2,564 results on '"Carcinoma, Squamous Cell chemically induced"'
Search Results
2. [Translated article] Risk of Skin Cancer Associated with Disease-Modifying Therapies in Multiple Sclerosis: A Comprehensive Evidence Review.
- Author
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Brufau-Cochs M, Mansilla-Polo M, and Morgado-Carrasco D
- Subjects
- Humans, Fingolimod Hydrochloride therapeutic use, Fingolimod Hydrochloride adverse effects, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Alemtuzumab adverse effects, Alemtuzumab therapeutic use, Sphingosine 1 Phosphate Receptor Modulators therapeutic use, Sphingosine 1 Phosphate Receptor Modulators adverse effects, Melanoma drug therapy, Cladribine therapeutic use, Cladribine adverse effects, Carcinoma, Squamous Cell etiology, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms, Multiple Sclerosis drug therapy, Multiple Sclerosis complications, Carcinoma, Basal Cell drug therapy
- Abstract
The use of disease-modifying therapies (DMT) has led to a paradigm shift in the management of multiple sclerosis. A comprehensive narrative review was conducted through an extensive literature search including Medline and Google Scholar to elucidate the link between DMT and the propensity of cutaneous malignancies. Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma. The associated physiopathological mechanisms are not fully understood. Alemtuzumab and cladribine show isolated associations with skin cancer. Regarding other DMT, no increased risk has ever been found. Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)
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- 2024
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3. Correlation between serum heavy metals and the risk of oral squamous cell carcinoma and oral potentially malignant disorders.
- Author
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Senevirathna K, Mahakapuge TAN, Ileperuma P, Jayawardana NU, Jayarathne L, Weerasekara R, Gamage CU, Senevirathna B, Perera U, Jayasinghe R, and Kanmodi KK
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Sri Lanka epidemiology, Aged, Case-Control Studies, Risk Factors, Squamous Cell Carcinoma of Head and Neck blood, Squamous Cell Carcinoma of Head and Neck chemically induced, Squamous Cell Carcinoma of Head and Neck epidemiology, Arsenic blood, Arsenic adverse effects, Metals, Heavy blood, Metals, Heavy adverse effects, Mouth Neoplasms blood, Mouth Neoplasms etiology, Mouth Neoplasms epidemiology, Mouth Neoplasms chemically induced, Carcinoma, Squamous Cell blood, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell etiology
- Abstract
Oral squamous cell carcinoma (OSCC) is a serious public health problem in various Asian countries, including Sri Lanka, and a combination of cultural practices, lifestyle factors, and genetic predispositions influences the incidence of these cancers. The examination of the connection between exposure to heavy metals and the probability of developing oral potentially malignant disorders (OPMD) and OSCC has been limited in its scope, and the overall consequences of such exposure remain largely unknown. This study aims to clarify the link between serum levels of heavy metals and the risk of OSCC and OPMD. The concentrations of seven heavy metals-namely, arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), and zinc (Zn)-were analyzed in serum samples from 60 cases and 15 controls in the Sri Lankan cohort. The Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) was used for the analysis. Subsequently, the data underwent statistical evaluation via the Kruskal-Wallis H test, using the Statistical Package for Social Sciences (SPSS) version 28 software, with a confidence interval set at 95%. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 48 men and 27 women, with 15 patients each diagnosed with OSCC, OSF, OLK, and OLP, and 15 healthy controls. The study used the Kruskal-Wallis Test to compare metal concentrations across groups, finding significant differences for all metals except As and Pb. Significant associations were observed between age, past medical history, drug history, gender, smoking, alcohol consumption, and betel chewing. The Spearman Correlation test showed significant correlations between the concentrations of Cr, Co, Cu, As, and Zn and the presence of cancer/precancer conditions. The study's findings suggest that heavy metal contamination may be linked to the development of OSCC and precancerous conditions. When comparing OSCC and OPMD cases with controls, the serum concentrations of As and Pb did not differ significantly. However, Cd, Cr, Co, Cu, and Zn exhibited significantly higher concentrations among cases compared to controls (p < 0.05). This study observed significant variations in the levels of these five heavy metals among cancerous (OSCC), premalignant (OPMD), and healthy tissues, suggesting a potential role in the progression of malignancies. These findings underscore the importance of environmental pollution in this specific context., (© 2024. The Author(s).)
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- 2024
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4. p27 specifically decreases in squamous carcinoma, and mediates NNK-induced transformation of human bronchial epithelial cells.
- Author
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Peng M, Meng H, Wang J, Guo M, Li T, Qian X, Chen R, Jin H, and Huang C
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- Humans, Gene Expression Regulation, Neoplastic drug effects, MicroRNAs genetics, MicroRNAs metabolism, Down-Regulation drug effects, Carcinogens toxicity, Nitrosamines toxicity, Bronchi metabolism, Bronchi pathology, Bronchi drug effects, Epithelial Cells metabolism, Epithelial Cells drug effects, Epithelial Cells pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell genetics, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic chemically induced, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic drug effects, Cyclin-Dependent Kinase Inhibitor p27 metabolism, Cyclin-Dependent Kinase Inhibitor p27 genetics, Lung Neoplasms metabolism, Lung Neoplasms pathology, Lung Neoplasms chemically induced, Lung Neoplasms genetics
- Abstract
Lung cancer remains the leading cause of cancer-related deaths, with cigarette smoking being the most critical factor, linked to nearly 90% of lung cancer cases. NNK, a highly carcinogenic nitrosamine found in tobacco, is implicated in the lung cancer-causing effects of cigarette smoke. Although NNK is known to mutate or activate certain oncogenes, its potential interaction with p27 in modulating these carcinogenic effects is currently unexplored. Recent studies have identified specific downregulation of p27 in human squamous cell carcinoma, in contrast to adenocarcinoma. Additionally, exposure to NNK significantly suppresses p27 expression in human bronchial epithelial cells. Subsequent studies indicates that the downregulation of p27 is pivotal in NNK-induced cell transformation. Mechanistic investigations have shown that reduced p27 expression leads to increased level of ITCH, which facilitates the degradation of Jun B protein. This degradation in turn, augments miR-494 expression and its direct regulation of JAK1 mRNA stability and protein expression, ultimately activating STAT3 and driving cell transformation. In summary, our findings reveal that: (1) the downregulation of p27 increases Jun B expression by upregulating Jun B E3 ligase ITCH, which then boosts miR-494 transcription; (2) Elevated miR-494 directly binds to 3'-UTR of JAK1 mRNA, enhancing its stability and protein expression; and (3) The JAK1/STAT3 pathway is a downstream effector of p27, mediating the oncogenic effect of NNK in lung cancer. These findings provide significant insight into understanding the participation of mechanisms underlying p27 inhibition of NNK induced lung squamous cell carcinogenic effect., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
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- 2024
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5. PD-1 Inhibitor Induced Hypertrophic Lichen Planus: A Case Report.
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Lim O, Maher E, and Miller DD
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- Humans, Male, Middle Aged, Immune Checkpoint Inhibitors adverse effects, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Lichen Planus chemically induced, Lichen Planus pathology, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell chemically induced
- Abstract
Background and Objective: PD-1 inhibitors have revolutionized cancer therapies and are being used to treat an expanding array of cancers. To best serve patients, clinicians should be familiar with the spectrum of skin manifestations associated with PD-1 inhibitor therapy. Here, we report a unique case of hypertrophic lichen planus (HLP) in a 64-year-old man treated with pembrolizumab; the presentation initially suggested a squamous cell carcinoma (SCC) morphology, then evolved into a morphology more typical of hypertrophic lichen planus. This case underscores the need for caution in diagnosing eruptive SCCs associated with PD-1 inhibitor therapy. In such instances, maintaining a high suspicion for lichenoid reactions as sequelae of PD-1 inhibitor treatment and starting an empiric trial of therapy for lichenoid dermatitis may be warranted to ensure timely management of lesions., Methods: We describe a case of hypertrophic lichen planus mimicking squamous cell carcinoma in the setting of PD-1 inhibitory therapy with pembrolizumab. A PubMed literature review was conducted to identify other cases and determine the incidence of lichenoid reactions imitating squamous cell carcinoma in the setting of PD-1 inhibitor use., Results: Our case is one of the few available pieces of literature describing eruptive hypertrophic lichen planus imitating SCC in the setting of PD-1 inhibitor use. Initial skin nodule biopsy appeared histologically compatible with squamous cell carcinoma. Repeat biopsy of the skin lesions revealed histological features consistent with hypertrophic lichen planus. Over time, lower extremity lesions evolved into a more typical appearance of hypertrophic lichen planus. Treatment with topical 0.05% clobetasol ointment and oral acitretin 25 mg led to complete resolution of lesions within 2-3 months., Conclusions: This case underscores the significance of maintaining vigilance for lichenoid reactions as potential sequelae of PD-1 inhibitor therapy. It highlights the variability in initial presentation and the potential for lesions to transform over time. Timely recognition and appropriate management, including high-potency topical corticosteroids and oral acitretin, are crucial for achieving favorable outcomes in patients experiencing such reactions. More studies are necessary to fully analyze the rate of HLP occurrence as a consequence of PD-1 inhibitor use., (© 2024. The Author(s).)
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- 2024
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6. A retrospective analysis of drugs associated with the development of cutaneous squamous cell carcinoma reported by patients on the FDA's adverse events reporting system.
- Author
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Jean-Pierre P and Nouri K
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- Humans, United States epidemiology, Male, Female, Retrospective Studies, Aged, Middle Aged, Adult, Risk Factors, Immunosuppressive Agents adverse effects, Aged, 80 and over, Thalidomide adverse effects, Thalidomide analogs & derivatives, Calcineurin Inhibitors adverse effects, Calcineurin Inhibitors administration & dosage, Adrenal Cortex Hormones adverse effects, Adrenal Cortex Hormones therapeutic use, Sex Factors, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms epidemiology, United States Food and Drug Administration, Adverse Drug Reaction Reporting Systems statistics & numerical data
- Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer arising from squamous cells of the epidermis. Most cases of cSCC have a good prognosis if detected and treated early; however, certain cases can be aggressive. The primary risk factor for cSCC is prolonged ultraviolet radiation from sun exposure, leading to DNA mutations. Other risk factors have also been observed, including adverse reactions to medications, particularly immunosuppressants. A query of the Food and Drug Administration Adverse Events Reporting System (FAERS) was done, and all reported events of cSCC as adverse events to medication were recorded along with demographic data of patients affected. A total of 4,792 cases of cSCC as an adverse event to medication were reported between 1997 and 2023. Lenalidomide, a chemotherapeutic drug, had the most cases of cSCC as an adverse event. Nine of the top 10 drugs associated with cSCC had immunosuppressive characteristics. While males had higher odds of cSCC associated with corticosteroids and calcineurin inhibitors, females had higher odds of cSCC related to monoclonal antibodies. Geriatric patients accounted for the majority of cSCC cases at 59.7%. Drawing on data from the FAERS database, there's been a consistent increase in cSCC cases as a side-effect to certain medications, with most having immunosuppressive characteristics. Since there is a lack of up-to-date literature overviewing the most implicated medications for cSCC, we aimed to illustrate this better, as well as patient demographics, to better guide clinicians when prescribing these medications., (© 2024. The Author(s).)
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- 2024
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7. DNA repair ability in a patient with voriconazole-related squamous cell carcinoma that required differential diagnosis from xeroderma pigmentosum.
- Author
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Fukumoto T, Harada T, Ito T, Fukushima S, Ono R, Furue M, and Nishigori C
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- Humans, Male, Diagnosis, Differential, Middle Aged, Antifungal Agents, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell chemically induced, DNA Repair, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Skin Neoplasms genetics, Skin Neoplasms chemically induced, Voriconazole adverse effects, Xeroderma Pigmentosum genetics, Xeroderma Pigmentosum diagnosis
- Abstract
Competing Interests: Conflicts of interest The authors have no conflict of interest to declare.
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- 2024
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8. An effective two-stage NMBzA-induced rat esophageal tumor model revealing that the FAT-Hippo-YAP1 axis drives the progression of ESCC.
- Author
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Zheng W, Yuan H, Fu Y, Deng G, Zheng X, Xu L, Fan H, Jiang W, and Yu X
- Subjects
- Humans, Rats, Mice, Animals, Cell Line, Tumor, Carcinogenesis, Esophageal Squamous Cell Carcinoma genetics, Esophageal Squamous Cell Carcinoma metabolism, Esophageal Neoplasms chemically induced, Esophageal Neoplasms genetics, Esophageal Neoplasms metabolism, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Papilloma, Dimethylnitrosamine analogs & derivatives
- Abstract
Rat model of N-nitrosomethylbenzylamine (NMBzA)-induced esophageal squamous cell carcinoma (ESCC) is routinely used to study ESCC initiation, progression and new therapeutic strategies. However, the model is time-consuming and malignant tumor incidences are low. Here, we report the usage of multi-kinase inhibitor sorafenib as a tumor promoter to establish an efficient two-stage NMBzA-induced rat ESCC carcinogenesis model, resulting in increments of tumor incidences and shortened tumor formation times. By establishing the model and applying whole-genome sequencing, we discover that benign papillomas and malignant ESCCs harbor most of the "driver" events found in rat ESCCs (e.g. recurrent mutations in Ras family, the Hippo and Notch pathways and histone modifier genes) and the mutational landscapes of rat and human ESCCs overlap extensively. We generate tumor cell lines derived from NMBzA-induced papillomas and ESCCs, showing that papilloma cells retain more characteristics of normal epithelial cells than carcinoma cells, especially their exhibitions of normal rat cell karyotypes and inabilities of forming tumors in immunodeficient mice. Three-dimensional (3-D) organoid cultures and single cell RNA sequencing (scRNA-seq) indicate that, when compared to control- and papilloma-organoids, ESCC-organoids display salient abnormalities at tissue and single-cell levels. Multi-omic analyses indicate that NMBzA-induced rat ESCCs are accompanied by progressive hyperactivations of the FAT-Hippo-YAP1 axis and siRNA or inhibitors of YAP1 block the growth of rat ESCCs. Taken together, these studies provide a framework of using an effective rat ESCC model to investigate multilevel functional genomics of ESCC carcinogenesis, which justify targeting YAP1 as a therapeutic strategy for ESCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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9. Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.
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Wu D, Li Y, Xu P, Fang Q, Cao F, Lin H, Li Y, Su Y, Lu L, Chen L, Li Y, Zhao Z, Hong X, Li G, Tian Y, Sun J, Yan H, Fan Y, Zhang X, Li Z, and Liu X
- Subjects
- Humans, Cisplatin, Squamous Cell Carcinoma of Head and Neck therapy, Neoadjuvant Therapy adverse effects, Immunotherapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms chemically induced, Albumins, Paclitaxel, Antibodies, Monoclonal, Humanized
- Abstract
Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m
2 ), and cisplatin (60 mg/m2 ) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC., (© 2024. The Author(s).)- Published
- 2024
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10. Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.
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Koushki M, Amiri-Dashatan N, Rezaei-Tavirani M, Robati RM, Fateminasab F, Rahimi S, Razzaghi Z, and Farahani M
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- Humans, Quercetin, Molecular Docking Simulation, Toxicogenetics, Protective Agents, Folic Acid adverse effects, Membrane Proteins, Molecular Chaperones, HSP40 Heat-Shock Proteins, Arsenic toxicity, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms metabolism
- Abstract
Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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11. Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.
- Author
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Martabano BB, Dow S, Chow L, Williams MMV, Mack MK, Bellone R, and Wotman KL
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- Horses, Humans, Animals, Interferon alpha-2 therapeutic use, Prospective Studies, Interferon-alpha, Antibodies therapeutic use, Recombinant Proteins, Conjunctival Neoplasms, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell veterinary, Carcinoma, Squamous Cell chemically induced
- Abstract
Objective: To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses., Animals Studied: Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent., Procedures: Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 months after treatment completion. A greater than 50% reduction in tumor size was considered positive response to treatment (i.e., partial or complete response). Development of anti-IFNα2b antibodies was assessed using serum samples obtained after treatment initiation and compared with treatment responses. Antibody concentrations were analyzed using a mixed model. Statistical significance was considered p < 0.05., Results: Each horse received four to six perilesional injections of IFNα2b. Five of 12 eyes (4/11 horses) responded to treatment. Two of five eyes showed complete resolution of gross PSCC. No systemic adverse effects were seen. Local swelling occurred during treatment protocol in 6/11 horses but resolved without intervention. All horses developed serum anti-IFNα2b antibodies. There was no evidence of statistical difference in antibody concentration between responders and non-responders., Conclusions: Perilesional administration of IFNα2b was found to be well-tolerated in horses with PSCC, and induced tumor regression in 42% of treated eyes. Treatment failure appears unrelated to the development of IFNα2b antibodies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martabano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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12. Carcinogenicity of butyraldehyde in rats by a two-year inhalation study.
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Furukawa Y, Senoh H, Hirai S, Misumi K, and Kasai T
- Subjects
- Animals, Male, Female, Carcinoma, Adenosquamous chemically induced, Carcinoma, Adenosquamous pathology, Administration, Inhalation, Nose Neoplasms chemically induced, Carcinosarcoma chemically induced, Carcinosarcoma pathology, Carcinogens toxicity, Carcinogens administration & dosage, Carcinogenicity Tests, Inhalation Exposure adverse effects, Rats, Time Factors, Papilloma chemically induced, Papilloma pathology, Carcinoma, Squamous Cell chemically induced, Rats, Inbred F344
- Abstract
We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.
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- 2024
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13. The Protective Effect of Sanggenol L Against DMBA-induced Hamster Buccal Pouch Carcinogenesis Induces Apoptosis and Inhibits Cell Proliferative Signalling Pathway.
- Author
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Fu Q, Zhang F, and Vijayalakshmi A
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- Animals, Cricetinae, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Carcinogenesis drug effects, Carcinogenesis chemically induced, Male, Mesocricetus, 9,10-Dimethyl-1,2-benzanthracene, Apoptosis drug effects, Cell Proliferation drug effects, Mouth Neoplasms drug therapy, Mouth Neoplasms chemically induced, Mouth Neoplasms pathology, Mouth Neoplasms metabolism, Signal Transduction drug effects
- Abstract
Background: Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its underlying mechanisms are desperately needed. The purpose of this study was to examine the chemopreventive effects of sanggenol L on oral squamous cell carcinoma (OSCC). The research focused on molecular signalling pathways in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis., Aim: The purpose of this study was to look at the biochemical and chemopreventive effects of sanggenol L on 7,12-dimethylbenz(a)anthracene (DMBA)-induced HBP (hamster buccal pouch) carcinogenesis via cell proliferation and the apoptotic pathway., Methods: After developing squamous cell carcinoma, oral tumours continued to progress leftward into the pouch 3 times per week for 10 weeks while being exposed to 0.5 % reactive DMBA three times per week. Tumour growth was caused by biochemical abnormalities that induced inflammation, increased cell proliferation, and decreased apoptosis., Results: Oral sanggenol L (10 mg/kg bw) supplementation with cancer-induced model DMBApainted hamsters prevented tumour occurrences, improved biochemistry, inhibited inflammatory markers, decreased cell proliferation marker expression of tumour necrosis factor-alpha (TNF- α), nuclear factor (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and induced apoptosis., Conclusion: Sanggenol L could be developed into a new medicine for the treatment of oral carcinogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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14. Letter to the editors: Development of malignant melanoma and squamous cell carcinoma in a patient receiving fingolimod treatment.
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Karabas M, Tepe N, and Esmeli F
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- Humans, Fingolimod Hydrochloride adverse effects, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Melanoma pathology, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Carcinoma, Squamous Cell chemically induced
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- 2024
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15. Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta-analysis.
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Pham JP, Rodrigues A, Goldinger SM, Sim HW, and Liu J
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- Humans, Retrospective Studies, Prospective Studies, Protein Kinase Inhibitors adverse effects, ErbB Receptors, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms, Skin Neoplasms drug therapy, Skin Neoplasms chemically induced, Antineoplastic Agents adverse effects
- Abstract
Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti-PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single-arm trials or retrospective studies. A systematic review and meta-analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18-36), median PFS was 4.8 months (95% CI 3.9-6.6) and median OS was 11.7 months (95% CI 9.2-14.1). Any grade AEs occurred in 93% of patients (95% CI 85-97) while grade 3 and higher AEs occurred in 30% (95% CI 14-54). These results were similar between anti-EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first-line anti-PD1 immunotherapy. Future studies should evaluate their activity and safety following anti-PD1, identify predictive biomarkers for their efficacy and explore combination approaches., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
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- 2024
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16. Usnic acid attenuates 7,12-dimethylbenz[a] anthracene (DMBA) induced oral carcinogenesis through inhibiting oxidative stress, inflammation, and cell proliferation in male golden Syrian hamster model.
- Author
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Azhamuthu T, Kathiresan S, Senkuttuvan I, Abulkalam Asath NA, and Ravichandran P
- Subjects
- Cricetinae, Animals, Male, Mesocricetus, Antioxidants metabolism, 9,10-Dimethyl-1,2-benzanthracene toxicity, Carcinogenesis chemically induced, Inflammation chemically induced, Inflammation drug therapy, Oxidative Stress, Cell Proliferation, Anthracenes, Carcinogens toxicity, Carcinoma, Squamous Cell chemically induced, Mouth Neoplasms chemically induced, Mouth Neoplasms prevention & control, Mouth Neoplasms pathology, Benzofurans
- Abstract
In this study, we investigated the chemopreventive efficacy of usnic acid (UA), an effective secondary metabolite component of lichens, against 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma (OSCC) in the hamster model. Initially, the buccal pouch carcinogenesis was induced by administering 0.5% DMBA to the HBP (hamster buccal pouch) region about three times a week until the 10th week. Then, UA was orally treated with different concentrations (25, 50, 100 mg/kg b.wt) on alternative days of DMBA exposure, and the experimental process ended in the 16th week. After animal experimentation, we observed 100% tumor incidence with well-differentiated OSCC, dysplasia, and hyperplasia lesions in the DMBA-induced HBP region. Furthermore, the UA treatment of DMBA-induced hamster effectively inhibited tumor growth. In addition, UA upregulated antioxidant levels, interfered with the elevated lipid peroxidation by-product of thiobarbituric acid reactive substances, and changed the activities of the liver detoxification enzyme (Phase I and II) in DMBA-induced hamsters. Furthermore, immunohistochemical staining of inflammatory markers (iNOS and COX-2) and proliferative cell markers (cyclin-D1 and PCNA) were upregulated in the buccal pouch part of hamster animals induced with DMBA. Notably, the oral administration of UA significantly suppressed these markers during DMBA-induced hamsters. Collectively, our findings revealed that UA exhibits antioxidant, anti-inflammatory, antitumor, and apoptosis-inducing characteristics, demonstrating UA's protective properties against DMBA-induced HBP carcinogenesis., (© 2023 Wiley Periodicals LLC.)
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- 2024
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17. Manifestation of subacute cutaneous lupus erythematosus during treatment with anti-PD-1 antibody cemiplimab - a case report.
- Author
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Fietz S, Fröhlich A, Mauch C, de Vos-Hillebrand L, Fetter T, Landsberg J, Hoffmann F, and Sirokay J
- Subjects
- Humans, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell drug therapy, Hepatitis, Lupus Erythematosus, Cutaneous chemically induced, Lupus Erythematosus, Cutaneous diagnosis, Lupus Erythematosus, Cutaneous drug therapy
- Abstract
Introduction: The anti-programmed cell death protein 1 (PD-1) antibody cemiplimab has shown promising results in the treatment of unresectable or metastatic squamous cell carcinoma, however, frequently leads to immune-related adverse events limiting therapy efficacy. Although cutaneous side effects are common, only very few cases of cutaneous lupus erythematosus have been reported under anti-PD-1 immunotherapy. So far, no case of cutaneous lupus has been described under treatment with cemiplimab., Case Report: For the first time, we report the case of a patient with advanced squamous cell carcinoma, who developed clinical and histological findings in sun-exposed skin that were consistent with anti-SS-A/Ro antibody-positive subacute cutaneous lupus erythematosus (SCLE) under treatment with cemiplimab. Additionally, laboratory chemical analyses revealed a severe immune-related hepatitis without clinical symptoms. Both, the SCLE and the hepatitis, resolved after the administration of topical and systemic steroids and the discontinuation of anti-PD-1 therapy., Conclusion: Treatment with cemiplimab can be associated with the appearance of cutaneous lupus erythematosus in sun-exposed areas. Application of topical and systemic glucocorticoids can lead to a rapid resolution of the skin eruptions. Moreover, our case illustrates the possibility of simultaneously occurring severe immune-related adverse events. This highlights the importance of additional diagnostics to avoid overlooking additional immune-related adverse events., Competing Interests: JS is a consultant/advisory board member and received speaker’s honoraria from Novartis, BMS, MSD, and Roche. JL is a consultant/advisory board member and received speaker’s honoraria from Novartis, BMS, MSD, and Roche. LV received financial support travel expenses from Pierre Fabre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fietz, Fröhlich, Mauch, de Vos-Hillebrand, Fetter, Landsberg, Hoffmann and Sirokay.)
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- 2023
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18. Spermidine Suppresses Oral Carcinogenesis through Autophagy Induction, DNA Damage Repair, and Oxidative Stress Reduction.
- Author
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Coeli-Lacchini FB, da Silva G, Belentani M, Alves JSF, Ushida TR, Lunardelli GT, Garcia CB, Silva TA, Lopes NP, and Leopoldino AM
- Subjects
- Humans, Mice, Animals, Spermidine adverse effects, 4-Nitroquinoline-1-oxide toxicity, Carcinogenesis pathology, Carcinogens, Squamous Cell Carcinoma of Head and Neck, DNA Damage, DNA Repair, Oxidative Stress, Ceramides, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell prevention & control, Carcinoma, Squamous Cell genetics, Mouth Neoplasms chemically induced, Mouth Neoplasms prevention & control, Mouth Neoplasms genetics, Tongue Neoplasms pathology, Head and Neck Neoplasms
- Abstract
Autophagy has been proposed to play a dual role in cancer-as a tumor suppressor in early stages and oncogenic in late stages of tumorigenesis. This study investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathologic aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. The comet assay indicated that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and the decrease of reactive oxygen species. As sphingolipid alterations have been reported in OSCC, sphingolipids in the tongue and plasma of animals were analyzed and plasma C16 ceramide levels were shown to increase proportionally to lesion severity, indicating its potential as a biomarker. Mice exposed to 4NQO plus SPD had lower levels of C16 ceramide than the 4NQO group, which indicated SPD's ability to prevent the 4NQO-induced carcinogenesis. Together, these data indicate that activation of autophagy has a tumor suppressor role during the early stages of oral carcinogenesis. Because of its ability to induce autophagy accompanied by reduced oxidative stress and DNA damage, SPD may have a protective action against chemically induced oral cancer., Competing Interests: Disclosure Statement None declared., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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19. Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial.
- Author
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Borghaei H, O'Byrne KJ, Paz-Ares L, Ciuleanu TE, Yu X, Pluzanski A, Nagrial A, Havel L, Kowalyszyn RD, Valette CA, Brahmer JR, Reck M, Ramalingam SS, Zhang L, Ntambwe I, Rabindran SK, Nathan FE, Balli D, and Wu YL
- Subjects
- Humans, Nivolumab adverse effects, B7-H1 Antigen metabolism, Neoplasm Recurrence, Local drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy
- Abstract
Background: In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression., Patients and Methods: Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint., Results: At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings., Conclusions: CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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20. Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis.
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Li L, Pei B, and Feng Y
- Subjects
- Humans, Female, Contraceptives, Oral adverse effects, Gonadal Steroid Hormones adverse effects, Keratinocytes pathology, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell complications, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I
2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones., (© 2023. BioMed Central Ltd., part of Springer Nature.)- Published
- 2023
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21. Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study.
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Fázio MR, Cristelli MP, Tomimori J, Koga CE, Ogawa MM, Beneventi GT, Tedesco-Silva H, and Medina-Pestana J
- Subjects
- Humans, Male, Middle Aged, Aged, Female, Sirolimus adverse effects, Immunosuppressive Agents adverse effects, Prospective Studies, Calcineurin Inhibitors therapeutic use, Graft Rejection epidemiology, Graft Rejection prevention & control, Kidney Transplantation adverse effects, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms epidemiology, Skin Neoplasms chemically induced
- Abstract
Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability., Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion., Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable., Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
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- 2023
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22. NITROSOGENESIS LESSONS FROM DERMATOLOGISTS-NITROSAMINES/ NDSRIS CONTAMINATION OF THE POLIMEDICATION IN POLIMORBID PATIENTS AS THE MOST POWERFUL SKIN CANCER INDUCTOR: DOUBLE HATCHET FLAP FOR SCC OF THE SCALP OCCURRING DURING TREATMENT WITH VALSARTAN/ HYDROCHLOROTHIAZIDE AND LERCANIDIPINE.
- Author
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Tchernev G
- Subjects
- Humans, Aged, 80 and over, Scalp, Dermatologists, Quality of Life, Valsartan, Carcinogens toxicity, Hydrochlorothiazide, Nitrosamines, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy
- Abstract
Nitrosogenesis remains to be a topic that is and, in all likelihood, will be relevant in the near and distant future. The reason for this actuality is mainly due to the official data of the regulatory authorities in the face of the FDA, starting back in 2018 with the announcement of the contamination of Valsartan with nitrosamines. This issue only became more profound in April 2023, when again the FDA declared over 250 of the most widely distributed drugs worldwide as actually or potentially contaminated with ˝hypothetical˝ carcinogens. Unfortunately, according to the literature, it is the intake of ˝hypothetical carcinogens˝ that is associated with the development of real carcinomas, including cutaneous tumours. Additionally, the type of carcinogens that could ˝hypothetically˝ be found in these drugs (in the regulatory agency recommendations) has been added to the list, and they are categorized as having a ˝hypothetical carcinogenic potency˝ between 1 to 5 according to the FDA regulation as to pharmaceutical companies from August 2023. Reference values have also been established for each carcinogen. Interestingly, in certain geographic regions such as Eastern Europe, for example, in certain institutions, over periods of 10 years or more, over 98.9% of cases of actual cutaneous tumours (keratinocytic, melanocytic, etc.), could be linked/associated primarily (not hypothetically) to polymedication, which according to official FDA data from April 2023, could be defined as actually/potentially contaminated with up to several ˝hypothetical˝ carcinogens simultaneously. The lack of official data on the contamination of these batches of drugs (with nitrosamines/ NDSRIs) remain even for the period 2018-2023 more than worrying and are one indirect evidence of their real rather than hypothetical availability. Nonetheless, the 2023 FDA data cast considerable doubt as to whether, within the polymorbidity and contamination of polymedication, the allowable daily doses of carcinogens are being substantially exceeded. An open question for regulators remains: Did the giant Pfizer withdraw its high blood pressure drugs in 2022 (hydrochlorothiazide, quinapril) due to the presence of ˝hypothetical carcinogens˝? In practice, Pfizer appears to be one of the few or only companies to have openly stated the reason for withdrawing their preparations due to contamination with real carcinogens and thus protect end users. With this official preventive act, the Giant Pfizer gained the trust of patients worldwide. Another and even more serious dilemma remains whether this is a controlled contamination of certain batches of medicines in certain geographical regions? Indicative therefore are recently published data on the absence of contamination of all batches of a certain class of medicines in certain geographical regions. The genesis of the 'sporadicity' and the 'selectivity' of contamination remain for the time being unresolved and open new and novel questions. We present an 82-year-old patient with arterial hypertension taking hydrochlorothiazide, valsartan and lercanidipine for 3 years who developed a short-term squamous cell carcinoma of the scalp after taking them (1,5- 2 years later) , operated successfully by double hatchet flap. The pathogenesis of the skin tumor/keratinocytic cancer is commented in the context of nitrosogenesis and the officially announced contamination by the FDA with ˝hypothetical carcinogens˝ leading once again to the appearance of a real squamous cell carcinoma of the skin. The polycontamination of multimedication within polymorbidity appears to be problematic. It is thanks to the official FDA data that the strength of these interrelationships is beginning to become clearer although not at the desired speed of clinicians and end users. Discovering the logical relationship between databases (concerning the incidence of skin cancer, but not only) from different periods should only be relative or consistent with current bulletins of regulators and contaminated polymedication. This is what guarantees that the objective truth will be brought to the surface and ensure, through the possible rapid elimination of the contaminants: 1) better survival for patients and 2) better quality of life.
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- 2023
23. Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies.
- Author
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Lang R, Welponer T, Richtig E, Wolf I, Hoeller C, Hafner C, Nguyen VA, Kofler J, Barta M, Koelblinger P, Hitzl W, Emberger M, and Laimer M
- Subjects
- Humans, Aged, 80 and over, Nivolumab therapeutic use, Nivolumab adverse effects, B7-H1 Antigen, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms chemically induced, Hematologic Neoplasms
- Abstract
Background: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)-1 have become the current standard of care and first-line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety., Objectives: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC., Methods: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non-progressing or stable under active therapy, were eligible for inclusion., Results: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration., Conclusion: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)
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- 2023
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24. Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice.
- Author
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Nguyen KA, DePledge LN, Bian L, Ke Y, Samedi V, Berning AA, Owens P, Wang XJ, and Young CD
- Subjects
- Humans, Animals, Mice, Phosphatidylinositol 3-Kinase, Carcinogenesis, Carcinogens toxicity, Squamous Cell Carcinoma of Head and Neck, Phosphatidylinositols, Myeloid-Derived Suppressor Cells, Carcinoma, Squamous Cell chemically induced, Mouth Neoplasms chemically induced, Head and Neck Neoplasms
- Abstract
Background: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC., Methods: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation., Results: In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner., Conclusions: Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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25. Corneal squamous neoplasia: masquerades and management outcomes at a rural eyecare centre.
- Author
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Agarwal A, Kaliki S, and Murthy SI
- Subjects
- Humans, Fluorouracil, Retrospective Studies, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Eye Neoplasms diagnosis, Eye Neoplasms drug therapy, Corneal Diseases diagnosis, Corneal Diseases drug therapy, Corneal Diseases chemically induced, Conjunctival Neoplasms pathology, Keratitis chemically induced
- Abstract
The authors describe two cases of corneal ocular surface squamous neoplasia (OSSN), presenting at our rural eyecare centre, which were initially misdiagnosed as viral epithelial keratitis and corneal pannus with focal limbal stem cell deficiency. Both the cases were refractory to initial treatment and corneal OSSN was suspected. Anterior segment-optical coherence tomography (AS-OCT) revealed a thickened, hyper-reflective epithelium with abrupt transition and an underlying cleavage plane, features typical of OSSN. Topical 1% 5-fluorouracil (5-FU) therapy was initiated and in two cycles (first case) to three cycles (second case), complete resolution was noted both clinically and on AS-OCT, with no significant side effects. Both patients are currently free of tumour at the 2-month follow-up period. The authors report the rare, atypical presentations of corneal OSSN, discuss the masquerades and highlight the role of primary topical 5-FU in managing corneal OSSN in limited resource settings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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26. To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma.
- Author
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Poole M, Schwartz RA, Lambert WC, and Alhatem A
- Subjects
- Humans, Immune Checkpoint Inhibitors therapeutic use, Nivolumab adverse effects, Retrospective Studies, B7-H1 Antigen metabolism, Biomarkers, Keratoacanthoma chemically induced, Keratoacanthoma drug therapy, Keratoacanthoma metabolism, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy
- Abstract
Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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27. Oral carcinogenesis triggers a nociceptive behavior and c-Fos expression in rats' trigeminal pathway.
- Author
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Alves JMDS, Viana KF, Pereira AF, Lima Júnior RCP, Vale ML, Pereira KMA, and Gondim DV
- Subjects
- Rats, Animals, Rats, Wistar, Nociception, Proto-Oncogene Proteins c-fos analysis, Proto-Oncogene Proteins c-fos metabolism, Carcinogenesis, Carcinoma, Squamous Cell chemically induced, Mouth Neoplasms chemically induced
- Abstract
Objective: To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control., Methods: Wistar rats were divided into control and 4-NQO groups for 8, 12, 16, or 20 weeks. 4-NQO suspension was administered on the animals' tongues. Mechanical hyperalgesia, assessment of facial expressions, and an open-field test were performed. After euthanasia, the animals' tongues were removed for macro- and microscopic analysis. c-Fos expression was analyzed in the trigeminal pathway structures., Results: 4-NQO induced time-dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c-Fos immunoexpression on the 20th week, and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long-term carcinogenic exposure caused changes in the nociceptive behavior and c-Fos expression in the rats' trigeminal pathway., (© 2022 Wiley Periodicals LLC.)
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- 2023
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28. Eruptive Squamous Cell Carcinomas Following Treatment With Fludarabine and Discussion of Treatment.
- Author
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Shah M, Wald J, and Hanke C
- Subjects
- Humans, Vidarabine adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Skin Neoplasms chemically induced, Skin Neoplasms diagnosis, Skin Neoplasms drug therapy
- Published
- 2023
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29. Low vitamin D and high cholesterol facilitate oral carcinogenesis in 4NQO-induced rat models via regulating glycolysis.
- Author
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Gumus R, Capik O, Gundogdu B, Tatar A, Altinkaynak K, Ozdemir Tozlu O, and Karatas OF
- Subjects
- Rats, Animals, Carcinogenesis metabolism, Squamous Cell Carcinoma of Head and Neck, Vitamin D, Glycolysis, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Mouth Neoplasms genetics, Vitamin D Deficiency complications, Head and Neck Neoplasms
- Abstract
Objectives: Diets and nutritional habits are critical during carcinogenic processes, where a diet poor in fruits and vegetables and rich in meat and other foods of animal origin facilitates carcinogenesis. In this study, we aimed at investigating the possible involvement of vitamin D deficiency (VDD) and high cholesterol (HC) together in oral squamous cell carcinoma (OSCC) through modulating glycolysis., Subjects and Methods: We compared total cholesterol, LDL, HDL, triglycerides, LDH, and vitamin D levels of OSCC patients and control individuals. We used GEO datasets for gene set enrichment and 4-nitroquinoline-1-oxide induced in vivo oral carcinogenesis models to investigate contribution of VDD and HC during carcinogenesis via possible modulation of glycolysis., Results: We found that VDD and HC co-exist in OSCC patients, and deregulation of cholesterol and vitamin D levels results in enrichment of genes related to glycolysis. We, then, demonstrated that VDD and HC on their own and together facilitated the formation of larger tumors in 4NQO-induced in vivo cancer models, which are suppressed by glycolysis inhibition., Conclusion: We reported collaborative contribution of HC and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells., (© 2022 Wiley Periodicals LLC.)
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- 2023
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30. Use of methotrexate and risk of skin cancer: a nationwide case-control study.
- Author
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Polesie S, Gillstedt M, Schmidt SAJ, Egeberg A, Pottegård A, and Kristensen K
- Subjects
- Humans, Methotrexate adverse effects, Case-Control Studies, Risk Factors, Melanoma, Cutaneous Malignant, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Psoriasis chemically induced, Psoriasis drug therapy, Psoriasis epidemiology
- Abstract
Background: Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM)., Methods: In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use., Results: Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively., Conclusions: We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis., (© 2023. The Author(s).)
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- 2023
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31. Ingenol Mebutate Is Associated With Increased Reporting Odds for Squamous Cell Carcinoma in Actinic Keratosis Patients, a Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS).
- Author
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Jedlowski PM
- Subjects
- Humans, Imiquimod therapeutic use, Pharmacovigilance, Treatment Outcome, Keratosis, Actinic drug therapy, Keratosis, Actinic pathology, Diterpenes adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell drug therapy
- Abstract
Background: Recently the production and marketing of ingenol mebutate in the European Union (EU) and Canada was halted due to a possible increased risk of squamous cell carcinoma (SCC) in patients with actinic keratosis (AK)., Objective: To investigate the relationship between SCC and topical AK medications including ingenol mebutate in the FDA Adverse Event Reporting System (FAERS)., Methods: Case/non-case analyses were performed in FAERS using data from 2012 to 2020 to examine the reporting odds ratio (ROR) signal for SCC for ingenol mebutate and all classes of topical AK medications under multiple conditions: i. comparison to all other drugs in FAERs, ii. comparison to other topical AK medications, iii. comparison to all other topical AK medications where only a single agent was implicated, iv. comparison of ingenol mebutate vs. imiquimod., Results: A statistically significant ROR for SCC was found for ingenol mebutate under all conditions (i. 31.57 (25.45, 39.16), ii. 50.35 (32.21, 78.82), iii 61.09 (35.36, 105.56), iv. 2.53 (1.27, 5.05). A significant but substantially smaller signal was observed for imiquimod (i. 12.38 (6.42, 32.84), ii. 5.18 (2.61, 10.26), iii 5.42 (2.49, 11.78), but not for fluorouracil or diclofenac. When compared to imiquimod directly, ingenol mebutate had a statistically significant ROR for SCC (2.53 (1.27, 5.05)., Conclusion: Our findings support an association between SCC and ingenol mebutate. This association is maintained under controls to limit bias and falsely elevated signal including controlling for disease state and cases with multiple drug exposures and when compared to imiquimod as in Phase IV studies of ingenol mebutate.
- Published
- 2023
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32. KARAPANDZIC FLAP FOR SQUAMOUS CELL CARCINOMA OF THE LOWER LIPP: POTENTIAL ROLE OF NITROSAMINES IN EPROSARTAN AS CANCER TRIGGERING FACTORS.
- Author
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Tchernev G, Lozev I, Pidakev I, and Kordeva S
- Subjects
- Humans, Acrylates, Imidazoles, Angiotensin II Type 1 Receptor Blockers, Carcinoma, Squamous Cell chemically induced
- Abstract
Chronic alcohol use, smoking, poor dental hygiene, absorbed sun radiation over the years, fair skin (Fitzpatrick type 1), light eyes, painful sunburns, congenital or acquired immunosuppression, certain rare syndromes, as well as infections with human papillomaviruses are perceived as risk factors for the development of squamous cell carcinoma of the lips. The new and at the same time modern aspects involving the pathogenesis of keratinocyte tumors in practice prove to be quite problematic for both patients and clinicians. These aspects are involved in the contamination or increased availability of certain nitrosamines in the antihypertensive medications. A serious international study in the last year has linked the intake of potentially contaminated (established availability without data on whether it exceeds the so-called ADI/acceptable daily intake dose) with nitrosamines valsartan with a relatively low, but still present risk of melanoma development. On the other hand, data from 2017 associate individual monotherapy of arterial hypertension with sartans with a significantly increased/statistically significant risk of squamous cell carcinomas development: more than a two-fold increased risk. It should be noted that at that time the problems with nitrosamines were completely unknown to the medical community. At the moment, there are numerous case studies that connect the use of sartans with the development of keratinocyte tumors - either single or multiple. We describe the first case of a patient who took eprosartan at a dose of 600 mg once a day for a total period of about 15 years with intake interruptions of no more than 6 years. Primary complaints in the lower lip area are from about 6 months. The preoperative biopsy showed evidence of squamous cell carcinoma. A multidisciplinary team performed a successful surgical treatment using the Karapandzic method, achieving an optimal aesthetic result. Based on the available literature data, the possible role of nitrosamines as a potential trigger for the development of squamous cell carcinoma is discussed.
- Published
- 2023
33. Oral Squamous Cell Carcinoma Following Acute Methotrexate Toxicity in a Psoriasis Patient: A Causal Association or Mere Co-Incidence.
- Author
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Choudhary R, Singh A, Chhabra N, and Gupta AK
- Subjects
- Female, Humans, Middle Aged, Methotrexate adverse effects, Squamous Cell Carcinoma of Head and Neck chemically induced, Squamous Cell Carcinoma of Head and Neck complications, Squamous Cell Carcinoma of Head and Neck drug therapy, Incidence, Immunosuppressive Agents adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Mouth Neoplasms chemically induced, Mouth Neoplasms complications, Mouth Neoplasms drug therapy, Psoriasis diagnosis, Psoriasis drug therapy, Head and Neck Neoplasms chemically induced, Head and Neck Neoplasms complications, Head and Neck Neoplasms drug therapy
- Abstract
Background: Methotrexate is an antimetabolite anticancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriasis patients on treatment with immunosuppressants have an increased risk of developing malignancies., Objective: To present a rare case of Oral Squamous Cell Carcinoma (OSCC) in a psoriasis patient postacute methotrexate toxicity., Case Report: A 47-year-old female, a known case of chronic plaque psoriasis for which she was on 15 mg/ week methotrexate therapy and accidentally consumed 15 mg for 7 consecutive days. She was successfully treated for methotrexate toxicity and 45 days later she presented with exophytic growth on the tongue. Histopathology confirmed the diagnosis of squamous cell carcinoma and the patient underwent surgical resection., Conclusion: There could be a causal association between psoriasis and OSCC in the setting of acute methotrexate toxicity, as in the present case., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2023
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34. A phase 2 study of first-line nivolumab in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma.
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Munhoz RR, Nader-Marta G, de Camargo VP, Queiroz MM, Cury-Martins J, Ricci H, de Mattos MR, de Menezes TAF, Machado GUC, Bertolli E, Barros M, de Souza CE, Franke F, Ferreira FO, Feher O, and de Castro G Jr
- Subjects
- Humans, Middle Aged, Aged, Aged, 80 and over, Progression-Free Survival, Response Evaluation Criteria in Solid Tumors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Nivolumab adverse effects, Carcinoma, Squamous Cell chemically induced
- Abstract
Background: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC)., Methods: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS)., Results: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities., Conclusions: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC., (© 2022 American Cancer Society.)
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- 2022
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35. Laser photobiomodulation does not alter clinical and histological characteristics of 4-NQO-induced oral carcinomas and leukoplakia in mice.
- Author
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Neculqueo GW, Estrázulas M, Cherubini K, Koth VS, and Salum FG
- Subjects
- Female, Mice, Animals, 4-Nitroquinoline-1-oxide toxicity, Leukoplakia, Oral, Carcinogens, Lasers, Semiconductor therapeutic use, Mouth Neoplasms chemically induced, Mouth Neoplasms radiotherapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell radiotherapy
- Abstract
Objective: This study evaluated the effect of laser photobiomodulation (PBM) on oral leukoplakia and squamous cell carcinomas (OSCC) in a model of oral carcinogenesis., Materials and Methods: Forty-one C57Bl/6 female mice were distributed in control group, 4-NQO group, Laser group 1.5 J and Laser group 9 J. Oral cancer was induced on the tongue by nitroquinoline oxide (4-NQO), diluted in the water for 16 weeks. In the 18th and 19th weeks, PBM with a diode laser, 0.028 cm
2 spot size, continuous emission mode, 660 nm wavelength was applied on the tongue of animals for seven sessions. Laser group 1.5 J received 30 mW power and 1.5 J energy. In the Laser group 9 J, 100 mW power, and 9 J energy were applied. In the 20th week the animals were euthanized., Results: All animals exposed to carcinogen developed clinical and histological alterations such as leukoplakia and OSCC on the tongue. There was no significant difference among Laser groups 1.5 and 9 J and 4-NQO group (not irradiated) regarding the area of leukoplakia and carcinomas (P > 0.05) or thickness of epithelial tissue and keratin (P > 0.05). There were also no association between PBM and histologic classification of the lesions (P = 0.87), frequency of OSCC (P = 0.57), grade of tumor differentiation (P = 0.88) or depth of invasion (P = 0.45)., Conclusion: Laser PBM, in both parameters used, does not influence on clinical and histological characteristics of oral leukoplakia and OSCC., Clinical Relevance: Results suggest that PBM may be a safe treatment for adverse effects of antineoplastic therapies in patients with leukoplakia and OSCC., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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36. Esophageal Squamous Cancer from 4NQO-Induced Mice Model: CNV Alterations.
- Author
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Liu Z, Su R, Ahsan A, Liu C, Liao X, Tian D, and Su M
- Subjects
- Humans, Mice, Animals, DNA Copy Number Variations, Hyperplasia, Esophageal Squamous Cell Carcinoma chemically induced, Esophageal Squamous Cell Carcinoma genetics, Esophageal Neoplasms chemically induced, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology
- Abstract
Squamous esophageal carcinoma is a common pathological type of esophageal carcinoma around the world. The prognosis of esophageal carcinoma is usually poor and diagnosed at late stages. Recently, research suggested that genomic instability occurred in esophageal cells during the development of esophageal squamous cell carcinoma (ESCC). Identifying prognostic and specific genomic characteristics, especially at the early hyperplasia stage, is critical. Mice were given 4-nitroquinoline 1-oxide (4NQO) with drinking water to induce esophageal cancer. The immortalized human esophageal epithelial cell line (NE2) was also treated with 4NQO. We performed histologic analyses, immunofluorescence, and immunohistochemical staining to detect DNA damage at different time points. Whole-exome sequencing was accomplished on the esophagus tissues at different pathological stages to detect single-nucleotide variants and copy number variation (CNV) in the genome. Our findings indicate that all mice were tumor-forming, and a series of changes from simple hyperplasia (ESSH) to intraepithelial neoplasia (IEN) to esophageal squamous cell carcinoma (ESCC) was seen at different times. The expression of γ-H2AX increased from ESSH to ESCC. In addition, mutations of the Muc4 gene were detected throughout the pathological stages. Furthermore, CNV burden appeared in the esophageal tissues from the beginning of ESSH and accumulated more in cancer with the deepening of the lesions. This study demonstrates that mutations caused by the early appearance of DNA damage may appear in the early stage of malignant tissue before the emergence of atypia. The detection of CNV and mutations of the Muc4 gene may be used as an ultra-early screening indicator for esophageal cancer.
- Published
- 2022
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37. Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer.
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Nguyen JH, Epling D, Dolphin N, Paccaly A, Conrado D, Davis JD, and Al-Huniti N
- Subjects
- Female, Humans, Neoplasm Recurrence, Local drug therapy, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Lung Neoplasms drug therapy, Skin Neoplasms drug therapy, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms chemically induced
- Abstract
A population pharmacokinetic (PopPK) model was previously developed for cemiplimab in patients with solid tumors, including advanced cutaneous squamous cell carcinoma (CSCC). Here, we update the existing PopPK model and characterize exposure-response relationships using efficacy and safety data obtained in patients with recurrent or metastatic cervical cancer (R/M CC). To improve model stability and robustness of the existing PopPK model in 1062 patients, the random-effect error model was revised, and structural covariates were removed from the base model to be tested in the covariate analysis. The updated model was used for external validation of cemiplimab pharmacokinetics (PK) in patients with R/M CC on cemiplimab monotherapy (350 mg every 3 weeks intravenously) from a phase III study (NCT03257267). Exposure-response relationships for cemiplimab efficacy (overall survival [OS], progression-free survival [PFS], duration of response [DOR], objective response rate [ORR]), and safety (immune-related adverse events [irAEs]) were analyzed in 295 patients with R/M CC from the aforementioned study. The updated PopPK model showed improved stability with 94.8% successful bootstrap runs vs. 47.6% in the prior model. Cemiplimab exposure was similar across tumor types, including basal cell carcinoma, CSCC, and non-small cell lung cancer. External validation showed the updated model adequately described cemiplimab PK in patients with R/M CC. In exposure-response efficacy analyses, Cox proportional hazard modeling (CPHM) showed no trend between exposure and OS, Kaplan-Meier plots showed no trend between exposure and PFS or DOR, and logistic regression analyses conducted on ORR showed no exposure-response relationship. In exposure-response safety analyses, CPHM showed no trend between exposure and irAEs., (© 2022 Regeneron Pharmaceuticals, Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2022
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38. Chemoprevention of 4NQO-Induced Mouse Tongue Carcinogenesis by AKT Inhibitor through the MMP-9/RhoC Signaling Pathway and Autophagy.
- Author
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Yin P, Chen J, Wu Y, Gao F, Wen J, Zhang W, Su Y, and Zhang X
- Subjects
- 4-Nitroquinoline-1-oxide toxicity, Animals, Autophagy, Carcinogenesis pathology, Chemoprevention, Disease Models, Animal, Humans, Matrix Metalloproteinase 9, Mice, Proto-Oncogene Proteins c-akt, Signal Transduction, Tongue pathology, rhoC GTP-Binding Protein, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell prevention & control, Mouth Neoplasms pathology
- Abstract
Oral cancer (OC), the most common cancer in the head and neck, which has a poor prognosis, histopathologically follows a stepwise pattern of hyperplasia, dysplasia, and cancer. Blocking the progression of OC in the precancer stage could greatly improve the survival and cure rates. AKT protein plays a critical role in the signal transduction of cancer cells, and we found that AKT was overexpressed in human OC samples through analysis of TCGA database. Therefore, this study is aimed at investigating the chemopreventive effect of an AKT inhibitor (MK2206 2HCl) on OC. In vivo , we established a 4-nitroquinoline-1-oxide- (4NQO-) induced mouse tongue carcinogenesis model to investigate the potential chemopreventive effect of MK2206 2HCl on mouse OC resulting from 4NQO. The results showed that MK2206 2HCl could significantly reduce the incidence rate and growth of OC, inhibit the transformation of dysplasia to cancer in the 4NQO-induced mouse tongue carcinogenesis model, and simultaneously markedly suppress cell proliferation, angiogenesis, and mast cell (MC) infiltration in 4NQO-induced mouse tongue cancers. In vitro , our results revealed that MK2206 2HCl could also inhibit oral squamous cell carcinoma (OSCC) cell malignant biological behaviors, including cell proliferation, colony formation, cell invasion, and migration, while promoting apoptosis. Mechanistic studies revealed that MK2206 2HCl suppressed matrix metalloproteinase 9 (MMP-9) and RhoC expression and promoted autophagy gene LC3 II expression. In summary, our findings demonstrated the chemopreventive effect of MK2206 2HCl on the 4NQO-induced mouse tongue carcinogenesis model, which likely has an underlying mechanism mediated by the MMP-9/RhoC signaling pathway and autophagy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Panpan Yin et al.)
- Published
- 2022
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39. Disruption of enhancer-driven S100A14 expression promotes esophageal carcinogenesis.
- Author
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Li X, Ding F, Wang L, Chen H, and Liu Z
- Subjects
- Animals, Carcinogenesis genetics, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic genetics, Gene Expression Regulation, Neoplastic, Mice, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Esophageal Neoplasms chemically induced, Esophageal Neoplasms genetics, Esophageal Squamous Cell Carcinoma genetics
- Abstract
Increasing evidence have revealed that epigenomic and genomic factors jointly contribute to the malignancy of esophageal squamous cell carcinoma (ESCC). However, little is known regarding how enhancers regulate tumor suppressors and drive the tumorigenesis of ESCC. Here, we characterized S100A14 as a tumor suppressor in ESCC and showed that S100A14 deficiency dramatically promoted 4-nitroquinoline-1-oxide (4NQO) -induced tumorigenesis of ESCC and shortened survival of mice. Intriguingly, we found that S100A14 expression was driven by enhancer, and disruption of enhancer decreased the S100A14 expression in ESCC. Mechanistic investigation showed that S100A14 deficiency triggered aberrant differentiated program. TP63, SOX2 and EP300 occupied the enhancer region of S100A14 gene locus and regulated the expression of S100A14. Consistently, S100A14 is downregulated in ESCC tissues compared with their corresponding adjacent normal tissues, and lower S100A14 expression predicts poorer overall survival. Collectively, disruption of enhancer-regulated S100A14 induces ESCC tumorigenesis and it acts as a critical driver of ESCC tumorigenesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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40. Occurrence of voriconazole-induced cutaneous squamous cell carcinoma in Japan: data mining from different national pharmacovigilance databases.
- Author
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Tanaka H, Okuma M, and Ishii T
- Subjects
- Humans, Pharmacovigilance, Adverse Drug Reaction Reporting Systems, Voriconazole adverse effects, Japan epidemiology, Databases, Factual, Data Mining, Epithelial Cells, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Drug-Related Side Effects and Adverse Reactions
- Abstract
Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60-48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.
- Published
- 2022
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41. Association between Air Pollution and Squamous Cell Lung Cancer in South-Eastern Poland.
- Author
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Gawełko J, Cierpiał-Wolan M, Bwanakare S, and Czarnota M
- Subjects
- Environmental Exposure analysis, Epithelial Cells, Female, Humans, Male, Nitrogen Dioxide analysis, Particulate Matter analysis, Poland epidemiology, Air Pollutants analysis, Air Pollution adverse effects, Air Pollution analysis, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell etiology, Lung Neoplasms chemically induced, Lung Neoplasms etiology
- Abstract
Air pollution is closely associated with the development of respiratory illness. The aim of the present study was to assess the relationship between long-term exposure to PM2.5, PM10, NO
2 , and SO2 pollution and the incidence of lung cancer in the squamous subtype in south-eastern Poland from the years 2004 to 2014. We collected data of 4237 patients with squamous cell lung cancer and the level of selected pollutants. To investigate the relationship between the level of concentrations of pollutants and the place of residence of patients with lung cancer in the squamous subtype, proprietary pollution maps were applied to the places of residence of patients. To analyze the data, the risk ratio was used as well as a number of statistical methods, i.e., the pollution model, inverse distance weighted interpolation, PCA, and ordered response model. Cancer in women and in men seems to depend in particular on the simultaneous inhalation of NO2 and PM10 (variable NO2 PM10) and of NO2 and SO2 (variable NO2 SO2 ), respectively. Nitrogen dioxide exercises a synergistic leading effect, which once composed with the other elements it becomes more persistent in explaining higher odds in the appearance of cancers and could constitute the main cause of squamous cancer.- Published
- 2022
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42. MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma.
- Author
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Zhang W, Huang X, Huang R, Zhu H, Ye P, Lin X, Zhang S, Wu M, and Jiang F
- Subjects
- Animals, Carcinogenesis genetics, Gene Expression Regulation, Neoplastic, Matrix Metalloproteinase 1 genetics, Matrix Metalloproteinase 1 metabolism, Mice, RNA, Small Interfering, Squamous Cell Carcinoma of Head and Neck genetics, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Head and Neck Neoplasms genetics, Matrix Metalloproteinase 13 metabolism, Tongue Neoplasms chemically induced, Tongue Neoplasms genetics
- Abstract
Matrix metalloproteinase-1 (MMP1) has been reported to play key roles in a variety of cancers by degrading the extracellular matrix. However, its carcinogenic roles have not been shown yet in head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate its expression pattern and functional roles as well as clinical significance in HNSCC. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and immunohistochemistry (IHC) were utilized to determine the MMP1 expression pattern and the associations between its expression and patients' outcome in HNSCC. Mice tongue squamous cell carcinoma model induced by 4-nitroquinoline 1-oxide (4NQO) and siRNA-mediated cellular assay in vitro were utilized to evaluate the oncogenic role of MMP1. The biological functions and cancer-related pathways involved in MMP1-related genes were found through bioinformatics analysis. Both mRNA and protein abundance of MMP1 were highly increased in HNSCC as compared to its non-tumor counterparts. MMP1 overexpression positively correlated with advanced tumor size, cervical node metastasis, and advanced pathological grade and lower patients' survival. In the 4NQO-induced animal model, MMP1 expression increased along with the progression of the disease. In HNSCC cells, siRNA-mediated knockdown of MMP1 significantly inhibited cell proliferation, migration, and invasion and activated apoptosis and epithelia-mesenchymal transition (EMT). GSEA, GO, and KEGG analyses showed that MMP1 expression was significantly related to cancer-related pathways and cancer-related functions. Together, our results demonstrated MMP1 serves as a novel prognostic biomarker and putative oncogene in HNSCC., Competing Interests: None of the authors reports any conflict of interest., (Copyright © 2022 Wei Zhang et al.)
- Published
- 2022
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43. Genistein anticancer efficacy during induced oral squamous cell carcinoma: an experimental study.
- Author
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Hussein AM, Attaai AH, and Zahran AM
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene toxicity, Animals, Carcinogenesis pathology, Cricetinae, Genistein adverse effects, Humans, Male, Mesocricetus, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms, Mouth Neoplasms chemically induced, Mouth Neoplasms drug therapy
- Abstract
Background: About 7 million people die from various types of cancer every year representing nearly 12.5% of deaths worldwide. This fact raises the demand to develop new, effective anticancer, onco-suppressive, and chemoprotective agents for the future fighting of cancers. Genistein exhibits pleiotropic functions in cancer, metabolism, and inflammation. It functions as an antineoplastic agent through its effect on the cell cycle, apoptotic processes, angiogenesis, invasion, and metastasis., Aim of the Study: The current study aimed to study the genistein onco-suppressive effects during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters' buccal pouch utilizing flow cytometry analysis (FMA), as a fast-diagnosing tool, in addition to the histopathology., Material and Methods: The buccal mucosa of adult male Syrian hamsters was painted with paraffin oil only (group 1), DMBA mixed in mineral oil (group 2), or orally administrated genistein along with painting DMBA (group 2B). The buccal mucosa was utilized for flow cytometric analysis and histopathological examination., Results: Grossly, DMBA-induced carcinogenesis started at the 9th week. Progressive signs appeared in the following weeks reaching to large ulcerative oral masses and exophytic nodules at the 21st week. Histologically, invasive well-differentiated oral squamous cell carcinoma (OSCC) appeared in the underlying tissues from the 12th week, showing malignant criteria. Genistein had delayed clinicopathological change, which started 6 weeks later, than the DMBA-painted hamsters, as mild epithelial dysplastic changes. This became moderate during the last 6 weeks, without dysplastic changes. Flow cytometry revealed that DMBA led to considerable variation in DNA proliferation activity, aneuploid DNA pattern, in 47.22% of hamsters and significantly raised the S-phase fragment (SPF) values, which drastically reduced after genistein treatment., Conclusion: Taken together, genistein could be employed as an onco-suppressive agent for carcinogenesis. Moreover, FMA could be used as an aiding fast tool for diagnosis of cancer., (© 2022. The Author(s).)
- Published
- 2022
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44. Non-Acid Fluid Exposure and Esophageal Squamous Cell Carcinoma.
- Author
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Soroush A, Etemadi A, and Abrams JA
- Subjects
- Acetaldehyde adverse effects, Animals, Humans, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell genetics, Esophageal Neoplasms chemically induced, Esophageal Neoplasms genetics, Esophageal Squamous Cell Carcinoma, Nitrosamines adverse effects
- Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for the large majority of esophageal cancer cases worldwide. In this review, we examine the potential role of non-acidic fluid (NAF) exposure in ESCC carcinogenesis. Esophageal NAF consists of a mixture of salivary, esophageal, gastric, and duodenal fluids, containing inflammatory constituents such as digestive enzymes and bile acids that induce DNA damage, as well as known carcinogens such as acetaldehyde and N-nitrosamines. Exposure to NAF can occur in the setting of increased non-acid reflux, decreased gastric acidity, and decreased esophageal fluid clearance. Non-acid reflux has been associated with ESCC in small observational studies, and in animal models bile reflux can promote the development of ESCC. Associations have been found between increased ESCC risk and atrophic gastritis, a history of partial gastrectomy, and proton pump inhibitor use, all of which raise the pH of refluxate. Additionally, a minimally or non-acidic gastric environment contains an altered microbiome that can increase the production of acetaldehyde and N-nitrosamines. Esophageal motility disorders such as achalasia and opioid-induced esophageal dysfunction result in increased stasis and exposure to these potentially proinflammatory constituents of NAF. NAF may promote the development of ESCC via multiple mechanisms and is an understudied area of research., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
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45. Squamous cell carcinoma or squamous proliferation associated with nivolumab treatment for metastatic melanoma.
- Author
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Vu M, Chapman S, Lenz B, and Wohltmann W
- Subjects
- Humans, Nivolumab adverse effects, Immune Checkpoint Inhibitors, Programmed Cell Death 1 Receptor, Cell Proliferation, Melanoma drug therapy, Melanoma pathology, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell chemically induced, Neoplasms, Second Primary, Lung Neoplasms drug therapy, Lung Neoplasms pathology
- Abstract
Nivolumab is a programmed death-1 (PD1) immune checkpoint inhibitor that treats various types of cancers including non-small cell lung carcinoma and melanoma, among others. Although it serves as an effective immunotherapy, there are many associated immune-related adverse events. Even years after the introduction of nivolumab, the breadth of its side effect profile continues to expand. We present a case of squamous cell carcinoma associated with nivolumab treatment for metastatic melanoma.
- Published
- 2022
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46. Periodontal disease affects oral cancer progression in a surrogate animal model for tobacco exposure.
- Author
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Spuldaro TR, Wagner VP, Nör F, Gaio EJ, Squarize CH, Carrard VC, Rösing CK, and Castilho RM
- Subjects
- 4-Nitroquinoline-1-oxide toxicity, Animals, Carcinogenesis, Disease Models, Animal, Humans, Rats, Rats, Wistar, Squamous Cell Carcinoma of Head and Neck, Nicotiana adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms, Mouth Neoplasms chemically induced, Mouth Neoplasms pathology, Periodontal Diseases, Periodontitis
- Abstract
For decades, the link between poor oral hygiene and the increased prevalence of oral cancer has been suggested. Most recently, emerging evidence has suggested that chronic inflammatory diseases from the oral cavity (e.g., periodontal disease), to some extent, play a role in the development of oral squamous cell carcinoma (OSCC). The present study aimed to explore the direct impact of biofilm‑induced periodontitis in the carcinogenesis process using a tobacco surrogate animal model for oral cancer. A total of 42 Wistar rats were distributed into four experimental groups: Control group, periodontitis (Perio) group, 4‑nitroquinoline 1‑oxide (4‑NQO) group and 4NQO/Perio group. Periodontitis was stimulated by placing a ligature subgingivally, while oral carcinogenesis was induced by systemic administration of 4NQO in the drinking water for 20 weeks. It was observed that the Perio, 4NQO and 4NQO/Perio groups presented with significantly higher alveolar bone loss compared with that in the control group. Furthermore, all groups receiving 4NQO developed lesions on the dorsal surface of the tongue; however, the 4NQO/Perio group presented larger lesions compared with the 4NQO group. There was also a modest overall increase in the number of epithelial dysplasia and OSCC lesions in the 4NQO/Perio group. Notably, abnormal focal activation of cellular differentiation (cytokeratin 10‑positive cells) that extended near the basal cell layer of the mucosa was observed in rats receiving 4NQO alone, but was absent in rats receiving 4NQO and presenting with periodontal disease. Altogether, the presence of periodontitis combined with 4NQO administration augmented tumor size in the current rat model and tampered with the protective mechanisms of the cellular differentiation of epithelial cells.
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- 2022
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47. Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.
- Author
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de Macedo Andrade AC, Felix FA, França GM, Ribeiro ILA, Barboza CAG, de Castro RD, and de Lisboa Lopes Costa A
- Subjects
- Aged, Female, Humans, Hydrochlorothiazide adverse effects, Lip pathology, Male, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell complications, Carcinoma, Squamous Cell epidemiology, Lip Neoplasms chemically induced, Lip Neoplasms complications, Lip Neoplasms epidemiology, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology
- Abstract
Purpose: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development., Methodology: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0)., Results: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg., Conclusions: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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48. Antidiabetic Treatment in Patients at High Risk for a Subsequent Keratinocyte Carcinoma.
- Author
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Misitzis A, Stratigos A, Mastorakos G, and Weinstock M
- Subjects
- Aged, Female, Humans, Hypoglycemic Agents adverse effects, Keratinocytes, Male, Retrospective Studies, Carcinoma, Basal Cell chemically induced, Carcinoma, Basal Cell epidemiology, Carcinoma, Basal Cell prevention & control, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell prevention & control, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 pathology, Metformin adverse effects, Skin Neoplasms chemically induced, Skin Neoplasms epidemiology, Skin Neoplasms prevention & control
- Abstract
Background: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40–1.56; P=0.49) and 0.94 (CI: 0.63–1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas. J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087.
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- 2022
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49. Skin lesions.
- Author
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Planelles-Ramos MV, Araujo Pérez R, Delcampo-Novales M, and Flores-Saldaña M
- Subjects
- Humans, Biopsy, Azathioprine adverse effects, Adrenal Cortex Hormones adverse effects, Immunosuppressive Agents adverse effects, Skin Diseases diagnosis, Skin Diseases etiology, Skin Diseases therapy, Kidney Transplantation adverse effects, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell pathology, Keratosis, Actinic chemically induced, Keratosis, Actinic pathology
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- 2022
- Full Text
- View/download PDF
50. Arsenical keratoses with squamous cell carcinoma.
- Author
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Neema S and Radhakrishnan S
- Subjects
- Humans, Skin pathology, Arsenicals, Carcinoma, Squamous Cell chemically induced, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Keratosis, Skin Neoplasms chemically induced, Skin Neoplasms diagnosis, Skin Neoplasms pathology
- Published
- 2022
- Full Text
- View/download PDF
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