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Autophagy leukemia

Shigeki Aoki, Michie Morita, Takuya Hirao, Masashi Yamaguchi, Reika Shiratori, Megumi Kikuya, Hiroji Chibana, Kousei Ito
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Treatments include glucocorticoids (GCs) such as dexamethasone (Dex) and prednisolone, which may be of value when used alongside cytotoxic anti-cancer drugs. To predict therapeutic efficacy of GCs, their activity against ALL cells is usually examined prior to chemotherapy; however, few studies have examined their effects when used in combination with other drugs. The paradox is that cytotoxic anti-cancer drugs that are effective against proliferating cancer cells show synergistic effects when used with GCs that prevent cell proliferation...
November 7, 2017: Oncotarget
A G Sanarico, C Ronchini, A Croce, E M Memmi, U A Cammarata, A De Antoni, S Lavorgna, M Divona, L Giacò, G E M Melloni, A Brendolan, G Simonetti, G Martinelli, P Mancuso, F Bertolini, F L Coco, G Melino, P G Pelicci, F Bernassola
The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WWP1 in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here, we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared to hematopoietic cells from healthy donors...
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Qiongyao Wang, Fanrui Zeng, Yanqin Sun, Qianqian Qiu, Jian Zhang, Weimei Huang, Jie Huang, Xiaomin Huang, Linlang Guo
PURPOSE: Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx), was found to be critical in modulating the chemoresistance of small cell lung cancer (SCLC) in our preliminary study. However, the molecular mechanisms of Etk in SCLC chemoresistance remain poorly understood. The present study investigated the downstream factor and pathway involved. EXPERIMENTAL DESIGN: We demonstrated first that knockdown of Etk by siRNAs suppressed autophagy in chemoresistant SCLC cells, and that direct inhibition of autophagy sensitized cells to chemotherapy...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Qicheng Chen, Li Ye, Jiajun Fan, Xuyao Zhang, Huan Wang, Siyang Liao, Ping Song, Ziyu Wang, Shaofei Wang, Yubin Li, Jingyun Luan, Yichen Wang, Wei Chen, Wenjing Zai, Ping Yang, Zhonglian Cao, Dianwen Ju
Asparaginase has been reported to be effective in the treatment of various leukemia and several malignant solid cancers. However, the anti-tumor effect of asparaginase is always restricted due to complicated mechanisms. Herein, we investigated the mechanisms of how glioblastoma resisted asparaginase treatment and reported a novel approach to enhance the anti-glioblastoma effect of asparaginase. We found that asparaginase could induce growth inhibition and caspase-dependent apoptosis in U87MG/U251MG glioblastoma cells...
October 31, 2017: Oncotarget
Gregory Segala, Marion David, Philippe de Medina, Mathias C Poirot, Nizar Serhan, François Vergez, Aurelie Mougel, Estelle Saland, Kevin Carayon, Julie Leignadier, Nicolas Caron, Maud Voisin, Julia Cherier, Laetitia Ligat, Frederic Lopez, Emmanuel Noguer, Arnaud Rives, Bruno Payré, Talal Al Saati, Antonin Lamaziere, Gaëtan Despres, Jean-Marc Lobaccaro, Silvere Baron, Cecile Demur, Fabienne de Toni, Clément Larrue, Helena Boutzen, Fabienne Thomas, Jean-Emmanuel Sarry, Marie Tosolini, Didier Picard, Michel Record, Christian Récher, Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a newly discovered cholesterol metabolite with tumor suppressor properties. Here, we explored its efficacy and mechanism of cell death in melanoma and acute myeloid leukemia (AML). We found that DDA induced lethal autophagy in vitro and in vivo, including primary AML patient samples, independently of melanoma Braf status or AML molecular and cytogenetic classifications. DDA is a partial agonist on liver-X-receptor (LXR) increasing Nur77, Nor1, and LC3 expression leading to autolysosome formation...
December 4, 2017: Nature Communications
Hu Lei, Weiwei Wang, Yingli Wu
Oncoproteins play a vital role in the pathogenesis of myeloid leukemia. Most targeted therapies for myeloid leukemia are small molecules or monoclonal antibodies that inhibit the activity of the oncoproteins. However, leukemia cells often develop resistance to these drugs through overexpression of the target protein and/or by obtaining new mutations in the target protein to render them resistant to the drug. Oncoproteins degradation induced by small molecules through ubiquitin or autophagy pathway is considered a better way to avoid drug resistance...
December 4, 2017: Leukemia & Lymphoma
Guohong Chen, Zhiteng Li, Shuai Su, Guobin Chang, Lingling Qiu, Pengfei Zhu, Yang Zhang, Qi Xu
Avian leukemia subgroup J (ALV-J) is one of the most detrimental neoplastic diseases in poultry production. However, the differences between somatic cells and immune cells post-infection remain poorly understood. The aim of our study was to detect the different responses in chicken to infection with ALV-J in different cell lines. In this study, we detected transcriptome expression changes during infection with ALV-J in chicken embryo fibroblast (CEF) and HD11 cell lines. RNA-Seq was used to determine the expression levels of mRNA transcripts from the two cell types after infection with ALV-J at 1, 4, and 7 dpi, and gene ontology analyses were used to cluster differentially expressed genes into pathways...
December 1, 2017: In Vitro Cellular & Developmental Biology. Animal
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
November 20, 2017: Journal of the National Cancer Institute
Qinghua Wu, Xu Wang, Eugenie Nepovimova, Anca Miron, Qianying Liu, Yun Wang, Dongxiao Su, Hualin Yang, Li Li, Kamil Kuca
Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated...
November 20, 2017: Archives of Toxicology
Manuela Mancini, Simona Soverini, Gabriele Gugliotta, Maria Alessandra Santucci, Gianantonio Rosti, Michele Cavo, Giovanni Martinelli, Fausto Castagnetti
Chibby 1 (CBY1) is a small and evolutionarily conserved protein, which act as β-catenin antagonist. CBY1 is encoded by C22orf2 (22q13.1) Its antagonistic function on β-catenin involves the direct interaction with: The C-terminal activation domain of β-catenin, which hinders β-catenin binding with Tcf/Lef transcription factors hence repressing β-catenin transcriptional activation. 14-3-3 scaffolding proteins (σ or ξ), which drive CBY1 nuclear export into a stable tripartite complex with β-catenin. The relative proximity of C22orf2 gene encoding for CBY1 to the BCR breakpoint on chromosome 22q11, whose translocation and rearrangement with the c-ABL is the causative event of chronic myeloid leukemia (CML), suggested that gene haploinsufficiency may play a role in the disease pathogenesis and progression...
October 20, 2017: Oncotarget
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
Xin-Yu Wang, Xue-Hong Zhang, Li Peng, Zheng Liu, Yin-Xue Yang, Zhi-Xu He, Hong-Wan Dang, Shu-Feng Zhou
Chronic myeloid leukemia (CML) treatment remains a challenge due to drug resistance and severe side effect, rendering the need on the development of novel therapeutics. CDDO-Me (Bardoxolone methyl), a potent Nrf2 activator and NF-κB inhibitor, is a promising candidate for cancer treatment including leukemia. However, the underlying mechanism for CDDO-Me in CML treatment is unclear. This study aimed to evaluate the molecular interactome of CDDO-Me in K562 cells using the quantitative proteomics approach stable-isotope labeling by amino acids in cell culture (SILAC) and explore the underlying mechanisms using cell-based functional assays...
2017: American Journal of Translational Research
San-Yuan Chen, Chun-Hsiang Lin, Jiun-Tsai Lin, Yi-Fang Cheng, Han-Min Chen, Shao-Hsuan Kao
AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69...
November 2017: Oncology Letters
Cavarretta Elena, Mastroiacovo Giorgio, Lupieri Annik, Frati Giacomo, Peruzzi Mariangela
Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms including breast adenocarcinoma, small cell lung cancer and acute leukemia. Early and late anthracycline-induced cardiotoxicity is a well-known phenomenon, and the incidence of heart failure in patients receiving doxorubicin is 2.2%, with a mortality rate over 60% at 2 years...
2017: Advances in Experimental Medicine and Biology
Aila Fakhimahmadi, Farinaz Nazmi, Marveh Rahmati, Nazila Moghtaran Bonab, Mehrdad Hashemi, Mohammad Amin Moosavi
Here, we report that targeting Nucleostemin (NS), a recently discovered stem cells-enriched gene, by a specific small interference RNA (siNS), decreases the rate of proliferation of acute promyelocytic leukemia (APL) NB4 cells and induces differentiation and autophagy. In addition, NS silencing promotes the effects of all-trans-retinoic acid (ATRA)-based differentiation therapy in NB4 cells. Autophagy inhibitors 3-methyladenine and bafilomycin block the effect of NS targeting on differentiation, indicating a new functional link between NS and autophagy as an important regulator of differentiation in NB4 cells...
October 26, 2017: Leukemia Research
Yujie Liu, Jianwei Pan, Lifang Liu, Wei Li, Ran Tao, Yinghu Chen, Huamei Li, Shiqiang Shang
BACKGROUND: Human cytomegalovirus (HCMV) infection is very common and latency can be reactivated in the future. And it can alter the intracellular environment, similar to other herpesviruses, for viral replication and survival. The aim of this study was to investigate the influence of HCMV infection on autophagy in human acute monocytic leukemia cell line (THP-1 cells). METHODS: Reverse transcription polymerase chain reaction (RT-PCR), western blot, and transmission electron microscope (TEM) were used to examine autophagy level...
November 2017: Medicine (Baltimore)
Amin Mokhlesi, Fabian Stuhldreier, Katharina W Wex, Anne Berscheid, Rudolf Hartmann, Nidja Rehberg, Parichat Sureechatchaiyan, Chaidir Chaidir, Matthias U Kassack, Rainer Kalscheuer, Heike Brötz-Oesterhelt, Sebastian Wesselborg, Björn Stork, Georgios Daletos, Peter Proksch
Investigation of the sponge Clathria basilana collected in Indonesia afforded five new peptides, including microcionamides C (1) and D (2), gombamides B (4), C (5), and D (6), and an unusual amide, (E)-2-amino-3-methyl-N-styrylbutanamide (7), along with 11 known compounds, among them microcionamide A (3). The structures of the new compounds were elucidated by one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of the constituent amino acid residues in 1-7 were determined by Marfey's analysis...
November 2, 2017: Journal of Natural Products
Jie Wang, Di Song, Yanzi Liu, Guangjian Lu, Shuai Yang, Lu Liu, Zhitao Gao, Lingling Ma, Zhixiang Guo, Chenguang Zhang, Hui Wang, Bo Yang
The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection...
October 31, 2017: Scientific Reports
Shen Tang, Yuyang Liu, Xinhang Wang, Ziwei Liang, Haiqing Cai, Laiming Mo, Deqiang Xiao, Songchao Guo, Yiqiang Ouyang, Bin Sun, Cailing Lu, Xiyi Li
PP2Acα2 is a recently discovered PP2Acα alternative splicing isoform that can be induced following serum withdrawal. It shows enhanced binding to immunoglobulin binding protein 1 and is overexpressed in chronic lymphocytic leukemia patients. Current knowledge concerning PP2Acα2 is limited. In this study, we induced and cloned PP2Acα2 from HL-60 cells and human lymphocytes, transfected them into human embryonic kidney 293 cells and constructed a stable overexpression cell line. We found that PP2Acα2 mRNA inhibits expression of its longer isoform PP2Acα mRNA but had no effect on the final protein expression and modification of this longer isoform...
October 21, 2017: Biochemical and Biophysical Research Communications
Q Heydt, C Larrue, E Saland, S Bertoli, J-E Sarry, A Besson, S Manenti, C Joffre, V Mansat-De Mas
In acute myeloid leukemia (AML), internal tandem duplication mutations in the FLT3 tyrosine kinase receptor (FLT3-ITD) account for up to 25% of cases and are associated with a poor outcome. In order to better target this AML subtype, a comprehensive view of how FLT3-ITD impacts AML cell biology is required. Here, we found that FLT3-ITD expression increased basal autophagy in AML cells, and that both pharmacological and genetic inhibition of the receptor reduced autophagy in primary AML samples and cell lines...
October 23, 2017: Oncogene
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