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Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Kohei Nakamura, Kentaro Nakayama, Noriyoshi Ishikawa, Masako Ishikawa, Razia Sultana, Tohru Kiyono, Satoru Kyo
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4R24C , and hTERT . Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction...
February 27, 2018: Oncotarget
Yukun Liu, Ran Zhao, Yanmei Wei, Mengna Li, Heran Wang, Weihong Niu, Yao Zhou, Yuanzheng Qiu, Songqing Fan, Yihao Zhan, Wei Xiong, Yanhong Zhou, Xiaoling Li, Zheng Li, Guiyuan Li, Ming Zhou
BACKGROUND: miR-141 is up-regulated and plays crucial roles in nasopharyngeal carcinoma (NPC). However, the molecular mechanism underlying the dysregulation of miR-141 is still obscure. METHODS: Thus, the ChIP-PCR was performed to identify the c-Myc-binding sites in miR-141 and BRD7. qRT-PCR, western blot and immunohistochemistry assays were used to detect the expression of miR-141 and its up/down stream molecules. The rescue experiments on the c-Myc/miR-141 axis were performed in vitro and in vivo...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
Duanyang Zhai, Chunhui Cui, Lang Xie, Lianxu Cai, Jinlong Yu
Metastasis is the primary cause of mortality in colorectal cancer (CRC), the mechanism of which remains unclear. In the present study, by detecting mRNA expression using a reverse transcription-quantitative polymerase chain reaction (qPCR), it was revealed that sterol regulatory element-binding protein 1 (SREBP1) is highly expressed in CRC. Using a cell wound healing assay and a cell invasion assay, a novel metastasis-promoting role for SREBP1 in CRC was identified. Furthermore, snail family transcriptional repressor 1 (SNAIL) was identified as a key downstream effector of SREBP1 in CRC by the use of small interfering RNA against SNAIL...
April 2018: Oncology Letters
Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
Jonathan Welti, Adam Sharp, Wei Yuan, David I Dolling, Daniel Nava Rodrigues, Ines Figueiredo, Veronica Gil, Antje Neeb, Matthew Clarke, George Seed, Mateus Crespo, Semini Sumanasuriya, Jian Ning, Eleanor Knight, Jeffrey C Francis, Ashley Hughes, Wendy S Halsey, Alec Paschalis, Ram S Mani, Ganesh V Raj, Steve Plymate, Suzanne Carreira, Gunther Boysen, Arul M Chinnaiyan, Amanda Swain, Johann S de Bono
PURPOSE:  Persistent androgen receptor (AR) signaling drives castration resistant prostate cancer (CRPC) and confers resistance to AR targeting therapies. Novel therapeutic strategies to overcome this are urgently required. We evaluated how bromodomain and extra-terminal (BET) protein inhibitors (BETi) abrogate aberrant AR signaling in CRPC. EXPERIMENTAL DESIGN:  We determined associations between BET expression, AR driven transcription and patient outcome; and the effect and mechanism by which chemical BETi (JQ1 and GSK1210151A; I-BET151) and BET family protein knockdown regulates AR-V7 expression and AR signaling in prostate cancer (PC) models...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huafeng Pan, Yudi Zhu, Wei Wei, Siliang Shao, Xin Rui
BACKGROUND: Prostate cancer is a common malignancy and the second leading cause of cancer death in men. Elevated expression of the transcription factor FoxM1 and c-Myc has been identified in prostate cancer. However, the potential mechanism of elevated FoxM1 and c-Myc to the development of prostate cancer has not been identified. METHODS: In this report, the mRNA level of FoxM1 and c-Myc was detected in 30 prostate cancer and para-cancer tissues. Then, we detected the expression level of FoxM1 by real-time PCR and Western blot after disturbance of the expression level of c-Myc in PC-3 cells...
March 20, 2018: World Journal of Surgical Oncology
Cong Zhang, Lian-Mei Zhao, Hao Wu, Guo Tian, Su-Li Dai, Ri-Yang Zhao, Bao-En Shan
BACKGROUND/AIMS: Small nucleolar RNAs (snoRNAs) play an important role in carcinogenesis. In this study, we identified a C/D box snoRNA, snord105b, and further investigated the function and mechanism of the snord105b in gastric cancer (GC). METHODS: The expression level of snord105b in GC tissures, sera and cell lines were detected by qRT-PCR. Cell viability was assessed using MTS assay. Transwell and wound healing assay were performed to evaluate migration and invasion, and protein expression was examined by western blotting...
March 15, 2018: Cellular Physiology and Biochemistry
Aarne Fleischer, Iván M Lorenzo, Esther Palomino, Trond Aasen, Fernando Gómez, Miguel Servera, Víctor J Asensio, Víctor Gálvez, Juan Carlos Izpisúa-Belmonte, Daniel Bachiller
Cystic Fibrosis (CF) is a monogenic, lethal disease caused by mutations in the cystic fibrosis transmembrane conductance (CFTR) gene. Here we report the production of CF-iPS cell lines from two different p.F508del homozygous female patients (Table 1). Two different primary cell types, skin fibroblasts and keratinocytes, were transfected with retroviral cocktails containing four: c-MYC, KLF4, OCT4 and SOX2 (MKOS) or three: KLF4, OCT4 and SOX2 (KOS) reprogramming factors. Two fibroblast-derived MKOS lines are described in the main text...
March 11, 2018: Stem Cell Research
Rinat Sultanov, Olga Lebedeva, Georgij Arapidi, Maria Lagarkova, Sergei Kiselev
The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e...
April 2018: Data in Brief
Ana Marzo-Mas, Eva Falomir, Juan Murga, Miguel Carda, J Alberto Marco
Several colchicine analogues in which the N-acetyl residue has been replaced by haloacetyl, cyclohexylacetyl, phenylacetyl and various aroyl moieties have been synthesized. The cytotoxic activities of the synthesized compounds have been measured on three tumor cell lines (HT-29, MCF-7 and A549) and on one non-tumor cell line (HEK-293). These compounds exhibit high antiproliferative activities at the nanomolar level, in many cases with a higher potency than colchicine itself. Some of the compounds, particularly the haloacetyl derivatives, inhibit the polymerization of tubulin in a similar manner as colchicine...
March 8, 2018: European Journal of Medicinal Chemistry
Hua Zhou, Abdul Mondal, Aleksandra Dakic, Lama Alhawas, Xuefeng Liu, Zhixu He
The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot...
2018: BioMed Research International
Chengzhi Fang, Lili Xie, Chunmei Liu, Chunhua Fu, Wei Ye, Hong Liu, Binghong Zhang
Neonatal necrotizing enterocolitis (NEC) is a severe acquired disease that predominantly affects the small intestine of neonates. NEC is caused by a combination of metabolic products, dysfunctions of the blood vessels, mucus and other unknown factors. Berberine may induce beneficial effects on necrotic and cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects on epithelial cells. In the present study, the therapeutic effects of berberine were investigated and the potential mechanisms by which it functions within a neonatal NEC mouse model were analyzed...
April 2018: Experimental and Therapeutic Medicine
Rokaya El Ansari, Madeleine L Craze, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Emad A Rakha, Andrew R Green
Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500)...
March 16, 2018: British Journal of Cancer
Krishna B Singh, Eun-Ryeong Hahm, Lora H Rigatti, Daniel P Normolle, Jian-Min Yuan, Shivendra V Singh
We have shown previously that dietary administration of phenethyl isothiocyanate (PEITC), a small molecule from edible cruciferous vegetables, significantly decreases the incidence of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. In this study, we investigated the role of c-Myc-regulated glycolysis in prostate cancer chemoprevention by PEITC. Exposure of LNCaP (androgen-responsive) and 22Rv1 (castration-resistant) human prostate cancer cells to PEITC resulted in suppression of expression as well as transcriptional activity of c-Myc...
March 15, 2018: Cancer Prevention Research
Laurens E Franssen, Inger S Nijhof, Suzana Couto, Mark-David Levin, Gerard M J Bos, Annemiek Broijl, Saskia K Klein, Yan Ren, Maria Wang, Harry R Koene, Andries C Bloem, Aart Beeker, Laura M Faber, Ellen van der Spek, Reinier Raymakers, Roos J Leguit, Pieter Sonneveld, Sonja Zweegman, Henk Lokhorst, Tuna Mutis, Anjan Thakurta, Xiaozhong Qian, Niels W C J van de Donk
No abstract text is available yet for this article.
March 15, 2018: Haematologica
Morgan L Shannon, Ryann M Fame, Kevin F Chau, Neil Dani, Monica L Calicchio, Gwenaelle S Géléoc, Hart G W Lidov, Sanda Alexandrescu, Maria K Lehtinen
Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous c-Myc is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to anterior choroid plexus and ciliary body. To uncover the consequences of persistent MYC (c-Myc) expression, c-Myc expression was forced in multipotent neural precursors (Nestin-Cre:MYC), which produced a fully penetrant model of choroid plexus carcinoma and ciliary body medulloepithelioma...
March 12, 2018: American Journal of Pathology
Jun-Ho Cho, Goo-Young Kim, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis...
March 12, 2018: Biochemical and Biophysical Research Communications
Nimantana He, Zhenguo Dong, Dapeng Tai, Hao Liang, Xudong Guo, Ming Cang, Dongjun Liu
In our previous work, we isolated Arbas Cashmere goat hair follicle stem cells (gHFSCs) and explored the pluripotency. In this study, we investigated the expression and putative role of Sox9 in the gHFSCs. Immunofluorescence staining showed that Sox9 is predominantly expressed in the bulge region of the Arbas Cashmere goat hair follicle, and also positively expressed in both nucleus and cytoplasm of the gHFSCs. When the cells were transfected using Sox9-shRNA, cell growth slowed down and the expression of related genes decreased significantly, cell cycle was abnormal, while the expression of terminal differentiation marker loricrin was markedly increased; cells lost the typical morphology of HFSCs; the mRNA and protein expression of gHFSCs markers and stem cell pluripotency associated factors were all significantly decreased; the expression of Wnt signaling pathway genes LEF1, TCF1,c-Myc were significantly changed...
March 14, 2018: Cytotechnology
Doron Feinsilber, Roberto J Leoni, Duminda Siripala, Julianne Leuck, Katrina A Mears
The pharmacological and medical management of complex chemotherapy regimens are vast and complex, requiring an intimate understanding of physiology, particularly when novel biologic agents are utilized with commonly used regimens. The molecular classification in patients with diffuse large B-cell lymphoma (DLBCL) is multifaceted, particularly with the expansion of novel molecular targets. The pharmacological and medical management of hematologic malignancies with a tendency to have central nervous system (CNS) involvement is complex and requires an understanding of physiology and pharmacology...
January 8, 2018: Curēus
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