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https://www.readbyqxmd.com/read/28903565/liquid-biopsies-the-clinics-and-the-molecules
#1
V Kubaczková, L Sedlarikova, B Bollová, V Sandecká, M Stork, L Pour, S Sevcikova
Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28899456/clc5-decreases-the-sensitivity-of-multiple-myeloma-cells-to-bortezomib-via-promoting-pro-survival-autophagy
#2
Huimin Zhang, Yuhui Pang, Chuanbao Ma, Jianying Li, Huaquan Wang, Zonghong Shao
Resistance to bortezomib (BZ) is the major problem that largely limits its clinical application in multiple myeloma treatment. In current study, we investigated whether ClC5, a member of the chloride channel family, involved in this process. The results of MTT assay showed that BZ treatment decreased cell viability in three multiple myeloma cell lines (ARH77, U266 and SKO-007), with the IC50 value of 2.83 nM, 4.37 nM and 1.91 nM, respectively. Moreover, BZ increased the conversion of LC3B-I to LC3B-II and expressions of Beclin-1 and ATG5, concomitantly with decreased p62 expression...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28876364/silencing-of-augmenter-of-liver-regeneration-inhibited-cell-proliferation-and-triggered-apoptosis-in-u266-human-multiple-myeloma-cells
#3
H Q Zeng, Y Luo, S F Lou, Q Liu, L Zhang, J C Deng
Augmenter of liver regeneration (ALR) is a thermostable cytokine that was originally identified to promote the growth of hepatocytes. This study was conducted to explore the expression and function of ALR in multiple myeloma (MM), a common hematologic malignancy. Real-time PCR and western blot analysis were performed to detect the expression of ALR in U266 human MM cells and healthy peripheral blood mononuclear cells (PBMCs). U266 MM cells were exposed to 20 or 40 μg/mL of recombinant ALR and tested for cell proliferation...
August 31, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28812060/reolysin-and-histone-deacetylase-inhibition-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#4
Alena C Jaime-Ramirez, Jun-Ge Yu, Enrico Caserta, Ji Young Yoo, Jianying Zhang, Tae Jin Lee, Craig Hofmeister, John H Lee, Bhavna Kumar, Quintin Pan, Pawan Kumar, Robert Baiocchi, Theodoros Teknos, Flavia Pichiorri, Balveen Kaur, Matthew Old
Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I-III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of ∼55%...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#5
Elizabeta Rojas, Luis Corchete, Laura San Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemi Puig, Ramón García-Sanz, Maria Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
<br />The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.<br /><br />Experimental Design:  <p>Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28770558/long-non-coding-rna-malat1-is-an-inducible-stress-response-gene-associated-with-extramedullary-spread-and-poor-prognosis-of-multiple-myeloma
#6
Hiroshi Handa, Yuko Kuroda, Kei Kimura, Yuta Masuda, Hikaru Hattori, Lobna Alkebsi, Morio Matsumoto, Tetsuhiro Kasamatsu, Nobuhiko Kobayashi, Ken-Ichi Tahara, Makiko Takizawa, Hiromi Koiso, Takuma Ishizaki, Hiroaki Shimizu, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saito, Hirokazu Murakami
Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28763347/ex-vivo-induction-of-multiple-myeloma-specific-immune-responses-by-monocyte-derived-dendritic-cells-following-stimulation-by-whole-tumor-antigen-of-autologous-myeloma-cells
#7
Spyridoula Vasileiou, Ioannis Baltadakis, Sosanna Delimpasi, Maria-Helena Karatza, Konstantinos Liapis, Maria Garofalaki, Eirini Tziotziou, Zoe Poulopoulou, Dimitri Karakasis, Nicholas Harhalakis
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation...
July 31, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28720704/cytosolic-interaction-of-type-iii-human-cd38-with-cib1-modulates-cellular-cyclic-adp-ribose-levels
#8
Jun Liu, Yong Juan Zhao, Wan Hua Li, Yun Nan Hou, Ting Li, Zhi Ying Zhao, Cheng Fang, Song Lu Li, Hon Cheung Lee
CD38 catalyzes the synthesis of the Ca(2+) messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with the catalytic domain facing outside. How it can catalyze the synthesis of intracellular cADPR that targets the endoplasmic Ca(2+) stores has not been resolved. We have proposed that CD38 can also exist in an opposite type III orientation with its catalytic domain facing the cytosol. Here, we developed a method using specific nanobodies to immunotarget two different epitopes simultaneously on the catalytic domain of the type III CD38 and firmly established that it is naturally occurring in human multiple myeloma cells...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28710768/panobinostat-sensitizes-kras-mutant-non-small-cell-lung-cancer-to-gefitinib-by-targeting-taz
#9
Wen-Ying Lee, Pin-Cyuan Chen, Wen-Shin Wu, Han-Chung Wu, Chun-Hsin Lan, Yen-Hua Huang, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
Mutation of KRAS in non-small-cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhibitor for treating myelomas and also shows potentiality in NSCLC. However, the therapeutic efficacy of panobinostat against gefitinib-resistant NSCLC is unclear. In this study, we demonstrated that panobinostat overcame resistance to gefitinib in KRAS-mutant/EGFR-wild-type NSCLC...
July 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28693796/regulatory-effects-of-berberine-on-micrornome-in-cancer-and-other-conditions
#10
REVIEW
Seyed Hasan Ayati, Badrieh Fazeli, Amir Abbas Momtazi-Borojeni, Arrigo F G Cicero, Matteo Pirro, Amirhossein Sahebkar
Berberine (BBR) is an isoquinoline alkaloid found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial, antiparasitic and fungicide activities. Multiple pharmacological actions of BBR stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are single-stranded, evolutionary conserved, small non-coding RNA molecules with a length of 19-23 nucleotides that are involved in RNA silencing and post-transcriptional regulation of gene expression through binding to the 3'-untranslated region (3'UTR) of target mRNA...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28677774/construction-of-a-recombinant-lentivirus-mediated-shrna-expression-vector-targeting-the-human-psmd10-gene-and-validation-of-rnai-efficiency-in-rpmi%C3%A2-8226-multiple-myeloma-cells
#11
Siyue Du, Wenjiao Qin, Haiyan Leng, Zi Chen, Tao Zhang
Multiple myeloma (MM) is one of the most common malignant blood cancers. Previous studies have reported that proteasome 26S subunit non-ATPase 10 (PSMD10) is an oncoprotein with complex roles in hepatocellular carcinoma and other malignant tumors. Notably, research on the relationship between PSMD10 and tumorigenesis of MM has rarely been reported. The present study was designed to explore the possibility of PSMD10 as a therapeutic target in the treatment of MM, and the use of RNA interference (RNAi) to determine the function PSMD10...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28677427/cul4a-as-a-marker-and-potential-therapeutic-target-in-multiple-myeloma
#12
Yougang Yang, Shanan Wang, Jinghong Li, Shipeng Qi, Debing Zhang
Multiple myeloma is the most common cause of death of hematological malignancy worldwide. Cullin 4A has been proposed as oncogene in several types of human cancer, but the expression and function of cullin 4A in multiple myeloma remain unclear. Here, we demonstrate that cullin 4A plays an oncogenic role in multiple myeloma development. The expression of cullin 4A was detected by quantitative real-time polymerase chain reaction in multiple myeloma patients and multiple myeloma cell lines. In addition, silencing of cullin 4A with small interfering RNA was performed in human multiple myeloma cells, and the impact on proliferation, cell cycle, apoptosis, migration, and invasion of the multiple myeloma cells was analyzed...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28670929/exploiting-the-pro-apoptotic-function-of-noxa-as-a-therapeutic-modality-in-cancer
#13
REVIEW
Jeroen E Guikema, Martine Amiot, Eric Eldering
Direct targeting of Bcl-2 members for therapeutic purposes in cancer has become a clinical reality with the FDA approval of ABT-199/Venetoclax. Other highly specific BH3-mimetics are in pre-clinical development. Understanding the functional interactions among the Bcl-2 family is of prime importance to fully exploit their potential. NOXA is considered a rather weak BH3-only member but it has unexplored potential in various settings, which are of relevance in cancer. NOXA is best known as a selective inhibitor of MCL1, itself overexpressed in many cancers, and this protein pair forms an important rheostat in many forms of cell stress...
August 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28669490/ilf2-is-a-regulator-of-rna-splicing-and-dna-damage-response-in-1q21-amplified-multiple-myeloma
#14
Matteo Marchesini, Yamini Ogoti, Elena Fiorini, Anil Aktas Samur, Luigi Nezi, Marianna D'Anca, Paola Storti, Mehmet Kemal Samur, Irene Ganan-Gomez, Maria Teresa Fulciniti, Nipun Mistry, Shan Jiang, Naran Bao, Valentina Marchica, Antonino Neri, Carlos Bueso-Ramos, Chang-Jiun Wu, Li Zhang, Han Liang, Xinxin Peng, Nicola Giuliani, Giulio Draetta, Karen Clise-Dwyer, Hagop Kantarjian, Nikhil Munshi, Robert Orlowski, Guillermo Garcia-Manero, Ronald A DePinho, Simona Colla
Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28665416/a-gene-expression-signature-distinguishes-innate-response-and-resistance-to-proteasome-inhibitors-in-multiple-myeloma
#15
A K Mitra, T Harding, U K Mukherjee, J S Jang, Y Li, R HongZheng, J Jen, P Sonneveld, S Kumar, W M Kuehl, V Rajkumar, B Van Ness
Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents...
June 30, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28664617/down-regulation-of-long-non-coding-rna-malat1-by-rna-interference-inhibits-proliferation-and-induces-apoptosis-in-multiple-myeloma
#16
Hui Liu, Huihan Wang, Bin Wu, Kun Yao, Aijun Liao, Miao Miao, Yang Li, Wei Yang
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by abnormal proliferation of monoclonal plasma cells in the bone marrow. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an evolutionarily highly conserved long non-coding RNA was originally identified in metastatic non-small cell lung cancer and has been reported to be up-regulated in many other cancers. However, the function of MALAT1 in MM remains unknown. In the present study, by transfecting MM cells with MALAT1-specific short hairpin RNA (shRNA) expression plasmids, the role of MALAT1 in the proliferation and apoptosis of MM cells was investigated in vitro, and the tumorigenicity of MALAT1-silenced cells was evaluated in vivo...
June 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28645097/raman-spectroscopy-differentiates-between-sensitive-and-resistant-multiple-myeloma-cell-lines
#17
Domenico Franco, Sebastiano Trusso, Enza Fazio, Alessandro Allegra, Caterina Musolino, Antonio Speciale, Francesco Cimino, Antonella Saija, Fortunato Neri, Marco S Nicolò, Salvatore P P Guglielmino
Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM...
June 15, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28612512/germline-factor-ddx4-functions-in-blood-derived-cancer-cell-phenotypes
#18
Natalie Schudrowitz, Satoshi Takagi, Gary M Wessel, Mamiko Yajima
DDX4 (the human ortholog of Drosophila Vasa) is an RNA helicase and is present in the germ lines of all metazoans tested. It was historically thought to be expressed specifically in germline, but with additional organisms studied, it is now clear that in some animals DDX4/Vasa functions outside of the germline, in a variety of somatic cells in the embryo and in the adult. In this report, we document that DDX4 is widely expressed in soma-derived cancer cell lines, including myeloma (IM-9) and leukemia (THP-1) cells...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28588253/nucleotide-excision-repair-is-a-potential-therapeutic-target-in-multiple-myeloma
#19
R Szalat, M K Samur, M Fulciniti, M Lopez, P Nanjappa, A Cleynen, K Wen, S Kumar, T Perini, A S Calkins, E Reznichenko, D Chauhan, Y-T Tai, M A Shammas, K C Anderson, J-P Fermand, B Arnulf, H Avet-Loiseau, J-B Lazaro, N C Munshi
Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents...
June 7, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28580305/expression-of-hsa-mir-204-runx2-ppar%C3%AE-and-bcl2-in-bone-marrow-derived-mesenchymal-stem-cells-from-multiple-myeloma-patients-and-normal-individuals
#20
Raziyeh Mansurabadi, Saeid Abroun, Abass Hajifathali, Amir Asri, Amir Atashi, Mansoureh Haghighi
OBJECTIVE: Multiple Myeloma (MM) is a heterogeneous cytogenetic disorder in which clonal plasma cells proliferate in the bone marrow (BM) and cause bone destruction. The BM microenvironment plays a crucial role in pathogenesis of this disease, and mesenchymal stem cells (MSCs) are one of the key players. Herein, we propose to investigate the expressions of hsa-MIR-204, runt-related transcription factor 2 (RUNX2), peroxisome proliferator-activated receptor gamma (PPARγ), and B-cell lymphoma 2 (BCL2) as factors involved in osteogenesis, adipogenesis, and MSC survival in BM-MSCs from MM patients and normal individuals...
2017: Cell Journal
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