366 research outputs found
The Role of HSP70 in the Diagnosis of HCC
No full textABSTRACT: Hepatocellular carcinoma (HCC) is a common tumor with a fatal clinical outcome if not diagnosed
at an early stage. To date there is still a lack of reliable tumor biomarkers to detect asymptomatic precursor lesions in early HCC. Conventional pathological analysis also often fails to achieve sufficient sensitivity and specificity to diagnose early HCC. Genetic, proteomic, immunohistochemical, and liquid biopsy analysis indicate a role for members of the heat-shock protein 70 (HSP70) family as potential tumor-specific markers for HCC. The aim of this review is to revisit the existing literature and to specifically explore HSP70 as a molecular tumor biomarker for the detection of HCC and its potential use as a tumor-specific target for future anticancer therapies in HCC
Correction: Wang, F.; Multhoff, G. Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies. Biomolecules 2021, 11, 582
No full textThere was a misplaced reference in the original article in the first paragraph of Section 6 “Clinical Trials with CBD” [...
FUNCTIONALIZED RIGIDIFIED PENTADENTATE CHELATORS USEFUL FOR THE [Al18F]2+ LABELLING OF BIOMOLECULES
No full textInfluence of tumours on protective anti-tumour immunity and the effects of irradiation
No full textInnate and adaptive immunity play important roles in the development and progression of cancer and it is becoming apparent that tumours can influence the induction of potentially protective responses in a number of ways. The prevalence of immunoregulatory T cell populations in the circulation and tumours of patients with cancer is increased, and the presence of these cells appears to present a major barrier to the induction of tumour immunity. One aspect of tumour-mediated immunoregulation which has received comparatively little attention is that which is directed towards natural killer (NK) cells, although evidence that the phenotype and function of NK cell populations are modified in patients with cancer is accumulating.Although the precise mechanisms underlying these localised and systemic immunoregulatory effects remain unclear, tumour-derived factors appear, in part at least, to be involved. The effects could be manifested by an altered function and/or via an influence on the migratory properties of individual cell subsets. A better insight into endogenous immunoregulatory mechanisms and the capacity of tumours to modify the phenotype and function of innate and adaptive immune cells might assist the development of new immunotherapeutic approaches and improve the management of patients with cancer.This article reviews current knowledge relating to the influence of tumours on protective anti-tumour immunity and considers the potential influence that radiation-induced effects might have on the prevalence, phenotype and function of innate and adaptive immune cells in patients with cancer
FUNCTIONALIZED RIGIDIFIED PENTADENTATE CHELATORS USEFUL FOR THE [Al18F]2+ LABELLING OF BIOMOLECULES
No full textFUNCTIONALIZED RIGIDIFIED PENTADENTATE CHELATORS USEFUL FOR THE [Al18F]2+ LABELLING OF BIOMOLECULES
No full textSynthesis and Preclinical Evaluation of the Hsp70 Specific Peptide Tracer TPP-PEG24-DFO-[89Zr] for tumor-selective PET imaging
No full textHigh precision in vivo PET/CT imaging of solid tumors improves diagnostic credibility and clinical outcome of patients. An epitope of the oligomerization domain of Hsp70 is exclusively exposed on the membrane of a large variety of tumor types, but not on normal cells, and thus provides a universal tumor-specific target. Here we developed a novel PET tracer TPP-PEG(24)-DFO[Zr-89] based on the tumor cell-penetrating peptide probe TPP, which specifically recognizes membrane Hsp70 (mHsp70) on tumor cells. The implemented PEG(24) moiety supported tracer stability and improved biodistribution characteristics in vivo. The K-d of the tracer ranged in the low nanomolar range (18.9 +/- 11.3 nmol/L). Fluorescein isothiocyanate (FITC)-labeled derivatives TPP-[FITC] and TPP-PEG(24)-[FITC] revealed comparable and specific binding to mHsp70-positive 4T1, 4T1(+), a derivative of the 4T1 cell line sorted for high Hsp70 expression, and CT26 tumor cells, but not to mHsp70-negative normal fibroblasts. The rapid internalization kinetics of mHsp70 into the cytosol and the favorable biodistribution of the peptide-based tracer TPP-PEG(24)-DFO[Zr-89] in vivo enabled a tumor-specific accumulation with a high tumor-to-background contrast and renal body clearance. The tumor-specific enrichment of the tracer in 4T1(+) (6.2 +/- 1.1% ID/g), 4T1 (4.3 +/- 0.7% ID/g), and CT26 (2.6 +/- 0.6% ID/g) mouse tumors with very high, high, and intermediate mHsp70 densities, respectively, reflected mHsp70 expression profiles of the different tumor types, whereas benign mHsp70-negative fibroblastic hyperplasia showed no tracer accumulation (0.2 +/- 0.03% ID/g). The ability of our chemically optimized peptide-based tracer TPP-PEG(24)-DFO[Zr-89] to detect mHsp70 in vivo suggests its broad applicability in targeting and imaging with high specificity for any tumor type that exhibits surface expression of Hsp70
Binding of heat shock protein 70 to extracellular phosphatidylserine promotes killing of normoxic and hypoxic tumor cells
No full textHypoxia is well known to limit curability of tumors by ionizing radiation. Here, we show that hypoxia treatment of tumor cells causes coexpression of heat shock protein 70 (Hsp70) and phosphatidylserine (PS) on the cell surface. Colocalization of Hsp70 and PS, as determined by confocal microscopy, also occurs when exogenous FITC-labeled Hsp70 protein is added to normoxic and hypoxic tumor cells. Moreover, the interaction of Hsp70 with PS was demonstrated in artificial unilamellar phosphatidylcholine/ phosphatidylserine (PC/PS) liposomes at the physiological ratio of 8/2. Indeed, the Hsp70-liposome interaction gradually increased with elevating PS molar ratios (8/2 > or = 7/3 < 5/5 < 4/6 < 3/7 < 2/8). In contrast, only a weak Hsp70 interaction was detected in phosphatidylcholine/phosphatidylglycerol (PC/PG) liposomes, thus demonstrating that the interaction was not a charge-related effect. The interaction of Hsp70 with surface PS significantly reduces clonogenic cell survival in normoxic (EC(50) of Hsp70=85 microg/ml) and hypoxic (EC(50) of Hsp70=55 microg/ml) tumor cells. The radiation-induced tumor cell killing was significantly enhanced by the addition of Hsp70 protein (50 microg/ml). Since apoptosis was not significantly enhanced in normoxic and hypoxic tumor cells by the addition of Hsp70, we hypothesize that the Hsp70 protein-induced reduction in clonogenic cell survival might be through necrosis rather than apoptosis
Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B
No full textBackground: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner
Heat shock protein 70 (Hsp70) serum levels differ significantly in patients with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma
No full textMembers of the heat shock protein 70 (HSP70) family play an important role in assisting protein folding, preventing protein aggregation and transport of proteins across membranes under physiological conditions. Following environmental (i.e. irradiation, chemotherapy), physiological (i.e. cell growth, differentiation) and pathophysiological (i.e. inflammation, tumorigenesis) stress, the synthesis of HSPs is highly up-regulated, whereas protein synthesis in general is reduced. In contrast to normal cells, many tumor entities including hepatocellular carcinomas (HCC) overexpress Hsp70, the major-stress-inducible member of the HSP70 family, present it on their cell surface and secrete it into the extracellular milieu. Herein, the prognostic relevance of serum Hsp70 levels in patients with chronic hepatitis (CH; n=50), liver cirrhosis (LC; n=46), and hepatocellular carcinoma (HCC; n=47) was analyzed. Similar to other tumor entities, Hsp70 is also present on the surface of primary HCC cells. The staining intensity of intracellular Hsp70 in HCC tissue is stronger compared to control and cirrhotic liver sections. Hsp70 serum levels in all HCC patients were significantly higher compared to a control group without liver disease (n=40). No significant age- and gender-related differences in Hsp70 serum levels were observed in male and female healthy human volunteers (n=86). Patients with chronic hepatitis (CH, n=50) revealed significantly higher Hsp70 serum levels compared to the control group, however, these values were significantly lower than those of HCC patients (n=47). Furthermore, a subgroup of patients with LC who subsequently developed HCC (LC-HCC, n=13) revealed higher Hsp70 serum levels than patients with LC (n=46, p=0.05). These data indicate that serum Hsp70 levels are consecutively increased in patients with chronic hepatitis, liver cirrhosis and liver carcinomas and thus might have a prognostic value
- …
