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Skin affecting adverse events of immunotherapies for the treatment of malignancies

Kuzmanovszki, Daniella ; Semmelweis University, Faculty of Medicine Department of Dermatology Venereology and Dermatooncology ; Kiss, Norbert ; [et al.]

Hungarian Dermatological Society ; 2022

In: Bőrgyógyászati és Venerológiai Szemle Vol. 98, No. 5 ( 2022-11-11), p. 264-274

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In: Bőrgyógyászati és Venerológiai Szemle, Hungarian Dermatological Society, Vol. 98, No. 5 ( 2022-11-11), p. 264-274

Abstract: As the fifth pillar of antitumor treatment, immunotherapies have brought a significant breakthrough in oncology. Immune checkpoint inhibitors have been shown to be the most effective modality among immunotherapies by stimulating the antitumor activity of the patient’s immune system. Monoclonal antibodies such as inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein ligand (PD-L1) as immune checkpoint blockers (ICIs) have been approved in many solid tumors. In addition to the introduction of immunotherapies, immunerelated side effects must also be expected. Skin reactions are one of the leading adverse immune-mediated adverse events. Below, we describe the typical immune-mediated adverse reactions affecting the skin during immunotherapy used in oncology.

Type of Medium: Online Resource

ISSN: 0006-7768 , 2064-261X

Uniform Title: Az onkológiában alkalmazott immunterápiák bőrt érintő mellékhatásai

URL: Issue

URL: Journal

URL: Article

DOI: 10.7188/bvsz.2022.98.5

DOI: 10.7188/bvsz

DOI: 10.7188/bvsz.2022.98.5.4

Language: Unknown

Publisher: Hungarian Dermatological Society

Publication Date: 2022

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Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma—A Retrospective Single-Center Study

Kuzmanovszki, Daniella ; Kiss, Norbert ; Tóth, Béla ; [et al.]

MDPI AG ; 2023

In: Journal of Clinical Medicine Vol. 12, No. 18 ( 2023-09-14), p. 5966-

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In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 18 ( 2023-09-14), p. 5966-

Abstract: Background: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. Methods: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. Results: Twenty-five patients were included with a median age of 78 (65–82) years. The median treatment duration was 48 (16–72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. Conclusions: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

Type of Medium: Online Resource

ISSN: 2077-0383

URL: Article

DOI: 10.3390/jcm12185966

Language: English

Publisher: MDPI AG

Publication Date: 2023

detail.hit.zdb_id: 2662592-1

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Herpesvirus-Mediated Delivery of a Genetically Encoded Fluorescent Ca 2 + Sensor to Canine Cardiomyocytes

Prorok, János ; Kovács, Péter P. ; Kristóf, Attila A. ; [et al.]

Hindawi Limited ; 2009

In: Journal of Biomedicine and Biotechnology Vol. 2009 ( 2009), p. 1-12

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In: Journal of Biomedicine and Biotechnology, Hindawi Limited, Vol. 2009 ( 2009), p. 1-12

Abstract: We report the development and application of a pseudorabies virus-based system for delivery of troponeon, a fluorescent Ca 2 + sensor to adult canine cardiomyocytes. The efficacy of transduction was assessed by calculating the ratio of fluorescently labelled and nonlabelled cells in cell culture. Interaction of the virus vector with electrophysiological properties of cardiomyocytes was evaluated by the analysis of transient outward current ( I to ), kinetics of the intracellular Ca 2 + transients, and cell shortening. Functionality of transferred troponeon was verified by FRET analysis. We demonstrated that the transfer efficiency of troponeon to cultured adult cardiac myocytes was virtually 100%. We showed that even after four days neither the amplitude nor the kinetics of the I to current was significantly changed and no major shifts occurred in parameters of [ Ca 2 + ] i transients. Furthermore, we demonstrated that infection of cardiomyocytes with the virus did not affect the morphology, viability, and physiological attributes of cells.

Type of Medium: Online Resource

ISSN: 1110-7243 , 1110-7251

URL: Article

DOI: 10.1155/2009/361795

Language: English

Publisher: Hindawi Limited

Publication Date: 2009

detail.hit.zdb_id: 2698540-8

detail.hit.zdb_id: 2512507-2

SSG: 12

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The Effect of a Novel Highly Selective Inhibitor of the Sodium/Calcium Exchanger (NCX) on Cardiac Arrhythmias in In Vitro and In Vivo Experiments

Kohajda, Zsófia ; Farkas-Morvay, Nikolett ; Jost, Norbert ; [et al.]

Public Library of Science (PLoS) ; 2016

In: PLOS ONE Vol. 11, No. 11 ( 2016-11-10), p. e0166041-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 11, No. 11 ( 2016-11-10), p. e0166041-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0166041

DOI: 10.1371/journal.pone.0166041.g001

DOI: 10.1371/journal.pone.0166041.g002

DOI: 10.1371/journal.pone.0166041.g003

DOI: 10.1371/journal.pone.0166041.g004

DOI: 10.1371/journal.pone.0166041.g005

DOI: 10.1371/journal.pone.0166041.g006

DOI: 10.1371/journal.pone.0166041.g007

DOI: 10.1371/journal.pone.0166041.g008

DOI: 10.1371/journal.pone.0166041.g009

DOI: 10.1371/journal.pone.0166041.g010

DOI: 10.1371/journal.pone.0166041.g011

DOI: 10.1371/journal.pone.0166041.g012

DOI: 10.1371/journal.pone.0166041.t001

DOI: 10.1371/journal.pone.0166041.t002

DOI: 10.1371/journal.pone.0166041.t003

DOI: 10.1371/journal.pone.0166041.t004

DOI: 10.1371/journal.pone.0166041.t005

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2016

detail.hit.zdb_id: 2267670-3

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Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise

Polyák, Alexandra ; Topal, Leila ; Zombori-Tóth, Noémi ; [et al.]

eLife Sciences Publications, Ltd ; 2023

In: eLife Vol. 12 ( 2023-02-23)

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In: eLife, eLife Sciences Publications, Ltd, Vol. 12 ( 2023-02-23)

Abstract: The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.

Type of Medium: Online Resource

ISSN: 2050-084X

URL: Article

DOI: 10.7554/eLife.80710

Language: English

Publisher: eLife Sciences Publications, Ltd

Publication Date: 2023

detail.hit.zdb_id: 2687154-3

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Automatic Field Detection of Western Corn Rootworm (Diabrotica virgifera virgifera; Coleoptera: Chrysomelidae) with a New Probe

Tóth, Zsolt ; Tóth, Miklós ; Jósvai, Júlia Katalin ; [et al.]

MDPI AG ; 2020

In: Insects Vol. 11, No. 8 ( 2020-08-01), p. 486-

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In: Insects, MDPI AG, Vol. 11, No. 8 ( 2020-08-01), p. 486-

Abstract: The Western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is a significant invasive pest of maize plantations in Europe. Integrated pest management demands an adequate monitoring system which detects the activity of insects with high accuracy in real-time. In this study, we show and test a new electronic device (ZooLog KLP), which was developed to detect WCR in the field. The ZooLog KLP consists of a trapping element that attracts insects with its color and species-specific sex pheromone. The other part is an opto-electronic sensor-ring which detects the specimens when they fall into the trap. At detection, the time of catch is recorded and sent to a web interface. In this study, we followed WCR flight patterns for six weeks in two locations, using ZooLog KLP probes. We investigated sensor precision by comparing the number of catches to the number of detections. The tool reached high accuracy (95.84%) in recording WCR. We found a peak in flight activity in August and a bimodal daily pattern. This method may be beneficial in detecting the WCR during their activity, and this new device may serve as a prototype for real-time monitoring systems and improve the management of this pest.

Type of Medium: Online Resource

ISSN: 2075-4450

URL: Article

DOI: 10.3390/insects11080486

Language: English

Publisher: MDPI AG

Publication Date: 2020

detail.hit.zdb_id: 2662247-6

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Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome

Igaz, Peter ; Toth, Geza ; Nagy, Peter ; [et al.]

BMJ ; 2022

In: Journal of Medical Genetics Vol. 59, No. 9 ( 2022-09), p. 916-919

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In: Journal of Medical Genetics, BMJ, Vol. 59, No. 9 ( 2022-09), p. 916-919

Abstract: Gorlin-Goltz syndrome (GGS) or nevoid basal cell carcinoma syndrome is a rare tumour-overgrowth syndrome associated with multiple developmental anomalies and a wide variety of tumours. Here, we describe a case of a man aged 23 years with GGS with bilateral giant tumours adjacent to both adrenals that raised the suspicion of malignancy on imaging. Histological analysis of both surgically resected tumours revealed perivascular epitheloid cell tumours (PEComas) that were independent of the adrenals. Exome sequencing of the patient’s blood sample revealed a novel germline heterozygous frameshift mutation in the PTCH1 gene. As a second hit, a somatic five nucleotide long deletion in the PTCH1 gene was demonstrated in the tumour DNA of both PEComas. To the best of our knowledge, this is the first report on PEComa in GGS, and this finding also raises the potential relevance of PTCH1 mutations and altered sonic hedgehog signalling in PEComa pathogenesis. The presence of the same somatic mutation in the bilateral tumours might indicate the possibility of a postzygotic somatic mutation that along with the germline mutation of the same gene could represent an intriguing genetic phenomenon (type 2 segmental mosaicism).

Type of Medium: Online Resource

ISSN: 0022-2593 , 1468-6244

URL: Article

DOI: 10.1136/jmedgenet-2021-108082

RVK:

WA 15000

Language: English

Publisher: BMJ

Publication Date: 2022

detail.hit.zdb_id: 2009590-9

SSG: 12

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The mechanosensitive Piezo1 channels contribute to the arterial medial calcification

Szabó, László ; Balogh, Norbert ; Tóth, Andrea ; [et al.]

Frontiers Media SA ; 2022

In: Frontiers in Physiology Vol. 13 ( 2022-11-10)

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In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-11-10)

Abstract: Vascular calcification (VC) is associated with a number of cardiovascular diseases, as well as chronic kidney disease. The role of smooth muscle cells (SMC) has already been widely explored in VC, as has the role of intracellular Ca 2+ in regulating SMC function. Increased intracellular calcium concentration ([Ca 2+ ] i ) in vascular SMC has been proposed to stimulate VC. However, the contribution of the non-selective Piezo1 mechanosensitive cation channels to the elevation of [Ca 2+ ] i , and consequently to the process of VC has never been examined. In this work the essential contribution of Piezo1 channels to arterial medial calcification is demonstrated. The presence of Piezo1 was proved on human aortic smooth muscle samples using immunohistochemistry. Quantitative PCR and Western blot analysis confirmed the expression of the channel on the human aortic smooth muscle cell line (HAoSMC). Functional measurements were done on HAoSMC under control and calcifying condition. Calcification was induced by supplementing the growth medium with inorganic phosphate (1.5 mmol/L, pH 7.4) and calcium (CaCl 2 , 0.6 mmol/L) for 7 days. Measurement of [Ca 2+ ] i using fluorescent Fura-2 dye upon stimulation of Piezo1 channels (either by hypoosmolarity, or Yoda1) demonstrated significantly higher calcium transients in calcified as compared to control HAoSMCs. The expression of mechanosensitive Piezo1 channel is augmented in calcified arterial SMCs leading to a higher calcium influx upon stimulation. Activation of the channel by Yoda1 (10 μmol/L) enhanced calcification of HAoSMCs, while Dooku1, which antagonizes the effect of Yoda1, reduced this amplification. Application of Dooku1 alone inhibited the calcification. Knockdown of Piezo1 by siRNA suppressed the calcification evoked by Yoda1 under calcifying conditions. Our results demonstrate the pivotal role of Piezo1 channels in arterial medial calcification.

Type of Medium: Online Resource

ISSN: 1664-042X

URL: Article

DOI: 10.3389/fphys.2022.1037230

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2022

detail.hit.zdb_id: 2564217-0

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Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

Toth, Csaba ; Klarik, Zoltan ; Kiss, Ferenc ; [et al.]

FapUNIFESP (SciELO) ; 2014

In: Acta Cirurgica Brasileira Vol. 29, No. 5 ( 2014-05), p. 320-327

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In: Acta Cirurgica Brasileira, FapUNIFESP (SciELO), Vol. 29, No. 5 ( 2014-05), p. 320-327

Type of Medium: Online Resource

ISSN: 0102-8650

URL: Article

DOI: 10.1590/S0102-86502014000500006

Language: Unknown

Publisher: FapUNIFESP (SciELO)

Publication Date: 2014

detail.hit.zdb_id: 2012156-8

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Following-up changes in red blood cell deformability and membrane stability in the presence of PTFE graft implanted into the femoral artery in a canine model

Toth, Csaba ; Kiss, Ferenc ; Klarik, Zoltan ; [et al.]

Springer Science and Business Media LLC ; 2014

In: Korea-Australia Rheology Journal Vol. 26, No. 2 ( 2014-5), p. 209-215

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In: Korea-Australia Rheology Journal, Springer Science and Business Media LLC, Vol. 26, No. 2 ( 2014-5), p. 209-215

Type of Medium: Online Resource

ISSN: 1226-119X , 2093-7660

URL: Article

DOI: 10.1007/s13367-014-0023-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2014

detail.hit.zdb_id: 2180153-8

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