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https://www.readbyqxmd.com/read/28078663/inhibition-of-hsp90-exerts-anti-tumor-effect-on-angiosarcoma-involvement-of-vegf-signaling-pathway
#1
S Yamada-Kanazawa, I Kajihara, S Fukushima, M Jinnin, M Masuzawa, M Masuzawa, Y Amoh, D Hoshina, R Abe, H Ihn
BACKGROUND: Angiosarcoma is a rare malignant neoplasm derived from endothelial cells and its prognosis is poor because advanced angiosarcoma is resistant to standard chemotherapy, and new therapies are urgently needed. Heat shock protein 90 (HSP90) has been identified as a molecular chaperone that regulates various cancer-related proteins. Numerous clinical trials are testing the effectiveness of HSP90 inhibitors in various types of malignancies. OBJECTIVES: To investigate the role of HSP90 in the pathogenesis of angiosarcoma and whether inhibition of HSP90 may have anti-tumor activity...
January 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28077287/iron-oxide-nanoparticles-modulate-heat-shock-proteins-and-organ-specific-markers-expression-in-mice-male-accessory-organs
#2
Kiruthika Sundarraj, Azhwar Raghunath, Lakshmikanthan Panneerselvam, Ekambaram Perumal
With increased industrial utilization of iron oxide nanoparticles (Fe2O3-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe2O3-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe2O3-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1)...
January 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28073914/serine-threonine-kinase-unc-51-like-kinase-1-ulk1-phosphorylates-the-co-chaperone-cdc37-and-thereby-disrupts-the-stability-of-cdc37-client-proteins
#3
Ran Li, Fengjie Yuan, Wan Fu, Luyao Zhang, Nan Zhang, Yanan Wang, Ke Ma, Xue Li, Lina Wang, Wei-Guo Zhu, Ying Zhao
The serine/threonine kinase Unc-51 like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is an Ulk1 substrate...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073608/design-synthesis-and-biological-evaluation-of-7-aryl-2-3-dihydro-1-4-dioxino-2-3-g-quinoline-derivatives-as-potential-hsp90-inhibitors-and-anticancer-agents
#4
Sina Omid Malayeri, Khalil Abnous, Atefeh Arab, Maryam Akaberi, Soghra Mehri, Afshin Zarghi, Razieh Ghodsi
A new series of quinoline analogues was designed and synthesized as Hsp90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines including MCF-7 (human breast cancer cells), DU145 (human prostate cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of Hsp90...
January 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28067803/regulation-of-viral-replication-apoptosis-and-pro-inflammatory-responses-by-17-aag-during-chikungunya-virus-infection-in-macrophages
#5
Tapas K Nayak, Prabhudutta Mamidi, Abhishek Kumar, Laishram Pradeep K Singh, Subhransu S Sahoo, Soma Chattopadhyay, Subhasis Chattopadhyay
Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively...
January 6, 2017: Viruses
https://www.readbyqxmd.com/read/28067273/validation-of-reference-genes-for-cryopreservation-studies-with-the-gorgonian-coral-endosymbiont-symbiodinium
#6
Gabriella Chong, Fu-Wen Kuo, Sujune Tsai, Chiahsin Lin
Quantification by real-time RT-PCR requires a stable internal reference known as a housekeeping gene (HKG) for normalising the mRNA levels of target genes. The present study identified and validated stably expressed HKGs in post-thaw Symbiodinium clade G. Six potential HKGs, namely, pcna, gapdh, 18S rRNA, hsp90, rbcl, and ps1, were analysed using three different algorithms, namely, GeNorm, NormFinder, and BestKeeper. The GeNorm algorithm ranked the candidate genes as follows in the order of decreasing stability: pcna and gapdh > ps1 > 18S rRNA > hsp90 > rbcl...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067111/extremely-low-level-microwaves-attenuate-immune-imbalance-induced-by-inhalation-exposure-to-low-level-toluene-in-mice
#7
Elena G Novoselova, Olga V Glushkova, Maxim O Khrenov, Tatyana V Novoselova, Sergey M Lunin, Eugeny E Fesenko
PURPOSE: To clarify whether extremely low-level microwaves (MW) alone or in combination with p38 inhibitor affect immune cell responses to inhalation exposure of mice to low-level toluene. MATERIALS AND METHODS: The cytokine profile, heat shock proteins expression, and the activity of several signal cascades, namely, NF-κB, SAPK/JNK, IRF-3, p38 MAPK, and TLR4 were measured in spleen lymphocytes of mice treated to air-delivered toluene (0.6 mg/m(3)) or extremely low-level microwaves (8...
January 9, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28064214/hsp90-promotes-burkitt-lymphoma-cell-survival-by-maintaining-tonic-b-cell-receptor-signaling
#8
Roland Walter, Kuan-Ting Pan, Carmen Doebele, Federico Comoglio, Katarzyna Tomska, Hanibal Bohnenberger, Ryan M Young, Laura Jacobs, Ulrich Keller, Halvard Bönig, Michael Engelke, Andreas Rosenwald, Henning Urlaub, Louis M Staudt, Hubert Serve, Thorsten Zenz, Thomas Oellerich
Burkitt lymphoma (BL) is an aggressive B cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Due to their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28062703/tas-116-a-novel-hsp90-inhibitor-selectively-enhances-radiosensitivity-of-human-cancer-cells-to-x-rays-and-carbon-ion-radiation
#9
Younghyun Lee, Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Jac A Nickoloff, Ryuichi Okayasu
Hsp90 inhibitors have been investigated as cancer therapeutics in monotherapy and to augment radiotherapy; however, serious adverse effects of early-generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here, we investigated the radiosensitizing effects of TAS-116 in low linear energy transfer (LET) X-ray and high LET carbon ion-irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of noncancerous human fibroblasts...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28062368/epothilone-b-based-3-in-1-polymeric-micelle-for-anticancer-drug-therapy
#10
Dae Hwan Shin, Glen S Kwon
Epothilones are microtubule inhibitors that are promising alternatives to paclitaxel due to enhanced anticancer efficacy. While epothilones are slightly more water soluble than paclitaxel and more active against paclitaxel-resistant cells, they still require formulation with Cremophor EL and/or cosolvents and drug resistance still limits therapeutic efficacy. In this report, we showed that the combinational treatment of epothilone B (EpoB), 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, Hsp90 inhibitor), and rapamycin (mTOR inhibitor) displays strong anticancer activity in vitro and in vivo...
January 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28060726/immunogenic-cancer-cell-death-selectively-induced-by-near-infrared-photoimmunotherapy-initiates-host-tumor-immunity
#11
Mikako Ogawa, Yusuke Tomita, Yuko Nakamura, Min-Jung Lee, Sunmin Lee, Saori Tomita, Tadanobu Nagaya, Kazuhide Sato, Toyohiko Yamauchi, Hidenao Iwai, Abhishek Kumar, Timothy Haystead, Hari Shroff, Peter L Choyke, Jane B Trepel, Hisataka Kobayashi
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28056051/mapping-the-interactome-of-a-major-mammalian-endoplasmic-reticulum-heat-shock-protein-90
#12
Feng Hong, Saleh Mohammad Rachidi, Debbie Lundgren, David Han, Xiu Huang, Hongyu Zhao, Yayoi Kimura, Hisashi Hirano, Osamu Ohara, Heichiiro Udono, Songdong Meng, Bei Liu, Zihai Li
Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96...
2017: PloS One
https://www.readbyqxmd.com/read/28054753/t-helper-2-cytokine-induced-heat-shock-protein-70-secretion-and-its-potential-association-with-allergic-rhinitis
#13
Hyun Jin Min, Kyung Soo Kim, Joo-Heon Yoon, Chang-Hoon Kim, Hyung-Ju Cho
BACKGROUND: Various inflammatory mediators have been found to be involved in the pathogenesis of allergic disease (AR). The role of heat shock proteins in AR has not been studied. The aim of this study was to investigate the levels of heat shock protein 70 (Hsp70) in the nasal lavage fluids of AR patients and controls to elucidate the role of Hsp70 in the pathogenesis of AR. METHODS: Using an enzyme-linked immunosorbent assay, the levels of Hsp70, Hsp90, interleukin (IL)-4, IL-13, and IL-8 in nasal lavage fluid from patients were measured and statistically analyzed...
January 5, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28054566/the-diverse-roles-of-hsp90-and-where-to-find-them
#14
Patricija Van Oosten-Hawle, Daniel N A Bolon, Paul LaPointe
No abstract text is available yet for this article.
January 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28053100/heat-shock-protein-90-ensures-efficient-mumps-virus-replication-by-assisting-with-viral-polymerase-complex-formation
#15
Hiroshi Katoh, Toru Kubota, Yuichiro Nakatsu, Maino Tahara, Minoru Kidokoro, Makoto Takeda
: Paramyxoviral RNAs are synthesized by a viral RNA-dependent RNA polymerase (RdRp) consisting of the large (L) protein and its cofactor phosphoprotein (P protein). The L protein is a multifunctional protein that catalyzes RNA synthesis, mRNA capping and mRNA polyadenylation. Growing evidence shows that the stability of several paramyxovirus L proteins is regulated by heat shock protein 90 (Hsp90). In this study, we demonstrated that Hsp90 activity was important for mumps virus (MuV) replication...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052723/inducing-heat-shock-proteins-enhances-the-stemness-of-frozen-thawed-adipose-tissue-derived-stem-cells
#16
Shahensha Shaik, Daniel Hayes, Jeffrey Gimble, Ram Devireddy
Extensive research has been performed to determine the effect of freezing protocol and cryopreservation agents on the viability of ASCs as well other cells. Unfortunately, the conclusion one may draw after decades of research utilizing fundamentally similar cryopreservation techniques is that a barrier exists, which precludes full recovery. We hypothesize that agents capable of inducing a subset of heat shock proteins (HSPs) and chaperones will reduce the intrinsic barriers to the post-thaw recovery of ASCs...
January 4, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signaling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#17
Feng Zhang, Meng Hao, Huanhuan Jin, Zhen Yao, Naqi Lian, Li Wu, Jiangjuan Shao, Anping Chen, Shizhong Zheng
BACKGROUND AND PURPOSE: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signaling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were intoxicated with carbon tetrachloride for in vivo evaluation of hepatic angiogenesis and fibrotic injury. Diversified molecular approaches including real-time PCR, Western blot, luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay, and co-immunoprecipitation were used to investigate the underlying mechanisms in vitro...
January 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28051275/ratio-of-proliferation-markers-and-hsp90-gene-expression-as-a-predictor-of-pathological-complete-response-in-breast-cancer-neoadjuvant-chemotherapy
#18
Michal Jarzab, Monika Kowal, Wieslaw Bal, Malgorzata Oczko-Wojciechowska, Justyna Rembak-Szynkiewicz, Malgorzata Kowalska, Ewa Stobiecka, Ewa Chmielik, Tomasz Tyszkiewicz, Malgorzata Kaszuba, Elzbieta Nowicka, Barbara Lange, Agnieszka Czarniecka, Jolanta Krajewska, Alicja Dyla, Miroslaw Dobrut, Dariusz Lange, Barbara Jarzab, Barbara Bobek-Billewicz, Rafal Tarnawski
INTRODUCTION: Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer...
January 4, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28049024/1-4-naphthoquinone-activates-the-hsp90-hsf1-pathway-through-the-s-arylation-of-hsp90-in-a431-cells-negative-regulation-of-the-redox-signal-transduction-pathway-by-persulfides-polysulfides
#19
Yumi Abiko, Liang Sha, Yasuhiro Shinkai, Takamitsu Unoki, Nho Cong Luong, Yukihiro Tsuchiya, Yasuo Watanabe, Reiko Hirose, Takaaki Akaike, Yoshito Kumagai
The current consensus is that environmental electrophiles activate redox signal transduction pathways through covalent modification of sensor proteins with reactive thiol groups at low concentrations, while they cause cell damage at higher concentrations. We previously exposed human carcinoma A431 cells to the atmospheric electrophile 1,4-naphthoquinone (1,4-NQ) and found that heat shock protein 90 (HSP90), a negative regulator of heat shock factor 1 (HSF1), was a target of 1,4-NQ. In the study presented here, we determined whether 1,4-NQ activates HSF1...
December 31, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28043331/avermectin-induced-global-dna-hypomethylation-and-over-expression-of-heat-shock-proteins-in-cardiac-tissues-of-pigeon
#20
Ci Liu, Ye Cao, Shuo Zhou, Pervez Ahmed Khoso, Shu Li
Despite increasing evidences pointing to residues of avermectin (AVM) pose toxic effects on non-target organisms in environment, but the data in pigeon is insufficient. The alteration of global DNA methylation and response of heat shock proteins (Hsps) are important for assessing the AVM toxicity in cardiac tissues of pigeon (Columba livia). To investigate the effects of AVM exposure in cardiac tissues of pigeon, we detected the expression levels of DNA methyltransferases (Dnmts), methylated DNA-binding domain protein 2 (MBD2), and Hsp 60, 70 and 90...
January 2017: Pesticide Biochemistry and Physiology
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