Search results for "HSP90"

The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90

2022

Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s)…

The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors

2022

Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary gland…

Chaperones in disease: quantitative changes in chronic obstructive pulmonary disease (COPD)

2010

Design, synthesis, and biological evaluation of pyridothienotriazolopyrimidine derivatives as new HSP90 inhibitors

2010

4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors.

2014

Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]-pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6.

Intratumoral Heterogeneity for hsp90β mRNA Levels in a Breast Cancer Cell Line

1997

BC-3A and BC-61 are two breast cancer cell lines that have been cloned from parental 8701-BC cells and exhibit different biosynthetic, proliferative, and invasive properties in vitro. In the attempt to search whether alterations in the profiles of gene expression could be detected, we have submitted both cytotypes to identification of differentially expressed cDNAs. In addition, steroid hormone receptor mRNA arrays and in vivo tumorigenesis of the two lines have been checked. The technique used allowed identification of changes in the expression of the 90-kD heat shock protein-beta (hsp90beta) which is prominently down-regulated in BC-61 cells. Because we have also found that these cells, w…

Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A …

2021

HSPs demonstrate a strong association with gamma-delta (γδ) T cells. Most of the studies regarding interactions between the parameters were conducted in the 1990s. Despite promising results, the concept of targeting γδ T cells by HSPs seems to be a forgotten direction due to potent non-peptidic phosphoantigens rather than HSPs have been found to be the essential stimulatory components for human γδ cells. Currently, with greater knowledge of lymphocyte diversity, and more accurate diagnostic methods, we decided to study the correlation once again in the neoplastic condition. Twenty-one children with newly diagnosed acute lymphoblastic leukaemia (ALL) were enrolled on the study. Serum HSP90 c…

Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects.

2012

Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N -(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) an…

Rôle des protéines de choc thermique dans la régulation du facteur de transcription HIF

2011

Both HIF1α and HIF2α proteins are highly involved in the development of pathologies, such as cancers, which are prime public health issues. These proteins are primarily controlled at the protein level by ubiquitin-dependant degradation, and regulate numerous cellular processes which are likely to favor the development of these diseases. A recent issue in therapeutic research is to identify partners that might regulate the expression and the activity of the HIFα proteins, with the aim to elaborate targeted therapies. Heat shock proteins (HSPs) form a family of proteins whose main function is to regulate protein homeostasis in cells, which they achieve through interaction with the ubiquitin-p…

Induction of heat-shock (stress) protein gene expression by selected natural and anthropogenic disturbances in the octocoral Dendronephthya klunzinge…

2000

Previously it was found that the expression of selected heat-shock proteins is upregulated in corals after exposure to elevated temperature. We published that HSPs are suitable markers in sponges to monitor the degree of environmental stress on these animals. In the present study the heat-shock proteins (HSPs) with a molecular weight of 90 kDa have been selected to prove their potential usefulness as biomarkers under controlled laboratory conditions and in the field. The studies have been performed with the octocoral Dendronephthya klunzingeri from which the cDNA coding for HSP90 was cloned first. The expression of the HSP90 gene is upregulated by thermal stress; treatment of the animals fo…