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Xiaofeng Qi, Wengguang Xu, Junqi Xie, Yufeng Wang, Shengwei Han, Zheng Wei, Yanhong Ni, Yingchun Dong, Wei Han
Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both in vitro and in vivo, and attempted to elucidate its possible underlying mechanisms...
October 20, 2016: Scientific Reports
Ying-Chun Lin, Rui-Yun Chen, Shang-Wen Chen, Te-Chun Hsieh, Kuo-Yang Yen, Ji-An Liang, Shih-Neng Yang, Yao-Ching Wang, Ya-Huey Chen, Nan-Haw Chow, Chia-Hung Kao
OBJECTIVES: This study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) and identified prognostic factors for radiotherapy (RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. METHODS: Genomic data from pretreatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met, and p16) of 76 patients were analyzed using tissue microarrays...
October 20, 2016: Clinical Otolaryngology
Darren M Hutt, Daniela Martino Roth, Christelle Marchal, Marion Bouchecareilh
Gene expression is regulated in part through the reversible acetylation of histones, by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). HAT activity results in the addition of acetyl groups on the lysine residues of histone tails leading to decondensation of the chromatin, and increased gene transcription in general, whereas HDACs remove these acetyl groups, thus leading to an overall suppression of gene transcription. Recent evidence has elucidated that histones are not the only components of the proteome that are targeted by HATs and HDACs...
2017: Methods in Molecular Biology
Hao Huang, Linfu Li, Weimei Shi, Hai Liu, Jianqiong Yang, Xiaoliang Yuan, Longhuo Wu
Nobiletin (NOB) chemically known as 5,6,7,8,3',4'-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca(2+)/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Theerawut Chanmee, Pawared Ontong, Tomomi Izumikawa, Miho Higashide, Nobutoshi Mochizuki, Chatchadawalai Chokchaitaweesuk, Manatsanan Khansai, Kazuki Nakajima, Ikuko Kakizaki, Prachya Kongtawelert, Naoyuki Taniguchi, Naoki Itano
Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. Like many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known on how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem-cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells...
October 6, 2016: Journal of Biological Chemistry
Natalya A Goloviznina, Santhosh Chakkaramakkil Verghese, Young Me Yoon, Oleh Taratula, Daniel L Marks, Peter Kurre
Mesenchymal stromal cells (MSC) present in the bone marrow (BM) microenvironment secrete cytokines and angiogenic factors that support the maintenance and regenerative expansion of hematopoietic stem and progenitor cells (HSPC). Here, we tested the hypothesis that extracellular vesicles (EVs) released by MSC contribute to the paracrine crosstalk that shapes hematopoietic function. We systematically characterized EV release by murine stromal cells and demonstrate that MSC-derived EVs prompt a loss of HSPC quiescence with concomitant expansion of murine myeloid progenitors...
October 7, 2016: Journal of Biological Chemistry
Yue Chen, Suhua Jiang, Jianzhou Zou, Yihong Zhong, Xiaoqiang Ding
The kidney is particularly susceptible to ischemia/hypoxia insult while dysfunction of proximal tubular epithelial cells (PTEC) is a primary pathologic hallmark in acute kidney injury. Hypoxia-inducible factor-1 (HIF-1) is a key regulator responsible for cellular hypoxic responses. Therefore, we investigated the effects of HIF-1 suppression, using small interference RNA (siRNA), upon the cell fate of PTEC under hypoxia, and explored the underlying possible molecular mechanism. Hypoxia was induced with hypoxia mimetic cobalt chloride...
October 19, 2016: Renal Failure
Dongmei Lu, Nanfang Li, Xiaoguang Yao, Ling Zhou
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex chronic inflammatory respiratory disease with multiple pathogenic factors and high morbidity and mortality. Serum levels of nuclear factor-κB (NF-κB), hypoxia-inducible factor-1 alpha (HIF-1α), and surfactant protein D (SPD) were investigated in OSAHS patients, to determine their clinical significance and correlation with the pathogenesis. Patients were classified into a mild and moderate OSAHS group (n = 25) and severe OSAHS group (n = 33). Twenty healthy patients served as a control group...
October 18, 2016: Bosnian Journal of Basic Medical Sciences
Yuen Ting Lam, Laura Lecce, Joanne T M Tan, Christina A Bursill, David J Handelsman, Martin K C Ng
Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout mouse strain that contains a transcriptionally inactive AR (AR(Δex3)KO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Castrated wildtype (AR(WT)) and AR(Δex3)KO mice were implanted with dihydrotestosterone (DHT) or placebo pellets following hindlimb ischemia (HLI)...
October 18, 2016: Endocrinology
Jonas Magno Santos Cesário, Rodrigo Barbosa Oliveira Brito, Camila Soares Malta, Chrisna Souza Silva, Yves Silva Teles Matos, Tânia Cristina Macedo Kunz, Jessica Julioti Urbano, Luis Vicente Franco Oliveira, Maria Aparecida Dalboni, Humberto Dellê
Angiogenesis is an essential process for the establishment, development, and dissemination of several malignant tumors including bladder cancer. The hypoxic condition promotes the stabilization of hypoxia-inducible factor 1 alpha (HIF-1α), which translocates to the nucleus to mediate angiogenic factors including the vascular endothelial growth factor A (VEGF-A). AnaeroGen system was developed for microbiology area to create a low oxygen tension required to the growth of anaerobic bacteria. Here, we hypothesized the use of AnaeroGen system to induce hypoxia in T24 human bladder carcinoma cells, in order to promote the overexpression of VEGF-A...
October 17, 2016: In Vitro Cellular & Developmental Biology. Animal
Young-Lan Park, Sun-Young Park, Seung-Hyun Lee, Rul-Bin Kim, Joong-Keun Kim, Sung-Yoon Rew, Dae-Seong Myung, Sung-Bum Cho, Wan-Sik Lee, Hyun-Soo Kim, Young-Eun Joo
Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells...
October 14, 2016: Oncotarget
María Noel Galardo, Agostina Gorga, Joaquín Pedro Merlo, Mariana Regueira, Eliana Herminia Pellizzari, Selva Beatriz Cigorraga, María Fernanda Riera, Silvina Beatriz Meroni
Hypoxia Inducible Factors (HIFs) are master regulators of glycolytic metabolism. HIFs consist of a constitutive HIFbeta (HIFβ) subunit and a HIFalpha (HIFα) subunit, whose half-life depends on prolyl-hydroxylases activity. Inhibition of prolyl-hydroxylases by hypoxia or transition metals, or augmentation of HIFα subunit levels by hormonal stimuli lead to a higher HIF transcriptional activity. On the other hand, it is well known that lactate produced by Sertoli cells is delivered to and used by germ cells as an energy substrate...
October 14, 2016: Biochimie
Hyoung Sook Park, Ji Hye Kim, Bo Kyung Sun, Sun U Song, Wonhee Suh, Jong-Hyuk Sung
It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia...
October 5, 2016: Molecular Medicine Reports
Ying Li, Bo Shi, Liping Huang, Xin Wang, Xiaona Yu, Baosheng Guo, Weidong Ren
Hypoxia-inducible factor-1α (HIF-1α) has been implicated in the pathogenesis of hypoxic pulmonary hypertension (PH). However, the potential clinical value of HIF-1α as a therapeutic target in the treatment of PH has not yet been evaluated. In this study, an animal model of hypoxia-induced PH was established by exposing adult rats to 10% O2 for 3 weeks, and the effects of the lentivirus-mediated delivery of HIF-1α short hairpin RNA (shRNA) by intratracheal instillation prior to exposure to hypoxia on the manifestations of hypoxia-induced PH were assessed...
October 14, 2016: International Journal of Molecular Medicine
Brij Bharti, Sachin Shukla, Ratnakar Tripathi, Suman Mishra, Mohan Kumar, Manoj Pandey, Rajnikant Mishra
BACKGROUND & OBJECTIVES: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP), activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin's lymphoma (NHL) are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis...
May 2016: Indian Journal of Medical Research
Sherihan Adel, Amal Mansour, Manal Louka, M Matboli, F Elmekkawi S, Nahed Swelam
BACKGROUND: The precise origin of Pre-eclampsia (PE) remains elusive. Multiple pieces of evidence support the existence of hypoxia in PE. MiRNA-210 (miR-210), which is induced by Hypoxia-Inducible Factor-1α (HIF-1α) during hypoxia, is one of the most hypoxia sensitive miRNAs. MiR-210 mediates these functions by regulating a lot of target mRNAs. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) was one of miR-210 targets and was found to be down regulated by hypoxia. OBJECTIVE: to assess the levels of relative expression of miR-210 and its target PTPN2 in Egyptian women with PE...
October 13, 2016: Gene
Ho Shin Kim, Mannkyu Hong, Jihyae Ann, Suyoung Yoon, Cong-Truong Nguyen, Su-Chan Lee, Ho-Young Lee, Young-Ger Suh, Ji Hae Seo, Hoon Choi, Jun Yong Kim, Kyu-Won Kim, Joohwan Kim, Young-Myeong Kim, So-Jung Park, Hyun-Ju Park, Jeewoo Lee
Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80...
September 30, 2016: Bioorganic & Medicinal Chemistry
Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang
Background: Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinico-pathologic implications of thymosin β4 expression in human colorectal carcinomas (CRCs). Materials and Methods: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series...
October 16, 2016: Journal of Pathology and Translational Medicine
Mariko Okamoto, Ai Asamura, Ko Tanaka, Takefumi Soeda, Kyo Watanabe, Hiroyuki Mizuguchi, Teruo Ikeda
Adenovirus (Ad) vectors are widely used in cancer gene therapies. However, compared to human patients, relatively limited information is available on gene transduction efficiency or cell-specific cytotoxicity in canine tumor cells transduced with Ad vectors. Since epidermal growth factor receptor (EGFR) is highly expressed on canine breast tumor cells, we sought to develop an Ad vector based on the RGD fiber-mutant adenovirus vector (AdRGD) that expresses canine caspase 3 under the control of EGFR promoter...
October 16, 2016: Veterinary Research Communications
Kristy Zera, Rebecca Sweet, Jason Zastre
Ensuring continuous intracellular supply of thiamine is essential to maintain metabolism. Cellular homeostasis requires the function of the membrane bound thiamine transporters THTR1 and THTR2. In the absence of increased dietary intake of thiamine, varying intracellular levels to meet metabolic demands during pathophysiological stressors, such as hypoxia, requires adaptive regulatory mechanisms to increase thiamine transport capacity. Previous work has established the up-regulation of SLC19A3 (THTR2) gene expression and activity during hypoxic stress through the activity of the hypoxia inducible transcription factor 1 alpha (HIF-1α)...
October 12, 2016: Gene
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