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Olena Odnokoz, Kyle Nakatsuka, Vladimir I Klichko, Jacqueline Nguyen, Liz Calderon Solis, Kaitlin Ostling, Marziyeh Badinloo, William C Orr, Svetlana N Radyuk
Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant...
October 19, 2016: Biochimica et Biophysica Acta
Yun Bai, Jia Wang, Jing Han, Xiao-Li Xie, Cheng-Guang Ji, Jie Yin, Lei Chen, Cun-Kai Wang, Xiao-Yu Jiang, Wei Qi, Hui-Qing Jiang
BACKGROUND AND AIMS: BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. METHODS: BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice...
October 22, 2016: Molecular Carcinogenesis
Bassem Refaat, Jawwad Ahmad, Shakir Idris, Fadi Fayez Kamfar, Ahmed Mohamed Ashshi, Sarah Abdullah Batwa, Faizah Ahmed Malibary
This is a prospective observational study that measures the expression of vitamin D (VD) metabolising and signalling molecules and Ca(2+) sensing receptor (CaSR) in human Fallopian tube (FT) during the menstrual cycle and ectopic pregnancy (EP). Fresh FTs were obtained during total abdominal hysterectomy at the follicular (n = 16) and midluteal (n = 16) phases. Specimens from remote and implantation sites as well as trophoblastic tissues were also freshly collected from each FT with EP (n = 10)...
October 22, 2016: Cell and Tissue Research
Anusha Sathyanarayanan, Karthik Subramanian Chandrasekaran, Devarajan Karunagaran
microRNAs (miRNAs) play significant roles in diverse biological processes and their deregulation is implicated in carcinogenesis. miR-146a executes tumour suppressive or oncogenic functions depending on the cancer type, but its effect on human cervical (CaCx) and colorectal (CRC) cancers have not been examined thus far. In this study, miR-146a exhibited high expression in CaCx but poor expression in CRC, in comparison to corresponding normal tissues. Nevertheless, ectopic expression of miR-146a inhibited proliferation in both CaCx and CRC cells and curbed their migration and invasion...
October 18, 2016: Biochemical and Biophysical Research Communications
Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
Judith Hagenbuchner, Martina Rupp, Christina Salvador, Bernhard Meister, Ursula Kiechl-Kohlendorfer, Thomas Müller, Kathrin Geiger, Consolato Sergi, Petra Obexer, Michael J Ausserlechner
Neuroblastoma is the most frequent, extracranial solid tumor in children with still poor prognosis in stage IV disease. In this study, we analyzed FOXO3-phosphorylation and cellular localization in tumor biopsies and determined the function of this homeostasis regulator in vitro and in vivo. FOXO3-phosphorylation at threonine-32 (T32) and nuclear localization in biopsies significantly correlated with stage IV disease. DNA-damaging drugs induced nuclear accumulation of FOXO3, which was associated with elevated T32-phosphorylation in stage IV-derived neuroblastoma cells, thereby reflecting the in situ results...
October 18, 2016: Oncotarget
Xia Wang, Qing Li, Hua Jin, Hua Zou, Wei Xia, Nan Dai, Xiao-Yan Dai, Dong Wang, Cheng-Xiong Xu, Yi Qing
Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells...
October 18, 2016: Oncotarget
Qiyong Jiang, Yimin Liu, Shijuan Zhang, Naikun Li, Gaoling Sun
MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues...
October 17, 2016: Oncotarget
Sundhar Ramalingam, Adva Eisenberg, Wen Chi Foo, Jennifer Freedman, Andrew J Armstrong, Larry G Moss, Michael R Harrison
Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome...
October 21, 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Tiziana Cavalli, Francesco Giudici, Gabriella Nesi, Andrea Amorosi, Raffaella Santi, Maria Luisa Brandi, Francesco Tonelli
Approximately 300 cases of sporadic parathyroid cyst (PCs) have been reported to date. Only two cases have been described in MEN1 so far. Detection by imaging could be challenging, especially in multiglandular primary hyperparathyroidism (HPT) and clinical outcome could be different. During the period 1990-2014, 71 MEN1 patients were operated for primary hyperparathyroidism in our centre. We report three cases of PCs in MEN1 patients affected by HPT, who underwent a total or subtotal parathyroidectomy with transcervical thymectomy...
October 20, 2016: Familial Cancer
Laura Olbrich, Eva Schmidt, Ertan Mayatepek, Markus Vogel
BACKGROUND: We report the case of a 6 year old boy suffering from adenohypophysis aplasia as well as ectopic neurohypophysis and delayed diagnosis of familial Mediterranean fever (FMF). CASE PRESENTATION: The boy was diagnosed with panhypopituitarism during the neonatal period and suffered from recurrent episodes during the following years suggesting infections. He also showed signs of adrenal insufficiency. Finally, at the age of 6 years, an additional diagnosis of familial Mediterranean fever (FMF) was clinically suspected and later confirmed by molecular analysis...
2016: International Journal of Pediatric Endocrinology
Jinlu Yu, Yunbao Guo, Baofeng Xu, Kan Xu
The middle meningeal artery (MMA) is a very important artery in neurosurgery. Many diseases, including dural arteriovenous fistula (DAVF), pseudoaneurysm, true aneurysm, traumatic arteriovenous fistula (AVF), moyamoya disease (MMD), recurrent chronic subdural hematoma (CSDH), migraine and meningioma, can involve the MMA. In these diseases, the lesions occur in either the MMA itself and treatment is necessary, or the MMA is used as the pathway to treat the lesions; therefore, the MMA is very important to the development and treatment of a variety of neurosurgical diseases...
2016: International Journal of Medical Sciences
Hiroko Mataki, Naohiko Seki, Keiko Mizuno, Nijiro Nohata, Kazuto Kamikawaji, Tomohiro Kumamoto, Keiichi Koshizuka, Yusuke Goto, Hiromasa Inoue
Patients with lung adenocarcinoma may benefit from recently developed molecular targeted therapies. However, analogous advanced treatments are not available for patients with lung squamous cell carcinoma (lung SCC). The survival rate of patients with the advanced stage of lung SCC remains poor. Exploration of novel lung SCC oncogenic pathways might lead to new treatment protocols for the disease. Based on this concept, we have identified microRNA- (miRNA) mediated oncogenic pathways in lung SCC. It is well known that miR-145-5p (the guide strand) functions as a tumor suppressor in several types of cancer...
September 27, 2016: Oncotarget
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAFV600E mutations activate MAP kinase signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer (CRC). In BRAFV600E mutant CRCs, treatment failure may be related to BRAFV600E -mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using CRC cell lines isogenic for BRAF. BRAFV600E -induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1...
October 7, 2016: Molecular Cancer Therapeutics
Peng Li, Ya-Ling Yin, Tao Guo, Xue-Ying Sun, Hui Ma, Mo-Li Zhu, Fan-Rong Zhao, Ping Xu, Yuan Chen, Guang-Rui Wan, Fan Jiang, Qi-Sheng Peng, Chao Liu, Li-Ying Liu, Shuang-Xi Wang
BACKGROUND: -GTP cyclohydrolase 1 (GCH1) deficiency is critical for endothelial nitric oxide synthase (eNOS) uncoupling in endothelial dysfunction. MicroRNAs (miR) are a class of regulatory RNAs that negatively regulate gene expression. We investigated whether statins prevent endothelial dysfunction via miR-dependent GCH1 upregulation. METHODS: -Endothelial function was assessed by measuring acetylcholine- induced vasorelaxation in the organ chamber. MiR-133a expression was assessed by RT-qPCR and fluorescence in situ hybridization...
October 20, 2016: Circulation
Y Liu, X Tan, Z Wang, Y Li, M Gao, Y Li, Z Fang, Y Sun, L Zhang, X Wang, Z Wei
OBJECTIVE: Adenomyosis is a common benign gynecological disease which has some malignant behaviors. Programmed cell death 4 (PDCD4) is a newly identified tumor suppressor gene which lowly expresses in various cancers. However, the expression status of PDCD4 in endometrium of adenomyosis patients has not been investigated. The aim of this study is to assess the expression levels of PDCD4 in endometrium of normal controls and adenomyosis patients. METHODS: The expression of PDCD4 in endometrium of normal controls and eutopic or ectopic endometrium of patients with adenomyosis was evaluated with quantitative real-time PCR, western blot and immunohistochemistry...
July 2016: Current Research in Translational Medicine
Ting-Ting Zhu, Li Wang, Hong-Lian Wang, Yu He, Xin Ma, Jun-Ming Fan
Increasing evidences have shown that Helicobacter pylori (Hp) is a pathogen closely related to extra-gastric disorders. Our previous in vitro studies had demonstrated that Hp infection, at least via cytotoxin-associated gene A protein (CagA), might play an important role in the pathogenesis of IgA nephropathy (IgAN) by stimulating proliferation and ectopic synthesis of aberrantly glycosylated IgA1 of B cells. However, the relevant clinical evidence of IgAN resulted from Hp infection remain to be elucidated...
October 20, 2016: Renal Failure
Yaoyao Shi, Yue Kuai, Lizhen Lei, Yuanyuan Weng, Friederike Berberich- Siebelt, Xinxia Zhang, Jinjie Wang, Yuan Zhou, Xin Jiang, Guoping Ren, Hongyang Pan, Zhengrong Mao, Ren Zhou
Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6...
October 15, 2016: Oncotarget
Indu Jose Thoompumkal, Krishnan Rehna, Kumaraswamy Anbarasu, Sundarasamy Mahalingam
Guanine nucleotide binding protein-like 3-like (GNL3L) is an evolutionarily conserved putative nucleolar GTPase belonging to the HSR1-MMR1 family. In the present study, using protein-protein interaction assays, we show that Leucine Zipper Down-regulated in Cancer-1 (LDOC1) is a novel interacting partner of GNL3L. Furthermore, our results reveal that ectopic expression of LDOC1 destabilizes endogenous GNL3L levels and down modulates GNL3L-induced cell proliferation, in contrast, the knockdown of LDOC1 potentiates cell proliferation upon GNL3L expression...
October 20, 2016: Cell Cycle
Marco Gottardo, Giuliano Callaini, Maria Giovanna Riparbelli
Mutations in Klp10A, a microtubule-depolymerising Kinesin-13, lead to overly long centrioles in Drosophila male germ cells. We demonstrated that the loss of Klp10A modifies the distribution of typical proteins involved in centriole assembly and function. In the absence of Klp10A the distribution of Drosophila pericentrin-like protein (Dplp), Sas-4 and Sak/Plk4 that are restricted in control testes to the proximal end of the centriole increase along the centriole length. Remarkably, the cartwheel is lacking or it appears abnormal in mutant centrioles, suggesting that this structure may spatially delimit protein localization...
October 20, 2016: Cell Cycle
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