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https://www.readbyqxmd.com/read/28339059/proteomic-based-identification-of-hsp70-as-a-tumor-associated-antigen-in-ovarian-cancer
#1
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
https://www.readbyqxmd.com/read/28331811/proteomic-analysis-of-bronchoalveolar-lavage-fluid-balf-from-lung-cancer-patients-using-label-free-mass-spectrometry
#2
Abduladim Hmmier, Michael Emmet O'Brien, Vincent Lynch, Martin Clynes, Ross Morgan, Paul Dowling
BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). METHODS: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#3
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28294381/cd3-cd8-nkg2d-t-lymphocytes-induce-apoptosis-and-necroptosis-in-hla-negative-cells-via-fasl-fas-interaction
#4
O K Ivanova, T N Sharapova, E A Romanova, L P Sashchenko, D V Yashin
An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4(+) CD25(+) lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+ lymphocytes...
March 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28291803/induction-of-hsp70-in-tumor-cells-treated-with-inhibitors-of-the-hsp90-activity-a-predictive-marker-and-promising-target-for-radiosensitization
#5
Vladimir A Kudryavtsev, Anna V Khokhlova, Vera A Mosina, Elena I Selivanova, Alexander E Kabakov
We studied a role of the inducible heat shock protein 70 (Hsp70) in cellular response to radiosensitizing treatments with inhibitors of the heat shock protein 90 (Hsp90) chaperone activity. Cell lines derived from solid tumors of different origin were treated with the Hsp90 inhibitors (17AAG, geldanamycin, radicicol, NVP-AUY922) or/and γ-photon radiation. For comparison, human cells of the non-cancerous origin were subjected to the same treatments. We found that the Hsp90 inhibitors yielded considerable radiosensitization only when they cause early and pronounced Hsp70 induction; moreover, a magnitude of radiosensitization was positively correlated with the level of Hsp70 induction...
2017: PloS One
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#6
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28277193/mir-202-promotes-cell-apoptosis-in-esophageal-squamous-cell-carcinoma-by-targeting-hsf2
#7
Xiangrui Meng, Xiaoqi Chen, Peng Lu, Wang Ma, Dongli Yue, Lijie Song, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant cancers with high mortality around the world. However, the regulatory mechanism of ESCC carcinogenesis is not completely known. Here we demonstrate the novel role of miR-202 in regulating ESCC cell apoptosis. The analysis of data obtained from the GEO database showed that the expression of miR-202 is aberrantly decreased in tumor tissue from ESCC patients and cultured ESCC cell lines. After transfection with miR-202 mimic or inhibitor, the apoptotic capacity of ESCC cells was significantly increased by miR-202 overexpression but reduced by miR-202 repression...
January 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28274158/heat-shock-protein-antagonists-in-early-stage-clinical-trials-for-nsclc
#8
Lizza E L Hendriks, Anne-Marie C Dingemans
Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors...
March 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28251053/laser-triggered-small-interfering-rna-releasing-gold-nanoshells-against-heat-shock-protein-for-sensitized-photothermal-therapy
#9
Zhaohui Wang, Siwen Li, Min Zhang, Yi Ma, Yuxi Liu, Weidong Gao, Jiaqi Zhang, Yueqing Gu
The resistance of cancer cells to photothermal therapy is closely related to the overexpression of heat shock proteins (HSPs), which are abnormally upregulated when cells are under lethal stresses. Common strategies that use small molecule inhibitors against HSPs to enhance hyperthermia effect lack spatial and temporal control of drug release, leading to unavoidable systemic toxicity. Herein, a versatile photothermal platform is developed which is composed of a hollow gold nanoshell core densely packed with small interfering RNAs against heat shock protein 70 (Hsp70)...
February 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28237487/hsp70-inhibitor-combined-with-cisplatin-suppresses-the-cervical-cancer-proliferation-in%C3%A2-vitro-and-transplanted-tumor-growth-an-experimental-study
#10
Jian Liu, Jing Liu, Su-Yang Guo, Hong-Li Liu, Sheng-Ze Li
OBJECTIVE: To study the regulating effect of HSP70 inhibitor (PES) combined with cisplatin on cervical cancer proliferation in vitro and transplanted tumor growth. METHODS: Cervical cancer Hela cell lines were cultured and divided into control group, cisplatin group, PES group and cisplatin + PES group that were treated with serum-free DMEM, cisplatin with final concentration of 10 μmol/L, PES 20 μmol/L and cisplatin 10 μmol/L combined with PES with 20 μmol/L, respectively; animal models with cervical cancer xenografts were established and divided into control group, cisplatin group, PES group and cisplatin + PES group who received intra-tumor injection of normal saline, 10 μmol/L cisplatin, 20 μmol/L PES as well as 10 μmol/L cisplatin + 20 μmol/L PES, respectively...
February 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28223424/hsp70-inhibition-synergistically-enhances-the-effects-of-magnetic-fluid-hyperthermia-in-ovarian-cancer
#11
Karem A Court, Hiroto Hatakeyama, Sherry Y Wu, Mangala S Lingegowda, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Lee Ju-Seog, Carlos Rinaldi, Eduardo J Juan, Anil K Sood, Madeline Torres-Lugo
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28219205/-preparation-of-chaperone-antigen-peptide-vaccine-derived-from-human-gastric-cancer-stem-cells-and-its-immune-function
#12
Y Q Jiang, Q M Guo, X P Xu, J C Liang, Y Y He, S H An, F Su, C Y Li, C X Huang
Objective: To explore the method of extracting chaperone antigen peptide complexes from gastric cancer stem cells and its immune function. Methods: Gastric cancer stem cells and gastric cancer cells were screened by low temperature ultrasonic lysis. After salting out and dialysis, the lysate supernatant was processed with SDS-PAGE to analyze the expression of chaperone antigen peptide complexes, and then was separated and purified with CNBr-activated SepharoseTM 4B. Reverse high pressure liquid chromatography (HPLC), SDS-PAGE and Western blotting were used to analyze the purity and nature of the acquired albumen...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28216622/effects-of-gene-polymorphisms-in-the-endoplasmic-reticulum-stress-pathway-on-clinical-outcomes-of-chemoradiotherapy-in-chinese-patients-with-nasopharyngeal-carcinoma
#13
Xiao-Bin Guo, Wan-le Ma, Li-Juan Liu, Yu-Ling Huang, Jing Wang, Li-Hua Huang, Xiang-Dong Peng, Ji-Ye Yin, Jin-Gao Li, Shao-Jun Chen, Guo-Ping Yang, Hui Wang, Cheng-Xian Guo
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28215707/hsp90-shapes-the-consequences-of-human-genetic-variation
#14
Georgios I Karras, Song Yi, Nidhi Sahni, Máté Fischer, Jenny Xie, Marc Vidal, Alan D D'Andrea, Luke Whitesell, Susan Lindquist
HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function...
February 23, 2017: Cell
https://www.readbyqxmd.com/read/28213333/hmba-is-a-putative-hsp70-activator-stimulating-hexim1-expression-that-is-down-regulated-by-estrogen
#15
Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-α transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bis-acetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation...
February 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28192510/downregulation-of-sp1-by-minnelide-leads-to-decrease-in-hsp70-and-decrease-in-tumor-burden-of-gastric-cancer
#16
Nivedita Arora, Osama Alsaied, Patricia Dauer, Kaustav Majumder, Shrey Modi, Bhuwan Giri, Vikas Dudeja, Sulagna Banerjee, Daniel Von Hoff, Ashok Saluja
BACKGROUND: Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11...
2017: PloS One
https://www.readbyqxmd.com/read/28165047/relevance-of-mortalin-to-cancer-cell-stemness-and-cancer-therapy
#17
Chae-Ok Yun, Priyanshu Bhargava, Youjin Na, Jung-Sun Lee, Jihoon Ryu, Sunil C Kaul, Renu Wadhwa
Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143990/microbiota-composition-hsp70-and-caspase-3-expression-as-marker-for-colorectal-cancer-patients-in-aceh-indonesia
#18
Fauzi Yusuf, Syafruddin Ilyas, Harun Al Rasyid Damanik, Fatchiyah Fatchiyah
AIM: to investigate the relationship between microbiota composition with HSP70 and Caspase-3 expressions in colon tissue as an initial study to develop the candidate for early detection of colorectal cancer for Indonesian patients. METHODS: this is a cross-sectional study on 32 patients undergoing colonoscopy; 16 patients of colorectal cancer (CRC) while the other 16 patients are not (colitis and internal hemorrhoid). The composition of microbiota in stool samples was examined using 16S rRNA Denaturing Gradient Gel Electrophoresis (DDGE) while expression of HSP70 was examined by immunohistochemistry and Caspase-3 by using Haematoxylin-Eosin(HE) staining to determine the morphological changes in colon tissue...
October 2016: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28128329/oridonin-triggers-chaperon-mediated-proteasomal-degradation-of-bcr-abl-in-leukemia
#19
Huilin Huang, Hengyou Weng, Bowen Dong, Panpan Zhao, Hui Zhou, Lianghu Qu
Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be exploited for new therapies. Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of oncoproteins; however, the direct cellular targets and underlying mechanisms remain unclear. Here we report that oridonin depletes BCR-ABL through chaperon-mediated proteasomal degradation in leukemia. Mechanistically, oridonin poses oxidative stress in cancer cells and directly binds to cysteines of HSF1, leading to the activation of this master regulator of the chaperone system...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108313/the-hsp70-inhibiting-peptide-aptamer-a17-potentiates-radiosensitization-of-tumor-cells-by-hsp90-inhibition
#20
Daniela Schilling, Carmen Garrido, Stephanie E Combs, Gabriele Multhoff
The inhibition of heat shock protein 90 (Hsp90) is a promising strategy to increase the radiosensitivity of tumor cells. However, Hsp90 inhibition induces the expression of Hsp70 which is a prominent cytoprotective protein. Therefore, dual targeting of Hsp70 and Hsp90 might be beneficial to increase the radiosensitivity of tumor cells. Hsp70 inhibiting peptide aptamers have been shown to increase the sensitivity of tumor cells to apoptosis induced by different anticancer drugs. Herein, we studied the radiosensitizing activity of the Hsp70 inhibiting peptide aptamer A17 in combination with the Hsp90 inhibitor NVP-AUY922...
April 1, 2017: Cancer Letters
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