Read by QxMD icon Read


Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Kenichi Aihara, Mariko Ikuo, Kohji Itoh, Koichiro Hayashi, Michihiro Nakamura, Masahiro Abe
Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death...
February 13, 2018: Oncotarget
Tom Zortel, Annette Schmitt-Graeff, Susanne Kirschnek, Georg Häcker
Background: Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Methods: Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of Bcl-2 in haematopoietic cells (Bcl-2-mice), and mice where mature neutrophils are lacking due to the deletion of Mcl-1 in myeloid cells (LysM-cre-mcl-1-flox-mice; Mcl-1-mice)...
March 7, 2018: Journal of Infectious Diseases
Zhi-Chuan Zhu, Ji-Wei Liu, Kui Li, Jing Zheng, Zhi-Qi Xiong
The nuclear import receptor karyopherin β1 (KPNB1) is involved in the nuclear import of most proteins and in the regulation of multiple mitotic events. Upregulation of KPNB1 has been observed in cancers including glioblastoma. Depletion of KPNB1 induces mitotic arrest and apoptosis in cancer cells, but the underlying mechanism is not clearly elucidated. Here, we found that downregulation and functional inhibition of KPNB1 in glioblastoma cells induced growth arrest and apoptosis without apparent mitotic arrest...
March 9, 2018: Oncogene
Yuzo Maeda, Hiroki Takahashi, Nozomu Nakai, Takeshi Yanagita, Nanako Ando, Tomotaka Okubo, Kenta Saito, Kazuyoshi Shiga, Takahisa Hirokawa, Masayasu Hara, Hideyuki Ishiguro, Yoichi Matsuo, Shuji Takiguchi
Apigenin is a natural flavonoid that exhibits anti-proliferative activity and induces apoptosis in various types of cancer, including colon cancer. The aim of the present study was to determine the mechanism underlying the apoptosis-inducing effect of apigenin in colon cancer. Apigenin reduced the proliferation of colon cancer cell lines, stimulated the cleavage of PARP and induced apoptosis in a dose-dependent manner. Apigenin treatment also suppressed the expression of the anti-apoptotic proteins Bcl-xL and Mcl-1...
March 7, 2018: International Journal of Oncology
Keigo Okada, Ayako Nogami, Shinya Ishida, Hiroki Akiyama, Cheng Chen, Yoshihiro Umezawa, Osamu Miura
FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells...
February 6, 2018: Oncotarget
Silvia Escudero, Elma Zaganjor, Susan Lee, Christopher P Mill, Ann M Morgan, Emily B Crawford, Jiahao Chen, Thomas E Wales, Rida Mourtada, James Luccarelli, Gregory H Bird, Ulrich Steidl, John R Engen, Marcia C Haigis, Joseph T Opferman, Loren D Walensky
MCL-1 is a BCL-2 family protein implicated in the development and chemoresistance of human cancer. Unlike its anti-apoptotic homologs, Mcl-1 deletion has profound physiologic consequences, indicative of a broader role in homeostasis. We report that the BCL-2 homology 3 (BH3) α helix of MCL-1 can directly engage very long-chain acyl-CoA dehydrogenase (VLCAD), a key enzyme of the mitochondrial fatty acid β-oxidation (FAO) pathway. Proteomic analysis confirmed that the mitochondrial matrix isoform of MCL-1 (MCL-1Matrix ) interacts with VLCAD...
March 1, 2018: Molecular Cell
Yunhui Hu, Ernesto Yagüe, Jing Zhao, Luyao Wang, Jingchao Bai, Qianxi Yang, Teng Pan, Hui Zhao, Jingjing Liu, Jin Zhang
Misregulation of BCL-2 family of proteins renders a survival signal to withstand cytotoxic anticancer drugs and is often found in drug resistant cells. The drug resistance phenotype is also associated with an enhancement of cancer stem cell-like (CSC) characteristics. Thus, inhibition of anti-apoptotic BCL-2 family proteins has been proposed as a possible antineoplastic strategy, and BCL-2 inhibitors are currently being clinically trailed in patients with leukemia, lymphoma or non-small cell lung cancer. However, the effects of BCL-2 inhibitors on drug resistant breast cancer have not yet been elucidated...
February 26, 2018: Cancer Letters
Lindsey A Miles, Nagyung Baik, Hongdong Bai, Helen P Makarenkova, William B Kiosses, Stan Krajewski, Francis J Castellino, Alex Valenzuela, Nissi M Varki, Barbara M Mueller, Robert J Parmer
BACKGROUND: Lactational competence requires plasminogen, the zymogen of the serine protease, plasmin. Plg-RKT is a unique transmembrane plasminogen receptor that promotes plasminogen activation to plasmin on cell surfaces. Plg-RKT -/- mice are viable, but no offspring of Plg-RKT -/- female mice survive to weaning. OBJECTIVES: We investigated potential lactational failure in Plg-RKT -/- mice and addressed causal mechanisms. METHODS: Fibrin accumulation, macrophage infiltration, processing of extracellular matrix components, effects of genetic deletion of fibrinogen, expression of fibrosis genes, and proliferation and apoptosis of epithelial cells were examined in lactating mammary glands of Plg-RKT -/- and Plg-RKT +/+ mice...
March 1, 2018: Journal of Thrombosis and Haemostasis: JTH
H V Sudeep, K Gouthamchandra, B J Venkatesh, K Shyam Prasad
Background: Withania somnifera is an Indian medicinal herb known for the multipotential ability to cure various therapeutic ailments as described in the ayurvedic system of medicine. Objective: In the present study, we have evaluated the antiproliferative activity of a standardized W. somnifera root extract (Viwithan) against different human and murine cancer cell lines. Materials and Methods: The cytotoxicity of Viwithan was determined using thiazolyl blue tetrazolium blue assay and crystal violet staining...
January 2018: Pharmacognosy Magazine
Anirut Hlosrichok, Somruethai Sumkhemthong, Boonchoo Sritularak, Pithi Chanvorachote, Chatchai Chaotham
Failure of current chemotherapeutic drugs leads to the recurrence of tumor pathology and mortality in lung cancer patients. This study aimed to evaluate the anticancer activity and related mechanisms of 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang, in human lung cancer cells. Cytotoxicity of TDB (0-300 µM) in different types of human lung cancer cells (H460, H292 and H23) and human dermal papilla cells (DPCs) was evaluated via MTT viability assay...
February 27, 2018: Journal of Natural Medicines
Srinivasan Perumal, Kulanthaivel Langeshwaran, Jayaraman Selvaraj, Rajagopal Ponnulakshmi, B Shyamaladevi, M P Balasubramanian
The aim of the present study was to evaluate the antioxidant and chemopreventive efficiency of diosmin against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in adult male rats. Rats were classified into four groups as follows: Group I: Control, Group II: NDEA-induced hepatocellular carcinogenic rats, Group III: Cancer-bearing animals treated with diosmin (200 mg/kg/body weight/day) orally for 28 days, Group IV: Control animals treated with diosmin (200 mg/kg/body weight/day) alone for 28 days...
February 26, 2018: Molecular and Cellular Biochemistry
Konstantinos V Floros, Timothy L Lochmann, Bin Hu, Carles Monterrubio, Mark T Hughes, Jason D Wells, Cristina Bernadó Morales, Maninderjit S Ghotra, Carlotta Costa, Andrew J Souers, Sosipatros A Boikos, Joel D Leverson, Ming Tan, Violeta Serra, Jennifer E Koblinski, Joaquin Arribas, Aleix Prat, Laia Paré, Todd W Miller, Mikhail G Dozmorov, Hisashi Harada, Brad E Windle, Maurizio Scaltriti, Anthony C Faber
HER2 ( ERBB2 ) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR -mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment...
February 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Andrana Karla Calgarotto, Victor Maso, Gilberto Carlos Franchi Junior, Alexandre Eduardo Nowill, Paulo Latuf Filho, José Vassallo, Sara Teresinha Olalla Saad
Quercetin is one of the most abundant flavonoids, present in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Green tea is a widely consumed beverage, known for a potential source of free radical scavenging and anti-cancer activities. Herein, we investigate the in vivo antitumor efficacy of quercetin and green tea in human leukemia. Human tumors were xenografted into NOD/SCID mice. Quercetin and green tea reduced tumor growth in HL-60 xenografts accompanied by decreased expression of anti-apoptotic proteins, BCL-2, BCL-XL and MCL-1 and increased expression of BAX, a pro-apoptotic protein...
February 22, 2018: Scientific Reports
Silvia Boffo, Angela Damato, Luigi Alfano, Antonio Giordano
Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety...
February 23, 2018: Journal of Experimental & Clinical Cancer Research: CR
Cheng-Yi Chang, Jian-Ri Li, Chih-Cheng Wu, Jiaan-Der Wang, Ching-Ping Yang, Wen-Ying Chen, Wen-Yi Wang, Chun-Jung Chen
Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly implicated in the prevention and treatment of cancers apart from their known inhibitory effects on eicosanoid production. One of the NSAIDs, indomethacin, in particular shows promising antineoplastic outcome against glioma. To extend such finding, we here studied in human H4 and U87 glioma cells the possible involvement of the ceramide/protein phosphatase 2A (PP2A)/Akt axis in the indomethacin-induced apoptosis. We found that the induced apoptosis was accompanied by a series of biochemical events, including intracellular ceramide generation, PP2A activation, Akt dephosphorylation, Mcl-1 and FLICE inhibiting protein (FLIP) transcriptional downregulation, Bax mitochondrial distribution, and caspase 3 activation...
February 19, 2018: Experimental Cell Research
Bao-Long Pan, Zong-Wu Tong, Ling Wu, Li Pan, Jun-E Li, You-Guang Huang, Shu-De Li, Shi-Xun Du, Xu-Dong Li
BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting...
February 15, 2018: Cellular Physiology and Biochemistry
Chandan Kanta Das, Benedikt Linder, Florian Bonn, Florian Rothweiler, Ivan Dikic, Martin Michaelis, Jindrich Cinatl, Mahitosh Mandal, Donat Kögel
Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity...
February 17, 2018: Neoplasia: An International Journal for Oncology Research
Jade K Pollock, Lisa M Greene, Seema M Nathwani, Paula Kinsella, Niamh M O'Boyle, Mary J Meegan, Daniela M Zisterer
Purpose The combretastatins (CAs) are known to exhibit anti-tumour activity but the underlying mechanism remains to be fully elucidated. Inflammation plays a critical role in altering the function of cancer cells and evasion of cell death and increased proliferation are characteristics of transformed malignancies. Many of the proteins involved in these pathways are regulated by the transcription factor NF-κB which can be activated by tumour necrosis factor (TNF-α), a pro-inflammatory cytokine released by both malignant and immune cells within the tumour microenvironment...
February 19, 2018: Investigational New Drugs
Colin Hockings, Amber E Alsop, Stephanie C Fennell, Erinna F Lee, W Douglas Fairlie, Grant Dewson, Ruth M Kluck
The prosurvival Bcl-2 family proteins Mcl-1 and Bcl-xL inhibit apoptosis by sequestering BH3-only proteins such as Bid and Bim (MODE 1) or the effector proteins Bak and Bax (MODE 2). To better understand the contributions of MODE 1 and MODE 2 in blocking cell death, and thus how to bypass resistance to cell death, we examined prescribed mixtures of Bcl-2 family proteins. In a Bim and Bak mixture, Bcl-xL and Mcl-1 each sequestered not only Bim but also Bak as it became activated by Bim. In contrast, in a Bid and Bak mixture, Bcl-xL preferentially sequestered Bid while Mcl-1 preferentially sequestered Bak...
February 19, 2018: Cell Death and Differentiation
Yena Jin, Young Hwan Kim, Jin Yong Park, Yu-Jin Lee, Hyun-Mi Oh, Sung-Kyu Choi, Dong Cho Han, Byoung-Mog Kwon
During the search for signal transducer and activator of transcription 3 (STAT3) inhibitors from natural products, methyllucidone, isolated from Lindera species (Lauraceae), was identified as a STAT3 inhibitor. Methyllucidone inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU145 prostate cancer cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in LNCaP cells. Methyllucidone decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, Bcl-2, Mcl-1, and survivin...
February 8, 2018: Bioorganic & Medicinal Chemistry Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"