-Chul Lee, Rachana Ohri, Wenwen Cai, Hongxiang Zhou, Katherine R Kozak, Keyang Xu, Gail D Lewis Phillips, Jiawei Lu, John Wai, Andrew G Polson, Thomas H Pillow
The tubulysins are promising anticancer cytotoxic agents due to the clinical validation of their mechanism of action (microtubule inhibition) and their particular activity against multidrug-resistant tumor cells. Yet their high potency and subsequent systemic toxicity make them prime candidates for targeted therapy, particularly in the form of antibody-drug conjugates (ADCs). Here we report a strategy to prepare stable and bioreversible conjugates of tubulysins to antibodies without loss of activity. A peptide trigger along with a quaternary ammonium salt linker connection to the tertiary amine of tubulysin provided ADCs that were potent in vitro...
October 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29042944/pien-tze-huang-induces-apoptosis-and-inhibits-proliferation-of-5-fluorouracil-resistant-colorectal-carcinoma-cells-via-increasing-mir-22-expression
#2
Zhaorong Chen, Aling Shen, Liya Liu, Youqin Chen, Jianfeng Chu, Qiaoyan Cai, Fei Qi, Thomas Joseph Sferra, Jun Peng
The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28969035/pleiotrophin-promotes-chemoresistance-to-doxorubicin-in-osteosarcoma-by-upregulating-p-glycoprotein
#3
Dapeng Wu, Liguo Liu, Xuebing Yan, Chunyan Wang, Yaling Wang, Kun Han, Shuchen Lin, Zhihua Gan, Daliu Min
Chemoresistance is a major hindrance to successful treatment of osteosarcoma (OS). Pleiotrophin (PTN), a neurotrophic growth factor, has been linked to the malignant characteristics of various cancer types. We retrospectively examined the correlation between PTN expression and chemoresistance in OS in a cohort of 133 OS patients. Immunohistochemistry revealed that PTN expression correlated with the necrosis rate and local OS recurrence. In a prognostic analysis, high PTN expression was associated with poor overall and disease-free survival, and was an independent adverse prognostic factor for disease-free survival...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28948903/pilot-study-duodenal-mdr1-and-cox2-gene-expression-in-cats-with-inflammatory-bowel-disease-and-low-grade-alimentary-lymphoma
#4
Jorge Castro-López, Mariana Teles, Camino Fierro, Karin Allenspach, Marta Planellas, Josep Pastor
Objectives Multidrug resistance 1 (MDR1) encodes a protein called P-glycoprotein (P-gp), which serves as an efflux pump membrane protein implicated in intestinal homeostasis and drug resistance. Cyclooxygenase-2 (COX2) is a key enzyme in the synthesis of proinflammatory prostaglandins, tumourigenesis and in mucosal defence. Despite the importance of MDR1 and COX2, changes in their mRNA levels have not been studied in cats with inflammatory bowel disease (IBD) and low-grade alimentary lymphoma (LGAL). The present study aimed to determine the mRNA levels of MDR1 and COX2 in cats with IBD and LGAL, and to evaluate their correlation with clinical signs, histological severity and between genes...
September 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28756726/mogamulizumab-for-the-treatment-of-relapsed-or-refractory-adult-t-cell-leukemia-lymphoma
#5
REVIEW
Frank T Winsett, Daniel J Lewis, Madeleine Duvic
Adult T-cell leukemia-lymphoma (ATL) is an aggressive variant of peripheral T-cell lymphoma of CD4+ T-malignant cells caused by human T-lymphotropic virus type-1. Despite aggressive treatment with multidrug combination chemotherapies, ATL confers a poor prognosis and commonly develops resistance to conventional treatments. Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL. In phase I and II clinical trials, it has achieved overall response rates of 31-50% in CCR4+ malignancies...
September 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28754855/pleiotrophin-promotes-chemoresistance-to-doxorubicin-in-osteosarcoma-by-upregulating-p-glycoprotein
#6
Dapeng Wu, Liguo Liu, Xuebing Yan, Chunyan Wang, Yaling Wang, Kun Han, Shuchen Lin, Zhihua Gan, Daliu Min
Chemoresistance is a major hindrance to successful treatment of osteosarcoma (OS). Pleiotrophin (PTN), a neurotrophic growth factor, has been linked to the malignant characteristics of various cancer types. We retrospectively examined the correlation between PTN expression and chemoresistance in OS in a cohort of 133 OS patients. Immunohistochemistry revealed that PTN expression correlated with the necrosis rate and local OS recurrence. In a prognostic analysis, high PTN expression was associated with poor overall and disease-free survival, and was an independent adverse prognostic factor for disease-free survival...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28679966/current-treatment-approaches-for-nk-t-cell-lymphoma
#7
Motoko Yamaguchi, Kana Miyazaki
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a form of lymphoma characterized by preferential extranodal involvement, Epstein-Barr virus (EBV) association, and geographic diversity in incidence. ENKL tumor cells express P-glycoprotein, which is related to multidrug resistance (MDR). This MDR phenomenon is thought to be the major reason why ENKL is resistant to anthracycline-containing chemotherapies and has led researchers to explore novel therapeutic strategies. Since the early 2000s, next-generation therapies, including upfront radiotherapy, chemotherapy, or concurrent chemoradiotherapy using non-MDR-related drugs, have markedly changed the management of ENKL...
July 6, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28606042/isolation-of-chlorogenic-acid-from-soil-borne-fungi-screlotium-rolfsii-their-reversal-of-multidrug-resistance-and-anti-proliferative-in-mouse-lymphoma-cells
#8
Bashir Ahmad, Muhammad Rizwan, Abdur Rauf, Muslim Raza, Shumaila Bashir, Joseph Molnáre, Ákos Csonka, Diána Szabó, Mohammad S Mubarak, Mah Noor, Bina S Siddiqui
BACKGROUND: Fungi performing a wide range of function in soil by secreting low molecular weight compound known as secondary metabolites. S. rolfsii is a soil borne phytopathogenic fungi was used for the production of bioactive compounds. OBJECTIVE: The present study belongs to evaluate the anticancer potentials of a secondary metabolites isolated from S. rolfsii, their multidrug resistance (MDR), and molecular docking study. METHOD: (1S,3R,4R,5R,E)-3-(3-(3,4-Dihydroxyphenyl)acryloyloxy)-1,4,5 trihydroxycyclohexanecarboxylic acid (1), or best known as chlorogenic acid, was isolated from the ethyl acetate fraction of crude secondary metabolites produced by the soil borne Fungus Screlotium rolfsii...
June 12, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28592719/effects-of-toceranib-phosphate-palladia-monotherapy-on-multidrug-resistant-lymphoma-in-dogs
#9
Hiroki Yamazaki, Naoki Miura, Yu-Chang Lai, Masashi Takahashi, Yuko Goto-Koshino, Momoi Yasuyuki, Munekazu Nakaichi, Hajime Tsujimoto, Asuka Setoguchi, Yasuyuki Endo
We examined whether multidrug resistant (MDR) canine lymphoma increases gene expression for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and c-KIT, and whether toceranib phosphate (TOC) has potential as a treatment for MDR canine lymphoma. The clinical data showed that PDGFRα expression was higher in canine subjects with MDR T-cell lymphoma than in those with untreated T-cell lymphoma, and that c-KIT expression was greater in subjects with T-cell lymphoma than in those with B-cell lymphoma...
July 19, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28587395/effectiveness-of-imatinib-mesylate-over-etoposide-in-the-treatment-of-sensitive-and-resistant-chronic-myeloid-leukaemia-cells-in-vitro
#10
Roslina Husaini, Munirah Ahmad, Zubaidah Zakaria
Chronic myeloid leukaemia (CML) is a form of leukaemia derived from the myeloid cell lineage. Imatinib mesylate, the breakpoint cluster region-abelson murine leukeamia kinase inhibitor, is a specific reagent used in the clinical treatment of CML. The DNA topoisomerase II inhibitor, etoposide, is also employed as a therapeutic, though it is used to a lesser extent. The present study aims to evaluate the effects of CML-targeted therapy, utilising imatinib mesylate and etoposide in the in vitro treatment of parental sensitive and adriamycin-resistant CML in the K562 and K562/ADM cell lines, respectively...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28528711/clinical-impact-of-colonization-with-multidrug-resistant-organisms-on-outcome-after-autologous-stem-cell-transplantation-a-retrospective-single-center-study
#11
Sebastian Scheich, Claudia Reinheimer, Christian Brandt, Thomas A Wichelhaus, Michael Hogardt, Volkhard A J Kempf, Uta Brunnberg, Christian Brandts, Olivier Ballo, Ivana von Metzler, Johanna Kessel, Hubert Serve, Björn Steffen
A significant increase in infections caused by multidrug-resistant organisms (MDRO) has been observed in recent years, resulting in an increase of mortality in all fields of health care. Hematological patients are particularly affected by MDRO infections because of disease- and therapy-related immunosuppression. To determine the impact of colonization with MDRO on overall survival, we retrospectively analyzed data from patients undergoing autologous hematopoietic stem cell transplantation at our institution...
September 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28483518/stat3-mediates-multidrug-resistance-of-burkitt-lymphoma-cells-by-promoting-antioxidant-feedback
#12
Ruolan Zeng, Youhong Tang, Hui Zhou, Yiping Liu, Junhui Huang, Li Li, Wei Liu, Yuhua Feng, Yangying Zhou, Taili Chen, Lu Zhang, Meizuo Zhong
Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28456891/ccmp-and-cump-in-apoptosis-concepts-and-methods
#13
REVIEW
Sabine Wolter, Fanni Dittmar, Roland Seifert
The cyclic nucleotides cAMP and cGMP are well-characterized second messenger molecules regulating many important intracellular processes, such as differentiation, proliferation, and apoptosis. The latter is a highly regulated process of programmed cell death wherein several regulatory proteins, like those belonging to the Bcl-2 family, are involved. The initiation of apoptosis is regulated by three different pathways: the intrinsic or mitochondrial, the extrinsic, and the ER stress pathway. Recently, it has been published that the pyrimidine cyclic nucleotides cCMP and cUMP also function as second messenger molecules, and additionally have an effect on apoptosis signaling pathways...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28454362/growth-of-tyrosine-kinase-inhibitor-resistant-philadelphia-positive-acute-lymphoblastic-leukemia-role-of-bone-marrow-stromal-cells
#14
Cheng Zhang, Xi Zhang, Shi-Jie Yang, Xing-Hua Chen
Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph(+) ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454332/zoledronic-acid-reverses-cisplatin-resistance-in-nasopharyngeal-carcinoma-cells-by-activating-the-mitochondrial-apoptotic-pathway
#15
Yanjie You, Haijun Li, Jiongyu Chen, Xin Qin, Yonggang Ran
Despite improvements to radiotherapeutic strategies, resistance to adjuvant chemotherapy remains the main problem underlying the low 5-year survival rate in patients with nasopharyngeal carcinoma (NPC). In the present study, the human NPC cell line HNE1 was exposed to gradually increasing concentrations of cisplatin (CDDP) in order to establish a drug-resistant sub-cell line, HNE1/CDDP. HNE1/CDDP cells exhibited multidrug resistance and a prolonged doubling time, as compared with the parent HNE1 cells. Furthermore, pretreatment with zoledronic acid (ZOL) appeared to resensitize the CDDP-resistant cells by inducing S-phase cell cycle arrest and the mitochondrial apoptotic pathway by upregulating the expression of B-cell lymphoma-2 (BCL-2)-associated X protein and caspase-9 and downregulating the expression of BCL-2...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28427190/pygopus2-inhibits-the-efficacy-of-paclitaxel-induced-apoptosis-and-induces-multidrug-resistance-in-human-glioma-cells
#16
Cefan Zhou, Hongxia Cheng, Wenying Qin, Yi Zhang, Hui Xiong, Jing Yang, Huang Huang, Yefu Wang, Xing-Zhen Chen, Jingfeng Tang
Anti-microtubule drugs, such as paclitaxel (PTX), are extensively used for the treatment of numerous cancers. However, growing evidence has shown that PTX resistance, either intrinsic or acquired, frequently occurs in patients and results in the failure of treatment, contributing to the high cancer mortality rate. Therefore, it is necessary to identify the genes or pathways involved in anti-microtubule drug resistance for future successful treatment of cancers. Pygopus2 (Pygo2), which contains a Zn-coordinated plant homeodomain (PHD) finger domain, is critical for β-catenin-dependent transcriptional switches in normal and malignant tissues and is over-expressed in various cancers, including human brain glioma...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421773/exploring-jolkinol-d-derivatives-to-overcome-multidrug-resistance-in-cancer
#17
Mariana A Reis, Omar B Ahmed, Gabriella Spengler, Joseph Molnár, Hermann Lage, Maria-José U Ferreira
Macrocyclic monoacyl lathyrane derivatives bearing a benzoyl moiety were previously found to be strong ABCB1 modulators. To explore the effects of different substituents of the aromatic moiety, 14 new compounds (1.1-1.7, 1.10, and 2.1-2.4) were prepared from jolkinol D (1), obtained from Euphorbia piscatoria, and from jolkinodiol (2), its hydrolysis derivative. Compounds 1.8 and 1.9, having aliphatic moieties, were also obtained. The reversal of ABCB1-mediated MDR was evaluated through functional and chemosensitivity assays on the human ABCB1-gene-transfected L5178Y mouse T-lymphoma cell line...
May 26, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28403692/severe-hypokalemia-due-to-a-possible-drug-drug-interaction-between-vinblastine-and-antiretrovirals-in-a-hiv-infected-patient-with-hodgkin-s-lymphoma
#18
Ezequiel Cordova, Laura Morganti, Andrea Odzak, Florencia Arcondo, Mariana Silva, Marcelo Zylberman, Claudia Rodriguez
A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir...
October 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#19
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28260044/microrna-125b-reverses-the-multidrug-resistance-of-nasopharyngeal-carcinoma-cells-via-targeting-of-bcl-2
#20
Tai-Ze Yuan, Huan-Huan Zhang, Xiao-Ling Lin, Jin-Xiu Yu, Qiu-Xiang Yang, Yin Liang, Jin Deng, Lai-Ji Huang, Xiu-Ping Zhang
Multidrug resistance (MDR) is a major clinical obstacle in the successful treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Results from previous studies suggest that microRNAs (miRNA) may be involved in promoting MDR in multiple cancer types. However, the role of miR‑125b in modulating the MDR of NPC is elusive. In the present study, miR‑125b expression in cisplatin (DDP) ‑resistant CNE2 cells (CNE2/DDP) was compared with parental counterparts, using reverse transcription‑quantitative polymerase chain reaction...
April 2017: Molecular Medicine Reports
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