Therapeutic Cancer Vaccines: Clinical Trials and Applications

Wandall, Hans H.; Tarp, Mads A.

doi:10.1002/9780470473283.ch11

Cited by 9 publications

(3 citation statements)

References 115 publications

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“…Is the binding of modified carbohydrates, as in the case of PSA, a general principle, not only of basic, but also of clinical interest, for instance, in relation to cancer immunotherapy? Different active and passive vaccines, including carbohydrate-based vaccines to aberrant glycostructures, are under clinical trials but have had limited success at proof of principle and efficacy stages [ 33 ]. Characteristic PSA glycoforms bound to IgM, as emerged from this study, direct further investigations to structural comparison of different tumor markers found in immune complexes and their free forms and hold promise for advancement of their use as targets for cancer detection and therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Molecular Species of Prostate-Specific Antigen Complexed with Immunoglobulin M in Prostate Cancer and Benign Prostatic Hyperplasia

Goč

Janković

2013

Disease Markers

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This study was aimed at defining molecular species of prostate-specific antigen (PSA) in immune complexes with immunoglobulin M (IgM). Having in mind the oligoreactivity of IgM and its preference for carbohydrate antigens, there is the possibility that it can selectively recognize known PSA glycoisoforms. PSA-IgM complexes and free PSA fractions were separated from the sera of subjects with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) by gel filtration and subjected to on-chip immunoaffinity and ion-exchange chromatography. PSA-immunoreactive species were detected using surface-enhanced laser desorption/ionization time of flight mass spectrometry. The obtained spectra were analyzed for protein and glycan composition. The general pattern of the molecular species of PCa PSA and BPH PSA found in complexes with IgM was similar. It comprised major peaks at 17 kDa and minor peaks at 28 kDa, corresponding to the entire mature glycosylated PSA. The main difference was the presence of incompletely glycosylated 26.8 kDa species, having putative paucimannosidic structures, observed in PCa PSA-IgM, but not in BPH PSA-IgM. Characteristic PCa PSA-IgM glycoforms pose the question of the possible role of glycosylation as a framework for immune surveillance and may be of interest in light of recent data indicating mannose-containing glycans as cancer biomarker.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Molecular Species of Prostate-Specific Antigen Complexed with Immunoglobulin M in Prostate Cancer and Benign Prostatic Hyperplasia

Goč

Janković

2013

Disease Markers

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“…The available published data testify to low toxicity of some close analogs. For example, in vitro and in vivo experiments showed that the hydrazide derivatives can induce the death of neoplastic cells without harming healthy cells (Wandall and Tarp, 2008). Antitubercular 1,3,4-thiadiazoles demonstrated low mutagenicity and toxicity against proliferating cell lines and isolated human hepatocytes (Karabanovich et al, 2016).…”

Section: Compoundmentioning

confidence: 99%

1,3-Thiazine, 1,2,3,4-Dithiadiazole, and Thiohydrazide Derivatives Affect Lipid Bilayer Properties and Ion-Permeable Pores Induced by Antifungals

Zakharova

Efimova

Yuskovets

et al. 2020

Front. Cell Dev. Biol.

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Over the past decade, thiazines, thiadiazoles, and thiohydrazides have attracted increasing attention due to their sedative, antimicrobial, antiviral, antifungal, and antitumor activities. The clinical efficacy of such drugs, as well as the possibility of developing resistance to antimicrobials, will depend on addressing a number of fundamental problems, including the role of membrane lipids during their interaction with plasma membranes. The effects of the eight 1,3-thiazine-, 1,2,3,4-dithiadiazole-, and thiohydrazide-related compounds on the physical properties of model lipid membranes and the effects on reconstituted ion channels induced by the polyene macrolide antimycotic nystatin and antifungal cyclic lipopeptides syringomycin E and fengycin were observed. We found that among the tested agents, the fluorine-containing compound N-(3,5-difluorophenyl)-benzenecarbothiohydrazide (C6) was the most effective at increasing the electric barrier for anion permeation into the hydrophobic region of the membrane and reducing the conductance of anion-permeable syringomycin pores. A decrease in the membrane boundary potential with C6 adsorption also facilitated the immersion of positively charged syringomycin molecules into the lipid bilayer and increases the pore-forming ability of the lipopeptide. Using differential scanning microcalorimetry, we showed that C6 led to disordering of membrane lipids, possibly by potentiating positive curvature stress. Therefore, we used C6 as an agonist of antifungals forming the pores that are sensitive to membrane curvature stress and lipid packing, i.e., nystatin and fengycin. The dramatic increase in transmembrane current induced by syringomycin E, nystatin, and fengycin upon C6 treatment suggests its potential in combination therapy for treating invasive fungal infections.

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“…The C(=S)-NH- group [3,4] and the -NH-NH- hydrazide fragment [5,6,7] play a very important role owing to their potentially high antifungal, antibacterial [8,9], antiviral (HIV-1) [10] and anti-malarial activity. Recent research has demonstrated the anticarcinogenic potential of modified hydrazide derivatives [11,12,13], and in vitro and in vivo experiments have shown that when administered in very small doses, the discussed compounds can induce the death of neoplastic cells without harming healthy cells [14]. Hydrazide derivatives can be applied in crop protection products, in particular those designed to fight phytopathogenic fungi such as Fusarium solani and Fusarium culmorum which cause head blight and contaminate crops with mycotoxins—Toxic metabolites of their biological activity [15].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a New Group of Aliphatic Hydrazide Derivatives and the Correlations between Their Molecular Structure and Biological Activity

Kostecka

2012

Molecules

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Abstract:In view of the growing demand for new compounds showing biological activity against pathogenic microorganisms, such as pathogenic and phytopathogenic fungi, the objective of this study was to synthesize a new group of aliphatic and aromatic derivatives of hydrazide. In consequence of the reactions observed during synthesis, the resulting compounds retained their linear structure. Their structure and lipophilicity, measured by high-performance liquid chromatography (HPLC), were analyzed. Correlations were determined between the compounds' molecular parameters and biological activity against Fusarium solani and Fusarium oxysporum fungi. The investigated compounds were also examined for their antifungal activity against Aspergillus fumigatus. The obtained results indicate that compounds with fluorine-containing substituents penetrate the cell structure more effectively and are characterized by higher antifungal potential than analogues with different substituents.

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Therapeutic Cancer Vaccines: Clinical Trials and Applications

Cited by 9 publications

References 115 publications

Evaluation of Molecular Species of Prostate-Specific Antigen Complexed with Immunoglobulin M in Prostate Cancer and Benign Prostatic Hyperplasia

Evaluation of Molecular Species of Prostate-Specific Antigen Complexed with Immunoglobulin M in Prostate Cancer and Benign Prostatic Hyperplasia

1,3-Thiazine, 1,2,3,4-Dithiadiazole, and Thiohydrazide Derivatives Affect Lipid Bilayer Properties and Ion-Permeable Pores Induced by Antifungals

Synthesis of a New Group of Aliphatic Hydrazide Derivatives and the Correlations between Their Molecular Structure and Biological Activity

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