Comparative Study of the Potential Cell-Penetrating Peptide ∆M4 on Apoptosis Cell Signaling in A375 and A431 Cancer Cell Lines.

In recent yearsjajajj, peptide-based therapeutics have attracted increasing interest as a potential approach to cancer treatment. Peptides are characterized by high specificity and low cytotoxicity, but they cannot be considered universal drugs for all types of cancer. Of the numerous anticancer-reported peptides, both natural and synthetic, only a few have reached clinical applications. However, in most cases, the mechanism behind the anticancer activity of the peptide is not fully understood. For this reason, in this work, we investigated the effect of the novel peptide ∆M4, which has documented anticancer activity, on two human skin cancer cell lines. A novel approach to studying the potential induction of apoptosis by anticancer peptides is the use of protein microarrays. The results of the apoptosis protein study demonstrated that both cell types, skin malignant melanoma (A375) and epidermoid carcinoma (A431), exhibited markers associated with apoptosis and cellular response to oxidative stress. Additionally, ∆M4 induced concentration- and time-dependent moderate ROS production, triggering a defensive response from the cells, which showed decreased activation of cytoplasmic superoxide dismutase. However, the studied cells exhibited a differential response in catalase activity, with A375 cells showing greater resistance to the peptide action, possibly mediated by the Nrf2 pathway. Nevertheless, both cell types showed moderate activity of caspases 3/7, suggesting that they may undergo partial apoptosis, although another pathway of programmed death cannot be excluded. Extended analysis of the mechanisms of action of anticancer peptides may help determine their effectiveness in overcoming chemoresistance in cancerous cells.

Photo-triggered caffeic acid delivery via psyllium polysaccharide- gellan gum-based injectable bionanogel for epidermoid carcinoma treatment.

Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.

[Synchronous association of two primary lung tumors: a case report]. / Association synchrone de deux tumeurs pulmonaires primitives: à propos d'un cas.

Synchronous multiple primary lung tumors are a relatively rare entity with an increasing incidence in recent years due to the development of thoracic imaging and immunohistochemical techniques. The second lesion is considered in most cases as a secondary location, which partly explains the decrease in the incidence of this entity. We report the observation of a 74-year-old patient with two synchronous primary lung tumors, an adenocarcinoma and an epidermoid carcinoma. Through this clinical observation, we highlight the difficulty of diagnosing synchronous tumors and the major interest of new imaging modalities and immunohistochemical techniques for the optimal management of these tumors.

ΔM4: Membrane-Active Peptide with Antitumoral Potential against Human Skin Cancer Cells.

Peptides have become attractive potential agents due to their affinity to cancer cells. In this work, the biological activity of the peptide ΔM4 against melanoma cancer cell line A375, epidermoid carcinoma cell line A431, and non-tumoral HaCaT cells was evaluated. The cytotoxic MTT assay demonstrates that ΔM4 show five times more activity against cancer than non-cancer cells. The potential membrane effect of ΔM4 was evaluated through lactate dehydrogenase release and Sytox uptake experiments. The results show a higher membrane activity of ΔM4 against A431 in comparison with the A375 cell line at a level of 12.5 µM. The Sytox experiments show that ΔM4 has a direct effect on the permeability of cancer cells in comparison with control cells. Infrared spectroscopy was used to study the affinity of the peptide to membranes resembling the composition of tumoral and non-tumoral cells. The results show that ΔM4 induces a fluidization effect on the tumoral lipid system over 5% molar concentration. Finally, to determine the appearance of phosphatidylserine on the surface of the cell, flow cytometry analyses were performed employing an annexin V-PE conjugate. The results suggest that 12.5 µM of ΔM4 induces phosphatidylserine translocation in A375 and A431 cancer cells. The findings of this study support the potential of ΔM4 as a selective agent for targeting cancer cells. Its mechanism of action demonstrated selectivity, membrane-disrupting effects, and induction of phosphatidylserine translocation.

Husk-like Zinc Oxide Nanoparticles Induce Apoptosis through ROS Generation in Epidermoid Carcinoma Cells: Effect of Incubation Period on Sol-Gel Synthesis and Anti-Cancerous Properties.

This study effectively reports the influence of experimental incubation period on the sol-gel production of husk-like zinc oxide nanoparticles (ZNPs) and their anti-cancerous abilities. The surface morphology of ZNPs was studied with the help of SEM. With the use of TEM, the diameter range of the ZNPs was estimated to be ~86 and ~231 nm for ZNPA and ZNPB, prepared by incubating zinc oxide for 2 and 10 weeks, respectively. The X-ray diffraction (XRD) investigation showed that ZNPs had a pure wurtzite crystal structure. On prolonging the experimental incubation, a relative drop in aspect ratio was observed, displaying a distinct blue-shift in the UV-visible spectrum. Furthermore, RBC lysis assay results concluded that ZNPA and ZNPB both demonstrated innoxious nature. As indicated by MTT assay, reactive oxygen species (ROS) release, and chromatin condensation investigations against the human epidermoid carcinoma (HEC) A431 cells, ZNPB demonstrated viable relevance to chemotherapy. Compared to ZNPB, ZNPA had a slightly lower IC50 against A431 cells due to its small size. This study conclusively describes a simple, affordable method to produce ZNP nano-formulations that display significant cytotoxicity against the skin cancer cell line A431, suggesting that ZNPs may be useful in the treatment of cancer.

Intracranial squamous cell carcinoma of the cerebello-pontine angle mimicking a cystic acoustic schwannoma. A case report with discussion of differential diagnosis and review of literature.

We report a case of a primary intracranial squamous cell carcinoma (SCC) of the cerebello-pontine angle extending through the internal auditory canal, with the unusual presentation of a completely cystic lesion with no diffusion restriction, internal necrotic-hemorrhagic changes and peripheral enhancement, mimicking a cystic acoustic schwannoma. The lack of diffusion restriction and the peripheral enhancement along the lesion, 2 unique findings, supposedly reflected complete cancerization of the epidermoid cyst from which the SCC originated. We discuss the differential diagnosis and review the literature on primary intracranial SCC.

American Head and Neck Society position statement on the use of PD-1 inhibitors for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: A position statement put forth by the American Head and Neck Society (AHNS) was constructed to provide evidence-based treatment recommendations for PD-1 inhibitor use in advanced cutaneous squamous cell carcinoma (cSCC). Secondarily, we sought to identify knowledge gaps warranting further investigation. METHODS: A literature search utilizing key terms: cutaneous squamous cell carcinoma, cutaneous cancer, checkpoint inhibitors, systemic therapy, Program Cell Death, PD-1 (PubMed, Cochrane, and Google Scholar) was carried out to generate evidence-based statements. The statements were distributed among the AHNS membership. Delphi methodology was applied to identify statements achieving 70% or greater consensus among the leadership team. RESULTS: Twenty-six position statements achieved consensus. Knowledge gaps for future research included: impact of immunosuppression on cSCC staging and associated treatment; role of PD-1 inhibitors in immunosuppressed patients. CONCLUSION: This comprehensive position statement put forth by the AHNS represents majority consensus by practicing head and neck surgeons throughout the country.

French AFU Cancer Committee Guidelines - Update 2022-2024: penile cancer.

OBJECTIVE: To update French oncology guidelines concerning penile cancer. METHODS: Comprehensive Medline search between 2020 and 2022 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update previous guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organsparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Its results determine the type of lymphadenectomy to be performed (for diagnostic or curative purposes). Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.

El pH salival como marcador biológico en pacientes diagnosticados con carcinoma epidermoide oral de Guantánamo / Salivary pH as diagnostic biomarker in patients diagnosed with oral squamous cells carcinoma in Guantanamo / pH salivar como marcador biológico em pacientes diagnosticados com carcinoma epidermóide oral de Guantánamo

RESUMEN Introducción: El cáncer bucal constituye un problema de salud de connotación mundial. Objetivo: Comparar las variaciones del pH salival entre pacientes con carcinoma epidermoide recién diagnosticados, después del tratamiento oncoespecífico y sujetos aparentemente sanos de la provincia Guantánamo, Cuba, en el período noviembre 2019- enero 2022. Método: Se realizó un estudio descriptivo, comparativo, transversal, en pacientes ambulatorios de la consulta de Cirugía Maxilofacial del Hospital General Docente "Dr. Agostinho Neto". El grupo de estudio estuvo conformado por 200 pacientes divididos en 3 subgrupos: subgrupo I (50 pacientes recién diagnosticados con carcinoma epidermoide oral, con diagnóstico concomitante de caries dental y periodontitis crónica del adulto); subgrupo II (50 pacientes con la referida patología después de tratamiento oncoespecífico, tratados por las enfermedades bucales antes citadas) y subgrupo III (100 pacientes controles aparentemente sanos). Se estudiaron las variables: edad, sexo, tipo de dieta y pH salival. Resultados: La edad media fue de 59,8 años, 70 % fueron hombres. Se asoció la dieta consumida y cada subgrupo (p=0,001). El pH salival de los pacientes con carcinoma epidermoide recién diagnosticados afectados por ambas enfermedades bucales fue ácido (6,25±0,37) en comparación a los otros subgrupos. El 98,6 % de los pacientes con pH salival ácido presentaron una dieta usual a base de carbohidratos y grasas (p=0,000). Conclusiones: Se evidenció que el pH salival de los pacientes con carcinoma epidermoide recién diagnosticados fue ácido en comparación a los otros subgrupos, por lo que este parámetro puede usarse como un marcador biológico de la enfermedad.

ABSTRACT Introduction: Oral cancer is a common health problem worldwide. Objective: Compare the salivary pH range changes among patients diagnosed recently with oral squamous cells carcinoma after receiving oncospecific treatment and subjects apparently healthy, Guantanamo, Cuba, period time November 2019 -January 2022. Method: A descriptive, comparative, cross-sectional study was carried out in outpatients of the Maxillofacial Surgery Consultation room at the Hospital General Docente "Dr. Agostinho Neto". The study group consisted of 200 patients divided into 3 subgroups: subgroup I (50 newly diagnosed patients with oral squamous cell carcinoma, with concomitant diagnosis of dental caries and chronic adult periodontitis); subgroup II (50 patients with the aforementioned pathology after oncospecific treatment, treated for the aforementioned oral diseases) and subgroup III (100 apparently healthy control patients). The following variables were studied: age, sex, type of diet and salivary pH. Results: Average age was 59.8 years, 70% were men. There was an association between the diet consumed and each subgroup (p= 0.001). The salivary pH of newly diagnosed squamous cell carcinoma patients affected by both oral diseases was acidic (6.25±0.37) compared to the other subgroups. The 98.6% of patients with acid salivary pH presented a usual diet based on carbohydrates and fats (p=0.000). Conclusions: It was shown that the salivary pH of newly diagnosed patients with squamous cell carcinoma was acidic compared to the other subgroups. Therefore, this parameter can be used as a biological marker of the disease.

RESUMO Introdução: O câncer bucal é um problema de saúde global. Objetivo: Comparar as variações do pH salivar entre pacientes com carcinoma espinocelular recém-diagnosticado, após tratamento oncoespecífico, e indivíduos aparentemente saudáveis da província de Guantánamo, Cuba, no período de novembro de 2019 a janeiro de 2022. Método: Estudo descritivo, comparativo, cruzado seccional, em pacientes ambulatoriais da consulta de Cirurgia Bucomaxilofacial do Hospital General Docente "Dr. Agostinho Neto". O grupo de estudo foi composto por 200 pacientes divididos em 3 subgrupos: subgrupo I (50 pacientes recém-diagnosticados com carcinoma espinocelular oral, com diagnóstico concomitante de cárie dentária e periodontite crônica do adulto); subgrupo II (50 pacientes com a patologia supracitada após tratamento oncoespecífico, tratados para as doenças bucais supracitadas) e subgrupo III (100 pacientes controles aparentemente saudáveis). As variáveis estudadas foram: idade, sexo, tipo de dieta e pH salivar. Resultados: A média de idade foi de 59,8 anos, 70% eram homens. A dieta consumida e cada subgrupo foram associados (p=0,001). O pH salivar de pacientes recém-diagnosticados com carcinoma espinocelular afetados por ambas as doenças bucais foi ácido (6,25±0,37) em comparação com os outros subgrupos. 98,6% dos pacientes com pH salivar ácido apresentaram dieta habitual baseada em carboidratos e gorduras (p=0,000). Conclusões: Evidenciou-se que o pH salivar dos pacientes com carcinoma espinocelular recém-diagnosticado foi ácido em relação aos demais subgrupos. Portanto, esse parâmetro pode ser utilizado como marcador biológico da doença.

A rare case of penile epidermoid carcinoma.

Penile neoplasms are rare. The main goal of our case report is to demonstrate the important role of imaging in local and regional cancer extension assessment, to guide the treatment plan. We report a case of penile epidermoid carcinoma in a 54 year old uncircumcised man, with a history of chronic smoking, presenting with a mass in the base of the penis.

Carcinoma epidermoide de piel tratado con HeberFERON®

RESUMEN Introducción: en la literatura biomédica son escasos los reportes sobre el uso de los interferones como tratamiento en el carcinoma epidermoide. En una unidad de atención primaria, en Colón, Matanzas, se implementó el HeberFERON® en este tipo de tumor, con experiencias favorables. Objetivo: describir la efectividad del HeberFERON® en el carcinoma epidermoide. Materiales y métodos: se realizó un estudio observacional, descriptivo en 33 lesiones de carcinoma epidermoide en 29 pacientes. La dosis fue de 7,0 y 10,5 MUI de actividad antiviral, infiltrada de forma perilesional tres veces por semana durante tres semanas. Se realizó el seguimiento clínico de los pacientes antes del tratamiento y a las 16 semanas del inicio del mismo. Las variables fueron: edad, sexo, fototipo de piel, procedencia, localización, tipo clínico, estadio y respuesta clínica al tratamiento. Se consideraron cuatro categorías de respuesta: completa, parcial, enfermedad estable y progresiva. Se incluyó la respuesta objetiva (completa más parcial). Se recogieron los datos en una historia clínica. Se utilizaron los programas Microsoft Excel y SPSS para el procesamiento estadístico. Resultados: el 65,5 % de los pacientes correspondió al sexo masculino. Un 58,6 % son fototipo II y de procedencia urbana. Predominaron las edades entre 61 y 80 años (55,2 %). Hubo respuesta objetiva en 57,6 % (cinco completas y 14 parciales). Las mejores respuestas la mostraron el carcinoma epidermoide queratósico superficial y el noduloulceroso. Conclusiones: la mezcla de interferones fue efectiva en el carcinoma epidermoide en todos los subtipos clínicos, aunque los autores sugieren un segundo ciclo de HeberFERON® o asociarlo con quimioterapia cuando la respuesta no sea completa.

ABSTRACT Introduction: there are few reports in the literature on the use of interferon in the treatment of the squamous cell carcinoma. In a primary care unit in Colon, Matanzas, HeberFERON® was implemented in this type of tumor with favorable experiences. Objective: to describe the effectiveness of HeberFERON® in epidermoid carcinoma. Materials and methods: an observational, descriptive study was conducted in 33 epidermoid carcinoma lesions in 29 patients. The doses were 7.0 and 10.5 MUI of antiviral activity, perilesionally infiltrated three times a week for three weeks. Clinical follow-up of patients was performed before the treatment and at 16 weeks from the beginning of the treatment. The variables were: age, sex, skin phototype, origin; location, clinical type, stage and clinical response to treatment. Four categories of response were considered: complete, partial, stable and progressive disease. The objective response (complete plus partial) was included. Data were collected in a clinical record. The Microsoft Excel and SPSS programs were used for statistical processing. Results: 65.5 % of patients were male. 58.6 % are phototype II and of urban origin. Ages ranging from 61 to 80 years (55.2 %) predominated. There was objective response in 57.6 % (five complete and 14 partials). The superficial keratotic squamous cell carcinoma and the nodular ulcerative one showed the best responses. Conclusions: interferon mixing was effective in all clinical subtypes of epidermoid carcinoma, although the authors suggest a second cycle of HeberFERON® or to associate it with chemotherapy when the response is not complete.

Recent Advanced in the Treatment of Advanced SCC Tumors.

Squamous cell carcinoma (SCC) is the second most frequent form of skin cancer after basal cell carcinoma. While most SCC can be treated by surgery or radiotherapy, some progress into an advanced form and are no longer suitable for these treatments. Guidelines and staging systems have help to define these advanced SCC (aSCC), for which prognosis was very poor until recently. Platin-based chemotherapy was traditionally used, but few prospective trials and no treatment regimen was recommended. Furthermore, toxicity in elderly patients limited its use. The development of immunotherapy has improved the prognosis of these difficult-to-treat aSCC. In this review, we define high risk and aSCC and explored current treatment strategies for these tumors.

Collagen Scaffolds Treated by Hydrogen Peroxide for Cell Cultivation.

Collagen in the body is exposed to a range of influences, including free radicals, which can lead to a significant change in its structure. Modeling such an effect on collagen fibrils will allow one to get a native structure in vitro, which is important for modern tissue engineering. The aim of this work is to study the effect of free radicals on a solution of hydrogen peroxide with a concentration of 0.006-0.15% on the structure of collagen fibrils in vitro, and the response of cells to such treatment. SEM measurements show a decrease in the diameter of the collagen fibrils with an increase in the concentration of hydrogen peroxide. Such treatment also leads to an increase in the wetting angle of the collagen surface. Fourier transform infrared spectroscopy demonstrates a decrease in the signal with wave number 1084 cm-1 due to the detachment of glucose and galactose linked to hydroxylysine, connected to the collagen molecule through the -C-O-C- group. During the first day of cultivating ASCs, MG-63, and A-431 cells, an increase in cell adhesion on collagen fibrils treated with H2O2 (0.015, 0.03%) was observed. Thus the effect of H2O2 on biologically relevant extracellular matrices for the formation of collagen scaffolds was shown.

Anti-Malignant Effect of Tensile Loading to Adherens Junctions in Cutaneous Squamous Cell Carcinoma Cells.

Actomyosin contractility regulates various cellular processes including proliferation and differentiation while dysregulation of actomyosin activity contributes to cancer development and progression. Previously, we have reported that actomyosin-generated tension at adherens junctions is required for cell density-dependent inhibition of proliferation of normal skin keratinocytes. However, it remains unclear how actomyosin contractility affects the hyperproliferation ability of cutaneous squamous cell carcinoma (cSCC) cells. In this study, we find that actomyosin activity is impaired in cSCC cells both in vitro and in vivo. External application of tensile loads to adherens junctions by sustained mechanical stretch attenuates the proliferation of cSCC cells, which depends on intact adherens junctions. Forced activation of actomyosin of cSCC cells also inhibits their proliferation in a cell-cell contact-dependent manner. Furthermore, the cell cycle arrest induced by tensile loading to adherens junctions is accompanied by epidermal differentiation in cSCC cells. Our results show that the degree of malignant properties of cSCC cells can be reduced by applying tensile loads to adherens junctions, which implies that the mechanical status of adherens junctions may serve as a novel therapeutic target for cSCC.

Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431.

Diterpenoid plant hormone gibberellic acid (GA) plays an important role in regulation of plant growth and development and is commonly used in agriculture for activation of plant growth and food production. It is known that many plant-derived compounds have miscellaneous biological effects on animals and humans, influencing specific cellular functions and metabolic pathways. However, the effect of GA on animal and human cells remains controversial. We investigated the effect of GA on cultured human cell lines of epidermoid origin-immortalized non-tumorigenic keratinocytes HaCaT and carcinoma A431 cells. We found that at a non-toxic dose, GA upregulated the expression of genes associated with the ER stress response-CHOP, sXBP1, GRP87 in both cell lines, and ATF4 predominantly in A431 cells. We also showed that GA was more effective in upregulating the production of ER stress marker GRP78, autophagy marker LC3B-II, and differentiation markers involucrin and filaggrin in A431 cells than in HaCaT. We conclude that GA induces mild ER stress in both cell lines, followed by the activation of differentiation via upregulation of autophagy. However, in comparison with immortalized keratinocytes HaCaT, GA is more effective in inducing differentiation of carcinoma A431 cells, probably due to the inherently lower differentiation status of A431 cells. The activation of differentiation in poorly differentiated and highly malignant A431 cells by GA may lower the level of malignancy of these cells and decrease their tumorigenic potential.

Clinical Characteristics and Prognosis of Patients With Pulmonary Mucoepidermoid Carcinoma: A SEER-Based Analysis.

BACKGROUND: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an extremely rare malignancy. Its clinical characteristics and prognosis are not fully understood. This study evaluated clinical characteristics and prognostic factors of PMEC and established a nomogram to predict its 1-, 3-, 5- and 10-year cancer-specific survival (CSS) rates. METHODS: In the Surveillance, Epidemiology, and End Results database from January 1, 2016 to December 31, 2016, patients pathologically diagnosed with PMEC were identified. Kaplan-Meier analysis and Cox regression were performed to evaluate the CSS stratified by different covariates. A predictive nomogram model was built and validated by the concordance index (C-index) and calibration curves. RESULTS: A total of 585 PMEC patients were identified. A total of 408 (70%) of patients were placed into the training cohort, and 177 (30%) patients were placed into the validation cohort. The 5- and 10-year CSS rates of stage I-II PMEC patients were 91.4 and 88.9, respectively. The 1-, 3- and 5-year CSS rates of stage III-IV PMEC were 56.5, 39.45, and 32.1%, respectively. Survival curves showed that older age, large tumor size, poor differentiation, and high TNM stage were associated with a significantly worse prognosis. CSS outcomes were significantly better in patients who received surgical treatments (surgical alone, surgery plus radiation and/or chemotherapy). Patients who received radiation and/or chemotherapy had the worst prognosis. Multivariate Cox results revealed that covariates, including age, tumor laterality, tumor sizes, pathological differentiation, lymph node metastasis, distant metastasis, TNM stage and therapy, were independent prognostic factors for PMEC. These factors were used to construct a nomogram. The C-index of the nomogram was 0.921. The calibration curve presented favorable consistency between the predicted CSS and actual observations. This nomogram was validated by the validation cohort. The C-index of the validation cohort was 0.968. CONCLUSION: Age, bilateral tumors, tumor size, pathological differentiation grade, lymph node metastasis, distant metastasis, TNM stage and therapy were independent prognostic factors of PMEC patients. The first nomogram for predicting the CSS of PMEC was built and validated, showing its potential value in practice.

Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives.

A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC50 = 1.39 µM). Some compounds were evaluated for DNA topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed topoisomerase inhibition activity with IC50 values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.

Identification of new fisetin analogs as kinase inhibitors: Data on synthesis and anti-skin cancer activities evaluation.

This article contains supplemental datasets of the recently published related research article "Synthesis, Inverse Docking-Assisted Identification and in vitro Biological Characterization of Flavonol-based Analogs of Fisetin as c-Kit, CDK2 and mTOR Inhibitors against Melanoma and Non-melanoma Skin Cancers" by Roy et al., [1]. It provides in-depth data not included in the original co-submission on the biophysical, molecular docking, and biological characterization of newly synthesized flavonol-based analogs of fisetin, a natural dietary small molecule with anticancer and anti-inflammatory properties. These synthetic small molecules were investigated as new, potential single and/or multi-kinase inhibitors of the cyclin-dependent kinase-2 (CDK2), receptor tyrosine kinases (c-KITs), and mammalian targets of rapamycin (mTOR) targets, potentially active against melanoma or non-melanoma skin cancers. Furthermore, this data-in-brief article comprises additional sets of results on several aspects of the properties of the dual and multiple kinase inhibitor compounds' effects that were not presented in the associated article, including the activated targets that are dysregulated in skin cancers; the effects on markers of apoptosis; on colony formation; and in scratch wound healing assays. The study has identified a panel of novel fisetin analogs that are either single- or multi-kinase inhibitors, which may be further developed as active for the treatment of melanoma and non-melanoma skin cancers. The dataset presented herein will be utilized for additional studies aiming to establish a biological platform to steer for predictive and experimental screening of novel flavonoids and analogs in relevant organoids, humanized animal models and in vivo disease models. The present results should also serve as a key stepping-stone towards enabling target-structure-based design, synthesis and initial testing of novel analogs or derivatives of fisetin. The current study may eventually lead to the development of safe, promising and preclinical candidate entities for treatment of skin and other forms of cancers as well as various other human diseases, which can possibly add to the general armamentarium of promising and safe drugs for health promotion.