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https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#1
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27893783/role-of-pten-in-oxidative-stress-and-dna-damage-in-the-liver-of-whole-body-pten-haplodeficient-mice
#2
Ezgi Eyluel Bankoglu, Oliver Tschopp, Johannes Schmitt, Philipp Burkard, Daniel Jahn, Andreas Geier, Helga Stopper
Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction...
2016: PloS One
https://www.readbyqxmd.com/read/27891174/combination-of-cisplatin-and-bromelain-exerts-synergistic-cytotoxic-effects-against-breast-cancer-cell-line-mda-mb-231-in-vitro
#3
Ahmad Zaim Mat Pauzi, Swee Keong Yeap, Nadiah Abu, Kian Lam Lim, Abdul Rahman Omar, Suraini Abdul Aziz, Adam Leow Thean Chow, Tamilselvan Subramani, Soon Guan Tan, Noorjahan Banu Alitheen
BACKGROUND: Bromelain, which is a cysteine endopeptidase commonly found in pineapple stems, has been investigated as a potential anti-cancer agent for the treatment of breast cancer. However, information pertaining to the effects of combining bromelain with existing chemotherapeutic drugs remains scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells. METHOD: MDA-MB-231 cells were treated with different concentrations (0...
2016: Chinese Medicine
https://www.readbyqxmd.com/read/27887849/inhibition-of-heat-shock-protein-hsp-90-potentiates-the-antiproliferative-and-pro-apoptotic-effects-of-2-4-fluoro-phenylamino-4h-1-3-thiazine-6-5-b-indole-in-a2780cis-cells
#4
Zuzana Solárová, Martin Kello, Lenka Varinská, Mariana Budovská, Peter Solár
Ovarian carcinoma is initially sensitive to platinum-based therapy, but become resistant over time. The study of cancer sensitizing substance is therefore the major challenge for a number of scientific groups. Our experiments were carried out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation assay, cell cycle analysis and monitoring of apoptosis were examined...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27887635/anisakis-pegreffii-nematoda-anisakidae-products-modulate-oxidative-stress-and-apoptosis-related-biomarkers-in-human-cell-lines
#5
Concetta Maria Messina, Federica Pizzo, Andrea Santulli, Ivana Bušelić, Mate Boban, Stjepan Orhanović, Ivona Mladineo
BACKGROUND: In countries with elevated prevalence of zoonotic anisakiasis and high awareness of this parasitosis, a considerable number of cases that associate Anisakis sp. (Nematoda, Anisakidae) and different bowel carcinomas have been described. Although neoplasia and embedded larvae were observed sharing the common site affected by chronic inflammation, no association between the nematode and malignancy were directly proved. Similarly, no data are available about the effect of secretory and excretory products of infecting larvae at the host's cellular level, except in respect to allergenic interaction...
November 25, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27881057/recent-patents-on-heat-shock-proteins-targeting-antibodies
#6
João Fernandes, Pedro Alves
BACKGROUND: Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation, differentiation, invasion and metastasis. High levels of extracellular Hsp90 and Hsp70 have been closely associated with a wide range of human cancers. Accumulating evidence suggests that the pharmacological inhibition of these molecules can play a pivotal role in non-surgical cancer treatment. Efforts have been taken to develop monoclonal antibodies (mAbs) and antibody fragments targeting extracellular Hsp90 and Hsp70, alone or conjugated with standard anticancer agents, to control several types of cancer, such as breast, colon, prostate or melanoma...
November 23, 2016: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#7
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27869678/correction-griffith-d-m-et-al-novel-improved-synthesis-of-hsp70-inhibitor-pifithrin-%C3%AE-in-vitro-synergy-quantification-of-pifithrin-%C3%AE-combined-with-pt-drugs-in-prostate-and-colorectal-cancer-cells-molecules-2016-21-949
#8
Aoife M McKeon, Alan Egan, Jay Chandanshive, Helena McMahon, Darren M Griffith
n/a.
November 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27859703/reinventing-hsp90-inhibitors-blocking-c-terminal-binding-events-to-hsp90-by-using-dimerized-inhibitors
#9
Yen Chin Koay, Hendra Wahyudi, Shelli R McAlpine
Heat shock protein 90 (Hsp90) is a molecular chaperone (90 kDa) that functions as a dimer. This protein facilitates the folding, assembly, and stabilization of more than 400 proteins that are responsible for cancer development and progression. Inhibiting Hsp90's function will shut down multiple cancer-driven pathways simultaneously because oncogenic clients rely heavily on Hsp90, which makes this chaperone a promising anticancer target. Classical inhibitors that block the binding of adenine triphosphate (ATP) to the N-terminus of Hsp90 are highly toxic to cells and trigger a resistance mechanism within cells...
November 11, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27846716/-mechanisms-of-protein-homeostasis-regulation-in-cancer-development
#10
F Trčka, P Müller, B Vojtěšek
BACKGROUND: The proteome of eukaryotic cells represents a complex system. Its components are exposed to various intrinsic and extrinsic stresses. Therefore, the function of the cellular proteome is dependent on the existence of compensatory mechanisms balancing the inner protein homeostasis - proteostasis. These mechanisms involve the network of molecular chaperones and transcriptional program regulating their expression. The process of cancerogenesis is accompanied by significant changes in the intracellular milieu of cancer cells - temperature, pH, availability of nutrients...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27822032/co-delivery-of-doxorubicin-and-recombinant-plasmid-phsp70-plk1-shrna-by-bacterial-magnetosomes-for-osteosarcoma-therapy
#11
Li Cheng, Youqun Ke, Shuisheng Yu, Juehua Jing
To explore a novel combination of chemotherapy, gene therapy, and thermotherapy for osteosarcoma, a targeted heat-sensitive co-delivery system based on bacterial magnetosomes (BMs) was developed. The optimal culture conditions of magnetotactic bacteria (MTB) AMB-1 and characterization of BMs were achieved. A recombinant eukaryotic plasmid heat shock protein 70-polo-like kinase 1-short hairpin RNA (pHSP70-Plk1-shRNA) under transcriptional control of a thermosensitive promoter (human HSP70 promoter) was constructed for gene therapy...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27809750/chaperoning-the-cancer-the-proteostatic-functions-of-the-heat-shock-proteins-in-cancer
#12
Sepideh Vahid, Daksh Thaper, Amina Zoubeidi
BACKGROUND: Protein homeostasis (proteostasis) is vital for the survival of cells in physiological and pathological conditions. Particularly, cancer cells are in constant state of cellular stress due to rapid proliferation and decreased quality control in proteosynthesis and therefore, are exceedingly dependent on the homeostasis pathways. Among the complex biological mechanisms regulating proteostasis are the highly conserved molecular chaperones, heat shock proteins (HSPs). HSPs assist cell survival by catalysing the proper folding of proteins, modulation of the apoptotic machinery and finally regulating the protein degradation machinery, providing either the stability or the degradation of selected proteins under stress conditions...
November 2, 2016: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/27809308/doxorubicin-attenuates-chip-guarded-hsf1-nuclear-translocation-and-protein-stability-to-trigger-igf-iir-dependent-cardiomyocyte-death
#13
Chih-Yang Huang, Wei-Wen Kuo, Jeng-Fan Lo, Tsung-Jung Ho, Pei-Ying Pai, Shu-Fen Chiang, Pei-Yu Chen, Fu-Jen Tsai, Chang-Hai Tsai, Chih-Yang Huang
Doxorubicin (DOX) is one of the most effective antitumor drugs, but its cardiotoxicity has been a major concern for its use in cancer therapy for decades. Although DOX-induced cardiotoxicity has been investigated, the underlying mechanisms responsible for this cardiotoxicity have not been completely elucidated. Here, we found that the insulin-like growth factor receptor II (IGF-IIR) apoptotic signaling pathway was responsible for DOX-induced cardiotoxicity via proteasome-mediated heat shock transcription factor 1 (HSF1) degradation...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27802968/calreticulin-exposure-by-malignant-blasts-correlates-with-robust-anticancer-immunity-and-improved-clinical-outcome-in-aml-patients
#14
Jitka Fucikova, Iva Truxova, Michal Hensler, Etienne Becht, Lenka Kasikova, Irena Moserova, Sarka Vosahlikova, Jana Klouckova, Sarah E Church, Isabelle Cremer, Oliver Kepp, Guido Kroemer, Lorenzo Galluzzi, Cyril Salek, Radek Spisek
Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called "damage-associated molecular patterns", DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death (ICD) to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from acute myeloid leukemia (AML) patients exposed multiple DAMPs including calreticulin (CRT), heat-shock protein 70 (HSP70) and HSP90 on their plasma membrane irrespective of treatment...
November 1, 2016: Blood
https://www.readbyqxmd.com/read/27770383/chalcone-templated-hsp90-inhibitors-and-their-effects-on-gefitinib-resistance-in-non-small-cell-lung-cancer-nsclc
#15
Ju Hui Jeong, Yong Jin Oh, Taeg Kyu Kwon, Young Ho Seo
The molecular chaperone Hsp90 has emerged as an attractive cancer therapeutic target due to its role in cellular homeostasis by modulating the stabilization and maturation of many oncogenic proteins. In this study, we designed and synthesized a series of Hsp90 inhibitors that hybridized NVP-AUY992 (2) and PU3 (3) in the chalcone scaffold using a structure-based approach. Our results indicate that compound 1g inhibited the proliferation of gefitinib-resistant non-small cell lung cancer (H1975) cells, downregulated the expression of client proteins of Hsp90 including EGFR, MET, Her2 and Akt, and up-regulated the expression of Hsp70...
October 21, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27751915/defining-the-na-h-exchanger-nhe1-interactome-in-triple-negative-breast-cancer-cells
#16
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 15, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27748139/nuclear-erk5-inhibits-progression-of-leukemic-monocytes-to-macrophages-by-regulating-the-transcription-factor-pu-1-and-heat-shock-protein-hsp70
#17
Ruifang Zheng, George P Studzinski
Differentiation therapy can supplement the therapy of APL, but other subtypes of AML are treated principally with cytotoxic agents, with few lasting remissions. While the induction of monocyte followed by macrophage differentiation by vitamin D derivatives (VDDs) is dramatic in cultured AML cells of all subtypes, attempts to translate this to the clinic have not been effective. Thus, better understanding of the mechanisms underlying VDD-induced differentiation may improve this approach. The key events in this form of differentiation include increased expression of CD11b, and the transcription factor PU...
October 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27713135/recombinant-heat-shock-protein-70-functional-peptide-and-alpha-fetoprotein-epitope-peptide-vaccine-elicits-specific-anti-tumor-immunity
#18
Xiao-Ping Wang, Qiao-Xia Wang, Huan-Ping Lin, Bing Xu, Qian Zhao, Kun Chen
Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27708405/a-fragment-based-approach-applied-to-a-highly-flexible-target-insights-and-challenges-towards-the-inhibition-of-hsp70-isoforms
#19
Alan M Jones, Isaac M Westwood, James D Osborne, Thomas P Matthews, Matthew D Cheeseman, Martin G Rowlands, Fiona Jeganathan, Rosemary Burke, Diane Lee, Nadia Kadi, Manjuan Liu, Meirion Richards, Craig McAndrew, Norhakim Yahya, Sarah E Dobson, Keith Jones, Paul Workman, Ian Collins, Rob L M van Montfort
The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority have poor physicochemical properties and for many the exact mode of action is poorly understood, more detailed mechanistic and structural insight into ligand-binding to HSP70s is urgently needed. Here we describe the first comprehensive fragment-based inhibitor exploration of an HSP70 enzyme, which yielded an amino-quinazoline fragment that was elaborated to a novel ATP binding site ligand with different physicochemical properties to known adenosine-based HSP70 inhibitors...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27704355/serum-heat-shock-protein-70-as-a-potential-biomarker-for-small-cell-lung-cancer
#20
Madaras Balázs, Horváth Zsolt, Gráf László, Gálffy Gabriella, Tamási Lilla, Ostoros Gyula, Döme Balázs, Mórocz Éva, Bártfai Zoltán, Prohászka Zoltán, Kocsis Judit
The 70 kDa heat shock protein (Hsp70) is a highly conservative molecular chaperone, that has important role in cell integrity. Recently considerable amount of data are accumulating on the potential role of Hsp70 in carcinogenesis and tumor progression. Most papers are focusing on intracellular or membrane bound protein, however very limited data exist on serum Hsp70, that can also induce innate and adaptive immune response. Previously we have published data on the correlation between coloretal cancer progression and serum Hsp70 concentration...
October 4, 2016: Pathology Oncology Research: POR
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