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https://www.readbyqxmd.com/read/28543919/-heat-shock-protein-70-in-pancreatic-diseases-friend-or-foe
#1
REVIEW
Bhuwan Giri, Vrishketan Sethi, Shrey Modi, Bharti Garg, Sulagna Banerjee, Ashok Saluja, Vikas Dudeja
The heat shock response in pancreatitis that is activated via HSP70 protects acinar cells through multiple simultaneous mechanisms. It inhibits trypsinogen activation and modulates NF-κB signaling to limit acinar cell injury. On the other hand, HSP70 is overexpressed in pancreatic cancer and is hijacked by the cellular machinery to inhibit apoptosis. Inhibition of HSP70 in pancreatic cancer by a novel compound, Minnelide, has shown considerable clinical promise.
May 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28542269/the-small-molecule-kinase-inhibitor-d11-counteracts-17-aag-mediated-up-regulation-of-hsp70-in-brain-cancer-cells
#2
Susanne Schaefer, Tina H Svenstrup, Barbara Guerra
Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years...
2017: PloS One
https://www.readbyqxmd.com/read/28536268/endoplasmic-reticulum-stress-induced-degradation-of-dnajb12-stimulates-bok-accumulation-and-primes-cancer-cells-for-apoptosis
#3
Pattarawut Sopha, Hong Yu Ren, Diane E Grove, Douglas M Cyr
DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation (ERAD) complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#4
James M Larner, Sukumar Sarkar, David L Brautigan
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#5
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28504248/the-flavonoid-tl-2-8-induces-cell-death-and-immature-mitophagy-in-breast-cancer-cells-via-abrogating-the-function-of-the-aha1-hsp90-complex
#6
Hui-Juan Liu, Xiao-Xiao Jiang, Yi-Zhen Guo, Fang-Hui Sun, Xin-Hui Kou, Yong Bao, Zhu-Qing Zhang, Zhao-Hu Lin, Ting-Bo Ding, Lan Jiang, Xin-Sheng Lei, Yong-Hua Yang
The flavonoid quercetin exhibits significant anticancer activities with few side effects. In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. Cell proliferation and viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay, respectively. Cell death was examined using PI staining or a TUNEL assay. Mitophagy was determined by measuring autophagic flux and by confocal imaging. Protein expression was examined by Western blotting...
May 1, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#7
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
https://www.readbyqxmd.com/read/28484090/inhibition-of-stress-inducible-hsp70-impairs-mitochondrial-proteostasis-and-function
#8
Julia I-Ju Leu, Thibaut Barnoud, Gao Zhang, Tian Tian, Zhi Wei, Meenhard Herlyn, Maureen E Murphy, Donna L George
Protein quality control is an important component of survival for all cells. The use of proteasome inhibitors for cancer therapy derives from the fact that tumor cells generally exhibit greater levels of proteotoxic stress than do normal cells, and thus cancer cells tend to be more sensitive to proteasome inhibition. However, this approach has been limited in some cases by toxicity to normal cells. Recently, the concept of inhibiting proteostasis in organelles for cancer therapy has been advanced, in part because it is predicted to have reduced toxicity for normal cells...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466152/suppression-of-heat-shock-protein-70-by-sirna-enhances-the-antitumor-effects-of-cisplatin-in-cultured-human-osteosarcoma-cells
#9
Yuki Mori, Ryu Terauchi, Toshiharu Shirai, Shinji Tsuchida, Naoki Mizoshiri, Yuji Arai, Tsunao Kishida, Hiroyoshi Fujiwara, Osam Mazda, Toshikazu Kubo
Although advances in chemotherapy have improved the prognosis for osteosarcoma, some patients do not respond sufficiently to treatment. Heat shock protein 70 (Hsp70) is expressed at high levels in cancer cells and attenuates the therapeutic efficacy of anticancer agents, resulting in a poorer prognosis. This study investigated whether small interfering RNA (siRNA)-mediated inhibition of Hsp70 expression in an osteosarcoma cell line would enhance sensitivity to cisplatin. The expression of Hsp70 with cisplatin treatment was observed by using Western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR)...
May 2, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28464914/efficacy-of-radiotherapy-for-the-treatment-of-cystic-echinococcosis-in-naturally-infected-sheep
#10
Rui Mao, Wen-Bao Zhang, Hong-Zhi Qi, Tao Jiang, Ge Wu, Peng-Fei Lu, Abudula Ainiwaer, Ge Shang, Lin Xu, Jie Hao, Xi Shou, Hai-Tao Li, Jun Li, Song-An Zhang, Yong-Xing Bao, Hao Wen
BACKGROUND: Radiotherapy is commonly used to treat cancers. To date, there has been no study focusing on the effects of radiotherapy on hydatid disease in large animals. In this study, we aim to investigate the efficiency and safety of radiotherapy for treating hydatid disease caused by Echinococcus granulosus in naturally infected sheep. METHODS: Ultrasound was used to screen naturally infected sheep in an echinococcosis endemic area in Xinjiang, China. A computer tomography (CT) scan confirmed the presence of hydatid cysts...
May 3, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28458133/scutellarin-derivatives-as-apoptosis-inducers-design-synthesis-and-biological-evaluation
#11
Tong Han, Jia Li, Jingjing Xue, He Li, Fanxing Xu, Keguang Cheng, Dahong Li, Zhanlin Li, Ming Gao, Huiming Hua
To explore novel antitumor agents with high efficiency and low toxicity, a series of NO-donating scutellarin derivatives (14-17) were synthesized and the antiproliferative activities against MCF-7, HCT-116, PC-3 and HepG2 cancer cell lines were assessed. Among them, compound 14b was the strongest with IC50 values of 2.96 μM, 7.25 μM, 0.09 μM and 0.50 μM, respectively, and displayed low toxicity against normal human liver L-O2 cells with an IC50 of 47.96 μM, showing good selectivity between normal and malignant liver cells...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28457411/immunoexpression-of-heat-shock-protein-70-glypican-3-glutamine-synthetase-and-beta-catenin-in-hepatocellular-carcinoma-after-liver-transplantation-association-between-positive-glypican-3-and-beta-catenin-with-the-presence-of-larger-nodules
#12
E C Ataide, S R Perales, M G Silva, F C Filho, A C Sparapani, P F Latuf Filho, R S B Stucchi, J Vassallo, C A F Escanhoela, I F S F Boin
BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. Its recurrence ranges from 6% to 26%. In the literature, many factors are associated with higher risk of recurrence, without a clear definition of the best method that could predict this highly lethal event. OBJECTIVE: The aim of this study was to evaluate the immunoexpression of immunohistochemical markers: HSP70, glypican 3, glutamine synthetase, and beta-catenin, as well as studying their association with tumor characteristics and prognosis of patients undergoing liver transplantation for HCC...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28454329/overexpression-of-heat-shock-factor-1-is-associated-with-a-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#13
Yukiko Tsukao, Makoto Yamasaki, Yasuhiro Miyazaki, Tomoki Makino, Tsuyoshi Takahashi, Yukinori Kurokawa, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Koshi Mimori, Masaki Mori, Yuichiro Doki
Heat-shock factor 1 (HSF1) is the primary regulator of the response to various stressors. A previous study showed that HSF1 expression is associated with a poor prognosis in breast cancer and hepatocellular carcinoma; however, the prognostic significance of HSF1 in esophageal squamous cell carcinoma (ESCC) is unknown. Therefore, the present study investigated the association between HSF1 expression and the clinicopathological parameters of patients, as well as the association between HSF1 expression, and heat shock protein (Hsp)27, Hsp70 and Hsp90 expression induced by HSF1, by cDNA microarray and immunohistochemistry analyses...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453394/expression-of-mir-23a-by-apoptotic-regulators-in-human-cancer-a-review
#14
Rabih Roufayel, Seifedine Kadry
MicroRNAs play fundamental roles in mammalian development, differentiation and cellular homeostasis by regulating essential processes such as proliferation, migration, metabolism, migration and cell death. These small non-coding RNAs are also responsible in RNA silencing, and in many developmental and pathological processes. Not surprisingly, miR-23a misexpression contributes to numerous diseases including cancer where certain miRNA genes have been classified as either oncogenes or tumor suppressor genes. Since a single microRNA is capable of targeting a large number of mRNA sequences, de-regulated miRNA expression has the ability to alter various transcripts and activate a wide range of cancer-related pathways...
April 28, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28430823/modulation-the-alternative-splicing-of-gla-ivs4-919g-a-in-fabry-disease
#15
Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang
While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA...
2017: PloS One
https://www.readbyqxmd.com/read/28415709/a-peptide-derived-from-apoptin-inhibits-glioma-growth
#16
Liqiu Zhang, Hengyu Zhao, Zhongqi Cui, Yueshan Lv, Wenjia Zhang, Xiaoyu Ma, Jianan Zhang, Banghao Sun, Danyang Zhou, Lijie Yuan
Glioblastoma (GBM) is associated with poor prognosis due to its resistance to surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic approaches for the treatment of GBM are urgently needed. HSP70 is an antiapoptotic protein that participates in the inhibition of both mitochondrial and membrane receptor apoptosis pathways and is highly expressed in glioma tissues. Here, we investigated a derivative of apoptin; specifically, a chicken anemia viral protein with selective toxicity toward cancer cells that can inhibit hyperactive molecules, including HSP70...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412969/engagement-of-cellular-prion-protein-with-the-co-chaperone-hsp70-90-organizing-protein-regulates-the-proliferation-of-glioblastoma-stem-like-cells
#17
Rebeca Piatniczka Iglesia, Mariana Brandão Prado, Lilian Cruz, Vilma Regina Martins, Tiago Góss Santos, Marilene Hohmuth Lopes
BACKGROUND: Glioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrP(C)) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28388555/targeting-mantle-cell-lymphoma-metabolism-and-survival-through-simultaneous-blockade-of-mtor-and-nuclear-transporter-exportin-1
#18
Kazumasa Sekihara, Kaori Saitoh, Lina Han, Stefan Ciurea, Shinichi Yamamoto, Mika Kikkawa, Saiko Kazuno, Hikari Taka, Naoko Kaga, Hajime Arai, Takashi Miida, Michael Andreeff, Marina Konopleva, Yoko Tabe
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor prognosis, characterized by aberrant expression of growth-regulating and oncogenic effectors and requiring novel anticancer strategies. The nuclear transporter exportin-1 (XPO1) is highly expressed in MCL and is associated with its pathogenesis. mTOR signaling, a central regulator of cell metabolism, is frequently activated in MCL and is also an important therapeutic target in this cancer. This study investigated the antitumor effects and molecular/metabolic changes induced by the combination of the small-molecule selective inhibitor XPO1 inhibitor KPT-185 and the dual mTORC1/2 kinase inhibitor AZD-2014 on MCL cells...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28364346/the-growing-world-of-small-heat-shock-proteins-from-structure-to-functions
#19
REVIEW
Serena Carra, Simon Alberti, Patrick A Arrigo, Justin L Benesch, Ivor J Benjamin, Wilbert Boelens, Britta Bartelt-Kirbach, Bianca J J M Brundel, Johannes Buchner, Bernd Bukau, John A Carver, Heath Ecroyd, Cecilia Emanuelsson, Stephanie Finet, Nikola Golenhofen, Pierre Goloubinoff, Nikolai Gusev, Martin Haslbeck, Lawrence E Hightower, Harm H Kampinga, Rachel E Klevit, Krzysztof Liberek, Hassane S Mchaourab, Kathryn A McMenimen, Angelo Poletti, Roy Quinlan, Sergei V Strelkov, Melinda E Toth, Elizabeth Vierling, Robert M Tanguay
Small heat shock proteins (sHSPs) are present in all kingdoms of life and play fundamental roles in cell biology. sHSPs are key components of the cellular protein quality control system, acting as the first line of defense against conditions that affect protein homeostasis and proteome stability, from bacteria to plants to humans. sHSPs have the ability to bind to a large subset of substrates and to maintain them in a state competent for refolding or clearance with the assistance of the HSP70 machinery. sHSPs participate in a number of biological processes, from the cell cycle, to cell differentiation, from adaptation to stressful conditions, to apoptosis, and, even, to the transformation of a cell into a malignant state...
March 31, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28339059/proteomic-based-identification-of-hsp70-as-a-tumor-associated-antigen-in-ovarian-cancer
#20
Xin-Xin Liu, Hua Ye, Peng Wang, Liu-Xia Li, Yi Zhang, Jian-Ying Zhang
Ovarian cancer commonly presents without prominent symptoms and is consequently diagnosed at advanced stages with unfavorable prognosis. Novel serological biomarkers for the early detection and clinical management of ovarian cancer are imminently needed. Proteomic-based methods for biomarker discovery are promising strategies implemented in cancer research. The aim of the present study was to identify new tumor antigens from the ovarian cancer cell line SKOV3 and their associated autoantibodies in sera of patients with ovarian cancer employing proteomic-based approaches...
March 24, 2017: Oncology Reports
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