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Jiancai Wang, Yuqian Li, Li Gao, Fengqi Yan, Guodong Gao, Lihong Li
Mitochondrial dysfunction plays significant roles in the pathogenesis of Parkinson's Disease (PD). The inactivation of c-Myc, a down-stream gene of Wnt/β-catenin signaling, may contribute to the mitochondria dysfunction. Inhibition of glycogen synthase kinase 3β (GSK-3β) with Alsterpaullone (Als) can activate the down-stream events of Wnt signaling. Here, we investigated the protective roles of Als against MPP+ -induced cell apoptosis in SH-SY5Y cells. The data showed that Als effectively rescued c-Myc from the MPP+ -induced decline via Wnt signaling...
2018: Frontiers in Cellular Neuroscience
Himisha Beltran, Clara Oromendia, Daniel C Danila, Bruce Montgomery, Christopher Hoimes, Russell Z Szmulewitz, Ulka Vaishampayan, Andrew J Armstrong, Mark Stein, Jacek Pinski, Juan Miguel Mosquera, Verena Sailer, Rohan Bareja, Alessandro Romanel, Naveen Gumpeni, Andrea Sboner, Etienne Dardenne, Loredana Puca, Davide Prandi, Mark A Rubin, Howard I Scher, David S Rickman, Francesca Demichelis, David M Nanus, Karla V Ballman, Scott T Tagawa
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. EXPERIMENTAL DESIGN: Sixty men were treated with alisertib50mg twice daily for 7 days every 21-days. Eligibility included metastatic prostate cancer and at least one: small cell neuroendocrine morphology; 50% neuroendocrine marker expression; new liver metastases without PSA progression; elevated serum neuroendocrine markers...
September 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Maha M Rashad, Mona K Galal, Adel M El-Behairy, Eman M Gouda, Said Z Moussa
The aim of this study was to investigate the effects of maternal exposure to di-( n-butyl) phthalate (DBP) on testicular development and function in pre-pubertal and post-pubertal male rat offspring. Fourteen pregnant female rats were equally divided into two groups: a control group and a DBP-treated group. During gestation day (GD) 12 to postnatal day (PND) 14, the control group was administered 1 ml/day corn oil, and the DBP-treated group was administered DBP 500 mg/kg/day by oral gavage. On PND 25 (pre-puberty) and PND 60 (post-puberty), blood for serum and the testes were collected from five male offspring of each group...
September 19, 2018: Toxicology and Industrial Health
Vamsidhar Velcheti, David Schrump, Yogen Saunthararajah
Self-replication is the engine that drives all biologic evolution, including neoplastic evolution. A key oncotherapy challenge is to target this, the heart of malignancy, while sparing the normal self-replication mandatory for health and life. Self-replication can be demystified: it is activation of replication, the most ancient of cell programs, uncoupled from activation of lineage-differentiation, metazoan programs more recent in origin. The uncoupling can be physiologic, as in normal tissue stem cells, or pathologic, as in cancer...
May 23, 2018: American Society of Clinical Oncology Educational Book
Yibin Wu, Wenjie Chen, Lifeng Gong, Chongwei Ke, Huipeng Wang, Yuankun Cai
BACKGROUND G-protein receptor 125 (GPR125), as a transmembrane signal transducer, is involved in regulating cancer development. Although GPR125 is related with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. Here, we investigated the clinical significance of GPR125 in CRC. MATERIAL AND METHODS We assessed the expression level of GPR125 in CRC tissues by analyzing 3 datasets in the Gene Expression Omnibus (GEO) database and in human samples. The correlation between GPR125 expression and clinicopathological features was further analyzed...
September 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Werner Mohl, Ernest Spitzer, Robert M Mader, Vilas Wagh, Filomain Nguemo, Dejan Milasinovic, Alem Jusić, Cesar Khazen, Edit Szodorai, Beatrice Birkenberg, Gert Lubec, Juergen Hescheler, Patrick W Serruys
AIMS: Cardiac repair has steered clinical attention and remains an unmet need, because available regenerative therapies lack robust mechanistic evidence. Pressure-controlled intermittent coronary sinus occlusion (PICSO), known to induce angiogenetic and vasoactive molecules as well as to reduce regional ischemia, may activate endogenous regenerative processes in failing myocardium. We aimed to investigate the effects of PICSO in patients with advanced heart failure undergoing cardiac resynchronization therapy...
September 19, 2018: ESC Heart Failure
Irina Alimova, Angela Pierce, Etienne Danis, Andrew Donson, Diane K Birks, Andrea Griesinger, Nicholas K Foreman, Mariarita Santi, Laura Soucek, Sujatha Venkataraman, Rajeev Vibhakar
Loss of SMARCB1 is the hallmark genetic event that characterizes rhabdoid tumors in children. Rhabdoid tumors of the brain (ATRT) occur in young children and are particularly challenging with poor long term survival. SMARCB1 is a member of the SWI/SNF chromatin remodeling complex that is responsible for determining cellular pluripotency and lineage commitment. The mechanisms by which SMARCB1 deletion results in tumorigenesis remain unclear. Recent studies demonstrate that ATRT consists of 3 genomic sub-groups with a subset of poor outcome tumors expressing high BMP and MYC pathway activation...
September 19, 2018: International Journal of Cancer. Journal International du Cancer
David Fiedler, Kerstin Heselmeyer-Haddad, Daniela Hirsch, Leanora S Hernandez, Irianna Torres, Darawalee Wangsa, Yue Hu, Luis Zapata, Josef Rueschoff, Sebastian Belle, Thomas Ried, Timo Gaiser
Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention; however, recurrence rates are high. We collected formalin-fixed paraffin-embedded tissue of fifteen primary adenomas with recurrence, fifteen adenomas without recurrence, and fourteen matched pair samples (primary adenoma and the corresponding recurrent adenoma). The samples were analysed by array-comparative genomic hybridisation (aCGH) and single-cell multiplex-interphase fluorescence in situ hybridisation (miFISH) to understand clonal evolution, to examine the dynamics of copy number alterations (CNAs) and to identify molecular markers for recurrence prediction...
September 19, 2018: International Journal of Cancer. Journal International du Cancer
F-H Wang, X-J Ma, D Xu, J Luo
OBJECTIVE: The aim of this study was to investigate the expression of UPK1B in bladder cancer (BCa), and to further explore the correlation between UPK1B expression and pathological parameters as well as the prognosis of BCa. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UPK1B in 92 pairs of BCa tissues and adjacent normal tissues. The relationship between UPK1B expression and pathological features as well as the prognosis of BCa patients was further analyzed...
September 2018: European Review for Medical and Pharmacological Sciences
Linlin Shan, Dongyang Wang, Qinwen Mao, Haibin Xia
DGKθ protein expression levels are closely related to the development of diseases including diabetes, cancer, and neuronal disease. To investigate the transcriptional regulation of the DGKθ gene, we used CRISPR/Cas9 to generate a DGKθ endogenous promoter luciferase reporter HepG2 cell line, in which the endogenous DGKθ promoter controls the expression of the luciferase reporter gene. To test the cell line, FXR, the transcription factor for upregulating the expression of DGKθ gene, was used to validate the cell line...
September 19, 2018: Applied Biochemistry and Biotechnology
Bingcong Xing, Lijun Liang, Lin Liu, Zhuoni Hou, Dongfeng Yang, Kaijing Yan, Xuemin Zhang, Zongsuo Liang
SmbHLH148 activated the whole biosynthetic pathways of phenolic acids and tanshinones, thus upregulated the production of both the two groups of pharmaceutical ingredients in Salvia miltiorrhiza. Phenolic acids and tanshinones are the two important groups of pharmaceutical ingredients presented in Salvia miltiorrhiza Bunge. The bHLH transcription factors could regulate secondary metabolism efficiently in plants. However, there are only some MYCs have been studied on regulation of either phenolic acids or tanshinones biosynthesis...
September 18, 2018: Plant Cell Reports
Pasquale L Fedele, Simon N Willis, Yang Liao, Michael S Low, Jai Rautela, David H Segal, Jia-Nan Gong, Nicholas D Huntington, Wei Shi, David C S Huang, George Grigoriadis, Julie Tellier, Stephen L Nutt
Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis...
September 18, 2018: Blood
Kelly E Henry, Megan M Dacek, Thomas R Dilling, Jonathan D Caen, Ian L Fox, Michael J Evans, Jason S Lewis
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers with a 5-year survival rate of less than 10%. Physicians often rely on biopsy or CT to guide treatment decisions, but these techniques fail to reliably measure the actions of therapeutic agents in PDAC. KRAS mutations are present in >90% of PDAC and are connected to many signaling pathways through its oncogenic cascade, including extracellular regulated kinase (ERK) and MYC. A key downstream event of MYC is transferrin receptor (TfR), which has been identified as a biomarker for cancer therapeutics and imaging...
September 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Peng Zhang, Fuhong He, Jie Bai, Shohei Yamamoto, Shi Chen, Lin Zhang, Mengyao Sheng, Lei Zhang, Ying Guo, Na Man, Hui Yang, Suyun Wang, Tao Cheng, Stephen D Nimer, Yuan Zhou, Mingjiang Xu, Qian-Fei Wang, Feng-Chun Yang
ASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with other gene mutations. However, the molecular mechanisms underlying the leukemogenesis associated with ASXL1 and cooperating mutations remain to be elucidated. Here we report that Asxl1 loss cooperated with haploinsufficiency of Nf1, a negative regulator of the RAS signaling pathway, to accelerate the development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic stem and progenitor cells resulted in a gain-of-function transcriptional activation of multiple pathways critical for leukemogenesis, such as MYC, NRAS, and BRD4...
September 18, 2018: Journal of Clinical Investigation
Rokibul Islam, Jae-Gyu Kim, Yohan Park, Jung-Yoon Cho, Kim-Cuong Cap, A-Ra Kho, Won-Suk Chung, Sang-Won Suh, Jae-Bong Park
Insulin is a critical signaling molecule in reducing blood glucose levels, and pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose metabolism. However, the insulin effect on PDH function has not been well established. We observed that insulin attenuated the phosphorylation (p) of Ser264 (p-Ser264) in the PDH E1α subunit (PDHA1) in normal rat hepatocyte. In contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1 levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase-3β (GSK-3β) in HepG2 cells...
September 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Bojin Su, Tao Xu, Jeff P Bruce, Kenneth W Yip, Ning Zhang, Zeli Huang, Guoyi Zhang, Fei-Fei Liu, Jiyong Liang, Huiling Yang, François X Claret
Distant metastasis is the major contributor to treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). The lack of effective treatment strategies for metastatic NPC is the major cause for the low survival rate. Therefore, it is crucial to understand the molecular mechanisms underlying NPC metastasis and to identify potential biomarkers for targeted therapy. MicroRNA (miRNAs or miRs) have been shown to play an important role in tumorigenesis and metastasis. In the present study, we aimed to evaluate the significance of hsa‑miR‑24 in NPC metastasis...
November 2018: Oncology Reports
Melpomeni G Akrivou, Vera P Demertzidou, Nikoleta F Theodoroula, Fani M Chatzopoulou, Konstantinos A Kyritsis, Nikolaos Grigoriadis, Alexandros L Zografos, Ioannis S Vizirianakis
The present study aimed to assess the pharmacological anticancer profile of three natural and five synthetic sesquiterpenes developed by total chemical synthesis. To this end, their properties at the cellular and molecular level were evaluated in a panel of normal and cancer cell lines. The results obtained by performing cytotoxicity assays and gene expression analysis by reverse transcription-quantitative polymerase chain reaction showed that: i) Among the sesquiterpene derivatives analyzed, VDS58 exhibited a notable anticancer profile within attached (U-87 MG and MCF-7) and suspension (K562 and MEL-745) cancer cell cultures; however, U-87 MG cells were able to recover their proliferation capacity rapidly after 48 h of exposure; ii) gene expression profiling of U-87 MG cells, in contrast to K562 cells, showed a transient induction of cyclin-dependent kinase inhibitor 1A (CDKN1) expression; iii) the expression levels of transforming growth factor β1 (TGFB1) increased after 12 h of exposure of U-87 MG cells to VDS58 and were maintained at this level throughout the treatment period; iv) in K562 cells exposed to VDS58, TGFB1 expression levels were upregulated for 48 h and decrease afterwards; and v) the re-addition of VDS58 in U-87 MG cultures pretreated with VDS58 resulted in a notable increase in the expression of caspases (CASP3 and CASP9), BCL2‑associated agonist of cell death (BAD), cyclin D1, CDK6, CDKN1, MYC proto-oncogene bHLH transcription factor (MYC), TGFB1 and tumor suppressor protein p53...
November 2018: International Journal of Oncology
Run Xiang, Yue Cui, Yanping Wang, Tianpeng Xie, Xiaojun Yang, Zhu Wang, Juan Li, Qiang Li
Period2 (Per2) is a key circadian clock gene, and its deregulation contributes to tumour development, including breast cancer. However, the biological function and clinicopathological significance of Per2 in non‑small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the role of Per2 and its relative clinical significance in NSCLC. To analyse Per2 expression in NSCLC specimens, reverse transcription‑quantitative polymerase chain reaction was performed, and the results indicated that Per2 expression was markedly downregulated in 83...
November 2018: Oncology Reports
Yiqi Li, Xinru Li, Jun Pu, Qi Yang, Haixia Guan, Meiju Ji, Bingyin Shi, Mingwei Chen, Peng Hou
BACKGROUND: c-Myc is overexpressed in different types of cancer including thyroid cancer, and is considered undruggable over the decades. There is evidence showing that MLN8237, a kind of Aurora A kinase (AURKA) inhibitor, destabilizes c-Myc proteins in liver cancer cells through disrupting c-Myc/AURKA complex. However, the role of MLN8237 in thyroid cancer remains largely unclear. Our aims were to test therapeutic potential of MLN8237 in thyroid cancer, and to analyze determinant factors affecting the response of thyroid cancer cells to MLN8237 and clarify corresponding mechanism...
September 18, 2018: Thyroid: Official Journal of the American Thyroid Association
Agnieszka Razim, Katarzyna Pacyga, Małgorzata Aptekorz, Gayane Martirosian, Andrzej Szuba, Edyta Pawlak-Adamska, Monika Brzychczy-Włoch, Andrzej Myc, Andrzej Gamian, Sabina Górska
Clostridium difficile (CD) infections are a growing threat due to the strain resistance to antibiotic treatment and the emergence of hypervirulent strains. One solution to this problem is the search for new vaccine antigens, preferably surface-localized that will be recognized by antibodies at an early stage of colonization. The purpose of the study was to assess the usefulness of novel immunoreactive surface proteins (epitopes) as potential vaccine antigens. Such approach might be tough to pursue since pathogens have acquired strategies to subvert adaptive immune response to produce humoral response against non-essential proteins for their survival...
September 17, 2018: Scientific Reports
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