Search results for "Therapeutic resistance"
showing 5 items of 5 documents
Dual disruption of aldehyde dehydrogenases 1 and 3 promotes functional changes in the glutathione redox system and enhances chemosensitivity in nonsm…
2020
AbstractAldehyde dehydrogenases (ALDHs) are multifunctional enzymes that oxidize diverse endogenous and exogenous aldehydes. We conducted a meta-analysis based on The Cancer Genome Atlas and Gene Expression Omnibus data and detected genetic alterations in ALDH1A1, ALDH1A3, or ALDH3A1, 86% of which were gene amplification or mRNA upregulation, in 31% of nonsmall cell lung cancers (NSCLCs). The expression of these isoenzymes impacted chemoresistance and shortened survival times in patients. We hypothesized that these enzymes provide an oxidative advantage for the persistence of NSCLC. To test this hypothesis, we used genetic and pharmacological approaches with DIMATE, an irreversible inhibito…
Hypoxia, Lactate Accumulation, and Acidosis: Siblings or Accomplices Driving Tumor Progression and Resistance to Therapy?
2013
This chapter briefly summarizes the most important processes by which hypoxia, lactate accumulation, and acidosis may influence malignant progression and therapeutic resistance of solid malignant tumors. While these phenomena are often elements of an integrated reaction, they may occur independently of each other under certain circumstances. The latter information may be of interest with regard to possible “targeted” therapeutic interventions.
Tumor hypoxia and therapeutic resistance
2008
For many years, the identification of tumor hypoxia, its systematic characterization and the assessment of its clinical relevance were not possible due to the lack of methods suitable for the routine measurement of intratumoral oxygen tensions in patients. In the late 1980s, a novel and clinically applicable standardized procedure was established enabling the determination of tumor oxygenation in accessible primary tumors, local recurrences, and metastatic lesions in patients using a computerized polarographic needle electrode system (Vaupel et al. 1991; Hockel et al. 1991). Within a relatively short period of time, the significance of tumor oxygenation for therapy outcome became evident in…
MTOR inhibitor-based combination therapies for pancreatic cancer
2018
Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…
Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives
2020
Heat shock protein 60 (HSP60) is a mitochondrial chaperone that is implicated in physiological and pathological processes. For instance, it contributes to protein folding and stability, translocation of mitochondrial proteins, and apoptosis. Variations in the expression levels of HSP60 have been correlated to various diseases and cancers, including hepatocellular carcinoma (HCC). Unlike other HSPs which clearly increase in some cancers, data about HSP60 levels in HCC are controversial and difficult to interpret. In the current review, we summarize and simplify the current knowledge about the role of HSP60 in HCC. In addition, we highlight the possibility of its targeting, using chemical com…