scholarly journals Murine Skin Carcinogenesis and the Role of Immune System Dysregulation in the Tumorigenicity of 2-Ethylhexyl Acrylate

2020 ◽  
Vol 5 (2) ◽  
pp. 1-16
Author(s):  
Craig A. Elmets ◽  
Nabiha Yusuf
Keyword(s):  
Cell Carcinoma ◽  
Animal Studies ◽  
Maximum Tolerated Dose ◽  
Skin Carcinogenesis ◽  
Histological Evaluation ◽  
Mouse Strains ◽  
Carcinogenic Activity ◽  
Single Strain ◽  
Human Squamous Cell Carcinoma ◽  
Organ Systems

Some chemicals act as human carcinogens in various organ systems including the skin. Mice have been an ideal model to study a wide variety of chemical carcinogens because the pathogenesis in that species often mirrors that in humans. However, different mouse strains vary in their susceptibility to these agents. Thus, reliance on a single strain may lead to inaccurate findings. 2-Ethylhexyl acrylate (2-EHA) is an acrylate used as a co-monomer in the production of polymer resins for adhesives, latex paints, cross-linking agents, finishes for textiles and leather, and paper coatings. Monomer exposure may occur in occupational settings where it is produced or used; the only exposure that may occur to consumers or construction personnel is trace amounts in the final polymer product. There are no reports of cancer in humans caused by exposure to 2-EHA. However, 2-EHA has been reported to cause cancer in one strain of mice. This is an important issue since recommendations about its safety in humans depend, in part, on information derived from animal studies. We reviewed the literature on the preclinical effects of acrylates on skin carcinogenesis in C3H/HeJ mice, which can be criticized because of peculiarities in the immunological composition of that strain, the lack of rigorous histopathologic characterization of tumors that developed, the high doses of 2-EHA that were used for evaluation, and the lack of reproducibility in a second strain of mice. The C3H/HeJ mouse model is not ideal as it has a mutation in Toll-like receptor 4 (TLR4) that impairs its innate and adaptive immune responses. Inconsistencies in the histological evaluation of tumors induced in C3H/HeJ mice provide further evidence that the tumorigenic effect of 2-EHA was strain specific, a result of chronic inflammation during the promotion stage and/or a skewed immune response caused by the TLR4 mutation. In conclusion, 2-EHA has not convincingly been demonstrated to have skin carcinogenic activity to date. More relevant mouse models that mimic human squamous cell carcinoma, basal cell carcinoma, and melanoma with amounts that do not exceed a maximum tolerated dose are needed to assess the carcinogenic effects of 2-EHA.

Characterization of the Eugenol Effects on the Bioenergetic Profile of SCC-4 Human Squamous Cell Carcinoma Cell Line

2018 ◽  
Vol 69 (9) ◽  
pp. 2567-2570 ◽  
Author(s):  
Oana M. Duicu ◽  
Ioana Z. Pavel ◽  
Florin Borcan ◽  
Danina M. Muntean ◽  
Adelina Cheveresan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Squamous Cell Carcinoma Cell ◽  
Human Squamous Cell Carcinoma ◽  
Extracellular Flux ◽  
Transport Chain

Eugenol (EU), the active ingredient in clove oil, is commonly used as successful therapeutic compound in dentistry due to its antiseptic and anti-inflammatory effects. Recent research studies suggest that eugenol has also a potential anti-cancer effect. This study was thereby purported to assess the effects of EU on the bioenergetic profile of the SCC-4 human squamous cell carcinoma cell line. To this aim, SCC-4 cells were treated for 24 hours with free EU and EU incorporated in polyurethane structures (50 �M each). Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured using the Seahorse XF-24e extracellular flux analyzer (Agilent Technologies Inc.). Analysis of the SCC-4 bioenergetic profile was performed in the presence of the classic modulators of the electron transport chain: oligomycin, FCCP, and antimycin A+rotenone. Our data showed that cells stimulated with free EU induced a decrease of OCR linked parameters and an increase of ECAR, effects that were abolished by the incorporation of EU in polyurethane structures. In conclusion, free eugenol elicits inhibitory effects on mitochondrial respiration in the SCC-4 cell line, a result that might be suggestive for its anti-tumoral effects.

scholarly journals Identification of Polyomaviruses in Skin Cancers

Intervirology ◽  
2021 ◽  
pp. 96-102
Author(s):  
Pedro V.A. Costa ◽  
Patricia S. Ishiy ◽  
Paulo R.P. Urbano ◽  
Camila M. Romano ◽  
Stephen K. Tyring ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Normal Skin ◽  
Dermatofibrosarcoma Protuberans ◽  
Epidemiological Data ◽  
Skin Carcinogenesis ◽  
P Value ◽  
Merkel Cell ◽  
Cross Sectional ◽  
Skin Tumours ◽  
Skin Tumour

Background: Polyomaviruses (PyVs) were initially described in animals. They have also been detected in humans with some evidence that could play a role in skin carcinogenesis. Objectives: This study aimed to verify the presence of PyVs in different skin tumour samples and to make clinical correlations with patients’ epidemiological data from Clinics Hospital of Medical School of University of São Paulo, Brazil. Methods: This is a cross-sectional study. A random selection was performed of 120 patients with histopathological exams of different cutaneous neoplasms equally divided into 6 groups and 20 patients with normal skin. The available skin specimens were analysed with 2 different techniques of PCR (conventional and real time) for detection of PyV DNA. Concomitantly, retrospective analysis of the respective medical records for the collection of epidemiological data was done. Analyses suitable for categorical data were used to compare the proportion of patients in each group. Results: PyV DNA was found in 25.69% of the samples: 15% in basal cell carcinoma group, 15% in squamous cell carcinoma, 28.57% in melanoma, 15% in dermatofibrosarcoma protuberans, 13.33% in Kaposi sarcoma, 65% in Merkel cell carcinoma (MCC), and none in normal skin. Merkel cell PyV detection was statistically significant in MCC patients (p value <0.01), but no correlations were found between PyVs and others skin tumours. Conclusion: This study demonstrated the presence of PyVs in different skin tumours; however, no association of any PyVs found in any skin tumour with epidemiological data could be shown. Further studies are still needed to elucidate the mechanisms of PyVs in skin carcinogenesis.

Human Squamous Cell Carcinoma: Establishment and Characterization of New Permanent Cell Lines

1981 ◽  
Vol 107 (11) ◽  
pp. 703-710 ◽  
Author(s):  
C. J. Krause ◽  
T. E. Carey ◽  
R. W. Ott ◽  
C. Hurbis ◽  
K. D. McClatchey ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Human Squamous Cell Carcinoma ◽  
Permanent Cell

scholarly journals C/EBP Transcription Factors in Human Squamous Cell Carcinoma: Selective Changes in Expression of Isoforms Correlate with the Neoplastic State

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112073 ◽  
Author(s):  
Sanjay Anand ◽  
John Ebner ◽  
Christine B. Warren ◽  
Manu S. Raam ◽  
Melissa Piliang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Human Squamous Cell Carcinoma

scholarly journals Genetic regulation of homeostatic immune architecture in the lungs of Collaborative Cross mice

2021 ◽  
Author(s):  
Brea K Hampton ◽  
Kara L. Jensen ◽  
Alan C. Whitmore ◽  
Colton L. Linnertz ◽  
Paul Maurizio ◽  
...  
Keyword(s):  
Immune Cell ◽  
Genetic Regulation ◽  
Reference Population ◽  
Collaborative Cross ◽  
System Stability ◽  
Mouse Strains ◽  
Cell Populations ◽  
Immune Homeostasis ◽  
Heritable Variation ◽  
Organ Systems

Variation in immune homeostasis, immune system stability, in organ systems such as the lungs is likely to shape the host response to infection at these exposed tissues. We evaluated immune homeostasis in immune cell populations in the lungs of the Collaborative Cross (CC) mouse genetic reference population. We found vast heritable variation in leukocyte populations with the frequency of many of these cell types showing distinct patterns relative to classic inbred strains C57BL/6J and BALB/cJ. We identified 28 quantitative trait loci (QTL) associated with variation in baseline lung immune cell populations, including several loci that broadly regulate the abundance of immune populations from distinct developmental lineages, and found that many of these loci have predictive value for influenza disease outcomes, demonstrating that genetic determinants of homeostatic immunity in the lungs regulate susceptibility to virus-induced disease. All told, we highlight the need to assess diverse mouse strains in understanding immune homeostasis and resulting immune responses.

scholarly journals Phase I Trial of Copanlisib, a Selective Pi3k Inhibitor, in Combination With Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Grégoire Marret ◽  
Nicolas Isambert ◽  
Keyvan Rezai ◽  
Jocelyn Gal ◽  
Esma Saada-Bouzid ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Maximum Tolerated Dose ◽  
Pi3k Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Best Response ◽  
Disease Stabilization

Abstract BackgroundThe phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. ObjectiveWe investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methodsCopanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m² loading dose followed by 250 mg/m² on days 8, 15, and 22, and weekly thereafter). ResultsThree patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response.ConclusionCopanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients. NCT02822482, Date of registration: June 2016.

Analysis of ras oncogene mutations in human squamous cell carcinoma of the head and neck

1992 ◽  
Vol 1 (6) ◽  
pp. 405-411 ◽  
Author(s):  
F. Nuñez ◽  
O. Dominguez ◽  
E. Coto ◽  
C. Suarez-Nieto ◽  
P. Perez ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Ras Oncogene ◽  
Human Squamous Cell Carcinoma
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